CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder

Abstract

© F e r r a t a S t o r t i F o u n d a t i o neral T-cell lymphomas (PTCL) but mainly in angioimmunoblastic T-cell lymphoma (AITL). [14][15][16][17][18] PTCLs have also been reported during CD3-CD4 + L-HES course. 6,9,[19][20][21][22][23][24] Two of 23 patients currently followed in the French Eosinophil Network, and one more patient recently reported by others, 25 developed well-defined AITL several years after L-HES diagnosis, which thus raised the problem of the diagnosis of well-defined T-cell lymphoma in patients who have clonal circulating T cells.In this study, we focused on the lymphoid infiltrates in lymph nodes, skin and other available biopsies of tissue involved in L-HES, to assess the presence of clonal T cells at diagnosis and during CD3 - CD4+ L-HES course. We secondly aimed to distinguish L-HES from AITL by comparing histopathological and immunophenotypic characteristics between both entities Methods PatientsTwenty-three hypereosinophilic syndrome (HES) patients with a documented presence of CD3 - CD4+ aberrant subset and a negative FIP1L1-PDGFRA fusion gene research are currently followed The clonal T-cell disease in CD3 -CD4 + L-HES haematologica | 2015; 100(8) 1087 © F e r r a t a S t o r t i F o u n d a t i o nSkin lesions in L-HES patients were pruritic papulo-nodular inpatients P1 and P2, pruritic papular lesions in patient P3, P5, P8, isolated pruritus in patients P7 and P9. Numbers in in the French Eosinophil Network. For the present study, 16 patients (P1-P16) were included, 12 of them had available tissue biopsies during L-HES course. All satisfied criteria for HES (n=15) or hypereosinophilia (HE) (n=1, P13, no organ damage or clinical manifestation) criteria in accordance with the latest up-dated consensus definitions.1 Main clinical characteristics are summarized in Table 1. For the 7 remaining patients, no complementary lymphocyte immunophenotyping was performed, no biopsy was performed (n=5) or biopsies were not available for analysis (n=2). The study was approved by the Lille Hospital Ethical Committee and carried out in accordance with the Declaration of Helsinki.Ten of these patients had bone marrow biopsies at CD3 -CD4 + L-HES diagnosis in order to exclude a T-cell lymphoma (Patients P2-4, P8, P9, P11, P12, P14-16) (data not shown). Four patients had lymph nodes biopsies for a suspicion of T-cell lymphoma during follow up (Patients P1, P3, P4 and P10). For this work, all their biopsies were retrieved for further investigation and for a centralized compared analysis to be made.Finally, Patients P4 and P16 developed a well-defined AITL during L-HES course (AITL/L-HES patients).Patient P4. Patient P4 was 18-years old when a CD3 -CD4 + L-HES diagnosis was made in 1999 and was previously reported by us. 26He presented with eczema-like lesions, rare episodes of angioedema and multiple adenopathy. Despite high circulating CD3 -CD4 + T-cell count (28 G/L), lymph node histological examination confirmed lymphoid reactive hyperplasia. As he was in really good G. Lefèvre ...

Blood and Bone Marrow Evaluation for Eosinophilia

“…49 These cells have moderately abundant cytoplasm, which is lightly basophilic and agranular (Figure 2, A through H). Mild nuclear-contour irregularities may occur, but the classic cerebriform nuclei of Sézary cells are not present.…”

“…Although abnormal T cells can be detected in skin biopsies of patients with L-HES, they usually show a perivascular and dermal pattern of infiltration and do not show significant epidermotropism or other features of mycosis fungoides, such as Pautrier microabscesses or formation of patches, plaques, and tumors. 49 A recent series of L-HES cases from the French Eosinophil Network (Lille, France) found that some patients had numerous abnormal, circulating T cells and infiltration of lymph nodes by atypical T cells but remained stable for many years, with only 2 patients progressing to overt lymphoma. 49 The published literature does not offer firm conclusions on what degree of lymphadenopathy, cytologic atypia, or peripheral blood involvement defines the border between L-HES and peripheral T-cell lymphoma, not otherwise specified; however, a rapid increase in peripheral blood involvement or lymphadenopathy is strongly suggestive of progression to malignancy.…”

“…49 A recent series of L-HES cases from the French Eosinophil Network (Lille, France) found that some patients had numerous abnormal, circulating T cells and infiltration of lymph nodes by atypical T cells but remained stable for many years, with only 2 patients progressing to overt lymphoma. 49 The published literature does not offer firm conclusions on what degree of lymphadenopathy, cytologic atypia, or peripheral blood involvement defines the border between L-HES and peripheral T-cell lymphoma, not otherwise specified; however, a rapid increase in peripheral blood involvement or lymphadenopathy is strongly suggestive of progression to malignancy. Cytogenetic abnormalities have been detected in a few cases of L-HES.…”

“…46 In reported case series, 10% to 25% of patients eventually developed an overt T-cell lymphoma. 45,47,[49][50][51] Secondary lymphomas reported in patients with L-HES include angioimmunoblastic T-cell lymphoma; peripheral T-cell lymphoma, not otherwise specified; cutaneous T-cell lymphoma, and ALK À anaplastic Table 6. Lymphocyte-Variant Hypereosinophilic Syndrome (L-HES)…”

“…45,47,[49][50][51][52][53] The diagnosis of angioimmunoblastic T-cell lymphoma or anaplastic large cell lymphoma after L-HES is straightforward because these lymphomas have highly specific morphologic and immunohistochemical features. In some cases, the differential diagnosis between L-HES and cutaneous T-cell lymphoma may be difficult because both can present with erythematous skin, eosinophilia, and abnormal T cells in the peripheral blood.…”