Diagnosis and Discussion

Diagnosis

HTLV-1 Associated Adult T-Cell Leukemia/Lymphoma

Discussion

Adult T-cell Leukemia/Lymphoma is a peripheral CD 4(+) T-cell neoplasm caused by the retrovirus human T-cell lymphotrophic virus type I (HTLV-I). HTLV-1 is endemic in parts of Japan, Caribbean, sub-Sahara Africa, and South America. Patients often present with widespread lymphadenopathy (above and below the diaphragm often sparing the mediastinum), skin lesions (variable from scaly and erythematous rash, plaques or nodules), and hypercalcemia. T-cell immunodeficiency is also common and patients can present with pneumocystis pneumonia and/or strongyloidiasis, Four clinical variants have been described: acute, lymphomatous, chronic, and smoldering.

Classic pathologic findings include markedly increased lymphocytes in peripheral blood smears with characteristic agranular basophilic cytoplasm and multi-lobulated nuclei (“flower cells”). In lymph nodes, ATLL involves a pleomorphic population of large and small lymphocytes that initially expand the paracortex and subsequently diffusely effaces lymph node architecture. Neoplastic cells are typically CD2, CD3, CD5, and T-cell receptor alpha-beta positive which aberrantly express CD25 and variable CD30. Neoplastic cells show loss of CD7 and have markedly increased CD4:CD8 ratio. Patients often have complex cytogenetic aberrancies and a monoclonal TCR gene rearrangement is present on molecular analysis.

The differential diagnosis includes Sezary syndrome/Mycosis fungoides (SS/MF), which can have similar clinical and histologic presentation of skin lesions with skin biopsies showing epidermotropism and Paturier microabscesses. Lymphocytes with atypical “cerebriform” nuclear contours in peripheral smears can mimic the “flower cells” seen in ATLL. Features that favor SS/MF over ATLL include a less acute clinical presentation, CD25 variability (as opposed to strong CD25  in ATLL), and absence of HTLV-1 seropositivity. Peripheral T-cell lymphoma (NOS) can also have overlapping histologic and immunohistochemical features, however it is negative for serologic or molecular evidence of HTLV-1 infection.1-7

References

1. Arango M: Adult T-cell leukemia/lymphoma. Blood. 126(20):2343, 2015

2. Qayyum S et al: Adult T-cell leukemia/lymphoma. Arch Pathol Lab Med. 138(2):282-6, 2014

3. Tokura Y et al: Skin manifestations of adult T-cell leukemia/lymphoma: clinical, cytological and immunological features. J Dermatol. 41(1):19-25, 2014

4. Yoshimitsu M et al: Prevention of human T-cell lymphotropic virus type 1 infection and adult T-cell leukemia/lymphoma. Recent Results Cancer Res. 193:211-25, 2014

5. Ahmadi Ghezeldasht S et al: Human T Lymphotropic Virus Type I (HTLV-I) Oncogenesis: Molecular Aspects of Virus and Host Interactions in Pathogenesis of Adult T cell Leukemia/Lymphoma (ATL). Iran J Basic Med Sci. 16(3):179-95, 2013

6. Yokote T et al: Flow cytometric immunophenotyping of adult T-cell leukemia/lymphoma using CD3 gating. Am J Clin Pathol. 124(2):199-204, 2005

7. Gonçalves DU et al: Epidemiology, treatment, and prevention of human T-cell leukemia virus type 1-associated diseases. Clin Microbiol Rev. 23(3):577-89, 2010