What criteria reliably distinguish melanoma from benign melanocytic lesions?

The differential diagnosis of melanocytic lesions is fraught with difficulty and a common source of litigation either if a lesion misreported as 'benign' recurs locally or re-presents with nodal metastases or if an atypical naevus is called 'malignant' leading to a cosmetically unsatisfactory wider resection, unwarranted anxiety about prognosis and adverse life insurance prospects. Several authors have claimed that there are valid morphological criteria which, alone or in combination, enable reliable distinction between benign and malignant melanocytic lesions. Others question these criteria and, doubting the extent to which unequivocal diagnoses can be rendered in all cases, believe that the diagnosis is purely subjective and that most diagnostic errors are non-negligent. To address these issues, expert opinions were commissioned from three sets of authors. Okun, Edelstein & Kasznica emphasize that a significant minority of melanocytic lesions are so borderline morphologically that diagnostic uncertainty is allowable and that such uncertainty can be handled responsibly. Kirkham, in favouring the methodical use of criteria, concedes that they are 'largely opinion-based rather than evidence-based, but do go beyond mere subjective pattern analysis'. In agreement with Okun and his colleagues. Slater emphasises that no single feature is reliable by itself and that all aspects, including clinical details, should be interpreted together; he has no hesitation in reporting the diagnosis as 'uncertain' in doubtful cases. In the absence of a specific marker pathognomonic of melanocytic malignancy, the diagnosis will continue to rely on the judicious application of morphological criteria with a small proportion of elusive cases in which diagnostic uncertainty should not be concealed.

Histological demarcation of lateral borders: an unsupportable criterion for distinguishing malignant melanoma from Spitz naevus and compound naevus.

AIMS: The objective of this study was to determine the validity of sharpness of lateral margins (an important component of the pattern analysis method) as a criterion for the histological distinction of naevi from malignant melanoma. METHODS AND RESULTS: The sharpness of lateral borders in a series of histologically unequivocal malignant melanomas, Spitz naevi and compound naevi, chosen at random from dermatopathology slide archives, was determined. The incidence of poor demarcation of lateral borders in malignant melanomas was about equal to that of Spitz naevi and was significantly less than in compound naevi. The sharpness of lateral borders frequently varies with level of sectioning. CONCLUSIONS: The proposal that malignant melanomas have a significantly greater incidence of poor demarcation of lateral borders than benign melanocytic neoplasms (Spitz naevi and compound naevi) was shown to be without validity on cited empirical grounds as well as theoretical grounds (the lack of constancy of pattern from a 3-dimensional standpoint).

Silhouette symmetry: an unsupportable histologic criterion for distinguishing Spitz nevi and compound nevi from malignant melanoma.

BACKGROUND: In 1989, Ackerman proposed that pattern analysis can be a more accurate method of evaluating neoplasms than assessment of nuclear morphology. He stated that malignant melanomas tend to be asymmetrical, and benign melanocytic neoplasms tend to be symmetrical. METHODS: We examined a series of typical Spitz nevi, compound nevi, and malignant melanomas with the loupe and with higher magnifications. We also considered pattern analysis from the standpoint of solid geometry. RESULTS: The ratio of symmetrical to asymmetrical lesions (visualized in histologic sections) in malignant melanomas approximated that of Spitz nevi and compound nevi. The configuration seen in sections does not necessarily reflect the three-dimensional configuration of a lesion. Lesions with three-dimensional reflective symmetry cannot be shown to have this property in sections unless cuts are made perpendicular to the plane of symmetry, which is an impossibility. CONCLUSIONS: The presence or absence of symmetry in sections of neoplasms must be considered coincidental or focal. Using symmetry as a criterion to distinguish malignant melanomas from Spitz nevi and compound nevi is without validity on both theoretical and empirical grounds.

The role of peroxidase in neuromelanin synthesis: a review.

There is currently no general agreement on the enzymatic basis of neuromelanin synthesis. It is generally agreed that neuromelanin synthesis must differ from melanin synthesis in skin, since "tyrosinase" (aerobic dopa oxidase) is not present in brain. Various proposals have suggested that monoamine oxidase, prostaglandin H synthetase, or peroxidase may catalyze neuromelanin formation from dopa, dopamine and norepinephrine. It has also been proposed that neuromelanin synthesis may be based on the pseudoperoxidase activity of metal ions. Our group was the first to demonstrate enzymatic peroxidase activity in brain, which was subsequently confirmed by three other laboratories. Our group was also the first to demonstrate the melanogenic activity of brain peroxidase (subsequently confirmed by another laboratory) and to propose that peroxidase is the key enzyme in neuromelanin synthesis because of this potential and because of its presence in lysosomes, the subcellular site of neuromalin.

The cell and the organism: the role of subdivisional cell replication in the development and maintenance of the multicellular organism.

Evidence of new cell formation from nucleoli (subdivisional cell replication) was observed in vitro and in vivo. Mouse melanoma cells, human fibroblasts, and rat mast cells were observed in tissue culture with phase contrast time-lapse cinematography. Evidence of subdivisional cell replication seen in tissue culture was supported by observations of mast cells, cervical epithelial cells, melanoma cells, keratinocytes, and fungal spores in vivo. Indirect evidence for subdivisional cell replication was the presence of differentiated form and function in nuclei and nucleoli. Synergism between subdivisional replication and mitotic replication (subdivisional expansion) is believed to be a key to morphogenesis, whereby cellular and subdivisional zones act as biologic "molds". It is believed that subdivisional cell replication has a key role in maintenance of differentiated form in multicellular organisms, as well as in morphogenesis.

Pseudolymphomatous reaction to tattoos. Report of three cases.

Three cases with pseudolymphomatous hypersensitivity reaction to tattoo pigment are described. One of the cases showed histologic features of Spiegler-Fendt pseudolymphoma. Awareness of this type of reaction to tattoo pigment can help prevent erroneous diagnosis of lymphoma. Several published reports are cited in which pseudolymphomatous reaction to tattoo pigment was erroneously diagnosed as lymphoma.

Oxidation of tyrosine to dopachrome by peroxidase isolated from murine melanoma.

Peroxidase, isolated from B16 mouse melanoma, converted tyrosine to dopachrome in the presence of either dopa or dihydroxyfumarate co-factor. A suspended homogenate of cloned, cultured B16 mouse melanoma cells also showed peroxidatic conversion of tyrosine to dopachrome in the presence of dihydroxyfumarate co-factor. The findings confirm previous histochemical, autoradiographic-histochemical, and EM-histochemical studies showing that melanoma peroxidase can convert tyrosine to melanin.

Apocrine adenoma versus pocrine carcinoma. Report of two cases.

Two examples of apocrine neoplasm are presented, contrasting the features of an apocrine adenoma with those of a possible apocrine adenocarcinoma. Apocrine adenocarcinoma, distinct from Paget's disease, is a rare neoplasm. Its recognition is complicated by long periods of benign growth and by subtle histologic differences from apocrine adenoma.

Melanoma resembling spindle and epithelioid cell nevus.

Three cases of malignant melanoma resembling spindle and epithelioid cell nevus histologically are presented. Lesions having histologic features of spindle and epithelioid cell nevus (Spitz nevus or juvenile melanoma) at or after puberty should be regarded with caution, particularly when they are heavily melanized. Such lesions are in a histologic "gray zone" and may be malignant.

Combined melanocytoma-mastocytoma in a case of nodular mastocytosis.

A patient with long-standing nodular mastocytosis developed a slate-blue lesion on the scalp which produced symptoms of histamine release on mechanical and thermal stimulation. Light and electron microscopic examination of the lesion showed zones of mast cells and zones of melanized cells. A transition zone showing cells with dual (melanosomal and mast) granulation, as well as granules representing intergrades between classical mast granules and melanosomes, was present. Features of this lesion add to the accumulated evidence that there is a histogenetic relationship between mast cells and melanocytes.

Inability to demonstrate hydroxylation of tyrosine by murine melanoma "tyrosinase" (L-DOPA oxidase), using the tritiated water assay technique.

Validity of the tritiated water assay technique for tyrosine hydroxylase activity as a qualitative method was demonstrated with mushroom tyrosinase. Using this method, isolated murine melanoma "tyrosinase" (L-dopa oxidase) showed no tyrosine hydroxylase activity. This finding supports previous studies in our laboratory which used a variety of histochemical and biochemical methods. The nonenzymatic production of tritiated water caused by tritium exchange with hydrogen peroxide complicates the use of the tritiated water assay technique with crude systems, since hydrogen peroxide is generated by a variety of oxidase reactions. For this reason, previous studies using the tritiated water assay technique with crude systems are ambiguous.