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Unusual Lymphoma Manifestations

CASE 3. CD8⁺ T-Cell Prolymphocytic Leukemia

Division of Hematology/Medical Oncology, Departments of Medicine Tokai University School of Medicine, Isehara, Japan

A 33-year-old Japanese woman was referred because of leukocytosis with increased abnormal lymphocytes on a routine blood test. She was completely asymptomatic. Physical examination was essentially normal with no lymphadenopathy, hepatosplenomegaly, or skin lesions. CBC showed WBC 24.5 x 10⁹/L with segmented neutrophils 10%, lymphocytes 5%, monocytes 2%, eosinophils 1%, basophils 1%, abnormal lymphocytes 81%, hemoglobin 12.0 g/dL, and platelets 210 x 10⁹/L. Blood chemistry including lactate dehydrogenase and calcium were normal. Immunoglobin M was slightly elevated at 360 mg/dL, but other immunoglobulin classes were normal. Serum protein electrophoresis showed no monoclonal protein. Her hepatitis serology, including hepatitis B antigen and hepatitis C antibodies, was negative. Human T-cell lymphotropic virus-1 and HIV antibodies were also negative. Peripheral blood smear (Fig 1) showed abnormal lymphocytes that were small and had indented and irregular nuclei with condensed chromatin and no apparent nucleolus. Cytoplasm was basophilic and lacked granulations. Bone marrow was hypercellular with diffuse infiltration by these same abnormal lymphocytes (Fig 2). Immunophenotype analysis (Fig 3) of peripheral blood revealed the abnormal lymphocytes were CD1^-, CD2⁺, CD3⁺, CD4^-, CD5⁺, CD7⁺, CD8⁺, CD10^-, CD16^-, CD19^-, CD20^-, CD22^-, CD23^-, CD25^-, CD30^-, CD34^-, CD38^dim+, CD45⁺, CD56^-, CD57^-, sIg^-, TCRß⁺, TCR^-, and TdT^-. Southern blot analysis for TCR-Cß1 showed rearranged bands, suggesting a clonal process of disease (Fig 4). No metaphase cells for cytogenetic analysis were obtained in unstimulated culture of peripheral blood. Cytogenetic study with phytohemagglutinin stimulation showed 42, X, -X, add(6)(p25), add(7)(q36), I(8)(q10), -11, add(12)(p13), +13, -14, -15, -15, -17, add(19)(q13.4), add(20)(q13.3), -22, +mar2 in all nine cells analyzed (Fig 5). A diagnosis of CD8⁺ T-cell prolymphocytic leukemia (T-PLL) was made. She developed progressive abnormal lymphocytosis, liver function test abnormalities, cervical lymphadenopathy, and erythematous skin lesions 3 months after diagnosis. She was treated with two courses of deoxycoformycin without any response. Therapy was changed to cyclophosphamide, doxorubicin, vincristine, and prednisone, resulting in resolution of liver function test abnormalities, decreased lymphadenopathy, and stable peripheral abnormal lymphocyte counts. She is awaiting an unrelated allogeneic bone marrow transplantation.

View larger version (102K): [in this window] [in a new window]   Fig 1.

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View larger version (26K): [in this window] [in a new window]   Fig 3.

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A new variant of T-cell chronic lymphocytic leukemia with CD8⁺ phenotype was described in 1987 [2]. T-cell chronic lymphocytic leukemia is now reclassified as T-PLL according to the WHO/revised form of European-American Classification of lymphoid neoplasms classification for lymphoid malignancies because of aggressive clinical behavior [3]. It represents approximately 30% of T-cell leukemias with a mature phenotype. Clinical features of T-PLL include occurrence in older patients, hepatosplenomegaly, lymphadenopathy, skin lesions, leukocytosis, anemia, and thrombocytopenia [4]. The majority of cases are CD4⁺ CD8^-; however, approximately 10% of T-PLL are CD4^- CD8⁺ [4,5]. Although no pathognomonic cytogenetic abnormalities have been identified, many cases show abnormalities involving chromosome 14 at bands q11 and q32 [4-8]. The clinical course is aggressive and tends to be resistant to chemotherapy. Median survival is approximately 1 year. Our case fulfills the clinical, morphologic, and immunophynotypic criteria for CD8⁺ T-PLL with unusual cytogenetic abnormalities. It is important to recognize T-PLL because it has a more aggressive clinical course than mature T-cell leukemias.

Authors’ Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Loughran TP Jr: Clonal diseases of large granular lymphocytes. Blood 82: 1-14, 1993[Abstract/Free Full Text]

2. Hui PK, Feller AC, Pileri S, et al: New aggressive variant of suppressor/cytotoxic T-CLL. Am J Clin Pathol 87: 55-59, 1987[Medline]

3. Harris NL, Jaffe ES, Stein H, et al: A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 84: 1361-1392, 1994[Free Full Text]

4. Matutes E, Brito-Babapulle V, Swansbury J, et al: Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood 78: 3269-3274, 1991[Abstract/Free Full Text]

5. Matutes E, Catovsky D: Mature T-cell leukemias and leukemia/lymphoma syndromes. Review of our experience in 175 cases. Leuk Lymphoma 4: 81-91, 1991

6. Heinonen K, Mahlamaki E, Hamalainen E, et al: Multiple karyotypic abnormalities in three cases of small cell variant of T-cell prolymphocytic leukemia. Cancer Genet Cytogenet 78: 28-35, 1994[Medline]

7. Brito-Babapulle V, Maljaie SH, Matutes E, et al: Relationship of T leukaemias with cerebriform nuclei to T-prolymphocytic leukaemia: A cytogenetic analysis with in situ hybridization. Br J Haematol 96: 724-732, 1997[CrossRef][Medline]

8. Brito-Babapulle V, Pomfret M, Matutes E, et al: Cytogenetic studies on prolymphocytic leukemia. II. T cell prolymphocytic leukemia Blood 70: 926-931, 1987

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nakajima, H. Articles by Ando, K. Search for Related Content PubMed PubMed Citation Articles by Nakajima, H. Articles by Ando, K. Social Bookmarking                            What's this?