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.     

Be Aware of the Patient With Benign Follicular Thyroid Lesion Histology and Rising Thyroglobulin Level

Objective: The accurate diagnosis of thyroid follicular/Hürthle cell tumors is challenging and a matter of controversy. We present a series of patients in whom a misclassification of follicular/Hürthle cell thyroid lesions as benign has led to devastating clinical outcomes.Methods: The Thyroid Cancer Registry of Rabin Medical Center was screened for patients with metastatic differentiated thyroid carcinoma (DTC) who had been initially diagnosed with benign follicular lesion between 1974 and 2015 and treated with hemithyroidectomy. Clinical, pathologic, and outcome data were collected from the medical files. Adequate pathology specimens, when available, were re-evaluated.Results: Seven patients met the inclusion criteria. The original pathologic diagnosis was follicular adenoma in 4 patients and Hürthle cell adenoma in 3 patients. Five patients had bone metastases, of whom one also had lung metastases and one, liver metastases. One patient had both cervical and lung metastases, and 1 patient had only meta-static neck lymph nodes. Six patients had a final diagnosis of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), and 1 patient was diagnosed as having follicular thyroid cancer metastasis by bone biopsy. In 3 of the patients, capsular invasion was detected retrospectively; only 1 patient had evidence of vascular invasion. All 7 patients had high levels of thyroglobulin at diagnosis of metastatic DTC.Conclusion: Misclassification of follicular thyroid lesions as benign may lead to progressive disseminated DTC. To minimize the clinical risk of misdiagnosis, especially if a thorough evaluation of the specimens by an experienced pathologist is unfeasible, we suggest long-term follow-up of serum thyroglobulin levels.Abbreviations: DTC = differentiated thyroid carcinoma; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma     

Mixed medullary-follicular thyroid carcinoma. Report of a case and review of the literature

OBJECTIVE: The aim was to describe the case of a female patient with a mixed medullary-follicular thyroid carcinoma. METHODS: The patient underwent thyroidectomy for the treatment of multinodular goiter. A tumor was found which exhibited the features of a mixed medullary-follicular thyroid carcinoma. Immunohistochemistry was performed. RESULTS: Immunohistochemistry was positive in the area of the carcinoma for calcitonin and thyroglobulin. She developed extensive metastatic deposits in the bones of the pelvis and in the calvarium causing hyperthyroidism. CONCLUSION: A patient with a mixed medullary-follicular thyroid carcinoma is described, who had elevated levels of both calcitonin and thyroglobulin and developed metastatic deposits, which could produce thyroid hormones.     

Adenoid cystic pattern in follicular variant of papillary thyroid carcinoma: a report of four cases

S. Mandal, and S. Jain
Adenoid cystic pattern in follicular variant of papillary thyroid carcinoma: a report of four cases Objective: An adenoid cystic pattern in thyroid tumours is a rare finding that may be seen in papillary carcinoma of thyroid (PCT), the follicular variant of PCT (FV‐PCT), a rare cribriform‐morular variant of papillary carcinoma of thyroid (CMV‐PCT) and follicular carcinoma. There is little published cytological literature describing these patterns. We report four cases of PCT with this unusual pattern. Methods: Fine needle aspiration (FNA) cytology was performed on four patients with a neck lump using a 22‐G needle; smears were stained with Giemsa and Papanicolaou stains. Immunocytochemical staining for thyroglobulin was done in all cases. Results: The patients were female and ranged in age from 18 to 46 years. They presented with a gradually increasing mass in the neck. FNA smears in all cases showed nuclear features of PCT. There were also prominent follicular areas with hyaline globules in some of the cell clusters reminiscent of adenoid cystic carcinoma and, in places, morula‐like groups of neoplastic cells were also seen. Immunocytochemistry for thyroglobulin was positive in all cases but negative in the hyaline globules. Conclusions: Adenoid cystic areas with morula‐like groups in PCT are a rare finding. Cytopathologists and clinicians should be aware of these distinct features in thyroid tumours to avoid diagnosing metastatic adenoid cystic carcinoma. It is also important to rule out CMV‐PCT since that variant is mostly associated with familial adenomatous polyposis, although sporadic occurrence is known.     

Renal cell carcinoma metastatic to follicular adenoma of the thyroid gland. A case report

BACKGROUND: Renal cell carcinoma is an unpredictable tumor that can recur many years after the original diagnosis and metastasize to uncommon sites, including the thyroid gland. Differential diagnosis from primary thyroid tumor is often difficult both clinically and pathologically. We report a case of metastatic renal cell carcinoma in follicular adenoma of the thyroid gland. CASE: A 48-year-old woman presented with a 3-cm-diameter, palpable mass in the left lobe of the thyroid gland. The patient's history included removal of a left renal mass, which was conventional renal cell carcinoma. Fine needle aspiration cytology smears contained a few small clusters of polygonal cells with abundant, clear cytoplasm and irregular, hyperchromatic nuclei as well as bland-looking thyroid follicle cells and stromal cells. A papillary or follicular growth pattern was not detected. A cell block made from the aspirated sample was composed mainly of clear cells. By immunohistochemical stains, the clear cells were completely negative for TTF-1, thyroglobulin, calcitonin and inhibin while equivocally staining for cytokeratin, CD10 and galectin-3. The histologic diagnosis was renal cell carcinoma metastatic to follicular adenoma of the thyroid gland. CONCLUSION: Renal cell carcinoma metastatic to the thyroid may masquerade as a primary thyroid neoplasm. A history of prior nephrectomy, the presence of unremarkable thyroid follicle cells, the absence of a papillary or follicular growth pattern and immunohistochemical study can help differentiating metastatic renal cell carcinoma from a primary thyroid lesion with clear cell change.     

Biochemical characterization of serum thyroglobulin from patients with bone metastases from follicular carcinoma of the thyroid.

The biochemical properties of serum thyroglobulin obtained from six patients with follicular carcinoma of the thyroid and distant metastases to bone(s) have been studied. Since it is difficult to isolate sufficient thyroglobulin from serum samples, in vivo radioiodinated serum thyroglobulin obtained after radioiodine administration was used. In contrast to a sharp salting-out pattern observed with native thyroglobulin isolated from normal thyroid tissue, a broad salting-out curve was seen with metastatic serum thyroglobulin. The metastatic serum thyroglobulin eluted with low ionic strength from ion-exchange column. More than 95% of metastatic serum thyroglobulin could be bound to concanavalin-A sepharose and be eluted with 0.5 M alpha-methyl mannoside. The reactivity of metastatic serum thyroglobulin and native thyroglobulin towards concanavalin-A was comparable. Both types of thyroglobulins showed identical mobilities on sucrose linear density gradient centrifugation. The metastatic serum thyroglobulin from follicular carcinoma of the thyroid thus appears to be 19 S thyroglobulin with near normal concanavalin-A binding sugars but altered surface charges.     

Malignant struma ovarii: report of a case and review of the literature

Malignant struma ovarii is a very rare disease and therefore there is neither common agreement on treatment regimens nor sufficient follow-up experience. The case of a 38-year-old woman with malignant struma ovarii is described. The patient presented with a clinically silent ovarian neoplasm discovered incidentally during investigations for metrorrhagia. The ovarian mass was resected and the tumor was found to be a teratoma. Within the teratoma a papillary thyroid carcinoma of the follicular variant was found. Subsequently, in order to make follow-up of the patient possible by thyroglobulin measurement and radioiodine whole body scintigraphy, near-total thyroidectomy was performed and the thyroid was found to be normal on histology. Whole body radioiodine scintigraphy with (131)I and ablation of the thyroid remnant by the administration of 80 mCi (131)I was performed. The patient recovered uneventfully and is now well.     

Long-Term Follow-Up of a Patient With Papillary Thyroid Carcinoma,Elevated Thyroglobulin Levels,and Negative Imaging Studies

ObjectiveTo describe a patient with papillary thyroid carcinoma who had measurable thyroglobulin (Tg) levels for 20 years without clinical or imaging evidence of a malignant lesion.MethodsWe reviewed the clinical course, pathologic findings, Tg measurements, and results of various imaging studies in our patient and reviewed the literature regarding Tg-positive, diagnostic total-body radioiodine scan-negative patients with thyroid cancer.ResultsFour months after a 3.5- by 3.5-cm follicular thyroid cancer was removed from the anterior neck area of a 5-year-old girl, a bilateral subtotal thyroidectomy was performed. At age 12 years, she presented with a 2-cm mass on the right side of the neck. After a completion thyroidectomy, recurrent mixed papillary-follicular thyroid cancer was found scattered throughout the remaining thyroid parenchyma. Although a postoperative diagnostic total-body radioiodine scan did not reveal uptake of ¹³¹I, the Tg level was 58 ng/mL. Despite Tg levels as high as 2,528 ng/mL, the patient had no clinical evidence of thyroid cancer during a 20-year period of follow-up. Moreover, numerous imaging studies, including total-body scanning after the administration of 150 mCi of ¹³¹I and [¹⁸F]fluorodeoxyglucose positron emission tomography, were negative. Review of pathologic specimens from both operations with use of updated diagnostic criteria indicated that the tumor was a papillary thyroid carcinoma.ConclusionOur observations and the observations of other investigators indicate that some thyroid cancers produce Tg so efficiently that high levels of Tg may be associated with tumors that remain too small to be detected by imaging studies. The Tg levels may remain stable, decline, or even disappear over time without treatment. (Endocr Pract. 2005;11:43-48)     

Simultaneous occurrence of medullary and papillary carcinoma of the thyroid gland identified by fine needle aspiration. A case report

BACKGROUND: Fine needle aspiration (FNA) diagnosis of simultaneous medullary and papillary thyroid carcinoma in independent thyroid lobes is exceedingly rare. CASE: A 36-year-old female presented with a one-month history of dysphagia. Thyroid ultrasound revealed a multinodular goiter. She was clinically and biochemically euthyroid. FNA of the right thyroid nodule was consistent with medullary carcinoma, and FNA of the left thyroid lobe was consistent with papillary carcinoma. Immunohistochemistry revealed strong calcitonin and CEA positivity in the right lobe and lack of staining in the left lobe. Conversely, staining for thyroglobulin was negative on the right lobe and positive on the left lobe. CONCLUSION: The patient developed tumors in separate lobes of the thyroid. Immunoreactivity of calcitonin, CEA and thyroglobulin made a sharp distinction between the two tumors. Therefore, we conclude that these tumors were not linked by either embryology or genetics.     

The immunohistochemical demonstration of thyroglobulin in human thyroid tumour xenografts using a monoclonal antibody

A monoclonal antibody (RBU/01) was raised against human thyroglobulin and its suitability for the immunohistochemical staining of thyroglobulin was determined on fixed, wax-embedded tissue, using the peroxidase anti-peroxidase (PAP) method. The antibody was then used to demonstrate the expression of human thyroglobulin in sections of a human follicular carcinoma of the thyroid which had been grown in immunodeficient mice. It is concluded that the immunohistochemical evaluation of the xenografts with the antibody provides useful information on this xenograft system as a potential model for thyroid carcinoma.     

The potential value of the demonstration of thyroglobulin by immunoperoxidase techniques in fine needle aspiration cytology

The peroxidase-antiperoxidase method for the demonstration of thyroglobulin was performed on 30 fine needle aspiration smears. All of the benign thyroid lesions plus the papillary and follicular carcinomas of the thyroid were positive for thyroglobulin. Two cases of metastatic thyroid carcinoma in lymph nodes were also positive. Medullary carcinoma of the thyroid and ten control smears from various other tissues were negative. This proves the sensitivity and the specificity of the method, which may be used in routine cytology and may add to the accuracy of diagnosing metastatic tumors suspected of being of thyroid origin. The intranuclear cytoplasmic vacuoles in papillary carcinoma of the thyroid were negative for thyroglobulin. This unexpected finding is demonstrated, and a possible explanation is offered.     

Immunohistochemistry of thyroid hormones as a functional parameter in thyroid pathology

The authors study by means of immunoperoxidase method the pattern of thyroglobulin, triiodothyronine and thyroxine distribution in 58 cases of thyroid disorders: 15 euthyroid goiters, 10 Graves' disease, 7 Hashimoto's thyroiditis, 11 folliculo-papillary carcinomas (6 primary tumors and 5 lymph node metastases), 8 follicular carcinomas, 4 anaplastic carcinomas and 3 medullary carcinomas. Thyroglobulin, triiodothyronine and thyroxine were present in most of the thyroid disorders, excepting anaplastic and medullary carcinomas. Thyroglobulin and thyroxine were localized both in the follicular epithelium and in the colloid, whereas triiodothyronine was present especially in the follicular cells. The thyroid hormones distribution in benign lesions is rather similar. In carcinomas, the pattern of thyroglobulin, triiodothyronine and thyroxine is more heterogeneous, but generally the triiodothyronine distribution is similar to that of thyroglobulin. In some carcinomas, triiodothyronine and thyroxine showed a weak or negative immunostaining. The immunoperoxidase method is a valuable tool in the study of functional disturbances in the thyroid pathology and in the diagnosis of thyroid carcinoma metastases as well. Positive thyroid hormones staining clearly indicates the thyroid origin of metastases.     

The immunohistochemical demonstration of thyroglobulin in human thyroid tumour xenografts using a monoclonal antibody

Summary A monoclonal antibody (RBU/01) was raised against human thyroglobulin and its suitability for the immunohistochemical staining of thyroglobulin was determined on fixed, wax-embedded tissue, using the peroxidase anti-peroxidase (PAP) method. The antibody was then used to demonstrate the expression of human thyroglobulin in sections of a human follicular carcinoma of the thyroid which had been grown in immunodeficient mice. It is concluded that the immunohistochemical evaluation of the xenografts with the antibody provides useful information on this xenograft system as a potential model for thyroid carcinoma.     

Anaplastic carcinoma of the thyroid with chondroblastoma features mimicking papillary carcinoma: a case report

BACKGROUND: An unusual case of anaplastic carcinoma of the thyroid arising from a metastatic focus of papillary carcinoma. CASE: The tumor affected a 69-year-old woman with a history of total thyroidectomy for papillary thyroid carcinoma 4 years previously. She presented with a rapidly enlarging neck mass that histologically simulated chondroblastoma. A small, embedded focus of residual follicular variant of papillary carcinoma was present. The patient died of disease 3 months later. CONCLUSION: This "chondroblastoma" variant of anaplastic thyroid carcinoma has not been reported to date.     

Use of Methotrexate to Treat Isolated Graves Ophthalmopathy Developing Years After Thyroidectomy and Iodine 131 Treatment of Papillary Thyroid Cancer

ObjectiveTo describe a case of Graves ophthalmopathy developing years after subtotal thyroidectomy and radioactive iodine treatment of papillary thyroid cancer.MethodsWe present a case report including clinical and laboratory data. Current relevant literature is reviewed and summarized with regard to Graves ophthalmopathy.ResultsIn 2001, a 51-year-old woman presented with an asymptomatic thyroid nodule. Fine-needle aspiration biopsy results showed Hürthle cells, and the patient had a subtotal thyroidectomy in 2002. Stage 2 follicular variant of papillary thyroid carcinoma was diagnosed. She received radioactive iodine (I 131) therapy (94.8 mCi and 147.2 mCi) in 2003. Thyrotropin was suppressed with levothyroxine. The patient remained asymptomatic and had undetectable thyroglobulin antibodies. In 2007, her eyes became irritated (ie, erythematous, pruritic, watery). Thyroperoxidase and thyroglobulin antibodies were undetectable, but thyrotropin receptor antibody was elevated to 44% (reference range, < 16%). On physical examination, moderate periorbital edema and conjunctival injection were present; orbital magnetic resonance imaging was normal. Computed tomography of her orbits showed symmetric bilateral exophthalmos and prominence of orbital fat. Other ophthalmologic etiologies were ruled out by 2 independent ophthalmologists. She had minimal improvement with oral and intravenous steroids. Subsequent treatment with methotrexate resulted in marked symptomatic improvement and lowered the thyrotropin receptor antibody level to 24%.ConclusionsIsolated Graves ophthalmopathy in a patient after treatment of thyroid cancer and radioactive iodine ablation has not been previously reported. Methotrexate therapy may be a useful therapeutic approach in this setting. (Endocr Pract. 2008;14:422-425)     

Metastatic anaplastic carcinoma of the thyroid mimicking squamous cell carcinoma: report of a case of a challenging cytologic diagnosis

BACKGROUND: The probability of anaplastic transformation in a differentiated thyroid carcinoma (DTC) is <2%. Admixture of DTC and undifferentiated carcinoma can occasionally be found in thyroidectomy specimens, or the undifferentiated tumor may develop in metastatic foci months or years after removal of the primary tumor. CASE: Anaplastic transformation of a metastatic DTC was diagnosed at autopsy in a 71-year-old female. At the time of her total thyroidectomy for follicular carcinoma, she already had several lung nodules, which diminished in size upon 131I treatment. Five years later the patient developed a new, pleura-based lung mass. The mass extended along the paraspinal soft tissue and involved the kidney. Fine needle aspiration biopsy of the paraspinal mass resulted in a diagnosis of metastatic squamous cell carcinoma. Two months later the patient died. Histologic evaluation of the lung nodules and pleura-based mass revealed areas of follicular carcinoma intermixed with a various patterns of undifferentiated carcinoma. The paraspinal and kidney mass consisted entirely of anaplastic tumor, including areas of squamoid differentiation. CONCLUSION: In patients with a history of DTC who develop a rapidly growing mass elsewhere, a possibility of metastatic DTC with anaplastic transformation must be considered.     

The Role of Recombinant Human Thyrotropin for Diagnostic Monitoring of Patients with Differentiated Thyroid Cancer

ObjectiveTo describe the evolving role of recombinant human thyrotropin in the diagnostic evaluation of patients treated for differentiated thyroid carcinoma.MethodsA systematic review was performed of published English language articles appearing in PubMed using terms “recombinant thyrotropin” and “thyroid cancer”. The author selected articles for inclusion based upon potential for clinical impact of the reported findings.ResultsThe addition of recombinant human thyrotropin to diagnostic testing replaced the requirement for thyroid hormone withdrawal and symptomatic hypothyroidism that had been necessary to generate sufficient endogenous thyrotropin for radioiodine scanning and thyroglobulin testing. The high negative predictive value of stimulated thyroglobulin testing removed the need for serial radioiodine scanning for many patients, but repeated stimulated testing rarely appeared to add significantly. The development of highly sensitive second generation thyroglobulin assays may replace the need for stimulated testing in a subset of patients.ConclusionRecombinant human thyrotropin-stimulated testing continues to be a valuable component of follow-up testing in the first year after initial treatment of differentiated thyroid cancer. (Endocr Pract. 2013;19: 157-161)     

A functioning pleomorphic carcinoma of the thyroid.

A metastasizing functioning pleomorphic carcinoma of the thyroid displayed a morphologic piture ranging from follicular to sarcomatous and carcinoid-like patterns. Spindle-cell elements were believed to be the result of metaplasia of the follicular epithelium. Development of carcinoid-like lesions in the secondary deposits of tumour supported the contention that so-called parafollicular or c-cells may be a phenomenon of metaplasia and not a histologic entity. The tumour was associated with a chromophobe adenoma of the pituitary and a benign schwannoma of the stomach. Clinically the patient did not show any other endocrinologic abnormalities and lived for 4 years from the time of diagnosis of the thyroid tumour.