Randall J. Margolis

Gamma-interferon inhibits collagen synthesis in vivo in the mouse.

Subcutaneous implantation of osmotic pumps into CAF1 mice resulted in the formation of thick fibrous capsules around the pumps. When pumps were loaded with recombinant murine gamma-interferon (rMuIFN-gamma) to deliver 2 X 10(3) U/h for 14 d, there was a marked decrease in thickness and collagen content of the capsules from rMuIFN-gamma-treated animals compared with capsules from animals receiving diluent alone. The collagen content of the capsules was estimated by hydroxyproline analysis of the tissue and by quantitative electron microscopy of collagen bundles. Heat-inactivated rMuIFN-gamma failed to reduce the fibrotic response in this assay. These results provide compelling evidence that gamma-interferon can down-regulate collagen synthesis in vivo and suggest the possibility that this lymphokine may be useful in the treatment of disease states characterized by excessive fibrosis.

Minimal Deviation Melanoma: A Histologic Variant of Cutaneous Malignant Melanoma in Its Vertical Growth Phase

Minimal deviation melanomas are uncommon nevo-melanocytic tumors of indeterminate risk that appear as pigmented or nonpigmented skin nodules and are clinically diagnosed as Spitz nevi, hemangiomas, or malignant melanomas. They are characterized histologically by expansile growth in the papillary dermis with reticular dermal infiltration (minimal deviation type) or without reticular dermal invasion (borderline type). The tumors exhibit lesser cytologic atypia in their vertical growth phase (histologic variance) than observed in common forms of melanoma. A retrospective study of outcome in 21 patients with minimal deviation melanoma (mean tumor thickness by Breslows measurement=3.6 mm) disclosed recurrent disease in only 3 patients after a mean observation period of 57 months, supporting the impression that these tumors are not as biologically aggressive as common malignant melanomas. The histologic subtypes of minimal deviation melanoma are reviewed along with a discussion of the concept of histologic variance.

The spectrum of minimal deviation melanoma: A clinicopathologic study of 21 cases

A retrospective study of 21 patients with the histopathologic diagnosis of minimal deviation melanoma (MDM; n = 18) and borderline melanoma (BM; n = 3) was undertaken to determine the prognosis for these patients compared with that for patients with other types of malignant melanoma. The findings indicate that the prognosis for these uncommon nevomelanocytic tumors is somewhat better than that for other malignant melanomas. Follow-up periods in this series ranged from 18 to 96 months (mean, 57 months). Primary lesions ranged in thickness from 1.6 to 10.4 mm. The histopathologic subtypes included the Spitz variant (nine patients), the spindle cell variant (six patients), the combined spindle and epithelioid cell type (three patients), and the small epithelioid cell type (three patients). Only two of the patients died of widespread metastatic disease. Comparison of the histologic and clinical prognostic indicators of mortality in patients who have malignant melanoma with the clinical and pathologic features seen in this series of 21 patients would appear to indicate a diminished tendency toward metastatic or recurrent disease in patients with MDM and BM.

Pulse Width Dependence Of Pigment Cell Damage At 694 nm In Guinea Pig Skin

351 nm, 20-nsec XeF excimer laser irradiation has previously been shown to selectively target and damage melanosomes in human skin. In the following studies selective targeting with melanosomal photodisruption has been demonstrated in pigmented guinea pig skin with a Q-switched 40-nsec ruby laser, and a 750-nsec pulsed dye laser but not with a 400-usec pulsed dye laser. The pulse width dependence of melanosomal disruption, occurring only at pulsewidths shorter than the thermal relaxation time of the melanosome (0.5 - 1.0 usec), is in accordance with the theory of selective photothermolysis. Possible mechanisms of melanosomal photodisruption include development of sudden thermal gradients leading to cavitation or shock wave production.

Erythema multiforme in a patient with T cell chronic lymphocytic leukemia

A patient with T4+ (helper-inducer) T cell chronic lymphocytic leukemia developed an erythema multiforme-like eruption, the diagnosis of which was supported by routine light microscopic findings. Immunopathologic studies using monoclonal antibodies demonstrate that despite an overwhelming majority of leukemic T4+ cells in the peripheral blood and dermal infiltrate, the predominant cells in the epidermal infiltrate are T8+ (cytotoxic-suppressor) cells. These findings are different from those seen in epidermotropic T cell leukemic infiltrates and are similar to those previously reported in erythema multiforme. Thus it is likely that the leukemic T4+ cells are participating in this cutaneous hypersensitivity reaction along with residual, normal T8+ cells.