Molecular Genetics in a Cohort of Patients With Concurrent PTC and Melanoma

PTC and melanoma are known to harbour common mutations, but this has not been extensively investigated. Targeted therapies for BRAF and PD-L1 have been used for melanoma and there are ongoing clinical trials for use of PD-L1 inhibitors in PTC but its utility is uncertain. Additionally, many of these patients have multiple cancers, so, whether they have a tumour predisposition syndrome is also unclear. Both germline and somatic mutations in BRCA1-associated protein 1 (BAP1) are associated with a wide spectrum of tumours. We hypothesized that a common genetic link may be present in our cohort of patients who have both PTC and melanoma. The aim of this study was to elucidate molecular genetics, specifically BRAF, NRAS, KRAS, KIT using OncoFocus Mass Array System as well as expression of PD-L1 and BAP1, using a standard antibody (SP263) and C-4 respectively, in an Australian cohort with concurrent PTC and melanoma. In our cohort of 21 patients (43% females, all Caucasian), melanoma was diagnosed about 8 years prior to PTC (50.3 ± 18.3 vs. 58.6 ± 12.8 years). The most common mutation was BRAFV600E seen in 88% of PTC, followed by NRAS mutation in 12% of PTC. Majority of the PTC (68%) stained negative for PD-L1. There was no significant association between PD-L1 tumour status and clinicopathologic outcomes. Interestingly, majority of multifocal, bilateral and both bilateral and multifocal PTC were PD-L1 negative (85%,69% and 69% respectively, P<0.05); only extrathyroidal extension was found to be associated with positive (≥1%) PD-L1 staining (83.3 vs.30.8; p=0.057). Regarding melanoma, clinicopathologic and mutation data were obtained for 15/21 patients and 8/15 patients respectively. Superficial spreading type of melanoma was present in 50% patients. The BRAFV600E and NRAS mutation were present in 3/8 patients each, and 2/8 patients had no mutations. PD-L1 staining was negative in 7/12 (58%) of melanoma tissues. Of the 5 cases that stained positive for PD-L1, 4 were at >25%, a much higher degree of staining compared to PTC group. Among 7 patients where data were available for both tissues, concordant mutations were found in only 2 patients (both BRAFV600E). In addition, 11 of the 21 patients had at least one other cancer apart from PTC and melanoma. Nine of the 11 patients who had more than one cancer were BRAF positive. BAP1 staining was retained in the majority of PTCs and melanoma tissues, indicating no loss of BAP1 protein. PTC and melanoma both share molecular markers including BRAF, NRAS, PD-L1 as shown in our cohort. This is the largest study describing the mutation status of both PTC and melanoma. It is also the only study describing the PD-L1 and BAP1 expression in PTC and melanoma. BRAFV600E was the most common mutation. Majority of the PTC and melanoma stained negative for PD-L1. BAP1 expression was retained in both either PTC and melanoma tissues thus making presence of BAP1 tumour predisposition syndrome unlikely.

Clinicopathological analysis of basal cell carcinoma – A retrospective study

Objectives: The objective of the study was to analyze the demographic profile, histopathological features, risk factors, and recurrence rates in patients with basal cell carcinoma. Materials and Methods: A retrospective study was conducted from 2012 to October 2018 in 29 patients with histopathologically confirmed basal cell carcinoma. All the patients had undergone either excision or cryotherapy as per the institution protocol. Information on the history of the disease, occupation, history of sun exposure and clinical and histopathological features were collected and analyzed. Results: A female preponderance was found (n = 18, 62.1%), majority of the patients were unemployed (44.8%), 19 patients (65.5%) gave a history of sun exposure, and the nose was the most common site of disease. Ten females (34.5%) did not have any excessive exposure to the sun, but gave a history of exposure to heat and fumes in the kitchen. Six patients (20.7%) had a preexisting nevus at the same site and superficial spreading type was the most common histopathological type (n = 24, 82.8%). Excision gave the best result. Four patients (13.8%) had recurrence of the disease. Limitations: Small sample size was the major limitation. The risk factors and occupation could not be analyzed objectively. Conclusion: This is a pioneer study from Kerala. A female preponderance (62.1%) was observed. The role of heat, fumes, type of oven, and use of reheated oil in cooking as risk factors for the development of BCC needs analysis in future studies. Superficial spreading type was the most common pattern observed in histopathology slides (82.8%). Excision gives near-complete clearance and a good cosmetic result with less risk of recurrence.