Sezary Syndrome



Sezary Syndrome


Sa A. Wang, MD










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

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