Small Cell Lymphoma Research Articles

Serum electrolyte abnormalities in cats with chronic inflammatory enteropathy.

Limited information is available on electrolyte abnormalities in cats with chronic inflammatory enteropathy (CIE). Report the prevalence of electrolyte abnormalities in cats with CIE compared to other gastrointestinal disorders, and determine their association with disease and outcome variables in cats with CIE. Three hundred twenty-eight client-owned cats from 2 referral hospitals: CIE (132), alimentary small cell lymphoma (29), acute gastroenteritis (48), and healthy controls (119). Retrospective study comparing serum electrolyte concentrations at time of diagnosis among the 4 groups of cats, and associations with clinical signs, intestinal mucosal fibrosis scores, treatment subclassification and outcome in CIE. Cats with CIE had lower sodium and higher potassium concentrations and lower sodium: potassium ratios compared with healthy cats (P < .001, P = .01, and P < .001, respectively). Cats with CIE and a duodenal mucosal fibrosis score of 2 had lower sodium and lower total calcium concentrations compared with cats that had a score of 0 (P = .02 and P = .01). Cats with CIE and a colonic mucosal fibrosis score of 1 had higher potassium concentrations and lower sodium: potassium ratios compared with cats that had a score of 0 (P = .03 and P = .01). Cats with CIE that died as a result of their disease had higher potassium concentrations and lower sodium: potassium ratios compared to cats that were alive (P = .02 and P = .01). Electrolyte abnormalities occur with CIE and, in particular, in cats with higher fibrosis scores and worse outcomes. Further research should aim to determine the pathogenesis of these findings and identify novel therapeutic targets for cats with CIE.

Cardiovascular and non-cardiovascular adverse events in patients with hematologic malignacies treated with BTK inhibitors: a real-world analysis

Abstract Background Bruton tyrosine kinase (BTK) inhibitors play an important role in targeted treatment of B-cell lymphoproliferative disorders. However, adverse events may limit the proper course of treatment in many patients. Purpose To compare the risk of cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia (CLL) or small cell lymphocytic lymphoma (SLL) treated with first-generation BTK inhibitor ibrutinib versus second-generation acalabrutinib, using real-world data from electronic medical records. Methods We used data from a large collaborative multinational network ( TriNetX), that emcompasses more than 100 healthcare organizations worldwide. We queried the databank for patients aged ≥ 18 years with chronic lymphocytic leukemia or small-cell lymphomas treated with ibrutinib or acalabrutinib in the past 10 years before the analysis. We used propensity score matching to balance the cohorts. The 3-year cumulative incidences and hazard ratios for the following outcomes were calculated: atrial flutter or fibrillation, other arrhythmias, heart failure, ischemic stroke or peripheral embolism, acute coronary syndrome, bleeding, and sepsis. Results We compared 2,107 patients in each group. The 3-year incidences of atrial fibrillation or flutter in the acalabrutinib and ibrutinib groups were 7.11% and 14.78% respectively, with a lower ratio in patients treated with acalabrutinib than those treated with ibrutinib (hazard ratio, HR 0.68, 95% CI 0.55-0.84). New-onset hypertension occurred during the 3-year follow-up in 16.29% patients in the acalabrutinib group versus 27.8% patients in the ibrutinib group (HR 0,81, 95% CI 0.66-0.98). The incidence of sepsis was 6.49% in patients treated with acalabrutinib versus 11.37% in those treated with ibrutinib group (HR 0.77, 95% CI 0.60-0.98). Concerning the other adverse events, there were no significant differences between the two groups. Conclusions In this large real-world analysis, patients with CLL or SLL treated with acalabrutinib had a better cardiovascular and non-cardiovascular safety profile than those treated with ibrutinib, with lower incidence of atrial flutter or fibrillation, new-onset arterial hypertension, and sepsis.Figure 1.Cardiovascular outcomesFigure 2.Non-cardiovascular outcomes

Characterization of faecal microbiota and serum inflammatory markers in dogs diagnosed with chronic enteropathy or small-cell lymphoma: a pilot study

Dogs diagnosed with chronic enteropathy (CE) or small-cell lymphoma (SCL) exhibit marked differences in faecal microbiota and organic acid profiles compared with healthy dogs, as well as immune abnormalities in intestinal mucosal tissue. However, few studies have analysed trace organic acids, such as succinic acid, which have been suggested to be associated with IBD in humans. Therefore, in this study, we compared the faecal microbiota and organic acid profiles as well as serum inflammatory markers between dogs with disease (n = 11; 6 with CE and 5 with SCL) and healthy controls (n = 16). We also performed machine learning and correlation analysis to obtain more detailed insights into the characteristics of affected dogs. These results revealed that dogs with CE and SCL had lower levels of Erysipelotrichaceae (e.g. Turicibacter and Allobaculum), exhibited abnormalities in the succinic acid metabolism (i.e. succinic acid accumulation and decreased levels of Phascolarctobacterium as succinic acid-utilising bacteria) and increased levels of pathobiont bacteria such as Escherichia-Shigella. Additionally, the presence of Dubosiella was significantly negatively correlated with Canine Inflammatory Bowel Disease Activity Index scores. These findings are expected to aid the development of microbiome-based medications and/or supplements, although further verification is needed.

Three-year cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia or small cell lymphocytic lymphoma treated with Bruton tyrosine kinase inhibitors acalabrutinib or ibrutinib: a real-world analysis.

Bruton tyrosine kinase (BTK) inhibitors play an important role in targeted treatment of B-cell lymphoproliferative disorders. However, adverse events may limit the proper course of treatment in many patients. The purpose of this study is to compare the risk of cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia (CLL) or small cell lymphocytic lymphoma (SLL) treated with the first-generation BTK inhibitor ibrutinib versus second-generation acalabrutinib, using real-world data from a collaborative multinational network. We used data from the network (TriNetX), which encompasses more than 100 healthcare organizations worldwide. We queried the database for patients aged ≥ 18 years with chronic lymphocytic leukemia or small-cell lymphomas treated with ibrutinib or acalabrutinib in the past ten years before the analysis. We used propensity score matching to balance the cohorts. The 3-year cumulative incidences and hazard ratios for the following outcomes were calculated: atrial flutter or fibrillation, other arrhythmias, heart failure, ischemic stroke or peripheral embolism, acute coronary syndrome, bleeding, and sepsis. We compared 2,107 patients in each group. Atrial fibrillation or flutter occurred in 150 (7.1%) patients with acalabrutinib and 310 (14.7%) patients with ibrutinib during the 3-year follow-up (hazard ratio, 0.68, 95% CI 0.55-0.84). New-onset hypertension occurred in 342 (16.3%) patients in the acalabrutinib group and 584 (27.7%) patients in the ibrutinib group (hazard ratio 0.81, 95% CI 0.66-0.98). Sepsis was diagnosed in 136 (6.5%) patients in the acalabrutinib group versus 239 (11.3%) patients in the ibrutinib group (hazard ratio 0.77, 95 CI 0.60-0.98). The two groups had no significant differences concerning the other adverse events. In a large retrospective cohort using real-world data from electronic medical registers, patients with CLL or SLL treated with acalabrutinib had a better cardiovascular and non-cardiovascular safety profile than those treated with ibrutinib, with lower risks of atrial flutter or fibrillation, new-onset arterial hypertension, and sepsis.

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

Regional lymph nodes are frequently sampled in cats with suspected intestinal lymphoma; however, their diagnostic value has not been explored. To investigate whether histologic and immunohistochemical analysis of mesenteric lymph nodes correlates with the diagnosis of intestinal lymphoma in cats. One hundred 2 client-owned cats diagnosed with intestinal lymphoma. 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. 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. 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.

Short colon syndrome in cats.

Shortening of the colon has been described in cats, but its imaging and clinicopathological features remain poorly understood. Description of the signalment, clinical presentation, imaging, endoscopic and histological features of short colon syndrome in cats. Ninety-three cats diagnosed with short colon. Multi-institutional, descriptive, retrospective case series study. Medical records were searched for a diagnosis of short colon on abdominal ultrasonography, computed tomography, endoscopy, autopsy, or a combination of these modalities. The median age of included cats was 12 years at the time of diagnosis. Diarrhea was the most common clinical sign (60/92; 65%), followed by vomiting (36/92; 39%), weight loss (36/92; 39%), and inappetence (24/92; 26%). Thirteen percent of cats (12/92) had no signs of gastrointestinal disease at the time of diagnosis. In addition to a shortened colonic length, 79% (66/84) of cats had concomitant colonic thickening on ultrasonographic examination. On colonoscopy, mucosal ulcerations of the colonic wall were seen in 39% (9/23) of cats. Histopathologically, all cats but 1 (diagnosed simultaneously with colonic small cell lymphoma) had lymphoplasmacytic colitis, and when small intestinal biopsies were performed, concurrent lymphoplasmacytic enteritis or small cell lymphoma of the small intestine. Lymphoplasmacytic colitis is seen commonly in cats with short colon, suggesting a potential link between these entities.

Persistent feline coronavirus infection in a cat with cardiac and gastrointestinal signs

Background Feline coronavirus infection causes feline infectious peritonitis in a subset of cats, but can also result in persistent infection. The tissue reservoirs of feline coronavirus and the role of viral persistence in pathogenesis are poorly understood. Aims This study aimed to identify sites of feline coronavirus persistence in a naturally infected cat, identify disease correlates and characterise within-host viral evolution. Methods The study followed a 5-year-old Bengal cat for 6 years and collected non-invasive samples, including faeces and conjunctival, oropharyngeal and saliva swabs. At 11-years-old, the patient was euthanised as a result of respiratory distress, and tissue samples were collected. The authors used hybridisation capture and next-generation sequencing methodologies focused on the feline coronavirus S gene, along with RNA in-situ hybridisation. Results During the study, the patient was diagnosed with inflammatory bowel disease, alimentary small cell lymphoma, chronic rhinitis and mitral valve regurgitation. Feline coronavirus was detected in the nasal cavity, intestine, faeces and conjunctiva in 2017, and in the intestine, faeces and heart in 2022. Sequence analysis showed that the virus adapted to tissue reservoirs over time. Conclusions This study identifies potential feline coronavirus reservoirs. The relationship of persistent feline coronavirus infection to chronic conditions warrants further investigation.

Abstract 6065: Identification and characterization of paralogue selective CBP degraders for potential use in cancer therapy

Abstract CBP and p300 are closely related epigenetic modulators that participate in chromatin remodeling and transcription and play an oncogenic role in a variety of cancers. Studies have indicated that the selective targeting of CBP is a highly attractive therapeutic strategy for cancers with p300 mutations because of synthetic lethality, those that are dependent on Wnt/β-catenin signaling and ERα and HER2-positive breast cancers. Prevalence of high mutation frequency of p300 in several cancers including skin cancers (27%), small cell lung cancers (8%), lymphoma (8-13%) and bladder cancer (9%) further highlight an opportunity for selective inactivation of CBP in cancer therapy. However, it has not been possible to identify selective inhibitors of p300 or CBP because of the conserved sequence and structure of functional domains such as HAT domain or bromodomain. We sought to achieve selective CBP targeting by utilizing the degrader approach, which in the recent time has proven to be useful in achieving paralog selectivity due to differentiated ternary complex formation. Additionally, the degrader approach offers several inherent advantages including stronger phenotype due to greater potency, sustained action due to catalytic mode of action, overcoming resistance and greater selectivity. Utilizing a combination of structure-guided modelling and iterative medicinal chemistry strategies, we identified first-in-class selective degraders targeting CBP with varying linker lengths and compositions. Our lead compounds exhibit remarkable bias in degrading CBP in cell lines harboring loss-of-function mutations in p300, while sparing wild-type cells. Selective CBP degraders disrupted β-catenin transactivation function in a dose-dependent manner and demonstrated good oral bioavailability and PK profile in preclinical species. Further optimization of potency, selectivity, ADME properties while evaluating in vivo efficacy in appropriate models and tolerability in higher species is ongoing towards identifying a development candidate. Citation Format: Saravanan Thiyagarajan, Chandrasekhar Abbineni, Krishna Chaitanya T, Achala Apte, Iram Khan Iqbal, Naveen Kumar R, Aravind A B, Avinash Kumar, Girish A R, Aishwarya B Kamath, Deepak Dattatray Mane, Gouri Raj A, Reshma Reghu, Subhasmita Mohapatra, Sivapriya Marappan, Suraj T Gore, Subhendu Mukherjee, Girish Daginakatte, Kavitha Nellore, Shekar Chelur, Murali Ramachandra, Susanta Samajdar. Identification and characterization of paralogue selective CBP degraders for potential use in cancer 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 6065.

Mesenteric small cell lymphocytic lymphoma presenting as acute intestinal obstruction: A rare case scenario

Small-cell lymphocytic lymphoma is a rare type of B-cell non-Hodgkin lymphoma. It is known as one of the indolent lymphomas. Moreover, sigmoid volvulus as an initial presentation is extremely uncommon. We encountered a unique case of mesenteric small cell lymphocytic lymphoma that presented with sigmoid volvulus as the initial clinical presentation. A 55-year-old male presented with 7-day history of abdominal pain, abdominal distension for 6 days, and non-passage of stool and flatus with recurrent vomiting for 3 days. Abdominopelvic computed tomography revealed a distended small bowel with volvulus of sigmoid colon with twisting of its mesentery with inter-ileal as well as free peritoneal collections of fluid. A manual untwisting counterclockwise of the volvulus followed by resection and anastomosis at a point where the bowel has apparent normal thickness and color along with excisional biopsy of the enlarged lymph node. Histopathology confirmed the diagnosis of small-cell lymphocytic lymphoma. Mesenteric lymphomas are less likely to present with sigmoid volvulus as the initial clinical presentation due to their extraluminal location and also they are indolent in course. Early diagnosis and its management reduce morbidity and mortality.

Contribution of Computed Tomography in the Diagnosis of Multifocal Non-Hodgkin’s Lymphoma at the Mother-Child University Hospital the ‘’Luxembourg’’ About a Case

Lymphoma is a malignant proliferation of lymphoid tissue cells. We report a case of multi-focal lymphoma of lymph node, pharyngeal, cardiac and splenic sites. This was a 19-year-old patient received in February 2023, at the radiology and medical imaging department of the Mother and Child University Hospital Center ''Luxembourg'' as part of the CT exploration of a lateral mass. -left cervical. On admission, the clinical examination found a patient with an altered general condition, moderately colored conjunctiva, normal blood pressure and temperature. Examination of the lymph node areas revealed a left latero-cervical swelling, and fixed bilateral axillary swellings, of firm consistency and irregular contours. Palpation revealed hepatosplenomegaly. Cardiopulmonary auscultation was normal. A cervico-thoraco-abdominal CT scan revealed irregular thickening of the left lateral wall of the oropharynx, a hypodense tissue mass in the right cardiac chambers, heterogeneous splenomegaly, cervical, mediastinal, axillary and abdominal ADP. The histological examination carried out after lymph node biopsy revealed a histological appearance of small cell lymphoma. Conclusion: Lymphoma is a very common malignant tumor that can occur at any age. This tumor can affect all organs, however its cardiac location is rare. The positive diagnosis remains histological. Imaging plays an important role in the initial assessment, extension and surveillance.

Faecal microbiota and fatty acids in feline chronic enteropathy

BackgroundFeline chronic enteropathy is a set of disorders defined as the presence of clinical signs of gastrointestinal disease for at least three weeks. The most common final diagnoses are inflammatory bowel disease and alimentary small cell lymphoma. The etiopathogenesis of these diseases is incompletely understood; however, it is hypothesised that they involve a combination of factors, including altered composition and/or functionality of the intestinal microbiome. An important factor in the interplay of the microbiome and host is the production of short- and branched-chain fatty acids. The aim of this study was to evaluate the possible differences in faecal microbiota diversity, composition and fatty acid production between cats suffering from chronic enteropathy and healthy cats. Sixteen cats suffering from chronic enteropathy and fourteen healthy control cats were enrolled in the study. The microbiota compositions of faecal samples were analysed by using next-generation amplicon sequencing of the V3V4 fragment of the 16S rRNA gene. Fatty acids were evaluated by high-performance liquid chromatography.ResultsBoth the alpha and beta diversities were significantly lower in samples obtained from cats with chronic enteropathy. The relative abundance of the phylum Proteobacteria, orders Lactobacillales and Enterobacterales, family Enteriobacteriaceae and genus Escherichia Shigella were higher in diseased cats, whereas the abundance of the phylum Bacteroidota and order Peptococcales were higher in control cats. The faecal concentrations of short-chain fatty acids were higher in cats with chronic enteropathy, with lower propionate proportions and higher butyrate proportions.ConclusionThe study revealed alterations in microbiota compositions and short-chain fatty acid concentration in cats suffering from chronic enteropathy, which is an important finding both for research on the pathogenesis of the disease and for potential therapeutic interventions in the form of faecal microbiota transplantation and/or probiotic supplementation.

Histopathologic diagnosis and patient characteristics in cats with small intestinal obstructions secondary to trichobezoars.

The aim of the present study was to describe the distribution of gastrointestinal histopathology findings associated with gastrointestinal obstructions secondary to trichobezoar formation in cats. A total of 100 surgical gastrointestinal biopsies were obtained from 44 cats with gastrointestinal obstructions secondary to a trichobezoar. Medical records, including signalment, type and duration of clinical signs, surgical reports and histopathologic analysis, were reviewed for each cat. Biopsies taken near the site of the trichobezoar were more likely to show neutrophilic inflammation and mucosal erosion/ulceration compared with biopsies taken elsewhere in the small intestine. Lymphoplasmacytic and mixed lymphocytic and eosinophilic populations were the most common histopathologic findings from all biopsies followed by alimentary small cell lymphoma. Biopsy samples were more likely to represent a diagnosis of alimentary lymphoma in cats older than 10 years. Gastrointestinal biopsies taken at the time of surgery in cats with trichobezoar obstructions may represent an important diagnostic tool for further evaluation of potential feline chronic enteropathy. Biopsies taken at the site of the obstruction should be interpreted cautiously as the presence of a trichobezoar may induce an acute inflammatory reaction. The resultant histologic interpretation at this site may not represent the chronic state of the intestinal mucosa, supporting the utility of obtaining multiple biopsies orad and aborad to the obstruction.

The role of surgery in the management of liver metastases from non-colorectal cancers: A review of the literature

Surgery for non-colorectal liver metastases is nowadays indicated due to advances in surgical techniques and patients multimodal management. The objective of our study is to evaluate the surgical management of liver metastases of non-colorectal cancers in the visceral surgery department of the Mohamed V military hospital in Rabat. This is a retrospective study on a series of 13 resections for non-colorectal liver metastases over a period of 6 years from January 2015 to December 2020. In our series, the average age is 53 years with a prevalence of women (62%). The primary cancer was ducal breast carcinoma 6 times (46.15%). There were 2 cases of stromal tumors (15.38%), 2 cases of neuroendocrine tumors (15.38%), one case of gastric adenocarcinoma, gastric small cell lymphoma, and of adrenocortical carcinoma. Liver metastases were synchronous in 76.92% of cases, metachronous in 23.08% of cases. They were unique in 84.62% of cases, bilobar in 15.38% of cases. The type of liver resection performed was 11 metastasectomy, 3 segmentectomy, 3 bi-segmentectomy. Mortality rate was zero and the morbidity rate was 15.38%. One patient had hepatic recurrence. With a follow-up of 3 to 36 months after resection, only one patient died after 12 months. The management of patients with non-colorectal liver metastases is based on a multimodal approach. Our results show that surgery, when feasible in selected patients, is a safe option and the only possibility for long-term survival. Future advances in chemotherapy, biotherapies and immunotherapy are likely to broaden the indications for surgery.

Deep learning analysis of mid-infrared microscopic imaging data for the diagnosis and classification of human lymphomas.

The present study presents an alternative analytical workflow that combines mid-infrared (MIR) microscopic imaging and deep learning to diagnose human lymphoma and differentiate between small and large cell lymphoma. We could show that using a deep learning approach to analyze MIR hyperspectral data obtained from benign and malignant lymph node pathology results in high accuracy for correct classification, learning the distinct region of 3900 cm-1 to 850 cm-1 . The accuracy is above 95% for every pair of malignant lymphoid tissue and still above 90% for the distinction between benign and malignant lymphoid tissue for binary classification. These results demonstrate that a preliminary diagnosis and subtyping of human lymphoma could be streamlined by applying a deep learning approach to analyze MIR spectroscopic data. This article is protected by copyright. All rights reserved.

Isolation of Malassezia yeasts from dogs with gastrointestinal disease undergoing duodenal endoscopy.

To culture Malassezia and other fungi from the duodenum of dogs with gastrointestinal signs undergoing routine endoscopic examination. Quantitative microbial culture was performed on duodenal juice aspirated from dogs with suspected enteropathy during routine upper gastrointestinal endoscopy; samples were cultured on Sabouraud's dextrose agar (30, 32 and 37°C) and modified Dixon agar (32°C) for 14 days. Isolates were identified phenotypically and by matrix-assisted laser desorption ionisation-time of flight, and internal transcribed spacer sequencing. Yeast presence was also evaluated by cytological and histopathological examination of smears and biopsy specimens. Forty-five dogs were recruited with chronic inflammatory enteropathy (n=38), granulomatous colitis (n=2), gastric adenocarcinoma (n=2), duodenal small cell lymphoma (n=1) and idiopathic severe gastrointestinal haemorrhage (n=2). Fungi were cultured from 14 dogs: Malassezia pachydermatis was isolated from eight [chronic inflammatory enteropathy (n=7) (along with Candida albicans n=1); granulomatous colitis (n=1)] and Malassezia sympodialis from another (gastric adenocarcinoma). Five dogs with chronic inflammatory enteropathy yielded other yeasts (C. albicans, Candida glabrata, Kazachstania slooffiae, Kazachstania telluris, Pichia kudriavzevii [syn. C. krusei]). Yeasts were never observed in histopathological specimens. Fluorescent microscopical examination of cytological specimens showed yeast in only one case, from which K. slooffiae was subsequently isolated. Based on a literature search, this is the first report of isolation of M. pachydermatis, M. sympodialis, K. slooffiae and K. telluris from the canine duodenum. Further studies are needed to determine whether these are resident or transient fungi in the canine duodenum and whether their presence has a pathogenic effect on the host.

Prognostic value of increased intraepithelial lymphocytes and lymphocytic clonality in dogs with chronic enteropathy or small-cell lymphoma

The clinical significance of severe infiltration of small intraepithelial lymphocytes (IEL) and the results of polymerase chain reaction for antigen receptor rearrangement (PARR) in dogs with chronic enteropathy (CE) and small-cell lymphoma (SCL) are controversial. This cohort study aimed to evaluate the prognostic significance of the IEL and PARR results in dogs with CE or SCL. Although definitive diagnostic histopathological criteria for SCL in dogs have yet to be established, dogs with the histopathological findings of severe IEL infiltration were diagnosed with SCL in this study. One hundred and nineteen dogs were recruited, with 23 dogs classified as having SCL and 96 dogs as having CE. The positive rate of PARR was 59.6 % (71/119) in the duodenum and 57.7 % (64/111) in the ileum. Subsequently, three dogs with SCL and four dogs with CE developed large-cell lymphoma (LCL). The median overall survival (OS) of dogs with SCL was 700 days (range, 6–1410 days), and that of dogs with CE was not reached. In the log-rank test, shorter OS was observed in cases with histopathological SCL (P = 0.035), clonal TCRγ rearrangement in the duodenum (P = 0.012), and clonal IgH rearrangement in the ileum (P < 0.0001). The Cox proportional hazards model adjusted for sex and age showed that histopathological SCL (hazard ratio [HR] 1.74; 95 % confidence interval [CI], 0.83–3.65), duodenal clonal TCRγ rearrangement (HR, 1.80; 95 % CI, 0.86–3.75), and ileal clonal IgH rearrangement (HR, 2.28; 95 % CI, 0.92–5.70) could shorten overall survival, although their 95 % CIs included 1.0. These results indicate that severe IEL infiltration could be a useful histopathological feature for diagnosing SCL, and clonality-positive results could be a negative prognostic factor in dogs with CE. Furthermore, the development of LCL should be carefully monitored in dogs with CE and SCL..

NKX3.1 immunohistochemistry and methylome profiling in mesenchymal chondrosarcoma: additional diagnostic value for a well-defined disease?

Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive tumour of soft tissue and bone that is defined by an underlying and highly specific fusion transcript involving HEY1 and NCOA2. Histologically, the tumours show a biphasic appearance consisting of an undifferentiated blue and round cell component as well as islands of highly differentiated cartilage. Particularly in core needle biopsies, the chondromatous component can be missed and the non-specific morphology and immunophenotype of the round cell component can cause diagnostic challenges. We applied NKX3.1 immunohistochemistry which was recently reported as a highly specific marker as well as methylome and copy number profiling to a set of 45 well characterised MCS cases to evaluate their potential diagnostic value. Methylome profiling revealed a highly distinct cluster for MCS. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. NKX3.1 immunohistochemistry showed positivity in 36% of tumours, the majority of which was rather focal and weak. Taken together, NKX3.1 expression showed a low sensitivity but a high specificity in our analysis. Methylome profiling on the other hand represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. Furthermore, it can aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.

Primary Cutaneous B-Cell Lymphomas with Large Cell Morphology: A Practical Review.

Most primary cutaneous lymphomas consist of T-cell lymphomas or small cell lymphomas; however, the skin may also be affected by lymphomas with large cell morphology, as a primary or secondary localization. A minority of cases consist of primary cutaneous B-cell lymphomas (PCBCLs). PCBCLs are a heterogeneous group of rare neoplasms with an overlapping morphological and immunohistochemical picture of the different subtypes. Nevertheless, differential diagnosis in the setting of this group of neoplasms is mandatory to identify the correct therapy and prognosis, but it may be challenging since, due to the rarity of these neoplasms, they may not always be familiar to pathologists. Indeed, immunohistochemistry may not be enough to distinguish the different histotypes, which overlap in immunohistochemical features. Furthermore, the ever-increasing knowledge of the molecular features of systemic B-cell lymphomas, such as gene rearrangements with clinical significance, has led in recent years to further investigation into the molecular landscape of PCBCLs with large cell morphology. This work aimed to provide a practical diagnostic guide for pathologists dealing with primary cutaneous large B-cell lymphomas.

SAFESTEREO: phase II randomized trial to compare stereotactic radiosurgery with fractionated stereotactic radiosurgery for brain metastases

BackgroundStereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases.MethodsPatients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15–24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life.DiscussionCurrently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure.Trial registrationClincalTrials.gov, trial registration number: NCT05346367, trial registration date: 26 April 2022.

Areas of Crush Nuclear Streaming Should Be Included as Tumor Content in the Era of Molecular Diagnostics

Degenerated tissues are frequently observed in malignant tumors, but are not analyzed. We investigated whether nuclear streaming and necrosis samples could be used for genetic analysis to expand the sample pool. A total of 81 samples were extracted from small cell carcinoma and lymphoma FFPE tissue blocks and classified into three histological cohorts: 33 materials with well-preserved tumor morphology, 31 nuclear streaming samples, and 17 necrosis samples. DNA and RNA integrity numbers, percentage of RNA fragments with >200 nucleotides, and next-generation sequencing quality metrics were compared among the cohorts. DNA quality did not significantly differ between nuclear streaming materials and materials with well-preserved morphology, whereas that of the necrosis samples was inferior. RNA quality decreased in the following order: materials with well-preserved morphology > nuclear streaming > necrosis. The sequencing metrics did not differ significantly between the nuclear streaming samples and materials with well-preserved morphology, and reliable variants were detected. The necrosis samples extracted from resections exhibited sequencing failure and showed significantly fewer on-target aligned reads and variants. However, variant allele frequency did not differ among the cohorts. We revelated that DNA in nuclear streaming samples, especially within biopsies, could be used for genetic analysis. Moreover, degenerated non-tumor cells should be counted when evaluating tumor content to avoid misinterpreting the variant allele frequency.