Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features

Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37‐year‐old female with a history of metastatic ductal carcinoma of the breast (modified Bloom‐Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly‐shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA‐3 (+), ER (+), PAX‐8 (?), and TTF‐1 (?) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA‐3, hormonal marker(s), PAX‐8, and TTF‐1, may be useful in some cases. GATA‐3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530–534. © 2016 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.     

Medullary carcinoma of thyroid metastasis to breast: A cytological experience

Medullary carcinoma of thyroid is a relatively uncommon malignancy, which can be sporadic and syndromic in nature. It commonly spreads to regional lymph nodes followed by spreading to distant sites. Breast is an uncommon site of metastasis of this malignancy. Our case is a 38‐year‐old woman married parous woman presenting to the outpatient department with complaints of lump in both the breasts. Fine‐needle aspiration (FNA) was attempted, which revealed a malignancy more suggestive of a metastasis, which was confirmed on CT scan. A detailed history revealed that the patient is a known case of medullary carcinoma of thyroid. The report was given as metastatic medullary carcinoma to the breast after confirming with a calcitonin immunostain. Given the versatility of primary lesions in the breast, minimally invasive FNA cytology (FNAC) technique with adequate sampling helps in identifying metastatic lesions. Differentiating primary from metastatic lesions changes the course of management to the patient. Metastatic lesions should always be kept in mind in the occurrence of known malignancies, however rare the site of occurrence may be. Morphological clues and immunohistochemical work up aid in arriving at correct diagnosis.     

Adenoid cystic carcinoma of the breast diagnosed by fine-needle aspiration

Fine-needle aspiration cytology remains a useful tool for preoperative diagnosis of breast lesions. We describe a case of adenoid cystic carcinoma (ACC) of the breast detected by ultrasound-guided fine-needle aspiration (FNA). Subsequent histopathology corroborated the diagnosis. ACC is a rare but distinctive neoplasm of the breast that can be accurately diagnosed by FNA. Its infrequent presentation, favorable prognosis, and relatively conservative management in the breast prompt us to reinforce its features.     

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.     

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.     

Metaplastic breast carcinoma with chondrosarcomatous differentiation: fine-needle aspiration cytology findings. A case report

Metaplastic carcinoma (carcinoma with pseudosarcomatous metaplasia) of the breast are high-grade carcinomas in which much of the tumor undergoes metaplastic change producing a pseudosarcomatous pattern. We report a case of metaplastic breast carcinoma (MBC) in whom fine-needle aspiration (FNA) cytology was performed with later histological confirmation. The lesion affected a 68-yr-old woman, with a tumor measuring 6.4 x 5.3 cm well demarcated mass located in the upper outer quadrant of the right breast. FNA cytology revealed a variety of markedly atypical cells, mainly spindle-shaped, and mitotic figures sporadically distributed against a severely necrotic background. Atypical chondrocytes were observed against a background of myxomatous substance that displayed metachromasia with May-Giemsa stain that resembled chondrosarcoma cells. Clusters of markedly atypical carcinoma cells that exhibited epithelial junctions were also seen, and immunostaining confirmed the presence of both mesenchyme-marker-positive sarcomatous and epithelial-marker-positive carcinoma cells. Careful attention to the precise cellular composition such as sarcomatous cells, chondrosarcomatous cells and carcinoma cells should allow the recognition of these neoplasms. Therefore, MBC seems to be very a characteristic tumor in which accurate cellular diagnosis may be achieved by FNA cytology.     

Lobular breast carcinoma metastasis to skeletal muscle,two case reports diagnosed by ultrasound guided FNA with evaluation of the roles of interventional cytopathology

Skeletal muscle metastasis from breast carcinoma is a relatively rare clinical entity. We report two cases of breast cancer metastatic to the skeletal muscle, diagnosed by ultrasound guided fine needle aspiration (US‐FNA) biopsy done by interventional cytopathologists at an outpatient cytopathology center. Our two patients presented with lower anterior neck firmness and chest wall mass, respectively. Ultrasound evaluation of our first case demonstrated hypo‐echoic thickened anterior strap muscles while in the second case there was significant distortion of the anatomy from previous surgeries. It was necessary to proceed with FNA biopsy even when their ultrasound findings were equivocal, to establish a definite rapid diagnosis. The immediate onsite evaluation findings were suggestive of malignancy in both cases with subsequent core biopsy confirming the diagnosis of metastatic breast carcinoma. In cytopathology, point‐of‐care (POC) ultrasound is used as an adjunct tool that offers visual guidance during FNA of nonpalpable masses and enables sampling of lesional “hot” spots to ensure specimen adequacy. Studies have demonstrated a reduction in FNA nondiagnostic rates with the use of ultrasound‐guidance consequently reducing health care costs associated with nondiagnostic FNAs. US‐FNA also provides adequate samples for cell block preparations. Metastatic lobular carcinoma of the breast has a wide range of clinical presentations and a high level of suspicion is advised. Cytopathologists‐performed US‐FNA is a proven, less‐invasive, cost‐effective tool that provides timely cytologic diagnosis.     

Merkel cell carcinoma metastatic to the thyroid gland: Aspiration findings and differential diagnosis

Clinically diagnosed metastasis to the thyroid gland is exceptionally rare and may present diagnostic issues on fine needle aspiration. The most common primary sites of metastases to the thyroid are cancers of the lung, breast, skin (especially melanoma), colon, and kidney. Herein, we report a case of metastatic Merkel cell carcinoma to the thyroid presenting as a 2.1‐cm solid nodule in a 50‐year‐old male with a previous history of Merkel cell carcinoma of the upper extremity. The aspirates were moderately to highly cellular featuring small to intermediate sized cells with scant to no cytoplasm, round‐to‐oval nuclei with finely dispersed chromatin, and predominantly arranged as scattered single cells. There was focal nuclear molding, numerous mitoses, and karyorrhectic nuclei. The differential diagnosis centered on the “small round blue cell” tumor group such as medullary thyroid carcinoma and non‐Hodgkin lymphoma. However, in light of our patient's previous history, the FNA findings were most consistent with a metastasis of Merkel cell carcinoma. In patients with a known history of a primary neoplasm, the differential diagnosis of a thyroid nodule should always include potential metastasis. Diagn. Cytopathol. 2010;38:754–757. © 2010 Wiley‐Liss, Inc.     

Cytopathologic analysis of thyroid lesions in the pediatric population

Fine-needle aspiration (FNA) of the thyroid is seldom performed in the pediatric population. Therefore, the clinical utility of thyroid FNA in this patient group has not been adequately addressed. A 15 yr retrospective review of the cytopathology archives at the participating institutions was performed to identify cases of thyroid FNA performed in pediatric patients. The medical records of these cases were reviewed, including the surgical pathology reports of those patients who had subsequently undergone surgical resection. One hundred one specimens from 82 patients were identified. Of these, 40 had a cytopathologic diagnosis of carcinoma, "suspicious" for carcinoma, neoplasm, or atypia, 48 were benign, and 13 were unsatisfactory. Of the 82 patients, 45 underwent partial or total thyroidectomy. Twenty-two (49%) of these were found to harbor a malignant neoplasm (18 papillary carcinomas). The diagnostic sensitivity for identifying a lesion was 87% (26/30) and the diagnostic specificity was 92% (47/51). There were four false-positives and four false-negatives in the review, yielding a positive predictive value of 87% and a negative predictive value of 92%. We conclude that FNA is a useful adjunct to the management of thyroid lesions in the pediatric population, with good diagnostic accuracy. Although thyroid neoplasms are relatively rare in children, our experience demonstrated that 40% of thyroid masses referred for FNA had an interpretation that caused concern, ranging from "atypical" to carcinoma. Additionally, a benign diagnosis by FNA may avoid unnecessary surgery with its potential complications, a significant consideration for this age group.     

Metastatic breast carcinoma involving the thyroid gland diagnosed by fine-needle aspiration: a case report

Secondary involvement of the thyroid gland from a remote primary malignancy is uncommon. The distinction of metastatic carcinoma (MC) or sarcoma from a primary thyroid malignancy is important because the treatment is different. We discuss a case of a 64-yr-old female with a history of breast carcinoma, who presented with pain and swelling in her neck 5 yrs after being diagnosed with breast cancer. She had undergone mastectomy with subsequent chemotherapy and radiation for infiltrating mammary carcinoma. During the 5-yr interval, she had been free of clinically evident metastatic disease. Subsequent work-up revealed two distinct nodules in the left lobe of her thyroid gland as well as a subcutaneous mass in her right shoulder. A fine-needle aspiration (FNA) of the larger thyroid nodule showed malignant epithelial cells with features consistent with breast carcinoma in a background of benign thyroid epithelial cells and colloid. The case was signed out as metastatic breast carcinoma. Subsequent FNA and biopsy of her right shoulder lesion also revealed metastatic breast carcinoma with similar morphology to the material in the thyroid FNA.     

Fine-needle aspiration of chromophobe renal-cell carcinoma metastatic to the thyroid gland

Chromophobe renal cell carcinoma is an unusual variant of renal carcinoma that has less aggressive behavior than clear cell carcinomas. There are few documented cases of metastases, none of which occurred in the thyroid gland. A case is presented of chromophobe renal cell carcinoma metastatic to the thyroid eight years after right nephrectomy, suspected by FNA-biopsy and confirmed histologically. Although metastases of chromophobe renal cell carcinoma are rare, they may also present in thyroid, even many years after primary tumor diagnosis, just like clear cell carcinomas. Even though the FNA cytology of chromophobe renal cell carcinoma has distinctive features, in the context of the thyroid, it can be mistaken for a primary tumor of that organ. In our case, the history of a previous renal tumor was essential in suggesting a metastatic lesion, and histologic and ultrastructural features allowed its precise identification.     

Fine-needle aspiration cytology of unsuspected metastatic thyroid carcinoma initially presenting in bone: report of three cases and a review of the literature

We present a series of three cases of unsuspected thyroid carcinoma presenting as bony lesions and initially studied by fine-needle aspiration (FNA). This series consists of two cases of follicular carcinoma and a third case of Hurthle cell carcinoma. FNA was performed on all three lesions. In two of these cases, a definitive diagnosis of metastatic thyroid carcinoma was made based on the FNA material. FNA smears of both follicular carcinomas displayed cohesive clusters of atypical round cells with nuclear overlapping and positive immunoperoxidase staining for thyroglobulin. The aspirates of the Hurthle cell carcinoma were composed of sheets and individually scattered oval oncocytic cells with prominent nucleoli. All three cases demonstrated the presence of marginal vacuoles consistent with "flame" cells. To the best of our knowledge, this is the first series discussing the cytologic features and differential diagnosis of unsuspected thyroid carcinoma initially presenting as metastatic bone lesions.     

Hyaline matrix in hyalinizing trabecular tumor

Hyalinizing trabecular tumor (HTT) is a rare neoplasm which usually follows an indolent clinical course. The cytologic diagnosis of HTT can be challenging as these neoplasms share cytomorphological features with other thyroid neoplasms and paraganglioma. In fine‐needle aspiration (FNA) smears a diagnosis of papillary thyroid carcinoma (PTC) or suspicion of PTC is often made. Herein we report cytologic findings in two patients with HTT examined by FNA. The key to a correct diagnosis is the recognition of a hyaline and colloid/amyloid‐like material in the background of the smears. Immunocytochemical examination showing aberrant membranous and peripheral cytoplasmic staining for MIB‐1 can help in rendering a correct diagnosis. Diagn. Cytopathol. 2015;43:710–713. © 2014 Wiley Periodicals, Inc.     

B3 thymoma mimicking poorly differentiated thyroid carcinoma: Diagnostic pitfalls of anterior mediastinal mass fine needle aspiration

B3 thymoma is a rare malignant type of thymic epithelial neoplasm found in the anterior mediastinum. Diagnosis of thymoma from fine needle aspiration (FNA) can be challenging due to the infrequency of sampling and its morphologic overlap with other entities such as squamous cell carcinoma, lymphoma or thyroid carcinoma. We report a case of B3 thymoma mimicking poorly differentiated thyroid carcinoma. We present its diagnostic pitfalls on cytology specimens, especially where it concerns identifying the correct location of the lesion, discuss the differential diagnosis, and correlation with the corresponding surgical resection specimen. A neck computed tomography angiogram (CTA) revealed a partially calcified 2.1 cm mass inferior to the left thyroid lobe in a 51 yr old woman being evaluated for stroke/TIA symptoms. She was referred for evaluation of the lesion. On the initial FNA and core needle biopsy, the lesion showed high-grade epithelioid cells with abundant lymphocytic infiltration and occasional necrosis, and was diagnosed as a high-grade carcinoma, favored to represent a poorly differentiated thyroid carcinoma considering the location on imaging. The patient subsequently underwent total thyroidectomy, central neck dissection, and thymectomy. Final surgical pathologic diagnosis indicated a type B3 thymoma. Due to the infrequency of sampling, thymoma poses a diagnostic challenge on preoperative FNA or core needle biopsy. Herein, we present a case of B3 thymoma with a preoperative cytologic specimen that consisted of hyperchromatic sheets of epithelioid tumor cells with a background of lymphocytes without definitive follicular cells or colloid. The core needle biopsy and cell block material showed abundant necrosis, intermixed lymphocytes and neoplastic epithelial cells with strong positive staining for pan-keratin and p40. The cytology and core needle biopsy material were interpreted as representing a probable thyroid neoplasm and raised a broad differential including anaplastic thyroid carcinoma, poorly differentiated thyroid carcinoma with squamous features, metastatic squamous carcinoma, and metastatic carcinoma to a lymph node. The final surgical resection specimen showed a B3 type-thymoma.     

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.     

Case report: metastatic renal carcinoid to the thyroid diagnosed by fine needle aspiration biopsy

We report a case of primary renal carcinoid arising in a horseshoe kidney. To the best of our knowledge this is the first case to be reported in the cytology literature, which has been diagnosed by fine needle aspiration (FNA). A 32-year-old male, presented to the Emory University Hospital, with a renal mass arising in a horseshoe kidney; along with a thyroid mass. FNA of the renal mass resulted in an initial diagnosis of renal cell carcinoma, unclassified. A thyroid aspiration was attempted later, and revealed a neuroendocrine morphology. This was compared with the renal aspiration and both of them were found to have similar morphology. With the help of immunostains, a diagnosis of renal carcinoid tumor metastatic to the thyroid was made. Thus, we demonstrate that renal carcinoid, being a rare entity, can pose a diagnostic challenge.     

Salivary duct carcinoma ex pleomorphic adenoma: Analysis of the findings in fine-needle aspiration cytology and histology

Salivary duct carcinoma (SDC) is an uncommon and highly aggressive neoplasm that reveals histopathologic features resembling infiltrating duct carcinoma of the breast and prostate. SDC arising on the basis of preexisting pleomorphic adenoma (PA) is very rare. This report describes the fine-needle aspiration (FNA) cytology of a case of SDC ex PA. FNA smears were cellular with cells with large, pleomorphic nuclei, some prominent nucleoli, and finely vacuolated cytoplasm. The neoplastic cells were forming groups, sheets, and papillary structures and a cribriform pattern was present in some sheets. Mitotic figures were frequently seen. Necrosis was prominent in the background. Histologic sections of the tumor revealed areas of comedo carcinoma, papillary carcinoma, and infiltrative carcinoma as well as multiple foci of PA. The presence of a cribriform pattern, tumor cells resembling breast ductal carcinoma cells, and a necrotic background are helpful features for an accurate cytodiagnosis of SDC. Diagn. Cytopathol. 1998;19:201–204. © 1998 Wiley-Liss, Inc.