Cholemic Nephrosis: An Autopsy Study of a Forgotten Entity.

OBJECTIVE: The aim of the study is to do a clinicopathologic study of post mortem kidney biopsies with significant deposition of bilirubin pigment within tubular epithelial cells and in the lumen of distal tubules as a bile cast. MATERIAL AND METHOD: All post mortem specimens with acute tubular necrosis, with the presence of bile casts in tubules or bile pigment deposition in the tubular epithelium during the period 2015-2018 were examined for gross and histopathology along with biochemical parameters and viral markers. RESULTS: Bile casts with sloughed renal tubular epithelial cells and occasional macrophages were present in the distal convoluted tubule in 78.6% of biopsies (11/14). The plugging of distal convoluted tubule with casts was similar to that seen in myeloma and myoglobin cast nephropathies. Bilirubin pigment deposition was present in 35.7% (5/14) of cases. The frequency of bile casts in each biopsy was variable and it did not have any association with serum bilirubin levels or etiology of liver dysfunction. A striking difference from earlier studies is the high number of toxin-induced liver damage including six cases of paraquat and 2 cases of yellow phosphorus poisoning. CONCLUSION: This study proves importance of the bile cast nephropathy as a reason for kidney injury, especially with varied hepatotoxic etiologies, especially paraquat and yellow phosphorus.

Gastrointestinal Stromal Tumor: Genotype Frequency and Prognostic Relevance.

BACKGROUND: Genotyping has an important role in the prognosis and prediction of response to tyrosine kinase inhibitor therapy. KIT exon 11 deletions serve as an adverse prognostic marker. Gastrointestinal stromal tumor (GIST) genotype has been described in developed countries; however, data from India are lacking. The aim of this study was to determine the genotype frequency and its prognostic relevance. MATERIALS AND METHODS: Eighty consecutive cases of resected GIST were evaluated for histologic and immunohistochemical findings. Mutation analysis for exons 9, 11, 13, and 17 of KIT and 12 and 18 of PDGFRA was carried out by PCR-Sanger sequencing. Genotypes were correlated with risk groups, recurrence, and imatinib therapy. RESULTS: Forty-seven of 80 cases (58.7%) showed mutations, including 30 cases (37.5%) in KIT exon 11, 9 cases (11.2%) in KIT exon 9, and 8 cases (10%) in PDGFRA exon 18. Codon 557-558 deletion was present in 15 cases. D842E was the most common in PDGFRA, with similar histologic features as D842V. KIT exon 11 deletion had higher mitotic rate, larger tumor size, high-risk stratification, and lower recurrence-free survival. Recurrences were seen in 12 (16.4%) patients. Nine patients (75%) with recurrence were on imatinib therapy. CONCLUSIONS: GIST genotype frequency is lower in Indians. KIT exon 11 deletion is associated with poor prognosis compared with wild-type and other missense mutations. D842E is a common PDGFRA mutation in Indian patients. Patients with a wild genotype are not suitable candidates for imatinib therapy. Genotyping can serve as an important prognostic marker.