Classification Of non-Hodgkin Lymphoma Research Articles

Real-World Impact of Differences in the World Health Organization (WHO) Classification and International Consensus Classification (ICC) Systems on the Diagnosis of Non-Hodgkin Lymphoma: An Analysis from the LEO Cohort Study

Introduction: The use of standardized, evidence-based classification systems is crucial for the accurate diagnosis and treatment of diseases. Moreover, standardized classification facilitates research and epidemiologic studies and promotes consistency in communication among healthcare professionals. Since 2016, the revised 4 th edition of the World Health Organization classification (WHO-HAEM4R) has been the global standard for diagnosis of lymphoid malignancies. With the emergence of new data, 2 new classification systems were developed and published in 2022: the 5 th edition of the WHO Classification (WHO-HAEM5) and the International Consensus Classification (ICC). Both WHO-HAEM5 and ICC maintain a shared fundamental concept of disease classification that integrates clinical, pathologic, and molecular data. However, they differ on nomenclature, establishment of new entities, and/or diagnostic criteria for some disease categories. To evaluate the impact of these differences on real-world diagnosis of non-Hodgkin lymphoma (NHL), we examined the diagnostic classification of NHL in the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study (NCT02736357). Methods: Initiated in 2015, LEO is an ongoing prospective observational study of patients aged ≥18 years with newly diagnosed NHL. Patients are enrolled at 8 major U.S. medical centers. Clinical, epidemiologic, pathologic, and treatment data are abstracted at baseline and active follow-up is conducted for all patients. Lymphoma subtype is coded for each case based on expert hematopathology re-review of the diagnostic pathology slides, the pathology report, biomarker data, and clinical data. Of note, NHL subtype distribution is similar to SEER data. We studied all patients enrolled in LEO between 7/1/2016 (the date LEO pathology review started using WHO-HAEM4R diagnostic codes) and 5/31/2020. WHO-HAEM4R diagnoses and additional clinicopathologic data, when relevant, were used to map cases into the corresponding WHO-HAEM5 and ICC diagnoses. Differences between WHO-HAEM5 and ICC were annotated for each case as: None - same disease entity; Minor - difference in nomenclature with similar diagnostic criteria; Major - difference in disease category and/or diagnostic criteria; or Unevaluable - insufficient data to assign WHO-HAEM5 and/or ICC diagnosis. Results: LEO enrolled 6143 patients during the study period. Of these, comparison between WHO-HAEM5 and ICC was evaluable in 5730 (93.3%). Unevaluable cases included those without a specific WHO-HAEM4R diagnosis at enrollment (N=384; e.g., patients with a low-grade B-cell lymphoma that could not be definitively sub-classified) and those with a specific WHO-HAEM4R diagnosis, but with insufficient clinicopathologic data to assign a specific WHO-HAEM5 and/or ICC diagnosis (N=29). Of the 5730 evaluable cases, 5376 (93.8%) showed no difference between WHO-HAEM5 and/or ICC diagnosis, 311 (5.4%) showed minor differences (nomenclature only), and 43 (0.8%) showed major differences (Table 1). The 43 major differences all involved B-cell NHLs; 20 (46.5%) were attributable to different approaches to classifying double-hit lymphomas, 21 (48.9%) to classification of splenic/leukemic B-cell lymphomas, and 2 (4.6%) to classification of B-cell lymphomas occurring at specific anatomic sites (Table 2). Conclusion: In a large, prospective lymphoma cohort reflecting real-world clinical practice at 8 major U.S. medical centers, major diagnostic differences in the classification of NHL using WHO-HAEM5 or ICC classification criteria were seen in 0.8%, whereas the remaining 99.2% of diagnoses were either the same or showed differences in nomenclature only. The existence of 2 concurrent classification systems presents potential for discrepancies in pathologic diagnosis, clinical practice, clinical trials, and other lymphoma research. Furthermore, some of the differences between WHO-HAEM5 and ICC are clinically and potentially therapeutically significant, and their resolution requires further study. Nevertheless, our findings argue that the proportion of patients affected would be small in real-world practice settings. This appears largely related to incidence rates of specific lymphoma subtypes, with major differences between the 2 classifications predominantly affecting rare entities, while there is general concordance on the most common forms of NHL.

BURKITT LYMPHOMA MIMICKING SEPTIC SHOCK: AN UNUSUAL PRESENTATION

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin B-cell lymphoma that typically presents with multiple metabolic derangements, kidney failure, involvement of the jaw or other facial bones, and enlarged lymph nodes. Our case report describes an initial presentation of (BL) with septic shock. CASE PRESENTATION: 25-year-old Caucasian female presented with a 4-day history of sharp non-radiating right upper quadrant abdominal pain, poor appetite, nausea, multiple episodes of loose watery stools, and polydipsia. Exam was notable for 2/4 SIRS criteria, with heart rate 134 and respiratory rate 29, and right upper quadrant was tender to palpation. Workup revealed white blood cell count 10.3 thou/uL, lactate 4.5 mmol/L, total bilirubin 1.5 mg/dL with direct bilirubin 0.8 mg/dL, AST 138 U/L, ALT 177 U/L, and alkaline phosphatase 601 U/L. Despite a 30cc/kg fluid bolus for resuscitation, lactate worsened to 5.2 mmol/L. With concern for septic shock, the patient was started on broad-spectrum antibiotics and admitted to the hospital with an intra-abdominal source suspected. Computed Tomography (CT) scan of the abdomen and pelvis with contrast demonstrated numerous hypoenhancing lesions of the liver (up to 80% of parenchyma), spleen, right kidney, and right adrenal gland. Blood cultures remained negative, with antibiotics discontinued after 48 hours, and lactate clearing with further fluid resuscitation. The patient underwent biopsy of the liver, which revealed findings consistent with Burkitt lymphoma (CD10, 19, 20 + on flow cytometry; Myc+, bcl2 and 6 – on FISH. PAX5, BCL6, and CD10 + and bcl2 - on immunochemistry). With improvement in symptoms, the patient was discharged with oncology follow-up. DISCUSSION: BL is a rare, but very aggressive, B-cell non-Hodgkin lymphoma, often associated with Ebstein Barr virus, human immunodeficiency virus, and overexpression of oncogene C-MYC on chromosome 8. It presents in three definite forms: endemic, sporadic, immunodeficiency-associated[4]. The sporadic variant is more common among caucasians[3] and in patients below 35 years of age with a median age at diagnosis of 30 years[1,2]. Patients usually present with abdominal signs and symptoms involving the small and large intestine mimicking acute appendicitis or intussusception. Excisional biopsy is preferred for the diagnosis of BL, with confirmation done by immunohistochemistry and cytogenetics. While aggressive, it is highly curable with a two-year survival rate of 80-90%, treatment consisting of multi-agent regimens. CONCLUSIONS: Clinicians, especially intensivists, should be aware of the numerous clinical conditions, such as Burkitt Lymphoma, which may mimic sepsis and septic shock as early diagnosis can improve outcomes and decrease overuse of antibiotics. Diagnosing Burkitt Lymphoma early can also improve patients' mortality with the initiation of early treatment to optimize survival. REFERENCE #1: World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008. REFERENCE #2: Armitage JO, Weisenburger DD ., New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project., J Clin Oncol. 1998;16(8):2780. REFERENCE #3: Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS., Lymphoma incidence patterns by WHO subtype in the United States, 1992-200., Blood. 2006;107(1):265. Epub 2005 Sep 8. DISCLOSURES: No relevant relationships by Bohdan Baralo, source=Web Response No relevant relationships by Shambo Guha Roy, source=Web Response No relevant relationships by SANA MULLA, source=Web Response No relevant relationships by Ruqqiya Mustaqeem, source=Web Response No relevant relationships by Monisha Panda, source=Web Response No relevant relationships by Mahati Paravathaneni, source=Web Response No relevant relationships by Rajesh Thirumaran, source=Web Response No relevant relationships by Vihitha Thota, source=Web Response

BRACHIAL PLEXOPATHY AND CARDIAC TAMPONADE: AN UNCOMMON PRESENTATION OF DIFFUSE LARGE B-CELL MEDIASTINAL LYMPHOMA

TOPIC: Disorders of the Mediastinum TYPE: Medical Student/Resident Case Reports INTRODUCTION: Primary mediastinal large B-cell lymphoma (PMLBCL) is a unique type of B-cell lymphoma probably arising from a putative thymic medulla B-cell. PMLBCL comprises seven percent of diffuse large B cell lymphomas (2.4 percent of all non-Hodgkin lymphomas). There is a female predominance and a median age at diagnosis in the third to fourth decade. In some cases, the presentation can be an oncological emergency with locally invasive anterior mediastinal mass arising from thymus causing external pressure on the heart and the surrounding structures. PMLBCL presenting as brachial plexopathy with cardiac tamponade is an uncommon presentation. CASE PRESENTATION: 37-year-old female, who presented to the ED with a 3-week history of left- sided neck pain and progressive swelling with associated 2 weeks history of numbness in the left wrist, tingling sensation in her 4th and 5th finger with weakness on the same side. She endorsed exertional dyspnea and palpitation that worsened over the last 4 days prior to presentation.On examination she was noted to have left sided neck mass about 6 x 8cm, firm, nontender, non-mobile with extension below the clavicle. Tachycardic with Muffled heart sounds and grade 3/6 Systolic Ejection Murmur at right upper sternal border. Flexion deformity with reduced sensation of the left 4th and 5th finger. Chest X-ray shows cardiomegaly with widened mediastinum. Computed Tomography scan was suggestive of anterior mediastinal mass. Echocardiogram done showed large pericardial effusion with Echocardiographic findings consistent with tamponade physiology.She underwent pericardiocentesis with 700 cc of serosanguinous fluid drained and subsequently had CT guided biopsy of the anterior mediastinal mass. Biopsy report showed high grade B-cell lymphoma with Immunostain showing lymphoma cells positive for CD20, BCL6 and negative for BCL2, CD5. She was diagnosed to be High grade stage IIB, commenced on chemotherapy and completed 6 cycles of DA-EPOCH-R.Left hand weakness and neuropathy resolved following chemotherapy. Repeat CT chest and Echocardiogram showed near resolution of the anterior mediastinal mass and pericardial effusion respectively. DISCUSSION: The majority of patients with primary diffuse large B-cell mediastinal lymphoma are symptomaticat the time of diagnosis. Patients present with a locally invasive anterior mediastinal massoriginating in the thymus, with frequent airway compromise and superior vena cava (SVC)syndrome. Symptoms related to the compression or invasion of local structures (i.e., cough, dyspnea, dysphagia, hoarseness) are common, systemic B-symptoms occurs in about 47% ofpatients, brachial plexopathy is an uncommon presentation. CONCLUSIONS: PMBL is a tumor of young adults who present with a rapidly proliferating tumor. At diagnosis, the tumor is usually limited to the mediastinum, therefore high index of suspicion is required in making the diagnosis. REFERENCE #1: A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997 Jun1;89(11):3909-18. PMID: 9166827 REFERENCE #2: Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas:clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma ClassificationProject. J Clin Oncol. 1998 Aug;16(8):2780-95. doi: 10.1200/JCO.1998.16.8.2780. PMID:9704731. REFERENCE #3: van Besien K, Kelta M, Bahaguna P. Primary mediastinal B-cell lymphoma: a review ofpathology and management. J Clin Oncol. 2001 Mar 15;19(6):1855-64. doi:10.1200/JCO.2001.19.6.1855. PMID: 11251018. DISCLOSURES: No relevant relationships by Regine Afable, source=Web Response No relevant relationships by Ibrahim Omore, source=Web Response No relevant relationships by Farbod Raiszadeh, source=Web Response

Detecting Fibroblast Activation Proteins in Lymphoma Using 68Ga-FAPI PET/CT.

Cancer-associated fibroblasts that overexpress fibroblast activation protein (FAP) are enriched in many epithelial carcinomas and in hematologic neoplasms. PET/CT with radiolabeled FAP inhibitor (FAPI) is a new diagnostic tool for visualizing the tumor stroma. This prospective study aimed to profile FAPs in different subtypes of lymphomas and explore the potential utility of 68Ga-FAPI PET/CT in lymphomas. Methods: In this prospective study, we recruited 73 lymphoma patients who underwent 68Ga-FAPI PET/CT and recorded and measured semiquantitative parameters and ratios of their scan results. FAPI expression was assessed by immunochemistry in samples obtained from 22 of the lymphoma patients. Results: We evaluated 11 patients with Hodgkin lymphoma and 62 with non-Hodgkin lymphoma (NHL). Significantly elevated FAP uptake was observed in Hodgkin lymphoma lesions, correlating with the intensity of FAP immunostaining (score, 3+). A positive association was found between the corresponding clinical classification of NHL and the 68Ga-FAPI uptake activity of the lesion. Aggressive NHL lesions, with moderate to strong FAP immunostaining (score, 2+ to 3+), exhibited intense to moderate 68Ga-FAPI uptake. Indolent NHL lesions showed weak FAP staining and mild to moderate 68Ga-FAPI uptake. No statistically significant correlation emerged between the sum of the product of the diameters and the corresponding SUVmax (P = 0.424). The tumor-to-liver ratios were 6.26 ± 4.17 in indolent NHL and more than 9 in other subtypes. Conclusion:68Ga-FAPI imaging can be used to detect FAP expression in lymphoma lesions and may be an alternate method for characterizing lymphoma profiles.

Deep Learning for the Classification of Non-Hodgkin Lymphoma on Histopathological Images.

Simple SummaryHistopathological examination of lymph node (LN) specimens allows the detection of hematological diseases. The identification and the classification of lymphoma, a blood cancer with a manifestation in LNs, are difficult and require many years of training, as well as additional expensive investigations. Today, artificial intelligence (AI) can be used to support the pathologist in identifying abnormalities in LN specimens. In this article, we trained and optimized an AI algorithm to automatically detect two common lymphoma subtypes that require different therapies using normal LN parenchyma as a control. The balanced accuracy in an independent test cohort was above 95%, which means that the vast majority of cases were classified correctly and only a few cases were misclassified. We applied specific methods to explain which parts of the image were important for the AI algorithm and to ensure a reliable result. Our study shows that classifications of lymphoma subtypes is possible with high accuracy. We think that routine histopathological applications for AI should be pursued.The diagnosis and the subtyping of non-Hodgkin lymphoma (NHL) are challenging and require expert knowledge, great experience, thorough morphological analysis, and often additional expensive immunohistological and molecular methods. As these requirements are not always available, supplemental methods supporting morphological-based decision making and potentially entity subtyping are required. Deep learning methods have been shown to classify histopathological images with high accuracy, but data on NHL subtyping are limited. After annotation of histopathological whole-slide images and image patch extraction, we trained and optimized an EfficientNet convolutional neuronal network algorithm on 84,139 image patches from 629 patients and evaluated its potential to classify tumor-free reference lymph nodes, nodal small lymphocytic lymphoma/chronic lymphocytic leukemia, and nodal diffuse large B-cell lymphoma. The optimized algorithm achieved an accuracy of 95.56% on an independent test set including 16,960 image patches from 125 patients after the application of quality controls. Automatic classification of NHL is possible with high accuracy using deep learning on histopathological images and routine diagnostic applications should be pursued.

RESEARCH CHARACTERISTICS HISTOPATHOLOGY AND APPLICATION IMMUNOHISTOCHEMISTRY TO CLASSIFY NON-HODGKIN LYMPHOMA IN 103 MILITARY HOSPITAL

Objective: Evaluate the macroscopic and microscopic characteristics of Non-Hodgkin's lymphoma. Application of the manifestation of immune markers to classification Non-Hodgkin's lymphoma. Matherial and Method: The cross-sectional descriptive, retrospective and prospective study of 75 patients diagnosed on histopathology and immunohistochemistry as Non-Hodgkin's lymphoma at Military Medical Hospital 103 from January 2018 to September 2020. Results: The disease occurred in men more than women: 2/1. The average age of diseases is 58.31 ± 17.62. Non-Hodgkin's lymphoma in the lymph node accounts for the highest proportion (57.3%). WF7 accounts for the highest percentage (54.7%). The majority of the disease is in intermediate malignancy with 76%. B-cell Non-Hodgkin's lymphoma accounts for 84%. Diffuse large B-cell lymphoma accounts for the highest rate of 66.67%, of which the GCB type accounts for 32%, the non-GCB accounts 68%. Conclusion: The diagnosis and classification of Non Hodgkin lymphoma helps clinicians predict the response to chemotherapy, extra life, which is indicative of monoclonal antibody therapy

Classification of non-Hodgkin lymphoma in the Middle Euphrates Region of Iraq according to the World Health Organization classification

BACKGROUND: Non-Hodgkin lymphoma (NHL) patterns vary worldwide in relation to demographic and environmental factors.AIM: The objective of our study was to identify subtypes of NHL in the Middle Euphrates Region of Iraq according to the World Health Organization (WHO) modified classification.MATERIALS AND METHODS: A retrospective descriptive study was carried out at Al-Hussein Cancer Center in Karbala, Iraq, on 385 patients diagnosed with NHL between January 2012 and August 2020. Patient ages ranged between 1 and 96 years. They included 204 males and 181 females. All patients were diagnosed by tissue biopsy, confirmed by immunohistochemistry markers, and classified according to WHO classification. Any patient with inconclusive results was excluded from the study.RESULTS: Among total NHL patients, males were (53%) and females were (47%) with a male: female ratio of (1.12:1). B-cell lymphoma was diagnosed in (92.47%) and T cell lymphoma in (7.53%). Diffuse large B-cell Lymphoma (DLBCL) was the most frequent B-cell subtype (54.02%) followed by Burkitt's lymphoma (BL) (14.02%), while peripheral T-cell lymphoma was the most common T-cell subtype (2.08%). About (61.82%) of patients were nodal, and (38.18%) were extranodal. The intestine was the most frequent extranodal site (34.69%).CONCLUSION: Among our patients, there were high frequencies of DLBCL, extra nodal primaries and intestinal BL. Follicular lymphoma and small lymphocytic lymphoma were uncommon in our region. These results were similar to the Middle Eastern NHL patterns but differed from the western patterns.

Clinical And Prognostic Features Of Non Hodgkin Lymphoma And Preliminary Effective Evaluation Of R-Chop Regimen In Patients With Diffuse Large B-Cell Lymphoma

Background: WHO 2008 classification of Non Hodgkin Lymphoma (NHL) has been introduced and got consensus internationally. However, studies on NHL according to WHO 2008 classification are limited in Vietnam. In terms of treatment, the R-CHOP regimen is still the most commonly used regimen for the treatment of moderate or high grade malignant lymphoma tumors. However, its effectiveness on each type has not been specifically studied. Purpose of this research is to evaluate of clinical and subclinical characteristics of NHL patients according to the 2008 WHO classification on lymphoid neoplasms and to evaluate preliminary effective of diffuse large B cell lymphoma (DLBCL) patients with R-CHOP regimen. Materials and methods: A prospective descriptive study was conducted on 48 patients diagnosed with NHL undergoing treatment at the Hue University Hospital from July 2019 and Hue Central Hospital from April 2020 to present. Results: The mean age was 52.4 years, male/female ratio = 1.3/1, the most common primary tumor site was lymph nodes with 54.3%. Stage IV was found in 37.5% of all cases. DLBCL was the most common type, accounted for 58.3%, whereas marginal zone lymphoma had the lowest incidence (2.1%). According to the International Prognostic Index (IPI), low risk, low-intermediate risk, high-intermediate risk, high risk group were 43.6%; 25.0%; 18.8%; 12.6% respectively. 34.8% patients responsed completely after 3 cycles and after 6 – 8 cycles, 58.8% patients achieved complete response. Grade III, IV neutropenia, grade I, II peripheral neuropathy and grade I, II thrompocytopenia were the most common side effect observed. Conclusions: DLBCL is the most common Non Hodgkin Lymphoma. R-CHOP regimen has a good response after 6-8 cycles in DLBCL diseases and is well tolerated that the adverse events are mostly able to control effectively.

Classification of digital pathological images of non-Hodgkin's lymphoma subtypes based on the fusion of transfer learning and principal component analysis.

Non-Hodgkin's lymphoma (NHL) is a serious malignant disease. Delayed diagnosis will cause anemia, increased intracranial pressure, organ failure, and even lead to death. The current main trend in this area is to use deep learning (DL) for disease diagnosis. Extracting classification information from the digital pathology images by DL may realize the automated qualitative and quantitative analysis of NHL. Previously, DL has been used to classify NHL digital pathology images with some success. However, shortcomings still exist in the data preprocessing methods and feature extraction. Therefore, this paper presents a method for the classification of NHL subtypes based on the fusion of transfer learning (TL) and principal component analysis (PCA). First, the NHL digital pathology images were preprocessed by image division and segmentation and then input into the transfer models for fine-tuning and feature extraction. Second, PCA was used to map the extracted features. Finally, a neural network was used as a classifier to classify the mapped features. During the fine-tuning of the transfer models, two methods, freezing all feature extraction layers and fine-tuning all layers, were employed to select the optimal model with the best classification result among all the preselected transfer models. On this basis, the use of freezing the layers' location was discussed and analyzed. The results show that the proposed method achieved average fivefold cross-validation accuracies of 100%, 99.73%, and 99.20% for chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL) tumor, and each category has standard deviations 0.00, 0.53, and 0.65, respectively, in the NHL reference dataset. The overall classification accuracy for fivefold cross-validation is 98.93%, which is an increase of 1.26% compared to the latest reported methods, having a lower standard deviation (1.00). The method proposed in this paper achieves a high classification accuracy and strong model generalization for the classification of NHL, which makes it possible to conduct intelligent classification of NHL in clinical practice. Our proposed method has definite clinical value and research significance.

Comparative evaluation of combined application of fine needle aspiration cytology and flow cytometry with histopathology for the diagnosis of Non-Hodgkin lymphoma

Context: Fine needle aspiration cytology (FNAC) is widely used in the investigation of lymphadenopathy. A combination of FNAC and Flow cytometric immunophenotyping (FCI) can help to establish an accurate diagnosis and classification in most cases of NHL (Non-Hodgkin lymphoma). Aims: We evaluated the effectiveness of FNAC along with flow cytometry (FCM) with histopathology in the diagnosis and classification of NHL by applying FCI on a sample obtained from the FNAC of lymphoid tissue. Settings and Design: A cross-sectional study was conducted in the Department of Pathology. Patients of all ages presenting peripheral lymphadenopathy were screened on FNAC. All Cases suggested as NHL were taken up for FCM as well as for excision biopsy. Methods and Material: FCI of lymph node aspirate was performed by using four-color FCM (FACScalibur; Becton Dickinson). The sections were processed in Shandon Citadel 2000 tissue processor for histopathology. Statistical analysis used: Descriptive statistics were used to describe the study sample. Data were analyzed using SPSS. Results: A total of 30 patients, 27 (90%) male, and 3(10%) female were included in the study. Generalized lymphadenopathy (46.7%) was prominent followed by cervical lymphadenopathy(40%). Out of the 30 cases, eight cases were not analyzed due to the paucity of events. Out of 22 cases, a total of 18 cases were diagnosed as B-cell lymphoma, two cases as T-cell lymphoma, and two cases as reactive lymphoid hyperplasia. Conclusions: FNAC in conjunction with FCI is a reliable method that can be used as a first-line investigation to give rapid results, which can guide further investigation and facilitate cost-effective patient management. Key Messages: Excision biopsy and histopathological examination remain the gold standard for the classification of NHL. However, the need for anesthesia and possible complications of excision biopsy limits its role. FNAC in conjunction with FCI is a reliable method that can be used as a

Drug Resistance in Non-Hodgkin Lymphomas.

Non-Hodgkin lymphomas (NHL) are lymphoid tumors that arise by a complex process of malignant transformation of mature lymphocytes during various stages of differentiation. The WHO classification of NHL recognizes more than 90 nosological units with peculiar pathophysiology and prognosis. Since the end of the 20th century, our increasing knowledge of the molecular biology of lymphoma subtypes led to the identification of novel druggable targets and subsequent testing and clinical approval of novel anti-lymphoma agents, which translated into significant improvement of patients’ outcome. Despite immense progress, our effort to control or even eradicate malignant lymphoma clones has been frequently hampered by the development of drug resistance with ensuing unmet medical need to cope with relapsed or treatment-refractory disease. A better understanding of the molecular mechanisms that underlie inherent or acquired drug resistance might lead to the design of more effective front-line treatment algorithms based on reliable predictive markers or personalized salvage therapy, tailored to overcome resistant clones, by targeting weak spots of lymphoma cells resistant to previous line(s) of therapy. This review focuses on the history and recent advances in our understanding of molecular mechanisms of resistance to genotoxic and targeted agents used in clinical practice for the therapy of NHL.

Tumor Identification of Less Aggressive or Indolent Lymphoma With Whole-Body 11C-Acetate PET/CT.

The aim of this study was to investigate the diagnostic performance of whole-body [C]acetate PET/CT in less aggressive or indolent lymphomas, wherein [F]FDG PET/CT would exhibit limited sensitivity. Between September 2016 and May 2018, we prospectively evaluated 17 patients (9 men, 8 women; mean age [range], 71 [45-87] years) with pathologically proven less aggressive or indolent lymphomas according to Non-Hodgkin's Lymphoma Classification Project, using both [F]FDG PET/CT and [C]acetate PET/CT (performed on the same day). Detected nodal lesions were recorded according to the Ann Arbor classification. Extranodal (EN) lesions were also evaluated. We compared whole-body lesion detection between [F] FDG PET/CT and [C]acetate PET/CT using the McNemar test. In all patients, significantly more nodal and EN lesions were detected using [C]acetate PET/CT than [F]FDG PET/CT (nodal: 84 vs 64 regions; P < 0.001; EN: 26 vs 19 regions, P = 0.039). Bone lesions were detected in 8 and 5 patients using [C]acetate PET/CT and [F]FDG PET/CT, respectively (P = 0.25). Among the 14 patients (82.4%) who underwent bone marrow biopsy, bone marrow involvement was detected with sensitivities of 100% (6/6 patients) and 80% (5/6 patients) using [C]acetate PET/CT and [F]FDG PET/CT, respectively. Multiple areas of focal uptake in the spleen of 1 patient were exhibited on [F]FDG PET/CT but not [C]acetate PET/CT. [C]acetate PET/CT exhibited greater sensitivity than [F]FDG PET/CT for lesion detection in patients with less aggressive or indolent lymphomas, thus promising applicability as a physiological tracer in the study of such lesions.

Features based on the percolation theory for quantification of non-Hodgkin lymphomas

Non-Hodgkin lymphomas are a health problem that affects over 70,000 people per year in the United States alone. The early diagnosis and the identification of this lymphoma are essential for an effective treatment. The classification of non-Hodgkin lymphomas is a task that continues to rank as one of the main challenges faced by hematologists, pathologists, as well as in the producing of computer vision methods due to its inherent complexity. In this paper, we present a new method to quantify and classify tissue samples of non-Hodgkin lymphomas based on the percolation theory. The method consists of associating multiscale and multidimensional approaches in order to divide the image into smaller regions and then verifying color similarity between pixels. A cluster labeling algorithm was applied to each region of interest to obtain the values for the number of clusters, occurrence of percolation and coverage ratio of the largest cluster. The method was tested on different classifiers aiming to differentiate three different groups of non-Hodgkin lymphomas. The obtained results (AUC rates between 0.940 and 0.993) were compared to those provided by methods consolidated in the Literature, which indicates that the percolation theory is a suitable approach for identifying these three classes of non-Hodgkin lymphomas, those being: mantle cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia.

Diagnosis and Classification of Non-Hodgkin Lymphoma with Endoscopic Ultrasound-Guided Fine Needle Aspiration

Diagnosis and Classification of Non-Hodgkin Lymphoma with Endoscopic Ultrasound-Guided Fine Needle Aspiration

Clinical and pathological evaluation of histopathological subtypes in patients with non-Hodgkin’s lymphoma

Objectives. Non-Hodgkin Lymphomas (NHLs) are tumours of the lymphoid system which originate from lymph nodes or extranodal lymphatic tissue. Since they represent a heterogeneous group of diseases, it is very important to determine prognostic factors apart from staging and identification of the patients with poor prognosis. The objective of our study is to investigate clinical characteristics, treatments applied, and their outcomes, survival rates, and prognostic factors which may be effective on survival. Methods. Clinical characteristics, treatments applied, and their outcomes, survivals, and prognostic factors which may be effective on the survival in 230 patients who were diagnosed as NHL, and consulted to our center between the years 2002, and 2015 were retrospectively evaluated. Results. Median age of our patients (male, 54.8 %, and female, 45.2 %) was 57 years. The most frequently seen histopathological subtype was diffuse large β cell lymphoma. We have seen that IPI score, β symptom, levels of LDH, albumin, β2 microglobulin, and lymphocyte counts are significant prognostic factors. Stomach was the most frequently involved extranodal organ. Advanced stage, higher IPI score, extranodal organ involvement were found to be correlated with shorter survival times. Conclusion. Everyday developments occur in the diagnosis, classification, and treatment of NHL. Therefore, it is important for medical centres to evaluate their treatment outcomes, and prognostic factors affecting their survival rates.

Retrospective Analysis of Treatment Outcomes and Geriatric Assessment in Elderly Malignant Lymphoma Patients.

In recent years, the Comprehensive Geriatric Assessment (CGA), which is used in gerontology to assess functioning in elderly individuals, has been said to be useful in geriatric oncology. Therefore, we examined whether items in the CGA were associated with survival time in elderly patients with non-Hodgkin lymphoma (NHL). We conducted the CGA for 93 patients aged ≥ 65 years who had undergone treatment for NHL retrospectively. The CGA includes activities of daily living, instrumental activities of daily living, mood, cognition, nutrition, and the Charlson comorbidity index. For each category, we divided subjects into a "good" group and a "poor" group. In regard to the Charlson comorbidity index, patients were divided into two groups using different cutoffs to divide the groups; the two groups were established according to the division with the largest significant difference in survival time. Multivariate analysis was then performed with the following prognostic factors affecting survival: all CGA items, NHL classification, stage, performance status, and doxorubicin use/non-use. We also performed similar analysis for 43 diffuse large B-cell lymphoma (DLBCL) patients who had undergone anthracycline treatment. Results are factors affecting survival in NHL cases included comorbidity score ≥ 6 (P < 0.0001), doxorubicin non-use (P = 0.005), and cognitive impairment (P = 0.0488). In cases of DLBCL, survival was affected by comorbidity score ≥ 5 (P = 0.0016). High comorbidity score was strongly associated with survival in both NHL and DLBCL.

Classification of Non-Hodgkin Lymphoma in Seven Geographic Regions Around the World: Review of 4539 Cases from the International Non-Hodgkin Lymphoma Classification Project

INTRODUCTIONThe distribution of non-Hodgkin lymphoma (NHL) subtypes varies around the world, but a large and systematic comparative study has not been done. This study is first to evaluate the relative frequencies of NHL subtypes in seven regions of the world.METHODSFive expert hematopathologists classified 4848 consecutive cases of NHL from 25 countries in seven regions, including North America, Central/South America, Western Europe, Southeastern Europe, Southern Africa, the Middle East/North Africa, and the Far East, using the WHO classification. Data from the developed world (North America and Western Europe) was compared to the developing world (all other regions combined).RESULTSAmong the 4848 cases reviewed, 4539 (93.6%) were confirmed to be NHL, whereas the other 309 (6.4%) had diagnoses other than NHL and were excluded from further analysis. A significantly higher male to female ratio was found in the developing regions (1.4:1) compared to the developed world (1:1; p<0.05). The median age at diagnosis was significantly lower for both low grade (LG) and high grade (HG) B-NHL in the developing regions (59 and 54 yrs, respectively) compared to the developed world (62 and 64 yrs, respectively). The developing regions had a significantly lower frequency of B-NHL (86.6%) and a higher frequency of T-NHL (13.4%) compared to the developed world (90.7% and 9.3%, respectively). Furthermore, the developing regions had significantly more cases of HG B-NHL (58.7%) compared to the developed world (43.9%). Among B-cell lymphomas, diffuse large B-cell lymphoma (42.5%) and Burkitt lymphoma (2.2%) were significantly more common in the developing regions, compared to the developed world (28.9% and 0.8%, respectively). Follicular lymphoma (15.3%), mantle cell lymphoma (3.8%), marginal zone lymphoma of mucosa-associated lymphoid tissue (5.2%), and lymphoplasmacytic lymphoma (0.3%) were significantly less common in the developing regions, compared to the developed world (25.5%, 7.8%, 8.8%, and 1.4%, respectively). Among T-cell lymphomas, precursor T-lymphoblastic lymphoma (2.9%) and nasal NK/T-cell lymphoma (2.2%) were more common in the developing regions, compared to the developed world (1.3% and 0.3%, respectively).CONCLUSIONOur study is the first to systematically compare the relative frequencies of NHL subtypes in different regions around the world, and provides new evidence of significant geographic differences. Our findings suggest that differences in etiologic and/or host risk factors are likely responsible, and more detailed epidemiologic studies are needed to better understand these differences. DisclosuresArmitage:Celgene: Consultancy; Ziopharm: Consultancy; Tesaro Bio, Inc: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Conatus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Spectrum: Consultancy.

Reduced-dose (two-thirds) R-CHOP chemotherapy for elderly patients with non-Hodgkin lymphoma

Elderly patients with non-Hodgkin lymphoma (NHL) have a poor prognosis. Owing to treatment-related toxicities, there is no standard chemotherapy for the elderly patients, especially those aged 70 years or older. In this study, we retrospectively evaluated the efficacy and toxicity of reduced-dose (two-thirds) R-CHOP chemotherapy as an initial chemotherapy for 45 patients aged 70 years or older with B-cell NHL. The WHO classification of NHL included diffuse large B-cell lymphoma (DLBCL) (31), mantle cell lymphoma (5), follicular lymphoma (4), extranodal marginal zone lymphoma (1), Burkitt lymphoma (1), and B-cell lymphoma whose further types were unclassified (3). The incidences of grade 4 neutropenia and febrile neutropenia (FN) were 51·1 and 15·6%, respectively. Efficacy was evaluated in patients with DLBCL. The overall and complete response (CR) rates were 96·7 and 90·0%, respectively. Two-year event-free survival (EFS) and overall survival (OS) were 84·4 and 89·2%, respectively. There was no treatment-related mortality. In conclusion, two-thirds R-CHOP chemotherapy is a promising treatment for elderly patients with B-cell NHL in terms of its efficacy and toxicity.

Classification of non-Hodgkin lymphoma in Algeria according to the World Health Organization classification

The relative distribution of non-Hodgkin lymphoma (NHL) subtypes differs markedly around the world. The aim of this study was to report this distribution in Algeria. A panel of four hematopathologists classified 197 consecutive cases according to the World Health Organization classification, including 87.3% B-cell and 12.7% T- or natural killer (NK)-cell NHLs. This series was compared with similar cohorts from Western Europe (WEU) and North America (NA). Algeria had a significantly higher frequency of diffuse large B-cell lymphoma (DLBCL: 52.8%) and a lower frequency of follicular lymphoma (FL: 13.2%) compared with WEU (DLBCL: 32.2%; FL: 20.0%) and NA (DLBCL: 29.3%; FL: 33.6%). The frequency of mantle cell lymphoma was lower in Algeria (2.5%) compared with WEU (8.3%). Smaller differences were also found among the NK/T-cell lymphomas. In conclusion, we found important differences between Algeria and Western countries, and further epidemiologic studies are needed to explain these differences.

Immunophenotyping of Non-Hodgkin's lymphomas in Sudan.

IntroductionNon-Hodgkin′s lymphomas (NHLs) are heterogeneous group of malignant lymphoproliferative disorders.Study objectivesThis was a retrospective study aimed to classify NHLs into B cell and T cell types; in addition to demonstrate the histological patterns and correlate it with gender, age and site of the biopsy.MethodsThe study was conducted in Histopathology Department, National Heath Laboratory, during the period 2007-2010. Formalin fixed paraffin wax embedded tissue blocks which were diagnosed as NHLs by routine Haematoxylin and Eosin (H&E) stain during the period 2000-2008 were used. Haematoxylin and Eosin (H&E) stain were done. Immunohistochemistry stains performed according to Dako cytomation protocol 2007. Lymphoid markers which were used in this study are CD45 (LCA), CD20 (B cell marker), CD3 (T cell marker), CD15 and CD 30. Epithelial marker which was used is CK MNF116. The total number of samples collected was 66; two of them were excluded because of poor processing. Another two specimens were excluded because they are non-reactive with lymphoid markers. The remaining 62 specimens were confirmed to be NHLs and classified into B cell and T cell types.ResultsThe study showed that B cell NHLs represented 87.1% while T cell NHLs were 12.9%. The Male: Female ratio was 1.6:1. The major affected age group was (47-67) years (38.1% of all specimens). The most frequent histological grade was intermediate grade NHLs (27% of all specimens). The most common site of NHLs in this study is the lymph node (40% of all specimens) followed by stomach (19.4%).ConclusionExtranodal locations are the most common sites affected with T cell NHLs. In conclusion; this study confirmed the fundamental role of immunohistochemistry in diagnosis and classification of NHLs.