Nodular Sclerosis Hodgkin Lymphoma Research Articles

Pulmonary Langerhans Cell Histiocytosis Post-Hodgkin Lymphoma Completely Resolved With Vinblastine in a Heavy Smoker: Coincidence or Causation?

The association among Langerhans cell histiocytosis, hematolymphoid malignancies, and heavy smoking has been addressed in medical literature to identify a possible potential link. Such occurrence can pose diagnostic challenges, as well as important clinical implications for disease progression and treatment approaches. We present pulmonary Langerhans cell histiocytosis instance in a 35-year-old male patient, with a 34-pack-year smoking history and nodular sclerosing Hodgkin lymphoma stage IIB who developed multiple bilateral lung nodules. The patient completed 6 cycles of doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine chemotherapy and radiotherapy 2 years earlier. CT chest scans revealed numerous micronodules scattered randomly throughout the upper and lower left lung lobes. Subsequent wedge resection exhibited cellular proliferation with grooved nuclei, eosinophilic cytoplasm, and surrounding inflammatory components. Immunohistochemical staining showed positive staining for S100 and CD1a confirming a diagnosis of pulmonary Langerhans cell histiocytosis. The patient responded to a 6-week treatment with vinblastine and prednisolone. A subsequent CT scan of the lungs revealed complete resolution after 3 years. This report underscores the importance of identifying pulmonary Langerhans cell histiocytosis in heavy smokers with Hodgkin lymphoma presenting with multiple nodular pulmonary lesions. For patients with Hodgkin lymphoma and a possible genetic predisposition, smoking may contribute to the overt development of pulmonary Langerhans cell histiocytosis. Therefore, smoking cessation and careful follow-up examinations are required. Further research is recommended to elucidate the underlying mechanisms of this intriguing association.

A Real-World Single-Center Study of Adult Hodgkin's Lymphoma

To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, β2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

High IL1-RA Plasma Levels at Baseline Allow to Identify Hodgkin Lymphoma Patients with High Risk of Treatment Failure

Introduction: About 10% of localized stages and 20-30% of advanced stages patients (pts) with classical Hodgkin lymphoma (cHL) progress or relapse after the first line of treatment. Therapeutic failures prediction at diagnosis is a major challenge to modulate treatments to minimize acute and long-term toxicities, while having optimal efficacy. The development of prognostic tools is crucial to help therapeutic decision. In 2007, Casasnovas et al. JCO 2007, demonstrated that a plasma cytokine signature composed of IL1-RA, IL-6 and sCD30 could predict pts outcomes and identify pts with high risk of treatment failure. However, it was unusable in routine practice as the ELISA technique used had extensive delay. Since interim PET during induction chemotherapy became the standard approach to guide the therapeutic strategy, and therefore the use of new pre-therapeutic biomarkers deserves to be investigated in the context of PET-guided treatment. As PD-L1, and thymus and activation-related chemokine (TARC) have an important role in cHL physiopathology we analyzed the prognostic impact on progression-free, and overall survival (PFS and OS) of pretherapeutic plasma levels of PD-L1 and TARC in addition to IL1-RA, IL-6, sCD30, in pts treated with a PET-guided strategy. Method: The dosage of IL1-RA, IL-6, PD-L1 and TARC was performed using the ELLA automated immunoassay system (Biotechne) while sCD30 was performed in triplicate using ELISA assay. Samples were prospectively collected (period 2016-2020) within the biocollection BIO-LYMPH (NCT04417803) in the pts treated in the department of Hematology at Dijon Hospital. X tile analysis was used to define the optimal cutoff for survival prediction for each cytokine. Survival functions of pts' subgroups defined by the cytokine circulating levels were estimated using the Kaplan-Meier product limit method and compared using the log rank test. The Cox proportional hazard regression model was used to estimate HRs and associated 95% CI in univariate and multivariate analyses. Results: Among the 105 pts enrolled in this study (Median age: 36 years, range: 17 - 85), 60% were under 45 years, 61% had advanced stage disease, 58% B symptoms, and 39% an IPS &amp;gt;2. 63% of pts had nodular sclerosis HL subtype and 22% had EBV associated HL. Response was assessed at the end of treatment: 89 pts (84 %) achieved a complete response, 4 pts (4%) a partial response, and 9 pts (9%) had progressive disease. With a median follow-up time of 40 months (1-78 months), 13 pts (12 %) relapsed with a median time to relapse of 16 months (range, 4 to 65 months), 14 pts (13 %) died (11 due to cHL progression; 1 due to septic shock; 1 from SARS covid infection; and 1 after a traumatism). While pretherapeutic plasmatic levels of IL-6, sCD30, TARC and PD-L1 did not impact pts survival, IL1-RA was an independent predictor of both PFS and OS. Indeed, 31% of pts harbored high IL1-RA plasma level (≥ 740 pg/ml) and had an unfavorable PFS (5y-PFS: 50.2% vs 86.7%; HR=4.2, CI=2.1-10.3, p=0.0001, figure 1A) and OS (5y-OS 71.4% vs 95%, HR=4.49, CI=1.3-14.2, p=0.006). PET2 positivity (17% of pts) had an unfavorable prognosis value on PFS (5y-PFS 58% vs 86.6%, HR 4.3, CI= 1.4-12.8, p=0.014) but not on OS (5y-OS 91.8% vs 74.1%; HR=3.2 CI=0.7-14.4, p=0.15) independent from pretherapeutic IL1-RA plasma level (PFS multivariate analysis: PET2 positivity HR=2.43, CI=1-6, p= 0.05; High level IL1-RA HR= 3.4, CI=1.5-8.3, p= 0.005). The combination of both PET2 results and pretherapeutic IL1-RA plasma levels allow to stratify pts' outcome into 3 groups (figure 1B): - Pts (57%) with low levels of IL1-RA and negative PET2 had a 5y-PFS of 89.3% and 5y-OS of 95.8%, - Pts with high levels of IL1-RA or positive PET2 (35%) had a 5y-PFS of 57% and 5y-OS of 74.8% whereas - Pts with both (8%) had a 5y-PFS of 42.9% and 5y-OS of 71.4%. The groups with one or 2 prognostic factors (PET2+ or high IL1RA and PET2+ &amp; high IL1RA) had a significantly different PFS compared to the double negative group (1 factor: HR=4.7, CI=1.8-12.2, p=0.0011 and 2 factors: HR= 8.57, CI=2.5-28.3, p=0.0004 respectively). The group with 1 prognosis factor had a significantly different OS (HR=4.1, CI=1.1-15.3, p=0.03) compared to double negative group but not the 2 factors group (HR= 4.9, CI=0.8-30, p=0.08). Conclusion: Pretherapeutic IL1-RA plasma levels allow to stratify the prognosis of pts with cHL treated with first line PET-guided strategies and add prognosis information to PET2 response.

Deceptive Presentation of Low-Grade Lymphoma with Grade 3 Marrow Fibrosis and Aplasia: Diagnostic and Clinical Considerations

AbstractBone marrow fibrosis with lymphoproliferative disorders is rare with the exception of hairy cell leukemia and nodular sclerosis Hodgkin's lymphoma. We report the case of a 63-year-old gentleman with indolent B-cell lymphoma presenting with myelofibrosis and aplasia. He was evaluated for pancytopenia with no organomegaly or lymphadenopathy. Bone marrow aspiration was a dry tap and biopsy revealed a hypocellular marrow with a cellularity of 10 to 20% with absent megakaryocytes and grade 2 to 3 reticulin fibrosis. Myeloproliferative neoplasms were ruled out based on morphology and absence of myeloid mutations on next-generation sequencing. Further sections revealed interstitial infiltrates of lymphoid cells with round, clumped chromatin and inconspicuous nucleoli, which on immunohistochemistry (IHC) were positive for CD20 and BCL2, and negative for CD5, CD10, BCL6, annexin A1, cyclin D1, and TdT. The final diagnosis was thus confirmed as CD5-negative low-grade B-cell lymphoma and he was initiated on therapy with a combination of Bendamustine and Rituximab. He had resolution of symptoms and cytopenia after six cycles of the same. Presence of significant myelofibrosis on the background of a hypocellular marrow can mimic several subtypes of myeloproliferative neoplasms or myelodysplastic syndromes, providing a diagnostic challenge. IHC is essential in determining the exact subtype to decide further therapy. Based on literature search, only a handful of patients with this presentation have been described and this case will be a valuable addition to the same.

Assessment of Changes in Tumor Volume Following Chemotherapy For Nodular Sclerosıng Hodgkin Lymphoma (NSHL)

Objective: Hodgkin lymphoma is a critical malignancy which may be seen during childhood and adolescence. Since it may be observed in younger patients, treatment strategies should be considered thoroughly to achieve optimal results in terms of local control and treatment related adverse effects. Systemic therapy plays a critical role in treatment of Hodgkin lymphoma. In this study, we evaluated changes in tumor volume following chemotherapy for nodular sclerosing Hodgkin lymphoma (NSHL).

Hodgkin lymphoma in the bone marrow aspirate of a young patient with human immunodeficiency virus.

Hodgkin lymphoma in the bone marrow aspirate of a young patient with human immunodeficiency virus.

Clinicopathologic and Immunohistochemistry Profile of Primary Mediastinal Large B-cell Lymphoma and Hodgkin Lymphoma Nodular Sclerosis in Mediastinum

Background&#x0D; Primary mediastinal large B-cell lymphoma (PMBCL) and Hodgkin nodular sclerosis (LHNS) lymphoma was the most common lymphomas involved the mediastinum. These two lymphomas had similar histopathological features. The purpose of this study was to analyzed clinical data, histopathological characteristics, and immunohistochemistry (IHC) profiles on PMBCL and LHNS.&#x0D; Methods&#x0D; This is a retrospective study. Data was collected from archive of Anatomical Pathology Department, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital in 2014-2020. The data collected included clinical data, hematoxylin-eosin (HE) and IHC slides and were reassessed by the researcher and supervisor. The histopathological characteristics data was analyzed statistically using statistical package for the social sciences version 25.0 with Chi-Square test.&#x0D; Results&#x0D; PMBCL and LHNS have similar histopathological features, included the characteristics of tumor cells and infiltration of many fibrosis and inflammatory cells, but difference in architecture, tumor cell types, clear cytoplasmic tumor cells, inflammatory cell and fibrosis types, with p value &lt;0.001. The characterized differences of PMBCL showed diffuse architecture, some cells with RS-like cell structure, clear/pale cytoplasm, lymphocyte cell infiltration, and compartmental fibrosis. Whilst, LHNS showed nodular architecture, Reed Sternberg cells, mixed inflammatory cell infiltration, and band-like fibrosis. PMBCL showed CD20, PAX5, MUM1 strongly positive, CD30 weakly positive, and CD15 negative, while LHNS showed negative CD20, CD30 and MUM1 strongly positive, PAX5 weakly positive, and CD15 positive.&#x0D;

Hodgkin lymphoma: 2023 update on diagnosis, risk-stratification, and management.

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8540 new patients annually and representing approximately 10% of all lymphomas in the United States. HL is composed of two distinct disease entities: classical HL and nodular lymphocyte-predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early-stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced-stage disease receive a longer course of chemotherapy, often without radiation therapy. However, newer agents, including brentuximab vedotin and anti-programmed death-1 (PD-1) antibodies, are now being incorporated into frontline therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, non-myeloablative allogeneic transplant, or participation in a clinical trial should be considered.

Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin Lymphoma.

Classical pediatric Hodgkin Lymphoma (HL) is a rare malignancy. Therapeutic regimens for its management may be optimized by establishing treatment response early on. The aim of this study was to identify plasma protein biomarkers enabling the prediction of relapse in pediatric/adolescent HL patients treated under the pediatric EuroNet-PHL-C2 trial. We used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics at the time of diagnosis—before any therapy—as semiquantitative method to profile plasma proteins specifically associated with relapse in 42 children with nodular sclerosing HL. In both the exploratory and the validation cohorts, six proteins (apolipoprotein E, C4b-binding protein α chain, clusterin, fibrinogen γ chain, prothrombin, and vitronectin) were more abundant in the plasma of patients whose HL relapsed (|fold change| ≥ 1.2, p < 0.05, Student’s t-test). Predicting protein function with the Gene Ontology classification model, the proteins were included in four biological processes (p < 0.01). Using immunoblotting and Luminex assays, we validated two of these candidate biomarkers—C4b-binding protein α chain and clusterin—linked to innate immune response function (GO:0045087). This study identified C4b-binding protein α chain and clusterin as candidate early plasma biomarkers of HL relapse, and important for the purpose of shedding light on the molecular scenario associated with immune response in patients treated under the EuroNet-PHL-C2 trial.

Occurrence and Severity of Adverse Reactions of Immune Checkpoint Inhibitors (PD-1 and PD L1) Based on Mordovian Dispensary Data Analysis

Background: Recently, a novel therapeutic technique has been revealed to recruit PDL1 and PD1 inhibitors to promote and enhance the cytotoxic T cell activity in combating the tumor. But unfortunately, several followed patients who didn’t tolerate the drug appeared unfavorable autoimmune side effects, such as anemia, pneumonitis, hepatitis, colitis, in addition to fatigue/ asthenia, decreased appetite, nausea, cough, dyspnea, constipation. Aim: To assess the severity of the adverse reactions of PD-1 and PD-L1 inhibitors in treating patients with positive PD-1 or PD-L1; non-small cell lung cancer patients (NSCLCs), small cell lung cancer (SCLC), nodular sclerosis Hodgkin lymphoma, classic Hodgkin's lymphoma, gastric cancer, renal cell carcinoma, caecal carcinoma, buccal mucosa carcinoma, nasopharyngeal carcinoma, laryngopharynx cancer, bladder cancer, cervical cancer, and melanoma. Materials and Methods: The study data was collected and analyzed randomly from the period of January 2019 to November 2020 from the Mordovian oncological dispensary. The data are collected from the electronic archive of the hospital. Then, we followed up with the patients for the same period, and we recorded the presented adverse reactions. The patients received anti-tumor drug; PD-L1/PD-L inhibitors (Atezolizumab; 1200mg, Pembrolizumab; 200mg, and Nivolumab; 240mg or 3 mg/kg) every 21 or 14 days they got IV infusion of PD-1 and/or PD-L1 inhibitors. After the progression and metastasis of the tumor, the patients received a combination of chemotherapy prior to the immunotherapy. Results: The analyzed data have shown 7.14% of the studied patients (n=28) have developed adverse reactions that ranged from mild to moderate severity (anemia and biochemical tests deviation). Conclusion: These clinical findings supported the moderate risk of developing life-threatening adverse reactions after administration of immune checkpoint inhibitors (Nivolumab, Pembrolizumab, Atezolizumab) to patients with advanced-stage tumors. The patients who were treated with PD-1 inhibitors developed less severe adverse reactions than patients who were treated with PD-L1 inhibitors. The adverse reaction severity depends on the period of administration and the type of the treated tumor, which consequently determines the dose of immunotherapy. Also, the aggressiveness of the autoimmune reactions depends on the patient's immune state and its reactivity.

Prognostic significance of CD163- and CD68-expressing macrophages in nodular sclerosis Hodgkin lymphoma

The objective of the study was to determine the clinical and morphological criteria and prognostic significance of CD163- and CD68-expressing macrophages in formalin-fixed paraffin-embedded (FFPE) lymph node samples of nodular sclerosis Hodgkin lymphoma.Materials and methods. We have studied clinical and laboratory characteristics and treatment results of 52 patients with newly diagnosed nodular sclerosis Hodgkin lymphoma. The treatment efficacy was assessed after 2–4 courses of chemotherapy by positron emission tomography combined with computed tomography scan (PET-CT) according to the Deauville scale.Results. In FFPE lymph node samples, differences in the localization and relative number of CD163-positive macrophages in patients of both study groups were determined. Morphometric counting of CD68-positive cells did not reveal statistically significant intergroup differences. The threshold of CD163-positive cells has been established. The relationship between the CD68 expression level and the response to frontline therapy was not revealed. The ratio of tumorassociated macrophages in each patient was assessed by the CD163/CD68 index. The threshold of the index was determined, which allows predicting the course of nodular sclerosis Hodgkin lymphoma.Conclusion. The following parameters could be used as additional morphological criteria for predicting the response to frontline therapy in patients with nodular sclerosis Hodgkin lymphoma: tissue distribution pattern and quantitative calculation of macrophage-histiocytic microenvironment subpopulation composition. The results could be used to risk group stratification of patients with nodular sclerosis Hodgkin lymphoma in order to predict the response to initial phase of therapy, as well as to determine personalized treatment approaches.

Clinicopathological features of syncytial variant nodular sclerosis Hodgkin lymphoma

The syncytial variant of nodular sclerosis Hodgkin lymphoma (SV-NSHL) is uncommon, and its clinicopathological features have not been well analyzed. In this study, we collected 142 cases of SV-NSHL. There were 76 (53.5%) males and 66 (46.5%) females with a median age of 28 years (range, 12-78); 59.9% were younger than 30 years. Patients usually presented with a mediastinal mass (97.6%) and often with bulky (35.7%) and advanced stage disease (3 or 4) (39.7%). Follow-up showed that 61.1% of patients developed relapse after standard therapy. Morphologically, the neoplasms were composed of sheets or large clusters of pleomorphic neoplastic cells with a cohesive appearance that were frequently associated with necrosis. Neutrophils and eosinophils were frequent in the background, whereas small lymphocytes were decreased. Immunohistochemical analysis showed that the following markers were frequently positive: CD30 (100%), MUM1/IRF4 (96%), PAX5 (95%), PD-L1 (91%), and CD15 (80%). CD45 was negative in all cases. Epstein-Barr virus-encoded small RNA (EBER) was detected in 19% of cases. In this cohort, age above 30 years (P=.0430), presence of B-type symptoms (P=.0394), elevated serum lactate dehydrogenase level (P=.0004), and disease relapse (P=.0108) were associated with a poorer overall survival. In contrast, patients with EBER-positive neoplasms had a better survival (P=.0418). Compared with a control group of non-SV-NSHL patients, patients with SV-NSHL were associated with a poorer overall survival (P=.011). These data suggest that SV morphology is associated with a poorer prognosis in patients treated with traditional standard-of-care therapy for classic Hodgkin lymphoma.

Axillary lymph nodes on PET in Hodgkin lymphoma after COVID-19 vaccination.

A 21-year-old woman presented with nodular sclerosis Hodgkin lymphoma stage IIIA, IPS 2 with a baseline 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) showing initial involved lymph nodes in both sides of the neck, left axilla, mediastinum, hili, para-aortic, left iliac, and involvement of the spleen. After one course of BrAVD (brentuximab-vedotin, adriamycine, vinblastine, dacarbazine), the interim FDG PET/CT scan was negative, classified as a complete metabolic response. A third FDG PET/CT scan was performed after completion of her chemotherapy consisting of six courses of BrAVD. This scan showed a reappearance of FDG avid lymph nodes, with a Deauville score of 5, in the original sites in the left axilla and neck. The most FDG avid lymph node was excised and revealed florid follicular hyperplasia instead of recurrence of Hodgkin lymphoma. In hindsight, she received a COVID-19 vaccination in her left arm several weeks prior to the last FDG PET/CT scan. In the meantime, various articles were published that relate the occurrence of FDG avid ipsilateral axillary and neck lymph nodes to COVID-19 vaccination of several manufacturers. We, therefore, concluded all FDG avid lymph nodes to be triggered by the vaccination. FDG PET/CT scan is valuable in steering therapy in Hodgkin lymphoma patients. However, enhanced FDG uptake only indicates that enhanced glucose metabolism and false positive results are possible, necessitating good clinical correlation. Documentation of the vaccination status including date(s), side, and manufacturer is of importance. In cancer patients, the side and timing of the vaccination should be discussed with the patient to prevent concern of recurrence and avoid unnecessary diagnostics and as in our case.

H2A.B is a cancer/testis factor involved in the activation of ribosome biogenesis in Hodgkin lymphoma.

Testis-specific regulators of chromatin function are commonly ectopically expressed in human cancers, but their roles are poorly understood. Examination of 81 primary Hodgkin lymphoma (HL) samples showed that the ectopic expression of the eutherian testis-specific histone variant H2A.B is an inherent feature of HL. In experiments using two HL cell lines derived from different subtypes of HL, H2A.B knockdown inhibited cell proliferation. H2A.B was enriched in both nucleoli of these HL cell lines and primary HL samples. We found that H2A.B enhanced ribosomal DNA (rDNA) transcription, was enriched at the rDNA promoter and transcribed regions, and interacted with RNA Pol I. Depletion of H2A.B caused the loss of RNA Pol I from rDNA chromatin. Remarkably, H2A.B was also required for high levels of ribosomal protein gene expression being located at the transcriptional start site and within the gene body. H2A.B knockdown reduced gene body chromatin accessibility of active RNA Pol II genes concurrent with a decrease in transcription. Taken together, our data show that in HL H2A.B has acquired a new function, the ability to increase ribosome biogenesis.

End-of-Treatment CT and Serial FDG-PET Imaging to Assess Residual Disease in Primary Mediastinal B-Cell Lymphoma

Background: Primary mediastinal B-cell lymphoma (PMBCL) is biologically related to classic nodular-sclerosis Hodgkin lymphoma. R-CHOP alone appears to be inadequate for many pts with retrospective studies indicating a benefit for consolidation XRT or use of intensive therapy regimens. End-of-therapy (EOT) FDG-PET is used to assess residual disease, but cannot accurately distinguish lymphoma from inflammation. We previously showed DA-EPOCH-R is effective in PMBCL, obviating the need for XRT in most pts, and showed that a positive EOT FDG-PET was typically not associated with treatment failure (Dunleavy et al. NEJM. 2013;368(15):1408-1416). We assessed the role of serial FDG-PET imaging to more accurately distinguish active disease from inflammation following DA-EPOCH-R for PMBCL.Methods: Ninety-three untreated PMBCL pts received DA-EPOCH-R without XRT. EOT FDG-PET was performed in 83 (89%) pts within 1 week of completing treatment and retrospectively scored per Deauville criteria in a blinded manner. Twenty-five (44%) of 57 pts with a negative (Deauville 1-3) EOT scan underwent follow-up FDG-PET imaging, mostly due to Deauville 3, which is no longer considered to indicate a positive FDG-PET scan. Twenty-three (88%) of 26 pts with a positive (Deauville 4-5) EOT scan underwent serial FDG-PET imaging approximately every 6 weeks. Three Deauville 4 pts (all non-progressors) did not have follow-up scans per protocol. If progressive SUV changes were noted on follow-up PET and/or size increase on concurrent CT, biopsy was attempted to confirm disease prior to implementing salvage therapy.Results: Characteristics were similar between the 83 pts with and 10 pts without evaluable EOT FDG-PET scans, aside from greater bulky tumor >/= 10 cm in the former group (63% vs. 20%, P = 0.014) (Table 1). All 93 pts were evaluable for response by CT with an ORR of 99% (88% CR, 11% PR). All 89 pts with complete tumor measurements had a reduction in the bi-dimensional product of the largest mediastinal tumor mass by CT. There was no relationship between EOT tumor reduction and EOT FDG-PET Deauville score (Figure 1). Furthermore, there was no difference in tumor reduction between pts with (6) and without (83) treatment failure (red arrows); median reduction 92% (range, 65-99) vs. 93% (range, 62-100), respectively (Figure 1).EOT FDG-PET scan was negative (Deauville 1-3) in 57 (69%) and positive (Deauville 4-5) in 26 (31%) pts. Disease progression occurred among 1/57 (2%) Deauville 1-3 pts, 1/18 (6%) Deauville 4 pts and 4/8 (50%) Deauville 5 pts. Two pts (both Deauville 5) died of progressive disease and 2 pts (Deauville 2 and 4, respectively) died without disease.In the 83 pts with EOT FDG-PET scans, 113 follow-up scans in 48 pts were performed (median, 1; range, 0-6). Pts with a negative EOT FDG-PET scan underwent a median of 0 (range, 0-4) scans compared to a median of 2 (range, 0-6) scans in pts with a positive EOT scan. Among pts who did not relapse/progress, the SUVmax remained relatively stable over time in the 21 pts with positive (Figure 2, upper) and 56 pts with negative EOT FDG-PET scans (data not shown). Five of 6 pts with treatment failure had a progressive increase in SUVmax on serial imaging (Figure 2, lower). Four of these pts (#2, 3, 5, and 6) had normalization of SUVmax following intervention (indicated by gray diagonal bars) with 1 pt (#1) having continued progression despite multiple salvage therapies. One patient (#4) with an elevated SUVmax at EOT had normalization of uptake following XRT.Conclusions: The degree of EOT tumor reduction by CT scan was unrelated to FDG-PET Deauville score or risk of disease recurrence. Negative EOT FDG-PET scans are highly predictive of cure following DA-EPOCH-R and further FDG-PET scanning should not be performed. Positive EOT FDG-PET scans were only indicative of residual disease in a minority of pts and should not be used alone to identify pts with residual disease. However, serial scans can identify pts with residual disease who require treatment. In conclusion, serial imaging should be performed in pts with positive EOT FDG-PET scans to accurately identify pts with disease. [Display omitted] DisclosuresAdvani:Merck: Research Funding; Agensys: Research Funding; Pharmacyclics: Research Funding; Nanostring: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Regeneron: Research Funding; Juno Therapeutics: Consultancy; Sutro: Consultancy; Infinity: Research Funding; FortySeven: Research Funding; Janssen: Research Funding; Pharmacyclics: Consultancy; Bayer Healthcare Pharmaceuticals: Research Funding; Cell Medica: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Kura: Research Funding; Gilead: Consultancy; Genentech: Research Funding; Spectrum: Consultancy; Millennium: Research Funding. Miljkovic:Pfizer Oncology: Research Funding.

NODULAR SCLEROSIS HOGDKINS LYMPHOMA GRADE 2 MIMICKING ANAPLASTIC LARGE CELL LYMPHOMA - A CASE REPORT

INTRODUCTION: Hodgkin's lymphoma (HL) is a lymphoproliferative neoplasm constituting less than 1% of all neoplasms. It has been categorized into- nodular lymphocyte predominant HL and classical type with subtypeslymphocyte rich, lymphocyte depleted, nodular sclerosis and mixed cellularity. Nodular sclerosis Hodgkin's lymphoma (NSHL) is difcult to diagnose on FNA because of the lack of Reed Sternberg (RS) cells, low cellularity and difculty in identifying the counterpart of lacunar cells. CASE A 16-year-old female presented with anterior chest wall swelling si REPORT: nce 6 months measuring 5x4cm along with incidentally noted cervical lymph nodes measuring 2x2cm and 1x1cm. On examination, multiple papular skin lesions were observed. FNAC smears from cervical lymph node showed high cellularity, with sheets of binucleated and multinucleated cells having multiple nucleoli, some showing pale bluish abundant cytoplasm whereas others showing dense cytoplasm; in a background of reactive lymphoid population with few neutrophils. Few giant cells showed hyperchromatic nuclei. Abnormal mitosis seen. No typical RS cell was seen. Peripheral blood smear showed neutrophilic leukocytosis with no atypical cell. Possibility of NSHL was considered and biopsy advised to rule out ALCL. Histological sections showed near total effacement of lymph node architecture by nodules separated by broad brotic bands. These nodules exhibit proliferating lymphocytes with clustered lacunar cells along with some mononucleate, binucleate and multinucleated cells. Prominent mitotic activity, angiogenesis, focal micro abscesses were noted. Immunohistochemistry showed CD 15+ and CD 30+ expression in the giant cells, conrming diagnosis of NSHL grade 2. NSHL poses a cytological diagnostic dilemma specially in abse CONCLUSION: nce of sclerosis on FNA, making histological examination and IHC mandatory

Proteomic Exploration of Plasma Exosomes and Other Small Extracellular Vesicles in Pediatric Hodgkin Lymphoma: A Potential Source of Biomarkers for Relapse Occurrence.

Exosomes and other small extracellular vesicles (EVs) are potential sources of cancer biomarkers. Plasma-derived EVs have not yet been studied in pediatric Hodgkin lymphoma (HL), for which predictive biomarkers of relapse are greatly needed. In this two-part proteomic study, we used two-dimensional difference gel electrophoresis (2D-DIGE) followed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) to analyze EV proteins of plasma collected at diagnosis from children with nodular sclerosis HL, relapsed or not. EVs isolated using membrane affinity had radii ranging from 20 to 130 nm and contained the programmed cell death 6-interacting (ALIX) and the tumor susceptibility gene 101 (TSG101) proteins, whereas calnexin (CANX) was not detected. 2D-DIGE identified 16 spots as differentially abundant between non-relapsed and relapsed HL (|fold change| ≥ 1.5, p < 0.05). LC–MS/MS identified these spots as 11 unique proteins, including five more abundant in non-relapsed HL (e.g., complement C4b, C4B; fibrinogen γ chain, FGG) and six more abundant in relapsed HL (e.g., transthyretin, TTR). Shotgun LC–MS/MS on pooled EV proteins from non-relapsed HL identified 161 proteins, including 127 already identified in human exosomes (ExoCarta data). This EV cargo included 89 proteins not yet identified in exosomes from healthy plasma. Functional interrogation by the Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that the EV proteins participate in platelet degranulation and serine-type endopeptidase activity as the most significant Gene Ontology (GO) biological process and molecular function (p < 0.01).

Incidence and survival of Hodgkin lymphoma patients treated at a national cancer center in a middle-income country from 1999-2018: A report of 1,382 cases.

e19523 Background: Hodgkin lymphoma (HL) is classically described as a malignancy with a good prognosis and bimodal pattern. We aim to describe the incidence and survival of HL patients treated at the National Cancer Institute (NCI) in Peru. Methods: We evaluated the database at the NCI Epidemiology Department in Peru from 1999-2018. The international classification of diseases (ICD)-10 codes C810-C813, C817, C819 and ICD for Oncology (version 3) codes 96503-96533, 96573-96593, 96533-96553, 96573, 99903 were used to classify both nodal and extra-nodal HL. The estimate of overall survival (OS) curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test. Results: During the study period 12,092 patients with lymphoma were found, of which 1,382 (11.4%) were HL. The median age was 24 years (range 2-88). Male patients were 62.4%. Patients of ≤14 years were 32.9%, with the most frequent 5-year interval group those aged 5-9 years-old representing 16.7% of patients. The adolescent and young adults (AYA) (15-39 years) group represented 38.4%. A total of 1,360 (98.4%) were classified as nodal HL. The classification according to the subtypes was as follows: 1,148 (83.1%) were one of the five subtypes [classical HL (cHL) and nodular lymphocyte-predominant HL (NLPHL)], 196 (14.2%) were HL, not otherwise specified, and 38 (2.7%) were HL without pathological confirmation. The classifiable 1,148 patients were categorized as follows: 1,107 patients (96.4%) were cHL and 41 (3.6%) were NLPHL. The cHL patients were classified as mixed cellularity HL (MCHL) in 52.3%, nodular sclerosis HL (NSHL) in 36.7%, lymphocyte-rich HL (LRHL) in 8.1%, and lymphocyte-depleted HL (LDHL) in 2.9%. The whole classifiable cohort (n = 1,148) showed a trimodal pattern. The MCHL subtype was most frequent in the 5-9 years group and in the 60-64 years group. The NSHL subtype was most frequent in the 20-24 years group. The median 5-year OS of the entire cohort (n = 1,382) was 86.3% (95%CI, 83.9-88.5). The OS according to the interval age groups were as follows: for the 0-14 years group the 5-yr OS was 94.9% (95%CI, 91.8-96.8), for the 15-39 years was 84% (95%CI, 79.5-87.68), for the 40-64 years group was 82.5% (95%CI, 75.2-87.8), and for the ≥65 years group was 58.6% (95%CI, 43.4-71.1). The OS according to age range showed a statistically significant difference p &lt; 0.01. Conclusions: In our study, patients with HL are younger compared to those in developed countries. The most frequent 5-year interval group is the 5-9 years group. HL incidence had a trimodal pattern. Extra-nodal presentation was extremely rare. NLPHL was also rare. The most frequent subtype was MCHL, however, in AYA patients the most frequent subtype was NSHL. Better OS was seen in the 0-14 year group, this being statistically significant compared to the older groups. Worse OS was observed in patients aged 65 and older.

Morphologic Spectrum of Lymphadenopathy in Adult-onset Immunodeficiency (Anti-interferon-γ Autoantibodies).

Adult-onset immunodeficiency syndrome (AOIS) caused by anti-interferon-γ autoantibodies is an emerging disease. Affected patients present typically with systemic lymphadenopathy, fatigue, and fever. We studied 36 biopsy specimens, 31 lymph nodes, and 5 extranodal sites, of AOIS confirmed by serum autoantibody or QuantiFERON-TB Gold In-Tube assay. We describe the morphologic features and the results of ancillary studies, including special stains, immunohistochemistry, and molecular testing. The overall median age of these patients was 60.5 years (range, 41 to 83 y) with a male-to-female ratio of 20:16. All biopsy specimens showed nontuberculous mycobacterial infection, and most cases showed the following histologic features: capsular thickening with intranodal sclerosing fibrosis, irregularly distributed ill-formed granulomas or histiocytic aggregates with neutrophilic infiltration, interfollicular expansion by a polymorphic infiltrate with some Hodgkin-like cells that commonly effaces most of the nodal architecture and proliferation of high endothelial venules. In situ hybridization analysis for Epstein-Barr virus-encoded RNA showed scattered (<1%) to relatively more common (4% to 5%) positive cells in 29 of 30 (97%) tested specimens, reflecting immune dysregulation due to an interferon-γ defect. In the 31 lymph node specimens, 23 (74%) cases showed increased immunoglobulin G4-positive plasma cells (4 to 145/HPF; mean, 49.7/HPF) with focal areas of sclerosis reminiscent of immunoglobulin G4-related lymphadenopathy, 4 (13%) cases resembled, in part, nodular sclerosis Hodgkin lymphoma, and 9 (29%) cases mimicked T-cell lymphoma. Among 33 patients with available clinical follow-up, 20 (61%) showed persistent or refractory disease despite antimycobacterial therapy, and 1 patient died of the disease. We conclude that the presence of ill-defined granulomas, clusters of neutrophils adjacent to the histiocytic aggregates, and some Epstein-Barr virus-positive cells are features highly suggestive of AOIS. A high index of clinical suspicion and awareness of the morphologic features and differential diagnosis of AOIS are helpful for establishing the diagnosis.

Prospects for predicting the course of nodular sclerosis Hodgkin lymphoma by morphometric analysis of CD163-positive macrophages

Background. In present days, much attention is paid to the study of the interrelation between the macrophage/hystiocytic microenvironment and the tumor substrate in lymphoproliferative disorders.Objective. The article is devoted to the morphometric and morphological assessment of CD163-positive macrophages in nodular sclerosis Hodgkin lymphoma.Materials and methods. Formalin fixed, paraffin-embedded (FFPE) lymph node samples of 45 patients were used for the study. To identify and visualize CD163-positive cells in the test material, an immunohistochemical staining method was used.Results. The study shows that the morphometric and morphological analysis of CD163-positive cells can be an effective and promising criterion for representing them as potential predictors of the disease course. Immunohistochemical study of 45 cases using the CD163 marker revealed a difference in the nature of macrophages localization in the lymph nodes nodules. The dependence of CD163-expressing cells number on the disease course was determined.Conclusion. The data obtained can be used to stratify patients with nodular sclerosis of classical Hodgkin lymphoma into risk groups and to determine personalized approaches to treatment. Immunohistochemical determination of the CD163 marker can be used in the complex diagnosis of the causes of refractoriness to the first and subsequent lines of therapy.