Low Absolute Lymphocyte Counts in the Peripheral Blood Predict Inferior Survival and Improve the International Prognostic Index in Testicular Diffuse Large B-Cell Lymphoma.

Low absolute lymphocyte counts (ALC) and high absolute monocyte counts (AMC) are associated with poor survival in patients with diffuse large B-cell lymphoma (DLBCL). We studied the prognostic impact of the ALC and AMC in patients with testicular DLBCL (T-DLBCL). T-DLBCL patients were searched using Southern Finland University Hospital databases and the Danish lymphoma registry. The progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods. We identified 178 T-DLBCL patients, of whom 78 (44%) had a low ALC at diagnosis. The ALC did not correlate with survival in the whole cohort. However, among the patients treated with rituximab (R) containing regimen, a pre-therapeutic low ALC was associated with an increased risk of progression (HR 1.976, 95% CI 1.267-3.086, p = 0.003). Conversely, intravenous (iv) CNS directed chemotherapy translated to favorable outcome. In multivariate analyses, the advantage of an iv CNS directed chemotherapy was sustained (PFS, HR 0.364, 95% CI 0.175-0.757, p = 0.007). The benefit of R and intravenous CNS directed chemotherapy was observed only in non-lymphopenic patients. The AMC did not correlate with survival. A low ALC is an adverse prognostic factor in patients with T-DLBCL. Alternative treatment options for lymphopenic patients are needed.

Clinical features and outcome of the patients with sinonasal tract diffuse large B-cell lymphoma in the pre-rituximab and rituximab eras.

PURPOSE: Sinonasal tract diffuse large B-cell lymphoma (SNT-DLBCL), a rare extranodal lymphoma, is not well characterized. We performed a population-based study to determine cell-of-origin, clinical presentation and impact of rituximab (R) and central nervous system (CNS) directed chemotherapy on survival. PATIENTS AND METHODS: Patients with SNT-DLBCL were identified from pathology databases. Clinical information was collected and outcomes between different treatment modalities evaluated. RESULTS: Thirty-two percent of the patients had germinal centre B-cell phenotype. Forty-six patients were treated with curative intent using CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like chemotherapy, 21 (46%) before and 25 (54%) in the R-era. Additionally, 24 (52%) received CNS-directed chemotherapy. Addition of R to chemotherapy reduced the risk of progression (RR = 0.368, 95% CI 0.138-0.976, P = 0.045) and death (RR = 0.245, 95% CI 0.068-0.883, P = 0.032), and translated into better survival (5-year PFS, 67% vs 38%, P = 0.037; 5-year OS, 81% vs 48%, P = 0.020). CNS-directed chemotherapy reduced the risk of progression (RR = 0.404, 95% CI 0.159-1.029, P = 0.057) and death (RR = 0.298, 95% CI 0.093-0.950, P = 0.041), and translated into favorable survival (5-year PFS, 67% vs 32%, P = 0.050; 5-year OS 82% vs 43%, P = 0.030). CONCLUSION: Patients with SNT-DLBCL benefit from rituximab and CNS-directed chemotherapy.

PD-L1+ tumor-associated macrophages and PD-1+ tumor-infiltrating lymphocytes predict survival in primary testicular lymphoma.

Primary testicular lymphoma is a rare and aggressive lymphoid malignancy, most often representing diffuse large B-cell lymphoma histologically. Tumor-associated macrophages and tumor-infiltrating lymphocytes have been associated with survival in diffuse large B-cell lymphoma, but their prognostic impact in primary testicular lymphoma is unknown. Here, we aimed to identify macrophages, their immunophenotypes and association with lymphocytes, and translate the findings into survival of patients with primary testicular lymphoma. We collected clinical data and tumor tissue from 74 primary testicular lymphoma patients, and used multiplex immunohistochemistry and digital image analysis to examine macrophage markers (CD68, CD163, and c-Maf), T-cell markers (CD3, CD4, and CD8), B-cell marker (CD20), and three checkpoint molecules (PD-L1, PD-L2, and PD-1). We demonstrate that a large proportion of macrophages (median 41%, range 0.08-99%) and lymphoma cells (median 34%, range 0.1-100%) express PD-L1. The quantity of PD-L1+ CD68+ macrophages correlates positively with the amount of PD-1+ lymphocytes, and a high proportion of either PD-L1+ CD68+ macrophages or PD-1+ CD4+ and PD-1+ CD8+ T cells translates into favorable survival. In contrast, the number of PD-L1+lymphoma cells or PD-L1- macrophages do not associate with outcome. In multivariate analyses with IPI, PD-L1+ CD68+ macrophage and PD-1+ lymphocyte contents remain as independent prognostic factors for survival. In conclusion, high PD-L1+ CD68+ macrophage and PD-1+ lymphocyte contents predict favorable survival in patients with primary testicular lymphoma. The findings implicate that the tumor microenvironment and PD-1 - PD-L1 pathway have a significant role in regulating treatment outcome. They also bring new insights to the targeted thera py of primary testicular lymphoma.

Clinical findings in 25 patients with sinonasal or nasopharyngeal extramedullary plasmacytoma in a four-decade single-centre series.

OBJECTIVES: Extramedullary plasmacytoma in the sinonasal tract or nasopharynx is rare. The aim of the study was to review data on symptoms, clinical findings, treatment and follow-up of plasmacytomas in the sinonasal and nasopharyngeal regions in order to delineate the main clinical characteristics and the optimal management. METHOD: Twenty-five patients with sinonasal or nasopharyngeal plasmacytoma, diagnosed and treated at the Helsinki University Hospital during a 39-year period from 1975 to 2013 were retrospectively reviewed. RESULTS: There were 18 males and 7 females with a median age of 66 years (range, 36-80). Sixty-eight percent received only radiotherapy or (chemo)radiotherapy. Forty-seven percent of them had a complete response to primary radiotherapy and one patient had a complete response after receiving additional brachytherapy. Four patients were treated primarily with surgery only. Two of them had a local recurrence, but were then successfully treated with radiotherapy. Altogether, four patients received a combination of surgery and (chemo)radiotherapy. Forty-four percent were alive with no evidence of disease after a median follow-up time of 78 months. Forty percent died of their disease and 16% died of other causes. CONCLUSIONS: Our study supports radiotherapy as a treatment of choice, but for small tumours surgery alone or in combination with radiotherapy may also be considered.

Clinical findings of extranodal SNT lymphoid malignancies in a four-decade single-centre series.

Sinonasally located lymphoid malignancies are rare lesions with first symptoms similar to other obstructive conditions. Additionally, they often coexist with nasal inflammation and mucosal necrosis. Therefore, time from the first symptoms to diagnosis tends to be long. Awareness and early diagnosis of this disease entity could improve treatment outcome. Altogether, 142 patients with sinonasal or nasopharyngeal (i.e. sinonasal tract, SNT) lymphoid malignancies, diagnosed and treated at the Helsinki University Hospital, during a 39-year period from 1975 to 2013, were retrospectively reviewed. There were 90 males (63 %) and 52 females (37 %) with a median age of 64 years (range 26-92). Eighty-four percent of the patients had primary diseases and 16 % had relapses of lymphoid malignancies primarily diagnosed at other locations. The mean duration of symptoms prior to diagnosis was 4.8 months (range 0.5-24). The most common histological entity was diffuse large B-cell lymphoma (43 %), followed by plasmacytoma (18 %). The most common location was nasopharynx (58 %) followed by nasal cavity (44 %) and paranasal sinuses (35 %). Sixty-nine percent of the lesions were at a single anatomic location of the sinonasal tract. Fifty-two percent of the cases were of Ann Arbor Stage I. Lymphoid malignancies form an important and diverse group in the differential diagnosis of SNT tumours. They most often present with general obstructive nasal symptoms due to tumour location. Most of them are primary lesions, highlighting the importance of an accurate diagnosis as early as possible.