RESUMO
Objective:To evaluate the interobserver variation of pathologists in the morphological evaluation of non-invasive follicular thyroid neoplasm with papillary-like nuclear features(NIFTP).Methods:Nine pathologists from different regions in China were selected to evaluate the digital slides of 30 cases of NIFTP. Three score system was applied, including nuclear size and shape, membrane irregularity, and chromatin features. Individual histologic features were scored as either present(1)or absent(0). A total score of 0 or 1 was considered inadequate for the diagnosis of NIFTP and a total score of 2 or 3 was considered sufficient for the diagnosis of NIFTP.Results:Overall, 9 doctors had weak consistency in the interpretation of the 30 cases(Kappa value 0.081 4), in which the interpretation of the membrane irregularity had the best consistency(Kappa value 0.193 6)and the interpretation of nuclear size and shape revealed the worst consistency(Kappa value 0.102 2). The overall consistency of the evaluation from the 7 senior pathologists was better than that of all the pathologists(Kappa value 0.134 1), but it was still weak. The consistency of nuclear membrane irregularity(Kappa value 0.267 4)and nuclear chromatin features(Kappa value 0.257 3)was weak, but much better than that of nuclear size and shape(Kappa value 0.073 0). The interobserver consistency in our study was lower than that in Asian study generally. However, the judgement on membrane irregularity in our senior pathologists was better than that in Asian study.Conclusion:The interobserver variation on the evaluation of the nuclear features of NIFTP is probably due to the education level, working experience, personal understanding of the diagnostic criteria, the regional difference, and some uncertain reasons. There is overall a weak consistency in the interpretation of NIFTP by Chinese pathologists, and it is necessary to popularize the diagnostic criteria and specify the criteria in detail. It is important to exclude high-risk genetic mutation using immunohistochemical staining or molecular examination on those patients with morphology of NIFTP.
RESUMO
Objective@#To investigate the clinicopathologic and molecular features of the rare cribriform morular variant of papillary thyroid carcinoma (CMV-PTC).@*Methods@#The clinicopathologic data of 10 patients with CMV-PTC were retrospectively reviewed. Immunohistochemical (IHC) staining was done using LSAB method. DNA sequencing for APC were applied using Sanger method. BRAF V600E mutation was examined using ARMS method. The cytological, morphological, IHC and molecular features were analyzed.@*Results@#All patients were female at an average age of 27 years old. The tumors were mostly located in the right lobe of thyroid. Fine needle aspiration cytology was performed in three patients; two were diagnosed as suspicious for PTC and one as PTC. Nine tumors presented as solitary nodule and two as multiple nodules in both lobes. Infiltration was demonstrated in three cases. The average size was 2.6 cm. The neoplastic cells were arranged in papillary, cribriform, solid and glandular patterns, with rare or without colloid inside the lumen. The number of morula varied, ranging from zero to many. The neoplastic cells were variably enlarged, showing round, oval or spindle shape. Nuclear irregularity was identified as irregular membrane, nuclear grooves or pseudoinclusion, but no typical ground glass feature. Peculiar nuclear clearing could be observed in the morular cells. IHC staining showed the neoplastic cells were negative for thyroglobulin and p63, but positive for TTF1, cytokeratin 19 and estrogen receptor. Diffuse staining with cytokeratin was seen in the neoplastic cells and the morula. Specific cytoplasmic and nuclear staining of β-catenin was seen in the neoplastic cells but not the morula. Ki-67 proliferation index was 1%-30%. No recurrence or metastasis was observed. One patient was demonstrated to harbor both somatic and germline mutations of the APC gene, who was found to have adenomatous polyposis and her mother died of colonic carcinoma. No BRAF V600E mutation was detected.@*Conclusions@#CMV-PTC is rare and shows atypical cytological and clinicopathological features, and it is easily misdiagnosed.TG, TTF1, ER and β-catenin are specific IHC markers for CMV-PTC. The morula is negative for cytokeratin 19, in contrast to squamous metaplasia. Although CMV-PTC has indolent clinical behavior, a definite diagnosis is necessary to rule out the possibility of APC gene mutation and related extra-thyroidal neoplasm, such as FAP and Gardner syndrome.