Arpit Jain

Non-gestational choriocarcinomas (NGCCs) are extremely rare and aggressive tumours that can develop without pregnancy. We present three cases in postmenopausal women in their early 60s and 70s who presented with abdominal symptoms. Evaluation included imaging, histopathology, immunohistochemistry and elevated serum β-hCG. One patient showed a partial response to chemotherapy, while two had disease progression and died. The case series illustrates the need for consideration of NGCC in older women with elevated β-hCG and no recent pregnancy, and the crucial role of early immunohistochemical diagnosis.

PURPOSE: Dihydropyrimidine dehydrogenase (DPD) deficiency, an autosomal recessive metabolic disorder, causes a considerable deficit in the patient's metabolism of fluoropyrimidine drugs, most notably 5-fluorouracil (5-FU) and capecitabine. There is a higher frequency of severe toxicities after a fluoropyrimidine regimen among patients with GI and hepatopancreaticobiliary (HPB) malignancies on chemotherapy because of this metabolic deficiency. This prospective study aims to assess the rate of DPD deficiency and clinical significance of DPD deficiency in patients receiving fluoropyrimidine chemotherapy at a tertiary oncology center in India. MATERIALS AND METHODS: From March 2024 to February 2025, we prospectively recruited 146 patients with histologic confirmation of GI and HPB cancers who were commencing a 5-FU– or capecitabine-based regimen. We performed pretreatment DPD tests on all patients using TRUPCR DPYD reverse transcriptase polymerase chain reaction for four known variants. Severe toxicities (Common Terminology Criteria for Adverse Events v5.0) were assessed after the first cycle of chemotherapy. Dose reductions, advances in therapy, and admissions were also noted. RESULTS: Of the 146 study participants, 11 (7.5%) had a DPYD mutation. HapB3 (rs56038477) was the most commonly encountered variant (72.7% of patients), along with registries of DPYD*2A (18.2%) mutation and mutation c.2846A>T (9.1%). Severe toxicities (grade ≥3) were above other grade toxicities (61.6%) in mutation carriers (72.7%) as compared with mutation noncarriers (37.0%, P = .03). Neutropenia, diarrhea, and thrombocytopenia were the common toxicities at a frequency of 18.5%, 12.3%, and 15.1%, respectively. After dose reduction, 90.9% of mutation carriers required a dose reduction versus 14.8% of mutation noncarriers ( P < .001). Both groups had no problems in completing treatment. CONCLUSION: Individuals with DPYD mutations experience increased toxicity and dose adjustments; however, treatment efficacy was not affected. This indicates that a coordinated effort that incorporates routine DPYD testing can mitigate treatment toxicities and individualized fluoropyrimidine dosing for patients with GI and HPB cancers.

Colorectal cancer (CRC) is a heterogeneous disease morphologically, histologically, and molecularly. Most of the studies are on this molecular heterogeneity and their clinicopathological correlation from the western world. Very few studies have been done in India. The aims of this study were to evaluate the clinical and pathological profile of CRCs, to determine the frequency of molecular subtypes of CRCs, to correlate between the molecular subtypes and their clinicopathological features, and to determine the association between different molecular subtypes of CRC. A prospective noninvasive interventional study was done on 50 patients (both outpatients and inpatients) with newly diagnosed CRCs presenting to the Rajiv Gandhi Cancer Institute and Research Centre, Rohini, Delhi, from February 2019 to March 2020. Clinical and histopathological data were collected from case sheets as per the study proforma: history and physical examination, noninvasive and invasive imaging, and histopathological reports. Patients in whom tissue was insufficient or not available for testing for at least three of five molecular markers (KRAS, NRAS, BRAF, MSI, and MLH1 methylation) were excluded. The results were analyzed with SSPS 23.0 software. For comparison of the frequencies among groups, the chi-squared test and the Fisher exact test were used. A p-value of less than 0.05 was considered statistically significant. The median age was 53 years. The majority of the males (54%) had CRC and 44% were right-sided colon tumors. Of the 50 patients with CRC, 40, 0, 4, and 4% had KRAS mutation, NRAS and BRAF mutation, and deficient mismatch repair (dMMR), respectively. KRAS mutation was significantly associated with upfront liver metastases (p = 0.02) and well/moderate differentiation (p = 0.02). BRAF wild-type tumors were likely to be well differentiated (p = 0.02), and moreover, half of them (52%) had MLH1 promoter methylation. The proportion of dMMR was higher in male patients (p = 0.04). Deficient mismatch repair was associated with well/moderate differentiation (p = 0.02), early stage (p =0.02), and mild peritumoral lymphocytes (p = 0.01). None of the dMMR patients had stage IV CRC. In all, 27% of the patients (3/11) with dMMR tumors had germline mutation of the dMMR genes. The majority of dMMR tumors (43%, 3 out of 7) had MLH1 promoter methylation. Overall, 45% (5/11) of dMMR tumors harbored KRAS mutation. In conclusion, this is a prospective study evaluating the correlations between RAS/BRAF mutation and dMMR status with clinicopathological characteristics in Indian CRC patients, which is slightly similar to worldwide reports with some exceptions. To the best of our knowledge, this is the first study to evaluate the molecular marker combinations in CRC in India.

Unveiling the uncommon: Disseminated intravascular coagulation as an unusual presentation of metastatic carcinoma prostate - ACHR- Print ISSN No: - 2581-5725 Online ISSN No:- 2456-9267 Article DOI No:- 10.18231/j.achr.2023.027, IP Archives of Cytology and Histopathology Research-IP Arch Cytol Histopathol Res