Adult T-cell lymphoma leukemia in western countries

A new T-cell disorder has recently emerged: the so-called adult T-cell lymphoma leukemia (ATLL) initially described in Japan. Subsequently, ATLL cases were recognized in patients from the Caribbean. We summarize the clinical and hematological features of 19 published cases from Western countries, in addition to a new case we encountered. The leukemic cells display characteristic morphological features and a T₃⁺ T₄⁺ T₈^? T₆^? surface antigenic phenotype. Overall survival is of short duration, but remission could be obtained in our case despite a subsequent relapse in skin and CNS. Geographic clusters of ATLL cases have led to the discovery of the possible role of a new retrovirus, HTLV, in the genesis of this rare malignancy.     

Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I.

We describe five patients with adult T-cell leukemia/lymphoma (ATL) with neither integration of human T-cell leukemia virus type I (HTLV-I) into their leukemia cells nor anti-HTLV-I antibody in their sera. These findings indicate that HTLV-I may not have been involved in leukemogenesis in these patients. The clinicohematological, cytopathological, and immunological features of HTLV-I-negative ATL were exactly the same as those of HTLV-I-associated ATL. Leukemia cells with pleomorphic nuclei, generalized lymphadenopathy, hepatosplenomegaly, skin lesions, hypercalcemia, and elevated lactate dehydrogenase levels, all of which are characteristic features of typical ATL, were also seen in these patients with HTLV-I-negative ATL. Leukemia cells expressed T3, T4, and pan-T-cell antigens in three cases, and T3 and pan-T-cell antigens in two. All five patients had lived in ATL-nonendemic areas. The finding of HTLV-I-negative ATL suggests that factor(s) other than HTLV-I infection may be involved in ATL leukemogenesis.     

Adult T-cell leukemia/lymphoma with initial deafness

In July 1995, a 43-year-old Japanese man presented with deafness in the right ear. On hospital admission, he had deafness in both ears and right facial palsy. Variously sized lymphoid cells with convoluted nuclei were observed in the cerebrospinal fluid. Surface marker analysis revealed monoclonality of T lymphocytes in the spinal fluid. Similar abnormal cells were observed in peripheral blood and bone marrow. Biopsy specimens of the stomach and prostate showed tight proliferation of large lymphoid cells in the interstitium and epithelium. Antibody against human T-lymphotrophic virus type 1 (HTLV-1) was present. The diagnosis of non-Hodgkin's lymphoma, diffuse type, was made. Seven months later, the patient died of sepsis. Autopsy revealed multiple lymphadenopathy in the abdomen and the infiltration of atypical lymphocytes to the pancreas, kidneys, and other organs. A monoclonal band of HTLV-1 provirus was detected by Southern blot analysis. To our knowledge, this is the first report of adult T-cell leukemia/lymphoma with auditory nerve abnormalities as the initial symptom.     

Adult T-cell leukemia initially manifesting as facial diplegia

We report an unusual case of adult T-cell leukemia (ATL) initially manifesting as facial palsy due to ATL meningitis, which was caused by lymphoid cells in the cerebrospinal fluid (CSF) with a different phenotype from those in the blood. A DNA southern blot analysis of the blood cells confirmed the diagnosis of ATL. The aberrant cells in the CSF contained nuclei with simple indentations and responded well to the initial chemotherapy, while leukemic cells in the blood showed lobulated or convoluted nuclei and were resistant to treatment. Flow cytometry performed before treatment demonstrated that the majority of the cells in the CSF were CD3 + CD4 + CD8-CD25 +, consistent with ATL, whereas they expressed the CD45R antigen, which the blood ATL cells did not. These differences in the subphenotype, cell morphology, and responsiveness to treatment among the ATL cells in blood and CSF suggest that a single clone or subclone with heterogeneous nature was not generated, before the final development of ATL.     

Adult T-cell leukemia with Ki-1 expression]

A 64-year-old man was admitted to our hospital complaining of fever and edema in February, 1990. Lymph node biopsy revealed diffuse lymphoma pleomorphic type according to the LSG classification. On hematological examination, leukocyte count was 23,500/microliters, of which 36% abnormal lymphocytes expressing CD2, CD3, CD4 and CD25 as same as the lymph node cells. Anti-HTLV-I antibody in serum was positive. From these data, the diagnosis of adult T-cell leukemia (ATL) was made. ATL cells in the blood and lymph node expressed CD30 (Ki-1). CD30 positive ATL cells derived from the blood was increased after short-term culture. The induction of Ki-1 antigen in cell lines and short-term cultured cells from ATL patients was accompanied by the appearance of the HTLV-I related antigen. Then, we suggest that there was some relation between expression of the Ki-1 antigen and activation by HTLV-I in ATL cells.     

Adult T-cell leukemia with various pulmonary complications]

A 59-year-old male, born in Wakayama prefecture, was admitted to our hospital because of cervical lymph node swelling, huge mass lesions in both liver and head of the pancreas, and multiple nodular shadows in the left lung. Lymph node biopsy revealed a necrotic lesion containing tuberculous bacilli with no epithelioid cells or giant cells. Adult T-cell leukemia (ATL) was diagnosed by the presence of atypical lymphocytes with a convoluted nucleus and positive anti-ATL antibody. During successful treatment of Mycobacterium tuberculosis with ethambutol, isoniazid and rifampicin, ATL transformed to the blastic phase. The new pulmonary infiltrates improved after treatment with both combination chemotherapy for ATL and antibiotics. However, new infiltrative shadows appeared in both lungs, and were resistant to treatment and the patient died of acute respiratory failure. Histological examination of the lung at autopsy showed interstitial fibrosis with infiltration of leukemic cells and cytomegalovirus infection.     

Adult T-cell leukemia with a solitary lung mass.

A 49-year-old woman was admitted to the hospital with supraclavicular lymph node swelling. On a chest x-ray film, a 4 x 4-cm nodular shadow was observed in the right middle lung field. The white blood cell count was 10,100/cu mm, showing 44 percent abnormal lymphocytes with lobulated nuclei. Since HTLV-I antibodies were markedly positive, she was diagnosed as having ATL. Transbronchial tumor biopsy revealed accumulation of ATL cells. Our patient is the first case with only a large nodular accumulation of ATL cells without diffuse infiltration of the cells in the lung.     

Adult T-cell leukemia/lymphoma presenting multiple lymphomatous polyposis

Multiple lymphomatous polyposis （MLP） is an unusual form of non-Hodgkin＇s lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma （ATLL）. Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL isreviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.     

Adult T-cell leukemia following long-term remission from non-Hodgkin's lymphoma

A female patient who had been initially diagnosed with non-Hodgkin's lymphoma (NHL) and achieved complete clinical remission with combined chemotherapy, developed overt adult T-cell leukemia (ATL) after 9 yr of disease-free survival. This is the first case of the development of ATL following the complete remission of NHL. Secondary malignant neoplasms are not well-documented in patients previously diagnosed with Hodgkin's disease. Although there have been a few reports concerning the occurrence of secondary malignancy in patients with non-Hodgkin's lymphoma (NHL), there has never been a documented case of ATL following long-term survival from NHL. Here, we report a case of typical adult T-cell leukemia (ATL) which occurred after 9 yr disease-free survival from NHL.     

Adult T-cell leukemia showing different immunophenotypes in invaded organs

We report here a case of adult T-cell leukemia (ATL) who presented acute renal failure and skin eruption. Renal and skin biopsies showed diffuse invasion of ATL cells. Furthermore, the surface phenotype of tumor cells taken from the bone marrow (BM) or peripheral blood (PB)(CD4-CD8-) differed from that of cells taken from the kidney or skin (CD4+CD8-). These findings suggested that CD4-CD8-ATL cells in the BM and PB had differentiated to CD4+CD8- cells in the kidney and skin.