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.     

Serum calcitonin negative mixed medullary‐follicular carcinoma initially diagnosed as medullary thyroid carcinoma by fine‐needle aspiration cytology: A case report and review of the literatures

Medullary thyroid carcinoma (MTC) is potentially lethal. A prompt and accurate diagnosis is the prerequisite for the treatment of MTC. Fine‐needle aspiration (FNA) is a reliable diagnostic tool in the assessment of thyroid nodules. However, cytologic assessment of MTC based on FNA has several drawbacks due to morphological variants. We present a case of MTC diagnosed through FNA cytology, which was eventually histologically confirmed as a mixed medullary‐follicular carcinoma with negative serum calcitonin expression. Hence, diagnosis of MTC based on FNA should be applied with caution. Ultrasound characteristics of suspicious thyroid nodules are recommended to be evaluated by FNA. However, calcitonin levels should be measured in both the FNA washout fluid and serum when features of MTC are presented or cytology result is inconclusive. If adequate FNA sample is available, a supplementary immunocytochemical staining of markers such as calcitonin, chromogranin, carcinoembryonic antigen, and thyroglobulin is helpful for a correct diagnosis of MTC.     

Cytologic diagnosis of recurrent medullary thyroid carcinoma with oncocytic change twenty-one years post-thyroidectomy: case report and review of the literature

A 66-year-old woman presented 21 years prior with diarrhea and elevated serum calcitonin levels. The left lobe of the thyroid was aspirated but specimen was unsatisfactory. Nevertheless, based on the radiological and clinical impressions, the patient underwent total thyroidectomy and the histologic examination established the diagnosis of medullary thyroid carcinoma (MTC). Approximately 5 years later, the patient had a recurrence of the disease and underwent a neck lymph node dissection, which showed metastatic MTC in a lymph node. Sixteen years later, the patient presented with left neck mass detected by ultrasound in the area of thyroid bed. Fine needle aspiration (FNA) of this area was performed and the FNA diagnosis was consistent with oncocytic variant of MTC. This case illustrates a first report of this uncommon variant of MTC diagnosed by FNA cytology of the thyroid bed.     

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.     

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.     

Laryngeal chondrosarcoma mimicking medullary thyroid carcinoma on fine‐needle aspiration cytology: A case report of a diagnostic pitfall

Chondrosarcoma (CS) of larynx is a rare laryngeal tumor accounting about 1% of laryngeal malignancies. When CS arises from thyroid cartilage, it may clinically present as a thyroid nodule. Here we report a rare case of CS of thyroid cartilage misinterpreted as medullary thyroid carcinoma. The main aim of this case report is to emphasize the important role of accurate clinical history, appropriate physical examination, and proper localization of the tumor and clear definitive imaging in conjunction with interpretation of cytologic smears. When any of these roles are unclear, it may result in misinterpretation of the cytologic smears. In these unusual circumstances, when cytomorphologic features does not completely fit an entity, communication with the physician and the consideration of a broad differential diagnoses in the head and neck pathology may lead to correct diagnosis and avoid diagnostic pitfalls. Also in certain conditions, ancillary studies including laboratory tests are necessary for definitive classification.     

Medullary thyroid carcinoma presenting as rectangular cell type on fine‐needle aspiration

Medullary thyroid carcinoma typically presents as dyscohesive plasmacytoid, spindled, or polygonal cells on fine‐needle aspiration smears. We recently encountered a case of sporadic medullary thyroid carcinoma that presented as a hypercellular aspirate composed of cohesive aggregates of rectangle‐shaped cells. The case was mistakenly reported as a hypercellular follicular neoplasm on cytology. Subsequent thyroidectomy revealed medullary carcinoma. We draw attention to this distinctive rectangular cell type as an additional morphology for medullary thyroid carcinoma. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

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.     

Melanotic medullary thyroid carcinoma: A case report with review of the literature

Melanotic medullary thyroid carcinoma is morphologically defined by the presence of melanin deposits in the cytoplasm of tumor cells. It is an extremely rare variant with only 15 cases described in the literature to date and only one report of diagnosis by fine needle aspiration (FNA) biopsy. A 51-year-old woman presented with neck swelling. An ultrasound examination revealed a single solid nodule in the right thyroid lobe that measured 5.4 × 4.7 × 4.3 cm. Laboratory examination revealed elevated levels of serum calcitonin (8643.0 pg/ml), carcinoembryonic antigen (CEA) (86.2 ng/ml), and chromogranin A (123.2 ng/ml). An FNA biopsy of the thyroid nodule revealed predominantly single plasmacytoid cells with round to oval eccentric nuclei and dark brown intracytoplasmic granules. Immunohistochemical studies with Melan-A performed on a cell block slide confirmed that the granules contained melanin. The tumor cells were also positive for calcitonin, CEA, synaptophysin, AE1/AE3, CAM5.2, and HMB-45(focal); the tumor cells were negative for chromogranin, thyroglobulin, PAX8 and TTF-1. The diagnosis was reported as melanotic variant of medullary thyroid carcinoma. The patient underwent a total thyroidectomy which revealed tumor cell expression of insulinoma-associated protein 1 and confirmed neuroendocrine differentiation. Shortly after she presented with tumor recurrence in the thyroidectomy bed. The tumor cells were positive for only S100, SOX10, and Melan-A. Molecular analysis with the SEMA4 Solid Tumor Panel revealed mutations in the HRAS, PIK3CA, PIK3R1, MYC, and CCND3 genes. The final diagnosis was reported as melanocytic medullary thyroid carcinoma with high grade transformation and loss of epithelial and neuroendocrine expression.     

Simultaneous medullary carcinoma of the thyroid gland and Hodgkin's lymphoma in bilateral lymph nodes of the neck: a potential pitfall in fine-needle aspiration cytology

The clinicopathological features and the cytological findings of Hodgkin's lymphoma (HL) and medullary carcinoma (MC) of the thyroid gland are described appearing simultaneously in different organs of the cervical region of the same patient. Although the cytological features of both entities are well known, the rare clinical presentation and the epithelium-like Hodgkin and Reed-Sternberg (HRS) cells of the syncytial variant of HL led to an erroneous cytological diagnosis of metastatic carcinoma of the upper aerodigestive tract.     

Mixed follicular-medullary thyroid carcinoma: a case report

We report on a 35-yr-old woman presenting with a single thyroid nodule. Fine-needle aspiration (FNA) of the nodule was reported to contain both follicular and parafollicular cells. The biphasic nature of the tumor was highlighted on immunohistochemical investigation of the cellblock. Positive staining for thyroglobulin was limited to the follicular structures and the dense areas stained positive for calcitonin. The serum calcitonin level was highly elevated. Surgery was recommended because of suspected malignancy. The patient underwent total thyroidectomy. The diagnosis of mixed medullary and follicular carcinoma of the thyroid was established by histological investigation using immunohistochemical staining for thyroglobulin, chromogranin, and calcitonin. The patient was well 1 yr after the operation. Repeated measurements of serum calcitonin levels were normal. Total body scan revealed no radioactive iodine uptake in the thyroid bed, bones, or lungs.     

Oncocytic variant of medullary thyroid carcinoma; a rare tumor with numerous diagnostic mimics by fine needle aspiration

Oncocytic variant of medullary thyroid carcinoma is rare form of thyroid carcinoma that is easily misdiagnosed on fine needle aspiration specimens due to it is low incidence and cytomorphologic overlap with other more common Hurtle cell lesions. A correct initial diagnosis by fine needle aspiration is imperative as the clinical treatment for medullary carcinoma differs significantly from the mimickers. We present a case of this rare variant tumor that on initial fine needle aspiration was described as a Hurthle cell lesion and was subsequently correctly classified on the resection specimen. In this brief review, we describe the cytomorphologic features of medullary carcinoma, oncocytic variant of medullary carcinoma and it is most common mimickers, and we discuss the ancillary studies required to confirm the diagnosis. This case highlights the importance of a complete clinical history and radiologic correlation, which in conjunction with a careful attention to the cytologic features of the fine needle aspiration sample, should in most cases ensure a correct initial diagnosis.     

Secretory activity in medullary thyroid carcinoma: a cytomorphological and immunocytochemical study

Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy of C-cell origin that secretes calcitonin. Although its varied cytomorphologic features are well described in literature, very little is mentioned about the morphologic manifestation of its secretory activity. This study, based on nine fine needle aspiration (FNA) samples from eight MTC patients, is an attempt to present the varied cytomorphologic features suggesting secretory activity in MTC as observed in Papanicolaou and MGG stained FNA smears and correlate them with the immunocytochemical (ICC) staining for calcitonin performed on FNA smears and the serum calcitonin values. The average number of cells in these nine samples was as follows: oval/triangular/plasmacytoid (56.7%), small round (23.6%), spindle-shaped (12.7%), and miscellaneous (7.1%). The cytomorphological features suggesting secretory activity, viz., fine cytoplasmic vacuoles, azurophillic granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions were present in eight, eight, five, and six samples, respectively. Material likely to be amyloid, based on morphological features, was present extracellularly in three samples and both intracellularly and extracellularly in six samples. Immunocytochemically, all the nine samples stained for calcitonin and all the three stained for chromogranin showed positive cytoplasmic reaction in the neoplstic cells. The background amyloid (in six samples), the coarse cytoplasmic granules (in two samples), and the contents of ICL (in one sample) were found to be positively stained for calcitonin. The intracytoplasmic secretory material appeared to be diffusing out of some cells both in the routine MGG stained smears and in the smears stained for calcitonin. Histopathology reports of seven samples in six patients confirmed the cytodiagnosis of MTC in all. Baseline serum calcitonin values in three cases and postoperative serum calcitonin levels during follow-up in three others were high. Thus, our study highlighted the morphological manifestations of secretory activity in MTC and the nature of secretory material as calcitonin, supported by immunocytochemical staining and serum calcitonin level.     

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.     

Risk of death due to disease for thyroid fine‐needle aspirations of well‐differentiated thyroid carcinomas

The risk of malignancy for some diagnoses in thyroid fine‐needle aspirations is higher than the actual risk of clinical progression. Other measures of prognosis may be helpful in managing patients with indeterminate thyroid fine‐needle aspiration diagnoses. We estimated the risk of death due to disease (RDDD) for well‐differentiated thyroid carcinoma using a series of over 15 000 aspirates with over 2000 excisions and data from the SEER database. RDDD was low (1.3% or less for all categories). The RDDD of some indeterminate thyroid aspirates was higher than for malignant aspirates. The RDDD may provide additional information for patients and clinicians seeking to manage patients with indeterminate thyroid fine‐needle aspirates.     

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.