We attempted to better define the subtypes of LLP by morphologic, phenotypic and genotypic features and to correlate those features to clinical presentation and outcome.
METHOD: Skin biopsy material was studied by conventional light microscopy, through immunophenotyping performed on sections from
paraffin-embedded,
formalin-fixed tissue and in some cases on sections of tissue frozen after receipt in physiological (Michel's) medium, and by polymerase chain reaction single-stranded conformational polymorphism analysis to assess for clonality of T-lymphocytes. Clinical features were correlated to histologic, phenotypic, and genotypic analyses.
RESULTS: Patients with LEP had a prior diagnosis of LE or overlying skin changes which light microscopically were characteristic of LE. Patients with ILLP had no concurrent or prior history of LE, no systemic symptoms or
cytopenias, and a
clinical course not suggestive of
lymphoma. Cases of SCTCL showed
hemophagocytic syndrome and/or lesional progression with demise attributable to the disease. Lesions in all groups showed proximal extremity predilection. Females predominated in the LEP group. The average age of onset was 38, 40 and 55 years in the LEP, ILLP and SCTCL groups, respectively.
Cytopenia was seen in 4 LEP patients; 1 also developed
fever. In LEP and ILLP, lesions resolved with
hydroxychloroquine and/or
steroid therapy, with recurrences following cessation of
therapy. In the SCTCL group 4 developed
hemophagocytic syndrome, 4 died within 2 years of diagnosis, and 3 went into remission following
chemotherapy. The LEP and SCTCL groups manifested histological similarities: dense perieccrine and lobular lymphocytic infiltration, lymphoid atypia, histiocytes with ingested debris, eosinophilic
necrosis of the fat lobule and
thrombosis. The atypical lymphocytes although pleomorphic did not have a cerebriform morphology. The infiltrate in ILLP had a similar cytomorphology and distribution with variable angioinvasion which in all save one case was of lesser intensity and was not associated with significant
fat necrosis or
vasculitis. Germinal centers, dermal/subcuticular
mucin deposition and an atrophying interface
dermatitis with hyperkeratosis and follicular plugging were largely confined to the LEP group. Erythrophagocytosis, characteristic of SCTCL, usually indicated a supervening subcuticular lymphoid dyscrasia when encountered in ILLP and LEP. SCTCL showed a selective loss of CD5 expression with or without diminution in CD7 and monoclonal CD3 expression. Of 4 cases studied, 3 showed a CD8 dominant infiltrate while 2 others exhibited CD56 and CD30 positivity, respectively. All cases of SCTCL with amplifiable
DNA showed T-cell clonality. Similar molecular and phenotypic features indicative of subcuticular lymphoid dyscrasia were encountered in cases of LEP and ILLP including a reduction in CD5, CD7, and/or monoclonal CD3 expression, a preponderance of CD8 lymphocytes within the subcutaneous fat and T-cell clonality. These cases showed lymphoid atypia with variable erythrophagocytosis. Cases of phenotypically abnormal and/or clonal LEP showed one or more of local destruction, lesional size progression,
fever, and
cytopenias, but lesions responded to
hydroxychloroquine and/or
prednisone therapy and death attributable to
panniculitis could not be documented. Cases that were phenotypically normal and without clonality had none of the aforesaid atypical clinical features.
CONCLUSION: Lymphoid atypia, erythrophagocytosis, loss of certain pan T-cell markers, a reduced CD4/8 ratio and TCR rearrangement define subcuticular T-cell lymphoid dyscrasia, including a subset of LEP and ILLP. The subcuticular lymphoid infiltrates represent a spectrum of histologic, immunophenotypic, and molecular abnormalities which range from those which are clearly benign to those which are clearly neoplastic, and also encompasses those cases which defy precise classification into the two aforesaid poles.