Follicular variant of papillary carcinoma of the thyroid: Fine-needle aspirates with histologic correlation

Crile and Hazard reported in 1953 a follicular pattern of papillary thyroid carcinoma. Little has been said about this pattern in the cytologic literature. From more than 8,000 thyroid aspirates in our files, we reviewed all those diagnosed as “follicular variant of papillary carcinoma,” “suspect follicular variant of papillary carcinoma,” and “follicular neoplasm vs. follicular variant of papillary carcinoma.” Also, we reviewed all aspirates in which a diagnosis of follicular variant of papillary carcinoma had been made on surgically excised glands, regardless of the cytologic diagnosis; 63 aspirates from 45 patients were collected. All smears were air-dried and stained with Diff-Quik. Most smears were very cellular (“tumor cellularity”), and the neoplastic follicular cells formed empty follicles, rosettes, tubules, and papillary structures. Nuclei were twice the size of red blood cells, had smooth contours, were hyperchromatic, and varied in shape but not much in size. Nuclear overlapping was common. Some nuclei had one small and almost pointed end, thereby resembling arrowheads. Intranuclear inclusions, multinucleated histiocytes, and psammoma bodies were uncommon. Pink-stained colloid was frequent. Diagn. Cytopathol. 16:207–213, 1997. © 1997 Wiley-Liss, Inc.     

Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma

AIMS: The purpose of this study was to investigate the significance of 'benign' encapsulated follicular thyroid nodules with papillary structures. METHODS AND RESULTS: Twenty-one cases of encapsulated neoplastic thyroid nodules with papillary structures and nuclear features not diagnostic of papillary thyroid carcinoma (PTC) were obtained. All cases were reviewed with particular attention to nuclear features (fine chromatin pattern, optical clearing, grooves and inclusions). Representative sections were submitted for measurement of the maximum diameter of 200 round or nearly round nuclei and for immunostaining for MIB1, CK19, HBME and Ret oncogene protein. Nine cases displayed scattered optically clear nuclei or nuclear grooves in less than 30% of total neoplastic cells. They were grouped in the category of thyroid nodules with limited nuclear features of papillary thyroid carcinoma (PTC), but not diagnostic of PTC. The other 12 cases had fine or coarse chromatin, but lacked other features of nuclei in PTC. The diameter of the nuclei ranged from 5.6 to 7.2 microm and were smaller than those of PTC (6.3-10.0 microm). Immunostaining revealed positive reactivity for MIB1 in the papillary structures. Immunostaining for CK19 and HBME varied from negative or focally weak to diffusely moderate reactivity. Ret oncogene protein immunostaining showed focal and weak reactivity in one case and was negative in other cases of the study. Clinical follow-up from 6 months to 15 years revealed no evidence of metastasis. CONCLUSIONS: The papillary structures in the study cases are unlikely to represent degenerative changes due to their proliferative activity. In view of (i) the encapsulation and the uniformity of the constituent cells, (ii) the varying degrees of immunoreactivity for CK19 and HBME and negative immunoreactivity for Ret oncogene protein, and (iii) the absence or insufficiency of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of follicular adenoma. Recognition of this pathological entity is important to avoid an over-diagnosis of PTC.     

Cribriform variant of papillary thyroid carcinoma

We report a case of papillary carcinoma of the thyroid exhibiting unusual cribriform structures. The thyroid origin of the tumor was confirmed by positive immunostaining for thyroglobulin.     

Macrofollicular variant of papillary thyroid carcinoma

A rare case of a macrofollicular variant of papillary thyroid carcinoma occurring in an 18-years-old male is described. The extirpated tumor, 5.5 × 5.5 × 3.5 cm In size, was well demarcated and multinodular, and histopathologically showed a predominantly macrofolllcular structure reminiscent of adenomatous goiter or macrofollicular adenoma. In the tumor tissue, however, there were several small foci of microfollicular or paplllary structure with the nuclei charae teristic of papillary carcinoma. Parts of the macrofollicular areas also showed similar nuclear characteristics with a transition to microfollicular or papillary areas. Incomplete capsular invasion and minimal vascular invasion were also present. Additional resected specimens contained small metastatic nodules in the residual left lobe and lymph nodes. Immunohistochemistry showed a small number of p53-positive tumor cells in the microfollicular or papillary areas. It is suggested that this tumor is a well-differentiated variant which should be distinguished from benign thyroid lesions, although there have been some cases of metastases which appear related to capsular and/or vascular invasion.     

Encapsulated papillary thyroid carcinoma, follicular variant: a misnomer

Papillary thyroid carcinoma (PTC) has long been diagnosed based on its unique nuclear features (PTC-N); however, significant observer discrepancies have been reported in the diagnosis of encapsulated follicular patterned lesions (EnFPLs), because the threshold of PTC-N is subjective. An equivocal PTC-N may often occur in non-invasive EnFPLs and benign/malignant disagreements often create serious problems for patients' treatment. This review collects recent publications focusing on the so-called encapsulated follicular variant of papillary thyroid carcinoma (EnFVPTC) and tries to emphasize problems in the histopathological diagnosis of this spectrum of tumors, which covers encapsulated common-type PTC (EncPTC), EnFVPTC, well-differentiated tumor of uncertain malignant potential (WDT-UMP), follicular adenoma (FA) with equivocal PTC-N and minimally invasive follicular carcinoma (mFTC). We propose that EnFVPTC and other EnFPLs with equivocal PTC-N should be classified into a unified category of borderline malignancy, such as well-differentiated tumor of uncertain behavior (WDT-UB), based on their homogeneous excellent outcome. It is suggested that the unified nomenclature of these lesions may be helpful to reduce significant observer disagreements in diagnosis, because complete agreement in the diagnosis of an EncPTC, EnFVPTC or FA by all pathologists may be not possible for this problematic group of tumors. In conclusion, a malignant diagnosis of EnFVPTC should not be used to cover this spectrum of tumors until uncertainty about the nature of this lesion is settled, whether it is benign, precancerous or malignant.     

Macrofollicular variant of papillary carcinoma: a potential thyroid FNA pitfall

Macrofollicular variant of papillary carcinoma (MFPC) is a rare variant of papillary carcinoma in which over 50% of the follicles are represented by macrofollicles. The cytologic features from 7 cases of histologically confirmed MFPC were evaluated. The cytology specimens were evaluated for the following criteria: cellularity, cluster arrangement (micro and macrofollicular), chromatin pattern, nuclear grooves, pseudonuclear inclusions, nuclear shape, nuclear overlap, nucleoli, presence of lymphocytes, macrophages and Hurthle cell, amount and characteristics of background colloid. Most cases were moderately to highly cellular with presence of both microfollicles as well as macrofollicles, but nuclear features of papillary thyroid carcinoma were absent or focal in all cases. MFPC is a variant of papillary carcinoma that can be extremely difficult to diagnose cytologically. The presence of abundant colloid, macrophages, macrofollicular follicular cell arrangement and/or absence of widespread cytologic features associated with papillary carcinoma can lead to an erroneous diagnosis of goiter.     

Distinguishing tall cell variant of papillary thyroid carcinoma from usual variant of papillary thyroid carcinoma in cytologic specimens

Tall cell variant (TCV) is an aggressive form of papillary thyroid carcinoma (PTC), usually associated with higher local recurrence and distant metastasis. Some authors have suggested that TCV can be effectively diagnosed on thyroid fine-needle aspiration (FNA); this diagnosis may help clinicians plan a more effective treatment regimen. The objective of this study was to compare the FNA specimens of TCV with those of usual variant of PTC (UV-PTC) and to define a set of distinguishing cytologic features. Thirty FNA specimens of histologically proven TCV were compared with 32 FNA specimens of histologically proven UV-PTC. All specimens were evaluated for the following features: papillary groups (PG), elongated/tall cells (EL/TC), oncocytic cytoplasm (OC), distinct cell borders (DCB), prominent central nucleoli (PCN), intranuclear grooves (NG), and intranuclear inclusions (NI). These features were semiquantitatively measured on a sliding scale of 0-4 in both air-dried Diff-Quik-stained and ethanol-fixed Papanicolaou-stained preparations. TCV showed distinctive cytologic features, which can distinguish them from UV-PTC. These included EL/TC, OC, and DCB and were also found to be statistically significant (P < 0.0001). No significant differences were noted for PG and NG. The NIs in TCV cases were qualitatively different than those in UV-PTC. In TCV there were multiple inclusions within the same nucleus imparting a "soap bubble appearance" to the nucleus. This feature was seen in almost all cases of TCV and was rarely seen in usual PTC. On the basis of the above-mentioned cytologic features, TCV can be distinguished from usual PTC in FNA specimens.     

Diffuse sclerosing variant of papillary thyroid carcinoma

Virchows Archiv - The recently published second edition of the WHO classification of thyroid tumours describes the diffuse sclerosing papillary carcinoma (DSPC) as a specific variant of papillary...     

C cell carcinoma of the thyroid. Follicular variant

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene-related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immunohistochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma.     

Follicular and papillary variants of medullary carcinoma of the thyroid

Two medullary carcinomas of the thyroid (MCT) with relatively unusual patterns are reported. The first was an aggressive tumour which occurred in a 66-year-old man and displayed in most areas follicular structures. The second tumour occurred in a 36-year-old woman, followed a benign course and showed papillary infoldings lined by multilayered neoplastic cells. The search for thyroglobulin yielded negative results whereas calcitonin immunoreactivity could be found in most neoplastic cells of both tumours. The diagnosis of MCT was further substantiated by the presence of scarce amyloid deposits and typical neuro-secretory granules by electron microscopy. These cases demonstrate once more that follicular and papillary structures can be a prominent feature of some MCTs reinforcing therefore the major role of immunocytochemistry in the differential diagnosis of thyroid carcinomas. Papillary MCT seems to carry a good prognosis in contrast to follicular MCT if one takes into account the follow-up data of the present cases together with those of similar cases reported in the literature; the whole series is nevertheless too small to allow for definite conclusions on this matter.     

Cytology of columnar-cell variant of papillary thyroid carcinoma

Columnar cell variant of papillary carcinoma (CCV-PC) thyroid is a rare and aggressive tumor composed of tall columnar cells that form papillae, glands and solid structures. This paper describes fine needle aspiration (FNA) cytologic features in a case of CCV-PC occurring in the right thyroid lobe of a 27-year-old female. Smears showed tall columnar cells in monolayered, three-dimensional, acinar and occasional papillary clusters. Nuclei were oval or elongated and monomorphic. Nuclear pseudostratification, resembling that seen in respiratory epithelial cells, was present in some of the cell clusters. Occasional cells showed squamous or Hurthle cell metaplasia. Nuclear grooves and intranuclear cytoplasmic inclusions were not seen. Sections of the right lobectomy specimen showed an well-encapsulated CCV-PC with capsular and vascular permeation. Tall cell variant of papillary carcinoma (TCV-PC) can be distinguished from CCV-PC by the oxyphilia of the tumor cells and the absence of nuclear pseudostratification. Colorectal and endometrial adenocarcinomas metastatic to the thyroid may be difficult to distinguish from CCV-PC.     

FNA diagnosis of a metastatic papillary thyroid carcinoma arising from a previously unknown follicular variant of papillary thyroid microcarcinoma

While metastatic tumors to bone or lymph nodes from previously known primaries are often successfully diagnosed via fine‐needle aspiration (FNA), a metastatic deposit in a patient with no previously known cancer may pose a diagnostic dilemma. Here, we present a case of metastatic papillary thyroid carcinoma that presented initially as a large pelvic bone mass. FNA was performed on this mass. The diagnosis was challenging due the fact that the tumor did not display the classic nuclear features associated with papillary thyroid carcinoma, instead the nuclear morphology was in keeping with a follicular thyroid carcinoma. Given the patient's concurrent, unremarkable thyroid imaging studies the final diagnosis required an extensive immunohistochemical work‐up. Diagn. Cytopathol. 2014;42:711–715. © 2013 Wiley Periodicals, Inc.     

Follicular variant of papillary carcinoma: cytologic findings on FNAB samples-experience with 16 cases

Between January 1, 1992 and December 31, 1997, a cytopathological diagnosis of follicular variant of papillary thyroid carcinoma (FVPC) was made on a series of 16 out of 18 patients with palpable nodules who underwent fine-needle aspiration biopsy (FNAB) in our Department. The results of aspiration biopsy were followed by histopathological examination of the surgically excised tissues. There were three false-negative aspirations (16.6%), of which two were probably bound to fine-needle sampling and one due to a mixture of benign and malignant cells which had originally gone unrecognized. The accuracy of the cytopathologic diagnosis in this variant was 88.8%. An analysis of the diagnostic cytopathological criteria was performed, which demonstrated the importance of both architectural features (monolayered and branching sheets, microacinar structures, and their combinations) and nuclear features (presence of nuclear grooves). Background -bound features were mainly represented by dense, nonfilamentous colloid. The cytopathologic findings in FVPC were compared to those found in a series of 10 usual papillary carcinomas (UPC) and 10 follicular neoplasms (FN). These latter had originally been diagnosed by FNAB and were subsequently classified histologically as follicular adenoma (n = 6), follicular carcinoma (n = 3), or adenomatoid colloid nodule (n = 1). Statistical evaluation was performed on the cytopathological findings in the three classes of lesions (FVPC, UPC, and FN) as to their presence and relative frequency or absence by using a nonparametric one-way ANOVA (Kruskall-Wallis) and, where necessary, a Mann-Whitney U test. Papillary cellular fragments and multinucleated giant cells (P < 0.005), nonfilamentous dense colloid, squamoid cells, and syncytia were significantly more represented in UPC than in FVPC (P < 0.05), while histiocytes were significantly more frequent in FVPC (P < 0.005). Other nuclear and/or background features were significant only in the distinction between papillary carcinomas as a group and FN. The cytological differential diagnosis of the FVPC is briefly discussed with relevance to the possible pitfalls caused by its peculiar cyto- and histomorphology.