A Case of Nasal Cavity and Laryngeal Involvement of Rosai–Dorfman Disease

Rosai–Dorfman disease (RDD) is a rare non-malignant disorder, characterized by painless multiple cervical lymphadenopathy, fever, and elevated inflammatory markers. Its diagnosis is difficult due to its rare incidence and various clinical presentations, especially in extranodal involvement. In this report, we demonstrate a patient with RDD who presented with a nasal septum and laryngeal tumor that caused dyspnea. We achieved a successful treatment outcome with combined surgical resection of the laryngeal mass and corticosteroid medication. The symptoms and tumors were resolved within 3 weeks after treatment. We reported our experiences with review of literatures.

Central Nervous System Involvement By Mantle Cell Lymphoma

Background: While extranodal involvement by mantle cell lymphoma (MCL) is relatively common, involvement of the central nervous system (CNS) is rare (<5% of cases), with limited treatment options. We report the outcomes of 36 patients (pts) with CNS involvement compared to 72 matched control MCL pts without CNS involvement. Methods: MCL pts with CNS involvement seen at Mayo Clinic between 1/1995-9/2020 were identified using the Mayo Data Explorer tool. CNS involvement was defined by tissue biopsy confirmed CNS MCL, CSF analysis demonstrating lymphoma cells, and/or neuroimaging findings compatible with CNS involvement. A 2:1 control group of MCL pts without CNS involvement, matched by age (+/- 2 years) and year of diagnosis (+/- 1 year), was selected among all MCL cases. Medical records were reviewed for baseline characteristics, treatment modalities, and outcomes. Kaplan-Meier method was used for time to event analysis. Wilcoxon test was used to compare continuous variables and Chi square test was used for categorical variables. Results: Out of 1,753 pts with MCL, 36 (2%) had evidence of CNS involvement, including 4 pts with CNS involvement at initial MCL diagnosis. Baseline characteristics of pts with CNS involvement (CNS MCL group) and those without CNS involvement (control group) are shown in Table 1. At MCL diagnosis, non-CNS extranodal involvement was seen in 30 (83%) pts in the CNS MCL group (24 pts with 1 site and 6 pts with ≥ 2 sites), with bone marrow being the most common extranodal site of involvement (n=24, 67%). For the control group, 54 (75%) pts had extranodal involvement (44 pts with 1 site and 10 pts with ≥ 2 sites), and bone marrow was also the most common extranodal site of involvement (n=50, 69%). Notably, advanced stage disease (stage 3-4) was more commonly seen in the CNS MCL group (n=32, 97%) than in the control group (n=59, 83%) (p=0.04) at MCL diagnosis. Blastoid variant was present in a higher proportion of pts in the CNS MCL group (n=11, 31%) compared to the control group (n=8, 11%) (p=0.02). The CNS MCL group also presented with a higher median serum LDH at diagnosis (239 U/L [range 153-1901] vs. 187 U/L [range 124-588], p=0.02), and higher Ki-67 (40% [range 15-100] vs. 30% [range 10-90], p=0.04) compared to the control group. The most common frontline treatment regimen was anthracycline-based therapies (i.e. R-CHOP, Nordic regimen, R-hyperCVAD) for both groups (58% in CNS MCL group and 56% in control group). 14 (39%) pts in the CNS MCL group underwent autologous stem cell transplant in CR1 vs. 31 pts (43%) in the control group. Similar use of rituximab maintenance was seen in both groups (31% in CNS MCL group and 25% in control group). Median total lines of therapy from initial MCL diagnosis was 3 (range 1-9) in CNS MCL group and 2 (range 1-9) in the control group. The median follow-up from MCL diagnosis was 134 months (95% CI:119-163) for the entire cohort. Median OS from MCL diagnosis was 50.3 months (95% CI: 20.9-71.1) for the CNS MCL group compared to 97.1 months (95% CI: 82.6-192.7; p=<0.001) for the control group (Figure 1). Median time from MCL diagnosis to CNS involvement was 25 months (range 0-167). Median OS from CNS involvement was 4.7 months (95% CI: 2.3-6.7). At last follow up, 31 (86%) pts were deceased from the CNS MCL group, compared to 38 (52%) pts in the control group. For the CNS MCL group, the causes of death were CNS lymphoma in 10 (32%) pts, systemic lymphoma in 9 (29%) pts, treatment-related complication in 7 (23%) pts, and other/unknown in 5 (16%) pts. For the control group, the causes of death were systemic lymphoma in 15 (39%) pts, treatment-related in 2 (5%) pts, and other/unknown in 21 (55%) pts. Conclusion: In pts with MCL, CNS involvement is associated with worse outcomes as evident by a shorter median OS from initial MCL diagnosis (50 months vs. 97 months). Involvement of the CNS by lymphoma is an important contributor for the shorter OS as suggested by the median OS of only 5 months from CNS involvement. Advanced stage, blastoid variant, elevated LDH, and elevated Ki67 at MCL diagnosis were features more commonly seen in the CNS MCL cohort. Validation of risk factors at initial MCL diagnosis associated with CNS involvement and exploring the role of CNS prophylaxis are important topics for further investigation. Figure 1 Figure 1. Disclosures Paludo: Karyopharm: Research Funding. Wang: Novartis: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Research Funding; InnoCare: Research Funding; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding. Bennani: Purdue Pharma: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Kyowa Kirin: Other: Advisory Board; Vividion: Other: Advisory Board; Kymera: Other: Advisory Board; Verastem: Other: Advisory Board. Nowakowski: Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene, NanoString Technologies, MorphoSys: Research Funding. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Habermann: Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Incyte: Other: Scientific Advisory Board; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding.

Peripheral T-Cell Lymphoma Involvement of the Central Nervous System: Impact of Novel Therapeutics on Clinical Outcomes

Primary Central Nervous System (CNS) involvement of peripheral T-cell lymphoma (PTCL) is a rare phenomenon, with a reported incidence ranging from 2% to 16.7%. Similarly, secondary CNS lymphoma with PTCL phenotype is rare, with an approximately 2-6% incidence. Both clinical situations lead to dismal outcomes. Given the rarity of CNS involvement with PTCL, our understanding of this clinical manifestation is limited to retrospective studies, which have identified risk factors for CNS involvement such as extranodal involvement, stage III-IV disease, bone marrow involvement as well as ATLL subtype. Herein, we characterize CNS involvement of PTCL over a 26-year time period at a single institution, identify if there are any factors that have a positive impact on survival, and extrapolate risk factors for CNS involvement from this dataset. From the years 1996-2020, 222 patients were diagnosed with PTCL, of those, 25 patients developed CNS involvement. All patients had secondary CNS involvement. Baseline characteristics including first-line therapy are noted in Table 1. Four patients received intrathecal methotrexate for CNS prophylaxis, all of which were patients with an ATLL diagnosis. The median time from initial diagnosis to CNS involvement was 4.77 months (0-64 months). Upon CNS diagnosis, the median time to death was 1.13 months. With a median of 2 lines of treatment (range 1-5), 12 patients were exposed to novel therapeutic agents (HDAC inhibitors [HDACis], brentuximab vedotin, pralatrexate) and/or clinical trials investigating epigenetic combinations. Of these patients, 10 patients were exposed to novel therapeutics and/or epigenetic based clinical trials in the 2 nd line setting. There was a trend towards improved overall survival with exposure to novel therapeutics and/or treatment on epigenetic based clinical trials (p=0.1) (Figure 1). With the majority of patients surviving <6 months from CNS diagnosis, there were three excellent responders that survived >12 months, all of which were exposed to novel therapeutics. Two of the three excellent responders were diagnosed with CNS involvement upon initial diagnosis, while 1 patient relapsed in the fourth-line setting with CNS involvement. All three of the excellent responders were exposed to novel therapeutics, particularly pralatrexate as a commonality in the second line setting. Using logistic regression, an ATLL diagnosis, extranodal involvement, and a high ECOG score were associated with a higher risk of CNS involvement. Unlike other studies, a high IPI score was not associated with a predilection for CNS involvement. In conclusion, we describe one of the largest single-center collection of CNS PTCL involvement. CNS involvement of PTCL is rare, with a reported cumulative incidence in this cohort of 11.3% over a 26-year time period. Risk factors that were identified include an ATLL diagnosis, extranodal involvement, and poor performance status. Exposure to novel therapeutics leads to a trend towards improved outcomes possibly secondary to improved disease control, but overall, the majority of patients had dismal outcomes. Notably, of the novel therapeutics interrogated, romidepsin and pralatrexate have low penetrance into the CNS, while there is no current evidence to suggest brentuximab vedotin is able to cross the blood-brain barrier. The possibility of a disturbed blood-brain barrier to permit improved penetrance of these drugs is plausible, but further studies are warranted to support this. Although a small percentage of patients will suffer from CNS PTCL, there is a dire need to improve therapy for this patient population and to establish universal metrics to identify patients that are at risk of CNS involvement. Moreover, given the rarity of CNS PTCL involvement, a future endeavor would be to validate these findings in larger, multicenter initiative. Figure 1 Figure 1. Disclosures Lue: AstraZeneca: Speakers Bureau; Kymera Therapeutics: Research Funding; TG Therapeutics: Consultancy; Epizyme: Consultancy; Kura Oncology: Consultancy. Marchi: Astex: Research Funding; Kyowa Kirin: Honoraria; Merck: Research Funding; BMS: Research Funding; Myeloid Therapeutics: Honoraria; Kymera Therapeutics: Other: Scientific Advisor. O'Connor: Myeloid Therapeutics: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Servier: Research Funding; Kymera: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astex: Research Funding; BMS: Research Funding; Merck: Research Funding; TG Therapeutics: Current Employment, Current equity holder in publicly-traded company.

Clinicopathological Features and Outcomes of EBV Positive and Negative DLBCL: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Introduction: Studies conducted in the pre-rituximab era found EBV positive diffuse large B-cell lymphoma (EBV+ DLBCL) as a disctinct entity carrying a dismal prognosis when compared with EBV negative (EBV-) DLBCL cases. However, studies evaluating this disparity in the rituximab era are lacking. Therefore, we aim to investigate the clinicopathological features and outcomes patterns among EBV+ and EBV- DLBCL managed in the modern era. Methods: We retrospectively analyzed patients 18 years and older diagnosed with DLBCL between 2006 to 2020. Seven centers from the Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL) participated in the study. Hematopathologists at each participating institution reviewed the pathological samples to confirm the diagnosis of EBV+ or EBV- DLBCL, not otherwise specified (NOS). EBV infection was confirmed with a positive EBER test ≥1%. The primary endpoint was overall survival (OS), defined as the time from the date of diagnosis until death from any cause or last follow up. The secondary endpoint was progression-free survival (PFS) defined as the time from diagnosis until death, progression, or last follow up. OS and PFS probabilities were computed with the Kaplan-Meier method and compared using the log-rank test. We used Cox regression analysis to evaluate the proportional hazard ratios (HRs) of each score for our study outcomes. Outcomes with a p-value <0.05 were considered statistically significant. Results: A total of 119 patients with EBV+ DLBCL, NOS and 122 patients with EBV- DLBCL, NOS were included in this analysis. The median age at diagnosis was 58 years (range 19-86 years) with an slight female (53%) predominance. Most cases (68%) had advanced stage (III/IV) at diagnosis. EBV+ DLBCL patients had higher-risk clinical features compared with EBV- DBCL: 34% presented ECOG performance status ≥2 (vs 18%, p=0.010), 45% had poor risk R-IPI score (vs 29%, p=0.03), 47% had high and high-intermediate risk NCCN IPI score (vs 40%, p=0.002). Germinal center B-cell was the most common phenotype in both groups (46% each); non-germinal center was more common in EBV+ (44%) than EBV- (34%). All patients received either R-CHOP (95%) or R-EPOCH (5%) as first-line treatment. The overall response rate was 91% for EBV- DLBCL (complete response, CR 81%) compared to 74% for EBV+ DLBCL (CR 65%, p=0.015). With a median follow-up of 60 months, the 5-year OS rates for EBV+ and EBV- DLBCL were 64% and 75% (p=0.062; Fig 1A), respectively; whereas the 5-year PFS rates for EBV+ and EBV- DLBCL were 53% and 68% (p=0.031; Fig 1B), respectively. In the univariate analysis, ECOG ≥2, extranodal involvement >1, elevated serum lactate dehydrogenase (LDH), and serum albumin <3.5 g/dL were statistically significant for OS (Table 1). On the other hand, EBV+ status, ECOG performance status ≥2, extranodal involvement >1, elevated serum LDH, and serum albumin <3.5 g/dL were significant predictors for PFS. In the multivariate analysis, no variable was statistically significant for OS or PFS (Table 1). Conclusions: In this large cohort of Latin American patients with EBV+ DLBCL, we found poor clinical features in EBV+ compared to EBV-DLBCL cases. Although shorter PFS was found in EBV+ DLBCL cases, in the multivariate analysis we could not identify EBV status as an independent risk factor for worse survival. Our results suggest that in the rituximab era, there has been an improvement on the survival outcomes of EBV+ DLBCL, NOS patients managed with chemoimmunotherapy. We are currently validating our findings in a prospective cohort of DLBCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality and relapse. Figure 1 Figure 1. Disclosures Ramirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Oliver: Abbvie: Other: conference support and fees ; Roche: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Combined Plasma Fibrinogen and Neutrophil-Lymphocyte Ratio As a Predictive Factor in Patients with Diffuse Large B-Cell Lymphoma

Background: A growing number of epidemiological evidence supports that the coagulation cascade and tumor-associated inflammatory indicators are related to the recurrence and survival of diffuse large B-cell lymphoma (DLBCL). Plasma fibrinogen and neutrophil-lymphocyte ratio (F-NLR) is a novel hallmark that is proposed as an adverse prognosticator in a variety of malignancies. The purpose of this study was to investigate the prognostic impact of the F-NLR score in DLBCL. Methods: In this retrospective study, 231 patients with DLBCL treated between October 2013 to January 2020 at Shandong Provincial Hospital were included. The critical values of fibrinogen and NLR were determined according to receiver operating characteristic (ROC) curve analysis. The included population was stratified into three groups according to the F-NLR score. The prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were screened by multivariate Cox regression analyses and log-rank test. Results: Within the 231 patients analyzed, 55.4% male and 44.6% female were enrolled in this study. There were 138 (59.7%) patients under 60 years old, with mean age of 55.23±15.02 years old. A total of 184 (79.7%) patients had advanced stage (III or IV) disease, and the great majority of people were defined as non-GCB (64.1%) subtypes and had extranodal involvement (86.6%). The cutoff value was identified as 3.12 for NLR (AUC: 0.628), 4.05 g/L for fibrinogen concentrations (AUC: 0.616), and the AUC value was 0.676 for the F-NLR (Fig 1) by OS outcome. The median follow-up period for all patients was 22 months, ranging from 1 to 90 months. After median follow-up time, 101 (43.7%) patients relapsed or progressed and 77 (34.2%) patients died during or after first-line therapy in total. In the further univariate and multivariate analyses, we demonstrated that F-NLR (HR=1.953, 95%CI=1.404-2.717, P=0.000) was an independent prognostic factor of DLBCL survival. We calculated the β for OS value of NLR and fibrinogen according to Cox regression equation. Since the HR for OS of each marker is approximation, we assigned the same weight to each factor in the prognostic scoring model (F-NLR). The model was simplified to 3 groups with F-NLR score of 0: neither hyperfibrinogenemia nor high NLR (low risk; 39.8% of pts), F-NLR score of 1: one of these hematological abnormalities (intermediate risk; 38.5% of pts), or F-NLR score of 2: both hyperfibrinogenemia and high NLR (high risk; 21.7% of pts). As a result, the PFS and OS were significantly worse in DLBCL pts with an F-NLR score of 2 than those with an F-NLR score of 0-1 (P=0.002 Fig 2A, P=0.000 Fig 2B). Moreover, the F-NLR score is significantly associated with clinical outcomes in elderly pts with advanced stage (III or IV) or extranodal involvement through subgroup analysis. Conclusion: This study validates that the F-NLR score, a new inflammation-based grading system, is a promising clinical predictor for DLBCL especially elderly patients with advanced stage (III or IV) or extranodal involvement. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Primary cutaneous precursor B-cell lymphoblastic lymphoma with concomitant skin and nodal involvement in a child

Primary cutaneous B-cell lymphoblastic lymphoma (PB-LBL) is an exceedingly rare malignant neoplasm in children. Skin lesions may represent the initial sign. Herein, we report a case of a PB-LBL with cutaneous lesions as a primary extranodal involvement, occurring in a 5-year-old infant.

A comparative study of non-Hodgkin lymphoma between public versus private institution in a middle-income country: A report of 2,317 cases.

e19569 Background: Non-Hodgkin lymphoma (NHL) is the most frequent hematological malignancy. B-cell (BCL) and T-cell (TCL) NHL subtypes differs in high income and low-and middle-income countries. In Peru, the healthcare system is divided mainly into public and private institutions. We aimed to describe the subtypes of NHL seen according to healthcare facilities. Methods: We reviewed medical records at National Cancer Institute and Oncosalud, both the leading public and private cancer centers in Peru, respectively. All patients diagnosed with NHL from 2015-2018 according to the 2016 WHO classification were included. Baseline characteristics were compared between public and private institutions using Student’s t test and Chi-square as appropriate. Results: A total of 2,317 NHL were included from both institutions. The median age was 61 years (range 15-99), 49.7% were male. Most patients NHL cases were encountered at the public institution (88.9%, n = 2,059); 84.4% (n = 1,957) were BCL and 15.5% (n = 360) TCL. Differences of BCL and TCL frequencies were seen among institutions. More BCL cases were seen at the private institution (96.6%, n = 230 versus 83.9%, n = 1,727, respectively) whereas TCL were common in the public institution (16.1%, n = 332 versus 11.8%, n = 28, respectively) (p < 0.035). The most frequent BCL was DLBCL with 70.0% (n = 1209) and 49.6% (n = 114) seen in public and private institutions, respectively (p < 0.001). The second most frequent BCL was follicular lymphoma (FL) with 10.8% (n = 187) and 20.4% (n = 47) seen in the public and private institutions, respectively (p < 0.001). Chronic lymphocytic lymphoma (CLL) and Burkitt lymphoma (BL) were most frequent in private institution (CLL 7%, n = 16 vs. 3.5%, n = 60, p = 0.017; BL 3.9%, n = 9 vs. 1.2%, n = 21, p = 0.004). The most frequent TCL was peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) (27.7%, n = 92) for the public institution and mycosis fungoides (MF) (39.3%, n = 11) for the private institution. The second most frequent TCL was natural killer/TCL (NKTCL) (22.6%, n = 75) for the public institution, and PTCL, NOS (17.9%, n = 5) for the private institution. There was significant difference in the number of NKTCL and MF cases seen during the study period among institutions (NKTCL public 22.6%, n = 75 vs. private 3.6%, n = 1, p = 0.033; MF public 15.1%, n = 50 vs. private 39.3%, n = 11, p = 0.003). The presence of extranodal involvement was more frequent in the public institution (52.3%, n = 1,049 vs. 35.3%, n = 84, p < 0.001). Conclusions: The distribution of NHL differs according to the type of healthcare system in Peru. Extranodal involvement, TCL, DLBCL and NKTCL are more frequent in patients treated at the public cancer center than in private center. On the contrary BCL, FL, CLL, BL and MF are more frequent in private cancer center. Our institutions are currently building the largest registry of NHL patients diagnosed and treated in Peru.

Presentation of External Ear Rosai-Dorfman Disease With Laryngeal Involvement

Rosai-Dorfman disease (RDD) is a rare benign systemic histiocytic proliferation characterized by massive lymph node enlargement and sometimes associated with extranodal involvement. Even though it is considered to be benign, death can occur depending on the extent and location. Our case highlights a primary extranodal site of the right pinna with extension through the Eustachian tube to the subglottis. A previously healthy 15-year-old female presented with 1-year right pinna swelling, slowly enlarging and becoming more bothersome. An incisional biopsy was performed on the ear along with S100 staining yielding a diagnosis. After multidisciplinary case discussion, clofarabine monotherapy and systemic therapy for Langerhans cell histiocytosis has started. Rosai-Dorfman disease can be a general disorder, often affecting the lymph nodes. Unlike a nodal disease, extranodal disease could involve any site on the patient’s anatomy. Head and neck lesions are the most common extranodal lesions. Rosai-Dorfman disease is self-limited in more than 20% of the cases with spontaneous regression without intervention; 70% of the patients have noticeable symptoms and vital organ involvement requiring treatments such as surgery, steroids, radiation, and chemotherapy. In our case, the patient had wide involvement and presented without any serious breathing difficulties; we decided to start with monotherapy with chemotherapy and systematic glucocorticoid treatment.