A Case of Dedifferentiated Melanoma With Lymph Node Metastasis Where Molecular Biological Tests Were Useful for Diagnosis

Abstract

Malignant melanoma is known to have an altered phenotype and loss of differentiation markers for melanoma due to metastasis. Here, we report a case in which the expression of the immunohistochemical markers for melanoma was changed due to lymph node metastasis of primary cutaneous malignant melanoma. The patient, a male in his 60s, was diagnosed with malignant melanoma after undergoing excision of a skin mass. The additional excision specimen showed a small number of tumor cell clusters infiltrating the dermis. The biopsied lymph node showed completely different histological findings from those of the skin lesion and consisted of spindle-shaped tumor cells. An immunohistochemical study revealed no significant positive reactions in the lymph node tissue indicative of melanoma. The additional genetic study revealed BRAF V600e mutations in both the primary tumor and a lymph node. Together with the histological findings, the diagnosis was of metastasis of dedifferentiated melanoma to a lymph node. In summary, there is a risk of underestimation or misdiagnosis of melanoma as undifferentiated sarcoma or other tumors when melanoma metastasizes to lymph nodes and findings show a dedifferentiated or undifferentiated tumor. Therefore, as in this case, it is necessary to add a genetic study in order to make a comprehensive judgment.

Utility of sequencing for ATP6AP1 and ATP6AP2 to distinguish between atypical granular cell tumor with junctional component and melanoma

“…12 Sequencing for recurrent melanoma-associated driver mutations such as BRAF and NRAS has been proposed as a more sensitive and specific method of establishing a diagnosis of melanoma when all melanoma immunostains are negative. [14][15][16][17][18][19][20] Recently, recurrent loss of function mutations in the vacuolar ATPase complex genes ATP6AP1 and ATP6AP2, which regulate endosomal pH, have been identified in 72% of GCTs, including atypical and malignant GCT. 21 These were frameshift mutations and premature stop codons.…”