A Rare Case of Metachronous Quadruple Primary Malignancies in a Single Patient: A Case Report and Comprehensive Literature Review.

Multiple primary malignancies (MPMs) in the same patient are rare. Over the past decade, the incidence of MPMs is increasing. The prevalence in the general population is 0.7-11.7%, with a higher incidence in the elderly. This increase in incidence can be attributed to advanced lifespan, environmental factors, early chronic disease/cancer screening, and advanced treatment leading to more metaplasia. The chances are higher in cancer patients due to the carcinogenic effect of chemoradiotherapy. Here, we present a 79-year-old female with a 27 pack-year smoking history without any significant genetic predisposition, who developed four different primary malignancies including (1) chronic lymphocytic leukemia in 2017 (stage I modified Rai), positive for CD23 and CD5, which did not require treatment; (2) melanoma in situ on the left cheek in 2019 status post excision; (3) lung adenocarcinoma with negative molecular study (epidermal growth factor receptor (EGFR)/ROS proto-oncogene, receptor tyrosine kinase (ROS)/v-Raf murine sarcoma viral oncogene homolog B1 (BRAF)/anaplastic lymphoma kinase (ALK)) and negative programmed cell death ligand 1 (PDL-1) in 2020 for which she received treatment with carboplatin, pemetrexed, and pembrolizumab; and (4) left lower pole renal mass on surveillance CT scan, which was highly suspicious for primary malignancy as opposed to metastasis, for which she underwent radical nephrectomy and biopsy positive for clear cell renal cancer. Regarding these multiple primary cancers, the thought of germline mutation was considered. But as she did not have a family history of malignancy, genetic testing was not needed as per the genetic counselor. Patients are being diagnosed with MPMs as there is more advancement in tumor detection and treatment. With the advancement in the treatment, cancer survivorship is improving. Given that there are no large studies, we believe that treatment modality for MPMs should be on a case-to-case basis and needs a multidisciplinary approach to tackle therapeutic challenges and provide radical treatment.