Although melanoma only accounts for 1% of skin cancers, it is responsible for most skin cancer deaths. Glioblastoma multiforme, a high-grade astrocytoma, is the most aggressive and devastating primary brain tumor. These two diseases remain to be the biggest therapeutic challenge in both specialties of dermatology and neuro-oncology. A 53-year-old Filipino male who presented with a 2-year history of generalized dark brown and black patches on the body developed weakness and numbness of the left extremities. Biopsy and immunohistochemical staining of the skin revealed nodular melanoma with adjacent regressing melanoma. Biopsy of the intracranial mass showed glioblastoma multiforme. One month after the partial excision of the intracranial mass, the patient expired due to brain herniation. Nodular melanoma and glioblastoma multiforme may occur concomitantly in a patient. A review of the literature suggests a shared genetic predisposition. Its existence carries a poor prognosis and requires early detection to start aggressive treatment.

The nervous system is commonly involved in a wide range of genetic tumor-predisposition syndromes. The classification of genetic tumor syndromes has evolved during the past years; however, it has now become clear that these syndromes can be categorized into a relatively small number of major mechanisms, which form the basis of the new 5th edition of the World Health Organization book (beta online version) on genetic tumor syndromes. For the first time, the World Health Organization has also included a separate chapter on genetic tumor syndromes in the latest edition of all the multisystem tumor series, including the 5th edition of CNS tumors. Our understanding of these syndromes has evolved rapidly since the previous edition (4th edition, 2016) with recognition of 8 new syndromes, including the following: Elongator protein complex-medulloblastoma syndrome, BRCA1-associated protein 1 tumor-predisposition syndrome, DICER1 syndrome, familial paraganglioma syndrome, melanoma-astrocytoma syndrome, Carney complex, Fanconi anemia, and familial retinoblastoma. This review provides a description of these new CNS tumor syndromes with a focus on imaging and genetic characteristics.

Knowledge about the prevalence and tumor types of CDKN2A-related melanoma-astrocytoma syndrome (MAS) is limited and could improve disease recognition. To estimate the prevalence and describe the tumor types of MAS. This retrospective cohort study analyzed all available MAS cases from medical centers in the US (2 sites) and Europe (2 sites) and from biomedical population genomic databases (UK Biobank [United Kingdom], Geisinger MyCode [US]) between January 1, 1976, and December 31, 2020. Patients with MAS with CDKN2A germline pathogenic variants and 1 or more neural tumors were included. Data were analyzed from June 1, 2022, to January 31, 2023. Disease prevalence and tumor frequency. Prevalence of MAS ranged from 1 in 170 503 (n = 1 case; 95% CI, 1:30 098-1:965 887) in Geisinger MyCode (n = 170 503; mean [SD] age, 58.9 [19.1] years; 60.6% women; 96.2% White) to 1 in 39 149 (n = 12 cases; 95% CI, 1:22 396-1:68 434) in UK Biobank (n = 469 789; mean [SD] age, 70.0 [8.0] years; 54.2% women; 94.8% White). Among UK Biobank patients with MAS (n = 12) identified using an unbiased genomic ascertainment approach, brain neoplasms (4 of 12, 33%; 1 glioblastoma, 1 gliosarcoma, 1 astrocytoma, 1 unspecified type) and schwannomas (3 of 12, 25%) were the most common malignant and benign neural tumors, while cutaneous melanoma (2 of 12, 17%) and head and neck squamous cell carcinoma (2 of 12, 17%) were the most common nonneural malignant neoplasms. In a separate case series of 14 patients with MAS from the US and Europe, brain neoplasms (4 of 14, 29%; 2 glioblastomas, 2 unspecified type) and malignant peripheral nerve sheath tumor (2 of 14, 14%) were the most common neural cancers, while cutaneous melanoma (4 of 14, 29%) and sarcomas (2 of 14, 14%; 1 liposarcoma, 1 unspecified type) were the most common nonneural cancers. Cutaneous neurofibromas (7 of 14, 50%) and schwannomas (2 of 14, 14%) were also common. In 1 US family, a father and son with MAS had clinical diagnoses of neurofibromatosis type 1 (NF1). Genetic testing of the son detected a pathogenic CDKN2A splicing variant (c.151-1G>C) and was negative for NF1 genetic alterations. In UK Biobank, 2 in 150 (1.3%) individuals with clinical NF1 diagnoses had likely pathogenic variants in CDKN2A, including 1 individual with no detected variants in the NF1 gene. This cohort study estimates the prevalence and describes the tumors of MAS. Additional studies are needed in genetically diverse populations to further define population prevalence and disease phenotypes.

The occurrence of both melanoma and glioma was first suggested by the observation of a familial association between these conditions, which was later confirmed by the description of the melanoma-astrocytoma syndrome, an extremely rare, inherited affliction in which people have an increased risk of developing melanoma and nervous system tumors. Taking into consideration the common embryologic precursor, the neuroectoderm, it was hypothesized that this syndrome is associated with a genetic disorder. While some families with germline CDKN2A mutations are prone to develop just melanomas, others develop both melanomas and astrocytomas or even other nervous-system neoplasms. Herein, we report the case of a 63-year-old male patient with no personal or family history of malignancy who had primary melanoma followed by glioblastoma. Our case report suggests that the occurrence of both melanoma and glioblastoma is most likely not coincidental but instead linked to genetic mutations of common embryologic precursors or signaling pathways.

Recently, we came across a patient with malignant melanoma and primary glioblastoma. Given this, we parsed the literature to ascertain the relationship, if any, between these 2 malignancies. We begin with a brief overview of melanoma and glioma in isolation followed by a chronologic overview of case reports and epidemiologic studies documenting both neoplasms. This is followed by studies detailing genetic abnormalities common to both malignancies with a view to identifying unifying genetic targets for therapeutic strategies as well as to explore the possibility of a putative association and an inherited cancer susceptibility trait. From a scientific perspective, we believe we have provided evidence favoring an association between melanoma and glioma. Future studies that include documentation of additional cases, as well as a detailed molecular analyses, will lend credence to our hypothesis that the co-occurrence of these 2 conditions is likely not serendipitous.