Unique Characteristics of Classical Hodgkin Lymphoma in Patients with Cutaneous T-Cell Lymphoma

Background: Patients (pts) with cutaneous T-cell lymphoma (CTCL) are at increased risk of developing second primary malignancies. Intrinsic or treatment-related immune dysregulation in this population may contribute to pathogenesis and impact prognosis and pathological features of CTCL-associated malignancies. We investigated characteristics of a large institutional cohort of CTCL pts to identify those with second primary malignancies, with a specific focus on classical Hodgkin lymphoma (HL).

Methods: We performed aretrospective review of CTCL patients seen at our institution from January 2000 through December 2014 with ≥1 additional malignancy. Pts with CTCL including Mycosis Fungoides (MF) and Sezary Syndrome (SS) were identified by querying our institutional database using ICD codes. Second malignancies were determined through chart review with confirmation by diagnostic pathology and clinical history. For pts with concurrent CTCL and HL, CTCL presentation was defined as symptom onset per patient self-report or clinical history. Incidence of HL in the general population was obtained from the SEER Cancer Statistics Review. Pt characteristics and clinical outcomes are reported through July 2015.

Results: In our cohort of 1,995 CTCL pts, we identified 192 (10%) pts with second malignancies [66 (3%) second hematologic malignancies, 107 (5%) second epithelial malignancies, and 30 (2%) second dermatologic malignancies excluding basal cell and squamous cell carcinoma of the skin]. Ten (1%) pts had third primary malignancies. Of those with second malignancies, 46 (24%) had B-cell malignancies including 31 with non-Hodgkin B-cell lymphomas and 4 with multiple myeloma. Twelve CTCL pts (0.6 % of the total CTCL cohort) developed HL, an incidence 3 times higher than the general population. Of pts with concurrent HL and CTCL, 11 (92%) had MF, 1 (8%) had SS, 8 (67%) were male and 9 (75%) were Caucasian. Nine (75%) were diagnosed with HL after CTCL presentation and 2 (17%) were diagnosed with CTCL within one year after HL diagnosis. Only 1 patient (8%) had a distant history of HL prior to CTCL presentation. Median age at HL diagnosis was 60 years (range 33-82). Six (50%) pts had nodular sclerosing subtype, 2 (17%) had mixed cellularity, and 4 (33%) were not specified. In the 8 patients who had EBV staining performed on HL biopsies, 2 (25%) were EBV positive. Two (17%) pts had single nodal involvement by both CTCL and HL. At presentation, 2 (17%) pts had B symptoms and 1 pt had advanced (Ann Arbor stage III) HL. Only one pt had received immunosuppressive CTCL-directed chemotherapy (pentostatin) prior to HL diagnosis, while 3 (25%) pts had phototherapy, and 1 had local radiation. In all pts, HL was treated with standard anthracycline-based chemotherapy with 8 (67%) pts receiving consolidative radiotherapy. Two (17%) pts required salvage therapy for progressive HL. There were no unique complications of HL therapy reported and all pts ultimately achieved complete remission of their HL. Six of 12 pts with HL expired (Figure, median follow up 51 months), with no deaths attributable to HL. Four (33%) pts died of CTCL or complications of therapy. While the course of CTCL varied in this cohort, any CTCL response to HL-directed therapy was transient and 8 pts (67%) had active CTCL at time of last follow-up. Three (25%) pts with HL had a third primary cancer during their lifetime (malignant melanoma, therapy-related acute myeloid leukemia, esophageal adenocarcinoma).

Conclusions: In this large institutional cohort, we identified 12 cases of concurrent CTCL and HL. We demonstrated an increased incidence of HL in the CTCL population. Compared to HL pts in the general population, those with concomitant CTCL appear to present in older age and with limited stage disease. Although the sample is small, our cohort tolerated HL therapy without unexpected toxicities and had excellent HL outcomes. Since most pts presented with HL prior to requiring systemic CTCL treatment, we conclude the etiology of CTCL-associated HL is more likely related to intrinsic vs. treatment-related immune dysregulation. Better understanding of HL features in relation to CTCL may guide clinical management for this complex population. The potential role of underlying T-cell biology will be studied in subsequent investigations.

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