Yoshihiko Katahira

Clinicopathologic Analysis of 124 Cases of Adult T-Cell Leukemia/Lymphoma with Cutaneous Manifestations : The Smouldering Type with Skin Manifestations Has a Poorer Prognosis than Previously Thought

Adult T‐cell leukemia/lymphoma (ATLL) commonly involves the skin as well as peripheral blood and lymph nodes. During the last 15 years we have studied 124 cases of ATLL with specific skin manifestations. Twenty‐one patients (16.9%) were classified as acute, 21 (16.9%) as chronic, 26 (21.0%) as lymphoma, and 56 (45.2%) as smouldering according to Shimoyamas classification. Many patiens had nodules/tumors (34.7%), erythematous plaques (22.6%), and erythematous papules (19.4%) similar to those occurring with other cutaneous T‐cell lymphomas. Some patients displayed characteristic skin manifestations resembling non‐neoplastic cutaneous disorders.

In vitro Induction of Cytotoxic T Lymphocytes against HTLV-I-infected T-Cells from Adult T-Cell Leukemia Patients, Asymptomatic HTLV-I Carriers and Seronegative Healthy Donors

We investigated an in vitro method to produce cytotoxic T lymphocytes (CTLs) against HTLV‐I‐infected T‐cells using peripheral blood mononuclear cells (PBMC) of adult T‐cell leukemia (ATL) patients, asymptomatic HTLV‐I carriers (AC) and seronegative healthy donors. The PBMC were restimulated repeatedly for 4 weeks with HLA‐matched HTLV‐I‐infected T‐cells which had been pretreated at 56deg;C for 30 min to inactivate infectious HTLV‐I. The culture medium included 10–100 units/ml of recombinant lymphokines (rIL‐1, rIL‐2, rIL‐4, rIL‐6 and rIL‐7) and 10% fetal calf serum in RPMI‐1640 medium. The cytotoxic activity was measured against HLA‐matched HTLV‐I‐infected T‐cell lines after CD4+ or CD8+ cells were positively panned from the cultured PBMC. The PBMC of ATL, AC and healthy donors were able to produce either CD4+ or CD8+ CTLs against HTLV‐I‐related antigens (env, gag, p21x, p27rex and p40tax) as well as the antigen(s) of as‐yet unknown specificity expressed on HTLV‐I‐infected T‐cells. All the CTLs recognized the specific antigens in the context of either class I or class II HLA types. These results indicated that ATL patients, AC and healthy donors were immunocompetent to generate CTLs against HTLV‐I‐infected T‐cells and probably against HTLV‐I‐transformed T‐cells.

Adult T-cell leukemia/lymphoma associated with noninfectious epithelioid granuloma in the skin : A clinicopathologic study

Hodgkins disease (HD) and non-Hodgkins lymphoma (NHL) are infrequently associated with noninfectious granulomas in involved or noninvolved organs. Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoproliferative neoplasm associated with T-lymphotropic virus type 1 (HTLV-1). We describe a case of cutaneous type ATLL, affecting mainly the skin as a maculopapular eruption, in which some skin biopsies contained epithelioid cell granulomas in the lymphoma cutis (ATLL) lesion. These Lennerts-like epithelioid clusters were also present in lymph nodes, which showed some degree of invasion by the ATLL lymphocytes. Although prognosis of ATLL is generally poor, our patient has had a less aggressive course, with a survival time to date of 13 years. Our findings suggest that the presence of epithelioid granulomata in an ATLL patient may be a manifestation of a host response which confers some protection against the disease progression. To our knowledge, this is the first report of a case of ATLL with a noninfectious granuloma similar to a Lennerts lesion.

Differences in HTLV-I integration patterns between skin lesions and peripheral blood lymphocytes of HTLV-I seropositive patients with cutaneous lymphoproliferative disorders

We examined HTLV-I integration patterns in nine cases of HTLV-I-seropositive patients with cutaneous lymphoproliferative disorders. The Southern blot on EcoRI digests of DNA revealed a discrete band of HTLV-I provirus (monoclonal integration) in either skin lesions or peripheral blood lymphocytes (PBL). Four cases showed the monoclonal integration of HTLV-I provirus only in skin lesions: one case showed only in PBL and two cases showed in both skin and PBL. The Southern blot on PstI digests of DNA revealed a 2.4 Kb band of the internal construct of HTLV-I provirus (polyclonal integration) in the PBL of EcoRI-negative samples. The difference in HTLV-I integration patterns between skin lesions and PBL in these cases suggests that the monoclonal outgrowth of HTLV-I-infected cells in the skin is causatively associated with the pathogenesis of cutaneous ATL.

Expression of Human T‐cell Lymphotropic Virus Type‐1 Gene Products in the Short‐term Cultured Skin Tissues of an Adult T‐cell Leukemia/Lymphoma Patient with Cutaneous Manifestations

Adult T‐cell leukemia/lymphoma (ATLL) is recognized as a disease etiologically associated with human T lymphotropic virus type‐1 (HTLV‐1) infection, but, neither viral replication nor specific virus antigen expression have been detected on ATLL cells distributed in organs, including skin. To examine the latent expression of HTLV‐1 in the cutaneous lesions of ATLL patients, we cultured the lesional skin tissues in vitro and applied immunofluorescence staining with mouse monoclonal antibodies Lt‐4, GIN‐14, and F10, which react with p40tax, p19 and gp21, respectively.

Human T lymphotropic virus‐1 infection

Human T lymphotropic virus‐1 (HTLV‐1) is a retrovirus which infects T lymphocytes (CD4+) to cause adult T cell leukaemia/lymphoma (ATL), tropical spastic paraparesis and several other HTLV‐1 associated disorders. ATL has been reported worldwide but areas of high incidence include Japan (particularly the south‐west), Central and South America, northern Iran, West and Central Africa and Melanesia. In the general Japanese population, HTLV‐1 carriage is 0.1% but this can be as high as 30% in endemic areas. Six per 10000 carriers are estimated to progress to ATL each year. The three major routes of infection are mother to baby through breastfeeding, sexual intercourse and blood transfusion. There is a lengthy latency period of up to 40 years before the development of ATL. Up to 50% of ATL patients present with a cutaneous eruption. Diagnosis is established by the detection in lymphocytes of monoclonal integration of HTLV‐1 proviral DNA. Even with aggressive treatment, ATL patients generally have a poor prognosis.

A Case of Factitious Skin Disease

To the Editor: Psychological conditions may play roles as triggers or deterioration factors in dermatological disorders such as atopic dermatitis, urticaria, and psoriasis (1). Therefore, the psychological conditions of patients should be evaluated by dermatologists. Psychiatric disorders also can lead to self-induced paradoxical skin conditions (1, 2). Such histories sometimes confuse dermatologists. We experienced a case of skin disease which had a unique appearance and history. Case Report: A 20-year-old Japanese woman with a five month history of eruptions on her ckeeks visited our hospital on May 3, 2000. Coin-sized, hyperpigmented, erythematous macules with scales were noted on both of her cheeks (Fig. 1). She had an extroverted character by nature. She had won an award in a regional beauty contest in July of 1999. She became anxious about the relationships in her office and suffered from maladjustment to society and withdrawal symptoms. In October of 1999, she had aphthosis stomatitis. When she pushed her cheeks to relieve the pain of the aphthosis stomatitis, she felt relaxed and gradually recovered her confidence. She felt that she could not live without always pushing her cheeks. A diagnosis of dermatitis artefacta was made. Her blood cell counts, liver and renal function tests, urinalysis, and electrocardiogram were all within the normal ranges. An intelligence test revealed her intelligence quotient (IQ) as 66. A discrepancy was observed between her language IQ (77) and action IQ (62). A YG character test revealed indecisiveness and pessimism. She was admitted to the psychiatry ward with a diagnosis of maladjustment and was given psychotherapy and medication (Triazoram Letters to the Editor

T-Cell receptor gene rearrangement in cells infiltrating skin eruptions specific to adult T-cell leukemia

We examined T-cell receptor gene rearrangement in skin lesions and peripheral blood from 6 patients with adult T-cell leukemia (ATL) using the Southern blot method and a c beta 1 probe. A rearrangement signal common to skin lesions of all 6 patients was observed. One patient (Case 4) exhibited another rearrangement signal in the skin lesion and an identical signal was detected in the peripheral blood. This is the first report describing a specific pattern of T-cell receptor gene rearrangement in ATL. The signal obtained is assumed to represent receptors of T cells involved in surveillance of HTLV-I infected T cells.