A time for dying. Working through end-of-life decisions.

"I think it's time," said Bruce, between sobs. I knew my husband meant it was time to help our son Roger die. Roger entered our family 18 years ago. He was a tiny (1 lb., 12 oz.) premature baby I met in the NICU. Because normal gestational age at birth is 38 to 41 weeks, Roger's gestational age of 28 weeks made him extremely vulnerable to many medical complications, such as chronic respiratory problems, intracranial hemorrhage, mental retardation, and seizures. He experienced all of these complications during his life.

Woringer-Kolopp disease (localized pagetoid reticulosis) or unilesional mycosis fungoides? An analysis of eight cases with benign disease.

BACKGROUND: The controversial nosology of Woringer-Kolopp disease (localized pagetoid reticulosis, unilesional mycosis fungoides) is being clarified by the systematic immunophenotypic and immunogenetic examination of infiltrating lesional T lymphocytes. The clinical course and immunohistochemical characteristics of eight cases of Woringer-Kolopp disease are described. OBSERVATIONS: Lesions measured 0.8 x 0.5 to 16.0 x 15.0 cm. Histologically, all cases resembled mycosis fungoides-type cutaneous T-cell lymphoma and phenotypic analysis supported their designation as an epidermotropic T-cell process. Phenotypic aberrancy was not noted on immunohistochemical analysis of paraffin-embedded tissue. Three of four patients with available fresh-frozen tissue specimens demonstrated reduced or absent expression of CD7 (Leu-9) and/or Leu-8, while loss of the pan-T-cell markers CD2, CD3, and CD5 was not observed. Only in half these patients was a lesional predominance of CD4+ T-cells revealed. Germline DNA was detected in a lesional skin specimen obtained from one patient tested for T-cell receptor gene rearrangements. After treatment, the observation of disease-free periods ranging from 18 months to 17 years (mean, 5.9 years) reinforces the view that Woringer-Kolopp disease is a focal pathologic event with a favorable prognosis. No patient experienced a local recurrence or distant spread of the disease. CONCLUSION: This and previous studies suggest that Woringer-Kolopp disease is a unique, benign unilesional T-cell lymphoproliferative process with certain histologic and phenotypic similarities to both early epidemotropic mycosis fungoides-type cutaneous T-cell lymphoma and other T-cell lymphoproliferations.

Microcystic adnexal carcinoma. Ten cases treated by Mohs micrographic surgery.

BACKGROUND: Microcystic adnexal carcinoma is a slow-growing, nondescript, locally aggressive, deeply infiltrating neoplasm histologically characterized by an infiltrative pattern of basaloid or squamous cells, a desmoplastic stromal reaction, keratin-filled cysts, and glandular structures. OBJECTIVE: Microcystic adnexal carcinoma is uncommon and may be mistaken microscopically for other benign and malignant entities. Perineural or intraneural involvement by tumor cells is characteristic and extension into underlying structures including muscle, fat, and bone are frequently encountered. Although local recurrences are common after standard surgical excision, metastases have not been reported. Extensive resections of lesions may be necessary to extirpate widespread tumor, particularly those that are long standing or recurrent. Because significantly increased morbidity is associated with recurrent disease, surgical and histopathologic techniques that stress examination of all margins are advantageous. METHODS: We review the course of 10 patients with microcystic adnexal carcinoma of the face (six primary and four recurrent lesions) and their treatment by Mohs micrographic surgery.

Cutaneous T-cell lymphoma associated with HIV infection.

BACKGROUND: Mycosis fungoides-type cutaneous T-cell lymphoma is uncommon in association with human immunodeficiency virus type 1 (HIV-1) infection. Reported patients have a high incidence of CD8+ T-cell lymphomas and erythroderma, are usually severely immunocompromised, and rapidly die. Chronic, more typical patch-plaque mycosis fungoides-type cutaneous T-cell lymphoma in association with HIV-1 infection has not been reported. OBJECTIVE: We report two cases of stage 1B epidermotropic mycosis fungoides-type cutaneous T-cell lymphoma in HIV-1-infected men with no history of the acquired immunodeficiency syndrome. METHODS: Clinical and laboratory data, including lesional immunophenotypic and immunogenotypic findings of two patients with HIV-1-associated cutaneous T-cell lymphoma, were studied. RESULTS: Immunohistochemical analysis of skin determined the lesional infiltrate of one patient to be CD8+ (Leu-2+), CD7- (Leu-9-), and Leu-8- with germline lesional skin and blood T-cell receptor genes. The other was CD4- (Leu-3+), CD2- (Leu-5-), CD7- (Leu-9-), and Leu-8- with beta-chain T-cell receptor gene rearrangement in lesional skin and blood. Circulating Sézary cells were not detected in either patient. Peripheral CD4/CD8 T lymphocyte numbers did not appear to correlate with cutaneous disease activity or the predominant lesional T-cell subtype. Both patients were responsive to standard therapies and have experienced prolonged survival in excess of that generally reported for HIV-1-associated systemic peripheral and cutaneous T-cell lymphomas. CONCLUSION: In the absence of severe immunodeficiency, HIV-1-infected patients with concomitant cutaneous T-cell lymphoma may follow a more typical slowly progressive course.

Mycosis fungoides--type cutaneous T-cell lymphoma arising before 30 years of age. Immunophenotypic, immunogenotypic and clinicopathologic analysis of nine cases.

BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) rarely arise before 30 years of age; therefore the characteristics of these lymphomas are largely unknown. OBJECTIVE: Our purpose was to assess the clinical and pathologic aspects of CTCL in young persons. METHODS: We identified nine patients who had epidermotropic CTCL by 30 years of age and analyzed their lymphoma phenotypes and genotypes. RESULTS: The diagnosis of CTCL was made an average of 6 years after the reported onset of the lesion. Histologic examination revealed the mycosis fungoides (MF) form of CTCL, and none of the patients underwent conversion to nonepidermotropic or large-cell variants of CTCL. The immunophenotypes were typical of MF-type CTCL; seven of eight lymphomas tested were predominantly CD4+ although in only three were abnormal CD4/CD8 ratios present. All four cases tested were CD7- (Leu-9-), and seven of eight specimens tested exhibited deficient Leu-8 expression. The loss of one or more pan-T-cell markers was found in four of eight patients tested. Clonal beta-chain T-cell receptor gene rearrangements occurred in skin samples from four of eight tested cases. CONCLUSION: A persistent eruption, even in youths and young adults, should be thoroughly evaluated for possible CTCL.

Intralesional cyclosporine for psoriasis. Relationship of dose, tissue levels, and efficacy.

UNLABELLED: BACKGROUND AND DESIGN--To avoid systemic side effects, topical and intralesional administration of cyclosporine has been used; however, only intralesional administration has been successful. To understand more about the dosing requirements and resultant tissue levels of intralesional cyclosporine, we injected psoriasis plaques in a double-blind fashion with three different concentrations of cyclosporine (17 mg/mL in seven patients, 10 mg/mL in 13 patients, and 2.5 mg/mL in 11 patients) or matching vehicle three times weekly for 4 weeks. RESULTS--Statistically significant improvement was observed in plaques treated with 17 mg/mL (P = .003) compared with vehicle-treated plaques; the improvements in plaques treated with 10 mg/mL (P = .078) and 2.5 mg/mL (P = .054) achieved marginal statistical significance compared with vehicle treatment. Four weeks after discontinuation of therapy, the change from pretherapy in plaques that had received 17 mg/mL of cyclosporine was statistically significantly better (P less than .0001) than that with vehicle treatment. A similar finding but of marginal statistical significance (P = .059) occurred in the plaques that had received 10 mg/mL of cyclosporine. Throughout the study, untreated psoriasis plaques did not improve. Transient pain was the most common side effect noted with both cyclosporine and vehicle injections. Tissue levels of cyclosporine tended to be highest in plaques receiving the 17-mg/mL concentration; blood levels of cyclosporine were low throughout the study. CONCLUSIONS: --Intralesional cyclosporine requires a sufficient dosage to improve psoriasis, apparently by a local mechanism of action. Improvement may persist for 4 weeks or longer.

Nodular cutaneous B-cell lymphoma of the scalp in the acquired immunodeficiency syndrome.

Aggressive B-cell non-Hodgkin's lymphoma frequently complicates human immunodeficiency virus type 1 infection. Although extranodal disease is an important feature of this condition, the incidence of cutaneous involvement has not been determined. A review of 754 published cases of B-cell non-Hodgkin's lymphoma associated with human immunodeficiency virus type 1 revealed an incidence of cutaneous extranodal involvement of 8.2%, approximately equal to that seen in non-Hodgkin's lymphoma not associated with human immunodeficiency virus. Lymphoma was the initial manifestation of acquired immunodeficiency syndrome in two thirds of these cases. In particular, although the head and neck are commonly involved in non-Hodgkin's lymphoma not associated with human immunodeficiency virus, scalp involvement is uncommon in human immunodeficiency virus-associated B-cell non-Hodgkin's lymphoma, and we report the second case. The natural history and proposed pathogenesis of human immunodeficiency virus-associated non-Hodgkin's lymphoma are discussed.

Cerulein induces hyperplasia of the pancreas in a rat model of chronic pancreatic insufficiency.

Chronic pancreatic insufficiency (CPI) was induced in male Wistar rats by the injection of a zein-oleic acid-linoleic acid solution into their pancreaticobiliary ducts. Animals injected developed severe pancreatic atrophy with fibrosis and greater than 90% loss of pancreatic enzyme content. The animals also developed malabsorption of fat and bentiromide. Three weeks after the CPI lesion was induced, animals were randomized to receive cerulein 2 micrograms/kg twice daily subcutaneously or saline twice daily subcutaneously for 2 weeks. Cerulein significantly increased pancreatic trypsinogen (p less than 0.03), amylase (p less than 0.01), lipase (p less than 0.02), DNA (p less than 0.02), and RNA (p less than 0.01) content and improved fat and bentiromide malabsorption as compared to saline (p less than 0.05). We conclude that cerulein therapy can cause significant hyperplasia of pancreatic acinar parenchyma in an animal model of CPI and that this therapy can partially reverse malabsorption.