Nevoid malignant melanoma

The term “nevoid malignant melanoma” (nevoid MM) is used here to describe rare nodular malignant melanomas that may escape detection in routine histological sections due to the lack of a prominent intraepidermal component, sharp lateral circumscription and evidence of partial maturation with descent in the dermis (1). Nevoid MM mimic ordinary compound or intradermal melanocytic nevi when the melanoma cells are small or Spitz’s nevi when the cells are large (2, 3) (Table 1). Reed et at. (4) proposed between 1975 and 1988 that two additional categories be added to the usual list of histological types of malignant melanomas, i.e., minimal deviation melanoma (MOM) and borderline melanoma (4). These categories have not been generally accepted and even some of the original authors have published the recommendation that these terms be avoided (5). Other investigators have included nevoid melanomas in the category of MDM and borderline melanoma (4, 6). In contrast to “nevoid melanoma”, MOM have all the heterogeneous architectural features found in melanomas in general but only less cytologic atypia (4). In 1985, Schmoeckel et al. (1) introduced the name “nevoid malignant melanoma” in their study of a series of 33 unusual melanomas. In their patients, 15 had developed metastases and eight had died of disseminated melanoma. These tumors were called nevoid because of certain architectural and cytologic features that strongly resembled those of ordinary benign compound or intradermal melanocytic nevi, with papillomatous or nodular shapes. Other names are preferable for those melanomas that mimic other types of nevi, for example ‘superficial spreading malignant melanoma” can mimic nevi with architectural disorder or “dysplastic nevi”, and “malignant blue nevus” can mimic cellular blue nevus. Certain unusual types of nevi are more difficult to differentiate from nevoid MM and include combined nevi, deep penetrating nevus (DPN) (7, 8), “atypical dermal melanocytic lesions with differentiation along schwannian lines” (9), and “dermal melanocytic tumors of uncertain potential” (10). In our work, we have selected for study a group of unusual nevoid nodular melanomas according to the criteria of Schmoeckel et at. (1), including: i) lack of considerable junctional proliferation and absence of scattered tumor cells within the epidermis; ii) presence of monomorphous nevocytic tumor cells; and iii) nevoid architectural pattern, i.e., poorly demarcated tumor base (often with little or no inflammatory reaction), sharp lateral demarcation, and symmetry of the whole lesion. For immunohistochemistry, the antibodies employed were HMB45 against a component of premelanosomes, and MIBi against the Ki-67 antigen in paraffin sections (11). The patterns of HMB-45 staining in 12 nevoid MM were compared with those in 107 melanocytic nevi, without antigen retrieval methods. HMB-45 staining was strong in the dermal component of the nevoid MM, even in the absence of a junctional component. In common acquired and congenital nevi, the upper dermal component stained less than the junctional component of the lesion. The deepest components of these nevi were negative. Spitz nevi and cellular blue nevi had positive dermal cells even without a junctional component. Additional staining for a proliferation marker, such as Ki-67 (with the antibody MIB-1 after microwave antigen retrieval), can help further in distinguishing a nevoid MM from a Spitz’s nevus. Melanomas have strong nuclear staining throughout the lesion. In contrast, Spitz’s nevi have more staining at the top of the lesion than at the bottom. The patterns of HMB-45 and MIB-1 staining can be used along with standard histological criteria for the diagnosis of nevoid MM, based on the detection of lack of true maturation of the tumor cells with progressive descent in the dermis. Clinical-pathological correlation is needed to distinguish some metastatic melanomas from primary nevoid MM. It seems likely that the nevoid MM are early stages in the evolution of nodular melanomas. Often in large nodular melanomas, there are regions with different morphologies of the melanoma cells that suggest an evolution in the dermis toward a more malignant cell type (4). Regarding prognosis, the study of Schmoeckel et a/. (1) concluded that the clinical characteristics and prognosis of nevoid MM were similar to those of the standard melanomas and depended on the measured depth of invasion into the dermis. In other studies, there are suggestions of a better than expected prognosis for patients with nevoid melanomas (6). In a study by TY. Wong et at. (12) seven nevoid MM were reported with criteria for case selection similar to ours and a better than expected prognosis was observed. Of the 14 patients that we reported in 1995 (2), one patient was dead at 3 years; three patients with skin metastases were alive Table 1. Histological comparison of nevoid melanoma and nevus.