Pleural effusion supernatant: a reliable resource for cell-free DNA in molecular testing of lung cancer.

INTRODUCTION: DNA extracted from malignant pleural effusion (PE) sediments is the traditional source of tumor DNA for predictive biomarker molecular testing (MT). Few recent studies have proposed the utility of cell-free DNA (cfDNA) extracted from effusion cytology centrifuged supernatants (CCS) in MT. The aim of this study was to assess the feasibility and utility of molecular testing on cfDNA extracted from PE CCS in lung cancer patients. MATERIALS AND METHODS: The study was of prospective design. All PE CCS were collected and stored. Subsequently, in patients confirmed as primary lung adenocarcinoma (LUAD) and where patient matched effusion sediment/tissue biopsy/plasma was being tested for EGFR mutations, cfDNA extraction and EGFR MT by real-time polymerase chain reaction (qPCR) were performed. Custom panel targeted next-generation sequencing (NGS) (Ion Torrent; Thermo Fisher, Carlsbad, CA) was also performed wherever feasible. RESULTS: Out of 299 PE CCS collected, 20 CCS samples were included in the study. Concordant EGFR mutations were detected in pleural effusion CCS of 10 of 11 (91%) EGFR mutant cases as per qPCR performed on the matched sediment DNA (n = 8), lung biopsy (n = 2), and plasma (n = 1) samples. In 1 positive sample, CCS detected additional EGFR T790M mutation. Among 10 CCS samples also tested by NGS, additional EGFR mutations missed by qPCR were picked up in 2 (2 of 10). Success of mutation detection in CCS cfDNA did not correlate with cfDNA quantity or tumor fraction in sediment. CONCLUSIONS: cfDNA from effusion CCS is a reliable and independent source of tumor DNA highly amenable for MT and complement results from other tumor DNA sources for comprehensive mutation profiling in LUAD patients.

Pediatric Primary Yolk Sac Tumour of the Kidney: Recommendations for Pretreatment Diagnosis.

Introduction Although nephroblastomas are frequently treated without prior biopsy, there are the occasional other pediatric renal tumors that require different management. In the literature, there are around 30 primary renal germ cell tumors (GCT), including four cases of Yolk sac tumor (YST). We present another primary renal YST.Case report: A five-year-old boy was diagnosed as Wilms tumor on radiology and needle biopsy. He received chemotherapy, with no response. The post-chemotherapy resection specimen revealed a YST.Conclusion: Renal YST may be indistinguishable from Wilms tumor clinically and radiologically. For pre-biopsy chemotherapy management protocols, serum tumor markers such as AFP may be recommended to identify the occasional GCT, including YST. Pre-chemotherapy needle biopsies may lead to misdiagnosis, and may require confirmation by an experienced pathologist or central review.

Primary Pulmonary Hyalinizing Clear Cell Carcinoma: Case Series With Review of Literature.

Background: Hyalinizing clear cell carcinomas of tracheobronchial origin are very rare salivary gland type tumors accounting for less than 1% of lung tumors with only 13 cases reported to date. Their radiological features, morphological spectrum, and molecular features are not well described. Aim: To perform a clinicopathological analysis of primary pulmonary hyalinizing clear cell carcinomas. Method: A retrospective search of primary pulmonary hyalinizing clear cell carcinomas was conducted from authors' institutions and the clinicopathological features including details of molecular testing were analyzed. Results: Five primary pulmonary hyalinizing clear cell carcinomas were identified. The mean patient age at diagnosis was 48.2 years (range: 33-64 years). Three patients were women. All patients were nonsmokers and 3 were symptomatic; 2 were detected incidentally during health screening. The tumors were located in the main lobar bronchi ranging from 1.3 to 4.9 cm in maximum dimension. Microscopy showed cords and nests of at least, focally clear tumor cells. Mucin cysts lacking goblet cells were seen. All tumors were uniformly positive for p40, p63, AE1/AE3, keratin 7, and epithelial membrane antigen but negative for TTF1, KIT, neuroendocrine markers, and other myoepithelial markers. All cases showed Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement. Perineural invasion and lymph node metastases were detected in patient 5. Two patients with available follow-up data were recurrence-free until 4 years (patient 1) and 9 months (patient 5) after resection. Conclusion: The present series adds to the scant available literature on primary pulmonary hyalinizing clear cell carcinomas highlighting the characteristic histomorphology, immunoprofiles, and benign outcomes of these rare tumors.

Rosai Dorfman Disease with malignant transformation to Histiocytic Sarcoma: A diagnostic conundrum.

ABSTRACT: Histiocytic disorders mostly occur as de-novo nodal or extranodal benign masses with rare secondary malignant transformation. A 10-year-old female presented with 10-cm cervical swelling since 9 months associated with fever. Computed tomography revealed left cervical lymphadenopathy and bilateral lung nodules. Lymph node excision biopsy showed effacement of architecture by atypical histiocytes with marked nuclear pleomorphism and frequent mitosis. Focal areas showed mature histiocytes with emperipolesis. The cells were immunopositive for CD68, CD163, and S100 (focal), whereas they were negative for Langerin and CD1a. The Ki67 proliferative index was 30%. A diagnosis of histiocytic sarcoma in a background of Rosai-Dorfman disease was made.

Chronic active Epstein-Barr virus infection mimicking tuberculosis - A diagnostic enigma.

ABSTRACT: Chronic active EBV infection is a rare disorder prone for misdiagnosis. They present with a wide range of symptoms from indolent to aggressive clinical course. Clinico-pathological correlation with confirmation by ancillary techniques is inevitable to diagnose this disease. We present a case of a 29-year-old male with fever, weight loss, and lymphadenopathy for 6 months. Lymph node biopsy showed occasional granuloma with preserved architecture. Suspected to have tuberculosis, he received antitubercular treatment (ATT) with no response for 3 months. Subsequently, additional workup showed many EBV-positive cells in sinusoids with high serum EBV titer, confirming the difficult diagnosis of CAEBV. The present case highlights the difficulty in the diagnosis of this entity and also emphasizes the necessity to recognize this disorder in countries endemic for tuberculosis, as it is no longer bound by ethnicity and geographical boundaries.

IgA Nephropathy and Atypical Anti-GBM Disease: A Rare Dual Pathology in a Pediatric Rapidly Progressive Glomerulonephritis.

Introduction: Anti-GBM nephritis in the pediatric age group is exceedingly rare with concurrent additional pathologies being even rarer. Tissue diagnosis requires a combination of crescentic histomorphology, immunofluorescence showing "paint brush stroke" pattern of linear IgG or rarely IgA, and serum anti-GBM antibodies subject to the disease course and treatment. The authors describe one such case with a dual pathology involving IgA nephropathy and atypical anti-GBM disease. Case Presentation: A 13-year-old girl presenting with features of rapidly progressive glomerulonephritis underwent a renal biopsy showing a mesangioproliferative histology with crescents and an immunofluorescence pattern indicating a dual pathology of IgA nephropathy and anti-GBM nephritis. Additional ancillary testing including staining for IgG subclasses and galactose-deficient IgA (KM55) helped to confirm the diagnosis. She responded to steroid pulses and plasma exchange therapy, was off dialysis after 8 weeks with a serum creatinine level of 1.5 mg/dL, and however remains proteinuric at last follow-up. Conclusion: Concurrent anti-GBM nephritis and IgA nephropathy is a rare occurrence and possibly arises from a complex interaction between the anti-GBM antibodies and the basement membrane unmasking the antigens for IgA antibodies. Additional newer techniques like immunofluorescence for KM55 are helpful in establishing the dual pathology.

Lymphocyte-Peppered Sclerotic Collagen: An Additional Histological Clue in Lichen Sclerosus, Morphea, and Systemic Sclerosis.

BACKGROUND: "Line sign," "cookie cutter sign," "square biopsy sign," "high eccrine glands sign" have been previously described in morphoea and lichen sclerosus. We found focal areas of thickened collagen bundles with lymphocytes interspersed between them in several biopsies of these conditions. MATERIALS AND METHODS: We reviewed slides of sclerosing disorders obtained from the archives of the pathology department in our hospital for the period 2013-2019. RESULTS: A total of 73 slides including 40 of lichen sclerosus, 24 of morphea, 2 of lichen sclerosus-morphea overlap, and 7 of systemic sclerosis were evaluated. Lymphocytes were noted between sclerotic collagen bundles in 46 (63%) slides, being most common in lichen sclerosus (80%, 32/40) followed by morphea (50%, 12/24), whereas it was seen in one case each of lichen sclerosus with morphea overlap (50%, 1/2) and systemic sclerosis (14.3%, 1/7). The finding was noted in the upper dermis in 20 of 32 (62.5%) slides of lichen sclerosus and in both the superficial and deep dermis in 11 (91.7%) of 12 slides of morphea. CONCLUSION: Lymphocyte-peppered sclerotic collagen may be a useful histological clue to the diagnosis of lichen sclerosus, morphea, and systemic sclerosis.

Fine needle aspiration cytology of mesenchymal hamartoma of liver mimicking hepatoblastoma: A case report.

Fine-needle aspiration cytology (FNAC) is an effective tool for early and quick diagnosis of malignant and metastatic liver masses. However, diagnosing a benign liver tumor on cytology is a challenging task as they are rarely assessed on cytology and also due to the limitations of the procedure. Mesenchymal hamartoma is an uncommon benign pediatric liver tumor and difficult to diagnose on cytology. We describe here a case of a child who presented with a huge liver mass and clinical suspicion of hepatoblastoma. The child underwent blind FNA, and was diagnosed as mesenchymal hamartoma based on the cytological features. A biopsy was performed subsequently which confirmed the same and then he underwent surgical resection of the tumor. The patient had an uneventful recovery and is disease free on follow up.