Anaplastic thyroid carcinoma: diagnostic challenges,histopathologic features and ancillary testing

Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid malignancy with high mortality rate. This malignancy arises in thyroid follicular cells either denovo or with an associated differentiated thyroid carcinoma component. Clinically, it usually presents as a rapidly enlarging mass, pain and locally compressive symptoms. Histopathologic variability and heterogeneity often pose diagnostic challenges, especially in scant and paucicellular specimens. This article describes the clinical, histopathologic and molecular features of ATC and also addresses the associated diagnostic limitations and challenges.     

Anaplastic carcinoma of the pancreas with rhabdoid features

The malignant rhabdoid tumor (MRT) is histologically characterized by the invasive proliferation of polygonal to ovoid cells with abundant eosinophilic cytoplasm and eccentric vesicular nuclei with a prominent nucleolus. MRT frequently occurs in the kidney, but may also arise in other organs. However, MRT should be strictly distinguished from carcinomas with rhabdoid features. A post-mortem examination of a 68-year-old woman found an anaplastic carcinoma of the pancreas with rhabdoid features displaying extensive invasion into the neighboring tissues. To the best of our knowledge, this is the first case of a pancreatic tumor with rhabdoid features. Pathologists should consider that carcinomas showing rhabdoid features may also appear in the pancreas. As pancreatic tumors with rhabdoid features have characteristic histopathological features and poor prognosis compared to other pancreatic tumors, careful histopathological differential diagnosis is important.     

Cytologic features of insular carcinoma of the thyroid: a case report

Fine-needle aspiration of the thyroid has been accepted as one of the initial diagnostic tools in the evaluation of thyroid nodules. As its use becomes more widespread, the demand for more precise diagnosis has increased. The histopathology of insular carcinoma of the thyroid is now well recognized. However, the cytologic diagnostic criteria are not well established. The reported series have been small (4-6 cases), which is not surprising because of the rarity of this tumor. They consist of retrospective reviews of the aspirates (after the histologic diagnosis had been made from the thyroidectomy specimens). Also, the case reports do not provide uniform cytologic criteria; this could be due to limited sampling of these tumors (which are usually large). A cytologic diagnosis of insular carcinoma can be suggested if multiple samples of a thyroidal mass are markedly cellular, with a cytologic pattern reminiscent of a follicular variant of papillary carcinoma. However, the follicular cells are arranged predominantly in rosettes, their nuclei appear more monotonous, some "intranuclear cytoplasmic pseudoinclusions" are seen, and there is an occasional large cell with a pleomorphic nucleus.     

Paraganglioma‐like medullary thyroid carcinoma: A case report and literature review

Medullary thyroid carcinoma (MTC) accounts for 3%‐5% of all thyroid malignancies. Most MTC can be diagnosed by their typical cytologic and histologic morphology and immunohistochemical features. However, some rare variants of MTC may pose diagnostic difficulties on both cytology and histology. Paraganglioma‐like MTC (PLMTC) is a rare, but widely recognized variant of MTC. PLMTC is known to share morphological and architectural similarities with paraganglioma, hyalinizing trabecular tumor, and carcinomas of thyroid follicular cell origin, such as follicular carcinoma and follicular variant of papillary thyroid carcinoma. The combination of clinicopathologic features and a battery of immunohistochemical markers is essential for making a correct diagnosis. Herein, we report one case of PLMTC with both cytologic and histologic features and review the clinicopathologic features of previously reported cases.     

Metastatic medullary thyroid carcinoma to the breast in a patient with combined medullary and papillary carcinoma of thyroid—A case report

We report the fine‐needle aspiration cytology of a case of medullary thyroid carcinoma (MTC) metastatic to the breast in a 66‐year old female within two years of diagnosis of the thyroid tumor. The aspirate of the breast metastases revealed a plasmacytoid population of cells in loose clusters and singly with mild to moderate pleomorphism. Nuclear groves and occasional intranuclear cytoplasmic inclusions were seen. The cells stained positive for calcitonin and negative for thyroglobulin. Use of immunocytochemical methods proved useful to diagnose metastasis which was essential in planning treatment. Cases of metastatic MTC to the breast diagnosed on fine‐needle aspirates reported in the literature are reviewed. Diagn. Cytopathol. 2015;43:343–348. © 2014 Wiley Periodicals, Inc.     

Mixed medullary-follicular carcinoma of the thyroid: diagnostic dilemmas in fine-needle aspiration cytology

Mixed medullary-follicular carcinoma (MMFC) of thyroid is an extremely rare tumor, characterized by coexistence of morphological and immunohistochemical features of both medullary carcinoma and follicular (or papillary) carcinoma. We herein present fine needle aspiration (FNA) findings of a histology-confirmed MMFC along with a review of literature. The patient was a 64-year-old woman who had a history of Hashimoto's thyroiditis and presented with enlargement of preexisting right thyroid nodule. An US-guided FNA of the thyroid nodule was performed and conventional smears were prepared. A cytologic diagnosis of "positive for malignancy, consistent with medullary thyroid carcinoma (MTC)" was rendered based on the presence of features characteristic for MTC, and the absence of components of follicular neoplasm (adenoma and carcinoma) or papillary carcinoma. However, microscopic examination of the follow-up total thyroidectomy specimen with the aid of immunocytochemical study detected minor portion of follicular carcinoma in addition to MTC. A histologic diagnosis of MMFC was then established. While specific identification of MMFC by FNA may be difficult, it should be emphasized that adequate sampling in conjunction with the proper immunostaining panel could have highlighted the different aspects of the mixed tumor.     

Esophageal carcinoma with a rhabdoid phenotype: a case report of diagnosis by endoscopic ultrasound-guided fine-needle aspiration

Malignant extra renal tumors with rhabdoid phenotype are aggressive neoplasms associated with a poor prognosis. These tumors have been reported in soft tissue and various organs including the gastrointestinal tract. We report one of such tumors arising in the esophagus and discuss the cytopathologic, immunohistochemical, and ultrastructural features. Endoscopic ultrasound-guided fine-needle aspiration (FNA) cytology revealed a highly cellular tumor, consisting of polygonal poorly cohesive cells with prominent eosinophilic paranuclear cytoplasmic inclusions. Immunohistochemical staining showed strong cytoplasmic positivity for vimentin and cytokeratin. Electron microscopy revealed presence of numerous intermediate filaments. To the best of our knowledge, this is the first example of carcinoma with rhabdoid phenotype of the esophagus diagnosed by FNA cytology.     

Mediastinal seminoma presenting as a neck mass falsely diagnosed as anaplastic thyroid carcinoma: A case report

Germ cell tumors can occur in the mediastinum. They account for about 20% of tumors at this location. The majority are located in the anterior mediastinum and usually occur in young adult males. Extension of mediastinal germ cell tumors into the neck with mass formation is a very rare and unusual event. Herein, we report a case of a 34 year old male who presented with a progressively enlarging neck mass. Fine Needle Aspiration (FNA) was performed as initial evaluation and showed cellular smears comprising atypical large cells with prominent irregular nucleoli and moderate amount of cytoplasm with lymphocytic infiltrate and some epithelioid granulomas in the background. The mass was misdiagnosed initially on the cytology smears as anaplastic thyroid carcinoma. The subsequent tissue core biopsy showed sheets and nests of atypical cells admixed with ill‐defined granulomatous inflammation. By immunohistochemistry, the tumor cells were immunoreactive with SALL4, PLAP and OCT3/4, compatible with malignant germ cell tumor, seminomatous type. It is very rare for patients with primary mediastinal seminoma to present initially with a neck mass. Fine Needle Aspiration (FNA) of this “neck mass” can lead to misinterpretation of findings due to similarities in cytological features between malignant germ cell tumors and other undifferentiated malignant neoplasms and the diagnosis, therefore, can be very challenging.     

A case of papillary carcinoma in a thyroglossal cyst without a carcinoma in the thyroid gland

The thyroglossal duct cyst is the most common developmental anomaly of the thyroid gland. We present a patient with a papillary thyroid carcinoma diagnosed after surgical resection of a thyroglossal cyst. The 39-year-old patient reported to our hospital due to a swelling of this throat. The results of the ultrasonography were reported as showing multiple nodules in both thyroid lobes, and an ~3-cm diameter image in the submental area, in keeping with lymphadenomegalia. In the fine-needle aspiration cytology (FNAC) evaluation from the nodules in the thyroid, it was observed that the thyrocites with uniform nuclei made up single-layer groups. FNAC from the thyroglossal cyst, a few histiocytes were observed on a ground with a large number of erythrocytes. The patient was subjected to a total thyroidectomy, pyramidal lobe excision, and total excision of the 3-cm diameter soft mass, starting at the tip of the pyramidal lobe. The case was diagnosed as papillary thyroid carcinoma in thyroglossal duct cyst with histopathological and immunohistochemical findings. If the thyroglossal channel cyst had been diagnosed preoperatively, total thyroidectomy and a Sistrunk operation would have been performed. For this reason, repeated FNAC, particularly, if performed under ultrasound guidance, may improve the diagnostic value of FNAC. Thus, in such patients, throat ultrasonography must be carried out in expert hands, thin-needle aspiration biopsy, computerized tomography, and thyroid scintigraphy must be done if necessary, and the necessary treatment protocols carried out after a definite diagnosis.     

Hypercalcitoninemia and thyroid nodules

Medullary thyroid carcinoma (MTC) can assume various cytomorphological and architectural forms, mimicking other thyroid and extra‐thyroid tumors and rendering the cytological and histological diagnosis challenging. Consequently, measurement of calcitonin (CT) levels is generally considered to be more accurate than cytology in diagnosing MTC. Here, we report on a patient with a multinodular goiter and significantly elevated basal CT levels; based on cytology examination and CT immunocytostains, neither MTC nor C‐cell hyperplasia was detected upon final histopathological examination. CT testing has a high false‐positive rate and low positive predictive value for detecting clinically relevant MTC. Judicious integration of cytological examination with immunocytochemical stains (when needed) may be useful for selecting the most appropriate therapy and avoiding overtreatment (i.e., central neck lymph node dissection in the present case). This case demonstrates that cytological examination with ancillary techniques is still valuable in patients with thyroid nodules and suspicious MTC. Diagn. Cytopathol. 2014;42:970–973. © 2014 Wiley Periodicals, Inc.     

Case report: Different metastatic components from anaplastic thyroid carcinoma in mediastinal and neck lymph nodes simultaneously diagnosed by FNA

Anaplastic thyroid carcinoma (ATC) is a rare but aggressive form of undifferentiated thyroid carcinoma which arises from previously well‐differentiated thyroid carcinomas, such as papillary carcinoma or follicular carcinoma. We report on an interesting case of ATC found in an enlarging neck mass with metastatic papillary carcinoma found in mediastinal lymph nodes sampled by endoscopic bronchial‐ultrasound guided‐ fine‐needle aspiration, due to the incidental finding of a lung mass by CT scan. Divergent morphologies on cytology preparations were resolved by immunohistochemistry, which aided in the identification of both sites of malignancy and the common thread between them. The eventual palliative resection demonstrated the various components including undifferentiated thyroid carcinoma, papillary carcinoma, and background lymphocytic thyroiditis. Diagn. Cytopathol. 2014;42:694–699. © 2013 Wiley Periodicals, Inc.     

Fine‐needle aspiration of a pancreatic neuroendocrine tumor with prominent rhabdoid features

Pancreatic neuroendocrine tumors (PanNETs) are uncommon neoplasms that conventionally possess architectural and cytomorphological features seen in neuroendocrine neoplasms found at other sites. When present, these features often allow rapid identification of neuroendocrine differentiation and an accurate diagnosis. Here, we report the cytologic findings seen on fine‐needle aspiration (FNA) of a PanNET with distinct rhabdoid features. This morphology is rare in PanNETs and has been reported in only two case series examining surgical resection specimens and has not been described on FNA. It is important to recognize this morphology as this variant appears to portend an aggressive clinical course. Furthermore, unfamiliarity with this morphologic variant may lead to a larger initial differential and thus delay final diagnosis.     

Cytological features of clear cell thyroid tumors,including a papillary thyroid carcinoma with prominent hobnail features

Primary thyroid tumors with extensive clear cell changes are extremely rare. More than 10,000 ultrasound‐guided thyroid fine needle aspirations examined over a period of 17 years by the first author, only one of the 530 (<0.2%) papillary thyroid carcinomas (PTCs) and three of the 42 (7.1%) follicular thyroid carcinomas (FTCs) had extensive cytoplasmic clearing. Thyroidectomies were performed for these cases at four different hospitals in New York City. Final pathology was available for review in each of the four cases. Histology showed a 1.5‐cm PTC with prominent hobnail features and clear cell change in a 31‐year‐old woman, a 4.3‐cm FTC without angioinvasion in a 31‐year‐old woman, a 4.5‐cm angioinvasive FTC in a 45‐year‐old man, and a 2‐cm FTC with extensive angioinvasion in a 41‐year‐old woman with McCune–Albright syndrome (previously published). On ultrasound, the FTCs were solid circumscribed nodules and the PTC had an irregular margin. In these cases, the etiology for the cytoplasmic clearing included accumulation of glycogen in the PTC, accumulation of vesicles in two of the FTCs, and accumulation of lipid droplets in a FTC with extensive angioinvasion. Review of the cytologic literature showed 17 cases of follicular‐derived thyroid tumors with extensive clear cell change. To the best of our knowledge, this is the first cytologic report of PTC with hobnail features and extensive clear cell change. Diagn. Cytopathol. 2013;41:757–761. © 2012 Wiley Periodicals, Inc.     

The triage efficacy of fine needle aspiration biopsy for follicular variant of papillary thyroid carcinoma using the Bethesda reporting guidelines

Diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) by ultrasound-guided fine-needle aspiration (FNA) is challenging. In this retrospective review, we evaluated triage efficacy (i.e., potential for triggering surgical intervention) in 44 archived FNA biopsies of surgically confirmed FVPTC obtained between December 2006 and December 2008. We compared the original FNA diagnoses with reclassified diagnoses based on 2007 National Cancer Institute (NCI)/Bethesda recommendations, and reviewed FNA cytologic features. Original FNA diagnoses included colloid nodule (7%, 3/44), atypical follicular cells (5%, 2/44), follicular lesion (11%, 5/44), follicular neoplasm (16%, 7/44), suspicious for malignancy/PTC (27%, 12/44), and papillary thyroid carcinoma (34%, 15/44). Reclassified diagnoses included indeterminate (5%, 2/44), colloid nodule (7%, 3/44), atypical cells of undetermined significance [ACUS] (7%, 3/44), Hurthle cell neoplasm (2%, 1/44), follicular neoplasm (7%, 3/44), suspicious for malignancy/PTC (25%, 11/44), and PTC (48%, 21/44). Triage efficacy was 77% (34/44) for original diagnoses versus 82% (36/44) for reclassified FNA diagnoses. We frequently observed cytologic features of PTC, such as nuclear grooves and fine chromatin; conversely, intranuclear inclusions, though present in 77% cases, were scant. Our review findings suggest that lack of characteristic cytologic features of PTC,coexistence with other thyroid lesions, and small tumor size arethe major obstacles to FNA diagnosis of FVPTC. Reclassification of thyroid FNA diagnoses does not significantly improve triage efficacy. Furthermore, FNA diagnoses of follicular neoplasm and suspicious for malignancy are valuable in patients with FVPTC because they trigger triage toward surgical intervention.     

Mucinous breast carcinoma metastatic to thyroid gland: Report of a case diagnosed by fine‐needle aspiration cytology

Mucinous breast cancer is a slow‐growing neoplasm, which has fewer lymph node metastases and favorable prognosis compared with invasive breast cancer no special type. The hematogenous spread of breast mucinous carcinoma is very rare. Though breast cancer involving thyroid has been reported before, there is still no report about thyroid metastatic breast mucinous carcinoma in the literature. Recently by performing thyroid fine‐needle aspiration, a 58‐year‐old woman who had breast cancer 13 years ago was diagnosed as thyroid metastatic mucinous breast carcinoma, cellular variant with neuroendocrine differentiation. For this patient, the thyroid was the only involved site without widespread metastatic diseases, so thyroidectomy and the right cervical lymph nodes dissection were performed to make better survival. As a result, the patient had not shown any signs of recurrence 9 months after the thyroid surgery.