A study of the effect of chronic applications of nitrogen mustard (HN2) on acute responses of mammalian skin to UVB irradiation in vivo.

The effect of chronic applications of HN2 on acute responses of DNA synthesis to UVB radiation was studied in Uscd strain hairless mouse skin in vivo. 0.1 mg of HN2 in 95% ethyl alcohol and the diluent were applied weekly to the backs of the mice for 69 wk. The mice were then exposed to 1.98 X 10(2) J/m2 of UVB energy and were sacrified 4 hours and 48 h post-irradiation. The effects on DNA synthesis were evaluated using TdRH3 as the radioactive tracer. The results of the study revealed that the chronic HN2 applications increased the number of basal cells in the DNA synthesis phase of the mitotic cycle. This was associated with acanthosis and cellular hypertrophy. 4 h post-irradiation there was the expected depression in DNA synthesis in both the HN2- and diluent-treated mice. In addition, 48 h post-irradiation the number of basal cells synthesizing DNA was accelerated in both the HN2- and diluent-treated mice. However, it was much more noticeable in the HN2-treated animals. Whether this increased activity is related to the additive carcinogenesis generated between UVB and HN2 remains to be determined.

Topical carmustine (BCNU) for mycosis fungoides and related disorders: a 10-year experience.

A 10-year experience in eighty-six patients confirms the effectiveness of topical carmustine (BCNU) in mycosis fungoides (MF). Complete remission (CR) was achieved in 84% of those with less than 10% involvement (stage IA), median CR, 12 months, and in 52% with greater than 10% involvement (stage IB), median CR, 23 months. The probability of freedom from relapse for 1 year was 72% in stage IA and 37% in stage IB. No deaths in stages IA or IB were attributable to MF. Including all causes of death, the probability of 5-year survival for stage IA was 93% and for stage IB, 48%. Good results were obtained with only local BCNU in fourteen patients with mostly less than 5% involvement. Five of seven with poikilodermatous MF, two with parapsoriasis en plaques (PEP), and three with lymphomatoid papulosis did well. Persistent local therapy cleared deeply infiltrated lesions in some patients. With present schedules, the hazard of bone marrow depression is slight. Erythematous reactions and telangiectasia are troublesome but have not been accompanied by premalignant changes.

Mycosis fungoides of the mastoid, middle ear, and CNS. Literature review of mycosis fungoides of the CNS.

Facial nerve paralysis developed in a man with tumor-stage mycosis fungoides (MF). Mastoidectomy disclosed that MF had involved the mastoid and middle ear. Meningeal lymphoma, confirmed by the finding of Sézary cells in the CSF, was subsequently established. Autopsy disclosed MF lymphoma in the leptomeninges, medulla, spinal cord, and cranial nerves. A unique feature was the formation of a communicating hydrocephalus. Case reports of 23 patients with MF of the CNS, including 21 autopsies, are reviewed. Practically all had tumor-stage or erythrodermic MF. Atypical mononuclear cells were found ante mortem in the CSF in eight patients. In contrast to other CNS lymphomas, bone marrow involvement was uncommon. Cranial, especially facial, nerve paralyses were often premonitory signs of meningeal lymphomas. Patients with MF having such symptoms should have cytologic examination of the CSF.

Mycosis fungoides presenting as areas of hypopigmentation: a report of three cases.

In three patients with histologically documented mycosis fungoides, all or most of the lesions were hypopigmented. Unsuspected microscopic foci of mycosis fungoides were found in a purely macular hypopigmented area in one of these patients who had been treated with vitiligo 15 years earlier. Two of the patients were black, and one was Latin American. Repigmentation in all patients followed treatment with carmustine (BCNU) and mechlorethamine.

Myopathy associated with sclerodermal facial hemiatrophy.

A patient who had linear scleroderma associated with ipsilateral hemiatrophy of the tongue and subsequent facial hemiatrophy was studied. Biopsy specimens of the plaque of scleroderma showed the skin changes of scleroderma as well as fascial and muscle changes. The fascia had an impressive plasma cell fasciitis with numerous plasma cells and scattered lymphohistiocytic cells. Histochemical study of the temporalis muscle underlying the plaque of circumscribed scleroderma disclosed severe localized atrophy of type 1 and type 2 fibers similar to the pathologic findings previously described in a patient with localized scleroderma.

Inhibition of ultraviolet-induced carcinogenesis by all-trans retinoic acid.

The effects of all-trans retinoic acid (RA) in 0.05%, 0.025% and 0.005% concentrations on ultraviolet (UV) induced carcinogenesis was investigated in the skin of Uscd strain hairless mice. A carcinogenic amount of UV energy was delivered over the 12-mo period of the study. The 0.025% and 0.005% RA solutions did not alter the development of cutaneous cancers. However, the 0.05% RA concentration significantly inhibited the tumor formation in this study.

Topical chemotherapy of mycosis fungoides.

Mycosis fungoides is a T-cell lymphoma which is often localized to the skin in the early stages. Untreated, the process eventually progresses through eczematous, plaque, and tumor stages to systemic involvement. Its course, however, is unpredictable. Topical chemotherapy is effective in early stages of mycosis fungoides. Possibly prognostic benefits can occur from the early use of these agents. Nitrogen mustard and BCNU, both alkylating agents, have been used topically to control the disease. A dermatitis may develop in persons treated with nitrogen mustard but systemic side-effects are rare. However, BCNU may rarely lead to marrow depression when used topically. The use of these agents in mycosis fungoides is discussed herein.

Topical chemotherapy and immunotherapy of mycosis fungoides: intermediate-term results.

A group of 220 patients with mycosis fungoides (MF) and other lymphomatous diseases was treated with sustained topical applications of dilute aqueous solutions of mechlorethamine hydrochloride for intervals ranging in excess of seven years. Response to treatment, immunologic responsiveness, and subsequent course and survival were inversely related to magnitude of disease at time of starting treatment. Relapses were common and in most instances were related to failure to maintenance of topical therapy rather than to drug resistance. In selected patients topical therapy with an analog of mechlorethamine (nor-mechlorethamine) and with topical immunogenic agents provided additional improvement.

Frequent low doses of intravenous mechlorethamine for late-stage mycosis fungoides lymphoma.

Ninety-two courses of daily low-dose intravenous nitrogen mustard were administered to 46 patients with advanced cutaneous lymphomas (mycosis fungoides, Sezary syndrome and lymphoma cutis). Seventy-eight % of patients showed objective clinical remission, and 35% reached a clinically disease-free state following 1 or more courses. The response rate was greater in patients with the plaque-tumor type of mycosis fungoides than in those with erythrodermic variants. Therapy was free of significant side effects.