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Lymphoma - Non B cell neoplasms

T/NK cell disorders

Sézary syndrome

Reviewer: Dragos Luca, M.D. (see Reviewers page)
Revised: 7 February 2012, last major update August 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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● Sézary syndrome (SS) is defined by the triad of erythroderma, generalized lymphadenopathy and the presence of clonally related neoplastic T cells with cerebriform nuclei (Sézary cells) in skin, lymph nodes and peripheral blood
● In addition, one or more of the following criteria are required: an absolute Sézary cell count of at least 1000/mm³, an expanded CD4+ T cell population resulting in a CD4/CD8 ratio of more than 10 and/or loss of one or more T cell antigens (WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, Lyon 2008)

Epidemiology
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● Rare, <5% of all cutaneous T cell lymphomas
● Adults, usually men over 60

Etiology
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● Unknown, but a syndrome clinically indistinguishable is occasionally seen in HTLV-1 associated leukemia/lymphoma

Sites
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● By defition, a leukemia, therefore a generalized disease
● All visceral organs may be involved in the terminal stages
● Remarkable sparing of the bone marrow

Clinical features
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● Generalized exfoliative erythroderma, generalized lymphadenopathy and blood involvement by Sézary cells (resemble cells of mycosis fungoides)
● Pruritus, alopecia, ectropion, palmar/plantar hyperkeratosis, onychodystrophy, leonine facies (resembles a lion)
● Associated with monoclonal gammopathy and secondary neoplasms (carcinoma, other non-Hodgkin lymphomas), attributed to the loss of normal circulating CD4+ cells
● Skin lesions rarely become tumor masses

Case reports
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● 63 year old man with thrombotic microangiopathy (Nephrol Dial Transplant 2004;19:733)
● 66 year old man without erythroderma (Indian J Dermatol Venereol Leprol 2002;68:225)
● 74 year old man with coexisting CLL (Ann Biol Clin (Paris) 2003;61:94)
● 75 year old man with large cell transformation (Am J Clin Pathol 2000;113:792)

Treatment and prognosis
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● Poor prognosis; better with categories LN 0-2 or Dutch classification I-II with negative T cell rearrangement by PCR
● 10-20% 5-year survival rate; most die of opportunistic infections
● May transform to anaplastic large cell lymphoma with poor prognosis
● Staging: ISCL/EORTC Revision to the classification of mycosis fungoides and Sézary syndrome

Postulated normal counterpart
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● Mature epidermotropic skin homing CD4+ T cells

Gross description
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● Erythroderma, generalized lymphadenopathy, rarely skin tumors

Gross images
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Leonine facies

Erythroderma

Various images

Micro description
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● Atypical lymphocytes (Sézary cells) are intermediate / large with basophilic cytoplasm, cerebriform nuclei, inconspicuous nucleoli; marrow usually normal, if involved the infiltrates are sparse and mainly interstitial
● May resemble mycosis fungoides in tissue, but more often monotonous infiltrates and sometimes no epidermotropism
● 1/3 of cases have non-specific histology of the skin biopsy
● Peripheral blood: Romanowsky stained smears show large cells with slight cytoplasm containing PAS+, perinuclear vacuoles and large, cerebriform, hyperchromatic nuclei

Flow cytometry images
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Various images

Positive stains
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● CD2, CD3, CD4 (most cases), CD5, TCRβ+, CLA, CCR4, CD45RO, P140, SCS

Negative stains
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● CD8 (most cases), CD7, CD26

Genetics and molecular
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● Clonal rearrangement of T cell receptor genes, but no specific chromosomal abnormalities
● Complex karyotypes including abnormalities of 1p, 6q, 10q, 17p, 19
● TP53 and p16 inactivation, JUNB amplification

Differential diagnosis
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● Drug-induced erythroderma, chronic actinic reticuloid; eczema and psoriasis for cases with non-specific histology

Additional references
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● WHO Classification of Skin Tumours, Lyon 2006
● Review articles: Am J Clin Pathol 2007;127:496, Am J Clin Pathol 2006;125:364, Blood 1996;88:2385

End of Lymphoma - Non B cell neoplasms > T/NK cell disorders > Sézary syndrome

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