Mucinous Cystadenocarcinoma of the Pancreas: Diagnosis by Fine-Needle Aspiration Cytology Raj K. Gupta, M.D.,F.I.A.C., John Scally, F.C.R., D.M.R.D., and Richard J. Stewart, CH.M., F.R.A.C.S.

Two cases of mucinoics cystadenocarcinorna of the pancreas are described in which the diagnosis was made f rom the material obtained by a computed tomography-guided jine-needle aspi- ration cytology examination. It is strongly fe l t that aspiration cytology, when performed under imaging guidance, is sensitive and specific in the diagnosis of mucinous cystadenocarcinoma and allows for a relatively simple yet confident diagnostic interpretation of this uncommon pancreatic tumour. Diagn Cytopathol 1989;5:408-411.

Key Words: Mucinous cystadenocarcinoma; Pancreas; Fine- nl-edle aspiration cytology

Percutaneous aspiration cytology using fine needles under the guidance of ultrasound and computed tomography (CT) is being practiced with a high degree of sensitivity and specificity for the diagnosis of pancreatic lesions.’** One tumor in which the use of fine-needle aspiration cytology (FNAC) has been suggested is the mucinous cystadenocarcinoma, which constitutes about 1%-2% of nonendocrine pancreatic turn or^.^'^ Although the histol- ogy of this tumor has been well de~c r ibed , ’~~ the FNAC features have previously been described in only two case reports.’.* In this article, we describe two further cases of this uncommon tumor in which the diagnosis was made by FNAC.

Case Reports Case I A 68-year-old male presented with increasing jaundice, loss of weight, pale stools, and loss of appetite following the administration of phenylbutazone for a suspected gouty arthritis. Detailed investigation included a CT

Received June 30, 1988. Accepted September 19, 1988. From the Departments of Cytopathology, Radiology, and Surgery,

Address reprint requests to Raj K. Gupta, M.D., F.I.A.C., Cytology Wellington Hospital and School of Medicine, Wellington, NZ.

Unit, Wellington Hospital, Wellington, New Zealand.

examination, which demonstrated a dilated common bile duct, which was ascribed to an extrinsic compression due to a neoplasm in the head of the pancreas. To alleviate the symptoms, a stent was placed in the bile duct under endoscopic retrograde cholangiopancreatography guid- ance. Over the next 2 mo, the patient’s symptoms showed a dramatic improvement with weight gain, disappearance of jaundice, and normal hematological and biochemical profiles. At follow-up C T examination, a partly cystic and solid mass in relation to the head of pancreas was again seen (Fig. 1). FNA was performed under CT guidance using a size 22 needle. Following the FNA diagnosis, an exploratory laparotomy was done, and a 5.5 x 5 cm infiltrating tumor was found in the head of the pancreas. A pancreaticoduodenectomy had to be abandoned since the tumor was found to be inoperable due to extensive involvement of the superior mesenteric vein. Although a Trucut biopsy was taken, histology was inconclusive for an exact classification of the tumor type and only showed extensive desmoplastic reaction with foci of an infiltrative tumor (Fig. 2). The patient is alive 1 year after the FNAC diagnosis, with no changes in the size of mass or his symptoms.

Case 2 A 77-year-old male presented with a 16-mo history of abdominal pain accompanied with a bloated sensation that was more marked during the night. In the previous 6 mo, he had lost about 28 lb, and the symptoms of nausea, tiredness, and weakness had become worse. A chest x-ray, barium enema, and endoscopic examination of the upper gastrointestinal tract were all reported as being normal. The hematologic and biochemical profiles were within normal limits. An abdominal C T scan demonstrated a partly solid and cystic mass in the region of the tail of pancreas (Fig. 3 ) . FNA was performed under CT guid- ance, using a size 22 needle. Following the FNAC diag-

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Fig. 1. CT scan from case 1 showing the partly cystic and solid mass in the head of the pancreas (shown by arrow).

nosis, exploratory laparotomy was done; a 4.5 x 4 cm tumor was found. It was considered inoperable because of extensive invasion of surrounding structures. A Trucut biopsy was insufficient for a histologic opinion since it only showed fibrous tissue with rare foci of tumor on which no classification was possible. The patient was alive 9 mo after the initial FNA diagnosis, with no change in the size of the mass.

Material and Methods In both cases, cytologic examination was performed immediately following the aspiration. The material was expelled directly onto clean glass slides, and eight smears were made. During the smear-making process, the mate- rial was noted to be of viscous consistency. Four of the smears in both the cases were immediately fixed in 95% ethyl alcohol, while four were air-dried. Following the

Fig. 2. Trucut biopsy from case 1 showing desmoplastic reaction and foci of infiltrative tumor (H&E, x500).

Fig. 3. CT scan from case 2 showing the partly cystic and solid mass in the tail of the pancreas (shown by arrow) with the needle in the tumor.

smear preparation, the syringe and needle contents in both cases were immediately washed in a cytology con- tainer in which 30% ethyl alcohol was present. This was accomplished by withdrawing 30% ethyl alcohol in the syringe barrel with the needle attached and gently flush- ing the contents back into the cytology container. From these washings, filter preparations were made using the Gelman cytosieve method’on 25-mm Gelman filters, pore size, 5 p.

All smears fixed in 95% ethyl alcohol were stained by the Papanicolaou technique, while the air-dried smears were stained by May-Griinwald-Giemsa (MGG), muci- carmine. and Alcian blue stains.

Results Papanicolaou-stained smears and filter preparations from the material in both cases showed cells of various types ranging from large to flat sheets, with some cells suggest- ing a cuboidal appearance and others suggesting papillary configurations. A number of malignant cells contained mucus in their cytoplasm, and the nuclei were enlarged and hyperchromatic and showed prominent nucleoli, coarse chromatin, and a somewhat irregular nuclear membrane (Fig. 4). A finding in all the smears and filter preparations was the presence of abundant mucus. This mucus stained pink by Papanicolaou stain and was enhanced by MGG, mucicarmine, and Alcian blue stains, with which it specifically stained; mucus was found to be in abundance in all the preparations (Fig. 5). In between the groups of malignant cells, an occasional group of benign-appearing cells lacking malignant criteria was identified in both the cases.

Discussion In recent years, the application of percutaneous and intraoperative FNAC has had a major impact in the

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GUPTA ET AL.

Fig. 4. (A) FNAC appearances in case 2 of groups of malignant cells with nuclear and nucleolar abnormalities (Papanicolaou, x 500). (B and C) Malignant cells in case 1 and case 2 with mucus content (Papanico- laou, x850).

diagnosis of carcinoma of the pancreas and its rarer subtype^.'^'^ The differential diagnostic problems asso- ciated with mucinous cystic neoplasms of the pancreas are well documented in two recent report^,^,' and we agree with these findings that the diagnostic problems are indeed greater than in other pancreatic tumors; these problems are due to the location of these tumors, late and nonspecific symptoms, and difficulty in differentiating these from other benign cystic lesions of the p a n ~ r e a s . ~ Occasionally, differentiation between a mucinous cystad- enocarcinoma and a centrally necrotizing adenocarci- noma of the pancreas may prove difficult, especially by irnaging techniques alone. We agree with Vellet et al.7 that it is. in these types of cases that a guided FNAC is most valuable in the diagnosis. The two cases described by u!s in this article and two other recent case reports7.' attest to this, since an important diagnostic criterion in all of these cases was the presence of abundant mucin, both macroscopically when the slides were being made and microscopically where mucus was seen intracelluiarly and in the background. Also, it should be noted that the

Fig. 5. Abundant mucus in cases 1 and 2. (A) Case 1 (Papanicolaou, x350). (B) Case 2 (Alcian blue, x350). (C) Case 1 (rnucicarmine, x550)

necrotizing material, in contradistinction to mucus, when seen in the background of a cavitating glandular or other type tumor, would appear more granular and flocculent, a situation that was not seen in either of our two cases or the two cases described by other^.'^'

We also agree with other that biopsy of the pancreas is not a preferred approach for a diagnosis because of the known complications and because of a relative anatomical inaccessibility for surgical explora- tion. As a matter of fact, in recent years some centers have even adopted a policy of not taking a biopsy for a histologic diagnosis, especially if the FNAC diagnosis correlates with the clinical and radiologic assessment of a pancreatic mass." In both of our cases, the Trucut biopsy did not help in classifying the tumor.

It is interesting that both of our cases were elderly male patients. Also, while in case 2 the tumor was located in the usual location, i.e., the tail of pancreas, in case 1, it was found to be in the head of pancreas. In this regard, it is important to emphasize that, in the majority of cases, the usual location of mucinous cystadenocarcinoma is in the body or tail of the pancreas, and most patients are females, with a peak incidence in the fifth and sixth decades of life.7 Also, in our two cases, the clinical and radiologic assessment strongly suggested a neoplastic

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cystic and solid mass. This was further confirmed by CT-guided FNAC, which showed abundant mucin and cell spectrums, as noted by others in mucinous cystadeno- carcinoma of the pancreas.'^^ W e are also of the opinion that FNAC is a safe, accurate, and reliable procedure both intraoperatively and percutaneously under imaging guidance and that the material obtained for FNAC has a greater reliability in the diagnosis of all types of pan- creatic carcinomas.

Acknowledgment T h e authors gratefully acknowledge the assistance of Nomeneta T o m a and Jenny O’Donnell in t h e typing of this manuscr ipt . T h e technical assistance of Rober t Fauck, Andrew Buchanan, and Sarla N a r a n is also acknowledged.

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pancreatic tumors with special reference to the classification of exocrine pancreatic carcinoma. J Pathol 1985;146:17-29. 6. Compagno J, Oertel JE. Microcystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinomd and cystadenoma). A clinicopathologic study of 41 cases. Am J Clin Pathol 1978;69:573-80. 7. Vellet D, Leiman G, Mair S, Bilchik A. Fine needle aspiration cytology of mucinous cystadenocarcinoma of pancreas. Further observa- tions. Acta Cytol 1988;32:43-8. 8. Emmert G, Bewtra C. Fine needle aspiration biopsy of mucinous cystic neoplasm of the pancreas. A case study. Diagn Cytopathol 1986;2:69-7 1. 9. Diagnostic cytology by membrane filter. Application bulletin 100R. Ann Arbor, MI: Gelman Sciences, 1984:ll-6. 10. Kline TS, Abramson J, Goldstein F, Neal HS. Needle aspiration biopsy of pancreas at laparotomy. Am J Gastroenterol 1977;68:30-3. 1 1. Leiman G, Markowitz S, Svensson LG. Intraoperative cytodiagno- sis of pancreatic adenosquamous carcinoma. A case report. Diagn Cytopathol 1986;2:72-5. 12. Walts AE. Osteoclast-type giant cell tumour of pancreas. Acta Cytol 1983;27:500-4. 13. Foote AF, Simpson JS, Stewart RJ, Wakefield SJ, Buchanan AJ, Gupta RK. Diagnosis of the rare solid and papillary epithelial neoplasm of the pancreas by fine needle aspiration cytology. Light and electron microscopic study of a case. Acta Cytol 1986;30:519-22. 14. Gupta RK, Wakefield SJ, Fauck RJ, Stewart RJ. Immunocyto- chemical and ultrastructural findings in a case of rare carcinoma of the pancreas with predominance of malignant squamous cells from an intraoperative needle aspirate. Acta Cytol (in press). 15. Moossa AR. Pancreatic cancer. Approach to diagnosis, selection for surgery and choice of operation. Cancer 1982;50:2689-8.

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