Primary pulmonary epithelial-myoepithelial carcinoma: Report of a rare and under-diagnosed low-grade malignancy.

Primary epithelial-myoepithelial carcinoma (EMC) is a rare low-grade malignant neoplasm of the lung that originates from the submucosal bronchial glands. It behaves in an indolent fashion, although rare cases with high-grade transformation have been reported. Because of the rarity, optimal therapy for this entity has not been clearly defined. Herein, we report a case of primary pulmonary EMC in a 38-year-old Indian man who had a short history of dyspnea and a computed tomographic (CT) scan revealed a 3 cm diameter homogeneous mass in the lower lobe of the right lung. A CT-guided biopsy revealed a mildly atypical and mitotically quiescent tumor with solid and focal acinar arrangement; foci with biphasic arrangement by inner epithelial and outer myoepithelial cells were identified. The neoplasm revealed cytokeratin (CK) 7 positivity in the epithelial cells, while the myoepithelium expressed smooth muscle actin and p63. The tumor had a low (8%) Ki-67 proliferation index. The neuroendocrine markers, thyroid transcription factor 1, CK5/6, p40, and napsin A were negative. Positron emission tomography-CT was negative for any other mass lesion. The mass was excised with negative margins and the patient was on close follow without any evidence of disease for the past 17 months. A custom made, targeted DNA- and RNA-based 5 gene lung cancer next-generation sequencing panel (Epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), Ros protocol-oncogene 1 tyrosine kinase (ROS1), B-rapidly accelerated fibrosarcoma family oncogene (BRAF), and mesenchymal epithelial transition molecule (MET)), compatible with the Ion S5 system was performed; however, no mutation was identified. This case depicts awareness about this entity and use of appropriate immunostains, particularly the myoepithelial markers are essential to arrive at a correct diagnosis. Importantly, high-grade transformation, recurrence, and metastases are not very uncommon in EMC, warranting a correct and timely diagnosis for therapeutic decision-making and prognostication of the patient.

A case of platelet transfusion refractoriness due to anti-CD36 with a successful treatment outcome.

CONCLUSIONS: Antibodies (Abs) against antigens on platelets (PLTs), including glycoprotein IV (CD36), can cause PLT refractoriness. Transfusing PLTs to patients with anti-CD36 is challenging because of the rarity of CD36-negative (CD36-) donors and the possibility of additional HLA Abs. We report a case of PLT refractoriness due to anti-CD36 and HLA Abs. A 21-year-old man (group O, D+) with assumed drug-induced aplastic anemia received multiple PLT transfusions and developed severe PLT refractoriness. He was found to have anti-CD36 as well as HLA class I Abs, with a CD36- phenotype on both PLTs and monocytes. He was diagnosed with type 1 CD36 deficiency and received intravenous immunoglobulin (IVIG) and rituximab to decrease future Ab production. The PLT corrected count increment (CCI) improved significantly with subsequent transfusions of flow crossmatchcompatible as well as uncrossmatched PLTs. He eventually received a bone marrow transplant and has been doing well since. The mean CCI before and after IVIG/rituximab treatment was 0.2 and 6.2, respectively. Soon after IVIG started, the patient's CCI after receiving CD36-, group AB, D+, and HLA untested PLTs was 0.8, but his CCI after receiving flow crossmatch-compatible PLTs was 12.6. Two months after IVIG was started, the mean CCIs for uncrossmatched apheresis PLTs and crossmatch-compatible PLTs were comparable (6.1 versus 6.0, respectively). Desensitization treatment with IVIG and rituximab lowered anti-CD36 and HLA Ab levels, and the CCI of PLT transfusion improved significantly. This case demonstrates that immune suppression is effective for successful PLT transfusion of patients with anti-CD36.

Subungual atypical lentiginous melanocytic proliferations in children and adolescents: A clinicopathologic study.

BACKGROUND: Most subungual melanocytic lesions in children are benign, but some are difficult to classify due to prominent lentiginous growth and high-grade cytologic atypia. OBJECTIVE: To characterize the clinicopathologic features of these rare lesions. METHODS: Subungual atypical lentiginous melanocytic proliferations from patients <20 years of age were collected for clinical and histopathologic review. Fluorescence in situ hybridization (FISH) was performed when possible. RESULTS: Eleven patients aged 2-19 years had expanding or darkening longitudinal pigmented streak(s) with or without Hutchinson sign. Microscopically, all revealed predominantly single-cell growth, pagetoid scatter, and poor circumscription. Eight (73%) cases showed focal or poor nesting, and 3 (27%) demonstrated confluence. Nuclear enlargement, hyperchromasia, and angulation were present in 8 (73%) cases, 7 (64%) cases, and 6 (55%) cases, respectively. One of 4 cases tested by FISH was positive. Three lesions recurred locally without other adverse outcome. LIMITATIONS: Small sample size and short clinical follow-up. Two cases were examined in partial biopsies only. CONCLUSION: Some subungual melanocytic lesions in children and adolescents are histologically indistinguishable from adult subungual melanoma in situ. While the biologic potential remains elusive, FISH might aid in risk stratification. Awareness of this rare group of lesions is crucial for facilitating future investigation into its biologic behavior.

Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival.

OBJECT: The extent of resection (EOR) is a known prognostic factor in patients with glioblastoma. However, gross-total resection (GTR) is not always achieved. Understanding the factors that prevent GTR is helpful in surgical planning and when counseling patients. The goal of this study was to identify demographic, tumor-related, and technical factors that influence EOR and to define the relationship between the surgeon's impression of EOR and radiographically determined EOR. METHODS: The authors performed a retrospective review of the electronic medical records to identify all patients who underwent craniotomy for glioblastoma resection between 2006 and 2009 and who had both preoperative and postoperative MRI studies. Forty-six patients were identified and were included in the study. Image analysis software (FIJI) was used to perform volumetric analysis of tumor size and EOR based on preoperative and postoperative MRI. Using multivariate analysis, the authors assessed factors associated with EOR and residual tumor volume. Perception of resectability was described using bivariate statistics, and survival was described using the log-rank test and Kaplan-Meier curves. RESULTS: The EOR was less for tumors in eloquent areas (p = 0.014) and those touching ventricles (p = 0.031). Left parietal tumors had significantly greater residual volume (p = 0.042). The average EOR was 91.0% in this series. There was MRI-demonstrable residual tumor in 69.6% of cases (16 of 23) in which GTR was perceived by the surgeon. Expert reviewers agreed that GTR could be safely achieved in 37.0% of patients (17 of 46) in this series. Among patients with safely resectable tumors, radiographically complete resection was achieved in 23.5% of patients (4 of 17). An EOR greater than 90% was associated with a significantly greater 1-year survival (76.5%) than an EOR less than 90% (p = 0.005). CONCLUSIONS: The authors' findings confirm that tumor location affects EOR and suggest that EOR may also be influenced by the surgeon's ability to judge the presence of residual tumor during surgery. The surgeon's ability to judge completeness of resection during surgery is commonly inaccurate. The authors' study confirms the impact of EOR on 1-year survival.

N-(3-fluoro-4-(4-(2-methoxy or 2,3-dichlorophenyl)piperazine-1-yl)butyl)arylcarboxamides as selective dopamine D3 receptor ligands: critical role of the carboxamide linker for D3 receptor selectivity.

N-(3-fluoro-4-(4-(2,3-dichloro- or 2-methoxyphenyl)piperazine-1-yl)butyl)arylcarboxamides were prepared and evaluated for binding and function at dopamine D3 receptors (D3Rs) and dopamine D2 receptors (D2Rs). In this series, we discovered some of the most D3R selective compounds reported to date (e.g., 8d and 8j, >1000-fold D3R-selective over D2R). In addition, chimeric receptor studies further identified the second extracellular (E2) loop as an important contributor to D3R binding selectivity. Further, compounds lacking the carbonyl group in the amide linker were synthesized, and while these amine-linked analogues bound with similar affinities to the amides at D2R, this modification dramatically reduced binding affinities at D3R by >100-fold (e.g., D3R K(i) for 15b = 393 vs for 8j = 2.6 nM), resulting in compounds with significantly reduced D3R selectivity. This study supports a pivotal role for the D3R E2 loop and the carbonyl group in the 4-phenylpiperazine class of compounds and further reveals a point of separation between structure-activity relationships at D3R and D2R.

Metastatic Signet-Ring Cell Gastric Carcinoma Masquerading as Breast Primary.

Metastasis to the breast from an extra-mammary primary is a rare phenomenon; metastasis from gastric carcinoma to the breast is extremely so. We report a case who initially presented as mucin-secreting and signet-ring cell tumor of the ovary, and after an interval of 8 months with breast and chest wall metastatic nodules. The covert gastric primary eluded the oncologists at both presentations.