Adult T-cell leukemia / lymphoma

Epidemiology and Etiology:

• HTLV-1 (human T-cell leukemia virus type 1)
• Long latency
• Transmitted in breast milk
• Blood products
• 2.5% cumulative incidence of ATLL among HTLV-1 carriers
• Peripheral CD4+ T cells in various stages of activation
• Endemic areas:
• Japan
• Caribbean basin
• Central Africa
• Adults
• 55y median

Common sites:

•  usually widely disseminated
• lymph nodes
• spleen
• peripheral blood
• bone marrow
• skin (>50%)

Gross features:

Histologic features:

•  acute and lymphomatoid variants:
• medium-sized to large lymphocytes
• pronounced nuclear pleomorphism often
• coarsely clumped nuclear chromatin with distinct or prominent nucleoli
• polylobated often (flower cells)
• deeply basophilic cytoplasm often (Giemsa)
• blast-like cells (small proportion)
• transformed nuclei
• dispersed chromatin
• giant cells with convoluted or cerebriform nuclear contours may be present
• skin:
• epidermal infiltration with Pautrier-like microabscesses frequently
• eosinophilia in some
• chronic and smoldering variants:
• small lymphocytes
• minimal cytologic atypia
• skin:
• sparse dermal infiltrate
• hyperkeratosis of overlying epidermis
• Hodgkin-like histology in lymph nodes may be seen in early or smoldering variants
• Usually progresses to overt TLL rapidly

Immunophenotype:

Marker:	Sensitivity:	Specificity:
T-cell antigens (CD2, 3, 5) BUT lacking CD7	Usually
CD4	Most
CD8 (neg)	Most
CD25	Nearly all
CD30 (transformed cells)
ALK (neg) (transformed cells)
TIA-1 (neg)
Granzyme B (neg)
TdT (neg)

Molecular features:

• TCR gene rearrangements 
• HTLV-1 DNA (integrated)

o abnormal karyotype (90%) (no changes are specific)

§ aneuploidy frequently

§ multiple breaks frequently

§ 14 rearrangements most freqeuntly

· t(14;14)(q11;q32)

o TCRAD and BCL11B

· inv(14)(q11q32)

· del(14)(q11q13)

· 14q11 breakpoint with multiple partners

o aCGH findings:

§ 7q gain

§ 3p gain (acute type)

§ 6q loss (6q15 and 6q21 breakpoints) (25%)

§ 13q loss

§ high-level amplifications:

· 1p36

· 6p25

· 7p22 (CARD11)

· 7q

· 14q32 gain/amplification with BCL11B overexpression

§ Various abnormalities have been associated with acute / lymphoma / prognosis but ?validated

Other features:

•  clinical variants:
• acute (most common)
• leukemic phase
• markedly elevated WBC count
• skin rash
• generallised lymphadenopathy
• hypercalcemia
• hepatosplenomegaly
• constitutional symptoms
• elevated LDH
• eosinophilia common
• T-cell immunodeficiency
• Opportunistic infections such as Pneumocystis carinii pneumonia and Strongyloidiasis
• Lymphomatous
• Prominent lymphadenopathy
• No peripheral blood involvement
• Chronic
• Skin lesions (exfoliative rash)
• Atypical lymphocytes not numerous in the blood
• Absent hypercalcemia
• Smoldering
• Normal WBC count
• <5% circulating, neoplastic cells
• skin or pulmonary lesions frequently
• hypercalcemia absent
• progression may occur from chronic or smoldering to acute variants (25%)

References:

• WHO blue book 2001
• Heim & Mitelman Cancer Cytogenetics, 2009