Adult T-Cell Leukemia/Lymphoma

 Epidermotropism &/or Pautrier microabscesses



• Peripheral blood with multilobated “flower cells”

• Lymph nodes with effaced architecture & diffuse infiltrate

• Bone marrow with patchy involvement & increased osteoclasts




Ancillary Tests




• Confirmation of HTLV-I infection by serology
• Immunophenotype

image Regulatory T cells CD3(+), CD4(+), CD25(+), FOXP3(+), CD194(+)

image Often lose CD7 expression

image Cytotoxic markers (-)

• Clonal T-cell receptor gene rearrangement

• Complex chromosomal abnormalities; no one abnormality is characteristic of ATLL


Top Differential Diagnoses




• Mycosis fungoides
image Similar clinical picture with epidermotropism & peripheral blood lymphocytosis

image Also CD4(+), CD8(-) T cells, but CD25(-), FOXP3(-), & CD30(-)

• Anaplastic large cell lymphoma
image FOXP3(-), CD194(-); ALK1 & EMA(+/-), unlike ATLL

image
Clinical Photograph of Adult T-Cell Leukemia/Lymphoma
This clinical photograph shows an ulcerating lesion image, which is 2.5 cm in the greatest dimension, from the foot of a person from the Caribbean region who was human T-cell leukemia virus type I (HTLV-I) (+).


image
Epithelial Involvement in Adult T-Cell Leukemia/Lymphoma
This adult T-cell leukemia/lymphoma (ATLL) involves the mucosal epithelium. Note the small lymphocytes with irregular hyperchromatic nuclei infiltrating the squamous mucosa, forming Pautrier-like microabscesses image. (Courtesy C. Bueso-Ramos, MD.)

image
Adult T-Cell Leukemia/Lymphoma at High Magnification
High magnification of ATLL shows a population of medium-sized, atypical, and pleomorphic-appearing cells image with hyperchromasia, atypical nuclear contours, focally prominent nucleoli, and vesicular chromatin. Mitotic figures image are also seen.

image
Lack of *ALK* Gene Rearrangements
This is a break-apart FISH test for the ALK gene, which shows fused (yellow) signals. This indicates that the lesion does not have ALK gene rearrangements. Unlike systemic anaplastic large cell lymphoma, ATLL does not show ALK gene rearrangements.


TERMINOLOGY


Abbreviations




• Adult T-cell leukemia/lymphoma (ATLL)


Synonyms




• Adult T-cell leukemia


Definitions




• T-cell lymphoma/leukemia of regulatory T cells [CD4(+), CD25(+), FOXP3(+)] caused by human T-cell leukemia virus type I (HTLV-I)


ETIOLOGY/PATHOGENESIS


Infectious Agents




• HTLV-I
image Type C retrovirus, composed of single-stranded RNA, which is converted into double-strand DNA during infection

image Virus is monoclonally integrated into host genome

image Progresses to leukemia/lymphoma in < 5% of infected individuals

image Long latency period

– Most exposed as infants/children

– Tumor often develops after 20 years of viral exposure

image Transmitted through blood, sexual intercourse, or breast milk

image HLA alleles A26, B4002, B4006, & B4801 may be predisposed to developing ATLL

image Inflammatory diseases related to HTLV-I include tropical spastic paraparesis, HTLV-I-associated myelopathy, HTLV-I-associated uveitis, & infective dermatitis

image Encodes tax (viral oncoprotein)

– Plays role in development of ATLL

– Activates transcription factors for T-cell proliferation genes


CLINICAL ISSUES


Epidemiology




• Age
image Adults; most commonly in 6th or 7th decades

• Sex
image M:F = 1.5:1.0

• Ethnicity
image Endemic to Southwest Japan, Caribbean, South America, Australia, & Central Africa


Presentation




• Skin lesions
image Develop in 50% of ATLL patients

image Usually multiple nodules/tumors, papules, plaques, or macules

– Papules may cover large segments of body

image Rarely, erythroderma, purpura, prurigo, or erythema multiforme

• Other sites of disease include lymph nodes, peripheral blood, bone, spleen & sometimes lung, liver, & CNS
image Most patients have generalized lymphadenopathy

image Hypercalcemia from increased osteoclast bone resorption

• 4 clinical subtypes of ATLL
image Acute subtype
– Most common subtype, 60%, often in children

– Severe peripheral blood lymphocytosis, ↑ WBC, ↑ lactate dehydrogenase (LDH), skin lesions, lymphadenopathy

– Hypercalcemia, lytic bone lesions, renal dysfunction, neuropsychiatric problems

– Immunodeficiency leads to other opportunistic infections

image Chronic subtype
– Lymphocytosis but ↓ WBC than acute subtype

– No hypercalcemia, exfoliative skin rash

image Lymphomatous subtype
– ↑ lymphadenopathy; usually no peripheral blood involvement

– Less hypercalcemia than acute subtype; skin often involved

image Smoldering subtype
– > 5% tumor cells in peripheral blood, even though normal WBC count

– Tumor cells small with less pleomorphism & lobation

– No hypercalcemia or lymphadenopathy

• Skin lesions are mostly in acute & lymphomatous subtypes


Treatment




• There is no standard modality of treatment
image Prevention of HTLV-I transmission prevents ATLL

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Apr 24, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Adult T-Cell Leukemia/Lymphoma
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