FNA diagnosis of a metastatic papillary thyroid carcinoma arising from a previously unknown follicular variant of papillary thyroid microcarcinoma

While metastatic tumors to bone or lymph nodes from previously known primaries are often successfully diagnosed via fine‐needle aspiration (FNA), a metastatic deposit in a patient with no previously known cancer may pose a diagnostic dilemma. Here, we present a case of metastatic papillary thyroid carcinoma that presented initially as a large pelvic bone mass. FNA was performed on this mass. The diagnosis was challenging due the fact that the tumor did not display the classic nuclear features associated with papillary thyroid carcinoma, instead the nuclear morphology was in keeping with a follicular thyroid carcinoma. Given the patient's concurrent, unremarkable thyroid imaging studies the final diagnosis required an extensive immunohistochemical work‐up. Diagn. Cytopathol. 2014;42:711–715. © 2013 Wiley Periodicals, 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.     

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.     

Metastatic chordoma of the breast: an extremely rare lesion mimicking mucinous cancer

Metastases in the breast are rare, with metastatic chordoma being one of the rarest. To our knowledge, only one such case has previously been published in the literature. We report a case of a 74-year-old woman who presented with a palpable lump in her right breast. The lump was mammographically suggestive of mucinous breast cancer because it was a solitary, small, circular, and moderately dense lesion yielding abundant mucoid aspirate. The tumor resembled mucinous carcinoma upon histologic and immunohistochemical examination: it had a mucinous stroma, and the tumor cells strongly expressed epithelial markers. However, the patient had previously undergone surgery for a recurrent sacral chordoma. In addition to the clinical history, the presence of typical physaliferous cells expressing neither estrogen receptors nor cytokeratin 7, but staining positively for S-100 protein, allowed the proper diagnosis. Although extremely rare, metastatic chordoma may represent a challenge in the differential diagnosis of breast lesions. Discriminating metastases of mucin-producing tumors in the breast from primary mucinous carcinomas is important with regard to the striking difference in prognosis of these lesions.     

Megakaryocytes mimicking metastatic breast carcinoma

False-positive diagnosis of lymph nodes occurs when a benign element in a lymph node, or in its capsule, is interpreted as metastatic carcinoma. This report describes a patient with breast carcinoma who had megakaryocytes in axillary sentinel lymph nodes mimicking metastatic carcinoma. The patient had no history of a hematologic disease, and we found no evidence of a concurrent hematopoietic disorder. The megakaryocytes were reactive for CD31, CD61, and von Willebrand factor, but not for cytokeratin (AE1/AE3). Megakaryocytes should be added to the list of benign histologic abnormalities that may simulate metastatic carcinoma in a sentinel lymph node.     

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.     

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.     

Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 4 cases with evidence of malignant potential

A new type of breast carcinoma resembling the tall cell variant of papillary thyroid carcinoma has recently been described. To date, rare cases are on record. Here, 4 new cases of the tall cell variant of papillary thyroid carcinoma of the breast are described in women aged from 45 to 80 years old. All patients presented with palpable breast nodules and were treated with quadrantectomy. One patient presented with a long clinical history and a metastatic intramammary lymph node. The patient is alive and well 3 months after surgery. The remaining 3 patients are disease free at mean 7.5 months (range, 5 to 10 months) after surgery. These data suggest that papillary thyroid-like carcinomas of the breast show malignant potential.     

Expression profile of endothelin 1 and its receptor endothelin receptor A in papillary thyroid carcinoma and their correlations with clinicopathologic characteristics

The endothelin axis is a group of signaling molecules and their receptors that have been implicated in vascularization of cancers, with their expression being observed to change in different cancer types. In this research, we examined the expression of endothelin 1 and endothelin receptor A at the protein and messenger RNA (mRNA) levels in 123 papillary thyroid carcinomas and 40 matched lymph nodes with metastatic papillary thyroid carcinomas. We found altered endothelin axis mRNA expression in several clinicopathologic parameters with increased endothelin 1 expression in thyroid papillary carcinoma showing stromal calcification, cancers in men, and primary cancers with lymph node metastases. Increased endothelin receptor A mRNA expression was noted in the larger cancers. There is a significant correlation between expression of endothelin receptor A and endothelin 1 in papillary thyroid carcinoma. Both endothelin receptor A and endothelin 1 mRNA expressions were significantly higher in metastatic carcinoma in the lymph node than in primary thyroid cancer. The metastatic carcinoma in the lymph node had increased expression compared with matched primary thyroid carcinoma. Expressions of endothelin 1 and endothelin receptor A were also documented as being high at the protein level. Our results indicate that in thyroid cancer, endothelin 1 and endothelin receptor A are associated with growth in advanced stages and lymph node metastases, likely through known angiogenic linkages. Targeting the endothelin axis may be useful in planning angiogenesis therapy for thyroid cancer.     

Metastatic mucinous carcinoma of the eyelid

Metastatic eyelid tumours are rare and account for less than 2% of all eyelid neoplasms. We report a case of metastatic breast carcinoma to the eyelid in a 60-year-old Chinese lady presenting with a 2-year history of enlarging, painless nodular lower eyelid swelling. The 1 cm diameter lesion was provisionally diagnosed as a sebaceous cyst. However the excision biopsy revealed a mucinous carcinoma expressing oestrogen receptor protein. She had a past history of mastectomy one year previously and histology showed an infiltrating ductal carcinoma (oestrogen receptor status negative) without evidence of axillary lymph node metastasis. She had completed adjuvant radio- and chemotherapy. Further treatment of the current lesion involved a wide excision which did not show any residual malignancy. She had no other evidence of metastasis and was treated with letrozol. We highlight this case to create awareness among clinicians and opthalmologists on the possibility of metastatic disease as a cause of eyelid swelling, especially in patients with a history of cancer. It may also be the first sign of metastatic disease of an internal malignancy. A review of the literature is also presented.     

Unusual metastases of papillary thyroid carcinoma: report of 2 cases

We present 2 cases of papillary thyroid carcinoma (PTC) with conventional morphology that metastasized to unusual sites. The first neoplasm was a PTC whose initial clinical manifestation was a large metastasis in the pancreas which mimicked a primary neoplasm. The mediastinal location of the thyroid gland was responsible for the delay in identification of the primary tumor. Eventually, the patient, a 72-year-old man, developed brain and vertebral metastases. The second case was that of a 58-year-old woman with a PTC with initial metastases in cervical lymph nodes; subsequently, the tumor spread to axillary lymph nodes and finally to the breast. Transformation to anaplastic spindle and giant cell carcinoma within the breast metastasis occurred 20 years after the primary thyroid tumor had been diagnosed and surgically treated. The metastatic anaplastic spindle and giant cell carcinoma contained rhabdoid inclusions further complicating identification. To the best of our knowledge, only 3 cases of PTC metastatic to the breast have been reported, none of them with anaplastic transformation. On the other hand, only 3 cases of PTC metastatic to the pancreas have been published, 2 of them of the tall cell variant, and in none of these cases were the first symptoms attributable to the metastasis. Brief comments about the differential diagnosis are included.     

Biochemical and ultrastructural correlations of calreticulin and thioredoxin expression in breast mucinous carcinoma and infiltrating ductal carcinoma non-special type

Mucinous infiltrating invasive ductal adenocarcinoma consists of 2-4% invasive breast cancer, but is a very interesting type due to its macroscopic similarity to non-special-type (NST) ductal carcinoma. The macroscopic similarity of mucinous and infiltrating ductal carcinoma NST adenocarcinomas consists of a loose and edematous stroma, which is often seen in portions of NST carcinoma and may mimic the mucin pools of mucinous carcinoma. In this study the authors examined the ultrastructural differences between mucinous carcinoma and infiltrating ductal carcinoma NST. They also examined the protein expression of the tissues by 2D electrophoresis due to their belief that from the results of these two levels it is possible to understand the changes that take place both in the ultrastructural and biochemical levels in these two types of breast cancer. The ultrastructural results from mucinous carcinoma have shown many changes in cytoplasmic organelles in comparison to normal samples, depending on the grade and the number of metastatic lymph nodes. At the 2D elecrophoresis level the authors studied two interesting polypeptides, calreticulin and thioredoxin. Both of these proteins were found in patterns of fibroadenoma, mucinous carcinoma, and NST carcinoma, but with different quantitative expression among them. In the future the quantitative differences of these two proteins may provide specific tumor markers for these two types of carcinoma.     

Primary neuroendocrine small cell carcinoma of the breast

A 60-year-old Turkish woman presented with a left breast mass, which was considered for neoadjuvant chemotherapy. By the end of the treatment cycles, the tumor had decreased in size, and the patient underwent modified radical mastectomy with axillary lymph node dissection. Pathologic examination of the tumor revealed a small cell carcinoma with neuroendocrine features confirmed by immunohistochemical stains. Multiple axillary lymph nodes were involved by metastatic small cell carcinoma carrying the same morphologic characteristics noted in the primary breast tumor. We hereby present this case as a primary neuroendocrine small cell carcinoma of the breast. This entity occurs very rarely in the breast, and fewer than a dozen cases have been reported in the literature. Extrapulmonary small cell carcinoma of the breast is reportedly a very aggressive tumor for which no consensus for treatment has yet been drawn.     

Metastatic breast carcinoma to parathyroid adenoma on fine needle cytology sample: report of a case

Metastases to the thyroid gland diagnosed by means of fine needle cytology or by excision have been reported in the literature. To our knowledge, metastatic neoplasms to the parathyroid gland have never been described up to now. In this article, we introduce a rare case of metastatic breast carcinoma to a parathyroid adenoma in a 56-year-old woman, which clinically simulated a left thyroid nodule. The patient had a history of left breast carcinoma; the recent discovery of a palpable mass in the left thyroid area had elicited fine needle cytology sampling for its diagnostic evaluation. The obtained cytopathological sample was cellular but limited to a single Diff-Quik-stained smear; hence, no ancillary studies could be entertained. A cytopathological diagnosis of positive for malignant cells of query metastatic breast origin was performed. The permanent histopathological examination of the surgical sample disclosed multiple small foci of metastatic high-grade carcinoma of ductal type within a somewhat atypical adenoma of the parathyroid gland. The cytopathological findings and some differential diagnostic considerations are briefly commented, as well as the deranging imaging data concerning this interesting case.     

Aspiration cytopathology of metastatic mucinous papillary thyroid carcinoma.

The light microscopic histopathology and cytopathology of papillary thyroid carcinoma (PTC) and its variants is amply depicted in reviews, books, and book chapters. One of the changes in PTC, however, that is infrequently discussed or illustrated in the literature is that of mucinous metaplasia. In the aspiration cytopathology literature, we are aware of only a rare report of PTC exhibiting extensive mucinous metaplasia. We present an example correlating the histopathology and fine needle aspiration cytopathology of a PTC that had metastasized on several separate occasions to cervical lymph nodes, and in the process demonstrated mucinous transformation. Without a prior history of PTC, the aspirate smears and tissue sections could have been mistaken easily for metastatic clear cell carcinoma of non-thyroidal origin. Mucinous metaplasia represents an extremely uncommon, but nonetheless potential, pitfall in the aspiration cytopathology and histopathology of metastatic PTC.     

Mucinous carcinoma of the breast with neuroendocrine differentiation

A case of mucinous carcinoma of the breast with neuroendocrine differentiation in an 89-year-old woman is presented. The patient presented with a rapidly growing right breast mass, which she had had for 2-3 years. The tumor, 15 x 8 x 5 cm, was located mainly in the upper outer quadrant. Light microscopy revealed a pure mucinous carcinoma of type B. Neuroendocrine differentiation was demonstrated by Grimelius stain and chromogranin A, as well as the presence of neurosecretory granules. The breast cancer cells were of luminal origin and had dedifferentiated to attain neuroendocrine properties.     

Fine needle aspiration cytology of primary cutaneous mucinous carcinoma of axilla‐report of a rare case

Primary mucinous eccrine carcinoma is a rare malignant adnexal tumor of older patients. The histopathological features of this tumor are well‐established but the cytomorphology of this neoplasm has only been documented in a few cases. The cytology and histology of this tumor may mimic metastatic mucinous carcinoma and may cause a diagnostic dilemma, especially when the tumor is located at axilla. A correct diagnosis is important because the prognosis is better than that of a metastatic mucinous carcinoma. Here we report the cytological and histological features of a case of primary cutaneous mucinous carcinoma of axilla in an elderly male patient.     

Immunohistochemical analysis of aromatase in metastatic lymph nodes of breast cancer

Aromatase is the key enzyme in intratumoral estrogen production in postmenopausal breast cancer and third generation aromatase inhibitors suppress this enzymatic reaction effectively. Aromatase inhibitor is administered to metastatic breast cancer patients customarily in which estrogen receptor had been demonstrated only in the primary tumor, not the metastatic sites. The status of aromatase in metastatic sites has not been well‐characterized to date. We immunolocalized aromatase in 46 estrogen receptor positive primary breast cancers and paired metastatic lymph nodes, using immunohistochemistry. Immunoreactivity was detected in 44/46 primary tumors and 40/46 metastatic lymph nodes. A significant correlation was detected between the status of aromatase in primary and metastatic sites. Aromatase immunoreactivity was correlated with age, size of primary tumor and Ki‐67 index. Aromatase immunoreactivity was also detected in adipose tissue surrounding the lymph nodes. In conclusion, aromatase status in primary tumors generally represents its status in metastatic lymph nodes. This indicates that the endocrine environment of estrogen receptor positive tumors remain stable during the metastatic process.     

An interesting case of a mucinous tumour of the breast

We report the case of a mucinous cystadenocarcinoma of the breast in an elderly patient who presented with a large breast mass. Mucinous cystadenocarcinoma is a rare subtype of breast carcinoma. It classically occurs in post-menopausal women and is usually negative for ER, PR and HER2. This tumour may be difficult to differentiate from other similar variants of breast carcinoma and particularly from metastatic mucinous cystadenocarcinomas originating from other organs, such as the ovary and pancreas.