Malignant Lymphoma Research Articles

Primary pancreatic peripheral T-cell lymphoma: A case report

BACKGROUND Primary pancreatic lymphoma (PPL) is an exceedingly rare tumor with limited mention in scientific literature. The clinical manifestations of PPL are often nonspecific, making it challenging to distinguish this disease from other pancreatic-related diseases. Chemotherapy remains the primary treatment for these individuals. CASE SUMMARY In this case study, we present the clinical details of a 62-year-old woman who initially presented with vomiting, abdominal pain, and dorsal pain. On further evaluation through positron emission tomography-computed tomography, the patient was considered to have a pancreatic head mass. However, subsequent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) revealed that the patient had pancreatic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin, decitabine, and oxaliplatin (brentuximab vedotin and Gemox). The patient had significant improvement in radiological findings at the end of the first cycle. CONCLUSION Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma, in which the clinical manifestations are often nonspecific. It is difficult to diagnose, and the prognosis is poor. Imaging can only be used for auxiliary diagnosis of other diseases. With the help of immunostaining, EUS-FNA could be used to aid in the diagnosis of PPL. After a clear diagnosis, chemotherapy is still the first-line treatment for such patients, and surgical resection is not recommended. A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma. However, identifying new CD30-targeted therapies for different types of lymphoma is urgently needed. In the future, further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.

Exophthalmos Revealing Malignant Lymphoma

Non-Hodgkin's lymphomas are malignant tumors whose aggressiveness depends on the histological type of the tumor. The orbital localization may be isolated or associated with a systemic lymphoma.
 The clinical polymorphism of malignant lymphomas is extreme, posing diagnostic problems and delaying therapeutic management, which is why anatomopathological examination of a tissue biopsy is the only key to diagnosis.
 We report the case of a patient who presented with exophthalmos revealing a lymphoma.

Optimizing random skin biopsies: a review of techniques and indications for intravascular large B-cell lymphoma.

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.

The Effect of Endobronchial Ultrasound-guided Miniforceps Biopsy to a Patient with Malignant Lymphoma: A Case Report

The Effect of Endobronchial Ultrasound-guided Miniforceps Biopsy to a Patient with Malignant Lymphoma: A Case Report

Diagnostic utility of cytology in a patient with Epstein-Barr virus-positive mucocutaneous ulcer in palatine tonsils: A case report.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly established immunodeficiency-related disease. Herein, we report a case of EBVMCU and focus on its cytological usefulness for diagnosis. An 82-year-old man manifested pharyngalgia, dysphagia, and oral pain. His medical history included rheumatoid arthritis that had been treated with methotrexate. Clinically, peritonsillar abscess was suspected, but since neoplastic lesions, including malignant lymphoma (ML), could not be excluded, a series of cytohistological examination was attempted. Despite some alarming findings (e.g., frequent mitoses), fine-needle aspiration and touch imprint cytology consistently revealed a heterogeneous population of lymphoid and plasmacytoid cells with mild nuclear atypia. The final diagnosis of EBVMCU was established based on the permanent histologic specimen; however, retrospectively, cytology was more representative of the benign nature of the lesion than histology, helping a great deal to differentiate it from ML. Cytology can be a useful tool for the correct diagnosis of EBVMCU.

Knockout of Brca1-interacting factor Ola1 in female mice induces tumors with estrogen suppressible centrosome amplification

Obg-like ATPase 1 (OLA1) is a binding protein of Breast cancer gene 1 (BRCA1), germline pathogenic variants of which cause hereditary breast cancer. Cancer-associated variants of BRCA1 and OLA1 are deficient in the regulation of centrosome number. Although OLA1 might function as a tumor suppressor, the relevance of OLA1 deficiency to carcinogenesis is unclear. Here, we generated Ola1 knockout mice. Aged female Ola1+/− mice developed lymphoproliferative diseases, including malignant lymphoma. The lymphoma tissues had low expression of Ola1 and an increase in the number of cells with centrosome amplification. Interestingly, the proportion of cells with centrosome amplification in normal spleen from Ola1+/− mice was higher in male mice than in female mice. In human cells, estrogen stimulation attenuated centrosome amplification induced by OLA1 knockdown. Previous reports indicate that prominent centrosome amplification causes cell death but does not promote tumorigenesis. Thus, in the current study, the mild centrosome amplification observed under estrogen stimulation in Ola1+/− female mice is likely more tumorigenic than the prominent centrosome amplification observed in Ola1+/− male mice. Our findings provide a possible sex-dependent mechanism of the tumor suppressor function of OLA1.

Miliary tuberculosis diagnosed by diffuse hepatic uptake on PET/CT and transjugular liver biopsy.

The patient was an 81-year-old man. In his 20s, he had been treated with pharmacotherapy for pulmonary tuberculosis for 1 year. He presented to the Department of Respiratory Medicine with a chief complaint of dyspnea. The possibility of respiratory disease appeared to be low, but hepatic impairment was detected. The patient was thus referred to our department. Though the cause of hepatic impairment was unknown, the soluble interleukin-2 receptor level was elevated, suggesting malignant lymphoma. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) revealed diffuse, homogenous, intense FDG uptake in the entire liver, and transjugular liver biopsy confirmed the diagnosis. Histopathological examination revealed an epithelioid granuloma, and auramine staining was positive for bacilli suggestive of tuberculosis. CT revealed diffuse micronodular shadows in the lung, yielding a diagnosis of miliary tuberculosis. Therefore, the patient was prescribed antituberculosis medication by the Department of Respiratory Medicine. His subsequent clinical course was good. The miliary (hepatic) tuberculosis was typical based on the diffuse, homogenous, intense FDG uptake throughout the liver observed on PET-CT.

Abstract 3913: Molecular mechanism of action and targets of glucocorticoids in lymphoma therapy

Abstract Prednisone is an anti-inflammatory glucocorticoid (GC) that is cytotoxic for normal and malignant B cells and, on this basis, has long been included in combination chemotherapies to treat aggressive B-cell lymphomas. However, the mechanisms by which GCs kill malignant lymphoma cells still largely remains elusive due to the pleiotropic consequences of GC binding to the glucocorticoid receptor (GR; NR3C1), a ligand-induced transcription factor. This prompted us to search for critical direct targets of GC action with the hypothesis that GCs may inhibit key survival pathways in lymphomas. To determine effector genes that increase glucocorticoid toxicity, we performed genome-wide CRISPR-Cas9 screens in the presence and absence of prednisolone. Screens in cell line models of Burkitt lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) revealed strong synergy between GC treatment and inactivation of genes encoding components of the B cell receptor (BCR) signaling pathway (≥2 SD). To identify direct transcriptional GR targets and binding sites genome-wide, we performed the cleavage under targets and release using nuclease (CUT&RUN) assay and integrated this dataset with RNA-seq upon GC treatment. The pairwise comparison analysis (p<0.05) for GR-bound genes across BL and DLBCL cell lines revealed a significant enrichment of negative regulators of BCR/PI3K signaling and BCR-related tumor suppressors (LAPTM5, KLHL14, ARID5B, DDIT4, DAPP1, INPP5D, and CSK). Interestingly, expression of CSK, an inhibitor of all Src-family kinases (SFKs), was repressed while that of other BCR negative regulators were directly activated by binding of GR. Combinatorial deletion of activated genes counteracted the toxicity of GC up to 83.9%. In contrast, depletion of CSK paradoxically increased the cytotoxic effects of GC in BCR-dependent aggressive lymphoma with decreased proximal BCR signaling. To gain further insights on CSK function in aggressive lymphomas, we performed phospho-proteome and ubiquitinome profiling by treating lymphoma models with a small molecule inhibitor of CSK kinase activity (CSKi). The CSKi treatment initially increased constitutive BCR signaling, as expected, but then triggered exuberant ubiquitination of the LYN, HCK and BLK, leading to their proteasomal degradation. Consequently, the CSKi blocked BCR-dependent NF-κB activation in ABC DLBCL models and BCR-dependent PI3 kinase activation in models of GCB DLBCL and BL. In summary, inhibition of oncogenic BCR signaling is a major mode of action for GCs. Furthermore, small molecule inhibition of CSK kinase activity potentiated the effect of GCs on oncogenic BCR signaling and strongly synergized with GCs in killing ABC and GCB DLBCL models in vitro and preventing the growth of ABC and GCB DLBCL and patient-derived xenografts, warranting the development of clinical-grade CSK inhibitors for the treatment of these aggressive cancers. Citation Format: Jaewoo Choi, Michele Ceribelli, James D. Phelan, Björn Häupl, Da Wei Huang, George W. Wright, Tony Hsiao, Vivian Morris, Francesco Ciccarese, Boya Wang, Sean Corcoran, Sebastian Scheich, Xin Yu, Weihong Xu, Yandan Yang, Hong Zhao, Joyce Zhou, Grace Zhang, Jagan Muppidi, Giorgio Ga Inghirami, Thomas Oellerich, Craig J. Thomas, Wyndham H. Wilson, Louis M. Staudt. Molecular mechanism of action and targets of glucocorticoids in lymphoma therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3913.

Abstract 6064: Discovery of potent and selective EP300 degraders with anti-cancer activity

Abstract E1A binding protein (EP300) and CREB binding protein (CBP) are paralog histone acetyltransferases involved in many cellular processes via their activity as transcriptional co-activators. Dysregulation of one or both proteins has been implicated in various cancers, and functional genomic screens have demonstrated a bidirectional synthetic lethal relationship between the two genes in tumor cells. Due to the high homology between EP300 and CBP, identifying chemical matter that selectively targets EP300 or CBP has proven challenging. Here, we describe a potent, highly selective heterobifunctional degrader of EP300 with biological activity in CBP-deficient and EP300-dependent tumor cells. Targeted degradation of EP300 protein resulted in a stronger suppression of cell growth and survival than targeting the bromodomain or HAT activity of EP300/CBP with small molecule inhibitors. Anti-proliferative effects have been demonstrated in multiple cancer types, including malignant lymphomas and castration-resistant prostate tumors, highlighting the essential role of EP300 in mediating oncogenic transcription required for tumor cell growth and survival. Degradation of EP300 in vivo attenuated androgen-driven transcription and inhibited tumor growth in VCAP (AR+) prostate tumor xenografts. Importantly, no evidence of overt toxicity or thrombocytopenia was observed at therapeutically efficacious doses. These findings indicate that selective targeting of EP300 with targeted protein degradation is a safe and effective treatment strategy for advanced tumors. Citation Format: Mark Zimmerman, Ammar Adam, Hafiz Ahmad, Benjamin Adams, Ketaki Adhikari, Wesley Austin, Breanna Bullock, Julie Di Bernardo, Thomas Dixon, Danette Daniels, Claudia Dominici, GiNell Elliot, Brian Ethell, Anais Gervais, Md Imran Hossain, David Huang, Dave Lahr, Mei Yun Lin, David Mayhew, Karolina Mizeracka, Solymar Negretti, Tyler Nguyen, Olga Prifti, Darshan Sappal, Shawn Schiller, Brenna Sherbanee, David Terry, Nihan Ucisik, Elizabeth Wittenborn, Qianhe Zhou, Laura La Bonte. Discovery of potent and selective EP300 degraders with anti-cancer activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6064.

Cutaneous lymphoproliferative disorders: Back to the future.

In the 1980s, immunohistochemistry and clonality analyses became instrumental in the recognition and definition of new types of cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL) and the development of new classifications. By accepting loss of pan-T-cell antigens and clonal T-cell receptor gene rearrangements as important criteria to differentiate between benign and malignant T-cell proliferations, and monotypic immunoglobulin light-chain expression and clonal immunoglobulin gene rearrangements as crucial criteria to distinguish between benign and malignant B-cell proliferations, many cases, until then diagnosed as cutaneous lymphoid hyperplasia or pseudolymphoma, were reclassified as primary cutaneous CD4+ small/medium T-cell lymphoma (PCSM-TCL) or primary cutaneous marginal zone lymphoma (PCMZL), respectively. However, in recent years there is growing awareness that neither these immunohistochemical criteria nor demonstration of T-cell or B-cell clonality is specific for malignant lymphomas. In addition, many studies have reported that these low-grade malignant CTCL and CBCL have an indolent clinical behavior and an excellent prognosis with disease-specific survival rates of or close to 100%. As a result, recent classifications have downgraded several low-grade malignant cutaneous lymphomas to lymphoproliferative disorder (LPD). Both the 5th edition of the WHO classification (2022) and the 2022 International Consensus Classification (ICC) of mature lymphoid neoplasms reclassified PCSM-TCL as primary cutaneous CD4+ small/medium T-cell LPD and primary cutaneous acral CD8+ T-cell lymphoma as primary cutaneous acral CD8+ T cell LPD. While the 2022 ICC introduced the term "primary cutaneous marginal zone LPD," in the 5th edition of the WHO classification PCMZL is maintained. In this review we describe the background and rationale of the continually changing terminology of these conditions and discuss the clinical consequences of downgrading malignant lymphomas to LPDs.

Chidamide enhances T-cell-mediated anti-tumor immune function by inhibiting NOTCH1/NFATC1 signaling pathway in ABC-type diffuse large B-cell lymphoma

Chidamide (CS055/HBI-8000, tucidinostat) has shown promising effects in the clinical treatment of various hematologic tumors. Diffuse large B-cell lymphoma (DLBCL) has shown highly heterogeneous biological characteristics. There are complex mechanisms of the role of chidamide in DLBCL for in-depth study. It is essential to probe further into the mechanism of drug-tumor interactions as a guide to clinical application and to understand the occurrence and progression of DLBCL. In vitro and in vivo models were utilized to determine the effects of chidamide on signaling pathways involved in the DLBCL tumor microenvironment. The experimental results show that chidamide inhibited the proliferation of DLBCL cell lines in a dose- and time-dependent manner, and down-regulated the expression of NOTCH1 and NFATC1 in DLBCL cells as well as decreased the concentration of IL-10 in the supernatant. In addition, chidamide significantly lowered the expression of PD1 or TIM3 on CD4+T cells and CD8+T cells and elevated the levels of IL-2, IFN-γ, and TNF-α in the serum of animal models, which augmented the function of circulating T cells and tumor-infiltrating T cells and ultimately significantly repressed the growth of tumors. These findings prove that chidamide can effectively inhibit the cell activity of DLBCL cell lines by inhibiting the activation of NOTCH1 and NFATC1 signaling pathways. It can also improve the abnormal DLBCL microenvironment in which immune escape occurs, and inhibit immune escape. This study provides a new therapeutic idea for the exploration of individualized precision therapy for patients with malignant lymphoma.

[Persistent Polyclonal B-Cell Lymphocytosis (PPBL): An Entity That Is Not What it Seems].

Persistent polyclonal B-cell lymphocytosis is a rare disease with chronic lymphocytosis of polyclonal origin, which is more frequent in mostly asymptomatic middle-aged female smokers. The hallmark of this entity is the presence of bilobed/binucleated B lymphocytes, which are polyclonal as demonstrated by immunophenotyping; an elevated IgM level is common. This disease shows, in most cases, an indolent course over many years and, although controversial, it may rarely convert to malignant lymphoma. In addition to smoking, a genetic predisposition for persistent polyclonal B-cell lymphocytosis is likely. Recurrent genetic aberrations have been described. The differential diagnosis includes non-Hodgkin's lymphoma and a clear distinction between both entities is of the utmost importance because treatment is generally not indicated in the former: instead, regular follow-up is recommended. The authors describe the case of a 46-year-old female smoker, who presented with chronic lymphocytosis, elevated IgM and circulating binucleated lymphocytes. Excluding lymphoma was important considering the unusual presentation with constitutional symptoms and splenomegaly.

A Case of Cervical Malignant Lymphoma with Carotid Sinus Syndrome Resoluted by Lymph Node Dissection and Subsequent Treatment

A Case of Cervical Malignant Lymphoma with Carotid Sinus Syndrome Resoluted by Lymph Node Dissection and Subsequent Treatment

Features of tattoo-associated cutaneous lymphoid hyperplasia on reflectance confocal microscopy and line-field confocal optical coherence tomography.

The popularity of tattoos has led to an increase in associated skin reactions, including complications such as infection, allergic reactions and rare conditions such as tattoo-induced cutaneous lymphoid hyperplasia (CLH). CLH is a benign lymphoproliferative reaction with clinical features resembling malignant cutaneous lymphomas. Non-invasive diagnostic tools like reflectance confocal microscopy (RCM) and the new line-field confocal optical coherence tomography (LC-OCT) are being studied in dermatology better to understand the morphological patterns of many dermatological diseases. Between September 2021 and May 2023, patients with suspicious lesions for tattoo-related CLH were analysed using RCM and LC-OCT before confirming the diagnosis of CLH through skin biopsy and histopathological examination. The study included five cases of CLH. It focused on the analysis of high-quality LC-OCT images/videos and RCM images to investigate the features of CLH in tattooed individuals. Most (80%) cases exhibited a mixed T and B lymphocyte infiltration subtype, while 20% showed a predominant T infiltration subtype. RCM and LC-OCT revealed characteristic features, including architectural disarray, fibrosis, lymphoid infiltrates, and pigment deposits in the epidermis and dermis. Non-invasive tools such as RCM and LC-OCT are valuable in diagnosing tattoo-related CLH. While skin biopsy remains the current standard for diagnosis, RCM and LC-OCT can serve as helpful adjuncts in identifying the most representative area for biopsy. They may potentially become alternative diagnostic options in the future, offering benefits in terms of cost, diagnostic efficiency, aesthetics and patient satisfaction as the prevalence of tattoo-related adverse reactions continues to rise.

Increased PD-1 Expression on Circulating T Cells Correlates with Inferior Outcome after Autologous Stem Cell Transplantation

High-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) is a well-established treatment option for multiple myeloma and malignant lymphoma patients. It is able to induce long-term progression-free survival (PFS) in both patient groups and even provide a cure in patients with aggressive lymphoma. However, relapse is common and has been associated with the pace and quality of immunologic reconstitution after transplantation, as well as with immune cell exhaustion and immunometabolic defects. We aimed to analyze the dynamics of the prototypical exhaustion marker PD-1 on immune cells during reconstitution on high-dose chemotherapy followed by auto-SCT and its impact on PFS. We performed a comprehensive analysis of exhaustion and metabolic markers on immune cells from myeloma and lymphoma patients undergoing auto-SCT using flow cytometry and NanoString technologies. The expression levels of PD-1 were increased during early reconstitution after transplantation on T cells and natural killer (NK) cells, as well as on monocytes. However, while PD-1 expression in NK cells and monocytes normalized over time, PD-1 expression on T cells demonstrated a variable course. Of note, lymphoma patients with continuously increasing PD-1 expression on T cells after auto-SCT had an inferior median PFS of only 146 days, whereas the median PFS was not reached in the lymphoma patients without such a PD-1 expression pattern. T cells from patients with increased PD-1 expression after auto-SCT exhibited an immunometabolic (over)activation and exhausted phenotype compared to T cells from patients with a low PD-1 expression after transplantation, including higher levels of the glycolytic pacemaker enzyme hexokinase 2 and the inhibitory receptor CTLA-4. In addition, proliferating Ki-67+ T cells were more abundant in patients with high PD-1 expression on T cells compared to those with low expression after auto-SCT (11.9% versus 4.2%). PD-1 expression on T cells might serve as an adverse biomarker for lymphoma patients undergoing auto-SCT; however, further validation by larger prospective studies is required.

Global burden, risk factors, and trends of non-Hodgkin lymphoma: A worldwide analysis of cancer registries.

Non-Hodgkin lymphoma (NHL) accounts for 90% of all malignant lymphomas. This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of NHL by sex, age, and country. Data from 185 countries globally were used for analysis. NHL incidence and mortality were collected via the GLOBOCAN (2020), CI5 series I-X, WHO mortality database, the Nordic Cancer Registries, and the SEER Program. The WHO Global Health Observatory provided country-level, age-standardized prevalence of lifestyle and metabolic risk factors. Trends were examined and reported based on average annual percentage change (AAPC) calculated using Joinpoint regression analysis. Incidence and AAPC are based on data for the last 10 years across countries. Globally, age-standardized incidence and mortality rates for NHL were recorded at 5.8 and 2.6 per 100,000 individuals, respectively. At country-level, NHL incidence was significantly associated with various factors, including HDI (Human Development Index), GDP per capita, prevalence of tobacco and alcohol consumption, sedentary lifestyle, obesity, hypertension, diabetes and hypercholesterolaemia. Rising trend in NHL incidence was observed, with the highest increase recorded in Estonia (AAPCmale  = 4.15, AAPCfemale  = 5.14), Belarus (AAPCfemale  = 5.13), and Lithuania (AAPCfemale  = 4.68). While overall NHL mortality has been decreasing, certain populations experienced increased mortality over the decade. In Thailand, AAPC for mortality was 31.28% for males and 30.26% for females. Estonia saw an AAPC of 6.46% for males, while Slovakia experienced an AAPC of 4.24% for females. Colombia's AAPC was 1.29% for males and 1.51% for females. This study indicates a rising trend of NHL incidence over the past decade- particularly in developed countries, older males, and younger populations. Further research should investigate deeper insights into specific etiology and prognosis of NHL across subtypes, and potential contributors towards these epidemiologic trends.

Bilateral Malignant Non-Hodjkin's Lymphoma Metastatic of the Testis: A Case Report and Review of the Literature

Primary non-Hodgkin’s malignant lymphoma (NHML) of the testis is common in older men and is rare, accounting for between 1 and 9% of testicular tumors. The most common clinical manifestation is a painless unilateral testicular swelling but bilateral involvement is observed in about 35% of patients. We present a 61 year old patient with a history of right orchiectomy 7 months ago. He consulted us with a left testicular pain that was 4 months old. Clinical examination of the patient revealed a large hard left bursa and inguinal adenopathy. Given the patient’s history, the clinical picture, and the lack of additional immunostaining from the anatomical study, a further workup revealed a LMNH of high grade of metastatic germ cell type “B”. After RCP, the patient was refered to oncology.

Carcinogenic mechanisms of virus-associated lymphoma.

The development of lymphoma is a complex multistep process that integrates numerous experimental findings and clinical data that have not yet yielded a definitive explanation. Studies of oncogenic viruses can help to deepen insight into the pathogenesis of lymphoma, and identifying associations between lymphoma and viruses that are established and unidentified should lead to cellular and pharmacologically targeted antiviral strategies for treating malignant lymphoma. This review focuses on the pathogenesis of lymphomas associated with hepatitis B and C, Epstein-Barr, and human immunodeficiency viruses as well as Kaposi sarcoma-associated herpesvirus to clarify the current status of basic information and recent advances in the development of virus-associated lymphomas.

Aplastic Anaemia Associated with Bendamustine Therapy - A Rare Side Effect.

During treatment for malignant lymphoma, cytopenia can develop for several reasons. This can range from mild cytopenias leading to infection and bleeding to full-blown drug-induced aplastic anaemia. While aplastic anaemia affects individuals of all genders and ages, here, we describe aplastic anaemia after chemotherapy exposure to bendamustine in a 65-year-old female with non-Hodgkin's lymphoma. A 65-year-old woman with recurrent indolent marginal zone lymphoma and post-chemotherapy with bendamustine and rituximab, presented with a neutropenic fever and was admitted with a leading diagnosis of sepsis. In the previous two weeks, the patient required regular transfusions of packed red blood cells and platelets and maintained a daily ZARXIO® regimen. Laboratory results revealed pancytopenia, and broad-spectrum antibiotics (cefepime/vancomycin) were given. The patient was subsequently admitted to the hospital under the care of the haematology/oncology team and was ultimately diagnosed with aplastic anaemia, likely as a consequence of bendamustine chemoimmunotherapy. She elicited a positive response to the triple immunosuppressive therapy (IST) regimen (two immunotherapeutic agents plus one anti-thymocyte globulin (ATG), after which her cell counts returned to normal. This case underscores the importance of recognising haematologic complications linked to bendamustine and advocates for further research to increase the understanding among healthcare professionals of drug-induced aplastic anaemia. Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia and may require multiple transfusions and a multidrug regimen for treatment. The use of ATG as a therapeutic intervention is appropriate because it has been effective in treating aplastic anaemia. Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia, a side effect which has rarely been reported but is of significant clinical importance.Drug-induced aplastic anaemia is a complex, potentially devastating consequence of treating blood cancers and is a relatively unexplored area that requires further understanding.Anti-thymocyte globulin is effective in treating bendamustine-induced aplastic anaemia as it degrades lymphocytes that destroy the bone marrow.

Male’s Primary Breast Lymphoma: Rare Entity of Breast Malignancy, Wad Madani Teaching Hospital, Gezira State, Sudan, August 2023

<i>Background</i>: Primary breast lymphoma is a malignant lymphoma primarily involving breast in absence of previously detected lymphoma localizations. <i>Method</i>: A male of forty years old admitted to Department of Surgery; Wad Madani Teaching Hospital; Gezira State; Sudan; complaining of left breast lump for three months. Condition observed as a painful swelling in left breast, increasing gradually in size, associated with continuous high-grade fever, no rigors and relieved by analgesia, no nipple discharges. Had significant weight loss, anorexia, fatigability, back pain, dry cough with no hemoptysis, no history of headache, and no past or family history of similar condition. Examination: patient looks ill, pale, and not jaundiced. Breast examination: Left breast was larger than right one. Left breast: no nipple destruction, nipple was directed downward medially, no skin changes or dimpling, and no ulceration. There was a mass in left upper outer quadrant, measuring 6*7 cm, smooth surface, hard in consistency with well-defined edges, and attached to muscles but not to skin. No palpable axillary lymph nodes. Right breast was normal. Chest and abdominal examination were unremarkable. Investigations: Fine needle aspiration cytology showed poorly differentiated carcinoma. Incisional biopsy revealed: high grade Non-Hodgkins Lymphomas (Diffuse Large B Cell Lymphoma). He was referred to oncological department for neoadjuvant chemoradiotherapy. Conclusion and <i>Recommendation</i>: Primarily breast lymphoma is extremely rare among male, showing features mimicking breast carcinoma. Incisional biopsy was recommended for investigation of breast lump especially among males.