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Background/Aim: We and others have previously shown that cell fusion plays an important role in cancer metastasis. Color coding of cancer and stromal cells with spectrally-distinct fluorescent proteins is a powerful tool, as pioneered by our laboratory to detect cell fusion. We have previously reported color-coded cell fusion between cancer cells and stromal cells in metastatic sites by using color-coded EL4 murine lymphoma cells and host mice expressing spectrally-distinct fluorescent proteins. Cell fusion occurred between cancer cells or, between cancer cells and normal cells, such as macrophages, fibroblasts, and mesenchymal stem cells. In the present study, the aim was to morphologically classify the fusion-hybrid cells observed in the primary tumor and multiple metastases EL4 formed from cells expressing red fluorescent protein (RFP) in transgenic mice expressing green fluorescent protein (GFP), in a syngeneic model. Materials and Methods: RFP-expressing EL4 murine lymphoma cells were cultured in vitro. EL4-RFP cells were harvested and injected intraperitoneally into immunocompetent transgenic C57/BL6- GFP mice to establish a syngeneic model. Two weeks later, mice were sacrificed and each organ was harvested, cultured, and observed using confocal microscopy. Results: EL4 intraperitoneal tumors (primary) and metastases in the lung, liver, blood, and bone marrow were formed. All tumors were harvested and cultured. In all specimens, RFP-EL4 cells, GFPstromal cells, and fused yellow-fluorescent hybrid cells were observed. The fused hybrid cells showed various morphologies. Immune cell-like round-shaped yellow-fluorescent fused cells had a tendency to decrease with time in liver metastases and circulating blood. In contrast fibroblast-like spindle-shaped yellow-fluorescent fused cells increased in the intraperitoneal primary tumor, lung metastases, and bone marrow. Conclusion: Cell fusion between EL4-RFP cells and GFP stromal cells occurred in primary tumors and all metastatic sites. The morphology of the fused hybrid cells varied in the primary and metastatic sites. The present results suggest that fused cancer and stromal hybrid cells of varying morphology may play an important role in cancer progression. [ABSTRACT FROM AUTHOR]

This article discusses a case of dermatomyositis in a 69-year-old man who was later diagnosed with diffuse large B-cell lymphoma. The article emphasizes the challenges in diagnosing and treating dermatomyositis when there is an underlying malignancy, and stresses the importance of thorough screening for malignancies in patients with dermatomyositis. It also mentions the association between anti-TIF1-γ antibodies and malignancies in dermatomyositis. The text suggests that dysphagia may be a useful clinical sign in diagnosing dermatomyositis and that cases with vesicular rash are generally associated with malignancies. The article discusses the use of steroids and IVIG as treatments for dermatomyositis and the potential use of 18F-FDG PET-CT as a screening test for malignancies. It highlights the challenges in diagnosing and treating malignancies in patients with dermatomyositis and emphasizes the need for aggressive screening for malignancies in older patients with anti-TIF-1γ antibody-positive dermatomyositis. [Extracted from the article]

Lymphomas are a diverse group of neoplastic disorders arising primarily in lymph nodes. They have been majorly classified into Hodgkin and Non-Hodgkin lymphomas(NHL). NHL can be of B, T and Null cell categories having further subtypes based on their histological characteristics. Lymphomas can be nodal and extra nodal. The head and neck area are the second most common site of extra nodal lymphoma, with tonsils being the most common site of involvement; other sites include the nasopharynx and tongue base. B- Cell type being the most common type. Predominantly occurs in elderly. Presentations depends on the site involved. Various modalities like surgical treatment, chemotherapy (or) radiotherapy is available. Each stage has varied survival rates and prognosis and responses to the treat depending on the patient factors. In this paper, we report two cases of patients with non-Hodgkin lymphoma of tonsil, where the preoperative clinical diagnosis and radiological diagnosis was inconclusive and final diagnosis was established based on histopathological examination. [ABSTRACT FROM AUTHOR]

Neurolymphomatosis (NL) is a rare complication of non-Hodgkin's lymphoma, characterized by the infiltration of lymphoma cells into the peripheral nerves. A 54-year-old woman initially presented with right facial palsy without any other significant symptoms and was diagnosed with Bell's palsy. Despite initial improvement, her condition recurred, prompting further evaluation. Magnetic resonance imaging (MRI) revealed contrast enhancement from the tympanic segment to the surface of the masseter muscle along the right facial nerve and an adjacent mass lesion. Biopsy of the mass revealed a diagnosis of T-cell/histiocyte-rich large B-cell lymphoma. Chemotherapy resulted in complete resolution of facial palsy. Follow-up MRI confirmed the absence of contrast enhancement along the facial nerve. Facial palsy was considered to be caused by NL. This case was classified as that of primary NL because the facial palsy was the first manifestation of a hematologic malignancy. Recurrent facial palsy, which is atypical in Bell's palsy, led to further evaluation with MRI, which finally resulted in the diagnosis of malignant lymphoma. In cases of recurrent facial palsy, clinicians should consider various diagnoses, including that of NL, and advocate early imaging tests and biopsy, if possible, for accurate diagnosis and improved outcomes. [ABSTRACT FROM AUTHOR]

Chylothorax is the presence of chylus in the pleural cavity and is due to the damage or blockage of the thoracic duct. Surgery or trauma is the most common cause of chylothorax. Malignant lymphoma is the most common cause among nontraumatic etiology. Whenever a chylothorax of unknown etiology occurs, we should rule out underlying malignant lymphoma. Here, we present a case of lymphoma presented with bilateral chylothorax.

This study aims to to establish a diagnosis model based on simple clinical features for children with cervical histiocytic necrotizing lymphadenitis or malignant lymphoma. Simple clinical features of pediatric patients were analyzed to develop a diagnosis model based on a comparison of classical machine-learning algorithms. This was a single-center retrospective study in a tertiary pediatrics hospital. Pediatric patients treated for cervical histiocytic necrotizing lymphadenitis or malignant lymphoma treated at our institution in recent 5 years were included. Demographic data and laboratory values were recorded and binary logistics regression analysis was applied to select possible predictors to develop diagnostic models with different algorithms. The diagnostic efficiency and stability of each algorithm were evaluated to select the best one to help establish the final model. Eighty-three children were included with 45 cases of histiocytic necrotizing lymphadenitis and 38 cases of malignant lymphoma. Peak temperature, white blood cell count, monocyte percentage, and urea value were selected as possible predictors based on the binary logistics regression analysis, together with imaging features already reported (size, boundary, and distribution of mass). In the ten-round random testing sets, the discriminant analysis algorithm achieved the best performance with an average accuracy of 89.0% (95% CI 86.2–93.6%) and an average AUC value of 0.971 (95% CI 0.957–0.995). Conclusion: A discriminant analysis model based on simple clinical features can be effective in differential diagnosis of cervical histiocytic necrotizing lymphadenitis and malignant lymphoma in children. Peak body temperature, white blood cell count, and short diameter of the largest mass are significant predictors. What is Known: • Several multivariate diagnostic models for HNL and ML have been proposed based on B-ultrasound or CT features in adults. • The differences between children and adults are nonnegligible in the clinical featues of HNL. What is New: • The study firstly report a large-sample diagnostic model between the HNL and MLin pediatric patients. • Non-imaging clinical features has also been proven with quite good diagnostic value. [ABSTRACT FROM AUTHOR]

Malignant lymphoma (ML) is a group of malignant tumors originating from the lymphatic hematopoietic system. Previous studies have found a correlation between circulating immune cells and ML. Nonetheless, the precise influence of circulating immune cells on ML remains uncertain.

The goal of the study involved the comparison of clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of malignant lymphoma (ML). The effectiveness of allo-HSCT versus auto-HSCT in the treatment of ML was compared by searching EMBASE, PubMed, Web of Science, and the Cochrane Library for relevant studies. The confidence intervals (CI) and odds ratio (OR) of the article’s outcomes were described by a forest plot. Finally, 972 patients in seven articles were included. Overall survival (OS) did not differ significantly between allo-HSCT and auto-HSCT groups (OR = 0.87, 95% CI: 0.66–1.14, P = 0.31). Furthermore, there was no significant difference in adverse reactions (AR) between the two groups (OR = 1.35, 95% CI: 0.81–2.24, P = 0.25). We observed a significant difference in progression-free survival (PFS) between the two groups (OR = 4.14, 95% CI: 2.93–5.35, P < 0.01). There was no evidence of publication bias in this meta-analysis. The incidence of OS and AR differ significantly between allo-HSCT and auto-HSCT, but the PFS was longer in ML patients who received allo-HSCT.

Background/Aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using a 19-gauge needle is an efficient sampling method for the diagnosis of lymphadenopathy. This study compared 19-gauge conventional and Franseen needles for the diagnosis of lymphadenopathy and classification of malignant lymphoma (ML). Methods Patient characteristics, number of needle passes, puncture route, sensitivity, specificity, and accuracy of cytology/histology for lymphadenopathy were analyzed in patients diagnosed with lymphadenopathy by EUS-FNA using conventional or Franseen needles. Results Between 2012 and 2022, 146 patients met the inclusion criteria (conventional [n=70] and Franseen [n=76]). The median number of needle passes was significantly lower in the conventional group than in the Franseen group (3 [1–6] vs. 4 [1–6], p=0.023). There were no significant differences in cytological/histological diagnoses between the two groups. For ML, the immunohistochemical evaluation rate, sensitivity of flow cytometry, and cytogenetic assessment were not significantly different in either group. Bleeding as adverse events (AEs) were observed in three patients in the Franseen group. Conclusions Both the 19-gauge conventional and Franseen needles showed high accuracy in lymphadenopathy and ML classification. Considering sufficient tissue collection and the avoidance of AEs, the use of 19-gauge conventional needles seems to be a good option for the diagnosis of lymphadenopathy.

Intravascular large B-cell lymphoma (IVLBCL), a rare subtype of malignant lymphoma, is diagnosed by observation of intravascular proliferation of tumor cells in samples taken from affected organs. However, diagnosis of IVLBCL is usually difficult due to the lack of mass formation. IVLBCL may be fatal when the diagnosis is delayed, so an accurate early diagnosis is the key to successful treatment. Random skin biopsy (RSB), in which specimens are sampled from normal-appearing skin, has been reported as useful. However, the specific method of RSB remains controversial, with individual institutions using either the punch method or the incisional method. Research has shown that the incisional method has higher sensitivity than the punch method. We discuss whether this difference might owe to the collection of punch specimens from an insufficient depth and whether the punch method might result in false negatives. For RSB, we recommend taking specimens not only from normal-appearing skin, but also from any lesional skin, because lesions may reflect micro IVLBCL lesions. To ensure accurate diagnosis, both dermatologists and hematologists should know the proper method of RSB. This review summarizes the appropriate biopsy method and sites for RSB. [ABSTRACT FROM AUTHOR]

Background: Biliary obstruction due to compression by a B-cell solid tumor occurs rarely. A few reports have described biliary reconstruction surgery for obstructive jaundice caused by Burkitt's lymphoma. However, there are no detailed reports on pediatric cases. We report a pediatric case of obstructive jaundice due to malignant lymphoma treated with biliary reconstruction surgery. Case presentation: A 5-year-old girl presented to our hospital with a massive abdominal tumor that caused biliary stricture. Chemotherapy was initiated after an open tumor biopsy. However, endoscopic biliary stent placement was performed owing to elevated bilirubin levels. We treated the patient with chemotherapy for 9 months while endoscopically replacing the biliary stent every few months. She achieved complete tumor remission. However, sclerotic lymph nodes were persistent on the dorsal side of the cholecystic duct junction, and biliary stricture at the same site had changed to stent-dependent biliary obstruction. Therefore, we performed choledochojejunostomy and retrocolic Roux-en-Y reconstruction 15 months after initial admission. There were no postoperative complications or tumor recurrences, and the bilirubin level remained low. Histopathologically, the resected bile duct wall was fibrotic and thick, and the bile duct lumen narrowed. Conclusions: Biliary reconstruction is effective to achieve long-term biliary patency in pediatric patients with stent-dependent biliary obstruction due to malignant lymphoma. However, the decision on when to stop biliary stent replacement and proceed to biliary reconstruction surgery is a matter of debate. Further case studies are required to address this issue. [ABSTRACT FROM AUTHOR]

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using a 19-gauge needle is an efficient sampling method for the diagnosis of lymphadenopathy. This study compared 19-gauge conventional and Franseen needles for the diagnosis of lymphadenopathy and classification of malignant lymphoma (ML). Methods: Patient characteristics, number of needle passes, puncture route, sensitivity, specificity, and accuracy of cytology/histology for lymphadenopathy were analyzed in patients diagnosed with lymphadenopathy by EUS-FNA using conventional or Franseen needles. Results: Between 2012 and 2022, 146 patients met the inclusion criteria (conventional [n=70] and Franseen [n=76]). The median number of needle passes was significantly lower in the conventional group than in the Franseen group (3 [1-6] vs. 4 [1-6], p=0.023). There were no significant differences in cytological/histological diagnoses between the two groups. For ML, the immunohistochemical evaluation rate, sensitivity of flow cytometry, and cytogenetic assessment were not significantly different in either group. Bleeding as adverse events (AEs) were observed in three patients in the Franseen group. Conclusions: Both the 19-gauge conventional and Franseen needles showed high accuracy in lymphadenopathy and ML classification. Considering sufficient tissue collection and the avoidance of AEs, the use of 19-gauge conventional needles seems to be a good option for the diagnosis of lymphadenopathy. [ABSTRACT FROM AUTHOR]

Summary: We report the outcome of 563 cases of newly diagnosed lymphoma registered in 2019–2021, including 176 cases (31.2%) of Hodgkin lymphoma (HL), 130 (23.1%) of diffuse large B‐cell lymphoma (DLBCL), 28 (5%) of follicular lymphoma (FL), 16 (2.9%) of mantle cell lymphoma (MCL) and 20 (3.5%) of peripheral T‐cell lymphoma (PTCL). After a median follow‐up of 30.1 months (95% CI: 28.8–31.3), the 3‐year overall survival rates were 95%, 83%, 86%, 100%, 61% and 42% for HL, DLBCL, CLL, FL, MCL and PTCL respectively. These data offer valuable information on the curability of lymphoma patients in Ukraine, in a real‐world setting. [ABSTRACT FROM AUTHOR]

Abstract A 20‐year‐old Japanese man visited our hospital because an enlarged mediastinal shadow had been detected on chest x‐ray. Chest computed tomography revealed a large mediastinal mass with multiple lymph node enlargement, pericardial effusion, and bilateral pleural effusion. He was diagnosed with inflammatory myofibroblastic tumor (IMT) based on a thoracoscopic tumor biopsy. Initial corticosteroid and celecoxib treatment was only partially effective; therefore, additional tumor rebiopsy and left axillary lymph node biopsy were performed. Based on the findings, the patient was rediagnosed with classical Hodgkin lymphoma (CHL). To date, there has only been one report of a case initially diagnosed as IMT and rediagnosed as CHL, as in our case, and only three reports of malignant lymphoma mimicking IMT. When IMT is suspected based on pathological findings and subsequently with treatment failure, possible CHL and performing rebiopsy should be considered.

Objective To investigate the status of disease perception and its related influencing factors in patients with malignant lymphoma (ML), and to provide reference for the formulation and implementation of targeted interventions. Methods A total of 142 ML patients hospitalized in the Department of Hematology of this hospital from February 2021 to March 2022 were investigated by using general information questionnaire, simple disease perception questionnaire and fear of disease progression simplified scale. Results The disease perception score of ML patients was（54. 81±10. 93). The results of multiple linear regression showed that the main influencing factors of disease perception in ML patients were disease stage, family relationship, self-efficacy and fear of disease progression（P＜0. 05). Conclusion The disease perception of ML patients is at a high level, and there are many factors affecting disease perception. Nursing staff can focus on patients with higher disease stage and poor family relationship, improve their positive cognitive ability and personal self-efficacy, so as to promote rehabilitation and improve the quality of life. [ABSTRACT FROM AUTHOR]

Aims: T‐follicular helper (TFH) cells are effector T‐cells that are crucial for B‐cell selection and differentiation. T‐cell lymphomas derived from TFH cells have distinct characteristics. Additionally, in the World Health Organization (WHO) classification 5th edition, three lymphomas were introduced as independent disease entities with TFH cell origin. We aimed to investigate the clinicopathological features of adult T‐cell leukemia/lymphoma (ATLL) with a TFH phenotype (TFHP). Methods and Results: We performed TFH immunohistochemistry analysis of five biomarkers for the biopsy specimen, with TFHP being indicated by a positive result for more than two markers. Among 75 cases of ATLL, 37.3% of them showed TFHP. Compared with cases of ATLL without TFHP, cases of ATLL with TFHP showed higher C‐reactive protein levels (p = 0.0219) and increased high endothelial venule proliferation (p = 0.024). However, there were no significant between‐group differences in overall survival as well as other clinical and morphological findings. Furthermore, there was no significant between‐group difference in TFH markers and FOXP3 expression. Conclusion: Some patients with ATLL may present a TFHP, which should not preclude the diagnosis of ATLL. Although presenting a TFHP does not affect prognosis, it is important to identify cases of ATLL with a TFHP since it may inform future treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: Vincristine (VCR) often induces peripheral neuropathy (PN) as an adverse event. Currently, there is no consensus on the prevention of vincristine-induced PN (VIPN). In this study, we aimed to investigate the efficacy of compression therapy using surgical gloves for preventing VIPN. Methods: Patients with malignant lymphoma (vincristine-naïve) who were receiving chemotherapy with cyclophosphamide, doxorubicin, VCR, and prednisolone, with or without rituximab, every 3 weeks for six cycles were eligible. For every VCR infusion, each patient wore two one-size-smaller gloves on one hand (study hand) for 90 min. The other hand was left bare (control hand). PN was assessed at each treatment using the Common Terminology Criteria for Adverse Events ver. 4.0. Results: Fifty-one patients with malignant lymphoma were enrolled and 44 were evaluated. At 1 month after treatment, the occurrence rates of grade ≥ 2 sensory PN were 13.6 and 13.6% in the study and control hands, respectively (p = 1.0), and those of grade ≥ 2 motor PN were 15.9 and 15.9% in the study and control hands, respectively (p = 1.0). Conclusion: Compression therapy using surgical gloves showed no significant effect for the prevention of VIPN. Trial registration: November 1, 2018, National University Hospital Council of Japan (UMIN 000034145). [ABSTRACT FROM AUTHOR]

Malignant lymphoma, which impacts the lymphatic system, presents diverse challenges in accurate diagnosis due to its varied subtypes—chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). Lymphoma is a form of cancer that begins in the lymphatic system, impacting lymphocytes, which are a specific type of white blood cell. This research addresses these challenges by proposing ensemble and non-ensemble transfer learning models employing pre-trained weights from VGG16, VGG19, DenseNet201, InceptionV3, and Xception. For the ensemble technique, this paper adopts a stack-based ensemble approach. It is a two-level classification approach and best suited for accuracy improvement. Testing on a multiclass dataset of CLL, FL, and MCL reveals exceptional diagnostic accuracy, with DenseNet201, InceptionV3, and Xception exceeding 90% accuracy. The proposed ensemble model, leveraging InceptionV3 and Xception, achieves an outstanding 99% accuracy over 300 epochs, surpassing previous prediction methods. This study demonstrates the feasibility and efficiency of the proposed approach, showcasing its potential in real-world medical applications for precise lymphoma diagnosis. [ABSTRACT FROM AUTHOR]

Agarose-based cell block (CB) technique can be modified to be combined with the frozen section technique for the preparation of a high-quality frozen-embedded CB (F-CB) from an effusion or fine-needle aspiration (FNA) cytology sample. This combined technique can be effectively used for the immunocharacterization of the hematolymphoid cells on F-CB. To demonstrate the applicability of performing diagnostic ICC on F-CB, we have analyzed the immunophenotype of the hematolymphoid cells in a series of eight cases of effusions and eight cases of FNA cytology specimens by using CB-ICC on sections cut from frozen-embedded CBs. The SurePathTM residue or cytologic material scraped off from the FNA cytology smear that was diagnostic for or suspicious of hematolymphoid malignancy was pelleted and pre-embedded in agarose. Half of the agarose-embedded pellet was frozen-embedded in OCT compound for the preparation of F-CB, while the other half was processed for the preparation of paraffin-embedded CB. Sections cut from the F-CB and P-CB were used for CB-ICC. Panels of ICC on the F-CBs could enable the immunocytochemical differential diagnosis of large cell hematologic malignancies that encompass anaplastic large cell lymphoma and other forms of large-cell hematolymphoid malignancies such as large B-cell lymphomas, anaplastic plasma cell myeloma, myeloid sarcoma, and T-lymphoblastic lymphoma. It also appeared that the small B-cell lymphomas in the effusions or FNAs could be differentially diagnosed with the aid of CB-ICC on the F-CB. A modified agarose-based CB technique can be combined with the frozen-embedded CB method for the preparation of F-CB that can be directly used for the immunocytochemical differential diagnosis of hematolymphoid cytology samples. [ABSTRACT FROM AUTHOR]

A 20‐year‐old Japanese man visited our hospital because an enlarged mediastinal shadow had been detected on chest x‐ray. Chest computed tomography revealed a large mediastinal mass with multiple lymph node enlargement, pericardial effusion, and bilateral pleural effusion. He was diagnosed with inflammatory myofibroblastic tumor (IMT) based on a thoracoscopic tumor biopsy. Initial corticosteroid and celecoxib treatment was only partially effective; therefore, additional tumor rebiopsy and left axillary lymph node biopsy were performed. Based on the findings, the patient was rediagnosed with classical Hodgkin lymphoma (CHL). To date, there has only been one report of a case initially diagnosed as IMT and rediagnosed as CHL, as in our case, and only three reports of malignant lymphoma mimicking IMT. When IMT is suspected based on pathological findings and subsequently with treatment failure, possible CHL and performing rebiopsy should be considered. [ABSTRACT FROM AUTHOR]

Pseudolymphoma is a reactive process involving lymphadenopathy, polyclonal proliferation of B or T-cells, simulating oral lymphoma. With its incidence being very rare, only four cases have been reported in oral cavity with the detailed immunocytochemical examination, which can be due to this entity's unawareness, underdiagnosis or overdiagnosis. It is prerogative to perform immunocytochemical investigations to prevent overdiagnosis as lymphoma, which can be debilitating to the patient. Wherein the treatment of pseudolymphoma initially includes topical or intralesional corticosteroid, antibiotics to surgical and radiotherapy based on its etiology. Herein, we discuss B-cell follicular lymphoid hyperplasia previously diagnosed as small round cell tumor. [ABSTRACT FROM AUTHOR]

Lymphoma refers to a group of heterogeneous malignancies originating from the reticuloendothelial and lymphatic systems. The clinical manifestations, treatment strategies, and disease outcomes of different types of lymphoma considerably vary. Recent developments in high-throughput sequencing technologies have enhanced understanding of the pathogenesis and molecular stratification of lymphoma. In the era of new drugs, precise stratification and targeted drug selection can not only improve the prognosis of patients with lymphoma but also reduce the toxic side effects of traditional chemotherapy, ultimately achieving the accurate diagnosis and individualized treatment of tumors. This article reviews the research progress of molecular diagnosis and individualized treatment of different lymphoma subtypes and lymphoma-related research in important meetings such as ASCO, EHA, and ICML in 2023.

Abstract Background Differentiation between head-and-neck malignant lymphoma and squamous cell carcinoma is crucial as their management is radically different, and this retrospective study aims at demonstrating the value of DWI-MRI for their discrimination. Forty-four patients with pathologically proved untreated head-and-neck ML and SCC (22 ML and 22 SCC) were included in the study, and they underwent conventional MRI imaging (T1WI and T2WI) with DW-MRIs at standard and high b-values with corresponding ADC maps which were generated along with a reference of the ADC values taken at the spinal cord and cerebrospinal fluid as an internal control. The sensitivity and specificity at the optimum cutoff point as well as the area under the receiver operating characteristic (ROC) curve were used for evaluation of diagnostic performance of DW-MRI at b 1000, b 1500, b 2000 s/mm2. Results The mean SCC ADC values were much higher than ML at standard (b 1000) and high b-values (b 1500 and b 2000). ROC curve analysis for the ADC values of SCC and ML at b 1000, b 1500 and b 2000 s/mm2 showed that the ADC cutoff values are > 0.83, > 0.75 and > 0.67 × 10−3 mm2/s, respectively, with diagnostic accuracy 95.5%. Conclusions As to sum up, we can safely say that we can fully rely on DWI MRI in differentiation between HNSCC and ML whether using standard or high b-values, as well as in discrimination of different histological grades of HNSCC as it revealed impressive results, which confer us to do without contrast in such cases.

Intravascular lymphoma is characterized by an exclusively intravascular distribution of tumor cells. Intravascular natural killer/T-cell lymphoma (IVNKTL) is extremely rare, highly aggressive, commonly Epstein-Barr virus (EBV)–positive, and predominantly affects the skin and central nervous system. Here we report a case of IVNKTL diagnosed in a 67-year-old female, presenting with persistent intermittent fever and skin rashes throughout the body. Incisional biopsy of an erythematous lesion on the chest exhibited aggregation of medium to large-sized atypical lymphoid cells confined to the lumen of small vessels that were positive for CD3, granzyme B, and CD56 on immunohistochemistry and EBV-encoded RNA in situ hybridization. EBV DNA was also detected in serum after diagnosis. With a review of 26 cases of IVNKTL to date, we suggest that active biopsy based on EBV DNA detection may facilitate early diagnosis of IVNKTL.

Objectives: To compare the [18F]FDG PET/CT findings of untreated sarcoidosis and malignant lymphoma (ML) and develop convolutional neural network (CNN) models to differentiate between these diseases using maximum intensity projection (MIP) [18F]FDG PET images. Methods: We retrospectively collected data on consecutive patients newly diagnosed with sarcoidosis and ML who underwent [18F]FDG PET/CT before treatment. Two nuclear radiologists reviewed the images. CNN models were created using MIP PET images and evaluated with k-fold cross-validation. The points of interest were visualized using gradient-weighted class activation mapping (Grad-CAM). Results: A total of 56 patients with sarcoidosis and 62 patients with ML were included. Patients with sarcoidosis had more prominent FDG accumulation in the mediastinal lymph nodes and lung lesions, while those with ML had more prominent accumulation in the cervical lymph nodes (all p < 0.001). For the mediastinal lymph nodes, sarcoidosis patients had significant FDG accumulation in the level 2, 4, 7, and 10 lymph nodes (all p < 0.01). Otherwise, the accumulation in ML patients tended to be in the level 1 lymph nodes (p = 0.08). The CNN model using frontal and lateral MIP images achieved an average accuracy of 0.890 (95% CI: 0.804–0.977), a sensitivity of 0.898 (95% CI: 0.782–1.000), a specificity of 0.907 (95% CI: 0.799–1.000), and an area under the curve of 0.963 (95% CI: 0.899–1.000). Grad-CAM showed that the model focused on the sites of abnormal FDG accumulation. Conclusions: CNN models based on differences in FDG accumulation sites archive high performance in differentiating between sarcoidosis and ML. Clinical relevance statement: We developed a CNN model using MIP images of [18F]FDG PET/CT to distinguish between sarcoidosis and malignant lymphoma. It achieved high performance and could be useful in diagnosing diseases with involvement across organs and lymph nodes. Key Points: • There are differences in FDG distribution when comparing whole-body [18F]FDG PET/CT findings in patients with sarcoidosis and malignant lymphoma before treatment. • Convolutional neural networks, a type of deep learning technique, trained with maximum-intensity projection PET images from two angles showed high performance. • A deep learning model that utilizes differences in FDG distribution may be helpful in differentiating between diseases with lesions that are characteristically widespread among organs and lymph nodes. [ABSTRACT FROM AUTHOR]

Background: Differentiation between head-and-neck malignant lymphoma and squamous cell carcinoma is crucial as their management is radically different, and this retrospective study aims at demonstrating the value of DWI-MRI for their discrimination. Forty-four patients with pathologically proved untreated head-and-neck ML and SCC (22 ML and 22 SCC) were included in the study, and they underwent conventional MRI imaging (T1WI and T2WI) with DW-MRIs at standard and high b-values with corresponding ADC maps which were generated along with a reference of the ADC values taken at the spinal cord and cerebrospinal fluid as an internal control. The sensitivity and specificity at the optimum cutoff point as well as the area under the receiver operating characteristic (ROC) curve were used for evaluation of diagnostic performance of DW-MRI at b 1000, b 1500, b 2000 s/mm2. Results: The mean SCC ADC values were much higher than ML at standard (b 1000) and high b-values (b 1500 and b 2000). ROC curve analysis for the ADC values of SCC and ML at b 1000, b 1500 and b 2000 s/mm2 showed that the ADC cutoff values are > 0.83, > 0.75 and > 0.67 × 10−3 mm2/s, respectively, with diagnostic accuracy 95.5%. Conclusions: As to sum up, we can safely say that we can fully rely on DWI MRI in differentiation between HNSCC and ML whether using standard or high b-values, as well as in discrimination of different histological grades of HNSCC as it revealed impressive results, which confer us to do without contrast in such cases. [ABSTRACT FROM AUTHOR]

Lymphoma refers to a group of heterogeneous malignancies originating from the reticuloendothelial and lymphatic systems. The clinical manifestations, treatment strategies, and disease outcomes of different types of lymphoma considerably vary. Recent developments in high-throughput sequencing technologies have enhanced understanding of the pathogenesis and molecular stratification of lymphoma. In the era of new drugs, precise stratification and targeted drug selection can not only improve the prognosis of patients with lymphoma but also reduce the toxic side effects of traditional chemotherapy, ultimately achieving the accurate diagnosis and individualized treatment of tumors. This article reviews the research progress of molecular diagnosis and individualized treatment of different lymphoma subtypes and lymphoma-related research in important meetings such as ASCO, EHA, and ICML in 2023. [ABSTRACT FROM AUTHOR]

Background: We report a case of diffuse large B-cell lymphoma that progressed rapidly after androgen deprivation therapy for prostate cancer in a patient with a history of IgG4-related disease. Estrogen has been reported to be a possible cause of acute exacerbations of malignant lymphoma only in mouse models. Therefore, its clinical significance has not been clarified. Case presentation: This case report describes a 75-year-old man with prostate cancer who had IgG4-related disease. Hormone therapy was initiated to treat prostate cancer, but he developed dyspnea and back pain. A diagnosis was made of diffuse large B-cell lymphoma. Immunohistochemistry was positive for estrogen receptor β, which led us to suspect rapid progression of diffuse large B-cell lymphoma due to estrogen suppression by gonadotropin-releasing hormone antagonists. Hormone therapy was discontinued, and the patient received R-CHOP therapy. Subsequently, the lymphoma masses shrunk, and the patient obtained remission. Conclusion: This case is the first report of clinical significance regarding the crucial role of estrogen and estrogen receptor β in malignant lymphoma in a patient with IgG4-related disease. Our report aims to raise awareness of the need to carefully select treatment options for prostate cancer patients with IgG4-related disease or lymphoma. [ABSTRACT FROM AUTHOR]

Introduction: Small bowel tumors (SBTs) are difficult to diagnose because of limited opportunities and technical difficulties in evaluating the small bowel. Asymptomatic conditions or nonspecific symptoms make SBT diagnosis more challenging. In Asia, SBTs are reported to be more frequently malignant lymphoma (ML), adenocarcinoma, and gastrointestinal stromal tumor (GIST). In this study, we examined 66 patients diagnosed with SBTs and determined their clinical characteristics. Methods: This retrospective study was conducted from January 2013 to July 2020 at Kurume University Hospital. The modalities used to detect SBTs were computed tomography (CT), positron emission tomography, magnetic resonance imaging, and ultrasonography. Endoscopy was also performed in some cases to confirm SBT diagnosis. The study included 66 patients. The medical data collected included presenting symptoms, tumor location, underlying condition, diagnostic modalities, pathologic diagnosis, and treatment. Results: ML and adenocarcinoma were the most common tumors (22.7%), followed by GIST (21.2%) and metastatic SBT (18.2%). Symptoms that led to SBT detection were abdominal pain (44.5%), asymptomatic conditions (28.8%), hematochezia (12.1%), and anemia (10.6%). CT was the most used modality to detect SBTs. Nineteen patients were asymptomatic, and SBTs were incidentally detected in them. GISTs and benign tumors were more often asymptomatic than other malignant tumors. Conclusion: Abdominal pain was the main symptom for SBTs in particular adenocarcinoma, ML, and metastatic SBT. In addition, GIST, which was highly prevalent in Asia, had fewer symptoms. An understanding of these characteristics may be helpful in the clinical practice of SBTs. [ABSTRACT FROM AUTHOR]

Abstract Aims T‐follicular helper (TFH) cells are effector T‐cells that are crucial for B‐cell selection and differentiation. T‐cell lymphomas derived from TFH cells have distinct characteristics. Additionally, in the World Health Organization (WHO) classification 5th edition, three lymphomas were introduced as independent disease entities with TFH cell origin. We aimed to investigate the clinicopathological features of adult T‐cell leukemia/lymphoma (ATLL) with a TFH phenotype (TFHP). Methods and Results We performed TFH immunohistochemistry analysis of five biomarkers for the biopsy specimen, with TFHP being indicated by a positive result for more than two markers. Among 75 cases of ATLL, 37.3% of them showed TFHP. Compared with cases of ATLL without TFHP, cases of ATLL with TFHP showed higher C‐reactive protein levels (p = 0.0219) and increased high endothelial venule proliferation (p = 0.024). However, there were no significant between‐group differences in overall survival as well as other clinical and morphological findings. Furthermore, there was no significant between‐group difference in TFH markers and FOXP3 expression. Conclusion Some patients with ATLL may present a TFHP, which should not preclude the diagnosis of ATLL. Although presenting a TFHP does not affect prognosis, it is important to identify cases of ATLL with a TFHP since it may inform future treatment strategies.

BackgroundOne of the exceptionally rare forms of non-Hodgkin’s lymphoma (NHL) is primary cardiac lymphoma (PCL). The principal clinical manifestation in patients with PCL involves cardiac symptoms resulting from myocardial infiltration by lymphoma, including arrhythmias, heart failure, and chest pain. 18F-FDG PET/CT serves as a reliable and indispensable imaging modality for assessing clinically staging NHL.Case reportWe present a rare case involving a 72-year-old woman diagnosed with primary intracardiac diffuse large B-cell lymphoma. For further staging, the patient underwent 18F-FDG PET/CT, revealing multiple nodular soft tissue density lesions in the heart and pericardium exhibiting increased FDG metabolism (SUVmax = 12.1). The supradiaphragmatic and infradiaphragmatic segments of the inferior vena cava exhibited irregular morphology with localized nodular changes and increased FDG metabolism in the surrounding area (SUVmax = 9.7). Additionally, multiple enlarged lymph nodes were identified in the left axilla, mediastinum, and adjacent to the abdominal aorta, displaying heterogeneous FDG uptake with an SUVmax of 9.3, indicating lymphoma involvement. The above imaging findings suggested that the mass was a PCL. Hence, the patient underwent a combination of chemotherapy and immunotherapy using R-CDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone). Following two courses of treatment within a span of 2 months, there was a partial remission observed in the cardiac lymphoma and the enlarged lymph nodes.ConclusionThe case elucidated in this report contributes to an enhanced understanding of the disease for clinicians, with 18F-FDG PET/CT providing comprehensive insights into the extent of cardiac involvement, as well as the engagement of extracardiac organs and pathologic lymph nodes. The 18F-FDG PET/CT examination not only visually delineates the lesion’s location and extent but also serves as a cornerstone for clinical tumor staging, offering valuable support for treatment monitoring and subsequent follow-up.

Abstract Background Previous research has already indicated an elevated risk of breast cancer (BC) among survivors of malignant lymphoma, but the underlying reasons remain unknown. Our objective is to elucidate the causal relationship between malignant lymphoma and BC through Mendelian randomization (MR). Genome-wide association studies (GWAS) data from 181,125 Hodgkin lymphoma (HL) patients and 181,289 non-Hodgkin lymphoma (NHL) patients from the FinnGen Consortium were utilized as exposure. We selected single nucleotide polymorphisms (SNPs) strongly associated with the exposure as instrumental variables to investigate their relationship with BC in a cohort of 107,722 participants. Subsequently, we obtained data from the UK Biobank containing gender-stratified information on HL, NHL, and BC. We validated the findings from our analysis and explored the impact of gender. The Inverse-Variance Weighted (IVW) method served as the primary reference for the two-sample MR, accompanied by tests for heterogeneity and pleiotropy. Results The analysis results from the FinnGen consortium indicate that there is no causal relationship between HL and NHL with BC. HL (OR = 1.01, 95% CI = 0.98–1.04, p = 0.29), NHL (OR = 1.01, 95% CI = 0.96–1.05, p = 0.64). When utilizing GWAS data from the UK Biobank that includes different gender cohorts, the lack of association between HL, NHL, and BC remains consistent. HL (OR = 1.08, 95% CI = 0.74–1.56, p = 0.69), HL-Female (OR = 0.84, 95% CI = 0.59–1.19, p = 0.33), NHL (OR = 0.89, 95% CI = 0.66–1.19, p = 0.44), and NHL-Female (OR = 0.81, 95% CI = 0.58–1.11, p = 0.18). Conclusions The two-sample MR analysis indicates that there is no significant causal relationship between malignant lymphoma (HL and NHL) and BC. The association between malignant lymphoma and breast cancer requires further in-depth research and exploration.

Introduction Urachus carcinoma is a rare malignancy with an aggressive potential and a poor prognosis, and evidence is limited for its diagnosis and treatment. Case presentation A 75‐year‐old man underwent fluorodeoxyglucose positron emission tomography/computed tomography for staging prostate cancer, and a mass (standardized uptake value max 9.5) was observed on the outside of the urinary bladder dome. T2‐weighted magnetic resonance imaging showed the urachus and a low‐intensity tumor, which suggested a malignant tumor. We suspected urachal carcinoma and performed total resection of the urachus and partial cystectomy. Pathological examination revealed mucosa‐associated lymphoid tissue lymphoma with cells positive for CD20 and negative for CD3, CD5, and cyclin D1. After the surgery, no recurrence has been observed for more than 2 years. Conclusion We encountered an extremely rare case of mucosa‐associated lymphoid tissue lymphoma of the urachus. Surgical resection of the tumor provided an accurate diagnosis and good disease control.

Abstract Background Pathological examination by endoscopic ultrasonography–guided fine-needle aspiration (EUS-FNA) has been reported to be useful in diagnosing pancreatic malignant lymphoma (ML), but some ML cases are difficult to be differentiated from pancreatic ductal adenocarcinoma (PDAC). Methods This retrospective study included 8 patients diagnosed with ML that had a pancreatic-head lesion at initial diagnosis and 46 patients with resected PDAC in the pancreatic head between April 2006 and October 2021 at our institute. ML and PDAC were compared in terms of patients’ clinical features and imaging examinations. Results The median tumor size was larger in ML than in PDAC (45.8 [24–64] vs. 23.9 [8–44] mm), but the median diameter of the caudal main pancreatic duct (MPD) was larger in PDAC (2.5 [1.0–3.5] vs. 7.1 [2.5–11.8] mm), both showing significant differences between these malignancies (both, P

Background: Previous research has already indicated an elevated risk of breast cancer (BC) among survivors of malignant lymphoma, but the underlying reasons remain unknown. Our objective is to elucidate the causal relationship between malignant lymphoma and BC through Mendelian randomization (MR). Genome-wide association studies (GWAS) data from 181,125 Hodgkin lymphoma (HL) patients and 181,289 non-Hodgkin lymphoma (NHL) patients from the FinnGen Consortium were utilized as exposure. We selected single nucleotide polymorphisms (SNPs) strongly associated with the exposure as instrumental variables to investigate their relationship with BC in a cohort of 107,722 participants. Subsequently, we obtained data from the UK Biobank containing gender-stratified information on HL, NHL, and BC. We validated the findings from our analysis and explored the impact of gender. The Inverse-Variance Weighted (IVW) method served as the primary reference for the two-sample MR, accompanied by tests for heterogeneity and pleiotropy. Results: The analysis results from the FinnGen consortium indicate that there is no causal relationship between HL and NHL with BC. HL (OR = 1.01, 95% CI = 0.98–1.04, p = 0.29), NHL (OR = 1.01, 95% CI = 0.96–1.05, p = 0.64). When utilizing GWAS data from the UK Biobank that includes different gender cohorts, the lack of association between HL, NHL, and BC remains consistent. HL (OR = 1.08, 95% CI = 0.74–1.56, p = 0.69), HL-Female (OR = 0.84, 95% CI = 0.59–1.19, p = 0.33), NHL (OR = 0.89, 95% CI = 0.66–1.19, p = 0.44), and NHL-Female (OR = 0.81, 95% CI = 0.58–1.11, p = 0.18). Conclusions: The two-sample MR analysis indicates that there is no significant causal relationship between malignant lymphoma (HL and NHL) and BC. The association between malignant lymphoma and breast cancer requires further in-depth research and exploration. [ABSTRACT FROM AUTHOR]

The anterior mediastinum is the most common location of mediastinal tumors, and thymic epithelial tumors are the most common mediastinal tumors. It is important to differentiate thymic epithelial tumors from malignant lymphomas and malignant germ cell tumors because of the different treatment strategies. Dynamic contrast-enhanced MRI and diffusion-weighted imaging can provide additional information on the differential diagnosis. Chemical shift imaging can detect tiny fat tissues in the lesion and is useful in differentiating thymic hyperplasia from other solid tumors such as thymomas. MRI findings reflect histopathological features of mediastinal tumors, and a comprehensive evaluation of MRI sequences is important for estimation of the histopathological features of the tumor. In this manuscript, we describe the MRI findings of anterior mediastinal solid tumors and the role of MRI in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Primary thyroid lymphoma (PTL) occurs rarely, its diagnosis is a challenge, and the prognosis of these patients depends on the time of diagnosis. Even though fine-needle aspiration cytology (FNAC) is recognized as the most accurate tool for detecting thyroid malignancies, its sensitivity for PTL is poor. Both clinical and ultrasound presentation of PTL can be atypical, and laboratory tests fail to furnish relevant data. Consequently, the reliability of a cytopathologist facing PTL can be poor, even when he is aware of its clinical information. In addition, the cases described in the literature are extremely rare and fragmentary, and consequently, the molecular data currently available for this neoplasm are practically negligible. Here, we present a case report in order to discuss the intrinsic limitations in achieving a final diagnosis of PTL and how using molecular diagnostics to identify potential mutational models can improve the evaluation of this neoplasm. [ABSTRACT FROM AUTHOR]

Primary malignant lymphoma confinement to the cauda equina is rare. Only 14 cases of primary malignant lymphoma in the cauda equina have been reported. In these cases, the clinical features were similar to those of lumbar spinal canal stenosis (LSCS). This report describes a case of diffuse large B-cell lymphoma of the cauda equina that was diagnosed after decompression surgery for LSCS. An 80-year-old man presented with gait disturbance due to progressive muscle weakness in the lower extremities over the previous two months. He was diagnosed with LSCS, and decompression surgery was performed. However, the muscle weakness worsened after surgery; therefore, he was referred to our department. Plain magnetic resonance imaging (MRI) revealed swelling of the cauda equina. It demonstrated marked homogenous enhancement by gadolinium-diethylenetriamine pentaacetic acid. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) revealed diffuse accumulation of 18F-FDG in the cauda equina. These imaging findings were consistent with those of cauda equina lymphomas. To confirm the diagnosis, we performed an open biopsy of the cauda equina. Histological examination indicated diffuse large B-cell lymphoma. Considering the patient's age and activities of daily living, further treatment was not performed. The patient died four months after the first surgery. Rapid progression of muscle weakness, which cannot be prevented by decompression surgery, and swollen cauda equina on MRI may be signs of this disorder. Gadolinium-enhanced MRI, 18F-FDG PET, and histological investigation of the cauda equina should be performed for diagnosing primary malignant lymphoma of the cauda equina. [ABSTRACT FROM AUTHOR]

While colorectal cancer is a likely complication associated with inflammatory bowel diseases such as ulcerative colitis, malignant lymphoma occurs less frequently. We report the case of a patient with ulcerative colitis having Epstein–Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified (EBV + DLBCL, NOS), which was maintained in clinical remission with 5-aminosalicylic acid. The patient had received a diagnosis of total ulcerative colitis 5 years ago. A recent colonoscopy revealed a 35 mm protruding lesion with depression in the sigmoid colon, and histopathological examination confirmed the presence of EBV + DLBCL, NOS. The patient has undergone six courses of chemotherapy without recurrence of lymphoma and will continue to be monitored periodically. Patients with ulcerative colitis must be followed up with periodic colonoscopies and imaging studies regardless of their background, treatment, and symptoms to ensure the prevention of complications. Furthermore, while special attention must be paid to the commonly occurring colorectal cancer on account of its association with the patient's prognosis, the possibility of the incidence of malignant lymphoma must not be ignored. [ABSTRACT FROM AUTHOR]

When using imaging to diagnose brain tumors, it is important to determine whether the tumor is intra- or extra-parenchymal. An 80-year-old man was found on magnetic resonance imaging to have an enhanced mass that appeared to be in the falx and a massive hematoma in the left frontal lobe; the provisional diagnosis was falx meningioma. However, the tumor and hematoma were found intraoperatively to be completely intraparenchymal. Additionally, the falx was intact and not adherent to brain tissue. Malignant lymphoma was diagnosed histologically on the basis of abnormal proliferation of atypical CD20-positive lymphocytes. Cerebral hemorrhage is an extremely rare presentation of primary central nervous system lymphoma. To the best of our knowledge, only 7 cases have been reported. All the reported cases had enhancement in the hematoma; however, in our case, there was definite enhancement outside the hematoma, making the correct diagnosis of lymphoma difficult.

Malignant lymphoma, which impacts the lymphatic system, presents diverse challenges in accurate diagnosis due to its varied subtypes—chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). Lymphoma is a form of cancer that begins in the lymphatic system, impacting lymphocytes, which are a specific type of white blood cell. This research addresses these challenges by proposing ensemble and non-ensemble transfer learning models employing pre-trained weights from VGG16, VGG19, DenseNet201, InceptionV3, and Xception. For the ensemble technique, this paper adopts a stack-based ensemble approach. It is a two-level classification approach and best suited for accuracy improvement. Testing on a multiclass dataset of CLL, FL, and MCL reveals exceptional diagnostic accuracy, with DenseNet201, InceptionV3, and Xception exceeding 90% accuracy. The proposed ensemble model, leveraging InceptionV3 and Xception, achieves an outstanding 99% accuracy over 300 epochs, surpassing previous prediction methods. This study demonstrates the feasibility and efficiency of the proposed approach, showcasing its potential in real-world medical applications for precise lymphoma diagnosis.

Objectives: The aim is to investigate the trends in risks of overall and site-specific malignancies in patients with rheumatoid arthritis (RA). Methods: Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort, all malignancies that occurred from 2000 to 2013 were extracted. The standardized incidence ratios and 95% confidence intervals for overall and site-specific malignancies were calculated during three periods: pre-biologics, 2000-04; early biologics, 2005-09; and recent biologics, 2010-13. Risk factors for overall and specific malignancies were analysed using time-dependent Cox regression models. Results: Among 11,299 patients with RA (68,483 person-years), 507 malignancies were confirmed. Similar risks were observed versus the general Japanese population for overall malignancies throughout the three periods, with standardized incidence ratios (95% confidence intervals) of 0.96 (0.80-1.14) in the pre-biologics period, 0.95 (0.82-1.09) in the early biologics period, and 0.87 (0.75-1.01) in the recent biologics period. A significantly increased risk for malignant lymphoma was observed throughout the observation period (standardized incidence ratio 4.61, 95% confidence interval 3.58-5.85). The disease activity was a significant risk factor for overall malignancies and lung cancer. Conclusions: Despite the expanding use of methotrexate and biologics, there were no increases in malignancy risk in Japanese patients with RA. [ABSTRACT FROM AUTHOR]

Malignant lymphoma is one of the most severe types of disease that leads to death as a result of exposure of lymphocytes to malignant tumors. The transformation of cells from indolent B-cell lymphoma to B-cell lymphoma (DBCL) is life-threatening. Biopsies taken from the patient are the gold standard for lymphoma analysis. Glass slides under a microscope are converted into whole slide images (WSI) to be analyzed by AI techniques through biomedical image processing. Because of the multiplicity of types of malignant lymphomas, manual diagnosis by pathologists is difficult, tedious, and subject to disagreement among physicians. The importance of artificial intelligence (AI) in the early diagnosis of malignant lymphoma is significant and has revolutionized the field of oncology. The use of AI in the early diagnosis of malignant lymphoma offers numerous benefits, including improved accuracy, faster diagnosis, and risk stratification. This study developed several strategies based on hybrid systems to analyze histopathological images of malignant lymphomas. For all proposed models, the images and extraction of malignant lymphocytes were optimized by the gradient vector flow (GVF) algorithm. The first strategy for diagnosing malignant lymphoma images relied on a hybrid system between three types of deep learning (DL) networks, XGBoost algorithms, and decision tree (DT) algorithms based on the GVF algorithm. The second strategy for diagnosing malignant lymphoma images was based on fusing the features of the MobileNet-VGG16, VGG16-AlexNet, and MobileNet-AlexNet models and classifying them by XGBoost and DT algorithms based on the ant colony optimization (ACO) algorithm. The color, shape, and texture features, which are called handcrafted features, were extracted by four traditional feature extraction algorithms. Because of the similarity in the biological characteristics of early-stage malignant lymphomas, the features of the fused MobileNet-VGG16, VGG16-AlexNet, and MobileNet-AlexNet models were combined with the handcrafted features and classified by the XGBoost and DT algorithms based on the ACO algorithm. We concluded that the performance of the two networks XGBoost and DT, with fused features between DL networks and handcrafted, achieved the best performance. The XGBoost network based on the fused features of MobileNet-VGG16 and handcrafted features resulted in an AUC of 99.43%, accuracy of 99.8%, precision of 99.77%, sensitivity of 99.7%, and specificity of 99.8%. This highlights the significant role of AI in the early diagnosis of malignant lymphoma, offering improved accuracy, expedited diagnosis, and enhanced risk stratification. This study highlights leveraging AI techniques and biomedical image processing; the analysis of whole slide images (WSI) converted from biopsies allows for improved accuracy, faster diagnosis, and risk stratification. The developed strategies based on hybrid systems, combining deep learning networks, XGBoost and decision tree algorithms, demonstrated promising results in diagnosing malignant lymphoma images. Furthermore, the fusion of handcrafted features with features extracted from DL networks enhanced the performance of the classification models. [ABSTRACT FROM AUTHOR]