Adult T-cell Leukemia Showing
Different Immunophenotypes in Invaded Organs
Tomoko Katagiri, Takashi Shimamoto, Goro Sashida, Yukihiko Kato,
Tomonari Okada, Kazuma Ohyashiki
First Department of Internal Medicine, Tokyo Medical University,
Tokyo, Japan
Correspondence: Takashi Shimamoto, MD, First Department of
Internal Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku,
Shinjuku-ku, Tokyo 160-0023, Japan. Phone:
international+81.3.3342.6111 - Fax: international+81.3.5381.6651 -
E-mail: takashis@cb3.so-net.ne.jp
Abstract
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.
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A 64-year-old woman complaining of general edema was admitted to our hospital. She had been born in Nagasaki Prefecture, in Kyushu. Physical examination revealed skin eruption on the anterior pectoral region but neither hepatosplenomegaly nor lymphadenopathy. Hematological data revealed a white blood cell count of 17,700/mL with 46% abnormal lymphocytes, which resembled ATL cells. Blood biochemical analysis showed that LDH was 978U/L, blood urea nitrogen was 92.8mg/dL, creatinine was 5.97 mg/dL, uric acid was 14.4mg/dL, and serum calcium was 10.9 mg/dL. Anti-HTLV-1-associated antibodies (ATLA) determined by ELISA and particle agglutination were positive. HTLV-1 proviral DNA was detected in PB mononuclear cells (MNC) DNA by Southern blot analysis. The patient was diagnosed as having ATL. Renal and skin biopsies were performed, and diffuse ATL cell infiltration was found in both. Surface marker analysis of PB using flowcytometry showed 2.8% CD4 (Leu3a) cells and 1.0% CD8 (Leu2a) cells. Immunohistochemistry confirmed the presence of double-negative ATL cells in BM (Figure 1) which is a rare form of ATL.1,2 Interestingly, tumor cells from renal and skin biopsy specimens expressed CD4 but not CD8 (Figure 1), consistent with typical ATL cells. Thus, the phenotype of tumor cells differed depending on their location. The patient transiently responded to combination chemotherapy, but her disease progressed rapidly and she died of cytomegalovirus-caused pneumonia 6 months after diagnosis.
In the present report, we have shown that the phenotype of ATL cells differs between BM or PB and kidney or skin. In most cases of ATL, the integration pattern of HTLV-1 proviral DNA has been thought to be identical in all tumor cells in all individuals, suggesting that all ATL cells originate from a single clone.3,4 However, a few reports have suggested the simultaneous presence of different clones of ATL cells in the same patient.5-7 We could not determine whether the ATL cells found in BM, PB, kidney and skin originated from the same clone, because we could not obtain enough DNA from kidney and skin specimens to analyze HTLV-1 proviral DNA integration. Possible explanations for the different phenotypes are 1) that ATL cells in this patient originated from different clones; and 2) that CD4-CD8- cells in the PB migrated in the kidney and skin and altered the phenotype for the stimulation under the different circumstances. Detailed investigation into such case is needed to clearly understand the diversity of ATL cells phenotype.
