Integration patterns of HTLV-I provirus in relation to the clinical course of ATL: frequent clonal change at crisis from indolent disease.

We examined human T-lymphotropic virus type I (HTLV-I) DNA integration in 68 patients with adult T-cell leukemia/ lymphoma (ATL) by Southern blotting using EcoRI, which does not cut within the 9 kb of the genome and probes for pX and gag-pol region of HTLV-I. We detected defective proviral integration as a monoclonal band of various sizes with the pX but not with the gag-pol probe, or a monoclonal band of less than 9 kb with the pX probe, in 20 patients (29.4%). These were designated defective (D) type. With both probes, a single band greater than 9 kb was detected in 34 (50.0%), designated complete (C) type, and two or more bands greater than 9 kb, were designated multiple (M) type, in 14 (20.6%). Advanced age, a high LDH value, and hypercalcemia were more frequent in D type patients. The median survival time (MST) was 6.8, 24.4, and 33.3 months, for D, C, and M types, respectively (log rank P = .006). Among 52 sequentially examined patients, the HTLV-I integration patterns changed in 4 (7.5%). In three of these four, the rearrangements of the T-cell receptor (TCR)b gene concomitantly changed, suggesting the appearance of a new ATL clone. Another patient had the same rearrangement of the TCRb gene, indicating clonal evolution. The HTLV-I integration pattern changed at crisis from indolent to aggressive ATL in three patients. These findings suggested that the HTLV-I integration patterns have clinical implications in ATL pathophysiology. In contrast to the clonal evolution characteristic of the multistep carcinogenesis of most human malignancies, the frequent clonal change of ATL at crisis is a peculiar phenomenon, probably reflecting the emergence of multiple premalignant clones in viral leukemogenesis as suggested in Epstein-Barr virus associated lymphomagenesis in the immunocompromised host.

Immunohistochemical studies of blood group antigens ABH in cutaneous angiosarcoma.

Eight angiosarcomas were clinicopathologically and immunohistochemically investigated. Four of the angiosarcomas originated in the scalp of the elderly, and four cases were angiosarcomas associated with chronic lymphedema after hysterectomy for uterine carcinoma or after mastectomy for breast carcinoma. Six of the angiosarcomas showed conventional histopathology, whereas the remaining two cases were considered cutaneous epithelioid angiosarcoma. Immunohistochemical studies for blood group antigens ABH were carried out. Three of the conventional angiosarcomas were weakly positive and three were moderately positive with antigens ABH. The antigens were strongly positive in the two epithelioid angiosarcomas. The biologic course of the two epithelioid angiosarcomas was longer than that of the other six cases. This study suggested that the strong positivity of blood group antigens may be one of the characteristics of epithelioid angiosarcoma.