Hormone receptor and HER2 assessment in breast carcinoma metastatic to bone: A comparison between FNA cell blocks and decalcified core needle biopsies.

BACKGROUND: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) guide the clinical management of breast cancer metastases. Decalcification of bone core needle biopsies (CNBs) can affect IHC. In the current study, the authors sought to define whether fine-needle aspiration (FNA) would be a better alternative to CNB for reliable IHC. METHODS: Patients with breast cancer metastases to bone that were sampled by both CNB and FNA were selected. ER, PR, and HER2 were performed in FNA cell blocks (FNA-CBs) and concurrent decalcified CNBs. Discrepancies were classified as minor when there was a difference of up to 30% nuclear staining in IHC for ER and PR between paired samples and as major when a clinically relevant change was observed (ie, positive vs negative). Quantitative reverse transcriptase-polymerase chain reaction of ESR1 messenger RNA levels was performed on FNA/CNB pairs with discrepancies for ER IHC. IHC status of the primary breast carcinoma was recorded. RESULTS: Concordance rates for ER, PR, and HER2 were 89%, 67%, and 93%, respectively, between FNA-CB and CNB pairs from 27 patients. Major discrepancies were noted in approximately 11% of FNA/CNB pairs for ER IHC and in 33% of FNA/CNB pairs for PR. ESR1 messenger RNA levels of FNA/CNB matched samples were similar and did not explain the differences in ER IHC expression in the majority of cases. Two of 27 FNA/CNB pairs had different results for HER2 IHC that changed from negative on CNB to equivocal (2+) on FNA-CB. Both cases had prior HER2 amplification by fluorescence in situ hybridization. CONCLUSIONS: FNA-CB and CNB appear to constitute acceptable methods for the assessment of ER, PR, and HER2 for clinical decision making.

Novel Modification of HistoGel-Based Cell Block Preparation Method: Improved Sufficiency for Molecular Studies.

CONTEXT: - Cell block preparation methods vary substantially across institutions and are frequently suboptimal. The growing importance of biomarker testing in the era of targeted therapies makes optimization of cell block preparation critically important. OBJECTIVE: - To develop an improved cell block preparation method. DESIGN: - Ex vivo fine-needle aspirates and scrapes from surgically resected tumors were used to develop an improved HistoGel (Thermo Fisher Scientific, Waltham, Massachusetts)-based cell block preparation method. Cellularity yield with the new versus the standard method was assessed in ex vivo split samples and in consecutive clinical fine-needle aspirates processed before (n = 100) and after (n = 100) the new method was implemented in our laboratory. Sufficiency of cell block material for potential molecular studies was estimated by manual cell quantitation. RESULTS: - The key modification in the new method was pretreatment of the pelleted cells with 95% ethanol before the addition of HistoGel (HistoGel + ethanol method). In addition, we optimized the melting conditions of HistoGel and added a dark, inorganic marker to the cell pellets to highlight the desired level of sectioning during microtomy. Cell blocks from ex vivo split samples showed that the HistoGel + ethanol method yielded, on average, an 8.3-fold (range, 1-20) greater cellularity compared with the standard HistoGel-only method. After the switch from the standard HistoGel method to the modified method in our clinical practice, sufficiency of positive fine-needle aspirates for some molecular studies increased from 72% to 97% ( P = .002). CONCLUSIONS: - We describe a simple and readily adoptable modification of the HistoGel method, which results in substantial improvement in cell capture in cell blocks, leading to a significant increase in sufficiency for potential molecular and other ancillary studies.

Cytological features contributing to the misclassification of pancreatic neuroendocrine tumors.

INTRODUCTION: Pancreatic neuroendocrine tumors are a diverse group of malignant neoplasms of varying biological behavior, with outcomes predicted by tumor differentiation and grade. Initial diagnosis is often made by fine-needle aspiration cytology via endoscopic ultrasound of the pancreas primary. We retrospectively reviewed our institutional experience with pancreatic neuroendocrine cytology diagnosis and evaluated for tumor typing accuracy and causes of misdiagnosis. MATERIALS AND METHODS: We searched our institutional database (1994-2012) for all pancreas fine-needle aspirations with corresponding pancreatic histology and a neuroendocrine diagnosis. Cases with discrepant cytology and histology diagnoses were reviewed for factors contributing to misclassification. RESULTS: 143 patients were identified with a neuroendocrine diagnosis either by cytology or histology. In the 129 cytology cases classified as positive/neoplastic/suspicious, tumor type was diagnosed correctly in 101 (78%) cases, incorrectly in 17 (13%), and unclassified (epithelioid neoplasm) in 11 (9%). The most common tumor classification error (7 cases) was misclassifying a neuroendocrine tumor as adenocarcinoma on cytology, which in one case led to inappropriate neoadjuvant chemotherapy. Features of neuroendocrine cytology misdiagnosed as adenocarcinoma included cell clustering and anisonucleosis. Features of non-neuroendocrine cytology misclassified as neuroendocrine included abundant acinar cells or problematic interpretation of immunohistochemical stains. CONCLUSIONS: Cytology can accurately identify neuroendocrine differentiation in the majority of cases; nevertheless, there are potential serious pitfalls. Misclassification of a neuroendocrine tumor as adenocarcinoma or vice versa can have significant clinical impact. Clinical and radiological correlation is essential.

Primary leiomyosarcomas of the gastrointestinal tract in the post-gastrointestinal stromal tumor era.

Most mesenchymal neoplasms of the gastrointestinal tract are currently classified as gastrointestinal stromal tumors (GIST). Gastrointestinal stromal tumors are diagnosed by immunopositivity for CD117, CD34, and DOG1.1, with or without molecular analyses. According to the World Health Organization classification, the diagnosis of primary leiomyosarcomas of the gastrointestinal tract is so rare that there are no significant data on demographic, clinical, or gross features of this tumor. A comprehensive literature search was performed to identify gastrointestinal leiomyosarcomas. Searches were limited to the past 12 years because definitive tools to differentiate leiomyosarcomas from GIST were introduced in the late 1990s. Cases were included only if convincing data were presented. Six cases of esophageal leiomyosarcoma and 5 cases of gastric leiomyosarcoma were confirmed. Furthermore, 26 cases of leiomyosarcoma of the small bowel, 11 cases of the colon, and 8 cases arising in the rectum were identified. Finally, 28 cases of infantile and adolescent leiomyosarcoma were reviewed. Although survival analysis is precluded by small case numbers and limited survival data availability, the trend identifies that increased size and mitotic activity portends to a worse prognosis in small bowel leiomyosarcomas. Colonic leiomyosarcomas appear to be aggressive tumors, regardless of tumor size and mitotic activity. Rectal leiomyosarcomas present as smaller tumors with favorable prognosis. Leiomyosarcomas in post-GIST era are rare tumors of the gastrointestinal tract with distinctive clinicopathologic characteristics. Owing to different treatment options, it is necessary to accurately differentiate these from GIST, using a combination of histologic appearance, presence of smooth muscle antigens, and absence of specific GIST immunomarkers.

Metaplastic variant of invasive micropapillary breast carcinoma: a unique triple negative phenotype.

Invasive micropapillary carcinomas (IMC) and metaplastic breast carcinoma (MBC) have different clinicopathologic features. This study reports an unusual case of multifocal grade III IMC associated with MBC component in a 35-year-old woman. MBC was vimentin positive, pancytokeratin negative, and showed focal p63 positivity. Immunostains for estrogen and progesterone receptor, and fluorescence in situ hybridization for Her2/neu amplification were negative. All the left axillary lymph nodes dissected were positive for metastatic carcinoma with ductal and IMC patterns, but without metaplastic component. Postmastectomy computed tomography and magnetic resonance imaging scans showed metastases to lungs, liver, brain, and vertebrae. The biologic behavior of tumor was in accordance with histology, so that the nodal and distant metastases were testament to the underlying inherently aggressive IMC, whereas large tumor size and triple negativity reflected the features of MBC. To the best of the authors' knowledge, this is the first report of a metaplastic variant of invasive micropapillary breast carcinoma with triple negative phenotype.

Primary combined small cell carcinoma of larynx with lateralized histologic components and corresponding side-specific neck nodal metastasis: report of a unique case and review of literature.

Combined small cell carcinoma (neuroendocrine) of the larynx has been rarely reported in the literature, and included in the current WHO classification. We hereby report an unusual case of combined carcinoma of the larynx; composed mainly of small cell neuroendocrine carcinoma nearly confined to the right side (mainly involving supraglottis extending to glottis) with synchronous minor in-situ and invasive squamous cell carcinoma component located on the left side of larynx (mainly glottis). Interestingly, this side-specific distribution of tumor was recapitulated in its metastatic nodal spread; so that right cervical lymph nodes showed only metastatic small cell carcinoma and left cervical lymph nodes only metastatic squamous cell carcinoma. To the best of our knowledge, the present case is the seventeenth reported case of a combined small cell carcinoma of larynx, second case in which individual tumor components were lateralized on either side of larynx, and the first case in which this side-specificity of tumor was reflected in its metastatic neck nodal spread. This report emphasizes the value of accurate pathologic diagnosis including diversity in differentiation and localization of laryngeal tumors, and underscores the need for thorough pathologic examination of bilateral laryngeal tumors. The pre-operative diagnostic yield of small cell carcinoma (pure or combined) can be enhanced by including deeper submucosal biopsies on laryngoscopy in all those cases in which the extent of disease on imaging is disproportionately larger than the apparent mucosal involvement on laryngoscopy. This approach can facilitate selection of neoadjuvant or palliative chemo-radiotherapy in large or unresectable tumors.