Increased in vitro and in vivo sensitivity of BRCA2-associated pancreatic cancer to the poly(ADP-ribose) polymerase-1/2 inhibitor BMN 673.

BRCA2-associated pancreatic ductal adenocarcinoma (PDAC) may be sensitive to agents that target homology-directed DNA repair, such as DNA crosslinking agents (DCLs) and PARP inhibitors (PARPis). Here, we assessed the sensitivities of BRCA2-deficient (Capan-1) and BRCA2-proficient (MIA PaCa-2) PDAC cell lines to a panel of DCLs and PARPis. Compared to MIA PaCa-2, Capan-1 was significantly more sensitive to all tested DCLs and PARPis, with similar increased sensitivities to cisplatin and the PARPi BMN 673 compared to other DCLs and the PARPi veliparib. We provide further support for this observation by showing that shRNA-mediated BRCA2 knockdown in PANC-1, a BRCA2-proficient cell line, induces sensitization to cisplatin and BMN 673 but not to veliparib. These findings were validated in a PDAC murine xenograft model derived from a patient with bi-allelic BRCA2 mutations. We found 64% and 61% tumor growth inhibition of this xenograft with cisplatin and BMN 673 treatments, respectively. Cisplatin and BMN 673 treatments reduced cellular proliferation and induced apoptosis. Our findings support a personalized treatment approach for BRCA2-associated PDAC.

Endosalpingiosis in axillary lymph nodes simulating metastatic breast carcinoma: a potential diagnostic pitfall.

Intraoperative assessment of sentinel lymph nodes at time of surgical excision of primary breast carcinoma is a crucial step in the determination of cancer extent and the need for further axillary dissection. Benign epithelial inclusions in axillary lymph nodes can mimic metastatic carcinoma and are a well-known pitfall during examination of these nodes in frozen or permanent sections. Most often, these inclusions consists of heterotopic mammary glands and are familiar to the practicing pathologist. Here, however, we present a rare case of endosalpingiosis in the axillary lymph nodes of a breast cancer patient and describe our experience and effort to characterize the lesion. Simulating a metastatic focus of invasive ductal carcinoma, the glandular inclusions lacked myoepithelial cells and failed to stain with myoepithelial markers. However, consistent with a Mullerian origin, the inclusions demonstrated strong staining with PAX-8 and WT-1. Although endosalpingiotic inclusions are not uncommonly encountered in subdiaphragmatic lymph nodes, they are an extremely rare finding above the diaphragm. Pathologists must be aware of these lesions and their ability to imitate metastatic gland-forming carcinoma during frozen section or permanent examination of axillary lymph nodes.

Stromal gene expression predicts clinical outcome in breast cancer.

Although it is increasingly evident that cancer is influenced by signals emanating from tumor stroma, little is known regarding how changes in stromal gene expression affect epithelial tumor progression. We used laser capture microdissection to compare gene expression profiles of tumor stroma from 53 primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumor-derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node-negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumor progression.

FNA diagnosis of retroperitoneal leiomyosarcoma metastasizing to the breast.

Fine-needle aspiration (FNA) biopsy is one of the first-line investigations in any breast lump, and hence cytomorphological recognition of nonmammary metastatic tumors to the breast and their distinction from primary tumors is important. Breast metastasis from extra-mammary malignancy is rare, constituting 2% of breast tumors; even rarer are metastatic leiomyosarcomas. Our patient presented with a breast lump 2 years after operative removal of a retroperitoneal leiomyosarcoma. The breast lump was confirmed to be a metastasis from the earlier primary. Herein, we report the first case of a retroperitoneal leiomyosarcoma metastatic to the breast diagnosed by Fine Needle Aspiration.

Myeloid sarcoma of the vulva as the presenting symptom in a patient with acute myeloid leukemia.

BACKGROUND: Myeloid sarcoma is a tumor of myeloblasts or immature myeloid cells occurring in an extramedullary site. Myeloid sarcoma of female genital tract is very rare with no cases of vulvar location reported in English-language literature. CASE: A 73-year-old female presented with an indurated mass encompassing her left labia majora and vulva. The mass was diagnosed as vulvar myeloid sarcoma. The patient's peripheral blood smear revealed Auer rods and other findings consistent with a diagnosis of acute myeloid leukemia (M-2 type, FAB classification). CONCLUSION: To the best of our knowledge this case is the first report in the English-language literature of the myeloid sarcoma of the vulva. Correct diagnosis of myeloid sarcoma in an otherwise asymptomatic patient is crucial for early administration of antileukemic chemotherapy.

Amiodarone lung toxicity in a cardiac transplant candidate initially diagnosed by fine-needle aspiration: cytologic, histologic, and electronmicroscopic findings.

A cardiac transplant candidate with ischemic cardiomyopathy developed bilateral small parenchymal opacities in lower lobes of the lung. A fine-needle aspiration (FNA) was performed that revealed changes characteristic of amiodarone toxicity. Subsequently performed lung biopsies and electron microscopic studies confirmed the initial FNA diagnosis. The patient has been successfully transplanted with marked improvement in his clinical findings. This is the first case of amiodarone lung toxicity where the diagnosis was initially suggested based on the FNA findings. We also describe the clinical, cytological, histological, and electron microscopic (EM) findings of amiodarone-related pulmonary toxicity and provide a review of the literature.