Lymphocytic variant of hypereosinophilic syndrome: A report of seven cases from a single institution

Abstract

Background: Lymphocytic variant of hypereosinophilic syndrome (L-HES) is a subtype of HES driven by cytokines produced by clonal T-cells. Due to the rarity of its occurrence and challenges in diagnosis, this subtype of HES is under recognized. Methods and Results: We report seven patients with L-HES, diagnosed from a group of 136 patients who were referred to our institution for the work-up of hypereosinophilia. The clinical presentation, symptoms and signs were heterogeneous and uncharacteristic; indistinguishable from idiopathic HES. Flow cytometry immunophenotypic analysis revealed aberrant T-cells in all patients, with a Th2 immunophenotype, CD2 + CD3−CD4 + CD5 + CD7dim+/−CD8− in six of seven (86%) cases. CD10 was partially expressed in one of seven (14%) cases, and clonal TCR gene rearrangement was detected by PCR in five of seven (71%) patients. All patients were treated with corticosteroids and two of seven (29%) patients received anti-IL5 antibody therapy. With a median follow-up time of 7.5 years (2.3-14.1 years), one (11%) patient developed peripheral T-cell lymphoma 6.1 years after the initial diagnosis of L-HES and responded well to chemotherapy. All patients were alive at the last follow-up. Conclusion: In conclusion, a combination of flow cytometry immunophenotyping and molecular analysis allows the identification of aberrant T-cells, facilitating a diagnosis of L-HES in patients with eosinophilia. A correct diagnosis is essential for the proper management of these patients.

CD3−CD4+ Lymphocytic Variant Hypereosinophilic Syndrome: Diagnostic Tools Revisited

“…In contrast, a significantly higher expression level was observed for CD2, CD45RO and CD95, appearing as a single tight histogram with high staining intensity on CD3 -CD4 + T cells, clearly demarcating these cells from the normal CD4 + cells in the same sample. Although we and others (13) commonly observe increased staining intensity for CD5 on these cells, the difference with CD3 + CD4 + cells was not statistically significant.…”

“…Although L-HES is an indolent lymphoproliferative disorder, the large majority of patients have normal circulating lymphocyte counts (10,11,13). We recently reported that the abnormal CD3 -CD4 + T cell subset represented less than 2% of total lymphocytes in 40% of patients (10), explaining that these cells rarely impact differential counts.…”

Issue Highlights — May 2021

“…This contrasts with more limited data that exists on the potential diagnostic utility of immunophenotyping in MPN, HES, or the altered proliferation profiles in these and other, myeloid neoplasms (Shameli et al, 2020;Ouyang et al, 2015;Herborg et al, 2018;Matarraz et al, 2012;Matarraz et al, 2011). In this issue of Cytometry B six original research papers and a case report have used flow cytometry to study MDS, MDS/MPN, MPN and HES (Shestakova et al, 2021;Davydova et al, 2021;Mestrum et al, 2021;Panda et al, 2021;Vijayasekharan et al, 2021;Hu et al, 2021;Espasa et al, 2021). In the first of these six papers, Shestakova et al (2021) explored the utility of automated leucocyte parameters including cell volume, conductivity and light scatter properties (VCS parameters) as assessed in an automated hematological analyzer, as a read-out for dysplastic MDSassociated features.…”

“…In the following manuscript, Panda et al (2021) investigate mast cell differentiation of blast cells in patients with myeloid neoplasias not fulfilling diagnostic criteria for systemic mastocytosis or myelomastocytic leukemia (Swerdlow et al, 2017). Overall, 9 patients showed blasts with a CD117 hi CD34 het HLADR -/lo CD203c + immature mast cell-associated immunophenotype, supporting the potential existence a small percentage of underdiagnosed myelomastocytic leukemia cases; diagnosis of these nine patients corresponded to CML at any phase of the disease (n=4), to newly diagnosed and secondary AML (n=4) and to one chronic myelomonocytic leukemia, whose features are described in detail in the manuscript (Panda et al, 2021) Finally, the sixth manuscript on myeloid neoplasms reports on flow cytometry immunophenotypic findings in seven patients diagnosed with lymphocytic variant of HES, out of a series of 136 patients referred to a single institution for the diagnostic work-up of eosinophilia (Hu et al, 2021). In this report, Hu et al (2021) showed that flow cytometry immunophenotyping was critical (and complementary to molecular analyses) for systematic demonstration of aberrant CD3-CD7-/lo CD4+ CD5+ CD2+ CD8-T-cells associated with T cell clonality, in all seven patients.…”

“…Preliminary results reported for the 12 CML patients included in this study showed that among 5 cases in which precursor cells with a mixed B‐myeloid (B/M or B/T/M) phenotype were detected a greater frequency (3/5 patients) of progression to acute leukemia associated with Imatinib‐resistant gene mutations was observed vs. that found in cases with aberrant myeloid‐only precursors (0/5 cases), suggesting immunophenotyping of pediatric CML patients during chronic phase of the disease could contribute to identify patients at higher risk of progression to acute leukemia with Imatinib‐resistant mutations (2021). Finally, the sixth manuscript on myeloid neoplasms reports on flow cytometry immunophenotypic findings in seven patients diagnosed with lymphocytic variant of HES, out of a series of 136 patients referred to a single institution for the diagnostic work‐up of eosinophilia (Hu et al, 2021). In this report, Hu et al (2021) showed that flow cytometry immunophenotyping was critical (and complementary to molecular analyses) for systematic demonstration of aberrant CD3‐ CD7‐/lo CD4+ CD5+ CD2+ CD8‐ T‐cells associated with T cell clonality, in all seven patients.…”