Andre Pinto

Searching for mammary analog secretory carcinoma of salivary gland among its mimics

Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly. Positivity for mammaglobin and S-100, and negativity for ANO1 are useful screening tools before confirmatory molecular studies.

Recurrent EML4–NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy

Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6–NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4–NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6–NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4–NTRK3 dual fusion FISH, and targeted RNA sequencing. The EML4–NTRK3 fusion was identified in two cases of infantile fibrosarcoma (one of which was previously described), and in one case of congenital mesoblastic nephroma, demonstrating that the EML4–NTRK3 fusion is a recurrent genetic event in these related tumors. The growing spectrum of gene fusions associated with infantile fibrosarcoma and congenital mesoblastic nephroma along with the recent availability of targeted therapies directed toward inhibition of NTRK signaling argue for alternate testing strategies beyond ETV6 break-apart FISH. The use of either NTRK3 FISH or next-generation sequencing will expand the number of cases in which an oncogenic fusion is identified and facilitate optimal diagnosis and treatment for patients.

Uterine rhabdomyosarcoma in adults

Rhabdomyosarcoma (RMS) is an aggressive mesenchymal tumor most commonly diagnosed in the pediatric population, and when occurring in adults, tends to develop in the deep soft tissue of the limbs. Primary uterine RMS comprises an even more restricted subset, with little known or reported when compared to most other gynecologic sarcomas. Our goal with this study was to retrospectively evaluate cases from two academic institutions and describe the main histopathologic findings of this rare gynecologic malignancy. A total of 8 cases were identified, consisting of 4 pleomorphic rhabdomyosarcomas (PRMS), 2 alveolar rhabdomyosarcomas (ARMS), and 2 embryonal rhabdomyosarcomas (ERMS). They occurred in patients ranging from 22 to 70 years old, and the most common presenting symptom was vaginal bleeding. Most patients presented with advanced stage at diagnosis, including metastatic disease to lymph nodes and to distant sites. The masses were mostly (6/8) centered in the myometrium, while two cases arose in the cervix (2/8). Histologic characteristics of the tumors were dependent on the RMS subtype, although all cases demonstrated a similar immunohistochemical profile regardless of their subclassification. RMS of the uterus has a very poor prognosis, and data regarding treatment of this rare malignancy is limited, and usually extrapolated from non-uterine sites.

Pelvic angiosarcoma occurring in a postmenopausal female: case report and review of the literature.

Sarcomas of the soft tissue are uncommon tumors which are difficult to diagnose due to their frequency and subtle presentation [1]. Angiosarcomas only count for less than 2 % from all soft tissue sarcomas, which makes the diagnosis even harder [2, 3]. Literature about them is scarce and obtained from small series and case reports. We present a clinicpathologic reported case of a biphasic pelvic angiosarcoma in a 55-year old female with abdominal pain and ascites.

Solving the mystery: Hyalinized cyst wall containing organism-like structures in a lung transplant donor

A 59‐year‐old man with non‐ischemic cardiomyopathy underwent orthotopic heart transplantation. The donor, a 31‐year‐old male declared brain dead after a gunshot wound to the head, was considered high risk due to history of incarceration, illicit drug use, and sex with a HIV‐positive partner. At organ procurement, the heart, kidneys, pancreas, and liver looked grossly normal. A small right lower lobe nodule was noticed, and lung biopsy was performed. Bronchoscopy showed purulent secretions in the right lower lobe. Images from pathology are presented. Lung biopsy confirmed the presence of hyalinized cyst wall containing organism‐like structures. A combination of culture, microscopic morphology, and gene sequencing was used to identify the causative organism. The patient and all other organ recipients received appropriate antifungal prophylaxis and remain asymptomatic 6 months post‐transplant.

Cost-Containment Protocols for Prostate Core Needle Biopsies: Hypothetical Scenarios to Reduce Procedural Costs

Background In recent years, anatomic pathology laboratories have been struck by new revenue policies secondary to the Affordable Care Act. In particular, modifications to compensation for processing prostatic core needle biopsies (PCNBs) have led to important reimbursement cuts. Herein, we explore a hypothetical reduction in the costs for the processing of PCNBs using three simple, hypothetical methods while maintaining high-standard patient care. Materials and methods We determined the number of blocks and slides used per case on all PCNBs performed at our institution from August 2013 to September 2014 and calculated the total procedural cost for each case and for the total number of cases processed during the study period based on a published estimated procedural cost. We then estimated the procedural cost of three different proposed hypothetical scenarios that consisted in reducing the number of blocks used per case. A Student t test was used to assess the difference between real and hypothetical costs. Results A total of 4,406 paraffin blocks were used to process 363 PCNBs with a total annual procedural cost of

Lymphoepithelioma-Like Carcinoma of the Uterine Cervix

26,303. By implementing any of the hypothetical scenarios, the annual procedural cost was significantly reduced; the reduction could potentially be as low as

Primary Peritoneal Carcinoma in a BRCA1/2-negative, PALB2-positive patient

8,978 (P < 0.0001). Conclusions This study illustrates three hypothetical alternatives that could dramatically reduce the procedural costs of PCNBs while maintaining high-quality care. Implementation of these scenarios at a global scale could potentially have an impact on health-care cost in the USA of several millions of dollars per year.

PD-L1 Expression in Carcinosarcomas of the Gynecologic Tract: A Potentially Actionable Biomarker

Objectives Lymphoepithelioma-like carcinoma (LELC) of the uterine cervix is a rare tumor. The goal of this study was to evaluate a series of cases of cervical LELC and to investigate possible association with human papillomavirus (HPV) and/or Epstein-Barr virus (EBV). Methods Immunohistochemistry for p63, p16, human leukocyte antigen-D related (HLA-DR), and B-cell lymphoma 2 (BCL-2); in situ hybridization (ISH) for EBV and HPV; and polymerase chain reaction (PCR) genotyping were performed. Mismatch repair (MMR) studies and PD-L1 status were obtained. Results We found eight cases of LELC. Tumors demonstrated sheets of cells containing vesicular nuclei, amphiphilic cytoplasm, and dense peri- and intratumoral lymphocytic infiltrates. All tumors stained for p63, p16, and HLA-DR; two also stained for BCL-2. When combining ISH and PCR results, seven tumors were HPV positive; they were all Epstein-Barr encoding region negative. All cases were MMR intact, and most overexpressed PD-L1. Conclusions This study shows that cervical LELCs are associated with HPV and not EBV.

Burkitt Lymphoma Presenting as Unilateral Deafness in an Immunocompetent Patient

Highlights • First reported case of PPC after BSO in a BRCA1/2-negative, PALB2-positive patient• The PALB2 mutation and genetic counseling is discussed• Multi-gene panel testing can benefit prognostic factors and targeted therapy