Germline VHL Mutation Discovered in Association with EGFR-Positive Lung Cancer and Metachronous Hepatocellular Carcinoma: A Case Report

VHL is a tumor suppressor gene located on chromosome 3 that is classically associated with tumors of the eye and CNS, renal cell carcinoma, and pheochromocytoma. We describe what appears to be the first report of an association between a germline VHL mutation and non-small cell lung cancer and metachronous hepatocellular carcinoma (HCC). Our case involves a 63-year-old nonsmoking male who was initially diagnosed with EGFR mutation-positive metastatic nonsquamous, non-small cell lung adenocarcinoma, who subsequently developed HCC and squamous cell carcinoma of the femur despite first-line treatment with EGFR-blocking osimertinib. Caris molecular profiling unexpectedly identified a shared underlying VHL mutation in all 3 lesions. Genetic mapping through a machine learning-based tool called Genomic Prevalence Score (GPSai^™) helped determine that the femur tumor was a metastatic lesion as opposed to a separate primary and that the HCC was a distinct primary malignancy. We not only highlight the association between these tumors and a VHL mutation but also emphasize the value of next-generation sequencing and a molecular disease classifier in a patient with multiple primaries, how it helps guide therapy, and its value in guiding future studies.

Metachronous prostate and colon adenocarcinomas

Multiple primaries in patients with prostate cancer are uncommon. We report a case of prostate adenocarcinoma who did not receive any form of treatment, diagnosed 7 months later with colon adenocarcinoma. The patient underwent right extended hemicolectomy and recovered well. He is planned to receive adjuvant chemotherapy and hormonal therapy. Management of such cases can present a dilemma and multiple factors must be taken into consideration, particularly when the first primary tumour is still active.

Synchronous Primary Tumors of Kidney and Bilateral Ovaries-A Diagnostic Challenge: Case Report

Multiple malignancies in the same patient account for 2% to 17% of all cancers. However, multiple synchronous primary tumours in the same patient are extremely rare. Most synchronous primary tumors involve the genitourinary and gastrointestinal tract, followed by both breast and genitourinary tract, and breast and gastrointestinal tract. Among gynaecological malignancies, synchronous primary carcinomas of the endometrium and ovary are the commonest. Synchronous primary neoplasm involving kidney and ovaries are extremely rare, with only few case reports in the literature; however, there are no reported cases in the Indian literature. We hereby report a case of 60 year old woman who underwent radical nephrectomy for renal cancer and primary cytoreductive surgery for her ovarian cancer. In this report we present the first case in the Indian literature of synchronous primary cancers in right kidney and bilateral ovaries. Based on the combination of factors (diagnosis, treatment and demographics), it is expected that in the course of the coming years, the prevalence of patients with multiple primaries will increase. Careful attention should be paid to the differential diagnosis between double primary and metastatic tumours, based on the pathologic, radiological and clinical characteristics.

SPORADIC AND HEREDITARY FORMS OF MULTIPLE PRIMARY MALIGNANT TUMORS IN CHILDREN

The article presents the features of the clinical manifestation of multiple primary sporadic and heritable malignant tumors in 104 children who observed at Pediatric Oncology and Hematology Research Institute of «NN Blokhin's National Medical Research Center of Oncology» from 1998 to 2012. The age of patients at the time of occurrence of the second malignant tumor ranged from 2.8 to 28 years and averaged 15.6 years. The second neoplasia occurred significantly more frequently in the group of primary hemoblastosis, compared with the group of solid tumors - 8.7% versus 3.4%, respectively (p <0.0001). In children with multiple primaries, were found tumors that occur in common the most frequency. Retinoblastoma patients have an increased risk of developing sarcoma. Patients with Hodgkin's lymphoma have an increased risk of developing leukemia. In surviving children after treatment of the first neoplasia the thyroid, bone tissue and breast have a specific risk for the development of metachronous cancer and are target organs for control. Children with new hematopoietic tumors may be candidates for metachronous development of leukemia and bone tissue tumors. The using methods Next Generation Sequencing (NGS) and Multiplex Ligation-dependent Probe Amplification (MLPA) revealed germinal mutations in 12 children with of multiple primary tumors. The mutations in the TP53, RB1, CHEK2, FANCN/PALB2, MLH1, PMS2 genes identified in patients were associated with hereditary syndromes and an increased risk of developing second tumors, among which: sarcomas, brain tumors, hematopoietic tumors were the most frequent. It was shown that the second tumors can appear at the any age. Children who survived the treatment of the first tumor in later life should be monitored annually. Clinical management of children with multiple primary tumors requires a multidisciplinary approach.