Immunotyping in tubo-ovarian high-grade serous carcinoma by PD-L1 and CD8+ T-lymphocytes predicts disease-free survival.

PD-L1 immune checkpoint inhibitor expression was evaluated in high-grade serous carcinoma (HGSC) ovary in the context of the overall immune landscape to determine its prognostic value. Consecutive cases of HGSC, 50 who underwent upfront surgery followed by adjuvant chemotherapy (HGSC-U) and 50 who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (HGSC-PC) were selected. In HGSC-PC cases, the pre-NACT ascitic fluid cell blocks were included. Tumor-infiltrating lymphocytes (TILs) were scored, hotspots chosen for tissue microarray construction and immunohistochemistry performed and scored for CD4 and CD8 lymphocyte subsets, CD68+ tumor-associated macrophages (TAMs), PD-1 and PD-L1 expression. HGSC-post-chemotherapy showed increased TILs, predominantly CD8+T-lymphocytes, compared to HGSC-U. HGSC showed PD-L1 expression on tumor cells and/or TAMs in 60% cases with a linear correlation to CD4+, CD8+ TIL levels. Concordant PD-L1 expression was seen in matched pre- and post-NACT tumor cells. HGSC-PC showed higher expression of PD-L1. There was no association of PD-L1 cumulative proportion score or tumor cell score with outcome. Taking a cutoff for PD-L1 CPS at 10%, immunotype I (PD-L1+/CD-8+), corresponding to tumors with adaptive immune evasion, showed worst disease-free survival compared to all other immunotypes (p = 0.03) and was more significant (p = 0.01) when compared to immunotype III (PD-L1+/CD8-). Immunotyping based on PD-L1/CD8+ expression correlates to prognosis and outcome.

Mystery of a Family with Recurrent Male Infant Deaths- Solved by Autopsy and Molecular Tests.

The authors report a case of a six weeks old boy who presented with acute febrile illness and progressive abdominal distension. There was a significant family history of early male sibling deaths. Autopsy showed multiorgan abscesses. Molecular test revealed final diagnosis of the child.

Spinal Muscular Atrophy: Autopsy Based Neuropathological Demonstration.

Spinal muscular atrophy (SMA) encompasses a group of disorders with loss of spinal motor neurons.The report describes the neuropathological findings including brain and spinal cord at autopsy in a five-and-half-month-old boy with suspected type 1 SMA. The anterior motor neurons, Clarke's column at all the levels of spinal cord showed neuronal loss and degeneration while neurons at all the deep grey nuclei were preserved apart from variable degree anoxic changes. Skeletal muscle biopsy revealed features of neurogenic atrophy consistent with SMA. A differential diagnosis like storage disorders was excluded using electron microscopy. No extra-neural manifestations were seen. Neuropathological features at autopsy have seldom been reported in the literature.

Morphologic and Immunocytochemical Features of High-Grade Serous Carcinoma of Ovary in Ascitic Fluid Effusion and Fine-Needle Aspiration Cytology.

OBJECTIVES: High-grade serous carcinoma (HGSC) is the most common ovarian malignancy. The role of cytopathology in obtaining tissue diagnosis before institution of neoadjuvant chemotherapy (NACT) was evaluated. METHODS: All histopathology-proven HGSC specimens between 2015 and 2018 with prior cytopathologic diagnosis by ascitic fluid evaluation or fine-needle aspiration (FNA) of ovarian mass were reviewed with cell block immunocytochemistry for CK7, CK20, PAX8, WT1, and p53. RESULTS: Of 288 cases of HGSC, pre-NACT cytology diagnosis was established in 32% (93/288), with specific HGSC diagnoses made on ascitic fluid in 88% (82/93) and by ovarian mass FNA in 12% (11/93). The ascitic fluid showed moderate/high cellularity with papillary clusters in 76% (71/93) cases. Cell block immunocytochemistry showed tumor cells positive for CK7, PAX8, and WT1. p53 showed mutant or null-type positivity in 65% (33/51) and 33% (17/51) of cases, respectively, with 100% concordance with subsequent histopathology specimens. Poor/intermediate response to chemotherapy was shown in 75% of cases. CONCLUSIONS: Combined assessment of cytomorphology, cell block histomorphology, and ancillary immunohistochemical testing, including PAX8, WT1, and p53, allows for specific pre-NACT diagnoses of HGSC in ascitic fluid and ovarian FNA cytology. This practice allows for initiation of chemotherapy and diminution of disease burden prior to definitive surgical therapy.

Severe Pulmonary Arteriopathy in a Neonate with Congenital Rubella Syndrome and Patent Ductus Arteriosus.

Neonates with congenital rubella syndrome (CRS) are known to have associated congenital cardiac malformations. Patent ductus arteriosus (PDA) is one the most common cardiac anomalies associated with CRS. PDA refractory to medical management and associated with ventilatory dependence is considered for surgical ligation. However, the management of PDA can be challenging in the presence of underlying lung disease or pulmonary vascular disease. Outcomes after closure in neonates are dependent upon age, weight, nutritional status, pre-operative pulmonary arterial hypertension and presence of chronic lung disease. We present a neonate with CRS who required surgical PDA closure. The neonate developed severe pulmonary arterial hypertension which led to fatal outcome. The clinical course is corroborated with histo-pathological changes observed on the autopsy of this neonate.