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.     

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.     

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.     

Histopathologic and immunohistochemical characterization of a primary papillary thyroid carcinoma in the lateral cervical lymph node

Lymph nodes in the neck are known to occasionally contain benign epithelial inclusions and can be rare primary site of various tumors usually occurring in other organs. Papillary thyroid carcinoma in the lateral neck lymph node with co-existing ectopic thyroid inclusions has not been reported previously. A 41-year-old male patient, who had normal thyroid function and no history of neck irradiation, was seen with a slowly enlarging mass in the right lateral neck. At surgery the cervical mass was found to be separate from the thyroid proper without any attachments in between. Papillary thyroid carcinoma and co-existing thyroid inclusions were identified within the lateral cervical lymph node. Immunohistochemistry detected strong and diffuse cytoplasmic positivity with antibodies against CK19 and CK903 in papillary thyroid carcinoma. Benign thyroid follicles within the lymph node were only weakly and focally stained. Thorough examination confirmed no malignancy in the total thyroidectomy specimen. Furthermore, small foci of metastatic papillary carcinoma were identified in two ipsilateral lymph nodes from neck dissection specimen. These findings suggest development of primary papillary thyroid carcinoma from malignant transformation of benign intranodal thyroid inclusions.     

Metastatic Small Cell Carcinoma to the Thyroid Gland: a Pathologic and Molecular Study Demonstrating the Origin in the Urinary Bladder

Small cell carcinomas may occur in the thyroid gland. Infrequently, they are primary tumors, and have been interpreted as variants of medullary thyroid carcinoma. However, the vast majority of small cell carcinomas involving the thyroid gland are metastatic tumors. In some cases, demonstration of the primary tumor is not easy. An example of a small cell carcinoma metastatic to the thyroid is presented in this report. The primary tumor was a small cell carcinoma that occurred as a minor component in a transitional carcinoma of the urinary bladder. The microscopical and immunohistochemical features of both tumors, in the thyroid and the bladder, were identical. Moreover, both tumors exhibited an identical mutation in p53, as well as similar loss of heterozygosity at 10q23 and RASSF1A promoter hypermethylation, clearly indicating that the bladder tumor was the site for the primary tumor of the patient.     

Tumor-to-tumor metastasis: lung adenocarcinoma metastasizing to a follicular variant of papillary thyroid carcinoma

Cancer-to-cancer metastasis into a thyroid neoplasm is an uncommon phenomenon with possible diagnostic difficulties. Here, we describe a case of lung adenocarcinoma metastatic into a follicular variant of papillary thyroid carcinoma (FVPTC). A 60-year-old woman with no prior history of malignant neoplasm presented with a nodule in the right lobe of the thyroid gland, some masses in the left lung were found by radiological examination. Histopathological examination of the thyroidectomy specimen demonstrated two different components of carcinoma in a single thyroid nodule; one was FVPTC and the other was high-grade adenocarcinoma. Although both components shared the TTF-1+/CK7+/CK19+/CK20-/SP-A- immunoprofile, only the former was positive for thyroglobulin, and only the latter was positive for CEA. The epidermal growth factor receptor (EGFR) gene mutation at exon21 (L858R) was present only in the latter. The lung biopsy specimen showed cytological, immunohistochemical, and EGFR genotypic features similar to those of the high-grade adenocarcinoma component of the thyroid nodule. These findings resulted in a reliable diagnosis of lung adenocarcinoma metastasizing into an FVPCT and treatment with EGFR-targeted therapy. These results demonstrate that a panel of immunohistochemical staining and molecular analysis is helpful for both diagnosis and appropriate postoperative treatment for a patient with cancer-to-cancer metastasis.     

Identification of immunohistochemical biomarkers for papillary thyroid carcinoma using gene expression profiling

We report the successful validation of a combined gene expression profiling and tissue microarray approach to papillary thyroid carcinoma (PTC) biomarker identification. Our ultimate goal is the identification of protein biomarkers that can be effectively used in immunocytochemical assays applied to thyroid fine needle aspiration biopsy (FNAB) samples. To that end, we designed our approach to prioritize molecules that were minimally expressed in normal thyroid and highly expressed in PTC. We first generated gene expression profiles from 11 normal thyroid tissue samples and 9 samples of classic PTC. The results were segregated to rank most highly those molecules not expressed in normal thyroid and up-regulated at least 6-fold in PTC. From this list, we chose 2 molecules (P-cadherin and Bax) for immunohistochemical analysis for which commercial antibodies were available. These were compared with 2 other molecules that have been previously studied in thyroid cancer (cytokeratin-19 and galectin-3). For immunohistochemistry, a tissue microarray was generated that contained the following tissues: classic PTC (n = 20), follicular variant of PTC (n = 9), normal thyroid (n = 19), Hashimoto thyroiditis (n = 11), follicular adenoma (n = 15), and follicular carcinoma (n = 14). Immunohistochemical staining was scored and compared with the gene expression profiling. As anticipated, cytokeratin-19 and galectin-3 were highly expressed in PTC and less expressed in other tissues. Bax and P-cadherin were also expressed in PTC, but to a lower level than cytokeratin-19 and galectin-3; however, Bax and P-cadherin demonstrated virtually no staining of normal thyroid, unlike cytokeratin-19 and galectin-3. These results validate our approach for PTC biomarker discovery and identify several candidate biomarkers for further development.     

Thyroid papillary carcinoma arising in ectopic thyroid tissue within a branchial cleft cyst

A case of papillary carcinoma arising in ectopic thyroid tissue within a branchial cleft cyst is described. A 46-year-old woman presented with a 2.0 x 2.0 cm mass in her left lateral neck. The excised mass showed a cystic lesion with a thyroid papillary carcinoma. Following a lateral cervical cystectomy, subsequent thyroid gland and lymph nodes dissections were performed. Pathological examination showed an adenomatous goiter and no primary carcinoma in the thyroid gland, as well as metastatic papillary carcinoma in the lymph nodes. Two cases of thyroid papillary carcinoma arising in ectopic thyroid tissue within a branchial cyst have been reported previously, but no lymph node metastases were recognized. The first case of papillary carcinoma arising in ectopic thyroid tissue within a branchial cleft cyst, and accompanied by lymph node metastasis is presented.     

Renal-cell carcinoma with intranuclear inclusions metastatic to thyroid: a diagnostic problem in aspiration cytology

A case of renal-cell carcinoma (RCC) exhibiting prominent intranuclear inclusions in a metastasis to the thyroid is presented. RCC had been treated in this patient by right nephrectomy 7 yr earlier and by left partial nephrectomy 5 yr earlier; the patient had also received radiation to the neck 4 yr earlier for carcinoma in situ of the left true vocal cord. Aspiration performed on a rapidly enlarging mass in the left lobe of the thyroid revealed both clusters of tumor cells and single tumor cells with prominent intranuclear inclusions. Definitive distinction between a primary and metastatic neoplasm was difficult on the aspiration specimen. Subsequent thyroidectomy confirmed the diagnosis of metastatic renal-cell carcinoma with intranuclear inclusions by histologic, immunohistochemical, and ultrastructural analysis. The differential diagnosis by aspiration cytology of thyroid neoplasms that contain intranuclear inclusions is discussed.     

Heterotopic intrathymic thyroid tissue

Heterotopic intrathymic thyroid tissue is an extremely rare condition, but it is important to distinguish it from metastases of clinically undetected thyroid carcinoma because metastatic papillary thyroid carcinoma is often so well differentiated, simulating normal thyroid tissue. Described herein are histological findings of heterotopic intrathymic thyroid tissue that was incidentally identified in a woman with papillary thyroid carcinoma during histological examination of a radical neck dissection specimen. These findings emphasize that this rare incidence may occur and should be differentiated from metastatic papillary carcinoma. Histologically, the patient's intrathymic thyroid follicles were identical to the normal thyroid follicles, having flat cuboidal cells with uniformly small nuclei without nuclear grooves or inclusions. The follicular cells had a low Ki-67 labeling index close to zero, and immunonegativity for galectin-3, HBME-1, and RET oncoprotein, in contrast to the tumor cells in primary papillary thyroid carcinoma of the patient. To the authors' knowledge this is the first case report of intrathymic heterotopic thyroid tissue posing a diagnostic difficulty in a patient with papillary thyroid carcinoma.     

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.     

Mucoepidermoid carcinoma of the thyroid

Clinical and morphological features of three cases of primary mucoepidermoid carcinoma of the thyroid are described. The tumours were composed of two cell types. One of these resembled squamous epithelium and ultrastructurally showed tonofilaments and numerous desmosomes. The other cell type contained Alcian blue and mucicarmine positive mucin and, on electron microscopy, showed mucigen granules. Marked stromal fibrosis and psammoma bodies were seen in all tumours. Immunohistochemical studies showed that the tumour cells were negative for thyroglobulin. A few calcitonin-containing cells were seen in one metastatic tumour. One tumour showed, in addition to the histological features of mucoepidermoid carcinoma, anaplastic areas with obvious transition between the two histological patterns. The same thyroid also had a small thyroglobulin-positive papillary carcinoma in the opposite lobe. All tumours presented lymph node metastases. In two cases the primary tumour was confined within the thyroid capsule but that with anaplastic areas invaded surrounding structures. This patient died 13 months after diagnosis; the other patients are alive and symptomless one and 10 years since diagnosis. Mucoepidermoid carcinoma of the thyroid appears to be a clinicopathological entity that resembles papillary carcinoma in its natural history. The origin of the tumour is unclear. There is, however, some histological and immunohistological data suggesting that the tumour might be related to the ultimobranchial system although some histological features also appear to favour a common origin with papillary carcinoma.     

Incidentally detected liver metastasis of well-differentiated follicular carcinoma of the thyroid, mimicking ectopic thyroid

A case of incidentally detected liver metastasis of follicular carcinoma of the thyroid, histologically mimicking ectopic thyroid, is described. The patient was a 48-year-old woman. A 2-cm mass was incidentally detected in the left lobe of the liver by abdominal computed tomography (CT) scan. Partial liver resection was performed for diagnosis and treatment. Histologically, the liver nodule was composed of small-to-large follicles containing colloid material. The lining epithelium was flat or cuboidal and showed no cellular or nuclear atypia. Immunohistochemical studies for thyroid-specific proteins, thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4), suggested that the nodule was of thyroid origin. Therefore, a differential diagnosis of metastasis of well-differentiated thyroid cancer, ectopic thyroid tissue and teratoma was made. The patient had a history of subtotal thyroidectomy performed 8 years ago due to a thyroid tumor. The original surgical specimens of the thyroid tumor were diagnosed as follicular adenoma. Additional sections of the specimen were reviewed and an area of convincing vascular invasion was found that was suggestive of follicular carcinoma. Subsequent whole-body examination failed to find other metastases. It was determined that the liver tumor was metastasized from well-differentiated follicular carcinoma of the thyroid.     

Mucoepidermoid carcinoma of the thyroid: a case report

Primary mucoepidermoid carcinoma (MEC) of thyroid is an uncommon tumour and reports on its' cytology are consequently scanty. A 46-year-old male presented with a thyroid nodule of nine months duration. Fine needle aspiration (FNA) cytology of the nodule showed features of a malignant tumor that was different from the usual types of thyroid carcinoma. Monolayers and syncytial clusters of round and spindle tumour cells with large vesicular nuclei and single macronucleoli were present. A diagnosis of carcinoma was given with the comment that this was unlike any of the usual types of thyroid cancer and that a metastatic malignancy should be ruled out. The cytological picture of MEC may not always be distinctive enough for accurate tumour typing. Nevertheless the cytological features are usually sufficiently different to rule out all of the usual types of thyroid carcinoma. This distinction may be important from the point of view of differing prognosis in MEC of thyroid (as compared to differentiated thyroid cancers) and the need to exclude a metastatic carcinoma, especially from a primary in one of the salivary glands.     

Clinical,cytological, and pathological characteristics of metastatic renal cell carcinoma to the thyroid: A study of 14 cases at a Japanese single institution

A preoperative diagnosis of metastatic renal cell carcinoma to the thyroid (MRCCT) is important for determining clinical management but is challenging even in cases with a clinical history of renal cell carcinoma (RCC). This study aimed to elucidate the clinical, cytological, and pathological characteristics of MRCCT. Fourteen MRCCT cases extracted from 18 320 malignant thyroid tumors were included in this study. Twelve MRCCT (85.7%) occurred as solitary lesions and the most frequently suspected lesions on ultrasonography were follicular tumors. On cytology, 46.2% of cases were reported as RCC or suspected RCC; a medical history of RCC and immunocytochemistry were helpful in interpretation. RCC metastasized to a follicular adenoma in 50.0% of the solitary lesions. MRCCTs with a long interval from the initial presentation, solitary lesion, and Ki-67 labeling index <10% showed significantly longer disease-free survival. MRCCT is characterized by a long interval from the initial presentation of RCC, appearance as a solitary nodule, ultrasonographic similarity to follicular tumors, sharing cytological findings with primary thyroid tumors, and high frequency of metastasis within follicular adenoma. A long interval from the initial presentation, occurrence as a solitary lesion, and low Ki-67 labeling index may be favorable prognostic factors.     

Parasitic nodule of the thyroid in a patient with Graves’ disease

 We report a case of a parasitic nodule of the thyroid in a patient with Graves’ disease, which mimicked a lymph node metastasis from a primary occult thyroid carcinoma. The patient was a 67-year-old Japanese woman with a past history of subtotal thyroidectomy for Graves’ disease, who was referred to our hospital because of a right cervical mass. A lymph node-like lesion measuring 1.5 cm in diameter was palpable, distinct from the remnant of the right thyroid lobe. Thyroid scintigraphy using ¹²³I-Na revealed a hot lesion at the upper lateral portion of the right thyroid lobe, and this was resected. Microscopically, the mass showed thyroid follicles with lymphocytic infiltration and lymphoid follicles. Clear ground glass nuclei, nuclear grooving and intranuclear inclusions were not observed. No morphological evidence of the lymph node was found in the mass by reticulin staining. Parasitic nodules of the thyroid in patients with Graves’ disease may mimic a metastatic carcinoma of the thyroid. Received: 21 January 1998 / Accepted: 15 April 1998     

Medullary thyroid carcinoma in a patient with Hashimoto's thyroiditis diagnosed by calcitonin washout from a thyroid nodule

Serum calcitonin is a tumor marker used in the diagnosis and follow‐up of medullary thyroid carcinoma. Calcitonin washout evaluation is a new method used for suspicious thyroid nodules and lymph nodes. Limited clinical data are present about the efficacy of this method. A 61‐year‐old female patient with known Hashimoto's thyroditis and an 8‐mm hypoechoic nodule was presented with one previously benign fine‐needle aspiration cytology (FNAC). On referral to our department, she had a moderately high‐serum calcitonin level, and we repeated the FNAC that was reported as nondiagnostic. We performed FNAC for the third time together with calcitonin washout evaluation from the thyroid nodule. The FNAC was again nondiagnostic, but the calcitonin washout level from the thyroid nodule was 152.569 pg/mL. Total thyroidectomy was performed, and the diagnosis was confirmed as medullary thyroid carcinoma. Calcitonin washout evaluation may be a useful method in the differential diagnosis of patients with thyroid nodules having moderately high‐serum calcitonin levels. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Fine needle aspiration of an intrathyroidal parathyroid carcinoma mimicking a primary thyroid anaplastic carcinoma: A case report with review of the literature

Intrathyroidal parathyroid carcinoma is an uncommon malignancy. A 46‐year‐old male presented with a left neck mass. Computed tomography (CT) scan revealed a hypodense mass in the left thyroid lobe along with evidence of metastatic lymphadenopathy. Aspiration of the left thyroid nodule was performed, and a diagnosis of malignancy was rendered, favoring a primary anaplastic carcinoma. Based on the cytologic diagnosis, the patient underwent a total thyroidectomy. Before the surgery, intact parathyroid hormone (PTH) and calcium level (PTH = 78 pg/mL; Calcium = 10.6 mg/dL) were found to be minimally elevated. On gross examination, a 3.2 cm mass within the left inferior thyroid lobe was seen. Histopathologic examination and ancillary studies supported the diagnosis of a parathyroid carcinoma. We, hereby present, an exceedingly rare presentation of an intrathyroidal parathyroid carcinoma with only minimal elevation of PTH and calcium, mimicking a primary anaplastic thyroid carcinoma on cytologic examination.