Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy.

Contrast-enhanced ultrasonography (CEUS) use for detecting lymphoma in the spleen was questioned because of the risk of its inadequate diagnostic accuracy. The aim of the present study was to validate CEUS exam for the identification of spleen involvement by lymphoma in patients at risk. A total of 260 nodules from the spleens of 77 patients with lymph node biopsy-proven non-Hodgkin lymphoma (NHL; n = 44) or Hodgkin lymphoma (HL; n = 33) at staging (n = 56) or follow-up (n = 21) were collected in a hematology Italian center and retrospectively analyzed. Nodules were classified as malignant lymphoma if ≥0.5 cm (long axis) with arterial phase isoen-hancement and early (onset <60 s after contrast agent injection) wash-out of marked (≤120 s after contrast agent injection) degree. Other perfusional combinations at CEUS scans qualified lesions as benign or inconclusive. Diagnostic reference standard was clinical laboratory imaging monitoring for 230 nodules, and/or histology for 30 nodules. The median nodule size was 1.5 cm (range 0.5–7 cm). According to the reference standard, 204 (78%) nodules were lymphomas (aggressive-NHL (a-NHL), 122; classic-HL (c-HL), 65; indolent (i)-NHL, 17) and 56 (22%) were benign (inflammation, infection, and/or mesenchymal) lesions. Sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy of CEUS for detecting lymphoma in the spleen were 95%, 100%, 100%, 85%, and 96%, respectively. Marked wash-out range of 55–90 s (median, 74 s), 92–120 s (median, 100 s), and 101–120 s (median, 114.5 s) was 100%, 96.6%, and 77% predictive of a-NHL, c-HL, and i-NHL splenic nodular infiltration, respectively. The CEUS perfusional pattern of arterial phase isoenhancement with early wash-out of marked degree was highly accurate for the detection of lymphomatous invasion of spleen in patients at risk, enabling its use for a confident non-invasive diagnosis.