A Study Of Primary Cutaneous CD30+ Lymphoproliferative Disease On Clinicopathologic Features, TCR Gene Rearrangements And JunB Expression

Objective:1) To investigate the clinicopathologic features,immunophenotypes and prognosis of primary cutaneous CD30+ lymphoproliferative disease (CD30+LPD);2) To evaluate the role of TCR gene rearrangement in the diagnosis of CD30+LPD;3) To explore JunB expression in CD30+LPD on protein,mRNA and DNA levels.Methods:Fifty-eight CD30+LPD cases including 44 CALCL cases and 14 LyP cases were studied.Clinical features and follow-up data were summarized. Histopathologic and immunohistochemistry studies were performed.The relationship between individual clinicopathologic features and replapse of CALCL was emphasized.TCRB,TCRG and TCRD gene rearrangement analysis by BIOMED-2 multiplex PCR tubes were performed in 20 CALCL cases,10 LyP cases and 10 inflammatory cases with house-keeping gene amplification products no less than 300bp.Immunohistochemistry and real-time PCR were applied to explore and compare JunB expression in the CD30+LPD group and the control group.Results:(1) The age of 14 LyP patients ranged from 24 to 72 years with a median of 43 years.Most patients presented with multiple disseminated papules and small nodules which usually evolved and regressed within 4 to 8 weeks.Most LyP patients had waxing and waning lesions within a median follow-up of 27 months (range:6 to 47 months),but the survival rate was 100%.The age of 44 CALCL patients ranged from 20 to 79 years with a median of 53 years.CALCL patients presented with nodules,masses and/or plaques,sometimes with ulceration. Extremities were the most commonly affected sites.Follow-up was available in 39 CALCL patients,ranging from 6 to 102 months,with a median of 27 months.The disease-specific survival of CALCL was 87.2%.46%of the patients experienced relapses.CALCL patients with age over 50 years or with no less than 2 anatomic sites involved were more likely to have relapses.(2) Histologically,LyP could be devided into type A,B and C.In type B,the infiltrate of atypical lymphocytes resembled mycosis fungoids.Morphology of type C was similar to CALCL.Among 44 CALCL cases,31 cases were classified as common variant,6 cases as small cell variant and 7 cases as neutrophil/eosinophil-rich type.(3) On immunohistochemistry,neoplastic lymphocytes in LyP type A,type C and CALCL showed similar immunophenotypes with positivity for CD30,while atypical lymphcytes in LyP type B were negative for CD30.In all CD30+LPD cases,the expression rate of CD45,CD45RO,CD43,CD3, cytotoxic proteins and EMA was 93%,80%,96%,63%,75%and 28%respectively. CD4+/CD8-,CD4-/CD8+ and CD4-/CD8-immunophenotypes were found in 58%, 23%and 19%of cases.Only 1 case(3%) was positive for CD56.(4) Clonal TCR gene rearrangement was documented in 8 LyP case(80%) and 20 CALCL cases (100%),indicating it can not help to distinguish CALCL from LyP.But TCR gene rearrangement can be used to differentiate between CD30+LPD and other cutaneous inflammatory lesions for clonality detection rate in control inflammatory lesions was only 30%.(5) JunB protein was expressed in both CD30+LyP(87.5%) and CALCL (94.6%),which was significantly correlated with CD30 expression.JunB mRNA expression was significantly up-regulated in 34 CD30+LPD cases relative to 22 control cases,while genomic expression of JunB showed no difference between these two groups.Conclusions:LyP is a type of T cell lymphoproliferative disease with multiple, recurrent and self-healing papulonodular eruptions,which can be devided into type A, B and C.Correct diagnosis and classification should be made with clinical correlation. CALCL is a type of low-grade malignant primary cutaneous T cell lymphoma with a wide spectrum of clincopathologic pattern.Special subtypes including small cell variant and neutrophil/eosinophil-rich type should not be confused with other CTCL or inflammatory lesions.CALCL patients with age over 50 years or with no less than 2 anatomic sites involved were more likely to have relapses.TCR gene rearrangement detection can be an adjuvant diagnostic tool in differentiating between CD30+LPD and cutaneous inflammatory lesions,but it can not help to distinguish CALCL from LyP.JunB expression is a common feature in both LyP and CALCL and it is correlated with CD30 expression.JunB protein expression is mainly due to up-regulation on mRNA level.