Cytologic diagnosis of a medullary carcinoma of the thyroid by Sevier-Munger silver staining and calcitonin immunocytochemistry

A medullary carcinoma of the thyroid was preoperatively diagnosed on ultrasonically guided fine needle aspiration biopsies. After cytocentrifugation, the tumor cells displayed a dense cytoplasmic silver granulation with the Sevier-Munger technique when applied to air-dried or acetone-ethanol-fixed samples and an obvious calcitonin immunoreactivity after fixation in Bouin's fluid. These methods may prove useful in the identification of nonpalpable metastases and recurrences of medullary carcinomas of the thyroid, especially since the cytologic typing of medullary thyroid carcinoma cells may be difficult with routine stainings.     

Fine needle aspiration biopsy of mixed medullary-follicular thyroid carcinoma. A report of two cases

BACKGROUND: Mixed differentiated thyroid carcinomas are rare tumors, difficult to recognize on fine needle aspiration biopsy (FNAB). Most cases are diagnosed only after histologic investigation. CASES: The cases entailed two cytologic samples and a thyroidectomy specimen. Two FNAB thyroidectomy specimens from a 60-year-old man presenting with a solitary thyroid nodule (case 1) were investigated. Both cytologic samples were referred as atypical, with a mixture of features indicating a proliferating follicular lesion but also containing some characteristics of medullary carcinoma. The serum calcitonin level was borderline. Surgery was recommended because of a suspicion of malignancy. The diagnosis of mixed medullary follicular carcinoma was established after a complex histologic investigation. The tumor was encapsulated, with partly microfollicular architecture. Immunohistochemistry was positive for both calcitonin and thyreoglobulin. Electron microscopy from the formol-paraffin block found neurosecretory granules in many cells. The patient was well one year after the operation. One FNAB and thyroidectomy specimen from a 47-year-old woman with long-treated lymphoplasmocellular thyroiditis (case 2) was investigated. The tumor in case 2 was diagnosed on FNAB as medullary carcinoma. Only after histologic and immunohistochemical investigation was mixed differentiation proven. CONCLUSION: Mixed differentiated thyroid tumors are a diagnostic challenge on fine needle aspiration. Irrespective of their rarity, they can be suspected if combined features are present. FNAB recognition of the medullary component in both cases was of crucial importance. Nevertheless, definitive diagnosis remains a histologic problem due to the necessity for topographic information.     

Intranuclear cytoplasmic inclusions in aspirates of follicular neoplasms of the thyroid. A report of two cases

Two cases are reviewed in which the presence of intranuclear cytoplasmic inclusions in fine needle aspiration biopsy specimens of the thyroid suggested a diagnosis of papillary carcinoma. Subsequent surgical specimens were consistent with diagnoses of microfollicular adenoma and follicular carcinoma. These cases suggest that the presence of intranuclear inclusions in epithelial thyroid cells is not limited to papillary and medullary carcinoma, as some authors have suggested.     

Synovial sarcoma of the thyroid. Report of a case with aspiration cytology findings and gene analysis

BACKGROUND: Synovial sarcoma, generally known as a soft tissue tumor, can also occur in the head and neck region, including the thyroid gland. Cytologic findings are important to differentiate the tumor from other types of neoplasms arising in the thyroid gland. CASE: A 60-year-old man complained of hoarseness. A palpable neck tumor was detected, and a computed tomography scan showed a thyroid tumor accompanied by destruction of the thyroid and cricoid cartilage. The results of a preoperative fine needle aspiration biopsy showed numerous spindle cells with pale cytoplasm and oval nuclei with fine, granular chromatin, all of which suggested a medullary carcinoma. The extirpated thyroid tissue weighed approximately 120 g, and a grayish white, elastic, solid tumor (6.8 x 6.5 cm) was present in the left lobe. Histologically, fasciculation of spindle cells that had proliferated solidly and densely was observed. Also, the expression of a chimera gene, SYT-SSX, was detected in the tumor tissue. CONCLUSION: Synovial sarcoma of the thyroid is extremely rare, and its diagnosis by fine needle aspiration biopsy is generally considered very difficult. The detailed cytologic findings observed here might be helpful with the differential diagnosis of thyroid neoplasms.     

Occult medullary carcinoma of thyroid with lymph node metastases: a case report

BACKGROUND: Occult thyroid malignancies presenting with secondary neck masses as the first clinical manifestation is well known. Although rare, medullary carcinoma serves a potential source for lymph node metastases. The characteristic cytomorphology of medullary thyroid carcinoma (MTC) should clinch the diagnosis. Further, fine needle aspiration cytology (FNAC) of the ultrasonography-detected occult nodules in thyroid serves as a useful preoperative diagnostic tool. CASE: A 22-year-old man presented with left-sided neck masses of 1 year duration. FNAC smears of the neck masses revealed cytomorphology characteristic of MTC. Ultrasonography of the thyroid led to ruling out the presence of an occult nodule and detected an 8-mm nodule in the left thyroid lobe. Ultrasound-guided FNAC of the nodule showed features similar to those with FNAC of the neck masses. Surgical resection of thyroid and neck masses further confirmed the diagnosis of a primary occult MTC with lymph node metastases. CONCLUSION: FNAC smears of lymph node masses showing the distinct cytomorphology of MTC should prompt suspicion for occult primary in thyroid. Ultrasound-guided FNAC of these occult nodules, if detected, further serves a diagnostic tool for accurate preoperative diagnosis when metastasis presents as the first clinical manifestation of an occult primary.     

Physical and radiological findings specific for medullary carcinoma of the thyroid gland.

Preoperative physical and radiological findings, if specific to a certain extent, are important for detecting patients with sporadic form of medullary thyroid carcinoma and especially for the first patient in the family having a hereditary form of medullary thyroid carcinoma and pheochromocytoma syndrome. To delineate clinical features of medullary thyroid carcinoma, a total of 9 patients with this tumor were reviewed retrospectively. In most patients, the thyroid lesions were located in the upper two thirds of the lobe, which was determined by careful palpation or 131I scintiscanning of the thyroid. The primary lesion in the thyroid could be felt more or less as a round, sharply demarcated nodule with fairly good mobility. These findings suggested rather a benign thyroid nodule when there was no lymph node involvement. However, it could be considered a sign suggesting medullary thyroid carcinoma when accompanied by marked lymph node metastasis. In our recent 2 cases, the diagnosis of medullary thyroid carcinoma was strongly suspected on these clinical bases, one of the cases being presented in detail. In 4 patients, lymph node metastasis in the central neck extended to either submandibular or upper mediastinal regions or both. In about one third of the patients, calcified deposits were shown in the cervical roentgenograms. With the use of soft tissue roentgenography, grossly punctate calcific deposits associated with psammoma-like shadows were recognized and the pattern was a criterion for definitive diagnosis of medullary thyroid carcinoma.     

Detection of medullary thyroid microcarcinoma using ultrasound‐guided fine needle aspiration cytology

G. C. H. Yang, K. Fried and P. H. Levine Detection of medullary thyroid microcarcinoma using ultrasound‐guided fine needle aspiration cytology Objective: Compared with incidental papillary thyroid microcarcinoma (microPTC), incidental medullary thyroid microcarcinoma (microMTC) is clinically more significant. The objective of the present study was to summarize our experience in detecting microMTCs. Methods: From 1995 to 2011, there were 10 825 thyroid fine needle aspirates (FNAs) guided using high‐resolution ultrasound with on‐site preparation and evaluation by a cytopathologist. Of the 140 microcarcinomas detected, 132 were microPTCs and eight were microMTCs, which are the subject of the present study. Results: All eight cases were incidentalomas and none of the five women and three men, age 37–70 years, had a family history of MTC. One patient had two FNAs at an interval of 10 months, two had a single lymph node metastasis and one had a 0.1‐cm tumour nodule near the main tumour. Four of five plasmacytoid cell microMCTs had irregular borders; two round cell and one rectangular cell tumours had smooth borders. In contrast, 17 larger MTCs diagnosed in the same period included seven plasmacytoid, four giant cell and six spindle cell types. All five plasmacytoid microMTCs were correctly diagnosed on FNA, but the round cell and rectangular cell tumours were undercalled as follicular lesions. Sampling of colloid from adjacent follicles was noted in microMTCs. Two were diagnosed on histology following recommended surgery and one was diagnosed on recommended repeat FNA. Conclusions: US‐guided FNA of thyroid lesions is a powerful tool in the detection of microMTCs, provided that cytopathologists are alerted to the pitfalls described in the present study.     

Asymptomatic intrathyroidal parathyroid adenoma. Report of a case with a cytologic differential diagnosis including thyroid neoplasms

BACKGROUND: Intrathyroidal parathyroid neoplasms (IPNs) are uncommon tumors with an indolent clinical course. When asymptomatic, they can be incorrectly diagnosed as thyroid neoplasms on fine needle aspiration biopsy (FNAB), leading to inappropriate surgical treatment. CASE: A case of unsuspected IPN occurred in which the cytologic picture mimicked that of a thyroid neoplasm. The histologic specimen of the total thyroidectomy showed 2 adjacent intrathyroidal nodules morphologically and immunohistochemically corresponding to a parathyroid adenoma. CONCLUSION: The incidence of IPN remains controversial, especially in asymptomatic patients. On FNAB it is a possible cause of inappropriate surgery for a suspicious thyroid neoplasm (follicular or medullary carcinoma). Immunostaining for parathormone on the cytologic smear is valuable in establishing the correct preoperative diagnosis when the morphologic features are strongly suggestive of IPN.     

Columnar cell carcinoma of the thyroid. Fine needle aspiration findings in a case

Columnar cell carcinoma is a recently described rare tumor of the thyroid. The fine needle aspiration cytologic findings of one example are reported. In the smears, the tumor fragments showed papillary and glandular patterns. The tumor cells were columnar and exhibited pseudostratification of the nuclei. The nuclei were oval to elongated and possessed stippled chromatin and inconspicuous nucleoli; occasional ones exhibited longitudinal grooving. It is important to distinguish this tumor from papillary carcinoma of thyroid because of its much more aggressive behavior, from metastatic adenocarcinoma for obvious treatment considerations, and from medullary carcinoma.     

Fine needle aspiration cytology of mixed medullary-follicular thyroid carcinoma: a case report

BACKGROUND: Mixed medullary-follicular thyroid carcinoma (MMFTC) is a rare tumor that has been regarded as a clinicopathologic variant of medullary thyroid carcinoma. MMFTC represents a diagnostic challenge by fine needle aspiration cytology (FNAC). CASE: A 77-year-old woman had a palpable mass on the left side of the neck. It was diagnosed as follicular neoplasm by FNAC; she underwent total thyroidectomy. Pathology revealed follicular carcinoma. Radioactive iodine was administered. An enlarging mass was present in the left mandible later. FNAC showed suspicious follicular neoplasm with predominance of oncocytic cells. Pathology revealed follicular carcinoma with parafollicular cell differentiation. Immunohistochemical analysis demonstrated positive status for thyroglobulin and calcitonin. Simultaneous expression of thyroglobulin and calcitonin within the same neoplastic cell was considered. She underwent several courses of radioactive iodine therapy without significant effect. Interestingly, her serum calcitonin level was not elevated. CONCLUSION: Coexpression of thyroglobulin and calcitonin in the same cell is very rare. The component of medullary carcinoma should be considered when encountering an atypical thyroid carcinoma with predominance of cells showing oncocytic changes on FNAC and with clinically poor response to conventional treatment. Immunohistochemistry and pathologic analyses are helpful to confirm the diagnosis, especially in the absence of elevated serum calcitonin level.     

Medullary thyroid carcinoma. Rare cytologic findings

OBJECTIVE: To describe some rare cytologic findings in medullary thyroid carcinoma. STUDY DESIGN: Review of the fine needle aspiration smears from 15 cases of medullary thyroid carcinoma that were confirmed on histologic sections. The ages ranged between 31 and 67 years; 10 were female and 5 male. Thirteen were sporadic forms, and two were familial forms. RESULTS: Eight cases were classified as pleomorphic cell type and seven as monomorphic cell type. The smears revealed round, oval, triangular, polygonal and spindle-shaped cells, intracytoplasmic red granules, occasional intranuclear inclusions, amyloid, binucleated and multinucleated cells, and thick, granular chromatin. CONCLUSION: The rare cytologic findings in this study were grape cells, cytoplasmic nippling, elongated cytoplasmic processes, carrot-shaped nuclei, nuclear buddings, mast cell-like cells and a Burkitt's lymphoma-like appearance. These findings were rarely reported before.     

Medullary thyroid cancer - the present state of art

Medullary thyroid cancer is a neuroendocrine tumour originating from the parafollicular C cells of the thyroid gland that accounts for about 5-10% of all thyroid carcinomas. It may occur either sporadically (75%) or in familial forms (25%) in familial medullary thyroid carcinoma and multiple endocrine neoplasia types 2A and 2B. Distinct clinical phenotypes in hereditary medullary thyroid cancer result from different missense germline mutations in the RET protooncogene. Medullary thyroid cancer produce calcitonin, measurement of which indicates the presence of tumour in at-risk individuals and the effectiveness of management in treated patients. Prognosis of patients with medullary thyroid cancer is variable, but the more constant factors that affect it are the stage of disease and the age of the patient. The goal of treatment of patients suffering from medullary thyroid cancer is to detect and surgically remove disease at its early stage. Total thyroidectomy with local nodal dissection leads to achievement of biochemical cure in more than 80% of cases. The tumour does not take up radioactive iodine, is relatively radioresistant, and there is no known effective systemic therapy for this cancer. The purpose of this article is to summarise the present state of knowledge on the etiology, clinical presentation, management, prognosis, and genetics of medullary thyroid cancer.     

Intranuclear vacuoles in nonpapillary carcinoma of the thyroid. A report of three cases

Three cases of nonpapillary carcinoma of the thyroid are reported in which intranuclear vacuoles or (pseudo)inclusions were observed in fine needle aspiration smears. Two of the cases had medullary carcinoma; one had a poorly differentiated follicular carcinoma. The cytologic, histologic and ultrastructural appearances of intranuclear vacuoles and of the so-called ground-glass nuclei of papillary carcinoma are described, and the diagnostic significance of these findings is discussed briefly. Intranuclear vacuoles are distinct and different from ground-glass nuclei.     

The number of nucleoli in benign and malignant thyroid lesions: a useful diagnostic sign in cytological preparations

The slides of fine needle aspiration cytology specimens from 99 cases of cold thyroid nodules with known histology were reviewed and the number of nucleoli per nucleus counted and correlated with the different histopathological groups. Significant differences were observed between benign and malignant thyroid lesions in the number of nucleoli in the cytological material. Lower values were present in nodular goitres and follicular adenomas compared to carcinomas. In benign lesions the majority of nuclei contained one nucleolus and nuclei with two, three or more nucleoli were less frequent than in follicular, papillary, medullary and anaplastic carcinomas. Only one case of follicular adenoma had cells containing three or more nucleoli compared to more than half the cases of follicular carcinoma.     

Linkage analysis of hereditary thyroid carcinoma with and without pheochromocytoma

Summary The use of polymorphic DNA segments as markers for the gene for the multiple endocrine neoplasia (MEN) syndrome, type 2a, allows the identification of family members at high risk for developing medullary carcinoma of the thyroid and other tumors, especially pheochromocytoma. Several families have also been identified in which medullary thyroid carcinoma is inherited, but pheochromocytoma is not seen. We have analysed 18 families, 9 with MEN 2A and 9 with medullary carcinoma of the thyroid without pheochromocytoma, with probes specific for the pericentromeric region of chromosome 10 and conclude that the mutations for the two presentations are closely situated. Genetic heterogeneity of the susceptibility locus was not seen among this sample of 18 families. The genetic mutation for medullary carcinoma was in disequilibrium with the marker alleles of the two closely linked probes. IRBPH4 and MCK2. These data suggest that different mutant alleles of the same gene or closely linked mutations account for the variation in penetrance of pheochromocytoma in families with hereditary, medullary thyroid carcinoma.     

Nuclear grooves in the aspiration cytology of papillary carcinoma of the thyroid

Nuclear grooving has recently been shown to be a useful morphologic feature in the diagnosis of papillary carcinoma of the thyroid in tissue sections and imprint smears. In order to assess the diagnostic value of nuclear grooving in cytologic specimens, the presence of this feature was evaluated in fine needle aspirates from 20 papillary carcinomas of the thyroid, 10 follicular adenomas, 3 follicular carcinomas, 1 medullary carcinoma, 10 nodular goiters and 4 cases of Hashimoto's thyroiditis. In each case, 30 random high-power fields (HPFs), or all fields in less cellular smears, were examined, and the percentage of the fields in which nuclear grooving could be seen was recorded. Seventeen of 20 papillary carcinomas (85%) showed nuclear grooves in more than 25% of the HPFs examined; in the remaining three cases, grooves were observed in less than 25% of the HPFs. In control cases (all other thyroid lesions), nuclear grooves either were absent or were present in less than 25% of the HPFs examined. These findings suggest that nuclear grooving, when seen in abundance, can be considered a reliable criterion for the diagnosis of papillary carcinoma in fine needle aspiration cytology of the thyroid. The presence of occasional grooves, however, should be regarded as a nonspecific finding.     

人甲状腺髓样癌TT细胞胃动素基因表达的调控

目的:研究人甲状腺髓样癌TT细胞系中胃动素基因表达调控.方法:通过人甲状腺髓样癌TT细胞体外培养,观察经cAMP,生长激素或甲状腺雌激素诱导后,胃动素表达的改变以及胃动素对TT细胞生长、侵袭和转移的影响.结果:甲状腺髓样癌TT细胞表达胃动素mRNA,胃动素可抑制TT细胞的生长.当胃动素基因沉默后,TT细胞转移和侵袭能力增加.当TT细胞分别经cAMP、胃动素、生长激素或甲状腺刺激素孵育48小时后,胃动素基因转录增加,降钙素基因相关肽与胃动素mRNA比值持续下降.环磷酸腺苷可降低TT细胞增殖和c-myc基因的表达.结论:人甲状腺髓样癌细胞生长活性可能与甲状腺C细胞(低的降钙素基因相关肽与胃动素比率)分化的表型有关.     

Lifestyle and clinical factors associated with elevated C-reactive protein among newly diagnosed Type 2 diabetes mellitus patients: a cross-sectional study from the nationwide DD2 cohort

The involvement of the testis by metastatic medullary thyroid carcinoma has never been described before. We describe the first case of metastatic medullary thyroid carcinoma affecting testis and inguinal lymph nodes. A 73-year-old Caucasian man was referred to undergo urologic surgery due to a painless nodule in the right testis and an homolateral inguinal lymphoadenomegaly. The patient had a history of medullary thyroid carcinoma with relapsing disease to the spine and lung nodules. Serum calcitonin and CEA levels were 175 pg/ml and 22 ng/ml, respectively. With suspected testicular cancer, the patient underwent radical right orchiectomy with the excision biopsy of the right inguinal lymph node. Histopathology and immunohistochemistry revealed that both the lesions were due to metastases from medullary thyroid carcinoma. Metastases to the testis and inguinal lymph nodes may be due to various solid and hematological tumors. This case, despite its rarity, suggests that testis and inguinal lymph nodes should be considered as potential secondary sites of medullary thyroid carcinoma as well.     

Isolated carcinoid tumor metastatic to the thyroid gland: report of a case initially diagnosed by fine needle aspiration cytology

BACKGROUND: Neuroendocrine tumor metastatic to the thyroid gland is rare and may be difficult to differentiate from primary thyroid neuroendocrine tumors, such as medullary thyroid carcinoma (M/ITC). This report describes an unusual case of bronchial carcinoid metastatic to the thyroid diagnosed by fine needle aspiration cytology (FNAC). CASE: A 42-year-old woman with an undiagnosed bronchial carcinoid tumor presented to our clinic with a solitary nodule in the thyroid gland. FNAC of the nodule showed loosely cohesive groups of cuboidal tumor cells with scant, slightly granular cytoplasm; centrally located nuclei with a coarsely granular, salt-and-pepper chromatin pattern and inconspicuous nucleoli. Immunocytochemically the tumor cells were positive for neuron-specific enolase, chromogranin and synaptophysin and negative for thyroglobulin, calcitonin and carcinoembryonic antigen. The cytologic diagnosis of a metastatic neuroendocrine carcinoma was confirmed histologically. CONCLUSION: Metastasis to the thyroid gland may pose a diagnostic problem, particularly with tumors of neuroendocrine origin, as these have similar cytologic features in various organs. The correct preoperative cytologic diagnosis of metastatic carcinoid tumor in patients without a prior history of cancer and differential diagnosis with MTC are crucial because prognosis, workup and treatment are different in each.