Evaluation of programmed cell death ligand 1 expression in a contemporary cohort of penile squamous cell carcinoma and its correlation with clinicopathologic and survival parameters: A study of 134 patients.

OBJECTIVES: Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC. METHODS: A cohort of 134 patients with PC was studied for PD-L1 immunohistochemistry. The PD-L1 expression was evaluated using a combined proportion score with a cutoff of 1 or higher to define positivity. The results were correlated with various clinicopathologic parameters. RESULTS: Overall, 77 (57%) patients had positive PD-L1 expression. Significantly high PD-L1 expression was observed in high-grade tumors (P = .006). We found that 37% of human papillomavirus (HPV)-associated subtypes and 73% of other histotype tumors expressed PD-L1, while 63% of HPV-associated tumors and 27% of other histotype tumors did not (odds ratio, 1.35; P = .002 when compared for HPV-associated groups vs all others). Similarly, PD-L1-positive tumors had a 3.61-times higher chance of being node positive than PD-L1-negative tumors (P = .0009). In addition, PD-L1 high-positive tumors had a 5-times higher chance of being p16ink4a negative than PD-L1 low-positive tumors (P = .004). The PD-L1-positive tumors had a lower overall survival and cancer-specific survival than PD-L1-negative tumors. CONCLUSIONS: Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1-based immunotherapeutics in PC.

Multifaceted Spindle Cell/Sclerosing Rhabdomyosarcoma With Role of Immunohistochemistry in Avoiding Misdiagnosis: A Multi-Institutional Study of 45 Distinct Tumors.

Background. Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Materials and Methods. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified. Demographics, clinical, histopathological, and immunohistochemistry data were reviewed and recorded. Results. The patients' age ranged from 1 to 85 years with a male to female ratio of 1.2:1. There were 15 children/adolescents and 30 adults. Eighteen (40%) tumors were located in the head and neck region. Twenty-four (53%) tumors displayed a bimorphic cellular arrangement with hypercellular areas having short, long, and sweeping fascicular and herringbone pattern, and hypocellular areas with stromal sclerosis and associated hyalinized and/or chondromyxoid matrix. Histomorphological differentials considered were leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, nodular fasciitis, liposarcoma, synovial sarcoma, sarcomatoid carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, and schwannoma. Six tumors exhibited marked stromal sclerosis. The myogenic nature was confirmed by immunohistochemistry. Positivity for at least one skeletal muscle-associated marker (MyoD1 and/or myogenin) was observed. Conclusion. Spindle cell/sclerosing rhabdomyosarcoma diagnosis can be challenging as a number of malignant spindle cell neoplasm mimic this entity. Thus a correct diagnosis requires immunohistochemical work up with a broad panel of antibodies. In view of rarity of this neoplasm, further studies on a large cohort of patients with clinical follow-up data are needed for a better understanding of this tumor.

Pregnancy Luteoma in Ectopic Pregnancy: A Case Report.

BACKGROUND: Pregnancy luteoma is a rare non neoplastic condition of the ovary. It is usually asymptomatic and found incidentally during imaging in pregnancy or during cesarean section. Pregnancy luteoma can also occur after ectopic pregnancy. CASE PRESENTATION: A 30 year old female presented to G.B. Pant Hospital, Andaman and Nicobar Islands institute of Medical Sciences, Port Blair in October 2015 with abdominal pain. After initial investigations, exploratory laporotomy was done for ruptured ectopic pregnancy. Enlarged ovary was removed along with the ruptured portion of fallopian tube. Histopathological examination revealed solid aggregates of large cells with abundant eosinophilic cytoplasm; diagnosis of pregnancy luteoma was given. CONCLUSION: It must be considered in the differential diagnosis of ovarian masses in pregnant females that early diagnosis of this entity may avoid unnecessary radical surgery.

Histopathological Spectrum of Soft-Tissue Tumors with Immunohistochemistry Correlation and FNCLCC grading: A North Indian Experience.

INTRODUCTION: Soft tissue tumors (STT) are mesenchymal neoplasms with a diverse spectrum and overlapping clinical, radiological and histological features. Histopathology and immunohistochemistry (IHC) are essential to make a diagnosis. Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) Sarcoma Group grading system based on tumour differentiation, mitotic rate and necrosis helps in predicting the tumour progression and treatment response. AIMS: The goal of this study was to analyze the incidence, histological spectrum and IHC features of STTs and to grade sarcomas according to FNCLCC grading system. MATERIAL AND METHODS: This is a four year study conducted in the Department of Pathology of a tertiary care centre from July 2009 to June 2013. All histopathologically diagnosed STTs were evaluated for gross and microscopic appearance. IHC was done wherever needed and clinical correlation was attempted. Sarcomas were graded according to FNCLCC grading system. RESULTS: Of the total 270 cases studied, benign, intermediate and malignant STTs were 67.0%, 7.0% and 25.9% respectively. Adipocytic, vascular and peripheral nerve sheath tumors (PNST) formed the bulk of overall STTs (34.1%, 18.5% and 11.1% respectively). Sarcomas not otherwise specified were found to be the most common soft-tissue sarcomas followed by smooth muscle sarcomas and tumors with uncertain differentiation (11.5%, 4.1%, and 3.3%, respectively). Benign STTs were seen two decades earlier and were superficial in location as compared to sarcomas. On FNCLCC grading, grade 3 soft tissue sarcomas were slightly higher in number than grade 2 (27 vs 24). On IHC a definitive diagnosis was reached in 33 malignant, all intermediate and nine benign cases. CONCLUSION: The incidence of intermediate and malignant STTs is increasing due to early detection and better diagnosis by ancillary techniques like IHC. FNCLCC grading helps to prognosticate the malignant STTs thus guiding further plan of action while in some tumors like MPNST and Angiosarcoma it has no prognostic significance.

Parathyroid Adenoma Associated with Granulomatous Inflammation: A Curious Cause of Hypercalcaemia.

Primary Hyperparathyroidism (PHPT) due to solitary parathyroid adenoma followed by parathyroid hyperplasia and carcinoma are the most frequent cause of hypercalcaemia. The most common granulomatous disorders causing hypercalcaemia are sarcoidosis and tuberculosis. We have reported a case where unexplained granulomas were seen along with parathyroid adenoma.

Percutaneous lidocaine administration via a new iontophoresis system in children: tolerability and absence of systemic bioavailability.

OBJECTIVE: Rapid achievement of dermal anesthesia in pediatric practice without discomfort is both desirable and difficult. The Northstar Iontophoretic Drug Delivery System (IDDS) is designed to achieve this objective in 10 minutes using a current of 1.78 mA, compared with the 40 to 60 minutes required for traditional percutaneous methods (eg, eutectic mixture of local anesthetics or EMLA cream). For evaluating the tolerance of this IDDS in pediatrics, 12 healthy children (5-15 years, 4 girls and 8 boys, 10 white, weight 19-79 kg) were evaluated. METHODS: An open-label trial with random applications of IDDS containing lidocaine (100 mg of 10%) and epinephrine (1.05 mg of 1:10,000) to 3 of the 4 possible sites (back, chest, dorsum of hand, and antecubital fossa) was conducted. Three successive applications (time = 0, 3 hours and 3.5 hours) were performed in each subject, with repeated blood sampling (n = 12 over 10 hours) for assessment of plasma lidocaine concentrations. Skin evaluation (by Draize scoring) at both anode and cathode sites was performed at 10 and 24 hours. RESULTS: Few of the subjects (0%-28%) experienced any dermal abnormalities at 10 hours. These findings were maintained at the 24-hour follow-up evaluation with the vast majority of subjects (92%-100%) having no evidence of erythema or edema irrespective of application site. Erythema associated with the anode seemed to be more prominent when the study device was applied to either the chest or the back as compared with the antecubital fossa or dorsum of the hand. No subjects complained of pain/discomfort associated with IDDS delivery. Plasma lidocaine levels in all subjects were below 10 ng/mL at all time points. CONCLUSIONS: The IDDS seems not to deliver a significant, systemic dose of lidocaine and to be well tolerated and potentially suitable for clinical use in pediatric subjects.