Amelanotic malignant melanoma: recognizing aberrant premelanosomes

The key to diagnosing cases of melanoma, a tumor of melanocytes, is to recognize cytoplasmic pigment called melanin. In most cases this can be done at the light microscopy level; however, in the rarer amelanotic (non-pigmented) melanomas, melanin is not present in detectable amounts. Thus it is necessary to do an ultxastructural investigation to detect melanosomes, the specific organelles of the melanocyte that synthesize melanin. Other non-melanoma cells can also possess melanin by internalization of melanin granules by phagocytosis or passive transfer (e.g. macrophages, keratinocytes) but they lack the premelanosome organelle, the precursor to the fully developed melanosome. In premelanosomes, the internal structures are not obscured by melanin. Thus it is the diagnostic feature of choice for the pathologist. In malignant melanoma, aberrant forms of premelanosomes and melanosomes are more typical than in normal melanocytes., These aberrant forms may not be well recognized. Amelanotic melanomas give us a good opportunity to study these structures. In studying premelanosomes,the investigator must be aware of variations of size, shape, appearance in different planes of sections, and knowledge of the four stages of normal melanosome development (melanogenesis).