Should paediatric tonsillar asymmetry be an indication for tonsillectomy? A single centre experience.

BACKGROUND: Paediatric tonsillar lymphoma (TL) is a rare diagnosis. Historically, the presence of clinical features such as tonsillar asymmetry, grossly abnormal tonsil appearance and cervical lymphadenopathy raise concern for this diagnosis. Tonsillar asymmetry is considered to be the most concerning clinical feature; however, asymmetry is often apparent due to differences in depth or shape of tonsillar fossa and tonsillar pillars, rather than a true difference in volume. There is debate whether a tonsillectomy is required in all cases of tonsil asymmetry to exclude lymphoma, and what clinical features should raise concern. The aim of this study was to establish whether the presence of clinical asymmetry can be deemed a reliable marker for genuine tonsil size discrepancies. We also sought to evaluate the clinical and examination characteristics that are concerning for lymphoma. METHODS: Retrospective review of clinical records for paediatric tonsil specimens sent for histological evaluation between 1 January 2012 and 1 January 2023 driven by a clinical suspicion of lymphoma at Starship Children's Hospital, New Zealand. Patient demographics and clinical data were recorded. A comparison was made between tonsil size asymmetry on clinical examination (Brodsky criteria) and tonsil volume difference based on dimensions given in pathology reports. RESULTS: One hundred and forty-three patients had tonsillectomies between 2012 and 2022 at Starship Children's Hospital due to concern for lymphoma. Of these, three were positive for lymphoma. Presence of pain and abnormal tonsil appearance were predictors for lymphoma (p<0.02). Interrater reliability agreement between clinical size difference and tonsil volume was poor, Kappa= -0.13 p<0.05. CONCLUSION: Clinical size difference is a poor predictor for true tonsil volume difference. We advise that assessment of tonsil size should be performed in conjunction with the examination of gross visual abnormalities and lymphadenopathy to guide clinical decision making.

Letter to editor: C­reactive protein levels, the prognostic nutritional index, and the lactate dehydrogenase­to­lymphocyte ratio are important prognostic factors in primary central nervous system lymphoma: a single­center study of 223 patients.

This critique evaluates a letter to the editor discussing prognostic factors in primary central nervous system lymphoma (PCNSL), focusing on C-reactive protein (CRP) levels, prognostic nutritional index (PNI), and lactate dehydrogenase (LDH)-to-lymphocyte ratio. While the letter provides valuable insights, limitations including reliance on a single-center dataset, lack of consideration for potential confounders, insufficient contextualization within existing literature, and limited discussion of clinical implications are identified. Addressing these limitations is crucial for enhancing the relevance and applicability of the findings in PCNSL management.

Assessment on the use of allopurinol to improve safety and efficacy of mercaptopurine in pediatric patients with Acute Lymphoblastic Leukemia and Lymphoma during maintenance therapy.

BACKGROUND: Mercaptopurine is an important component of acute lymphoblastic leukemia (ALL) and lymphoma (LLy) maintenance therapy. The 6-thioguanine nucleosides (6-TGN) are believed to be the primary contributor to myelosuppression and immunosuppressive effects, while 6-methylmercaptopurine (6-MMPN) is believed to be responsible for several toxicities including hepatotoxicity, pancreatitis, and hypoglycemia. Previous reports suggest the addition of allopurinol may reduce these toxicities. AIMS: To assess the use of allopurinol to improve both safety and efficacy of mercaptopurine in pediatric patients with ALL and LLy during maintenance therapy. Secondary objectives included evaluating patient tolerability and skewed metabolism. In addition, we also analyzed mercaptopurine daily dose reduction upon allopurinol initiation. METHODS AND RESULTS: The primary endpoint was time within goal ANC prior to and after initiation of allopurinol. Secondary endpoints included; improvement in selective toxicities (hepatotoxicity, pancreatitis, and hypoglycemia) and 6-MMPN to 6-TGN ratio prior to and after allopurinol initiation. In addition, an exploratory endpoint assessing mercaptopurine daily dose reduction prior to and after allopurinol initiation was included. Sixteen patients met inclusion criteria and 15 (94%) of which were included in this study. Median percent of maintenance days within goal ANC prior to and after initiation of allopurinol was 27.8 (IQR 22.6-44.9) and 41.6 (IQR 20.2-58.2) respectively. All patients experienced selective toxicities; 15 (100%) hepatotoxicity, 1 (7%) pancreatitis, and 3 (20%) hypoglycemia. Improvement of toxicities was seen in 13/15 (87%), 1/1 (100%), and 2/3 (67%) respectively. Average 6-MMPN:6-TGN ratio prior to allopurinol initiation was 304:1 and after, allopurinol initiation improved to 15:1, resulting in a 95% reduction. Average mercaptopurine dose prior to and after allopurinol initiation decreased by about 56% (63 to 28 mg/m2 /day). CONCLUSION: Results suggest that the use of allopurinol in pediatric patients with ALL and LLy receiving mercaptopurine during maintenance therapy is both safe and effective.

Clinical Utility of Stepwise Bronchoalveolar Lavage Fluid Analysis in Diagnosing and Managing Lung Infiltrates in Leukemia/Lymphoma Patients With Febrile Neutropenia.

PURPOSE: Febrile neutropenia (FN) is a serious complication in hematologic malignancies, and lung infiltrates (LIs) remain a significant concern. An accurate microbiological diagnosis is crucial but difficult to establish. To address this, we analyzed the utility of a standardized method for performing bronchoalveolar lavage (BAL) along with a two-step strategy for the analysis of BAL fluid. PATIENTS AND METHODS: This prospective observational study was conducted at a tertiary cancer center from November 2018 to June 2020. Patients age 15 years and older with confirmed leukemia or lymphomas undergoing chemotherapy, with presence of FN, and LIs observed on imaging were enrolled. RESULTS: Among the 122 enrolled patients, successful BAL was performed in 83.6% of cases. The study used a two-step analysis of BAL fluid, resulting in a diagnostic yield of 74.5%. Furthermore, antimicrobial therapy was modified in 63.9% of patients on the basis of BAL reports, and this population demonstrated a higher response rate (63% v 45%; P = .063). CONCLUSION: Our study demonstrates that a two-step BAL fluid analysis is safe and clinically beneficial to establish an accurate microbiological diagnosis. Given the crucial impact of diagnostic delays on mortality in hematologic malignancy patients with FN, early BAL studies should be performed to enable prompt and specific diagnosis, allowing for appropriate treatment modifications.

Hypercalcaemia of malignancy: a case of vitamin-D-mediated hypercalcaemia in lymphoma.

Hypercalcaemia of malignancy (HCM) is a paraneoplastic syndrome that often portends a poor prognosis. We present an extremely rare (<1%) case of HCM due to extrarenal calcitriol (1,25-(OH)2D) production in a patient with splenic marginal zone lymphoma. A man in his 80s presented with a 3-week history of fatigue, unsteadiness and abdominal pain, and new findings of anaemia, kidney injury and hypercalcaemia. Laboratory evaluation, bone marrow biopsy and positron emission tomography/computed tomography (PET/CT) confirmed the diagnosis of splenic marginal zone lymphoma which produced calcitriol (1,25-(OH)2D3), causing the patient's hypercalcaemia.

Enhanced CT Findings in a Case of Recurrent Pelvic Follicular Dendritic Cell Sarcoma.

INTRODUCTION: Follicular Dendritic Cell Sarcomas (FDCS)was first found in 1986; the specificity of the disease is its rarity, with an incidence of only 0.4%, numerous doctors for its lack of understanding, the accuracy of imaging diagnosis is not great, which is easy to delay the treatment. This article summarizes several characteristic imaging manifestations of FDCS to provide imaging physicians with an understanding of the imaging properties of this rare disease. When faced with complex cases, the radiologist can consider this disease and include it in the differential diagnosis. FDCS occurs mainly in lymph nodes, mainly in the head and neck. The main symptoms are fatigue, local pain, or painless mass. The treatment method is not uniform, but scholars agree that we should strive for the opportunity of surgery as much as possible. CASE PRESENTATION: This paper reported a case of FDCS with pelvic recurrence 3 years after surgery. The patient was suspected to have lymphoma by postoperative pathology in the local hospital, and it is recommended that the patient be reexamined regularly. A soft tissue mass was recently found again in the left pelvic cavity. After an enhanced CT examination, the radiologist was skeptical of the previous diagnosis of lymphoma. Subsequently, a needle biopsy was performed at Peking University Shougang Hospital. The pathological results rejected the prior diagnosis of lymphoma after consultation with additional hospitals, and the patient was diagnosed with FDCS. CONCLUSIONS: The imaging manifestations of FDCS lack absolute specificity, but it also has imaging characteristics, such as large areas of necrosis in the huge mass, rough mass calcification in the mass, enhanced scan showed "fast in and slow out" mode, and there were blood vessels in the tumor. FDCS mainly occurs in lymph nodes and is easily misdiagnosed as GIST, inflammatory myoblastoma, lymphoma, etc. Radiologists should continue to collect cases of this disease and include suspected cases in the differential diagnosis in clinical work.

Indolent T-Cell/Natural Killer-Cell Lymphomas/Lymphoproliferative Disorders of the Gastrointestinal Tract-What Have We Learned in the Last Decade?

Primary gastrointestinal (GI) T-cell and natural killer (NK)-cell lymphomas/lymphoproliferative disorders (LPD) are uncommon, and they are usually aggressive in nature. However, T-cell and NK-cell lymphoma/LPD of the GI tract with indolent clinical course has been reported over the past 2 decades. Indolent T-cell LPD was formally proposed a decade ago in 2013 and 4 years later recognized as a provisional entity by the revised fourth edition of WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues in 2017. Indolent T-cell LPD of the GI tract has been changed to indolent T-cell lymphoma of the GI tract as a distinct entity by the fifth edition of WHO Classification of Haematolymphoid Tumours, but the International Consensus Classification of mature lymphoid neoplasms prefers indolent clonal T-cell LPD of the GI tract instead. In the past decade, indolent lymphoma/LPD of the GI tract has been expanded to NK cells, and as such, indolent NK-cell LPD of the GI tract was recognized as an entity by both the fifth edition of WHO Classification of Haematolymphoid Tumours and the International Consensus Classification. The underlying genetic/molecular mechanisms of both indolent T-cell lymphoma/LPD of the GI tract and indolent NK-cell LPD of the GI tract have been recently discovered. In this review, we describe the history; salient clinical, cytohistomorphologic, and immunohistochemical features; and genetic/genomic landscape of both entities. In addition, we also summarize the mimics and differential diagnosis. Finally, we propose future directions with regard to the pathogenesis and clinical management.

Interventional treatment of giant tracheal lymphoma under rigid bronchoscopy: A case report and literature review.

INTRODUCTION: Lymphoma can appear in all parts of the body and present with different symptoms. However, bronchial lymphoma is rare and can be misdiagnosed as airway malignancy or lung disease.Patient: An older adult woman with tracheal lymphoma experienced severe breathing difficulties, and chest computed tomography indicated severe narrowing of the airway. She did not respond to repeated antibiotic treatment, and she was eventually diagnosed with lymphoma based on pathology after surgical removal of the tumor. DIAGNOSIS: The patient received a diagnosis of thoracic tracheal stenosis due to intratracheal inflammatory granulomatous lesions or a tumor. INTERVENTIONS: Treatment involved the use of a high-frequency electrotome, freezing, and argon plasma coagulation. OUTCOMES: The patient reported improvements in dyspnea, cough, and other symptoms after the operation. The pathological results confirmed follicular lymphoma. Reexamination by fiberbronchoscopy indicated that the degree of stenosis in the middle and upper tracheal segments was significantly reduced following interventional therapy. CONCLUSION: Endoscopic interventional therapy can be an effective treatment for tracheal lymphoma.

Lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH): a scoping review unveils clinical and diagnostic patterns of a lymphoma subgroup with poor prognosis.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome driven by pathologic activation of cytotoxic T-lymphocytes and macrophages. Despite advances in diagnostics and management, adult patients with lymphoma-associated HLH (LA-HLH) harbor particularly poor prognosis and optimal treatment remains challenging. As systematic data on LA-HLH are scarce, we aimed to synthesize research evidence by thorough analysis of the published literature in PubMed (MEDLINE-database) within the context of a scoping review. Of 595 search results, 132 articles providing information on 542 patients were reviewed and analyzed. Median patient age was 60 years (range, 18-98) with male predominance (62.7%). B- and T-NHL were equally represented (45.6% and 45.2%), Hodgkin's lymphoma was reported in 8.9% of the cases. The majority of patients (91.6%) presented in Ann-Arbor-Stages III and IV, and bone marrow infiltration was observed in a significant proportion of patients (61.5%). Soluble CD25 levels were markedly elevated (median 10,000 U/ml), with levels beyond 10,000 U/ml indicating unfavorable prognosis for 30-day and overall survival. 66.8% of the patients died after median 5.1 months. LA-HLH remains a clinical challenge requiring specialized management. Timely diagnosis and appropriate lymphoma-specific treatment are of utmost importance to enhance patient outcomes.

Cell-Free DNA Extraction of Vitreous and Aqueous Humor Specimens for Diagnosis and Monitoring of Vitreoretinal Lymphoma.

Vitreoretinal lymphoma (VRL) represents an aggressive lymphoma, often categorized as primary central nervous system diffuse large B-cell lymphoma. To diagnose VRL, specimens such as vitreous humor and, more recently, aqueous humor are collected. Diagnostic testing for VRL on these specimens includes cytology, flow cytometry, and molecular testing. However, both cytopathology and flow cytometry, along with molecular testing using cellular DNA, necessitate intact whole cells. The challenge lies in the fact that vitreous and aqueous humor typically have low cellularity, and many cells get destroyed during collection, storage, and processing. Moreover, these specimens pose additional difficulties for molecular testing due to the high viscosity of vitreous humor and the low volume of both vitreous and aqueous humor. This study proposes a method for extracting cell-free DNA from vitreous and aqueous specimens. This approach complements the extraction of cellular DNA or allows the cellular component of these specimens to be utilized for other diagnostic methods, including cytology and flow cytometry.

Predictive and prognostic molecular biomarkers in lymphomas.

Recent advances in molecular diagnostics have markedly expanded our understanding of the genetic underpinnings of lymphomas and catalysed a transformation in not just how we classify lymphomas, but also how we treat, target, and monitor affected patients. Reflecting these advances, the World Health Organization Classification, International Consensus Classification, and National Comprehensive Cancer Network guidelines were recently updated to better integrate these molecular insights into clinical practice. We summarise here the molecular biomarkers of lymphomas with an emphasis on biomarkers that have well-supported prognostic and predictive utility, as well as emerging biomarkers that show promise for clinical practice. These biomarkers include: (1) diagnostic entity-defining genetic abnormalities [e.g., B-cell acute lymphoblastic leukaemia (B-ALL) with KMT2A rearrangement]; (2) molecular alterations that guide patients' prognoses (e.g., TP53 loss frequently conferring worse prognosis); (3) mutations that serve as the targets of, and often a source of acquired resistance to, small molecular inhibitors (e.g., ABL1 tyrosine kinase inhibitors for B-ALL BCR::ABL1, hindered by ABL1 kinase domain resistance mutations); (4) the growing incorporation of molecular measurable residual disease (MRD) in the management of lymphoma patients (e.g., molecular complete response and sequencing MRD-negative criteria in multiple myeloma). Altogether, our review spans the spectrum of lymphoma types, from the genetically defined subclasses of precursor B-cell lymphomas to the highly heterogeneous categories of small and large cell mature B-cell lymphomas, Hodgkin lymphomas, plasma cell neoplasms, and T/NK-cell lymphomas, and provides an expansive summary of our current understanding of their molecular pathology.

The 5th edition of the World Health Organization Classification of mature lymphoid and stromal tumors - an overview and update.

The purpose of this review is to give an overview on the conceptual framework and major developments of the upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid tumours (WHO-HAEM5) and to highlight the most significant changes made in WHO-HAEM5 compared with the revised 4th edition (WHO-HAEM4R) of lymphoid and stromal neoplasms. The changes from the revised 4th edition include the reorganization of entities by means of a hierarchical system that is realized throughout the 5th edition of the WHO classification of tumors of all organ systems, a modification of nomenclature for some entities, the refinement of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities. For the first time, tumor-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms are included in the classification.

Lymphoma-related intussusception in children: diagnostic challenges and clinical characteristics.

Intussusception is a common cause of acute abdominal pain in children and the most frequent cause of intestinal obstruction in infants. Although often idiopathic, it can stem from conditions like lymphoma. This study delves into lymphoma-related intussusception in children, aiming to enhance early detection and management. A retrospective review encompassed children admitted from 2012 to 2023 with intussusception due to intestinal lymphoma. Demographic, clinical, and imaging data were meticulously extracted and analyzed. The study included 31 children in the lymphoma-related intussusception group. Contrasted with non-lymphoma-related cases, the patients of lymphoma-related intussusception were notably older (median age: 87 months vs. 18.5 months), predominantly male, and demonstrated protracted abdominal pain. Ultrasound unveiled mesenteric lymph node enlargement and distinct intra-abdominal masses; enema reduction success rates were notably diminished. Detecting lymphoma-related intussusception remains intricate. Age, prolonged symptoms, and distinctive ultrasound findings can arouse suspicion. Timely surgical intervention, based on preoperative imaging, proves pivotal for accurate diagnosis. CONCLUSION:  Swift identification of lymphoma-related intussusception, distinguished by unique clinical and ultrasound features, is imperative for timely intervention and treatment. Further research is warranted to refine diagnostic approaches. WHAT IS KNOWN: • Intussusception in pediatric patients can be caused by a wide spectrum of underlying diseases including lymphoma. • Early Identifying the exact underlying cause of intussusception is crucial for tailored therapy, however often challenging and time-consuming. WHAT IS NEW: • Lymphoma-related intussusception may present with increased abdominal fluid accumulation, intestinal obstruction, and a higher likelihood of failed reduction during enema procedures. • For high-risk children, repeated ultrasound examinations or further investigations may be necessary to confirm the diagnosis.

INTRAVITREAL MELPHALAN INJECTION AS A SECOND-LINE LOCAL THERAPY IN VITREORETINAL LYMPHOMA: Case Series.

PURPOSE: To evaluate the effectiveness and safety of intravitreal melphalan (IVM) injection therapy in vitreoretinal lymphoma. METHODS: Eight eyes of five biopsy-proven vitreoretinal lymphoma patients who were treated with IVM injection as a second-line therapy after intravitreal methotrexate and rituximab injections were retrospectively evaluated between January 2011 and March 2023. RESULTS: The medical records of five vitreoretinal lymphoma patients (mean age of 62 years at the diagnosis) including 4 (80%) female patients and 1 (20%) male patient were retrospectively analyzed. Three patients (60%) either had a history of central nervous lymphoma or developed it during the follow-up. Patients were previously treated with a mean of five cycles of monthly intravitreal methotrexate and rituximab injections. All eyes showed complete response by the disappearance of vitreal and/or subretinal neoplastic cells within 6 weeks after IVM injections (range, 1-4 injections per eye). Of 12 IVM injections, 3 (25%) injections were associated with macular edema diagnosed on optical coherence tomography at 1-month follow-up and resolved spontaneously within 5 months. The IVM administration induced new retinal pigment epithelium changes in three eyes (37%). CONCLUSION: Intravitreal melphalan injection may be effective in the management of vitreoretinal lymphoma as a second-line local therapy. Randomized clinical trials with larger numbers of patients are needed to establish the efficacy, treatment protocol, and safety of IVM injection.

Presentation, Diagnostic Testing and Initial Treatment of Vitreoretinal Lymphoma.

PURPOSE: Vitreoretinal lymphoma is a malignancy with high mortality. Incidence is rare, and there is a lack of medical evidence to direct management. This work describes presentation, diagnostic testing, and first treatment approaches in a recently diagnosed and treated patient cohort. DESIGN: Clinical registry-based observational study. SUBJECTS: Forty-eight women and 32 men (age range, 32-91 years; median age, 64 years) diagnosed with vitreoretinal lymphoma. METHODS: An international network of ophthalmologists reported clinical features and management of patients presenting with vitreoretinal lymphoma between January 1, 2020 and December 31, 2022 via an electronic platform. MAIN OUTCOME MEASURES: Visual acuity at presentation (logarithm of the minimum angle of resolution [logMAR]); basis for diagnosis; first treatment. RESULTS: Vitreoretinal lymphoma was bilateral at presentation in 65% of patients (n = 52) and an initial site of lymphoma in 78% (n = 62). Of 127 eyes with lymphoma at presentation, vitreous was involved in 89% (n = 113) and was the only involved eye tissue in 40% (n = 51), and retina was involved in 46% (n = 59) and was the only involved eye tissue in 9% (n = 11). Median logMAR visual acuity of the worse-seeing eye was 0.50. The lymphoma was diagnosed from ocular specimens in 80% of patients (64/80), usually vitreous (57/64 patients [89%]), and on other clinical information in 20% of patients (16/80). Cellular studies were performed on ocular specimens from 59 of 64 patients (92%), most often cytology. Tumor gene analysis was used in 21 of 64 patients (33%), and cytokine assays were used in 13 of 64 patients (20%). For 76 patients (95%), treatment was initiated within 6 months of diagnosis and included ocular (38/76 [48%]), extraocular (17/76 [21%]), and ocular plus extraocular (21/76 [26%]) approaches. Intravitreal methotrexate was the most common ocular treatment (83/87 eyes [95%]). CONCLUSIONS: Using data collected from 80 patients diagnosed with vitreoretinal lymphoma since 2020, we show that visual impairment is common, and that management often involves diagnosis by cellular tests and treatment with intravitreal chemotherapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.