Eric C. Vonderheid

Background: Lymphomatoid papulosis (LyP) is a self-healing CD30+ cutaneous lymphoproliferative disorder (CLPD) with paradoxical histology of a malignant lymphoma. Case reports and small patient series suggest an association of LyP with atopy. However, the prevalence of atopy depends on patients’ recall which is not always reliable. More objective criteria of atopy include skin reactivity to allergens and IgE reactivity to allergens. This study was undertaken to determine if atopy is prevalent in LyP patients using IgE specific antibodies to aeroallergens, and if Staphylococcal aureus enterotoxins might be a pathogenic factors for LyP as proposed for other skin disorders. Methods: Thirty-one samples of CD30CLPD were tested for total serum IgE (IgE-t) and 10 IgE- specific airborne allergens with the Phadiatop multiallergen test, which if positive, is regarded as evidence of atopy. Sera was tested for IgE reactive against three Staphylococcal enterotoxins with superantigenic properties (SSAg-IgE). Control sera were obtained from adult subjects evaluated for rhino-sinusitis and a negative Phadiatop test. Patients’ history of atopy was obtained by retrospective chart review. Findings: Nearly 50% of patients with the most common LyP types had a positive Phadiatop test and IgE-t was increased compared to non-atopic controls. Seven of 28 (25%) LyP patients had at least one SSAg-IgE at the concentration used to define serologic atopy (≥ 0.35 kUa/L) compared to 3/52 (6%) controls (P= 0.028). TSST1-IgE was detected in 7 (23%) specimens of CD30CLPD, often together with SEB-IgE; SEA-IgE was not detected. TSST1-IgE exceeded the 0.35 kUa/L threshold in 3 (6%) controls. Conclusions: LyP patients have an increased prevalence of atopy as determined by the Phadiatop test and increased prevalence of SSAg-IgE compared to controls. Prevalence of serologic atopy exceeded that reported by patients’ medical history. The results support the hypothesis that an atopic diathesis and possibly SSAg contribute to the pathogenesis of LyP. Summary: Contrary to patients’ recall of atopic disorders, IgE specific antibodies to aeroallergens, Staphylococcal aureus superantigens and total serum IgE are increased in patients with lymphomatoid papulosis.

The prevalence of atopy was investigated in 20 patients with Sézary syndrome (SS), 20 patients with plaque phase mycosis fungoides (MF), 9 patients with primary cutaneous marginal zone lymphoma (pcMZL) and 8 patients with primary cutaneous follicle center lymphoma (pcFCL) with the Phadiatop multi‐allergen test. The relationship among serologic atopy, IgE reactivity against Staphyloccocal enterotoxin superantigens, and serum total IgE (IgE‐t) levels and their prognostic implications in SS was investigated. Phadiatop test was positive in 45%, 15%, 33% and 0% of samples of SS, MF, pcMZL and pcFCL, respectively. IgE‐t levels were also increased in SS, pcMZL and marginally MF. No correlation was found with patients’ history of atopic disorders. Staphylococcal superantigen‐specific IgE ≥ 0.35 kUa/L, most often against toxic shock syndrome toxin‐1, was detected in 40% of Sézary samples followed by MF (20%). In the absence of serologic atopy (negative Phadiatop test), IgE‐t levels for patients with SS and MF were not significantly higher than controls whereas the levels for pcMZL remained high. Furthermore, even with a negative Phadiatop test, IgE‐t values were higher in sera of patients with SSAg‐IgE ≥ 0.35 kUa/L vis‐à‐vis < 0.35 kUa/L across all diagnostic categories including controls albeit the difference was statistically significant only for SS. The presence of specific IgE antibodies ≥ 0.35 kUa/L, IgE‐t > 122 kU/L or eosinophils > 500/µL had no impact on survival of patients with SS. These results indicate that a pathogenic link may exist between an atopic diathesis and development of SS and possibly pcMZL

Background: Sézary syndrome (SS) and erythrodermic mycosis fungoides (E‐MF) represent two expressions of erythrodermic cutaneous T‐cell lymphoma (E‐CTCL).Methods: Histopathologic features were compared on skin specimens from 41 patients with SS and 70 patients with E‐MF. Immunopathologic findings were compared on 42 SS and 79 E‐MF specimens.Results: Specimens of SS usually showed band‐like dermal infiltrates with intermediate‐sized lymphoid cells and few plasma cells; on the other hand E‐MF more often had a perivascular infiltrative pattern, predominance of small/mixed lymphoid cells and eosinophils. SS also had lower numbers of CD8+ cells and higher numbers of CD62L+ cells compared to E‐MF. For E‐MF patients, the presence of large Pautrier collections, infiltrates with intermediate‐sized cells, increased number of mitotic figures and ≥50% CD62L+ cells in the dermal infiltrate correlated with a relatively poor disease‐specific survival. However, only the presence of mitotic figures retained prognostic significance with clinical stage as a covariate.Conclusions: Clinical stage provides the most important prognostic information for patients with E‐CTCL. However, mitotic activity for E‐MF and CD8+ cells <20% for SS have additional value. We hypothesize that observed differences in plasma cell and eosinophil numbers may reflect the influence of CD62L+ central memory T‐cells in the microenvironment.

Our knowledge about Sezary syndrome has rapidly increased since the development of immunopathology, flow cytometry and molecular genetics in the 1970s.

Bernengo et al. reported that >30% CD4⁺CD26⁻ lymphocytes detect blood involvement in patients with mycosis fungoides (MF) and Sézary syndrome. In addition, the ISCL/EORTC suggested that this threshold might serve as a criterion for the B2 blood rating for staging. In this manuscript, we report our experience with measurement of CD4⁺CD26⁻ and CD4⁺CD7⁻ cells, Sézary cell counts, and aberrant T cells with diminished expression of CD2, CD3, or CD5 antigens. CD4⁺CD26⁻ ≥30% occurred in 15 of 373 (4.0%) patients with MF, 33 of 47 (70%) patients with erythrodermic cutaneous T cell lymphoma (ECTCL) and 2 of 54 (4%) patients with inflammatory skin diseases. CD4⁺CD26⁻ measurements provided a more reliable assessment of neoplastic cell numbers in the blood than Sézary cell or CD4⁺CD7⁻ percentages. CD4⁺CD26⁻ measurements may be used to define B ratings for staging with B2 defined as CD4⁺CD26⁻ ≥ 1000/μL, plus clonality or phenotypically abnormal cells.

Papular mycosis fungoides: Six new cases and association with chronic lymphocytic leukemia