Immuno-diagnosis of malignant melanoma

The diagnosis of malignant melanoma must be followed by treatment shown to be effective. Therefore a correct diagnosis, including staging, that will permit a meaningful prognosis and treatment, is essential. The usefulness and great specificity of immunological methods is based on the detection of antigens characteristic of neoplastic and reactive cells. In cases of malignant melanoma, immunohistochemistry has limited practical value in the routine diagnosis of melanocytic lesions. The method may be important, however, in the differential diagnosis of, for example, malignant melanoma vs. non-melanocytic anaplastic neoplasia, malignant vs. benign melanocytic lesions, etc. Recent advances in relating the immunostaining of antigens to the development of tumor cells, such as proliferation and apoptosis, metastatic potential, etc. have given considerable importance to the immunomorphological evaluation of malignant melanomas. Likewise, immunotherapy requires the immunophenotyping of the reactive cells of the immune system.     

An oligomeric hydroxyphenylalanine in malignant melanoma: a new type of melanogen

A new compound designated MM2 has been isolated by ion exchange chromatography from tumor extracts and urine of patients with malignant melanoma. This material was purified by G-25 sephadex chromatography and studied by standard spectroscopic techniques including nuclear magnetic resonance, ultraviolet, infrared, and mass spectrometry. These data are consistent with an oligomeric structure of four dihydroxyphenylalanine subunits with subunit bonding made between phenyl rings. The appearance of large quantities of such an oligomer in malignant melanoma suggests the existance of intermediate stages of polymerization of melanin precursors before the final melanin high polymer is formed.     

Immunotherapy for malignant melanoma

Treatment of metastatic melanoma is a challenge for clinicians as most agents have failed to demonstrate improved survival in phase III trials. Despite the immunogenicity of this tumor entity, different immunological interventions including cytokine therapy, vaccination, biochemotherapy or allogeneic hematopoietic cell transplantation did not lead to a satisfactory response. However, continuous investigation on the immune mediated rejection of melanoma cells has led to the development of effective antibodies blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4), a critical negative regulator of the antitumor T-cell response. Based on data from rodent models, the anti-CTLA-4 antibody ipilimumab was developed into clinical studies where it had encouraging activity in advanced melanoma with unusual response patterns. As in most immunostimulatory therapies, acute toxicities were severe and clearly mechanism-related. Although some patients developed signs of autoimmunity, the toxicities were overall manageable and mostly reversible. This review summarizes different immunotherapeutical approaches against melanoma that have been applied in the past and focuses on CTLA-4 blockade with respect to its mechanism, clinical effectiveness and immunological side effects.     

Congenital malignant melanoma.

The diagnosis and management of a 3-day-old infant with an exophytic pigmented growth on her back and chest are discussed. At 3 days of age, the child underwent a complete surgical excision of this lesion with immediate coverage by partial-thickness skin grafts. Pathologically, the lesion proved to be a thoracolumbar congenital melanocytic nevus with multiple focal areas of malignant melanoma. The child is now 3 years past surgery and shows no evidence of recurrence or distant metastases. The importance of this case lies in the presence of overt malignant melanoma at birth within a giant congenital nevocytic nevus.     

The role of surgery in the treatment of malignant melanoma

Surgical interventions have important role in the treatment of all stages of malignant melanoma. Surgery is the primary treatment of localized cutaneous melanoma. Excision of the primary tumor makes it possible to set up the histological diagnosis and to determine pathological prognostic factors. Appropriate surgical margin is important for local disease control. Sentinel lymph node biopsy with detailed histological examination has gained prominent importance for correct histological staging and for determining adjuvant oncological treatment. Surgery is the primary treatment of isolated regional metastases. Surgical methods also have a role in the palliative management of distant metastatic melanoma. In the present review the most important issues of the surgical treatment of malignant melanoma have been discussed in detail.