Sezary Syndrome



Sezary Syndrome


Sa A. Wang, MD





Key Facts


Terminology



  • Sézary syndrome (SS) is defined by triad of



    • Pruritic erythroderma


    • High number of Sézary cells in blood (> 1,000/µL )


    • Lymphadenopathy, usually generalized


Clinical Issues



  • SS presents de novo in most patients


  • Can be preceded by mycosis fungoides (MF)



    • Cases should be designated as “SS preceded by MF”


  • Skin: Intractable pruritus and generalized erythroderma with edema (≥ 80% of skin surface)


  • Extracutaneous sites of involvement



    • Lymph nodes, lung, liver


    • Spleen, central nervous system, other organs


    • Bone marrow is relatively spared


  • Most treatments are palliative, not curative


  • Total skin electron beam radiation with nonmyeloablative allogeneic SCT may be curative


  • Poor survival: Median < 2.5 years


Microscopic Pathology



  • Sézary cells (cells with cerebriform nuclei) in peripheral blood


  • Skin changes are very similar to mycosis fungoides


  • Lymph nodes show partial or total effacement of normal architecture


Top Differential Diagnoses



  • Nonneoplastic causes of erythroderma


  • Adult T-cell leukemia/lymphoma (ATLL)


  • T-cell prolymphocytic leukemia


  • Leukemia cutis (especially monocytic leukemia)


  • Peripheral T-cell lymphoma, not otherwise specified







Skin of patient with Sézary syndrome shows erythroderma. The patient’s back and left arm are shown in this field.






Peripheral blood smear from a patient with Sézary syndrome shows many large Sézary cells with folded cerebriform nuclei and scant to moderate cytoplasm; they are larger than neutrophils.


TERMINOLOGY


Abbreviations



  • Sézary syndrome (SS)


Synonyms



  • Erythrodermic cutaneous T-cell lymphoma (E-CTCL)


Definitions



  • SS defined by triad of



    • Pruritic erythroderma


    • High number of Sézary cells in peripheral blood (> 1,000/µL ) with



      • Confirmed T-cell clonality or


      • Increased CD4:CD8 ratio > 10 or


      • T-cell immunophenotypic aberrancies demonstrated by flow cytometric immunophenotyping


    • Lymphadenopathy, usually generalized


ETIOLOGY/PATHOGENESIS


Unknown



  • Genetics, infectious agents, or environmental exposures may play a role


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 5% of all cutaneous T-cell lymphomas


  • Age



    • Adults; median: 60 years (range: 45-70 years)


  • Gender



    • M:F = 1.5:1


  • Ethnicity



    • Incidence in blacks 2x as high as in whites


Presentation



  • SS occurs de novo in most patients


  • Can be preceded by prodromal phase



    • Pruritus or nonspecific dermatitis


  • Can be preceded by mycosis fungoides (MF)



    • Patients must fulfill blood criteria for SS (T4B2)


    • These cases should be designated as “SS preceded by MF”



      • Recommendation of International Society for Cutaneous Lymphomas (ISCL)


  • Skin: Intractable pruritus and generalized erythroderma with edema (≥ 80% of skin surface)



    • Associated with alopecia, ectropion, leonine facies


    • Nail dystrophy, plantar hyperkeratoses with extremely painful fissuring


    • Secondary bacterial infection


    • Some cases show marked photosensitivity



      • Mimic chronic actinic dermatitis


  • Extracutaneous involvement



    • Lymph nodes


    • Liver, lung, spleen, central nervous system, and any other organs


    • Bone marrow is relatively spared


  • Increased prevalence of secondary malignancies, especially lymphoma



    • May be attributable to decreased normal CD4(+) T cells


  • Hypereosinophilic syndrome has been reported to be associated with SS



    • Can cause end organ dysfunction


Laboratory Tests



  • Work-up should include



    • Complete blood count with differential


    • Serum chemistry tests of liver and renal function, electrolytes, and lactate dehydrogenase (LDH)


    • Serologic tests for viruses



      • HTLV-1, HIV, hepatitis B



  • Flow cytometric immunophenotyping of peripheral blood useful for



    • Confirming clonality


    • Detecting immunophenotypic aberrancies


  • Molecular analysis of T-cell receptor (TCR) genes for assessment of clonality



    • T-cell clone can be seen in up to 20% of reactive skin conditions


Treatment



  • Most therapies are palliative and not curative



    • Extracorporeal photoimmunotherapy


    • Bexarotene (retinoid)


    • Methotrexate


    • Vorinostat (histone deacetylase inhibitor)


    • Alemtuzumab (anti-CD52)


    • Denileukin diftitox (anti-CD25 IL-2 diphtheria fusion protein)


    • High-dose chemotherapy



      • Etoposide, vincristine, doxorubicin, bolus cyclophosphamide, oral prednisone (EPOCH)


    • Autologous hematopoietic stem-cell transplantation following high-dose chemotherapy



      • Can produce remissions, but early relapses are common


  • Total skin electron beam radiation with nonmyeloablative allogeneic stem cell transplantation (SCT)



    • Possibly curative approach


Prognosis



  • Poor; median survival < 2.5 years



    • Predictors of poor prognosis



      • Advanced age


      • Elevated serum LDH


MICROSCOPIC PATHOLOGY


Histologic Features



  • Peripheral blood



    • Cells with cerebriform nuclei (Sézary cells)



      • Can range in size from small to large


    • Small Sézary cells (< 12 µm in diameter)


    • Large Sézary cells (> 14 µm in diameter)


    • Sézary cells are not completely specific



      • Especially small forms can be seen in reactive conditions


      • Most large cells are neoplastic


  • Skin



    • Changes are very similar to MF


    • In ˜ 2/3 patients with SS, skin biopsy shows diagnostic findings


    • Epidermotropism is variable



      • Can be absent in some biopsy specimens


      • Atypical cells are present only in dermis; often perivascular


    • Tumor cell size can be variable



      • Cell population is often monotonous (more so than MF)


    • In ˜ 1/3 of patients, only nonspecific changes without abnormal lymphocytes



      • Cannot distinguish from nonneoplastic erythroderma using histologic criteria


  • Bone marrow



    • Often not involved or only minimal involvement


    • When involved, Sézary cell infiltrate is often sparse



      • Mainly interstitial pattern; often patchy


Cytologic Features



  • Cerebriform cells; can be small, medium, or large


Lymph Nodes



  • Involved lymph nodes show partial or total effacement of normal architecture by Sézary cells



    • Dense, monotonous infiltrate of Sézary cells


    • Capsular invasion or extranodal invasion is often present


    • B-cell follicles may be reduced in number or small


  • Changes of dermatopathic lymphadenopathy are often present with



    • Increased interdigitating dendritic and Langerhans cells



    • Increased epithelioid venules and scattered melanophages


ANCILLARY TESTS


Immunohistochemistry



  • Pan-T-cell antigens(+), TCR-αβ(+)



    • Loss or dim expression of T-cell antigens(+/-)


  • CD4(+), CD8(-)


  • CD25(-/+), CD30(-/+), CD52(+)


  • B-cell antigens(-)


  • Ki-67 moderate to high


Flow Cytometry



  • CD2(+), CD3(+), CD5(+), CD7(+), TCR-αβ(+)


  • CD4(+), CD8(-)


  • TdT(-), CD1a(-), CD10(-), B-cell antigens(-)


  • Immunophenotypic aberrancies are common; best detected by flow cytometry



    • Increased CD4:CD8 ratio


    • Loss of CD7, CD26, or other antigens


    • Altered expression levels of CD2, CD3, CD4, or CD5


  • Vβ analysis is useful to confirm clonality and for quantifying neoplastic cells



    • Can be used for initial diagnosis and monitoring treatment response


Cytogenetics

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Sezary Syndrome

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