Joint Region and Nucleus Segmentation for Characterization of Tumor Infiltrating Lymphocytes in Breast Cancer.

Histologic assessment of stromal tumor infiltrating lymphocytes (sTIL) as a surrogate of the host immune response has been shown to be prognostic and potentially chemo-predictive in triple-negative and HER2-positive breast cancers. The current practice of manual assessment is prone to intra- and inter-observer variability. Furthermore, the inter-play of sTILs, tumor cells, other microenvironment mediators, their spatial relationships, quantity, and other image-based features have yet to be determined exhaustively and systemically. Towards analysis of these aspects, we developed a deep learning based method for joint region-level and nucleus-level segmentation and classification of breast cancer H&E tissue whole slide images. Our proposed method simultaneously identifies tumor, fibroblast, and lymphocyte nuclei, along with key histologic region compartments including tumor and stroma. We also show how the resultant segmentation masks can be combined with seeding approaches to yield accurate nucleus classifications. Furthermore, we outline a simple workflow for calibrating computational scores to human scores for consistency. The pipeline identifies key compartments with high accuracy (Dice= overall: 0.78, tumor: 0.83, and fibroblasts: 0.77). ROC AUC for nucleus classification is high at 0.89 (micro-average), 0.89 (lymphocytes), 0.90 (tumor), and 0.78 (fibroblasts). Spearman correlation between computational sTIL and pathologist consensus is high (R=0.73, p<0.001) and is higher than inter-pathologist correlation (R=0.66, p<0.001). Both manual and computational sTIL scores successfully stratify patients by clinical progression outcomes.

Metastatic choriocarcinoma presenting in a gravid woman.

Choriocarcinoma coexistent with an intrauterine pregnancy is rare and requires decisions affecting mother and child to treat this aggressive tumor. An instance of this situation is presented to highlight clinical circumstances that warrant departure from accepted dogma. Pathologic aspects of choriocarcinoma are also discussed. Diagnosis of choriocarcinoma during an otherwise normal pregnancy requires a high index of suspicion and consideration of unconventional diagnostic maneuvers.

The Merkel cell carcinoma challenge: a review from the fine needle aspiration service.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin that occurs primarily in elderly or immunocompromised patients. For this report, the authors reviewed the diagnostic challenges associated with MCC encountered on their fine-needle aspiration (FNA) service and also conducted an in-depth review of the literature on MCC. A computer search for patients who were diagnosed with MCC by FNA at the authors' institution from 2006 to 2010 was conducted, and 5 patients were selected for cytologic and immunochemical analyses based on their varied and diagnostically challenging clinical presentations. The 5 selected patients had clinical findings commonly associated with MCC, including advanced age (4 of the 5 patients were ages 75-85 years) and a history of previous malignancies (3 of the 5 patients had a history of previous malignancy), and 1 patient was diagnosed with a concomitant low-grade lymphoma. The patients and their disease illustrated the protean clinical presentation of MCC and the clinical and cytologic challenges associated with this neoplasm. The current findings indicate the need for cytopathologists to be aware of the deceptive presentation of this neoplasm and its cytologic and immunochemical features to correctly diagnose this insidious neoplasm.

Monitoring of BK viral load in renal allograft recipients by real-time PCR assays.

BK virus (BKV) is a nonenveloped, double-stranded DNA virus of the polyomavirus family that primarily affects immunocompromised people. BKV may cause nephropathy in renal transplant recipients receiving immunosuppressive therapy, resulting in renal dysfunction and, possibly, graft loss. Monitoring of BK viral load in urine and blood has been used as a surrogate marker of BKV nephropathy (BKVN). Although real-time polymerase chain reaction (PCR) is the method of choice, currently there is no US Food and Drug Administration-approved or standardized BK viral load assay. Different PCR assays vary significantly in sample types, DNA extraction method, PCR primers and probes, and reference materials used to generate a standard curve. These differences can affect the accuracy, specificity, and dynamic ranges of various real-time PCR assays. These analytic differences cause difficulty in comparing test results, making it impossible to establish universal standardized cutoff values that correlate with clinical manifestations of BKVN. In this review, we summarize real-time PCR assays used for managing BKVN.

Basal cell carcinoma with perineural invasion: reexcision perineural invasion?

BACKGROUND: Perineural invasion (PI) in basal cell and squamous cell carcinomas, especially of the head and neck, has been reported to indicate an increased morbidity. Reexcision perineural invasion (RPI), a benign mimic of tumoral perineural invasion, may present a difficult histologic differential diagnosis. METHODS: We surveyed the medical literature for PI occurring in basal cell carcinomas to investigate the degree to which the reported cases occurred in reexcision specimens vs. primary biopsy specimens. RESULTS: We found large retrospective studies of 14,120 basal cell carcinomas evaluated for PI in which 310 cases of PI were identified (2.2%), and 20 sporadic case reports of basal cell carcinomas with PI. Of 310 cases of basal cell carcinoma with PI, 196 (63%) were in reexcision specimens. Of 20 sporadic reports, 17 (85%) were in reexcision specimens. CONCLUSION: The high percentage of PI occurring in reexcision specimens vs. primary excisions may indicate that many of the reported cases of basal cell carcinomas with PI are actually examples of RPI.

von Hippel-Lindau disease: epididymal cystadenoma targeted by metastatic events.

Cases of renal clear cell carcinoma in patients with von Hippel-Lindau disease often exhibit extensive metastasis. Several investigators have shown these tumors to specifically invade central nervous system hemangioblastomas, which are commonly associated with the disease. We report on multiple metastatic events within a single von Hippel-Lindau disease-associated tumor outside the central nervous system, epididymal cystadenoma. The multiplicity of these metastatic events suggests the epididymal cystadenoma as a preferential site of metastasis for von Hippel-Lindau disease-associated renal clear cell carcinoma.