Controversies in Thyroid Pathology: The Diagnosis of Follicular Neoplasms (original) (raw)
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Bangladesh Medical Research Council Bulletin, 2017
A significant increase in incidence of papillary thyroid carcinoma (PTC) has been noticed in recent decades worldwide. This is due to advances in medical surveillance, increased use of ancillary tests, and a minor component due to over diagnosis of PTC. Follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common variant of PTC and comprises about 23-41%. It is difficult to diagnose histologically when the distinctive nuclear features are either not well developed or present focally within the lesion. Several immunohistochemical markers (CD56, HMCK, GAL3, HBME-1 and CK19) either alone or combined in panels can be used to improve diagnostic accuracy. This study was aimed to differentiate FVPTC from other follicular patterned lesion of thyroid by histopathology and immunohistochemistry (IHC). A total of 50 histologically diagnosed cases of thyroid neoplasm were studied. The neoplastic cases included 40 cases of follicular variant papillary carcinoma (FVPC), 04 classic papillary carcinoma (PTC), 04 follicular carcinoma and 02 follicular adenoma. All cases were evaluated by IHC for the expression of CD56 and CK19 antibody. In case of FVPTC (n=40), 21 cases (52.5%) were CK19 positive and CD56 negative as expected. Both markers were found positive in 06 (15%) cases and CD56+ alone was found positive in 11 (27.5%) cases of FVPTC, and a finding that goes against the diagnosis of FVPTC. The histopathological slides of these cases were reviewed and findings were recorded. All cases (n=4) of classic PTC were CK19 positive and 03 (75%) cases were found CD56 negative. Diagnoses of thyroid follicular lesions are primarily based on histological and cytomorphological criteria. However, there was a subset of follicular patterned tumors like FVPTC which lack unequivocal features of malignancy. Immunohistochemistry can improve diagnostic accuracy but needs additional studies for controversial cases. It may be considered these lesions as differentiated tumor of uncertain malignant potential (WDT-UMP) to avoid the using term carcinoma. Additional studies are needed for establishing more precise morphologic criteria and for identifying useful markers for differentiating benign from borderline or malignant thyroid lesions.
Postgraduate Medical Journal, 2008
The follicular variant of papillary thyroid carcinoma (FVPTC) presents a type of papillary thyroid cancer that has created continuous diagnosis and treatment controversies among clinicians and pathologists. In this review, we describe the nomenclature, the clinical features, diagnostic problems and the molecular biology of FVPTC. It is important for clinicians to understand this entity as the diagnosis and management of this group of patient may be different from other patients with conventional PTC. The literature suggests that FVPTC behaves in a way similar, clinically, to conventional papillary thyroid carcinoma. However, there are some genotypic differences which may characterise this neoplasm. These parameters may account for the phenotypic variation described by some scientists in this type of cancer. Further understanding can only be achieved by defining strict pathological criteria, in-depth study of the molecular biology and long term follow-up of the optional patients with FVPTC.
Virchows Archiv, 2002
In an attempt to advance and improve the characterization of the so-called diffuse follicular variant of papillary thyroid carcinoma (diffuse FVPTC) we studied a series of 59 thyroid carcinomas consecutively treated in a specialized center. The clinicopathologic and some of the immunohistochemical characteristics (uPA-R, Lewis X, Sialyl Lewis X, and MIB-1) of ten cases of FVPTC displaying a multinodular or diffuse pattern of growth, and histologic features similar to those previously described in diffuse FVPTC, were compared with those of common papillary thyroid carcinoma (PTC, 25 cases) and common FVPTC (8 cases). Cases of diffuse FVPTC differed significantly from common PTC and FVPTC in targeting younger patients and in exhibiting a prevalence of multicentricity, extrathyroid extension, nodal metastasis, and vascular invasion. Immunohistochemically, diffuse FVPTC cases were characterized by the overexpression of uPAR and sialyl Lewis X. No differences were observed regarding MIB 1 immunoreactivity. Regardless of the term used to designate the multicentric, invasive form of FVPTC (diffuse or multinodular FVPTC) it is crucial to acknowledge the existence of cases of FVPTC with a guarded prognosis that should be distinguished from the classic, uninodular form of FVPTC.
Immunohistochemical profile of well-differentiated thyroid neoplasms with follicular architecture
Hellenic Journal of Surgery, 2010
Aim-Background: Well-differentiated thyroid neoplasms with follicular architecture may often cause diagnostic difficulties, due to ambiguous pathological features. The aim of the present study was to investigate the immunohistochemical expression of a panel of markers, comprising cytokeratin-19, cytokeratin-20, galectine-3, ceruloplasmin, lactoferin, secretory component, HBME-1, calcitonin, chromogranin-A, TTF-1, synaptophysin and thyroglobulin, in well-differentiated thyroid neoplasms with a special emphasis on atypical neoplasms and to investigate their possible diagnostic role. Methods: A series of 148 cases of papillary carcinomas, 21 cases of follicular carcinomas, 50 cases of follicular adenomas and 21 cases of atypical neoplasms was collected from the registry or the files of the Department of Pathology of Areteion Hospital. Each case was examined for its immunohistochemical expression of markers. Results: Atypical neoplasms expressed Cytokeratin-19 in 15/21 cases, Cytokeratin-20 in 3/21 cases, galectine-3 in 12/21 cases, ceruloplasmin in 7/21 cases, secretory component in 8/21 cases, lactoferin in 4/21 cases, HBME-1 in 9/21 cases, TTF-1 in 3/21 cases and thyroglobulin in 4/21 cases. No reactivity was noted for calcitonin, chromogranin-A and synaptophysin in any of the cases we studied. Conclusions: The immunohistochemical reactivity of atypical neoplasms seems to be located between those of either papillary carcinomas and follicular adenomas or follicular carcinomas and follicular adenomas, which supports the theory of their possible common histogenetic link. The above mentioned panel of markers seems to contribute only slightly, if at all, in the differential diagnosis of those lesions.
The diagnostic dilemma of follicular variant of papillary thyroid carcinoma* 1
Surgery, 2003
Background. Given the difference in surgical management between follicular neoplasms and papillary thyroid carcinoma (PTC), we sought to determine the sensitivity of fine-needle aspiration (FNA) and intraoperative pathologic study (IP), frozen section and cytologic study, in establishing a diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) and how these techniques impact operative management. Methods. A retrospective chart review was performed of patients who underwent thyroidectomy for nodular disease between June 1997 and June 2002 identifying patients with a final diagnosis of FVPTC. FNA and IP results were reviewed in this group of patients and correlated with those of final histopathologic study. The sensitivity of FNA and IP was calculated. Results. Eighty-two patients had a final diagnosis of FVPTC. Eighty-six preoperative FNAs were obtained in 80 patients, leading to a diagnosis of PTC in 7 (sensitivity 9%). Intraoperative pathologic study was performed in 31 patients with suspicious FNA results, of which 13 were definitive for PTC (sensitivity 42%). Overall, IP was obtained in 42 patients, of which 15 were positive for PTC (sensitivity 36%). Conclusion. Although the sensitivity of FNA in establishing a diagnosis of FVPTC is low, FNA identifies patients with suspicious lesions in whom IP is important in guiding operative management. (Surgery 2003;134:1005-12.
JAMA otolaryngology-- head & neck surgery, 2014
The follicular variant (FV) of papillary thyroid carcinoma (PTC) is an important subtype that can be difficult to diagnose using preoperative cytologic analysis. To compare conventional and FV PTC with regard to preoperative cytologic diagnosis using a tiered thyroid cytologic reporting system, tumor size at diagnosis, presence of invasion, and implications on prognostic scores. This retrospective study was conducted in an academic teaching hospital and included 99 patients with conventional (n = 65) or FV (n = 34) PTC. Preoperative thyroid cytologic findings, originally reported using the tiered British Thy system, were recategorized according to the Bethesda classification system. Pathologic features recorded included tumor size, presence of extrathyroid extension (ETE), and metastases. Prognostic scores were calculated according to the MACIS system. Differences in patient demographics, preoperative cytologic findings, tumor pathologic features, and prognostic risk categories betw...
2015
Background: Papillary thyroid carcinoma (PTC) is the most common among the thyroid malignancies. Fine needle aspiration cytology (FNAC) is the first line investigation in the diagnosis of thyroid lesions. Here we review the significance of certain features conventionally considered to be diagnostic of papillary thyroid carcinoma on FNAC – including type of background, type of colloid, presence or absence of papillary clusters, intranuclear inclusions and nuclear grooves which were also considered for their importance in early diagnosis of PTC. Methods: We reviewed all the thyroid FNACs performed over 18 months period and correlated them clinically and histopathologically, wherever available. Results: Out of a total of 354 cases of thyroid FNACs, histopathological correlation was possible in 90 cases, with a concordant diagnosis in 82 cases. Analysis of the 8 discordant FNAC smears revealed papillary clusters along with nuclear features, especially nuclear grooves to be the most impo...
Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma
The American Journal of Surgical Pathology, 2004
The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Recent reports have suggested that this neoplasm may be frequently overdiagnosed by pathologists. We examined the observer variation in the diagnosis of FVPCA in 87 tumors by 10 experienced thyroid pathologists. The criteria that the reviewers considered most helpful for making a diagnosis of FVPCA were also assessed. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. In this series, 24.1% of the patients had metastatic disease (n = 21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7%, and 7 of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100%. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable even among experienced thyroid pathologists, most reviewers agreed on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve the consistency in diagnosing FVPCA. Since most cases with metastatic disease had obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.
Immunohistochemical Diagnosis of Papillary Thyroid Carcinoma
Modern Pathology, 2001
In thyroid, the diagnosis of papillary carcinoma (PC) is based on nuclear features; however, identification of these features is inconsistent and controversial. Proposed markers of PC include HBME-1, specific cytokeratins (CK) such as CK19, and ret, the latter reflecting a ret/PTC rearrangement. We applied immunohistochemical stains to determine the diagnostic accuracy of these three markers. Formalin-fixed, paraffin-embedded tissue from 232 surgically resected thyroid nodules included 40 hyperplastic nodules (NH), 35 follicular adenomas (FA), 138 papillary carcinomas (PC; 54 classical papillary tumors and 84 follicular variant papillary carcinomas [FVPC]), 4 follicular carcinomas (FC), 6 insular carcinomas (IC), 7 Hürthle cell carcinomas (HCC), and 2 anaplastic carcinomas (AC). HBME-1 and ret were negative in all NH and FA; some of these exhibited focal CK19 reactivity in areas of degeneration. Half of the FC and AC exhibited HBME-1 staining but no positivity for CK19 or ret. In PC, 20% of cases stained for all three markers. Classical PC had the highest positivity with staining for HBME-1 in 70%, CK19 in 80%, and ret in 78%. FVPC were positive for HBME-1 in 45%, for CK19 in 57%, and for ret in 63%; only 7 FVPC were negative for all three markers. The six IC exhibited 67% staining for HBME-1 and 50% positivity for CK19 and ret. The seven HCC had 29% positivity for HBME-1 and CK19, and 57% positivity for ret. This panel of three immunohistochemical markers provides a useful means of diagnosing PC. Focal CK19 staining may be found in benign lesions, but diffuse positivity is characteristic of PC. HBME-1 positivity indicates malignancy but not papillary differentia-tion. Only rarely are all three markers negative in PC; this panel therefore provides an objective and reproducible tool for the analysis of difficult thyroid nodules.