Primary dermal melanoma in a patient with a history of multiple malignancies: a case report with molecular characterization.

Abstract
Introduction: Primary dermal melanoma (PDM) is a recently described clinical entity
accounting for less than 1% of all melanomas. Histologically, it is located in the dermis or
subcutaneous tissue, and it shows no connections with the overlying epidermis. The
differential diagnosis is principally made along with that of metastatic cutaneous melanoma.
Case Report: A 72-year-old Caucasian woman with a history of multiple cancers (metachronous
bilateral breast cancer, meningioma, clear cell renal cell carcinoma, uterine fibromatosis
and intestinal adenomatous polyposis), came to our attention with a nodular lesion on her
back. After removal of the lesion, the histology report indicated malignant PDM or metastatic
malignant melanoma. The clinical and instrumental evaluation of the patient did not reveal
any other primary tumour, suggesting the primitive nature of the lesion. The absence of an
epithelial component argued for a histological diagnosis of PDM. Subsequently, the patient
underwent a wide surgical excision with sentinel node biopsy, which was positive for
metastatic melanoma. Finally, the mutational status was studied in the main genes that
regulate proliferation, apoptosis and cellular senescence. No pathogenetic mutations in
CDKN2A, BRAF, NRAS, KRAS, cKIT, TP53 and PTEN genes were observed. This suggests that
alternative pathways and low-frequency alterations may be involved. Conclusions: The differential diagnosis between PDM and isolated metastatic melanoma depends on the
negativity of imaging studies and clinical findings for other primary lesions. This distinction is
important because 5-year survival rates in such cases are higher than in metastatic cases (80–
100 vs. 5–20%, respectively).