CALIFORNIA TUMOR TISSUE REGISTRY

EIGHTY-NINTH SEMI-ANNUAL SLIDE SEMINAR

ON

GASTRO-INTESTINAL TUMORS

MODERATOR:

RODGER C. HAGGITT, M. D.

DIRECTOR, DIVISION OF HOSPITAL PATHOLOGY UNIVERSITY DF WASHINGTON

SEATTLE, WASHINGTON

ASSOCIATE MEDICAL STAFF HARBORVIEW MEDICAL CENTER

SEATTLE, WASHINGTON

CHAIRMAN:

WILLIAM H. HARTMANN, M. D.

DIRECTOR OF LABORATORY LONG BEACH MEMORIAL HOSPITAL

LONG BEACH, CALIFORNIA

SUNDAY - DECEMBER 9, 1990 9:00 A.M - 5:00 P.M.

REGISTRATION: 7:30A.M.

PARC FIFTY FIVE HOTEL SAN FRANCISCO, CALIFORNIA

(415)392-8000

/6~

Please bring your protocol, but do not bring sl ides or microscopes to the meeting.

CONTRIBUTOR: William H. Hartmann, M. D. William Talbert, M. D. Long Beach, California

TISSUE FROM: Esophagus

CLINICAL ABSTRACT:

DECEMBER 1990 - CASE NO. 1

ACCESSION NO. 26707

History: This 59-year-old Caucasian male recently developed a severe headache wfth a subsequent CT scan showing a mass in the pari eta 1 area. A craniotomy was performed and biopsy reported a presence of an adenocarcinoma, suggestive of g.i. primary. He had no gastrointestinal symptoms, except for "bloating" and "full sensation in the sternal area after eating quickly".

Significant past history w.as a small benign ~olonic polyp removed in 1977. with subsequent colonoscopy in 1988 showing no a.bnormalities.

Laboratory report: Liver function tests revealed normal bilirubin and enzymes. TSP 5 ( n 1 6 - 8. 2} and a 1 bumi n 3. 2 ( n 1 3. 5 - 5. 5} . Gamma GT 132 (nl 10- 70} and CEA 6.6 (nl 0- 2.5}.

Endoscopy: There was a 10 em. hiatal hernia noted with the gastro­esophageal junction being seen at 30 em. in the diaphragmatic imprint at 40 em. There was a large bulky friable mass which began just below the squamocolumnar junction and involved most of the cardia in a circumferential manner with some extension into the distal esophagus.

SURGERY: (January 18, 1990}

At surgery, there was a bulky, predominantly intraluminal, partially transmural, tumor involving the distal esophagus extending down to the gastro-esophageal junction. Although there was no obvious continuous spread in the peri-esophageal tissue, there were two suspicious lesions in the right lobe of the liver, one on fts anterior edge, measuring approximately 1 em. in diameter, and a second smooth but hard lesion located in the right lateral portion of the liver, measuring approximately 2. 5 em. Rema·i nder of the abdomen was unremarkable. The nodes appeared uninvolved. An esophagogastrectomy was performed.

GROSS PATHOLOGY:

The specimen consisted of the distal esophagus and proximal stomach, a .portion of this had been opened to reveal the mucosa and a fungating lesion within the lumen of the distal es.ophagus and the gastro-esophageal junction. The portion of the stomach had a length of 7 em. and B em. at its widest point; the portion of esophagus had a length of 6.7 em. and a diameter of 3.1 em. at its widest point and 3 em. at the gastro­esophageal junction. The tumor was pink-red and fungating, measuring 4.2 x 2.5 x 0.3 em.

CONTRIBUTOR: Rodger C. Haggitt, M. D. DECEMBER 1990 - CASE NO. 2 Seattle, Washington

TISSUE FROM: Esophagus ACCESSION NO. 26846

CLINICAL ABSTRACT:

History: A 76-year-old white male with a long standing history of hiatal hernia, gastroesophageal ref l ux disease and 80 pack years· of cigarette smoking developed progressive dysphagia in November of 1989.

Endoscopy disclosed a mass in the distal esophagus that was resected.

CONTRIBUTOR: Nelson Quigley, M. 0. 0[C£MB[R 1990 - CASt ~0. 3 Anaheim, California

TISSUE FROM: Stomach ACCESSION NO. 26837

CLIN ICAL ABSTRACT:

History: This 56-year-old Caucasian male was admitted to the hospital complaining of abdominal pain, nausea and vomiting, increasing in intensity over the last six months. There has been a 10 lb. or more weight loss over the past year and 40 lb. weight loss over the previous 4-5 years . He also had food seemingly sticking in the lower esophageal area. He had a history of alcohol intake up to two pints of bourban a day and smoking in excess of two packs a day for many years. He denied DT' s but admitted a history of seizures with Dilantin Rx. He noted on one.occasion that his stool was black. He has not vomited blood.

Physical examination: The patient was alert, oriented, cooperative and apprehensive. There was moderate abdominal tenderness in the epigastr ium and the right upper quadrant, no rebound. Bowel sounds were normoactive. There were no masses. Liver and spleen were not enlarged. There was no evidence of ascites. Rectal examination revealed no blood on glove.

Laboratory report : WBC 15,300; hemoglobin 11 gm%; hematocrit 35.9; Di l antin 1 eve 1 11.9.

Radiograph: The upper G.I. showed nearly complete obstruction of the pylorus with ulcerations.

Esophagogastroduodenoscopy: The esophagus showed evidence of grade 2+/5+ distal esophageal varices. There was a large amount of fluid and barium in the stomach . The distal antrum was markedly deformed with significant narrowing. Mul tiple biopsies were taken and reported as benign gastri c mucosa with focal chronic inflammation.

SURG ERY: (May 1, 1990)

A subtotal gastrectomy , Bi11roth II , was performed after submitting mul tiple biopsy specimens. Findings at surgery revealed a grossly normal abdomen except for a huge mass that was inflamed and showed scarring pulling the common duct into the massive scarring as well as the pancreas.

GROSS PATHOLOGY:

The stomach was submitted in numer9us fragments that contained a fibrotic ulcer base with the additional segments showing pale-tan mucosa with fi brous thickening of the ulcer bed. The fina l gastrectomy specimen weighed 180 grams, 10 x 11 x 2 em., with the proximal surgical rim measuring 18 ems . The specimen was opened along the greater curvature, revealing a rugated tan mucosa with prominent rugal folds. with flecks of white barium. The serosal surface was glistening tan, smooth with an adherent mahogany red blood clot. No definite areas of ulceration were noted. There was hyperemic hemorrhagic erosion of the mucosa along the distal surgical margin which could be superficial ulcers.

CONTRIBUTOR: Albert Garib, M. D. DECEMBER 1990 - CASE NO. 4 Huntington Beach, California

TISSUE FROM: Cecum ACCESSION NO. 26790

CLINICAL ABSTRACT:

History: Aprroximately 5 days prior to admission this 24-year-old Caucasian male noticed abdominal discomfort with bloating, feeling of gaseousness and constipation for which he took two Correctol tablets. The next few days he developed frequent nausea and vomiting with generalized abdominal pain, followed by low grade fever with frequent watery stool s. He no ticed smal l amount of hematemesis during one of his emeses as wel l as blood with his diarrhea. He was treated in the past for anemia with iron medications .

Physical examination revealed mild-to-moderate general abdominal tenderness. Bowel sounds were hypoactive. There was no mass or organomegaly. Ampulla was empty on rectal examination.

Gastrocaffeine (coffee) enema showed a large mass in the cecum. Colonoscopy revealed its postition to the right of the mi dline (light of colonscope seen through abdominal wall in this position). A possible likely explanation was the large mass (? polyp) caused an intussusception with this portion of colon containing the mass acting as the intussusceptum.

SURGERY: (June 14, 1990)

At surgery the l iver , gallbladder, spleen , stomach and smal l intestines appeared grossly normal. An irregular soft mass, 1.5 inch in diameter, was palpated in the lumen of the cecum. The mass was around the base of the appendix and obviously obstructed the opening of the appendix, as that organ was found to be tremendously dilated, measuring approximately 3 inches in length and 1 inch in diameter . There was no evidence of acute inflammation. The apppendix, at its base, was partially intussuscepted into the cecum for an estimated dis­tance of approximately 2 em. A dozen or so lymph nodes were noted along the mesentery of the ascending colon, measuring between 3 mm. and 1 em. in diameter. They were all soft and mobile . The rest of the large intestine and the small intestine appeared grossly normal. A radical right hemicolectomy was then performed.

GROSS PATHOLOGY:

A papillary, multilobulated, soft, pink polyp, measuring 4.8 em. in diameter and 2.8 ems . in height originated from the mucosal surface of the cecum. It had a broad base and extended from the edge of the ileocecal val ve to the area of the appendiceal orifice. On section it was soft and pink.

CONTRIBUTOR: Rodger C. Haggitt, M. D. DECEMBER 1990 - CASE NO. 5 Seattle, Washington

TISSUE FROM: Colon ACCESSION NO. 26B50

CLINICAL ABSTRACT:

History: This 20-year-old man underwent a prophylactic colectomy for multiple polyps, as had his father and two uncles. His grandfather died at the age of 29 from wide spread metastatic colonic carcinoma.

CONTRIBUTOR: James F. Keefe, M. 0. DECEMBER 1990 - CASE NO. 6 Inglewood, California

TISSUE FROM: Jejunum ACCESSION NO. 26797

CLINICAL ABSTRACT:

History: This 24-year-old Hispani c female presented with severe upper abdominal pain associated with persistent nausea and vomiting. The pain began B hours prior to admission and had become progressively worse. She had similar episode two weeks prior to admission whi ch resol ved spontaneously.

Physical examinati on: Abdominal examination revealed a protuberant abdomen with no bowel sounds present. There was a large pa lpable mass in the epigastric region, as wel l as in the left Kemi-abdomen just l ateral to the umbilicus. Both masses appeared to be tender, however, on palpation were tympanitic. There was 4+ tenderness over the mass, as well as 1+ peritoneal irritation. Rectal examination revealed no palpable intra-anal or recti ampullary lesions.

Laboratory report: Hgb 8.8; Hct 29.5; WBC 10,000.

Radiograph: Abdominal ultrasound and CT revealed a large intra-luminal mass in the right lower quadrant suggestive of intussusception.

SURGERY: (June 15, 1990}

An intussussception with i schemic changes was present in t he mid jejunum. This had looped on itself to form a vol1vulus emcompassing about 2 feet of bowel. Two additional "tumors" were pal pated proximal and distal to t his site.

GROSS PATHOLOGY:

A 55 em. length of intussuscepted bowel with dark red coloring was submitte Also received were two separate segments of bowel, measuring 14 em. and 4.5 em. containing separate polypoid masses, measuring 4 x 3.5 x 3.0 em and 3.0 x 3.2 x 3.4 em. The surface of both polyps showed a reddish granular surface.

CONTRIBUTOR: Rodger C. Haggitt, M. D. DECEMBER 1990- CASE NO. 7 Seattle, Washington

TISSUE FROM: Stomach ACCESSION NO . 26849

CLINICAL ABSTRACT:

History: This 67-year-old man presented to a gastroenterologist with the chief complaint of diarrhea.

Colonoscopy disclosed numerous polyps throughout the colon.

The patient subsequently deve1oped a protein losing enteropathy followed by the clinical picture of toxic megacolon. A colectomy was performed and revealed polyposis affecting the entire colonic mucosa with polyps measuring up to 0.7 em. in diameter. The pati·ent then began passing a large amount of fluid from the e~terostomy stoma, at which time he underwent upper endoscopy and endoscopy through enterostomy stoma. Multiple polyps similar to those found in the colon were identified in the stomach and small bowel.

CONTRIBUTOR: Douglas Kahn, M. D. DECEMBER 1990 - CASE NO. 8 Sherman Oaks, California

TISSUE FROM : Stomach ACCESSION NO. 26146

CLINICAL ABSTRACT:

History: This 62-year-old white male was seen with a 30 to 40 years' history of bright red blood per rectum attributed to hemorrhoids. More recently he had experienced a rapid drop in hemoglobin from 17 to 8.5. He was admitted for elective surgery.

Physical examination: Height 5.'7". Weight 290 lb. Temperature 98.5. Pulse· 88. Blood pressure 164/86. The abdomen was obese, soft and nontender. There were no masses or organomegaly. The bowel sounds were normal.

laboratory report: Hemoglobin 8.5

Radiographs: Barium enema was negat ;l ve; however· an upper G. I. series and CAT scan revealed a lesion in the fundus of the stomach.

Upper G.I. endoscopy demonstrated a large fundal mass with central ulceration suggestive of leiomyoma.

SURGERY: (December 23, 1987)

At surgery, large amounts of lipomatous matter were encountered within the abdomen, but no tumor was identified in the liver or omentum. A large soft mass was palpated in the stomach fundus. An anterior gastrostomy was performed. A very granular, friable hyperplastic mucosa was encountered and a polypoid mass with central ulceration was present. A subtotal gastrectomy was performed.

GROSS PATHOLOGY ;

A section of stomach, measuring 23 x 16 x 5 em. was received. The rugal folds were heightened and exaggerated with innumerable sli-ghtly raised knobby protuberances. An area, 3 em. in diameter, with an irregular slightly polypoid area had central ulcerations.

CONTRIBUTOR: Rodger C. Haggitt, M. 0. DECEMBER 1990 - CASE NO. 9 Seattle, Washington

TISSUE FROM : Stomach ACCESSION NO . 26851

CLINICAL ABSTRACT:

History : Over a period of 5 months, this 60-year-old man developed epigastric pain accompanied by .a 20 pound weight loss and occasional vomiting. During the week prior to admission , he developed peripheral edema .

laboratory report: Pertinent laboratory data included a total protein of 5.2 grams/dl with al bumin 2.7 and gamma globulin 0.8.

At endoscopy, the folds in the fundus and body of the stomach were found to be enlarged, nodular and covered by mucous. Because of a progressive diminution in serum albumin levels and the onset of anasarca, a gastrectomy was performed.

CONTRIBUTOR: Douglas Kahn, M. D. DECEMBER 1990 - CASE NO . 10 Sylmar, California

TISSUE FROM: Rectosigmoid ACCESSION NO. 26755

CLIN ICAL ABSTRACT:

History: This 53-year-old obese Armenian female had a total abdominal hYSterectomy and bilateral salpingo-oophorectomy for Stage IIA adenocarcinoma of the endometrium in June 1gsg. In March 1990, she presented with a 4 to 5 months' history of lower abdominal pain and rectal bleeding. There was no history of weight loss , fever, chi l l s , and constipa tion.

Physical examination: The abdomen was obese wi t h no masses or organomegaly. The bowel sounds ·were normal. There was mild tenderness in the mid abdomen and right lower quandrant.

Laboratory report: Hgb 12.0; Hct 36.2; WBC 77, normal differential; SMAL within normal l imi ts .

Radiograph: Bar ium enema (1-90 ) demonstrated 3-4 em. stricture in mid sigmoid colon with irregular margins. Cannot rule out malignancy. CT scan showed questionable fibrosis or neoplasm of sigmoid colon below which were densities and the lymph nodes did not appear enlarge.d.

SURGERY: (March 21, 1990)

Gynecological int raoperative pel vi c examination reveal ed a mass on the right pel vic wal l with surrounding hypogast ri c lymph nodes and sigmoid stuck to it wi th growth through wall of the sigmoid. The upper abdomen was clear. A right lateral wall biopsy, sigmoid resection with colostomy were performed.

GROSS PATHOLOGY:

The specimen consi sted of a si gmoid colon measuri ng 20 em. and 8 em. in circumference. There was transmural involvement by a polypoid­shaped, 4 x 4 x 2 em. tumor, 3. 5 em. from the surgical margin. The tumor appeared sessile in growth; however, there was transmural involvement with involvement of surrounding gut. The lymph nodes appeared uninvolved .

Lat eral wall mass was a white-ta~ firm tumor, 1.5 x 1 x 0.3 em. in maximum dimension.

CONTRIBUTOR: Rodger C. Haggitt, M. D. DECEMBER 1990 - CASE NO. 11 Seattle, Washington

TISSUE FROM: Colon ACCESSION NO . 26853

CLINICAL ABSTRACT :

History: This 36-year-old man had a 19 year history of ulcerative colitis involving the entire colon. Because his disease was quiescent, he had not seen a physician in many years. He developed signs of colonic obstruction and underwent colectomy.

CONTRIBUTOR: James Keefe, M. D. Tom Bassler, M. D. Inglewood, California

TISSUE FROM: Stomach

CLINICAL ABSTRACT :

DECEMBER 1990 - CASE NO . 12

ACCESSION NO . 26798

History : This 39-year-old white male presented in June 1990 with syncope resulting in a right frontal temporal laceration. Current problems started in October 1988 when he fe ll injuring his back. He had undergone psychiatric t reatment for depression . Despite his marathon running, he had generally felt li ght headed and weak over the past week. He also had vague complaints of "indigestion" forcing him to drink Pepto Bismol "by the bottle". Black stools he felt were secondary to the Pepto Bismol .

Physical examination: BP I26/68; pul se 60; respiratory rate 18; temperature 37. The abdomen was soft and nontender without organomegaly or masses. Bowel sound were normal. Rectal within normal limits; positive for occult blood.

Laboratory report: WBC 10.7; Hgb 5.4; Hct. 18.4.; MCV 63.6:MCH 18.7; platelets 442,000.

Endoscopy : Along the greater curvature of the distal stomach was a sub­mucosal lesion with an ulceration overlying it.

SURGERY: (June 18, i990)

Intraoperative exploration disclosed a normal liver and gallbladder, with no evidence of metastatic disease. In the stomach, a readily palpable proximal gastric tumor was felt. A partial gastric resection was performed.

GROSS PATHOLOGY:

The specimen consis ted of a stomach, measuring 4.5 x 4 x 4 em. and weighed 19 grams. Cut surface was lobulated, gl i stening and gray in color with a 3.5 x 2 em. serosal surface.

CONTRIBUTOR: J. A. Carney, M. 0. Rochester, Minnesota Avram Jacobson , M. 0. Los Angeles , California

TISSUE FROM : Stomach (Case 13A) Mediastinum (Case 13B)

CLINICAL ABSTRACT:

DECEMBER 1990 - CASE NO. 13A & 138

ACCESSION NO. 26829 (Case 13A) 26818 (Case 138)

History: This woman was first seen when she was a 15-year-old school girl. Her blood pressure was 150/110 mm. Hg. A year later she developed generalized weakness and melena with assoc iated anemia. She received iron and blood transfusions. At the age of 17 years; she developed anorexia and postprandial upper abdominal pain.

Physical examina tion: The patient was pale. The blood pressure was 150/ 110. An abdominal mass was palpated, which was described as lemon-sized.

Laboratory report: Urinary level of metanephrines was elevated.

Radi ograph: Upper G.!. examination revea led mul tiple smooth intraluminal filling defects. During a right renal arteriography, a rapid increase in blood pressure occurrred (from 150/110 to 220/150 mm Hg) which was responsive to phento 1 amine.

SURGERY:

Laparotomy and wedge resections of t he st omach were performed . The findings were 10 nodular lesions ranging in size from 0.4 to 5 em. in diameter. There were three additi onal para-aortic tumors, the largest of which was 1.5 em. in diameter, and a tumor in t he omentum .

GROSS PATHOLOGY:

Case 13A: The first gastric resection specimen measured 5.5 x 4.7 x 2.5 em. A polypoid tumor, measuring 3 x 2 x 2 em., was covered by mucosa except for a 1 em. ulcer over the tip of the mass . Numerous sections revealed at least t en different neoplasms in the gastric wall, some no more than 0.4 em. in diameter . Sections of these tumors revealed a soft lobulate gray parenchyma.

The second wedge-shaped specimen measured 8 x 7 x 4 em. and again showed polypoid l esions both under the mucosa and projecting from the serosa . Sections showed numerous tumors in the gastric wall, measuring from 5 to 0.4 em. in diameter. Some of these tumors were fused.

Case 138: The para-aortic tumors meas ured up to 1.5 and 1.2 em. in greatest dimension respectively. Sections showed a homogeneous gray center. Also received were a 3 x 2 x 0. 7 em. segment of adrenal gl and and a 0.6 em. gray-tan nodule from the omentum.

CONTRIBUTOR: Horace L. Spear, M. D. DECEMBER 1990 - CASE NO. 14 Hemet, California

TISSUE FROM: Appendix ACCESSION NO. 23090

CLINICAL ABSTRACT:

History: This 90-year-old Caucasian male presented with a one day history of abdominal pain . Clinical ly the patient was felt to have acute appendicitis.

SURGERY: (October 6, 1978)

A resection of the vermiform appendix was performed.

GROSS PATHOLOGY:

The specimen consisted of a mottled tan to reddish-brown, irregularly-shaped appendix, measuring 8.8 em. in length and up to 1.5 em. in diameter. The adjacent mesoappendix was indurated.

CONTRIBUTOR: Rodger C. Haggitt, M. D. DECEMBER 1990 - CASE NO. 15 Seattle, Washington

TISSUE FROM : Stomach ACCESSION NO . 26847

CLINICAL ABSTRACT:

History: This 67-year-old white woman developed dysphagia, anorexia and a 20 pound weight loss.

Upper GI endoscopy revealed a 4 em. mass at the GE junction. Multiple nodules varying in siz~ from several mil limeters to 2 em. were scattered throughout the body and antrum of the stomach .

Biopsies revealed a squamous cell carcinoma of the GE junction and multiple carcinoids in the stomach .

CONTRIBUTOR: Gene F. Pawl ick, M. D. DECEMBER 1990 - CASE NO. 16 South San Francisco , California

TISSUE FROM: Duodenum ACCESS ION NO. 22021

CLINICAL ABSTRACT:

History: This 55-year-old male was admitted on September 6, 1975 complaining of dizziness, sweating and heaviness in his chest.

On admission the hematocrit was 33.2% and despite mul tiple blood transfusions on September 8, 1975, the hematocrit fe ll to 22%. He was taken to surgery the fol lowi ng day for continued upper gastrointestinal hemorrhage.

Past history: He had vagot.omy and pyloroplasty for upper gastro­intestinal bleeding 15 years ago.

SURGERY: (September 8, 1975)

Exploratory celiotomy , duodenostomy, excision of duodenal mass, co11111on duct exploration, tube jejunostomy and tube gastrostomy were performed .

Findings: A tumor of the second portion of the duodenum was demonstrated at the site. of bleeding . The duodenum was opened longitudinally. The site of bleeding was from a mass which was removed. The mucosa was approximated and cl osed.

GROSS PATHOLOGY:

The specimen consisted of a 6 x 5 x 4.5 em. rounded tan tumor, partially covered by mucosa on ! of the ext ernal surface and bosselated by tumor nodules on the remaining half. The mucosa overlying the tumor was focally ulcerated. On cut surface, there was a soft fish-flesh gray- tan tumor composed of multiple nodules with central hemorrhagic congestion.

CONTRIBUTOR : W. Carroll , M. D. DECEMBER 1990 - CASE NO. 17 Santa Barbara, California

TISSUE FROM: Rectum ACCESSION NO. 18546

CLINICAL ABSTRACT:

History: Thi s 64-year-old woman suddenly developed severe constipation six mont hs prior to admi ssion. Enema at that time yielded bright red blood. Consti pation and bloody stools increased.

Physical examination: Rectal examination revealed a polypoid lesion just above the dentate line that was estimated at 3 x 5 em. in size. The lesion felt mobile.

Laboratory report: Class V Pap smear.

SURGERY: (April 14, 1970)

A 3 em. lesi on was identi fied just above the dentate margai n. A 6-8 em. hepatic lesion felt to be a metastasis was palpabl e on the superior aspect of the right lobe of the liver. An abdominoperineal resection and total hysterectomy were performed.

GROSS PATHOLOGY:

The anorectal resection specimen contained a 4.7 x 3. 4 em. irregular tumor mass st arting 0.6 em . above t he ana l verge. The mass projected 1.3 em. above the surrounding bowel mucosa. The tumor appeared covered by anal epithel ium over the lower hal f and by bowel mucosa at its upper half. Sections showed the tumor to have a gray~white granular appearance. The tumor appeared to extend into the muscularis. Three nodes were identified and one was replaced partially by neoplasm.

CONTRIBUTOR: Jerry Higgins, M. D. DECEMBER 1990 - CASE NO. 18 Panorama City, California

TISSUE FROM: Anus ACCESSION NO. 26810

CLINICAL ABSTRACT:

History: This 37-year-old male had a 10 years' history of passing bright red blood per rectum.

Physical examination: A single hemorrhoid was identified at the- anal verge.

SURGERY:

A hemorrhoidect omy was perfor~ed without incidence.

GROSS PATHOLOGY:

The specimen was a tan n.odule, measuring 2.0 x 1.2 x 1. 1 em. Cut sections showed a congested stroma.

CONTRIBUTOR: Atilia Martinez, M. D. DECEMBER 199D • CASE NO. 19 Costa Mesa, California

TISSUE FROM: Duodenum ACCESSION NO. 25999

CLINICAL ABSTRACT:

Hi story: This 65-year-old woman had symptoms suggestive of gallbladder disease for at least two years. Three weeks prior to admission , she developed right upper quadrant pain with increasing severity.

Radiograph: Upper G.I. series showed a possible ulcer crater in the duodenum.

Endoscopy revea led a polypoid mass projecting into the first portion of the duodenum near the pylorus. There was a possible ulceration of this mass .

SURGERY :

At laparotomy , a mass was seen to be protruding into the duodenum near the pylorus. The distal stomach, pylorus and proximal duodenum with associated lymph nodes were excised. The liver and spleen appeared unremarkable.

GROSS PATHOLOGY:

Upon opening the stomach and duodenal specimens, the gastric mucosa was found to have flattened mucosal folds. As it approached the pylorus, the mucosa took on a deep red appearance with ulceration. At the pylorus , a polypoid mass, measuring 1.5 em. in diameter was noted. The mucosa over this polyp was also bright red in color. Sections through the polypoid mass revealed a thickened mucosa up to 0.9 em. The adjacent duodenum was focally ulcera ted and sections of the duodenal wall showed a fish-flesh appearance. The duodenal ulcer measured 2.4 x 1.3 em. Lymph nodes measured up to 1.6 em.

CONTRIBUTOR: Rodger C. Haggitt, M. D. DECEMBER 1990 - CASE NO. 20 Seattle, Washington

TISSUE FROM: Colon ACCESSION NO. 26B48

CLINICAL ABSTRACT:

History: A 42-year-old woman had a history of intractable diarrhea of 3 months' duration.

Upper GI endoscopy showed a normal esophagus, stomach and duodenum.

At colonoscopy, the endoscope was advanced into the terminal i 1 eum, which was said to 1 ook 1 ike ·~ ha1111burger". The right co 1 on was described as slightly red while the remainder of the colon appeared grossly normal.

Biopsies of the terminal ileum and colon ~/ere obtained and the diagnosis of possible lymphocytic colitis was made. Corticosteroids were administered, but the patient did not respond and required a resection of part .of the small bowel and colon.

CALIFORNIA TUMOR TISSUE REGISTRY

EIGHTY-NINTII SEMI-ANNUAL SLIDE SEMINAR

ON

GASTROINTESTINAL TUMORS

RODGER C: HAGGITI, M.D.

Professor of Pathology Adjunct Professor of Meai.cine DJiector, Hospital Pathology

University of Washington Seattle, Washington

Sunday, December 9, 1990

San Francisco

CASE NO .

I

2

3

4

5

6

7

8

9

10

11

12 13A

13B

14

15

16

17

18

19

20

ACCESSION NO.

26707

26846

26837

26790

26850

26797

26849

26146 26851

26755

26853 26798 26829

26818

23090 26847

22021

18546

26810

25999

26848

MODERATOR:

RODGER C. HAGGITT, M. D. GASTROINTESTINAL TUMORS

PARC FIFTY FIVE HOTEL SAN FRANCISCO, CALIFORNIA

DECEMBER 9, 199D

DIAGNOSIS

Barrett's esophagus with epithelial dysplasia and adenocarcinoma Barrett's esophagus with adenocarcinoma and choriocarci noma Poorly differentiated adenocarcinoma , di ffuse type, with l initis plastica pattern Tubular and villous adenoma involving appendix and cecum with Paneth cells, endocrine cells, and high grade Familial adenomatous polyposis

Hamartomatous polyp of jejunum in a patient with Peurtz-Jeghers syndrome Cronkhi te-Canada syndorme Adenomyoma (myo-epithelial hamartoma) Menetrier's disease

Colon with metastatic endometrial adena­squamous carcinoma of "glassy" cell type Dysplasia compl icating ulcerative colitis Gastric stromal tumor Carney's syndrome with gastric stromal sarcoma (leiomyosarcoma) Carney's syndromre with functioning extra­adrenal paraganglioma Goblet cell carcinoid (adenocarcinoid} Chronic atrophic gastritis with foca l intestinal and pyloric metaplasia and micronodular endocrine cel l hyperplasia Gangl iocytic paragangl ioma

Carcinoma of keratinizing cloacagenic)

the anal canal wi t h non­squamous ( transitional­and pseudoadenoid cystic

Heterotopic gastric mucosa patterns

Well differentiated Jymphoproliferative dis­order of stomach and duodenum (polymorphic lymphoma of MALT vs "pseudolymphoma"} Epitheliot ropic T-cell lymphoma

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CASE I

Diagnosis: Barrett's esophagus with epltheUal dysplasia and adenocarcinoma.

The diagnosis of Barrett's esophagus and its complications presents three challenges for the pathologist: First, does the patient have Barrett's esophagus? Second, does the patient have dysplasia? Third, does the patient have invasive carcinoma or only high-grade dysplasia?

The diagnosis of Barrett's esophagus is complicated by the fact that normal individuals may have columnar epithelium within the lower esophageal sphincter (LES) region, i.e., within the distal 3 em of the esophagus. Thus, in order to document the presence of Barrett's esophagus, columnar epithelium must be identified above the LES region, or above the distal3 em. Since metaplastic columnar epithelium, as defined by the presence of goblet ceUs, is not normally found within the tubular esophagus, its presence is therefore diagnostic of Barrett's esophagus, even when only small amounts of it are present (•short segment" Barrett's esophagus). The forgoing comments should make it apparent that clinical information is essential for the pathologist to conclude that the columnar epithelium present in biopsies said to be from the esophagus is consistent with the diagnosis of Barrett's esophagus.

The diagnosis of dysplasia, as defined by the presence of a neoplastic population of cells still confined within the basement membrane of the epithelium within which it arose, is complicated by the fact that reactive and regenerative changes induced by inflammation or ulceration may closely mimic neoplastic transformation. Typically, neoplastic epithelium in Barrett's esophagus is characterized by progressive distortion of the glandular architecture, decreased mucus secretion in the neoplastic epithelial cells, enlarged, hyperchromatic, crowded, stratified nuclei that tend to lose their polarity as the dysplasia progresses and extension of the above cytologic changes to involve the surface epithelium. We have found excellent correlation between the histologic diagnosis of dysplasia and flow cytometric abnormalities; thus, flow cytometry may prove to be a valuable adjunct in the diagnosis of dysplasia in Barrett's esophagus.

Not all authorities agree on the indications for esophagectomy in Barrett's esophagus. Some recommend this procedure for hlgh-grade dysplasia alone, while others recommend esophagectomy, in general, only for invasive carcinoma and for a few selected patients with high-grade dysplasia alone. Thus, the distinction between high-grade dysplasia and invasive carcinoma is a critical one. If malignant cells invade through the basement membrane and permeate the lamina propria, the diagnosis is usually fairly easy. When sheets of neoplastic epithelial ceUs expand in a cribriform pattern of back-to-back glands, the diagnosis is Jess obvious and I am not aware of objectively tested criteria for recognizing invasion in thls context. Occasionally, adenocarcinoma in Barrett's esophagus is well differentiated to the point that it could only be recognized by noting that it had invaded into the submucosa, a requirement that usually cannot be fulfilled with endoscopic biopsies because of their superficial nature.

Our prospective follow-up studies suggest that flow cytometric abnormalities, and particularly the development of multiple aneuploidies, may prove to be valuable in planning management for these patients in the future.

References

! . Haggitt RC, Reid BJ, Rubin CB, et al: Barrett's esophagus: Correlation between mucin histochemistry, flow cytomctry and histologic diagnosis ror predicting increased cancer risk. Am J l'atho/1988;131:53.{;1.

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Haggitt, RC, Dean PJ: Adenocarcinoma in Barren's Epithelium. In: Spechicr SJ, Goyal R, eds: Bamtt's Esophagus: Pathophysiology, Diagnosis, Md MMG~tnt. Elsevier, New 'York,198S, pp. 153-166.

Hameeteman W, Tvtgat GNJ, Houthoff HJ, et al: Barrett's esophagus: Development of dysplasia and adenocarcinoma. Gastrocnttn:>iogy !989:96:1249-1256.

Hamilton SR, Smith RRL, Camerson n.: Prevalence and charaaeri.slics of Barren's esophagus in patients with adenocarcinoma of the esophagus or csophagogutric junaion. Hum Patho/1988;19:942-943.

Paull A1 Trier JS, Dalton MD, et al; The histologic spectrum of Barren 's esophagus. N El>g J Mcd 1976;29):476-480.

Rabinovitch PS, Reid BJ, Haggill RC, et a1: Progression to cancer in Barrett's esophagus is associated with genomic instability. lAb lnvut 1989;60:65-71.

Reid BJ, Haggitt RC, Rubin CE, et al: Observer variation in the diagnosis of dysplasia in Barren's esophagus. Ilum Pathoi!988;19:!66-J18.

Reid BJ, Haggitt RC, Rubin CE, Rabinoviteh PS: Flow cytometry complements histology in detecting patients at risk for Barrett's adenocarcinoma. G~nrtnt>logy 1987;93:1-11.

Reid BJ, Weinstein WM, Lewin KJ, Haggiu RC. eta!: Endoscopic biop>ies diagnose hish grade c!ysplasio or early operable adenocarcinoma in Barrett's esophagus. without g<O$.!Iy recognizable neoplastlc lesions. Gasu-o.nterology 1988:94:81-90.

10. Spechler SJ, Goyal RJ<; Barrett's esophagu•. N EngJ Mod 1986;315:362-371.

CASE2

Diagnosis: Barrett's esophagus wllh adenocarcinoma and choriocarcinoma.

The histologic sections from the esophageal neoplasm in this patient disclose a spectrum of changes including Barrett's specialized metaplastic epithelium, dysplasia, adenocarcinoma and areas of choriocarcinoma as defined by the presence of syncytiotrophoblastic and cytotrophoblastic differentiation. Immunohistochemical staining demonstrated beta-hCG. Choriocarcinoma of tne gastrointestinal tract is rare. Most of the reponed cases arose in the stomach, but all areas of the gastrointestinal tract have been the site of these neoplasms, including the esophagus. In the majority of cases, the choriocarcinoma is associated with otherwise typical adenocarcinoma of the site. The prognosis for patients with choriocarcinoma of the gaSlrointestinal tract is poor with a mean survival of a few months.

Non-gestational choriocarcinomas may arise in germ cells in the gonads, in teratomas and in "ectopic" sites such as the retroperitoneum, mediastinum and pineal body. They have also been described in association with carcinoma in many different organs, particularly the gastrointestinal tract, including the pancreas, biliary tree and liver. They have also been described in the lung, breast, prostate, bladder and other sites.

In contrast to choriocarcinoma, hCG is commonly present in adenocarcinomas of the gastrointestinal tract that have no morphologic evidence of trophoblastic differentiation. Detectable serum hCG has been reported in 17% of patients with gastric cancer, and the beta subunit has been found in up to a third of gastric cancers by immunohistochemistry. The beta subunit can also be demonstrated in adenocarcinomas of the colon and has been found in up to 28% of such tumors by immunohistochemistry. Beta-hCG is present in the mucous neck cells of the normal gastric antrum and in the gastric body and fundus in glands with pyloric metaplasia. The beta subunit has not been detected in the normal colon. The presence of beta-hCG in normal stomach raises the

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question of whether choriocarcinomas of the stomach arise from these ceUs or whether they arise from neoplastic ceUs in which there is deregulation of gene expression. The answer to this question is not known.

The alpha subunit of human chorionic gonadotropin is identical to the alpha subunits of the other glycoprotein hormones (LH, FSH and TSH). The alpha subunit is found in normal gut endocrine cells and in carcinoids, but bas been described only rarely in neoplastic epithelium.

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References

Fukayama M, Hayashi Y, Koike M: Human chorionic gonadotropin in the rectosigmoid colon. Am I Pa~hol 1987;127:83-89

Garcia RL, Shali VS: Gastric choriocarcinoma and yolk sac tumor in a man: Obsetvations about its possible origin. Hum Patho/ 1985;16:955-958

Kikuchi Y, Tsuneta Y, Kawai T, Aizawa M: Choriocarcinoma of the esophagus producing chorionic gonadotropin. Acta Patlrol Ipn 1988;38:489-499

Kodama T, Kameya T, Hirota T, et al: Produaion of alpha-fetoprotein, normal serum proteins, and human chorionic gonadotropin in sromach cancer. Cancer 1981;<13:1647-1655

Krulewski T, Coh.en LB: Choriocarcinoma of Ihe stomach: Palhogenesis and clinical characteristics. Am J Gastrotnterol 1988;&3: 1172-1175

Kubosawa H, Nagao K, Kondo Y, er al: Coexistence oi adenocarcinoma and choriocarcinoma in the sigmoid colon. Cancer 1984;54:866-868

Mana beT, Adachi M, Hirao K: Human chorionlc gonadotropin in normal, inflammatory and carcinomatous gastric tissue. Gastroe11terology 1985;89:1319·1325

Ordonez NG, Luna MA: Choriocarcinoma of the colon. Am I Gastrotntero/1984;19:39-42

Ramponi A, Angeli G, Arceci F, Puuuoli R: Gas<ric choriocarcinoma; an immunohistochemical srudy. Path Res l'ract 1986;181:390-396

10. Saigo PE, Brigati DJ, Sternberg SS, et al: Primary gastric choriocarcinoma. Am J Surg Parho/1981;5:333-341

CASE3

Diagnosis: Poorly differentiated adenocarcinoma of stomach, diffuse type, with linitis plastica pattern.

This case represents a carcinoma of the diffuse type as defined by Lauren, who classified gastric carcinomas as intestinal (resembling colonic cancer) (53%), diffuse (33%) and mixed (14%), and found epidemiologic and prognostic differences in these patterns. The diffuse type occurs more frequently in females, in younger patients, is more frequently distal and infiltrating, and has a poorer 5 year survival rate when compared to carcinomas of the intestinal type.

Carcinomas of the intestinal type form glands whose histologic appearance, ultra­structure and histochemistry denote a close resemblance to intestinal epithelium. Since many, or most, of these carcinomas are associated with intestinal metaplasia, they are presumed to arise from it. The diffuse type of gastric cancer does not form the clearly defined glands seen in the intestinal type but infiltrates as individual ceUs, often signet ring cells, or has only abortive, ill-defined gland formation. Histochemical ·and ultrastructural studies .show that the cells of diffuse carcinomas also have features suggesting intestinal differentiation. The term "diffuse" is somewhat of a misnomer for these lesions as they do

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not always have diffuse infiltration, and in fact the diffuse pattern may be seen in early gastric cancers (defined as a cancer that is limited to the mucosa and submucosa). The diffuse type of gastric cancer is not synonymous with linitis plastica, as this term refers to a gross pattern of a diffusely thickened gastric wall and can be produced by either the diffuse type (85%) or the intestinal type (15% ). The diffuse type of gastric cancer often shows wider dissemination than the intestinal, and is more frequently associated with peritoneal metastasis, pulmonary lymphatic permeation and Krukenberg tumors of the ovary. The intestinal type involves the liver more frequently and extensively.

Many diagnostic pitfalls confront the pathologist faced with a gastric biopsy in which the clinical or pathologic differential diagnosis includes gastric cancer. The diffuse type of cancer can be very subtle in biopsies as individual cells may sparsely infiltrate the lamina propria and be difficult to identify. Regenerative hyperplasia, as seen in erosive gastritis, may be mistaken for the intestinal type of gastric cancer. In general, atypical foveolar or surface mucous cells are much more likely" to indicate a reactive change, even though their nuclei may be quite atypical. Reactive epithelial cells in individuals who have received hepatic arterial infusion chemotherapy may be particularly atypical. The granulation tissue in benign ulcer craters may contain very atypical, even bizarre endothelial cells, fibroblasts and other unidentifiable cells. One avoids the pitfall of calling these malignant by being very circumspect about making the diagnosis of carcinoma when granulation tissue is present, and then insisting upon seeing sheets or clusters of cells with malignant features, rather than individual stromal cells.

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References

Cady B, Ramsden DA, Stein A, et al: Gastric cancer: contemporary aspects. Am I Surg 1977;133:423-429.

Cady B, Rossi RL, Silvennan ML, eta!: Gastric adenoca:rcinoma.An:h Surg 1989;124:303·308

Da•essar K, Pezzullo JC, Kessimian N, et al: Gastric adenocarcinoma: Prognostic significance of =eral pathologic param.eters and histologic classifications. Hum Patho/1990;21:325-332

Duane I, Uanos 0: Patterns of metastases in intestinal and diffuse types of carcinoma of the stomach. Hum Palho/1981;12:231·242.

Eckardt VF, Giebler W, Kanzler G, et a!: Clinical and morphologic characteristics of early gastric cancer. Gastroenterology 1990;98:70&. 714

Isaacson P: Biopsy appearances easily mistaken for malignancy in gastrointestinal endoscopy. Histopalhotogy 1982;6:377.389.

lauren P: The two histol~cal main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt a l a histoclinical classification. Acta Path Microbiol Scand I%5;64:31-49.

Ne.alainen TJ, JaJVi OH: Ultrastructure of intestinal and diffuse type gastric carcinoma. J Pat/to/ 1977;122:129·136.

Noguchi Y, Imada T, Matsumoto A, et al: Radical surgery for gastric cancer. Cancer 1989;64:2053·2062

10. Thunnissen E: Biopsy appearances easily mistaken for malignancy in gastrointestinal endoscopy. Histopathology 1983;7:141-142.

CASE4

Diagnosis: Tubular and villous adenoma Involving appendix and cecum with Paneth cells, endocrine cells! and high-grade dysplasia.

This case was selected for presentation to highlight some of the problems in diagnosis and nomenclature of colonic neoplasms. This case was originally classified as an

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adenocarcinoma ansmg in a villous tumor of the appendix and cecum. Although cytologically malignant cells are present within the lesion, there is no invasion outside of the basement membrane of the glands or villi within which these cells are present. Thus, if we define adenocarcinoma of the colon by the presence of invasion below the muscularis mucosae, as most gastrointestinal pathologists do, this tumor does not contain cancer. There is no convincing report of metastasis from a colorectal neoplasm that did not have invasion below the muscularis mucosae. Accordingly, while the cells within an adenoma may be cytologically malignant, and may even invade the lamina propria, as a practical matter, the diagnosis of adenocarcinoma should be restricted to those tumors in which there is invasion below the muscularis mucosae. AlternatiVely, the diagnosis of adenocarcinoma could be made but qualified by appending "in-situ" or "intramucosal" and by making a comment to the effect that these lesions have no biologic malignant potential and require nothing more than complete local excision.

Other interesting aspects of this tumor include the presence of numerous Paneth cells and endocrine cells. These cells within adenomas and carcinomas of the colon are well recognized and have no influence on prognosis.

The young age of this patient raises the possibility of whether he has a genetic syndrome predisposing him to the development of colonic neoplasms. Since he does not have multiple adenomas, familial adenomatous polyposis seems unlikely. A more likely possibility is that he has one of the hereditary nonpolyposis colorectal cancer (HNPCC) syndromes (Lynch syndromes). A family is defined as having the HNPCC syndrome if the following clinical features are present: An increased incidence of colonic carcinoma with an early age of onset, an autosomal dominant pattern of .inheritance, a predominance of proximal colon cancers, an excess of multiple primary cancers and a more favorable five year survival than a control group of patients. Lynch divided the HNPCC syndromes into two categories, one in which the patients have a predisposition to colorectal carcinoma alone and the other group having an association with other forms of cancer, including endometrial, ovarian and possibly gastric and breast cancers. Because of the autosomal dominant pattern of inheritance, the theoretical !lifetime prevalence of colon and/or other cancers in these syndromes is 50%. The adenomas from which the cancers in these patients presumably arise tend to be located in the right colon, as one would expect because of the predominance of carcinomas in the right colon. These adenomas are often only slightly elevated above the mucosa and have been referred to as "flat" adenomas.

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References

Gibbs NM: Incidence and significance of Paneth celts i!n some tumors oJ the large intestine. J Clin Parhol 1967;20:826-831

Ho SB, Itzkowitz SH, Fricra AM, et al: Cell lineage markers in premalig>1ant and malignant colonic mucosa. Gastroenterology 1989;97:392-404

Lanspa SJ, Lynch HT, Smyrk TC, et al: Colorcctat adenomas in the Lynch syndromes. Gastroenterology 1990;98:1117-1122 '

Lewin K: Neoplastic paneth cells. J Clin Path()/ 1968;21:476479

Lynch HT, Watson P, Kriegler M, et al: Differential diagnosis of hereditary nonpolyposis cotorecrat cancer (Lynch syndrome I and Lynch S)ondrome m. Dis Colon Recrwn 1988;31:372-377

Smith DM, Haggilt RC: The prevalence and progn.ostic significance of argyrophil cells in colorectal carcinomas. Am I SurgPmllo/1984;8:123-128

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CASES

Diagnosis: Familial adenomatous polyposis of the colon.

The colectomy specimen from this patient contained several hundred adenomas, and is therefore diagnostic of familial adenomatous polyposis of the colon. More than 100 adenomas within the colon is considered diagnostic of FAPC as all patients with the hereditary syndrome in the St. Mark's Hospital (London) Register had more than 100 polyps. F APC is transmitted as an autosomal dominant trait and the gene responsible for the condition has recently been mapped to chromosome 5. The adenomas first appear at around the age of puberty and by the age of 35 years, approximately 50% of affected individuals will have developed adenomas. Patients in whom the phenotype did not become manifest until they were over the age of 70 have been reported. Gardner syndrome, in which FAPC is accompanied by osteomas of the skull and mandible, multiple epidermoid cysts, abnormal dentition, dentigerous cysts, abnormal mandibular bone structure and desmoid tumors, is now known to be caused by an abnormality in the same gene on chromosome 5 responsible for F APC, but may be due to a different point mutation within the gene. Adenomas in FAPC are not limited to the colon and have been reported in the stomach and small intestine as well; however, carcinoma in these sites is much less common than in the colon and reaches a peak of 12% at the ampulla ofvater.

Investigators at the University of Utah have recently shown that •sporadic" colonic adenomas and, by extrapolation, carcinomas, are the resull of an inherited susceptibility. They drew this conclusion from a study of kindreds who had sporadic colorectal cancers and calculated that the inheritance was autosomal dominant and the gene frequency in the generall?opulation approached 20%, a level that is high enough to account for the majority of colome neoplasms observed clinicaJJy. Environmental factors are clearly important in producing adenomas/carcinomas in genetically susceptible individuals.

The advances in molecular biology that permilled localization of the gene for F APC to chromosome 5 have also been applied to investigations of the genetic events in •sporadic• colon cancers. A high prevalence of allelic deletions in multiple chromosomes has been identified, but there is a particularly high frequency of deletions in chromosomes 17p and 18q. The total number of allelic deletions, expressed as fractjonal allelic loss, correlates withJ>rognosis, as do deletions in chromosomes 17p and 18q.

The importance of environmental effects in the pathogenesis of colorectal carcinoma is emphasized by the observations that rectal adenomas regress in F APC patients who undergo subtotal colectomy with ileoproctostomy, by fluctuation in size of adenomas seen in pregnant females and most recently by the observation that Sulindac, a non-steroidal antiinflammatory drug, can cause regression of adenomas in FAPC patients.

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References

Alexander JR, Andrews JM, Buchi KN, et a1: High prevalence or adenomatous polyps or the duodenal papilla in familial adenomatous polyposis. Dig Dis Sci 1989;34:167·170

Baker SJ, Fearon ER, Nigro JM, ct al: Chromosome 17 deletions and pSJ gene mutations in colorcctal carcinomas. Science 1989;244:217·221

Burt RW, Bishop T, Cannon LA, et al: Oom_inanr inheritance of adenomatous colonic polyps and colorectal cancer. N Eng J Med 1985;312:1S40-IS44

Cannon·Albright IA, Skolnick Mli, Bishop T, et al: Common inheritance or susceptibility to colonic adcnomatous polyps and associated colorectal cancers. N Eng J Mtd 1988;319:533-537

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Iida M, Yao T, ltoh H, et a!: Natural history of duodenal lesions in Japanese patients with famil.iaJ adenomatous coli (Gardner's syndrome), Gastro<nt<rology 1989;96:1301-1306

lida M, Yao T,ltoh H, et at: Natutal l)istory of gastric adenomas in patients with familial adenomatous coli/Gardner's syndrome. Cancer 1988;61:60~11

Jagelman DG, DeCosse JJ, Bussey HJR, et al: Upper ,gastrointestinal cancer in familial adenomatous polyposis. The Lancet, May21, 1988;1149·1150

Kern SE, Fearon ER, Tcrsmette KWF, et al: Allelic loss in colorectal carcinoma. lAMA 1989;261:3099·3103

Law OJ, Olschwang S, Monpezli.t J.p, et al: Concened nonsystemic allelic loss in human colorectal carcinoma. Science 241;961·965

10. Leppert M, Dobbs M, Scambler P, et al: The gene for familial adenomatous polyposis coli maps to the long arm of chromosome 5. Science 1987;238:1411-1413

11. Solomon .E,. Voss R, Hall V, et al: Chromosome 5 allele loss in human colorectal carcinomas. Naltll'f! 1987;328-616-619

12. Vogelstein B, Fearon ER, Hamilton SR, et lit Genetic alterations during colorectal-tumor development. N Eng J Med 1988;319:525-532

13. Vogelstein B, Fearon ER, Kern SE, et al: Allelotype of oolorectal ea.rcinomas. Science 1989;244:207-211

14. Waddell WR, Ganser GF, Cerise EJ, {.()ughry RW: Sulindac for polyposis of the colon. Am J Swg 1989;157:175-179

CASE6

Diagnosis: Hamartomatous polyp of jejunum in a patient with Peutz·Jeghers syndrome.

Peutz-Jeghers syndrome (PJS) is an inherited condition defined by the presence of hamartomatous polyposis of the gastrointestinal tract and melanin spots on the lips and buccal mucosa. PJS is inherited as an autpsomal dominant trait. The hamartomas are found most frequently in the smaJJ bowel ( 64-96% of cases), but are only slightly less frequent in the stomach and colon. Because rectal polyps have been reported in only 24-32% of cases, sigmoidoscopy is less useful in diagnosis than it is in F APC. The polyps of PJS are composed of normal elemen.ts in_cjjgcmQY~ to. the site in !Vhich they_a~ise1 but in which the architecture -IS markedly abnormal. Histologically, the lesions usually have an arbonzmg pattern with fronds covered by normal epithelium that incorporates all the cell types usually located in the site of origin. Smooth muscle forms an important component of the lesions and extends into the branching fronds of the polyp. Benign glands may be surrounded by smooth muscle and may extend into the submucosa, the muscularis propria, or even completely through the intestinal wall in a manner analogous to misplaced epithelium in a colonic adenoma.

Carcinoma of the gastrointestinal tract appears to be an infrequent complication of PJS and occurs in 2-12% of patients. Well documented ~eports of carcinoma arising in PJS hamartomas have appeared, and in some cases there was associated hamartomatous or dysplastic change within the hamartoma. Most of the reported carcinomas of the gastrointestinal tract in patients with PJS have not had evidence of origin from a hamartoma, but rather from co-existing adenomas. Recent evidence suggests a high risk of death from non-gastrointestinal carcinomas in patients with PJS that may be as much as 18 times greater than the expected rate in the general population.

The melanin spots of PJS are present in over 95% of the patients and occur most commonly on the !ie_s (95%) and bu~ mucosa (66-83%), but a:re found also on circumoral and faciaf'skin, on the palrris and soles, and on the digits. ·----

An unusual ovarian tumor known as "sex cord tumor with annular tubules" can be identified in almost all female patients with PJS if the ovaries are examined carefully. These tumors are usually asymptomatic, small, multifocal and bilateral. In patients without PJS •. they are typically larger, unilateral, and do not have foci of calcification as frequently. Another ovarian tumor thought to be unique to PJS is the "distinctive ovarian sex cord· stromal tumor with sexual precocity". Well differentiated adenocarcinoma of the uterine cervix (adenoma malignum) has also been described with increased frequency in patients with PJS.

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References

Banholomew LG, Moore CE, Dahlin DC, Waugh JM; lntestinal polyposis associated with mucocutaneous pigmentation. Surg Gynecol Obste/1962;115:1-11.

Erbe RW: Inherited gastrointestinal-polyposis syndromes. N Eng! Mtd 1976;294:1JOJ.i104

Giardicllo FM, Welsh SB, Hamilton SR, et al: Increased risk of cancer in the Peutz.Jeghers syndrome. N Eng J Med 1987;316:1511-1514

Gilles CB,. Young RH, Aguirre P, et al: Adenoma malignum (minimal de•;iation adenocarcinoma) of Lhc. uterine c.ervi>r. a elinic.opathological and immunohistochemical analysis of 26 cases. Am J Surg /'athol 1989;13:717·729

Hart WR, Kumar N, Crissman m: Ovarian neoplasms resembling sex cord tumors with annular tubule.~. Cancer 1980;45:2352-2363

Linos DA, Dozois RR, Dahlin DC, Banholomew LG: Does Peutz.Jeghers syndrome predispose to gastrointestinal malignancy? Arch Surg 1981;116:1182·1184

Matuehansky C, Babin P, Coutrot S, et al: Peutz-Jeghers syndrome with metastasizing carcinoma arising from a jejunal hamanoma. Ga.rtrMnterr>lOt:J 1979;77:1311-1315

Miller U, Banholomew LG, Dozois RR, Dahlin DC: Adenocarcinoma of the rectum arising in a hamanomatous polyp in a patient with Peutz.Jeghers syndrome. Dig Dis Sci 1983;28:1047-1051

Perzin KH, Bridge MF: Adenomatous and carcinomatous changes in hamanomatous polyps of the small intestine (Pcutz..Jeghers syndrome): report of a case and review of the literature. Cancer 1982;49:971·83

10. Scully RE: Sex cord tumor "'ith annular tubules: a distinctive ovarian tumor of the Peutz-Jeghers syndrome. Canctr 1970;25:1107·1121

U. Shepherd.NA, Bussey HJR, Jass JR: Epithelial misplacement in Peutz.Jeghers polyps: a diagnosric pitfall. Am J Surg /'athol 1987;11:743-749

12. Utsunomiya J, Gocho H, Miyanaga T, et al: Peutz·Jeghers syndrome: its natural course and management. John H Mod J 1975;136:71~2

13. Young RH, Diclcersin GR. Scully RE: A distinctive ovarian sex cord-stromal tumor causing sexual precocity in the -peutz.Jeghers syndrome. Am J Surg l'at!toll983;1:233-243

14. Young RH, Welch WR. Dickcrsin GR, Scully RE: Ovarian sex cord tumor with annular tubules. Review of 74 cases includin.ll 27 with Peutz-Jeghers syndrome and four with adenoma malignum of the cervix. Cancer 1982;50:1384-1402

CASE7

Diagnosis: Cronkhite-Canada syndrome

Cronkhite·Canada syndrome is a rare, non-inherited condition characterized by generalized gastrointestinal polyposis, cutaneous ~hyperpigmentation, alopecia and atrophy of the nails. = A:lthough nutritional; infectious and immunologic associations have been considerea, the etiology of this syndrome remains unknown. The entire gastrointestinal tract is involved with polyps that may number in the hundreds and range from a few

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millimeters to 3 em or more in diameter. Microscopically, the polyps are quite similar to juve'li!_e..!X>Iyp~-with dilated, irre~arly shaped glands set in an inflamed and edematous stroma. llnlikeJuve@e polyposis;Jiowever, the mucosa between the polyps is also liiStOrogicalJy abnormal with edema, dilated crypts, and variable degrees of inflammation of * lamina propr-ia. Adenomatous change and colon cancer have tieen reported in Cronkhite-Canada syndrome polyps and the overall prevalence of colon cancer in these patients is around 15%.

Most patients with Cronkhite-Canada syndrome present with diarrhea and weight loss secondaey to excess mucus secretion bY...£.rypLcell$, Variable degrees of fat and disaccharide malabsorption alSo occur, probably because of a decreased absorptive surface. The syndrome has an acute onset and a rapidly progressive course that frequently leads to death from profound malnutrition. -I.

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References

Burke M, Sobin LH: The patholoSY of Cronkhite-Canada polyps: a comparison to juvenile polyposis. Am 1 Suf8 Patho/1989;13:940.946

Cronkhite LW Jr, Canada WJ: Generalized ga.'itrointescinal polyposis: on unusual syndrome, /'ostgmd M<d 1 I 973;252: 1011

Daniel ES, Ludwig SL, Lewin KJ, et al: The Cronkhite-Canada syndrome: an analysis or clinieal and pathologic features and therapy in 55 patients. Medicine 1982;61:293

Jenldns D, S<ephenson PM, Scou BB: The Cronkhile-Canada syndrome: an ultrasuuctural Study of pathogenesis. 1 Clitt l'<Uhol 1985;38:271

Ka1ayama Y: Cronkhite-Canada syndrome associated with r ectal cancer and adenomatous changes in colonic polyps. Am I SUf8 Palho/1985;9:65

Lin H-J, Tsai Y-T, Lee S.D, et al: The Cronkhite-Canada syndrome with focus on immunity and infection. 1 C/111 Grutro<tttero/1981;9:568

Malhotra R, Sheffield A: Cronkhite-Canada syndrome associa1ed wilh colon carcinoma and adenomotous changes in C.C polyps. Am I Grutrotntcro11988;83:m

Peart AG Jr, Sivak MV, Rankin OB, et al: Spontaneous irnpr011cmcnt of Cronkhite-Canada S)'ndromc in a postpartum female. Dig Dis Sci 1984;29:470

Rapp.aport LB, Sperling HV, S<ovrides A: Colon cancer in the Cronkhite-Canada syndrome. J Clin GDStrO<nttro/1986;8:199

10. RusseU DM, Bhathal PS, St. John DJB: Complete remission in Cronkhitc-Canado syndrome. Gruuwnterology 1983;85:180

CASES

Diagnosis: Adenomyoma (myo-epithelial hamartoma) or stomach.

Adenomyoma of the stomach occurs almost exclusively in the antral or pyloric region and presents as a polypoid mass projecting into the lumen, as an expansile mass within the gastric wall, or as a mass projecting from the serosal surface of the stomach. All the reported examples have been solitaey and localized. Histologically, the lesions are composed of gi.!!Dl:!ula(_or ... ductular elements that are lined by cells that resemble gastric foveolar (surface) cells, cells of the antral glands, the cells of "6runner's glands or the columnar ceUs of pancreatic ductal epitnelium. Squamous metaplasia Is occasionally present. The cnaracteristic feature of the lesion is bundles of hypertrophic smooth muscle surrounding the epithelial lined structures. The lesion may be located in the submucosa, the muscularis propria or the subserosa! region. In one-third of the reported cases,

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heterojopic pancreatic tissue was present within the lesion. Such tissue, when present, may be confineoto sma.tl. foci and difficult to identify without multiple sections. Most authors prefer to designate adenomyomas in which pancreatic tissue is identified as heterotopic pancreas, but the biologic significance is precisely the same. Another name applied to these lesions is myo-epithelial hamartoma.

Radiologically and by endoscopy, adenomyomas of the stomach have the appearance of benign extramucosal, intramural lesions that are covered by normal mucosa or by....mucosa f!iat IS iiiillst"lrtJ!Ulsha@e- from that in the remainder df the sfomach. Occasionally a dimple projecting into the center of the lesion is seen and may be the orifices of ductular or glandular structures within the lesion.

Adenomyoma of the stomach must be differentiated from a lesion known as diffuse cystic glandular malformation of the stomach. Synonymous terms for this abnormality include diffuse submucosal cysts, gastritis glandularis et cystica profunda and gastritis cystica profunda. In each of these, the "process differs from adenomyoma in that it is diffuse and consists of herniations of gastric mucosa through the muscularis mucosae into theSubmucosa. A significant number of cases of diffuse submucosal cysts of the stomach have been associated with either dysplasia or adenocarcinoma. A similar lesion may be seen in patients with Menetrier's disease and in the gastric mucosa adjacent to gastroenterostomy stomas. The presumed common pathogenetic mechanism in Menetrier's disease and in the post-gastrectomy stomach is mechanical trauma from peristalsis pulling on the enlarged folds of gastric mucosa with secondary hyperplasia of the muscularis mucosae and herniation of glands into the submucosa. The mechanism by which the mucosa herniates into the submucosa in patients with diffuse submucosal cysts is not clear from the few reported cases, but may be similar.

References

1. Franzin G, Novelli P: Gastritis cyaticn profunda. }[l$topalhofcgy t981;5:SJS-S47

2. Honore LH, Lewis AS, O'Hara KE: Gastric glandularis e1 cysllcn profunda: a report of three c:~ses with discussion or etiology and pathogenesis. Dig Dis Sci 1979;24:48-52

3. Hui Y -z. Qian-Xin G: Adenomyoma or the stomach presenting u an antral polyp. Hi.stopaJIJology 1989;99· 101

4. lwanaga T, Koyama If, Takah!Uhi Y, ct al; Diffuse wbmveosal cysu and carcinoma of the stomach. Canctr 1975;36:606-614

5. LaMer A, Kovfman WB: Adenomyoma or the stomach. Dig .Dis 19n;22:965-969

6. Pillny !, Petrelli M: Diffuse cystic glandular malfonnation <or the Slomach associated with adenocarcinoma. Ca11ctr 1976;38:915-920

CASE9

Diagnosis: Menetrier's disease

Menetrier's disease is a hyperplastic gastropathy in which the essential lesion is foveolar ~urface) cell hyperplasia producing large gastric folds. The hyperplastic foveolar cells displace parietal ceUs, causing hypochlorhydria, and secrete large quantities of mucin resulting in hypoproteinemia. There may also be "leaky" tight junctions between epithelial ceUs in this condition. The etiologic factor responsible for initiating the foveolar cell hyperplasia has yet to be elucidated, with the possible exception of Menetrier's disease in children, in whom a relationship to cytomegalovirus infection has been proposed. Gastric

10

biopsies from patients with Menetrier's disease show foveolar cell hyperplasia with dilatation of gastric glands. Parietal cells are usually not recognizable in clinically symptomatic cases. Strands of smooth muscle may extend from the muscularis mucosae into the lamina propria, a reflection of traction on the large folds. The hyperplastic foveolar cells may be depleted of mucin and have hyperchromatic, enlarged nuclei that can be mistaken for dysplasia or carcinoma. Since patients with Menetrier's disease have an increased incidence of carcinoma of the stomach, the biopsy should be carefully examined for evidence of this complication. Menetrier's disease in children differs from that in adults in being a benign, self-limited condition and, as mentioned above, has been related to cytomegalovirus infection in a few patients.

Menetrier's disease is one of the less common causes of foveolar cell hyperplasia in gastric biopsy material. Hyperplastic foveolar cells are highly characteristic of the post­gastrectomy stat.e and are the main histologic hallmark of •reflux• gastropathy. This lesion is thought to be caused by reflux of bile into the stomach and is characterized by capillary congestion, edema, smooth muscle ·extension into the lamina propria and a paucity of inflammatory cells, in addition to the foveolar hyperplasia. Foveolar hyperplasia may also be seen in patients taking non-steroidal antiinOammatory compounds, in the regenerating mucosa at the edge of ulcer craters, and in a number of different types of polyp, including hyperplastic, juvenile, Peutz..Jeghers and Cronkhite-Canada polyps. The biopsy alone may not be adequate to differentiate these various entities and the clinical history becomes critical in establishing the correct diagnosis.

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References

Bechi P, Amorosi A, Mazzanti R. Romagnoli P, Tortclli L: Gastric hlstolog)' and fasting bile rcOux after partial gastrectomy. Gastr()tnttrology 1987;93:335-343.

Chouraqui JP, Roy CC, Brochu P, ct al: Menerrier's .disease In children: repon of a patient ond review of sixteen other cases. GastrO</It<rology 1981;80:1042-1047

Davis JM, Gray, GF, and Thorbjamarson B: Menetrier's disease: A ciinicopathologic •tudy or six cases. Ann Swg 1977;185:456-461.

Dixon MF, O'CoMor HJ, Axon ATR. King RFJG, Johnston D : ReOux gaotritis: Distina histopathological entity? J Clin Pl11hoi1986;39:52.4-S30.

Franzin G, Novclli P: GAStritis cystica profunda. H'wopalhology 1981;5:535-547

Kelly DG, Miller U , Malagelada J-R. et al: Giant hypen.rophic gastropathy (Menetrler's disease): pharmacologic effeas on protei.n leakage and mucosal ultra5tNaurc. Gastroenterology 1982;83:581-589

Lam SK, Hui WKK, Ho J, et al: Pachydermoperiostoob, hypertrophic gastropathy, and peptic ulcer. Gastrotnttrology 1983;84:834-839

Palmer ED: What Mcnetrier really said. GastrointtstinQ/ Etodoscopy 1968;15:83-90

Scharsclunidt BF: The natural history of hypenrophic gaslropathy (Menetrier's disease): Report of a case with 16 year foUo:>w-up and review of 120 cases from the literature. Am J Mtd 1977;63:~2..

10. Searcy RM, Malagelacla J-R: Meneuiet's disease and idiopathic hypenrophic gastropathy. Ann lnt Mtd 1984;100:565-5'10

11. Sferra TJ, Buk U , Qualman SJ, et al: Menetriet's dise~ in children: a cytomegaloviNs (CMV) induced gastropathy? Gastroenterology 1990;98:A122

\2. Wood GM, Bates C, Brown RC, Losowsky MS: lntramueosal carcinoma of the gastric antNm. J CU11 Patio of 1983;36:1071-1075

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CASElO

Diagnosis: Colon with metastatic endometrial adenosquamous carcinoma of "glassy" ceU type

The colonic carcinoma in this patient is a poorly differentiated adenocarcinoma in which areas with a "squamoid" appearance are present. The latter are characterized by large cells with sharply defined cell borders, abundant, granular, pale pink cytoplasm and large nuclei with prominent nucleoli. This histologic appearance is identical to that of the adenosquamous carcinoma of the endometrium removed 9 months previously. The large cells with abundant, pale pink cytoplam and sharply deftned cell borders indicate this is the "glassy• cell variant of adenosquamous carcinoma of the endometrium, a rare variant that was ftrst described by Christopherson and AlberhaskY in 1982. The glassy cell variant of adenosquamous carcinoma accounts for 7.4% of their cases and for 0.5% of all endometrial carcinomas. Adenosquamous carcinomas with a glassy cell component have a poor prognosis in both the cervix and endometrium. They not infrequently contain a signet ring cell component and vascular invasion is common.

A number of ancillary techniques are available to help identify the possible primary site of origin of tumors in which there is a question of metastatic versus primary carcinoma. Electron microscopy is quite helpful in demonstrating the characteristic ultrastructural profile of tumors of gastrointestinal origin. These include microvilli with m~ents-extending as !.Q.ng .rootlets in~o the agical...cy!opla:;.m, apical electron dense bodtes, and ab~n.Lg!y£()Caly.ceal bodies. The long rootlets extending from the microvilli are-the most characteristic feature of adenocarcinoma of the colon as opposed to other primary sites. lrnrnunohistochemicaUy, carcinomas of the colon characteristically express exclusively low molecular weight cytokeratin whereas those from the endometrium also express low molecular weight cytokeratins but often have some focal positivity with high molecular wejght cytokeratins as well. Epitope specific monoclonal antibodies against CEA are also helpful. in diagnosis, particularly when the question is between a pr imary colonic or metastatic endometrial carcinoma. Such antibodies to CEA react with colonic but not endometrial tumors. A relatively new monoclonal antibody known as villin is also helpful in this differential diagnosis as it reacts with most intestinal carcinomas but only occasionally with endometrial neoplasms.

The presence of an in situ component in the mucosal surface of an organ from which a carcinoma has arisen has been taken as evidence that it is primary in that site. Shepherd and Hall however, recently reported two convincing cases in which metastatic carcinomas in ·the small bowel and appendix underwent morphologic differentiation indistinguishable from an in situ component and postulated that this was due to a mesenchymal influence exerted by the lamina propria on the epithelium to cause it to differentiate into structures that appeared to be in continuity with the surrounding mucosa.

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References

Alberhasky RC, Connelly PJ, Clui.slopherson WM: Carcinoma of the endometrium. N . M ixed adcnosquamous carcinoma. A clinical-pat1tologital Stlldy of 68 cases with long term follow-up. Am J Clin Pathol [982;77:655-664

Bacchi CE, Gown AM: Distnllution and pattern of expression of villin, a gastrointestinal-associated cytoskelctal protein, in human carcinomas. Lab<>ratory Investigation (In press)

Christopherson WM, Alberhasl<y RC, ConncUy PJ: Glassy cell carcinoma of the endometrium. Hum Patho/ 1982;13:41S-421

Hickey WF, Seiler MW: Ultrastructural markers of colonic adenocarcinoma. Cane<r 198!;47:140-145

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Maier RC, Norrish HJ: Glassy ceU carcinoma of the cervix. Obsret Gyntco/·1982;60:2!9

Ramaekers F, Van Niekerk C, Poels L, et al: Use of monoclonal antibodies to keratin 7 in the differential diagnosis of adenocarcinomas. Am J PaJilo/ 1990;136:641-655

S~igo PI; Cain JM, Kim WS, et al: Prognostic faaors in adenocarcinoma of rhe urerlne cervix. C011ur 1980;57:1584

Sheahan K, O'Brien MJ, Burke B, et al: Differential reactivities of carcinoembrionic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies. Am J Clin Pathol 1990;94:157-164

Shepherd NA, Hall PA: Epithelial-mesenchymal interactions can influence the phenotype of carcinoma metastases in the mucosa ofthe intesrine.J Parho/ 1990;1 60:103-109

CASEll

Diagnosis: Dysplasia complicating ulcerative colitis . .

Cancer complicating ulcerative colitis accounts for 1% or less of all colorectal carcinomas diagnosed annually in the United States, yet it has generaiea Clisproportionate interest because it is potentially preventable. We hypothesize that neoplastic progression to carcinoma in ulcerative colitis has an intermediate stage of dysplasia, during which it is potentially preventable by colectomy. Patients at highest risk for carcinoma in ulcerative colitis include those with a disease duration of lqnger than lOy ears, disease extending proximal to the sigi!Ioid colon, and disease beginning at an early age. In this select group of patients, the riskis quite"iligh and m~ittier propllyliictic "Colectomy or endoscopic biopsy surveillance.

Problems confronting the pathologist in interpreting endoscopic biopsies for dysplasia in ulcerative colitis .are primarily related to the close similarity between reactive lesions induced by the inflammatory process and dysplasia. For this reason, the clinician should be encouraged not to undertake surveillance biopsies unless the disease is in remission. If the disease cannot be brought into remission, a colectomy on the basis of chronic active disease is probably indicated. In the relatively asymptomatic patient who has "smoldering• histologic inflammation, the pa'lhologist may not be able to confidently diagnose or exclude dysplasia. In my view, this constitutes reason for considering colectomy.

One is best advised to avoid attempting to make the diagnosis of dysplasia in the face of active inflammation, unless the changes are overt and produce a biopsy appearance that is indistinguishable from that seen in an adenoma. The interpretation of dysplasia and its grading are subjective, leading to disagreement among pathologists as to whether or not dysplasia is present and to its grade. Recent data utilizing flow cytometry show good correlation between the presence of dysplasia a:nd flow cytometric abnormalities. Flow cytometric abnormalities may also be present in the absence of dysplasia or in biopsies interpreted as indefinite for dysplasia. Such ·patients appear to be at high risk for progressing to develop overt dysplasia on prospective follow-up, but only a few such patients have been followed.

Refe.rences

1. Blackstone MO, Riddell RH, Rogers GBH and Levin B: Dysplasia associated lesion or mass (DALM) detected py colonoscopy in long-standing ulcerative colitis: An indication for colectomy. Gastroemerotogy 1981;80:366-74.

2. Collins RH, Feldman M, f'ordtran JS: Colon cancer, dysplasia and surveillance in patients with ulcerative colitis. N Engl Med 1987;316:1654-1658.

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Bkbom A, Helmick C, Zach M, Adami H-0: Ulcerative colitis and eolorcctal cancer: a population-based StUdy. N Eng J M•d 1990;323:12.28-1233

Haggitt RC, Rubin CE, Levine DS, et al: Aneuploidy in ulcerative colitis biopsies that arc histologically indefinite for dysplasia may predict future progression to defutite dysplasia. Gastroenterology 1990;98:AJ 73 (abstract)

Hamilron SR: Colorectal carcinoma in patients with Crohn's disease. Gastroemerology 1985;89:398-407.

Lennard~Jones JE, Ritchie JK. Morson BC et al: Cancer surveillance in ulcerative colitis: experience over 15 years. Lane., 1983;ii:'l49-152.

Lofberg R, Brostrom 0, Xarlcn P, eta!: Colonoscopic surveillance in long-standing <otal ulcerative colitis- a 15 year follow-up study. Gastroenterology 1990;99:1021-1031

Nugent FW, Haggitt RC, Gilpin PA: Cancer surveillance in ulcerative colitis: results of a 13 year prospective biopsy surveillance program. Gastroenterology (In press, 19'90) ·

Riddell RH, Goldman H, Ransohoff DF, et al: Dysplasia in inflammatol}' bowel disease: Standardized classification with provisional clinical implications. Hum Pathol1983;14:931-%8.

10. Rosenstock E, Farmer RG, Perras R, ct al: Surveillance for colonic carcinoma in ulcerat ive colitis, Gastroenterology 1985;89:134Ui.

CASE12

Diagnosis: Gastric stromal tumor (see comment).

Comment: The biologic behavior of gastric stromallumors is difficult to predict. In general,

tumors that are less than ,6 em in diameter and which have__~;nitgtic counts of le~ .than..5 p_e.r ~ high power fields (0.63 mitoses per sq mm) behave in a biologiC'allfbenlgnmanner while tumors more tlian 6 em in diameter and those with more than 5 mitotic figures per 50 high power fields tend to be biologically aggressive. Some authorities consider tumors with more than 5 mitotic figures per 10 high power fields (3 mitoses per sq mm) to be malignant. This tumor measures 4.5 em in diameter and has a mitotic count of 6 mitoses per 50 high power fields (0.75 mitoses per sq mm)- For both benign and malignant gastric stromal tumors, complete local resection with a margin of normal tissue represents appropriate management.

There is perhaps nothing as controversia[ in gastrointestinal pathology (except perhaps lymphomas!) than the interpretation of gastrointestin.al stromal tumors. The two major points of controversy are the histogenesis of the tumors and prognostic factors that will predict their outcome. Most or all gastrointestinal stromal tumors were considered to be of smooth muscle origin during the first half of this century. More recently with the application of electron microscopy and immunohistochemical techniques, it has become apparent that many tumors originally classified as being of smooth muscle origin lack features diagnostic of this derivation. In many tumors, the phenotype as determined by EM and immunohistochemistry is that of an undifferentiated neoplasm while in others there is evidence of Schwann cell or autonomic nerve differentiation. The references cited will direct you to pertinent literature.

As the diagnostic comment above indicates, there is much controversy about predicting the biologic behavior of smooth muscle tumors. Appelman and Helwig, in a series of studies from the AFIP that was published in the 1970's, found that cell size and density were the best predictors Of malignant behavior. In tumors that they had diagnosed as malignant using the cell size and density criteria, 50% of those with less than 5 mitotic figures per 50 high power fields metastasized while 95% of those with more than 5 mitotic

14

figures per 50 high power fields did so. This work is reviewed in the 1986 paper by Appelman in which he summarizes his thinking by stating that high mitotic rates tend to correlate with biologically malignant behavior a·nd that high mitotic rates should be considered anything more than 5 per 50 high power fields. Ranchod and Kempson, in contrast, draw the line between benign and malignant tumors at 5 mitoses per 10 high power fields, a rather striking difference. I do not know the explanation for these differences, but I caution you that the size of a high power field can vary by as much as 5 to 6 fold, and that mitotic counts can be affected by a delay in fixation of the tissue.

One final note of caution concerns the observation that smooth muscle cells may express cytokeratins. Also, multiple benign and malignant smooth muscle tumors have been reported in children with AIDS and the HJV infection was postulated to play a role in their formation.

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References

AntonioU DA: Ga.nrointe.slinal autonomic nerve tumors. Expanding the specuum of gastrointestinal stromal tumors.An:h Patholl.Ab Med 1989;113:1131-&33

Appelman HD: Smooth mw;cle tumor1 of the gastrointestinal tract. Am J Swg Patho/ 1986;10:83-99

Chadwick EG, Connor EJ, Hanson CG, c:t a!; Tumor1 of smooth-muscle origin in HTV-infected children. JAMA 1990;263:3182-3184

Daimaru Y, Kido H, Hashimoto H, Enjoji M: Beni.gn Schwan.noma of the gastrointestinal tract: a clinicopathologic and immunohistochemical Study. Hum Pat/ro/1988;19:251-264

Donhuijsen K, Schmidt U, H(rche H, ct aJ; Changes in mitotic rate and cell cycle fractions caused by delayed fixation. Hum Pathol 1990;21:709-714

Ellis PSJ, Whitehead R: Mitosis counting- a n.eed for reappraisal. Hum Patho/1981;12:3

Evans H L: Smooth muscle tumors of the gastrointestinal tract. A Study of 56 cases followed for a minimum of 10 years. Cancer 1985;56;2242-2250

Gown AM, ilayd HC, Chang Y, et al: Smooth muscle cells can express cytokcratins of "simple" epithelium. Am J Patho/1~;132:223-232

Hencra GA, Cerezo L, Jones JE, et al: Gastrointestinal autonomic nerve tumors. Arch Patho/ Lab Mcd 1989;113:846-853

10. Miettinen M; G3$lroint~al stromal tumOt$. An immunohistochemieal soudy of cellular differentiotion. Am J Ciin Patho/1988;89:601~10

11. Miettinen M: Immunoreactivity for cytokeratin and epithelial membrane antigen in leiomyosarcoma. Arch Ptuholl.Ab Med 1988;112:63740

12. Pike AM, Uoyd RV, Appelman HD: CeU marker1 ito gaStrointestinal stromal tumors. Hum Pathol 1988;19:820-834

13. Ranchod M, Kempson RL: Smooth muscle tumor1 of the gamrointestiroal traa and retroperitoneum. A pathologic analysis of 100 eases. Cancer 1977;39:255-262

14. Saul SH, RaSt MI., Brooks JJ: The immunohistochemistry of gastrointeStinal Stromal tumors. Evidence supponing an origin from smooth muscle. Am J Swg PtUnoll981;fl:464-413

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CASE13

Diagnosis: Carney's syndrome with: A: Gastric stromal sarcoma (leiomyosarooma) B: Flmctlonlng extra-adrenal paraganglioma

J. Aidan Carney, of the Mayo Clinic, described the triad of gastric leiomyosarcoma, functioning extra-adrenal paraganglioma and pulmonary chondroma in 1977. He has since coUected additional cases of this syndrome and published a review article in 1983 in which data on 24 cases are summarized. Only 6 of the 24 patients (25%) described at that time had the complete triad while the remaining 18 patients had 2 of the 3 neoplasms. The tumors at all sites in these patients tend to be multiple, and indeed, in the present case there were 10 gastric tumors and multiple paragangliomas. Affected patients are usually young with the mean age in Carney's series being 16 years. 22 of the 24 reported patients have been female. Patients with Carney's syndrome who have leiomyosarcomas of the stomach have a more favorable prognOsis than those who lack the syndrome, as the tumor in this context appears to have a relatively indolent course, even when metastatic disease is present.

Carney believes that when 2 of the 3 neoplasms are present, the presumptive diagnosis of his "triad" shou.ld be made, particularly if the age and sex are appropriate. He recommends that any patient less than 35 years of age with one of these 3 tumors be examined periodically in search for the others.

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The cause of Carney's syndrome, although presumably genetic, is not known.

References

Carney JA, Sheps SG, Go VLW, Gordon H: The triad of gastric lciomyosareoma, functioning extra-adrenal paraganglioma and pulmonary chondroma. N EngJ Merl t9TI;296:1S17-1518

Carney JA: The triad of gastric epithelioid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma. COncer 1979;43:374-382

Carney JA: The triad of gastric epithelioid leiomyosarcoma, pulmonary chondroma, and runc:~ioning extra· adrenal paraganglioma: a fiVe year review. Mttfidnt 1983;62:159-169

Margulies KB, Sheps SG: Carney's triad: guidelines for management. Mayo Clin Pnx 1988;63:4%-502

Raafat F, Salman WD, Roberts K, et al: Carney's triad: gostri< leiomyosarcoma, pulmonary chondroma and extra-adrenal paraganglioma In young fcmales.lrrstopalhology 1986;10:132.5-1333

Tisell L-E, AngervaU L. Dahl I, et al: Recurrent and metastasizing gastric leiomyoblastoma (epithelioid leiomyosarcoma) associated with multiple pulmonary chondro-ltamartomas. Canctr 1978;41:259·265

Wiek M.R, Ruebner BN, Carney JA: Gastric tumors in patic.ntS with pu.lmonary chondroma or extra-adrenal paraganglioma. Arch PathollAb Med 1981;105:527-531

CASE14

Diagnosis: Goblet cell can:lnold (adenocan:inoid) of appendix.

This case represents an example of a so called goblet cell carcinoid of the appendix. Adenocarcinoid, one of the numerous synonym.s used for this tumor, is perhaps a more appropriate name as not all of these tumors contain goblet cells. Other synonyms that have been applied to this lesion include mucinous carcinoid, crypt cell carcinoma and microg!andular carcinoma. These tumors were frrst described in 1969 and although found

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almost exclusively in the appendix, have rarely been reported elsewhere in the GI tract. The adenocarcinoid arises from endocrine cells within the lamina propria at the base of the mucosa and contains endocrine cells, goblet cells, occasionally paneth cells, and undifferentiated cells. Some of these tumors contain foci of otherwise typical carcinoid or they may have dedifferentiated foci of adenocarcinoma. Because the lesion is often grossly inapparent, a section of the proximal margin of the appendix should always be taken regardless of the appearance of the appendix. In contrast to typical carcinoids of the appendix, in which an adverse outcome is essentially limited to patients with tumors exceeding 2 em in diameter (Moertel, et al) adenocarcinoma has a fatality rate of about 13% (Edmonds, et al). Factors that appear predictive of an adverse outcome in adenocarcinoid are involvement of the appendiceal margin, implying that the tumor has extended into the cecum, and dedifferentiation with areas that histologically resemble poorly differentiated adenocarcinoma of the colon. In patients with either of these two prognostic features, a right colectomy is probably indicated.

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References

Burke AP, Sobin LH, Federspiel BH: Goblet cell carcinoids and related tumors of the vermifonn appendix. Am J Clin Pathol 1990;94:27-35

Cooper PH, Warkel RL: UltrastruCtUre of the goblet cell type of adenocarcinoid of the appendix. Cancer 1978;42:2687-2695

Edmonds P, Merino MJ, LiVolsi VA, Duray PH; Adcnocarcinoid (muci.nous carcinoid) of the appendix. Gastro<nterology 1984;86:302-309

Isaacson 1': Crypt <dl carcinoma of the appendix (so-c:alled adenocarcinoid tumor). Am J Su'lf Pat!Jol 1981;.5:213-224

Lewin K: Carcinoid tumors and the mixed (composite) glandular-endocrine cell carcinomas. Am J Su'15 Patho/1981;11:11.86

Moenel CG, Weiland LH, Nagomey DM, Dod eny MB: Carcinoid tumor of the appendix: treatment and prognosis. N EngJ Med 1937;311:1699-1701

Subbuswamy SG, Gibbs NM, Ross CF, Morson BC: Goblet cell carcinoid of the appendix. Conur 1974;34:333-344

Warkel RL, Cooper PH, Helwig EB: Adenocarcinoid, a mucin-producing carcinoid tumor of the appendix. a Sludy of 39 cases. Cancer 1978;4~:2781·2793

CASE IS

Diagnosis: Chronic atrophic gastritis with focal intest inal and pyloric metaplasia and mlcronodular endocrine cell hyperplasia.

In patients with chronic atrophic gastritis, the parietal cells are progressively destroyed by the inflammatory process and the patient's ability to secrete acid progressively diminishes. As the patient becomes hypo· or achlorhydric, the negative feedback loop that regulates gastrin secretion is interrupted and the serum gastrin level becomes chronically elevated. Because gastrin has a trophic affect on the gastric mucosa, this results in increased numbers of antral G cells and of enterochrornaffin·like cells in the body and fundus. These cells are argentaffin and argyrophilic and contain serotonin. In individuals with normal or relatively normal gastric mucosa, chronically elevated serum gastrin levels, as in Zollinger-EWson syndrome, for example, the trophic affect of gastrin extends to the parietal and peptic cells resulting. in increased numbers of these cells and an increased mucosal mass. Most patients with chronically elevated serum gastrin levels remain asymptomatic and endocrine cell hyperplasia develops in only about 40%.

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Carcinoids develop in 2-10% of patients. Endocrine cell hyperplasia arising in this context is relatively stable over time, as if the endocrine cell population had been upregulated by the elevated gastrin and then continues in its new state. The carcinoids arising in patients with atrophic gastritis tend to be indolent and regression of them has been reported. The endocrine cell hyperplasia and carcinoids may diminish or reverse with antrectomy.

Because the drug omeprazole blocks acid secretion by non-competitively inhibiting the H+, K+ -A TPase, it shuts off gastric acid secretion and therefore results in an elevated serum gastrin. In rats, this drug has been reported to cause carcinoids, but in humans with reflwc esophagitis treated for up to 12 weeks, the serum gastrin stabilized at levels in the range of 3 to 5 times normal. No good study on the prevalence of endocrine cell hyperplasia in patients treated with omeprazole is available, but no carcinoids in this setting have been reported in man. Patients with Zollinger-Ellison's syndrome have increased numbers of ECL cells in the gastric body and fundus, but this increase is not heightened by therapy with omeprazole.

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References

Dorch K, Renvall H, Kullman E, Wilander E: Gastric carcinoid associated with the syndrome or hypcrgastrinemic attophic gaSiritls. Am I Surg Patho/1987;11 :435-444

Dorch K, R envall H, Liedberg _G: Gwric endocrine a:U hyperplasia and carcinoid tumors in pernicious anemia. Gastro<nt<ro/ogy 1985;118:638-648

Bordi C, Gabrielli M, Missale G: Pathological changes of endOcrine cells in chronic attophic gastritL<. An ultrasuuctutal study on peroral gastric biopsy specime11$.An:h !'athol Lob Med 1978;102;129-135

Cattan 0, Rouc:ayrol A-M, l..aunay J-M, et al: Circulating gi!Jlrin, endOcrine ceUs, histamine eontent, and hiMidine decarboxylase activiry in atrophic gaJtritis. GastrtHmtrOiogy 1989;97:58&-596

lt&uno M, Watanabe H, Iwafuehi M, et al: Multiple car cinoid.• and endocrine cell micronests in rype A ga.\tritis. CDIIar 1989;63:881-890

Jansen J, Klinkenberg-Knol EC, Meuwissen SGM, et at: Effect of long-term treattne nt with omcprozole on serum gastrin and serum g10up A and C pepsiJ\ogens in patient& with reflux esophagitis. Gastroenterology 1990;00:62Hi28

Kem SE, Yardley ffi, l.a2.enby AJ1 e1 at; Reversal by anttectomy of endocrine eeU hyperplMia in the gastric body in pernicious anemia: a morpnometric srudy. Mod Patho/1990;3:561-566

Maton PN, V'm8)-ek R, Frucht H, et al: Long-<errn efficacy and S3fety or omepraxole in patients "'ith Zollinger-EUison ~dromc: A prospective study. Gastrr><nt•rology 1989-.97:827-836

Rouc:ayrol A-M, Cattan 0: Evolution of fundic argyrophil cell hyperplasia in nonanrral atrophic gastritis. Gastroenttrology 1990;99:1307-1314

CASE16

Diagnosis: Gangliocytic parag;mglioma or the duodenum

The morphologic characteristic of this tumor share features in common with paraganglioma, ganglioneuroma and carcinoid. This unusual combination of histologic patterns is well recognized in tumors of the duodenum and has been called "gangliocytic paraganglioma" by Kepes and Zacharias. Most of the reported cases have arisen in the duodenum, especially the second portion, but a few have been described in the jejunum. Stromal amyloid may be present within the lesion. Gangliocytic paragangliomas have been considered to be transitional or hybrid forms between ganglioneuroma and paraganglioma and as expressions of differentiation by a pluripotential stem cell, presumable of neuralcrest origin. Another view is that the lesion is a result of halted migration and

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subsequent alteration of cells from the ventral primordium of the pancreas. These cells then presumably interact with neuroectodermal cells and attempt to recapitulate endodermal-neuroectodermal complexes. Whether or not gangliocytic paraganglioma is a hyperplasia, a hamartoma or choristoma or a neoplasm is not settled. There are no reported patients who died from gangliocytic paraganglioms, but the potential for aggressive behavior has been emphasized by some authors.

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s.

6.

7.

8.

9.

References

Anders KH, Glasgow BJ, Lewin KJ: Gangllocytic paraganglioma woeiatcd with duodenal adenocnrcinoma. Arch Pt1thol Lab M<d 1987;111 :49-52

Beltrami CA, Monrironi R, Cinti S: Gangliocytic paraganglioma of the duodenum: case report. Tw11ori l980;66:63H4l

Burke AP, Helwig EB: Gangliocytie paraganglioma. Am J Clin P4tho/l989;92:l-9

Hamid QA, Bishop AE, Rode J, ct al: Duodenal gangliocytie J>Gl11g11ngllomas: a study of 10 = with Immunocytochemical neuroendocrine markers. Hum Pathol 1986;17:1131-1157

Kepcs JJ, Zacharias DL: Gn"'IUocytiefaragan2[ioma.~ of the duodenum: a report of two cases with light and electron microscopic examination. 197 ;27:61-10

Perrone T, Sibley RK, Rosai J: Duoocnal gangliocytic paragan~;lioma: an Immunohistochemical and ultrastnu:tural study and a hypothesis concerning its orig;in.Am J Surg Patho/1985;9:31-41

Qizilbash AH: Benign paragalll!lioma of the duodenum: case report with light and ele«ron microscopic examination and brief review of literature. An:.h Patlool !973;96:27~2BO

Reed RJ, Daroea PJ, Harkin JC: Gangliocyticparaganglioma.Am 1 Surg Pathol 1977;1:207-216

Scheithauer BW, Nora FE, LeChago J, et al: Duodenal gangllOcyt!c par.tgalll!lioma: clinicopathologic and immunocytochemical study of II cases. Am 1 Clin Pathol 1986;86:SS9-56S

10. Taylor HB, Helwig EB: Benign non-chromaffin paragangliomas or the duodenum. Virchow Arch Path A nat 1962;335:356-366

CASE17

Diagnosis: Carcinoma of lhe anal canal with non-keratinizing squamous (transitlonal­cloacagenic) and pseudoadenold cystic patterns.

The anal canal is a morphologically complex :zone that gives rise to neoplasms with a variety of histologic appearances, including keratinizing squamous cell carcinomas, non­keratinizing squamous cell carcinoma (often called transitional-doacagenic), basaloid and pseudoadenoid cystic patterns. Because mixtures of these different histologic types occur and because they behave in a biologically similar manner when similar grades and stages are compared, it has been proposed that they all be lumped together as carcinomas of the anal canal. The present case is predominantly composed of the pseudoadenoid cystic pattern with areas of non-keratinizing squamous cell carcinoma present as well. In Evans' series, the pseudoadenoid cystic pattern was associated with a higher prevalence of distant metastasis.

Increasingly strong evidence links squamous cell carcinoma of the anal canal to infection with human papillomaviruses. HPV types 6 and 11 are commonly found in benign squamous proliferations about the anus while types 16 and 18 are frequently detected in carcinomas. The data linking HPV to anal cancer are primarily related to keratinizing squamous cell carcinoma; the relationship with the other varieties is not present or at least not strong. There is a strong relationship between homosexual behavior,

19

specifically, receptive anal intercourse in males, and squamous cell carcinoma of the anal canaL A strong association between carcinoma of the anal canal and carcinoma of the female genital tract and perineum has also been noted. Rena.! transplant recipients have a strikingly increased prevalence of cancers of the anogenital region.

Carcinomas of the anal canal that penetrate only the submucosa have a highly favorable prognosis and can probably be treated with local excision. Tumors that penetrate into the muscularis propria (internal anal sphincter) have a high prevalence of local recurrence and nodal metastasis and abdomino-perineal resection was the standard therapy for these deeply invasive tumors for many years. Combination radiation therapy and chemotherapy has now been demonstrated to provide survival that is as good as or exceeds that with abdomino-perineal resection and is now considered to be the therapy of choice for these tumors.

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3.

4.

s.

6.

7.

8.

9.

References

Adam YG, Efron G: Current conc:epts and controversies concerning the etiology. pathogenesis, diagnosis, and treatment of malignant tumors or the anus. Swguy 1987;10t:2SJ-266

Dating JR, Weiss NS. Hislop TG, et a!: Sexual practices, sexually transmitted diseases, and the incidence of anal cancer. N Eng J Mtd 1987;317:m-9n

Dougherty BG, Evans HL: Carcinoma of the anal canal: a study of 79 eases. Am J Clin Patllol 1985;83:159-164

Duggan MA, Boras VF, Inque M, et al: Human PapiUomavirus DNA determination of anal condylomata, dysplasias, and squamous carcinomas with in sltu hybridiz.ation.Am J Clin Patho/1989;92:16-21

Fenger C, Nielsen VT: Intraepithelial neoplasia in the anal canal. Acta Path Miar>biol Jmmunol Scand Sta. A 1986;94:343-349

FcngerC: Histology of the anal canal. Am J Surg Pathol 1988;12:41-SS

Ferenczy A, Mitao M, Nagai N, et at: Latent papillomavirus and recurring genital wans. N Eng I Mer! 1985;313:784-788

Holmes F, Borek D, Owen·Kummer M, et al: Anal cancer in women. Gastro<nterology 1988;95:107-lll

Penn I: Cancers of the anogenital region in renal transpbnt recipients. Analysis of 6S C8SC$. Canur 1986;58:611-616

10. Taxy JB, Gupta PIC, Gupta JW, Shah !CV: Anal Cana:r. Microscopic condyloma and tissue demonstration of human papillomavirus capsid antigen and vinll DNA.An:/o Patloo/Lab Mtd 1989;113:1127-1131

ll. Wolber R, Dupuis B, Thiya~aratnam P, Owen D: Anal cioacogenie und squamous carcinomas. Comparative histologic analysis using in sJtu hybridization for human papillomavirus DNA. Am J SurgPnthol 1990;14:176-182

eASElS

Diagnosis: Heterotopic gastric mucosa in rectum.

Heterotopias of gastric mucosa have been described throughout the gastrointestinal tract, in the tongue, mouth, within intestinal duplications and Meckel's diverticula, in the gall bladder and bile ducts, within intrathoracic, intraabdominal, pancreatic and spinal cysts and within the urinary bladder. When gastric fundic-type mucosa is present, the lesion is best considered a congenital or developmental abnormality. When only the pyloric-type of mucosa is present, the lesion is probably a metaplasia developing as a consequence of chronic inflammation. The most common heterotopia in the gastrointestinal tract is probably that represented by patches of gastric fundic-type mucosa in the upper esophagus

20

and known as an "inlet• patch. This lesion bas been described in 10-20% of normal individuals at autopsy. It is typically immediately beneath the cricopharyngeus muscle (upper esophageal sphincter) and is separated from the stomach by an intact zone of squamous mucosa, an observation that p·ermits its ready distinction from Barrett's esophagus, in which the gastric-type epithelium is in direct continuity with the gastric mucosa. below. Gastric heterotopia in the duodenum occurring as nodules of fundic type mucosa is also rather common. Metaplasia of the duodenal surface epithelium is found frequently in normal individuals and almost always in patients with duodenitits. Foci of pyloric-gland metaplasia are found in many different kinds of chronic inflammatory processes in the intestine, but they are especially common in Crohn's disease of the small bowel

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l .

3.

4.

s. 6.

7.

8.

9.

Heterotopic gastric mucosa in the rectum, as in this patient, is rare indeed.

References

De La Pava S, Pickren JW, Adler RH: Ectopic gastric mucosa of the esophagus. A study on histogenesis. New York Stau 1 Med 1964;65:1831-1835

Hoedemaeker J: Heterotopic gastric mucosa in the duodenum. Digestion 1970;3:165-173

Jabbari M, Gorcsky CA, Lough J, et 81: The inlet pat ell: Heterotopic gastric mucosa in the upper esophagus. Gastrcx:nttrology 1985;89:352-356

Kalani BP, Mams, Vaexzadeh K, Sieber WK: Gastric heterotopia in r~um complicated by rectovesical fiStula. Dig Dis Sci 1983;28:378-380

Lcssells AM, Martin DF: Heterotopic gastric mucosa in the duodenum. l C/in Patflo/ 1982;35:591-595

t.UnJ.t S.C, Simon M, Tandon BN: Gross gascric metapJ:a~ia of ileum after regional enteritis. Gastroenterolog}' 1963;44:63-68

Schwarzenbcrg SJ, Whitington PF: ReaaJ gastric mucosa heterotopia as a cause of hcmatochez.ia in an infant. Dig Dis Sci 1983;28:470-472

Shousha S, Parkins RA, Bull TB: Chronic duodenitis with gastric metaplasia: electron microscopic study including comparison with normal. Histopathology 1983;7:87~5

Van Asche C, Rahm AE, Goldner F, Crumbaker D: Columnar mucosa in the proximal esophagus. GastrOinr.stinal Endoscopy 1988;34:324-326

10. Variend S, Howat AJ: Upper oesophageal gastric heterotopia: a prospective necropsy study in children. I Ctin Ptuho/ 1988;41:742-745

11. Wolff M: Heterotopic gastric epithelium in the rectum: A repon of t.hree new eases with a review of 87 cases of gastric heterotopia in the alimentary canal. Am 1 Clin PtUho/1971;55:607-<il6

12. Yokoyama I, Kozuka S, Ito K, ct al: Gastric gland metaplasia in the small and large intestine. Gut 1977;18:214-218

CASES 19 and 20

Diagnosis:

Case 19: Well-dltrerentiated lymphoproliferative disorder of stomach and duodenum (polymorphic lymphoma of MALT vs "pseudolyrnphoma")

Case 20: Epitheliotropic T -ttU lymphoma or small bowel and colon.

The diagnosis and Classification ·of gastrointestinal lymphomas are in a state of flux, primarily because of the recognition by Isaacson and colleagues that lymphomas of the

21

mucosa-associated lymphoid tissue (MALT) could be polymorphic, contain lymphoid follicles, and were diagnoseable as lymphomas only by demonstrating clonality by light chain restriction or gene rearrangement studies. In faet, in retrospective reviews of cases that had been previously interpreted as pseudolymphomas of the stomach, Isaacson and colleagues found monotypic cytoplasmic immunoglobulin in all. These workers therefore recommended abandoning the term "pseudolymphoma" and claimed that all such lesions were low-grade lymphomas of MALT. Thus, one could differentiate a reactive lymphoid hyperplasia from a true lymphoma only by demonstrating that the latter was a clonal proliferation. The Isaacson concept of low-grade polymorphic lymphomas of MALT requires that one accept the hypothesis that clonality is equivalent to malignancy. Sigal and colleagues have questioned whether this is appropriate.

As defmed by Isaacson and colleagues, the low-grade polymorphic B-ceU lymphoma of MALT is charaCterized by the presence of a polymorphic lymphoid infiltrate, often accompanied by eosinophils and plasma cells, in which the lymphoid ceUs infiltrate gastric epithelium ('lymphoepithelial" lesion) and destroy it. The plasma cells not infrequently contain Dutcher bodies. Since reactive germinal centers may be present, and even numerous, the diagnosis of lymphoma of MALT requires demonstration of light chain restriction or gene rearrangements.

Case 20 represents an example of an epitheliotropic T-cell lymphoma. Such lymphomas differ from the so-called Mediterranean type of lymphoma in that the latter is a proliferation of B-ceUs. The diagnosis in this case was a difficult one on endoscopic biopsies and required gene rearrangement studies for confirmation and differentiation from lymphocytic colitis, a benign condition in which there is prominent lymphocytic infiltration of the epithelium.

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3.

4.

s. 6.

7.

8.

9.

References

Chan JKC, Ng CS, Isaacson PG: Relationship between high-grade lymphomas and low-grade B-ccU mucosa­a$$0ciated lymphoid tissue lymphoma (MALToma) of the s1omaeh.Arn J Patho/1990;!36:1153-1164

Fouear K, Fouear E, Mitros F, et al: Epilheliotrapic lymphoma of the smaU bowel. Canctr 1984;54:54-60

Hall PA, Jass JR, Levison DA, et al: 03S$ilieation of primlll)' gut lymphomas. Lanut 1988;2:958

baacson P, Wright DH: Malig~~ant lymphoma of mueosa4SSOCiated lymphoid tissue. Canc.r 1983;52:1410-1416

Isaacson PG, Spen.eer J, Finn T: Primary B-ceU gastric lymphoma. Hum Patho/1986;11:12-82

Levison DA, HaU PA, Blackshaw AJ: The gut-associated lymphoid tissue and its tumours. Curr Top Pa~l>ol 1990;81:133-175

Moller P, Mielke B, Moldenhauer G: Monoclonal antibody HM!A, a marker for intraepithelial T cells and lymphomas derived thereof, also rceogniz.es hairy eeU Jeu'k~a and some B ceU lymphomas. Am J Patlrol 1990;136:509-12

Shepherd NA, Blad<shaw AJ, Hall PA, et a!: Malignant lymphoma with ecninophilia of the gurrointwinal tract. Histopotltol<>g 1987;11:115-130

Shepherd NA, Hall PA, Coate$ PJ, Levison DA: Primary malig~~ant lymphoma of the colon and rectum. a histopathological and immunohistochemical analysis of 45 cases with clinicopathological correlations. flistop<Jtlrology 1988;12:235-252

10. Sigal SH, Saul SH, Auerbach HE , c1 al: Gastric smaU lymphocytic proliferation with immunoglobulin gene rearrangement in pseudolymphoma ve.-.us lymphoma. Gastro<nttrology 1989;97:195-201

11. Spencer J1

Ccrf-Bensussan N, Jarry A, et al: Enteropathy-assodated T cell lymphoma (mnlJgnont histiocyrosts of the intestine) is reoog~~ized by a monoclonal antibody (HMIA) that defines a membrane molecule on human muoosallymphocytes.Am I Patho/1988;132:1-S

22

12. Spencer J, Diss TC, Isaacson P: A Sluc!y of the propenies or a low-grade mucosal B-ceU lymphoma using a monoclonal annl>oc!y specific for the tumour immunoglobulin. J Palho/1.990;160:231-3

13. Spencer J, Diss TC, Isaacson PG: Primary B ceO gasuic lymphoma . .Am I Patloo11989;13S:SS1-564

23

SEMI-ANNUAL SEMINAR ON GASTROINTESTINAL TUMORS DECEMBER 9, 1990

SAN FRANCISCO, CALIFORNIA

CASE NO. 1 - ACCESSION NO. 26707

Follow-up: He expired on August 28 . 1990 of metastases to brain, bone and l iver . Autopsy was not per formed.

CASE NO. 2 - ACCESSION NO. 26846 (No follow-up)

CASE NO. 3 - ACCESSION NO. 26837

Fol low-up: He was seen two 'months ago - admitted to St. Jude Hospital for closure of a duodenal fistula at the site of t he catheter duodenostomy. At surgery cancer was noted everywhere - carc inomatosis in his belly. He is still surviving on chemotherapy.

CASE NO . 4 - ACCESSION NO. 26790

Follow-up: No evidence of di sease .

CASE NO. 5 - ACCESSION NO. 26850 {No follow-up)

CASE NO. 6 - ACCESSION NO. 26797

Fol low-up: No evidence of disease.

CASE NO. 7 - ACCESSION NO. 26849 {No follow-up)

CASE NO. 8 - ACCESSION NO. 26146

Follow-up: Unfortunately the patient did not survive post-operative complications. Autopsy showed multiple pulmonary embol i and there was no evidence of metastatic disease. The gastro-intestinal tract was examined grossly but the mucosa was not examined.

CASE NO. 9 - ACCESSION NO. 26851 {No follow-up)

CASE NO. 10 - ACCESSION NO. 26755

Follow-up: Patient lost to follow-up .

CASE NO. 11 - ACCESSION NO. 26853 (No follow-up)

CASE NO. 12 - ACCESSION NO . 26798

Fol low-up: No evidence of disease.

CASE NO. 13A - ACCESSION NO. 26829 CASE NO. 138 - ACCESSION NO. 26818

Follow-up: November 12, 1990: She was last seen a week ago at which time she had recurrence in her stomach and developed a tumor in her lung which has calcium in it and is thought to be a chondroma.

CASE NO. 14 - ACCESSION NO . 23090

Follow-up: As of January 30, 1979 the patient (90 years old) was asymtomatic and doing well .

CASE NO. 15 - ACCESSION NO. 26847

Follow-up: (No follow-up)

CASE NO . 16 - ACCESSION NO. 22021

Follow-up: He was re-admitted to the hospital in February 1980 for recurrent g.i. bleeding for which he did not respond to supportive care therapy. His hematocrit dropped to 25% and prompted surgery (60% gastrectomy) on February 14, 1980 for a benign posterior gas tric ul cer .

The patient was last seen in February 1990 - no evidence of disease.

CASE NO. 17 - ACCESSION NO. 18546

Follow-up: Last seen in 1971 and had metastatic liver.

CASE NO. 18 - ACCESSION NO. 26810

Follow-up: No recurrence.

CASE NO. 19 - ACCESSION NO. 25999

Follow-up: She is seen by her phys is. ian once or twice a year and i s doing well. She is fully functional.

CASE NO. 20 - ACCESSION NO. 26848 (No follow-up)