[Cancer genomic panels for lymphoid malignancies].

Cancer precision medicine (genome-based individualized treatment for cancer patients) has already been introduced for solid tumors, and involves identifying driver genes in the development and progression of tumors and suggesting optimal treatments targeting those genes. So far, many patients have received this style of treatment. Meanwhile, preparations for cancer genomic medicine based on cancer gene panel testing are also underway for hematopoietic tumors. In this article, I would like to share fundamental information about the main genetic mutations in malignant lymphomas and their clinical significance, and discuss how this information should be utilized in cancer genomic medicine in the future.

The National Swedish Lymphoma Register - a systematic validation of data quality.

BACKGROUND AND PURPOSE: The Swedish Lymphoma Register (SLR) was initiated in the year 2000 with the aim to monitor quality of care in diagnostics, treatment and outcome of all lymphomas diagnosed nationally among adults. Here, we present the first systematic validation of SLR records as a basis for improved register quality and patient care. PATIENTS AND METHODS: We evaluated timeliness and completeness of register records among patients diagnosed with lymphoma in the SLR (n = 16,905) compared with the National Cancer Register for the period 2013-2020. Comparability was assessed through evaluation of coding routines against national and international guidelines. Accuracy of 42 variables was evaluated through re-abstraction of data from medical records among 600 randomly selected patients diagnosed in 2016-2017 and treated across all six Swedish healthcare regions.  Results: Completeness was high, >95% per year for the period 2013-2018, and >89% for 2019-2020 compared to the National Cancer Register. One in four patients was registered within 3 months, and 89.9% within 2 years of diagnosis. Registration instructions and coding procedures followed the prespecified guidelines. Missingness was generally low (<5%), but high for occasional variables, for example, those describing maintenance and consolidative treatment. Exact agreement of categorical variables was high overall (>80% for 24/34 variables), especially for treatment-related data (>80% for 17/19 variables). INTERPRETATION: Completeness and accuracy are high in the SLR, while timeliness could be improved. Finetuning of variable registration guided by this validation can further improve reliability of register reports and advance service to lymphoma patients and health care in the future.

Non-neoplastic B-cell predominant lymphoid proliferations at the organs exposed to external environment mimicking lymphoma: A potential diagnostic pitfall.

Background: Typically, lymphatic tissue proliferative lesions include either benign lesions or lymphoma. However, not all lymphatic lesions can currently be accurately classified into one category, particularly in mucosal areas that are in contact with the external environment.Aims: To explore the morphology, immunophenotype, and molecular changes of Non-neoplastic B-cell predominant lymphoid proliferations (NBPLP) in pathological areas that are exposed to external surroundings which mimicked lymphoma.Methods and Results: 18 cases of Atypical lymphoid hyperplasia (AtLP)  were retrieved in this study. The biopsy samples were mucosal samples obtained from areas exposed to external surroundings, including intestines, urethra, cervix, tonsils, and tongue. Microscopically, there is a different level of B cell hyperplasia accompanied by morphological atypia. We categorized the morphology into 4 groups: type A (7/18), type B (3/18), type C (3/18), type D (5/18). Part of the AtLP was found positive for BCR gene rearrangement (6/15), and TCR gene rearrangement (1/4). The follow-up period ranged from 14.2 to 70 months. No evidence of lymphoma was found. Therefore, we diagnosed all of the presented cases as NBPLP. We illustrated the key differential points and provided valuable diagnostic experience on each subtype.Conclusions: Areas exposed to the external environment are commonly exposed to antigen and easily present with AtLP of NBPLP, accompanying with positive IGH rearrangement. Therefore, a comprehensive evaluation of macroscopic, morphology, immunophenotype, and molecular diagnostics is required to prevent the overdiagnosis of lymphoma.

A case of equine multicentric lymphoma: Clinical, microscopical, and molecular findings.

Background: Although relatively uncommon, lymphoma is the most prevalent haematopoietic neoplasia in horses, and multicentric lymphoma remains the most common presentation of the disease. The pathogenesis of equine lymphoma is still poorly understood and the diagnosis is usually confirmed at an advanced stage of the disease, compromising the prognosis. This study investigated the clinical, pathological, and molecular features of a case of equine multicentric lymphoma. Case Description: An apparently healthy 5-year-old crossbreed mare hospitalized at the Centre of Animal Reproduction of Vairão, Portugal, suddenly presented clinical signs of supraorbital oedema and mandibular lymph node enlargement, developing fever, facial oedema, and generalized lymphadenopathy. The mare ended up dying twenty-four days after the first clinical signs due to multisystem organ failure. Haematological and biochemical analyses, necropsy, and microscopic and molecular evaluation of affected tissues were performed. At necropsy, the main findings were multiple multinodular lesions, distributed along the serous surface of oropharynx, trachea, pericardium, gastrointestinal tract, and mesentery. Microscopically, these consisted of solid proliferations of neoplastic round cells that exhibited immunopositivity for CD3 (T cells). Based on these findings, a medium-grade multicentric T-cell lymphoma was diagnosed. Conclusion: There is still very little research regarding the molecular characterization of lymphoma in horses. As an entity itself is quite heterogeneous, it is important to describe the interspecies particularities to understand its development and behaviour.

Lymphoma for the acute physician: diagnostic challenges and initial treatment decisions.

Prompt diagnosis of lymphoma facilitates early treatment and improves outcomes for patients. For non-haemato-oncologists, it is important to have an understanding of how lymphoma can present and the initial work-up. This review is intended to provide clinicians with background to aid clinical decisional making at presentation and when managing treatment related complications. There will be particular emphasis on emergency presentations (tumour lysis syndrome, management of patients with a mediastinal mass, infections in lymphoma patients) and novel treatment options which have unique toxicities often requiring multi-specialty expertise.

Molecular diagnosis of primary CNS lymphoma in 2024 using MYD88Leu265Pro and IL-10.

Early diagnosis is crucial for the successful treatment of primary CNS lymphoma (PCNSL), a rapidly progressing tumour. Suspicion raised on brain MRI must be confirmed by a histopathological diagnosis of a tumour specimen collected by stereotactic biopsy. In rare cases, cerebrospinal fluid (CSF) or vitreous humour might aid in providing a cytological diagnosis. Several disease-related, patient-related, and treatment-related factors affect the timing and accuracy of diagnosis and patient outcome. Some molecules detected in CSF, aqueous and vitreous humour, and peripheral blood were proposed as diagnostic biomarkers for PCNSL; however, detection methods for most of these molecules are not yet standardised, have a long turnaround time, are expensive, and have little reproducibility among labs. By contrast, the MYD88Leu265Pro somatic hotspot mutation, revealed by PCR-based assay, is currently and reliably used during the diagnosis of some lymphomas, and IL-10, measured by enzyme-linked immunosorbent assay, is routinely used to diagnose and monitor different common metabolic and immunological diseases. Several independent studies have shown that MYD88Leu265Pro and IL-10 can be easily assessed in peripheral blood, plasma, aqueous and vitreous humour, and CSF of patients with PCNSL with substantial sensitivity and specificity, especially when evaluated in combination. In this Viewpoint, evidence supporting the routine use of MYD88Leu265Pro and IL-10 in diagnosing PCNSL is considered, and some examples of the frequent difficulties found in the diagnosis of PCNSL are provided, highlighting the role and indications of these two biomarkers to improve the timely recognition of this aggressive tumour.

The diagnostic relevance of mesenteric lymph node biopsy in small intestinal lymphoma in cats.

BACKGROUND: Regional lymph nodes are frequently sampled in cats with suspected intestinal lymphoma; however, their diagnostic value has not been explored. OBJECTIVES: To investigate whether histologic and immunohistochemical analysis of mesenteric lymph nodes correlates with the diagnosis of intestinal lymphoma in cats. ANIMALS: One hundred 2 client-owned cats diagnosed with intestinal lymphoma. METHODS: Retrospective study. The inclusion criteria required a full-thickness biopsy of the small intestine and concurrent excision of mesenteric lymph nodes. Histologic and immunophenotypic analyses were performed on intestinal biopsies and corresponding lymph nodes. Selected nodal samples diagnosed with reactive lymph nodes underwent clonality testing. RESULTS: Transmural T-cell lymphomas, encompassing small and large cell types, were predominant (64 cases, 62.7%), with large B-cell lymphomas being more frequently transmural (68.8%) than mucosal (31.2%). Among all lymph nodes examined, 44 (43.1%; 95% CI: 33.9%-52.8%) exhibited neoplastic infiltration. Among cases of small cell lymphoma, 51 out of 72 (70.8%; 95% CI: 59.4%-80.1%) showed no nodal involvement. Clonality results correctly identified 19/30 (63.3%; 95% CI: 45.5%-78.2%) reactive lymph nodes. Concerns were raised regarding clonal identification in the remaining cases and potential misdiagnoses based on phenotypic characteristics. CONCLUSION AND CLINICAL IMPORTANCE: The study underscores the potential drawbacks of relying solely on mesenteric lymph nodes for diagnosing intestinal lymphomas in cats, particularly small cell subtypes. It emphasizes the importance of full-thickness biopsies for assessing transmural infiltration and recommends caution when utilizing mesenteric lymph nodes for histologic, immunohistochemical and clonality evaluations in mucosal lymphomas. Despite limitations, this research highlights the need for comprehensive diagnostic strategies in cats with intestinal lymphoma.

Diagnostic potential of vitreoretinal lymphoma by detection of gene mutations with NGS in 25 Chinese patients.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare malignant lymphoproliferative tumor. Our study aimed to investigate the mutational profile of VRL distinguishing from uveitis using next-generation sequencing (NGS) analysis on small amounts of vitreous fluid. METHODS: Vitreous samples from twenty-six eyes of twenty VRL patients and six eyes of five uveitis patients were enrolled. All vitreous samples underwent cytology, immunocytochemistry for B-cell markers, cytokines analysis of IL-10 and IL-6, and flow cytometry. NGS was performed in vitreous specimens from the 25 patients using 82 DLBCL-targeted mutation panels. Vitreous fluids from 8 cases were performed paired NGS-based mutation analysis on both cell-free DNA (cfDNA) and genomic DNA. RESULTS: The sensitivity and accuracy rates for vitreous cytology were 70 % and 76 %, and for cytokine analysis (IL-10/IL-6 > 1) were 65 % and 72 %, respectively. Overall, the common mutations in VRL were PIM1 (88.5 %), IGLL5 (88.5 %), KMT2C (73 %), MYD88 (77 %), CD79B (50 %) and TBL1XR1 (46.2 %). In addition, the genetic mutation in cfDNA was consistent with that in genomic DNA in eight VRL cases. CONCLUSIONS: The mutation analysis of 82 DLBCL-targeted spectrum mutation panels by NGS on the vitreous samples is a sensitive and specific tool for distinguishing VRL from uveitis. Utilizing cfDNA for NGS analysis may serve as a liquid biopsy to aid in the diagnosis of VRL, particularly when using small-volume aspirate.

Diagnosis of renal lymphoma by Wright-Giemsa-stained cytocentrifuged urine evaluation in a cat.

Lymphoma represents up to 30% of neoplasms diagnosed in cats. Diagnosis of lymphoma in the urinary system by examination of urine sediment has been described in a dog, but apparently not previously in cats. Concurrent samples of serum, EDTA whole blood, and urine were submitted from a 15-year-old spayed female domestic shorthair cat exhibiting weight loss, polyuria, and polydipsia. Hematology and biochemical abnormalities included a mild normocytic, normochromic, non-regenerative anemia; an inflammatory leukogram; and azotemia. Urinalysis evaluation revealed inadequate urine concentration and marked proteinuria. Wet-mount urine sediment examination revealed moderate numbers of leukocytes and erythrocytes. A uniform population of intermediate-to-large lymphocytes was observed on a fresh, Wright-Giemsa-stained preparation from cytocentrifuged urine. The cat was euthanized and necropsy was completed. Bilateral renomegaly was identified and characterized by multifocal, pale-yellow, coalescing, poorly defined, homogenous nodules. Microscopically, these nodules were composed of dense sheets of CD3-positive round cells, consistent with T-cell renal lymphoma. Key clinical message: Lymphoma is a common neoplasm in cats that can affect many organ systems, including the upper urinary tract. This case represents an uncommon method of identifying neoplastic lymphocytes via evaluation of cytocentrifuged urine, and emphasizes the benefits of examining Romanowsky-stained urine sediment in animals.

Diagnostic du lymphome rénal chez un chat par évaluation d'urine cytocentrifugée avec coloration Wright-Giemsa. Le lymphome représente jusqu'à 30 % des néoplasmes diagnostiqués chez le chat. Le diagnostic d'un lymphome du système urinaire par examen des sédiments urinaires a été décrit chez un chien, mais apparemment pas à ce jour chez le chat. Des échantillons simultanés de sérum, de sang total dans un tube avec EDTA et d'urine ont été soumis provenant d'une chatte domestique à poils courts stérilisée de 15 ans présentant une perte de poids, une polyurie et une polydipsie. Les anomalies hématologiques et biochimiques comprenaient une légère anémie normocytaire, normochrome et non régénérative; une formule leucocytaire inflammatoire; et une azotémie. L'analyse d'urine a révélé une concentration urinaire insuffisante et une protéinurie marquée. L'examen microscopique des sédiments urinaires a révélé un nombre modéré de leucocytes et d'érythrocytes. Une population uniforme de lymphocytes de taille intermédiaire à grande a été observée sur une préparation fraîche colorée au Wright-Giemsa à partir d'urine cytocentrifugée. Le chat a été euthanasié et une autopsie a été réalisée. Une rénomégalie bilatérale a été identifiée et caractérisée par des nodules multifocaux, jaune pâle, coalescents, mal définis et homogènes. Au microscope, ces nodules étaient composés de feuilles denses de cellules rondes CD3-positives, compatibles avec un lymphome rénal à cellules T.Message clinique clé :Le lymphome est une tumeur courante chez le chat qui peut affecter de nombreux systèmes organiques, y compris les voies urinaires supérieures. Ce cas représente une méthode rare d'identification des lymphocytes néoplasiques via l'évaluation de l'urine cytocentrifugée et met l'emphase sur les avantages de l'examen des sédiments urinaires avec coloration de Romanowsky chez les animaux.(Traduit par Dr Serge Messier).

Diagnostics and treatment delay in primary central nervous system lymphoma: What the neurosurgeon should know.

PURPOSE: The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a multidisciplinary diagnostic work up, which associated with diagnostic delay and could result in treatment delay. This article offers recommendations to neurosurgeons involved in clinical decision-making regarding (novel) diagnostics and care for patients with PCNSL with the aim to improve uniformity and timeliness of the diagnostic process for patients with PCNSL. METHODS: We present a mini review to discuss the role of stereotactic biopsy in the context of novel developments in diagnostics for PCNSL, as well as the role for cytoreductive surgery. RESULTS: Cerebrospinal fluid-based diagnostics are supplementary and cannot replace stereotactic biopsy-based diagnostics. CONCLUSION: Histopathological diagnosis after stereotactic biopsy of the brain remains the gold standard for diagnosis. Additional diagnostics should not be a cause of diagnostic delay. There is currently no sufficient evidence supporting cytoreductive surgery in PCNSL, with recent studies showing contradictive data and suboptimal study designs.

Lymphoma presenting as preauricular tumor in unilateral parotid gland agenesis: a case report and review of literature.

BACKGROUND: Parotid gland agenesis is a rare, congenital, usually asymptomatic disorder. Until now, only 24 cases with unilateral, incidentally found, parotid gland agenesis have been described. Here, we present the first reported case of an ipsilateral preauricular neoplasm in a patient with unilateral parotid gland agenesis. During surgery, the position of the greater auricular- and facial nerves was documented. Furthermore, we performed the first sialendoscopy for this rare disorder to assess the number of duct branches, which might be indicative of the abundance of parotid tissue. Moreover, we looked for sialendoscopic characteristic features that could aid in identifying these patients in the ambulatory setting. CASE PRESENTATION: A 50-year-old Greek man presented with a painless, slowly enlarging mass in the right parotid space. Magnetic resonance imaging revealed a complete absence of the right parotid gland without accessory parotid tissue. The right parotid gland was replaced by fatty tissue and the radiologist suggested a benign parotid tumor. Fine needle aspiration was indicative of a reactive lymph node. Sialendoscopy revealed only two branches within the right parotid duct. Surgical resection was performed through a conventional lateral parotidectomy. This revealed typical anatomic position of the greater auricular- and facial nerves despite the parotid tissue agenesis. Histopathology revealed a small lymphocytic lymphoma. CONCLUSIONS: Surgeons should feel confident to resect tumors of the parotid space in patients with parotid gland agenesis. Reduced branching observed during sialendoscopy might indicate parotid gland agenesis. Physicians should be even more cautious than usual with the watch and wait strategy in patients with tumors of parotid gland agenesis, since the probability of a tumor being a benign salivary gland tumor might be lower than usual.

A multicenter proof-of-concept study on deep learning-based intraoperative discrimination of primary central nervous system lymphoma.

Accurate intraoperative differentiation of primary central nervous system lymphoma (PCNSL) remains pivotal in guiding neurosurgical decisions. However, distinguishing PCNSL from other lesions, notably glioma, through frozen sections challenges pathologists. Here we sought to develop and validate a deep learning model capable of precisely distinguishing PCNSL from non-PCNSL lesions, especially glioma, using hematoxylin and eosin (H&E)-stained frozen whole-slide images. Also, we compared its performance against pathologists of varying expertise. Additionally, a human-machine fusion approach integrated both model and pathologic diagnostics. In external cohorts, LGNet achieved AUROCs of 0.965 and 0.972 in distinguishing PCNSL from glioma and AUROCs of 0.981 and 0.993 in differentiating PCNSL from non-PCNSL lesions. Outperforming several pathologists, LGNet significantly improved diagnostic performance, further augmented to some extent by fusion approach. LGNet's proficiency in frozen section analysis and its synergy with pathologists indicate its valuable role in intraoperative diagnosis, particularly in discriminating PCNSL from glioma, alongside other lesions.

[Malignant lymphomas - quo vadis? - What developments await us in diagnostics and therapy?] / Maligne Lymphome ­ Quo vadis?

The diagnosis and treatment of malignant lymphoma is rapidly advancing, offering hope but also highlighting inherent limitations. Technological breakthroughs in sequencing technologies enable more precise subtyping and risk stratification. For example, in diffuse large B-cell lymphoma (DLBCL), exome sequencing revealed molecular subtypes. Understanding these subtypes sheds light on lymphomagenesis and prognosis, and may provide targets for tailored therapies. Additionally, tumor-derived cell-free DNA (ctDNA) detected in blood plasma allows for genotyping, risk stratification, and measurement of minimal residual disease (MRD). Current studies often examine drug effectiveness through "all-comer" approaches or in transcriptionally defined subtypes. Molecular agnostic studies increasingly focus on clinically defined high-risk patients (e.g., using the IPI) to better demonstrate the statistical significance of therapy effects. Improved patient selection can enhance the cost-effectiveness of modern, often expensive, therapies.

Molecular Pathology of Mature Lymphoid Malignancies.

Lymphoid malignancies are a broad and heterogeneous group of neoplasms. In the past decade, the genetic landscape of these tumors has been explored and cataloged in fine detail offering a glimpse into the mechanisms of lymphomagenesis and new opportunities to translate these findings into patient management. A myriad of studies have demonstrated both distinctive and overlapping molecular and chromosomal abnormalities that have influenced the diagnosis and classification of lymphoma, disease prognosis, and treatment selection.

[New classifications of malignant lymphomas - What changes are relevant for practice?] / Neue Klassifikationen maligner Lymphome ­ Welche Änderungen sind für die Praxis relevant?

An internationally uniform lymphoma classification is of fundamental importance for the comparability of clinical studies. There are currently 2 parallel classifications: the "International Consensus Classification" and the WHO-classification. Follicular lymphoma 3B is classified separately as follicular large cell lymphoma in WHO-HAEM5. The diagnostic criteria of lymphoplasmocytic lymphoma (LPL) have been adjusted, both classifications recommend molecular testing for MYD88 and CXCR4 mutations. There are no significant diagnostic changes in aggressive B-cell lymphomas. The ICC classify NLPBL and THRLBCL into the group of large B-cell lymphomas (LBCL). NLPHL/NLPBL-specific therapy must be considered, which differs greatly from the therapy of DLBCL, especially in the early stages. Peripheral T-cell lymphomas are a group of nodal T-cell lymphomas with a TFH phenotype and frequent mutations; peripheral T-cell lymphoma (NOS) is therefore a diagnosis of exclusion. Indolent T-cell lymphomas/lymphoproliferations of the GI tract are rare but must be differentiated from aggressive T-cell lymphomas. The WHO-HAEM5 also includes reactive/non-neoplastic lymph node lesions classified according to B or T cell predominance.

Primary colon lymphomas: An analysis of our experience over the last 18 years.

Colon lymphoma is a rare type of gastrointestinal lymphoma and represents 0.2% to -1.2% of all primary colon cancers. This study aimed to retrospectively examine the general characteristics, treatment methods, and survival characteristics of patients with colon lymphoma who were followed-up at our center. This retrospective study included patients diagnosed with colon lymphoma who were followed up at Ankara Numune Training and Research Hospital and Ankara Bilkent City Hospital between December 2005 and June 2023. Clinicopathological features, radiological findings, treatments, and modalities of patients were obtained from their medical records. Fourteen patients with primary colon lymphoma were included in the study. Thirteen patients (92.9%) were diagnosed with diffuse large B-cell lymphoma. The median age of the patients was 55 (28-84) years. The tumor location was the terminal ileum/cecum in 50% of the patients. At the time of diagnosis, 10 patients (7 with stage 1E-2E disease, 2 with stage 3E disease, and 1 with stage 4E disease due to tumor obstruction) underwent surgery. Twelve patients received chemotherapy (6 patients as adjuvant and 6 patients as first-line treatment). The median overall survival (OS) was 10 years (0.1-21.5) years, the 5-year median OS was 71%, and the 10-year median OS was 53%. Primary colon lymphoma is a rare disease and its optimal treatment is not clearly defined. The primary treatment for primary colon lymphoma is a combination of surgery and chemotherapy. A clear consensus on the treatment can be established through prospective studies.

[Analysis on the ultrasonic characteristics of tonsillar lymphoma].

Objective: To analyze the ultrasonic features of tonsillar lymphoma to improve the diagnostic accuracy. Methods: The clinical, pathological and ultrasonic data of nine patients with tonsillar lymphoma confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital during June 2015 and June 2022 were analyzed retrospectively, and the characteristics of their ultrasonic images were summarized. Results: All 9 cases of tonsil lymphoma were unilateral tonsil disease, including 4 cases on the left side and 5 cases on the right side. The average maximum diameter of tonsil lymphoma in 9 cases was 4.32 cm. There were 3 cases with simultaneous involvement of tonsil and cervical lymph nodes, all of which were ipsilateral lymph nodes. Gray scale ultrasound showed that the lesions were hypoechoic, with clear boundaries in 7 cases and unclear boundaries in 2 cases. The shape was full and irregular in 5 cases and oval in 4 cases. The echo was uniform in 7 cases and uneven in 2 cases. Color Doppler ultrasonography showed abundant internal blood flow signal in 1 case, a little dotted linear internal blood flow signal in 5 cases, and no obvious internal blood flow signal in 3 cases. Conclusions: The ultrasonic features of tonsillar lymphoma include hypoechoic area, clear boundary, full shape, irregular and uniform internal echo, no or low linear signal of internal blood flow. Ultrasonography is of great value in the diagnosis of this disease and can help clinical decision-making.