Metastatic metaplastic breast carcinoma mimicking pulmonary squamous cell carcinoma on fine‐needle aspiration

Metaplastic squamous cell carcinoma (SCC) of the breast is a rare type of breast cancer. Metastases to the lung, which can be a major site of second primary tumor development among breast cancer patients, are difficult to distinguish from primary SCC of the lung and present a unique challenge for pathologists. There are few available discriminating immunohistochemical markers as squamous differentiation typically leads to loss of expression of characteristic primary epithelial cell markers of both breast and lung origin. GATA protein binding 3 (GATA‐3) is a useful marker of breast origin in metastatic ductal and lobular carcinomas including poorly differentiated triple‐negative carcinomas and some metaplastic carcinomas. Here, we present a case of metastatic SCC presenting as a solitary lung mass with regional lymph node metastases and a single satellite lesion in a patient with a history of metaplastic SCC of the breast. In addition to the routine markers of squamous differentiation, the metastases were also positive for estrogen receptor (ER) and GATA‐3 on cytologic material obtained by transbronchial FNA. This suggests that immunoreactivity for ER and GATA‐3 may support a diagnosis of metastatic SCC in the context of a prior metaplastic SCC of the breast. Diagn. Cytopathol. 2015;43:844–849. © 2015 Wiley Periodicals, Inc.     

Intrathyroidal oxyphilic parathyroid carcinoma: A potential diagnostic caveat in cytology?

Oxyphilic (oncocytic) parathyroid lesions are very uncommon and their cytological features are rarely described. Due to the similarities in anatomical location and indistinguishable cytomorphological features, these lesions are easily confused with neoplastic and non‐neoplastic thyroid lesions on fine needle aspiration (FNA). The diagnosis becomes more challenging in cases of unusual intrathyroidal location of the parathyroid lesions in the absence of clinical evidence of hyperparathyroidism, which simulate thyroid nodules clinically. We describe a case of intrathyroidal oxyphilic parathyroid carcinoma in a 66‐year‐old female, who presented with a dominant left “thyroid” nodule. FNA smears were cellular, comprising predominantly of oxyphilic cells arranged in papillary‐like architecture with occasional nuclear grooves, which was mistaken for oncocytic variant of papillary carcinoma of the thyroid. The histological diagnosis of oxyphilic parathyroid “adenoma” was made following total thyroidectomy. The tumor, unfortunately, recurred 7 years later with associated multiple lung metastases. When dealing with thyroid lesions comprising predominantly of oncocytic cells, one should consider oxyphilic parathyroid neoplasms as one of the differential diagnosis. In difficult equivocal cases, a panel of immunocytochemical stains (PTH, GATA3, TTF‐1, PAX8, and thyroglobulin) can be helpful. In addition, a combination of valuable clinical, radiological, and laboratory data, including serum calcium and parathyroid hormone levels are key to arriving at an accurate cytological diagnosis. Diagn. Cytopathol. 2016;44:688–692. © 2016 Wiley Periodicals, Inc.     

Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung

Differentiating metastatic breast carcinoma in the lungs from primary lung tumors and mesotheliomas is important for determining prognosis and treatment. We evaluated novel breast specific markers, androgen receptor (AR) and GATA binding protein 3 (GATA3) immunohistostaining, for this differential, and compare to other traditional markers. The specimens comprised 33 metastatic breast carcinomas to the lung, 566 primary lung tumors (170 adenocarcinomas, 157 squamous cell carcinomas, 31 pleomorphic carcinomas, 115 large cell neuroendocrine carcinomas, 43 small cell carcinomas, and 49 typical carcinoids) and 42 malignant mesotheliomas. They were analyzed by immunohistochemistry using antibodies to AR, GATA3, estrogen receptor (ER), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein‐15 (GCDFP‐15). Of the metastatic breast carcinomas, immunohistostaining of AR, GATA3, ER, PgR, mammaglobin, GCDFP‐15 were positive in 27 cases (81.8%), 24 cases (72.7%), 26 cases (78.8%), 13 cases (39.4%), 12 cases (36.4%), 9 cases (27.3%), respectively. Of primary lung tumors and mesotheliomas, staining of AR, GATA3, ER, PgR, mammaglobin, GCDFP‐15 were positive in 18 cases (3%), 3 cases (0.5%), 4 cases (0.7%), 2 cases (0.3%), 0 case (0%), 2 cases (0.3%), respectively. Immunohistochemistry of AR and GATA3 are reliable for differentiating metastatic breast carcinoma from primary lung tumors and mesotheliomas.     

Pulmonary metastasis of cribriform‐morular variant of thyroid carcinoma mimicking primary adenocarcinoma of the lung: A potential pitfall

Cribriform‐morular variant of papillary thyroid carcinoma (CMV‐TC) shows a peculiar mixture of follicular, cribriform, papillary, trabecular, and solid patterns with squamoid morules. Ocassionally, lung metastasis may be interpreted incorrectly as primary lung adenocarcinoma. We illustrate a case of pulmonary meastasis of CMV‐TC mimicking a primary adenocarcinoma, 7 years after diagnosis of CMV‐TC. The lung metastases may be easily missed if the pathologist is unaware of the patient's prior history and a limited immunohistochemical panel (CK7 and TTF‐1) is used. The histologic and immunohistochemical (β‐catenin+, ER+, PR+, TTF‐1 +, and CK7+) findings were diagnostic of CMV‐TC and ensured adequate treatment.     

A case report of papillary thyroid carcinoma dedifferentiated to squamous cell carcinoma presenting as a lung metastasis: A potential diagnostic pitfall

Papillary thyroid carcinoma (PTC) tall cell variant (TCV) with squamous dedifferentiation is a rare entity. We present a case of 90‐year‐old woman who initially had a 2.8 cm conventional PTC in right lobe of thyroid who, couple decades later, had metastatic dedifferentiated PTC to right neck lymph nodes level II and IV with tall cell features; to right level IV and V lymph nodes with tall cell and squamous components, which recently presented exclusively as squamous cell carcinoma (SCC) metastasizing to lung. The squamous component in the lymph node and SCC in the lung were both positive for squamous marker p63 and PTC markers TTF1, PAX‐8 and BRAF V600E while negative for thyroglobulin and p16. The papillary component was positive for TTF‐1, BRAF V600E and P63 (majority); negative for thyroglobulin and p16. Final diagnoses were rendered based on combination of cytological features and immunohistochemical profiles. This report highlights the utilization of current biomarkers to distinguish between metastatic dedifferentiated PTC with squamous features and primary lung SCC, as well as the importance of recognizing this rare entity.     

乳腺癌肉瘤1例报道及文献复习

目的探讨乳腺癌肉瘤的临床病理学特征及其鉴别诊断。方法对1例乳腺癌肉瘤进行组织病理学和免疫表型观察并复习文献,了解该肿瘤的特征。结果镜检显示病变边界清楚,以软骨肉瘤为主,其边缘有少量分化较差的浸润性导管癌成分。免疫表型：软骨肉瘤细胞vimentin强阳性,S-100蛋白阳性,ER、PR,c-erbB-2和CK（AE1／AE3）均阴性;癌细胞CK（AE1／AE3）、ER、PR及c—erbB—2均阳性,vimenfin、S—100蛋白阴性。结论原发于乳腺的癌肉瘤较罕见,诊断需与乳腺恶性分叶状肿瘤以及软组织肉瘤鉴别。     

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.     

Anaplastic thyroid carcinoma with rhabdoid features

Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive neoplasm, characterized by complete or partial composition by undifferentiated cells. We report a case of ATC with rhabdoid features in a 68‐year‐old male, who presented with a rapidly enlarging neck mass. Fine‐needle aspiration (FNA) of the thyroid mass showed discohesive, pleomorphic round to polygonal rhabdoid cells with one to multiple eccentric, large, rounded nuclei with a prominent nucleolus, moderate to abundant, globoid cytoplasm which oftentimes harbor a pale para‐nuclear inclusion. The cytoplasm of some cells contained variously sized, eosinophilic granules. Rare cells contained neutrophils in their cytoplasm. Mitoses including atypical mitotic figures and necrosis were readily seen. Histologic examination of needle core biopsy (NCB) revealed individual dispersed and sheets of pleomorphic neoplastic cells with similar cytomorphologic features as described above. The tumor extensively infiltrated a myxocollagenous stroma containing lymphocytes and neutrophils, and demonstrated foci of necrosis. Tumor cells were immunoreactive for keratins AE1/AE3, CAM5.2, and CK19; PAX‐8, and p63, but negative for S‐100, HMB‐45, calcitonin, TTF‐1, thyroglobulin, CD56, HBME‐1, glypican‐3, PAX‐5, myogenin, CD31, and INI‐1. The differential diagnosis of this malignant rhabdoid tumor is discussed. Diagn. Cytopathol. 2015;43:416–420. © 2015 Wiley Periodicals, Inc.     

Tubulolobular carcinoma of the breast with grooved and cerebriform nuclei: failure to identify this specific subtype in a case during routine fine needle aspiration cytology and histopathological diagnosis

Tubulolobular carcinoma (TLC) is a rare tumor of the breast in which histologic features of both tubular and lobular carcinoma are combined. We report a case of TLC, in which the specific subtype was missed at routine cytologic and histopathological examination. A 69-year-old woman presented with a right breast lump. Imaging studies indicated a malignant lesion in right upper quadrant. Routine fine needle aspiration (FNA) cytology diagnosis was a duct cell carcinoma (small cell type). In a setting of cystic thyroid lesions, presence of excessive nuclear grooves, and rare intranuclear cytoplasmic inclusion, metastatic papillary thyroid carcinoma was also considered. However, both these possibilities were not supported by immunocytochemical findings (estrogen receptor+, thyroglobulin-, and chromogranin-). The histopathology diagnosis was invasive duct cell carcinoma. Review of FNA smears and paraffin sections led to the diagnosis of TLC, which was supported by positive immunohistochemical stainings for markers like e-cadherin and β-catein.     

Biomarkers to diagnose metastatic breast carcinoma to the pancreas: A case report and update

The patient is a 72‐year‐old female who presents with new onset jaundice. The patient has a past medical history significant for right‐sided estrogen receptor (ER)‐positive and left‐sided ER‐negative breast cancers in 2005 and 2009, respectively, and recent 1‐year history of ER‐positive right‐sided breast cancer with bone and brain metastases. CT scan and endoscopic ultrasound (EUS) revealed a new 2 cm mass in the head of the pancreas, leading to EUS‐guided fine‐needle aspiration of the lesion. Pathologic workup revealed adenocarcinoma with signet‐ring cells, representing either metastatic breast or primary pancreatic cancer. Immunohistochemistry and molecular diagnostic workup identified positive GATA‐binding protein 3 (GATA3) immunoreactivity and a mutation in Erb‐B2 receptor tyrosine kinase 2 (ERBB2), also known as human epidermal growth factor receptor 2 (HER2). Here, we review the diagnostic markers commonly used to differentiate metastatic breast vs primary pancreatic adenocarcinoma, and discuss the challenges of utilizing GATA3 immunoreactivity and ERBB2 mutations for diagnosis.     

GATA3 expression in clinically useful groups of breast carcinoma: a comparison with GCDFP15 and mammaglobin for identifying paired primary and metastatic tumors

GATA3 has been recognized as the novel marker for identifying primary and metastatic breast carcinomas, consistently showing that GATA3 was significantly more sensitive than traditional markers gross cystic disease fluid protein 15 (GCDFP15) and mammaglobin (MGB). However, clinically useful groups of breast carcinomas status were not identified, which were determining appropriate treatment strategy, affecting the prognosis. In this study, we undertook a comparative study of the marker GATA3 and GCDFP15 and MGB in clinically useful groups of paired primary and metastatic breast cancer. We retrieved 64 cases of matched primary and metastatic breast cancer from the surgical pathology archive at our institution. According to the emerging 2015 St. Gallen Consensus, the clinically useful groups were divided into ER and/or PR (+), HER2 (−), abbreviated as A; ER and/or PR (+), HER2 (+), abbreviated as B; ER and PR (−), HER2 (+), abbreviated as C; ER, PR and HER2 (−), abbreviated as D; each group contained 16 cases (n = 16). Tissue microarrays were created, with three 1-mm punch specimens from each case. The tissue microarrays were cut at 4-μm thickness and stained with monoclonal antibodies to GATA3, GCDFP15, and MGB. Staining intensity (0-3+) and extent (0%-100%) were scored with an H-score calculated (range, 0-300). Sensitivities by varying H-score cutoffs (any; ≥50; ≥150) for a positive result in the clinically useful groups of matched primary or metastatic breast cancer among GATA3, GCDFP15, and MGB. GATA3 was significantly more sensitive than GCDFP15 and MGB A and B groups (P < .05) rather than C and D groups (P > .05). However, GATA3 in conjunction with GCDFP15 and MGB detection could improve the sensitivity of C group (P < .05) rather than D group (P > .05). Significantly, good coincidence was observed between primary and metastatic tumor GATA3 expression (κ value = 0.826 > 0.75) as compared with the coincidence of GCDFP15 (κ value =0.492 < 0.75) and MGB (κ value =0.593 < 0.75) (both P < .05). In conclusion, GATA3 expression did not show the same sensitivity for the clinically useful groups of breast cancer. GATA3 expression is positively correlated with ER-positive, PR-positive, and HER2-positive carcinomas. In addition, the matched primary and metastatic tumor expression of GATA3 shows good coincidence. We propose the careful selection of GATA3 for identifying hormone receptor negativity of breast cancer, especially in the case of triple-negative breast cancer.     

Fine‐needle aspiration diagnosis of high grade adenoid cystic carcinoma metastatic to the pancreas

Pancreatic tumors are mostly primary tumors, with only rare metastatic tumors described in the literature. Here we report an unusual case of fine‐needle aspiration (FNA) diagnosis of high grade adenoid cystic carcinoma of the parotid gland metastatic to the pancreas. The aspirate smears were moderately cellular and revealed numerous basaloid neoplastic cells. The cytomorphologic differential diagnosis included primary pancreatic tumor with small cell morphology as well as metastatic tumors. By immunocytochemistry, the tumor cells were positive for cytokeratins (AE1/AE3, CAM5.2, and CK7), and CD117 (C‐KIT), and negative for CD45, WT1, synaptophysin, chromogranin, CD56, TTF‐1, and CK20. The cytomorphologic features and immunoprofile in our case were consistent with high‐grade carcinoma metastases from patient's known salivary gland primary. To the best of our knowledge, this case is the first reported encounter of FNA diagnosis of pancreatic metastasis with small cell morphology from a salivary gland neoplasm as primary site. Diagn. Cytopathol. 2015;43:117–120. © 2014 Wiley Periodicals, Inc.     

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.     

Combined use of SOX10 and GATA3 in mammary carcinoma

The complementary coverage of different subsets of breast cancer by GATA3 and SOX10 makes their use in combination appealing for routine clinical use, but study of these markers has been largely limited to cases with high or absent ER expression. Here we report SOX10 and GATA3 immunostaining in parallel using a tissue microarray containing 246 invasive breast carcinoma cases with a range of ER expression. GATA3 and SOX10 were positive in 93 % (229/246) and 15 % (38/246) of cases overall and in 63 % (24/38) and 74 % (28/38) of triple negative breast carcinomas (TNBC), respectively; SOX10 was positive in 15 of the 17 cases that lacked GATA3 expression (88 %). SOX10 was also positive in 3 % (6/196) of ER + cases, including 50 % of cases with low ER (3/6), 20 % with intermediate ER (3/15), and 0 % with high ER (n = 175), so that ER-low cases more strongly resembled TNBC than those with high ER expression. GATA3 expression was lower in cases that co-expressed SOX10 in comparison to those that were positive for GATA3 alone. Less than 1 % (2/246) of cases were negative for both GATA3 and SOX10. Therefore, SOX10 is a useful adjunct to GATA3 in the detection of TNBC and cases with low ER expression and/or reduced GATA3 intensity relative to that typical of breast cancers with higher ER expression. Moreover, given such high sensitivity, metastatic tumors lacking either GATA3 or SOX10 are unlikely to be of breast origin. Additional study is necessary to determine the extent to which SOX10 may also improve specificity and to characterize its biologic significance in breast cancers with low ER expression.     

ER,PR, and Her2 immunocytochemistry on cell‐transferred cytologic smears of primary and metastatic breast carcinomas: A Comparison Study With Formalin‐Fixed Cell Blocks and Surgical Biopsies

The use of formalin‐fixed cell blocks (CBs) for detection of ER, PR, and Her2 status of primary and metastatic breast carcinomas sampled by fine‐needle aspiration (FNA) has been extensively used in clinical practice; however, CBs sometimes lack adequate cellularity even when direct smears are cellular. The aim of this study is to assess the reliability of ER, PR, and Her2 status as demonstrated by immunocytochemical staining (ICC) on alcohol‐fixed direct smears using the cell transfer (CT) technique. FNA cases diagnosed as primary or metastatic breast carcinoma in which the status of ER, PR, and Her2 had been determined either on CB or concurrent biopsy were identified over a period of 18 months. ICC for ER, PR, and Her2 was performed on alcohol‐fixed direct smears using the CT technique. Results were compared with those reported for the corresponding formalin‐fixed tissue. A total of 47 FNA specimens from 46 patients were included in this study. ICC results were excluded from analysis if the CT smear contained fewer than 50 cells. Correlation between the ICC performed on the CT smears and the corresponding CB or biopsy revealed a sensitivity rate for ER, PR, and Her2 of 95%, 90%, and 88%, respectively with a specificity of 100% for all three markers. ICC performed on the FNA smears using the CT technique is a reliable method for assessment of the ER, PR, and Her2 status of breast carcinomas, especially when the direct smears are highly cellular and the CB lacks adequate cellularity. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.