Ultrastructural evidence for destruction in the halo nevus.

Nine halo nevi in various stages of regression were examined by electron microscopy for fine structural evidence of an immunological mechanism of tumor cell destruction and halo formation. Early regressing lesions (Stage I) showed nevus cells associated with infiltrating lymphocytes, monocytes, and plasma cells, but without nevus cell destruction. In later lesions (Stages II and III), vacuolar cytolysis was commonly observed in nevus cells. In Stage III lesions, portions of nevus cells are found within macrophages. The electron microscopic findings of lymphocyte, monocyte, and plasma cell infiltration of the tumor followed by vacuolar cytolysis support the concept of an immune reaction in regressing halo nevi.

Inability of murine melanoma melanosomal "tyrosinase" (L-dopa oxidase) to oxidize tyrosine to melanin in polyacrylamide gel systems.

Melanosomal "tyrosinase" (L-dopa) was isolated from trypsin digest of B-16 mouse melanoma melanosomes, using polyacrylamide gel disc electrophoresis. The enzyme was represented by a single band, having characteristics similar to the T1 dopa-positive band observed when using supernatants of crude melanoma homogenates as the source. When gels with this band were incubated in solutions containing tyrosine and dopa in varying ratios , there was no enhancement of melanin formation by tyrosine when compared with incubations in corresponding concentrations of dopa alone. These data further support previous studies in our laboratory demonstrating an inability of so-called mamalian "tyrosinase" to convert tyrosine to melanin; since this enzyme readily converts L-dopa to melanin, it seems more reasonable to term this enzyme an L-dopa oxidase.

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.

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.

Cellular blue nevus. An ultrastructural study.

Cellular blue nevus can be clinically and histogenetically confused with malignant melanoma but remains a benign neoplasm of uncertain histogenesis. This paper reports the ultrastructural features of three cases of cellular blue nevus and emphasizes melanosomal alterations, including immature and granular forms, multiple layers of basement membrane around vessels, nerve fibers and tumor cells; endothelial fenestrations and banded structures within the nerve and outside in the stroma. A unifying concept of neural crest derived tumors is presented to better understand the histogenesis of cellular blue nevus.

Multiple layers of basement membrane around myelinated and unmyelinated fibers in cellular blue nevus.

Concentric multiple layers of basement membranes around Schwann cells in cellular blue nevus are reported.

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.

Peroxidatic oxidation of tyrosine to melanin in supernatant of crude mouse melanoma homogenates.

Peroxide-dependent enzymic oxidation of tyrosine to dopachrome and melanin was demonstrated in cell-free melanoma homogenates. Histochemical methods for distinguishing peroxidase activity from aerobic dopa (3,4-dihydroxyphenylalanine) oxidase activity are not reliable with cell-free preparations. Therefore the presence of peroxidase activity in such preparations precludes assay of cresolase activity of mammalian ;tyrosinase'.

Quantification of melanin in hepatic and cardiac lipofuscin.

Melanin pigment in liver and heart tissue, obtained at autopsy from patients, was isolated and quantified. The quantity of melanin extracted was directly proportional to lipofuscin granule counts. Infrared and electron spin resonance spectographs of the isolated pigments from liver and heart showed absorption characteristics identical to those of known melanins. The pigment was absent in fetal and neonatal life, increased in brown atrophy of the heart and liver, and diminished in livers with fatty metamorphosis.

Pili bigeminy induced by low fluence therapy with hair removal alexandrite and ruby lasers.

BACKGROUND: Lasers are being widely used for the hair removal. Several complications including hyperpigmentation, erythma, hypopigmentation, and burns have been reported. OBJECTIVE: To study laser hair removal complications. METHODS: Pubic hairs were treated with alexandrite and ruby lasers. RESULTS: Pili Bigeminy can be induced by low fluence therapy with hair removal Alexandrite and Ruby lasers as a complication. CONCLUSION: To our knowledge, this is the first report of pili bigminy as a complication of laser-assisted hair removal.