observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma lloyd,...
TRANSCRIPT
![Page 1: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/1.jpg)
![Page 2: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/2.jpg)
Observer Variation in the Diagnosis of Observer Variation in the Diagnosis of Follicular Variant of Follicular Variant of
Papillary Thyroid CarcinomaPapillary Thyroid Carcinoma
Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam, King Y MBBS, FRCPA; Lohse, Christine M BS;
Asa, Sylvia L MD, PhD; Chan, John K. C MBBS, FRCPA; DeLellis, Ronald A MD; Harach, H Ruben MD, PhD; Kakudo, Kennichi MD, PhD; LiVolsi, Virginia A MD; Rosai, Juan MD; Sebo, Thomas J MD, PhD; Sobrinho-Simoes,
Manuel MD, PhD; Wenig, Bruce M MD;
Lae, Marick E MD
Am J Surg Pathol • Vol. 28, No. 10, Oct 2004
![Page 3: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/3.jpg)
PROLOGUE
• Encapsulated tumors with a follicular architecture? Whether minor nuclear changes of the type seen in typical papillar
y caricnomas justify a diagnosis of follicular variant of papillary carcinoma (FVPCA)
? Whether minor degrees of capsular penetration justify a diagnosis of malignancy
Williams ED. Two proposals regarding the terminology of thyroid tumors.Two proposals regarding the terminology of thyroid tumors.
Int J Surg Pathol. 2000;8:181-183
![Page 4: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/4.jpg)
![Page 5: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/5.jpg)
MATERIALS
• 4000 cases from the Mayo Clinic, 1961 - 2000 including all cases diagnosed as FVPCA, follicular adenoma, and f
ollicular carcinoma
• 105 cases with one or more of the major features of FVPCA
• 87 cases had sufficient materials 85 cases (97.7%) had been originally diagnosed as FVPCA 2 cases were originally diagnosed as follicular adenoma and were
not associated with invasive growth or metastatic disease
![Page 6: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/6.jpg)
MATERIALS
• Cytoplasmic invagination in the nucleus (nuclear pseudoinclusions)
• Abundant nuclear grooves
• Enlarged overlapping nuclei
• Ground glass nuclei
• Irregularly shaped nuclei
• Psammoma bodies
![Page 7: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/7.jpg)
dark staining colloid in the FVPCA on rightdark staining colloid in the FVPCA on right
![Page 8: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/8.jpg)
nuclear clearing / colloid scalloping / irregularly shaped folliclesnuclear clearing / colloid scalloping / irregularly shaped follicles
![Page 9: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/9.jpg)
irregularly shaped, overlapping nuclei with clearing and groovingirregularly shaped, overlapping nuclei with clearing and grooving
![Page 10: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/10.jpg)
psammoma bodies / ground glass nuclei / nuclear pseudoinclusionpsammoma bodies / ground glass nuclei / nuclear pseudoinclusion
![Page 11: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/11.jpg)
nuclear pseudoinclusionnuclear pseudoinclusion
![Page 12: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/12.jpg)
capsular invasion / suspicious vascular invasion capsular invasion / suspicious vascular invasion
![Page 13: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/13.jpg)
METHODS
• One representative slide from each case was selected
• The same H&E section was seen by all 10 reviewers
• The reviewers did not know about follow-up information
• Statistical analysis: cumulative number and percent of diagnoses by reviewers concordant diagnoses among reviewers criteria for diagnosis
![Page 14: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/14.jpg)
RESULTS
• Capsular invasion: 67%
• Lymphovascular invasion: 5.7%
• Metastasis: 24.1% cervical lymph nodes: 18.3% lung: 4.6% others (e.g. bone, brain, etc.): 3.4%
• Die of disease:2.2 %
• Mean follow-up duration: 8.4 years
![Page 15: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/15.jpg)
![Page 16: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/16.jpg)
![Page 17: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/17.jpg)
![Page 18: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/18.jpg)
Other WDT-UMP WDC-NOSOther WDT-UMP WDC-NOS
12.6 10.3 2.312.6 10.3 2.3
26.4 25.2 2.3 26.4 25.2 2.3
![Page 19: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/19.jpg)
![Page 20: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/20.jpg)
![Page 21: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/21.jpg)
![Page 22: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/22.jpg)
Diagnosis by ReviewersDiagnosis by Reviewers
• 19 of 21 (90.4%) tumors associated with metastases were clearly invasive with lymphovascular and/or capsular invasion
• There were no significant morphologic differences between invasive and non-invasive carcinomas.
![Page 23: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/23.jpg)
TABLE 4.TABLE 4. Most Important (Major) Criteria Most Important (Major) Criteria for the Diagnosis of FVPCAfor the Diagnosis of FVPCA
![Page 24: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/24.jpg)
TABLE 4.TABLE 4. Less Important Criteria Less Important Criteria for the Diagnosis of FVPCAfor the Diagnosis of FVPCA
![Page 25: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/25.jpg)
DISCUSSION
• Most reviewers were able to diagnose the FVPCA cases that were capable of metastasizing. (concordant diagnosis: 39% 66.7%)
• Cases capable of metastasizing were usually associated with lymphovascular and/or capsular invasion
• Altough the diagnosis of FVPCA is somewhat controversial, most experienced pathologists generally concurred in making this diagnosis in cases with metastatic disease
![Page 26: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/26.jpg)
DISCUSSION
• One case with metastatic disease to a lymph node was diagnosed as an adenoma by the one reviewer The case did not have invasive growth.
• Three cases with metastatic disease were diagnosed as follicular carcinoma
• Two other cases were diagnosed as WDT-UMP
![Page 27: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/27.jpg)
DISCUSSION
• The most inportiant criteria included nuclear pseudoinclusion nuclear grooving ground glass nuclei
![Page 28: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/28.jpg)
DISCUSSION
• Nuclear pseudoinclusion Close to 50% of all papillary thyroid carcinoma (2
5.3% in this study) Common in the usual papillary carincoma, in solid variant, and ta
ll cell variant Uncommon in the columnar cell variant Rarely in follicular carcinoma Not in follicular adenoma
![Page 29: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/29.jpg)
DISCUSSION
• Nuclear grooving Papillary carcinoma: 100% Follicular carinoma: 0% Follicular adenoma: 10.8 %
103 consecutive cases of thyroid carcinoma (including 89 cases of papillary carcinoma)100 consecutive cases of noncancer thyroidectomy specimens5 cases of Hashimoto’s thyoiditis
Chan JK, Saw D. The grooved nucleus: a useful diagnostic criterion of The grooved nucleus: a useful diagnostic criterion of papillary carcinoma of the thyroid.papillary carcinoma of the thyroid. Am J Surg Pathol. 1986;10:672-679
![Page 30: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/30.jpg)
DISCUSSION
• Ground glass nuclei Focally seen in many types of thyroid tumors,
including follicular carcinoma Usually diffusely seen only in papillary carcinoma
(100% cases in this study, ranged from focal to diffuse)
![Page 31: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/31.jpg)
DISCUSSION
• Major criteria:Nuclei are ovoid rather than roundNuclei are crowded, often manifesting as lack of polari
zation in the cells that line a follicle Nuclei show a clear or pale chromatin pattern or exhibit
prominent grooveingPsammoma bodies
![Page 32: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/32.jpg)
DISCUSSION
• Minor criteria:Presence of abortive papillaePredominant elongated or irregularly shaped folliclesDark-staining colloidPresence of rare nuclear pseudoinclusionsMultinucleated histiocytes in lumens of follicles
![Page 33: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/33.jpg)
Differential Expression of Cytokeratins in Differential Expression of Cytokeratins in Follicular Variant of Papillary Carcinoma: Follicular Variant of Papillary Carcinoma: An Immunohistocehmical Study and Its DAn Immunohistocehmical Study and Its D
iagnostic Utilityiagnostic Utility
Zubair W. Baloch, MD, PhD; Susan Abraham, MD; Shelly Roberts, MS; Virginia A. LiVolsi, MD
Human Pathology • Vol. 30, No. 10, Oct 1999
![Page 34: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/34.jpg)
MATERIALS
• 50 cases with formalin-fixed paraffin-embedded tissue University of Pennsylvania Medical Center Personal consultation files of Virginia A. LiVolsi
• Classification of cases 26: FVPCA (2 cases with lymphocytic thyroiditis)
10: classic papillary carcinoma (1 case with lymphocytic thyroiditis)
1: Warthin’s-like papillary carcinoma (1 case with lymphocytic thyroiditis)
2: columnar cell carcinoma 2: angioinvasive follicular carcinoma 4: follicular adenoma 5: hyperplastic / adenomatous nodules
![Page 35: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/35.jpg)
![Page 36: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/36.jpg)
METHODS
• 0 : no positive cells
• + / - : rare scattered cells positie
• 1+ (weak): 1% to 10% cells positive
• 2+ (moderate): 10% to 50% cells positive
• 3+ (strong): more than 50% cells positive
![Page 37: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/37.jpg)
RESULTS
• CK19, CK20, CK7
• CKs 5/6/18 (LP34) 1 case of classic papillary carcinoma 1 case of hyperplastic nodule
• CKs 10/13 (DEK13) 2 cases of classic papillary carcinoma 1 case of follicular adenoma
• CK18 Strong intense positivity in all cases of carcinoma, adenoma, benig
n nodules, and normal thyroid parenchyma
![Page 38: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/38.jpg)
![Page 39: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/39.jpg)
![Page 40: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/40.jpg)
RESULTS
hyperplastic / adenomatous nodules (5), follicular adenoma (4), follicular carcinoma (2)
• CK19 All negative
• CK 20 1 case of follicular adenoma showed weak positivity The remaining cases are all negative
• CKs 17 1 case of hyperplastic nodule showed focal staining The remaining cases are all negative
![Page 41: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/41.jpg)
DISCUSSION
• 116 surgically resected thyroids 31 nodular hyperplasias 18 follicular adenomas 48 papillary carcinomas 19 follicular carcinomas
• CK-19, HMW-CK, EMA
Raphael SJ, MacKeown-Essyen G, Asa SL.
High-molecular-weight cytokeratin and CK-19 in the diagnosis of thyroid tumors. High-molecular-weight cytokeratin and CK-19 in the diagnosis of thyroid tumors.
Modern Pathology. 7(3):295-300, 1994 Apr.
![Page 42: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/42.jpg)
DISCUSSION
• 87 cases 41 papillary carcinomas 10 follicular carcinomas 2 poorly differentiated carcinomas 34 normal thyroid parenchyma and lymphocytic thyroiditis
• CK 7, CK 18, CK 8, CK 19, CK 5/6, CK 13
Fonseca E , Nesland JM, Hoie J, Sobrinho-Simoes M. Pattern of expression of intermediate cytokeratin filaments in the thyroid gland: an iPattern of expression of intermediate cytokeratin filaments in the thyroid gland: an i
mmunohistochemical study of simple and stratified epithelial-type cytokeratins. mmunohistochemical study of simple and stratified epithelial-type cytokeratins. VVirchows Archiv.irchows Archiv. 430(3):239-45, 1997 Mar. 430(3):239-45, 1997 Mar.
![Page 43: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/43.jpg)
DISCUSSION
• > 200 non-neoplastic and neoplastic thyroid papillary and follicular lesions
• CK19 was strongly and uniformly expressed in virtually all papillary carcinomas
• About half of the follicular carcinomas were also strongly CK19-positive
Miettinen M, Kovatich AJ, Karkkainen P.Keratin subsets in papillary and follicular thyroid lesions. A paraffin section analyKeratin subsets in papillary and follicular thyroid lesions. A paraffin section analy
sis with diagnostic implications.sis with diagnostic implications.Virchows Archiv.Virchows Archiv. 431(6):407-13, 1997 Dec. 431(6):407-13, 1997 Dec.
![Page 44: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/44.jpg)
![Page 45: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/45.jpg)
Combined Hepatocellular–Cholangiocarcinoma: Combined Hepatocellular–Cholangiocarcinoma: A Histopathologic, Immunohistochemical, and IA Histopathologic, Immunohistochemical, and I
n Situ Hybridization Studyn Situ Hybridization Study
Tickoo, Satish K. M.D.; Zee, Sui Y. M.D.; Obiekwe, Sam M.D.; Xiao, Hong B.S.; Koea, Jonathan M.D.; Robiou, Christian M.D.; Blumgart, Leslie H. M.D., F.A.C.S.; Ja
rnagin, William M.D.; Ladanyi, Marc M.D.; Klimstra, David S. M.D.
Am J Surg Pathol • Vol. 26, No. 8, Aug 2002
![Page 46: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/46.jpg)
INTRODUCTION
• A rare tumor (< 1% of all liver carcinoma) containing unequivocal elements of both hepatocellular and cholangiocarcinoma that are intimately admixed
• This tumor should be distinguished from separate hepatocellular carcinoma and cholangiocarcinoma arising in the same liver. Such tumor may be widely separated or close to each other (“collision tumor”)
• The category should not be used for tumors in which either form of growth is insufficiently differentiated for positive identification
![Page 47: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/47.jpg)
MATERIALS
• 56 cases from the Memorial Sloan-Kettering Cancer Center, New York, 1978 - 1998
• Diagnosis on a morphologic basis27: CHC (including 3 previous reported as CC) 7: pure peripheral CC12: pure HCC
![Page 48: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/48.jpg)
MATERIALS
• Goodman et el.: tumors with intermediate differentiation and identifiable transition between HCC and CC, or with the presence of discrete and separate nodules of HCC and CC
• HCC: Trabecular growth pattern Without significant desmoplasia Bearing cells with eosinophilic cytoplasm, large vesicular nuclei containing promin
ent nucleoli With or without cytoplasmic bile
• Peripheral CC: Significant desmoplsia Prominent glandular formations lined by cuboidal cells With or without mucin production
![Page 49: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/49.jpg)
MATERIALS
• Scoring (CK & EMA): 0: no staining 1+: 5% positive cells 2+: 6-25% positive cells 3+: 26-50% positive cells 4+: > 50% positive cells
• pCEA: canalicular staining
• AFP: any cytoplasmic staining
![Page 50: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/50.jpg)
![Page 51: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/51.jpg)
In Situ Hybridation for Albumin mRNA
• Albumin is a ubiquitous protein that is synthesized only by hepatocytes
• 69 hepatic tumors 29 extrahepatic tumors 50 non-neoplastic, noncirrhotic liver
Krishna, M. M.D.; Lloyd, R. V. M.D.; Batts, K. P. M.D. Detection of Albumin Messenger RNA in Hepatic and Extrahepatic Neoplasms: A Marker of
Hepatocellular Differentiation
Am J Surg Pathol. 1997;21:147-152
![Page 52: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/52.jpg)
![Page 53: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/53.jpg)
Statistical Analysis
• Fisher exact test: relationship between the IHC/ISH profile and different morphologic phenotypes in the tumors
• Kaplan-Meier method: survival analyses
• Long –rank test: differences in survival between different clinical groups
![Page 54: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/54.jpg)
![Page 55: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/55.jpg)
HCC CC CHC
Serum AFP usually very high
most low
HBV / HCV 50%up to 90%
15%
Cirrhosis 48%39%-78%
0
Survivalmean
3 years5 years
46 m54%37%
37 m58%35%
38.4 m38%24%
![Page 56: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/56.jpg)
Pathologic Features of CHC
• 9 single; 12 mutiple
• Gross features: HCC vs. CC
• Histologic features: All (27 cases) show intermediate features between HCC and CC (2
5% to >75% in areas) 4 tumors contains distinct HCC- and CC-like areas None was classified as “collision”-type tumor
![Page 57: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/57.jpg)
![Page 58: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/58.jpg)
![Page 59: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma Lloyd, Ricardo V MD; Erickson, Lori A MD; Casey, Mary B MD; Lam,](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649ca15503460f94960406/html5/thumbnails/59.jpg)
Thank youThank you