22 September 2005 – Case of the Week #21
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We thank Dr. Shylashree Chikkamuniyappa, Hematopathology fellow, University of Texas Health Science Center, San Antonio, Texas (USA) for contributing this case. We invite you to contribute a Case of the Week by emailing NPernick@PathologyOutlines.com with microscopic images (any size, we will shrink if necessary) in JPG or GIF format, a short clinical history, your diagnosis and any other images (gross, immunostains, EM, etc.) that you have and that may be helpful or interesting. We will write the discussion (unless you want to contribute to it), list you as the contributor, and send you a check for $35 (US) for your time if we use the case. Please only send cases with a definitive diagnosis.
Case of the Week #21
The patient is a 64 year old Japanese woman with a history of disseminated nocardial infection, with abscesses in the brain and lung and a facial herpetic infection. A complete blood count showed a hemogloblin of 12.2, platelet count of 313 and elevated white blood cell count of 45.6 with 73% lymphocytes.
A bone marrow biopsy was hypercellular for age with 15% large, atypical cells.
Flow cytometry of peripheral blood showed bright CD45/LCA staining with 98% T cells. 98% of the T cells marked with CD2, CD3, CD4 and CD5, and 4% marked with CD8 and CD7.
Other lab tests were: calcium of 8.4 mg/dl, LDH: 452 U/L (high), HTLV-1: 2+ positive by ELISA, Western Blot: bands present at p16, gp21 and gp46-1.
What is your diagnosis?
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Diagnosis: Adult T cell leukemia / lymphoma
Adult T cell leukemia/lymphoma occurs most commonly where the HTLV-1 retrovirus (human T cell leukemia virus-1) is endemic, namely in southwest Japan, western or central Africa, South America, the Caribbean and the southeast US. Infection is sexually transmitted or spreads from mother to child (through the placenta or breast milk), through intravenous drug abuse or blood transfusion. There is usually a delay of several decades before clinical features appear. Leukemia / lymphoma occurs in 1-5% of HTLV-1 positive patients, and usually affects adults. These patients also have defects of cell-mediated immunity and are at risk for multiple opportunistic infections (Archives 2000;124:1241). Of note, HTLV-1 infection also causes tropical spastic parapesis, a chronic progressive demyelinating disease affecting the spinal cord and CNS white matter, causing weakness and spasticity, predominantly in the lower limbs (Emedicine.com)
Adult T cell leukemia/lymphoma is divided into different subtypes. The most aggressive and most common is the acute subtype (55-65% of patients), in which greater than 50% of cells have characteristic morphology. Patients present with generalized lymphadenopathy, hepatosplenomegaly, bone marrow infiltration and skin lesions. Patients have a high white blood count with lymphocytosis and hypercalcemia. Cutaneous infiltrates may resemble mycosis fungoides due to epidermotropism with Pautrier’s microabscesses. Median survival is less than 1 year. The lymphomatous subtype (20-25% of patients) is characterized by prominent lymphadenopathy without significant peripheral blood involvement. The chronic subtype has an increased white blood count and absolute lymphocytosis, but only 10-50% of white blood cells are abnormal. These patients may have mild lymphadenopathy or hepatosplenomegaly, but no CNS, bone or GI involvement. The smoldering subtype has 5% or more malignant cells in the peripheral blood, with a normal total lymphocyte count and no lymphadenopathy, hepatosplenomegaly or marrow infiltrates. Patients with the chronic and smoldering subtypes may evolve into the acute subtype after years of indolent disease.
Microscopically, the most distinctive feature are cells with basophilic and agranular cytoplasm and multilobated nuclei that resemble cloverleafs or flowers (cloverleaf-type cell). The nuclei have thick nuclear membranes and course chromatin, with small or absent nucleoli. Reed-Sternberg like cells may be present.
By flow cytometry or immunohistochemistry, tumor cells are positive for CD2, CD3, CD4 and CD5, as well as CD25, CD52 and HLA-DR. They are usually negative for TdT, CD7, CD8 and CD30. Molecular studies demonstrate the HTLV-1 provirus in tumor cells, and a clonal T cell receptor rearrangement.
At present, no curative treatment or vaccine is available. Multiagent chemotherapy can cause complete remission, but relapse is common. Antibodies to CD52, called Campath-1H, are currently undergoing investigational studies (Clinical Trial: Campath-1H for Treating Adult T-Cell Leukemia/Lymphoma)
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