Infiltration Of Neoplastic Cells Research Articles

DIAGNOSTIC TEST OF POSTERIOR SEGMENT OCULAR EXAMINATION ON THE SEVERITY OF PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) AT DR. MOHAMMAD HOESIN GENERAL HOSPITAL PALEMBANG

Background: Acute lymphoblastic leukemia (ALL) is one of the highest incidence of all cancers in children. Ocular involvement can diagnose the development of the disease. Patients with ALL often have ocular manifestations either resulting from direct infiltration or indirect causes of neoplastic cells. The aim of this study to diagnose from posterior segment findings on disease severity in pediatric patients with acute lymphoblastic leukemia (ALL) at Muhammad Hoesin Hospital Palembang
 Methods: A diagnostic test to determine the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of posterior segment findings in disease severity diagnostic of pediatric patients with ALL from November 2021 to May 2022. Posterior segment findings that were evaluated included retinal hemorrhages, roth spots, exudate and papilledema. Disease severity of pediatric ALL is divided into high risk and standard risk. All data were analyzed using SPPS version 22.0
 Results: There were 68 patients who selected by inclusion criteria. A total of 30 (44.1%) subjects with high risk and 38 (55.9%) with standard risk. in this study there is no patient have papilledema and only one patient (1.5%) has retinal hemorrhage, roth spot and exudate. From statistical analysis, it was found that the three posterior findings had a sensitivity of 0% and a specificity of 97.4%.
 Conclusion: The results of this study show that the findings of the posterior eye segment can be used as a screening tool for the severity of acute lymphoblastic leukemia, because only one component of sensitivity and specificity has a value of > 80%.

Subcutaneous Panniculitis-like T-cell Lymphoma: A Case Report of A Solved Conundrum

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma which often be very complexed to be diagnosed. Here we reported a case of a 38-year-old lady with wax and wane course of left facial swelling associated with prolonged pyrexia of unknown origin, lethargy and prominent weight loss. Multiple investigations were conducted to reach to the conclusive diagnosis. Histopathological showed infiltration of neoplastic lymphoid cells within the adipocyte clusters with hyperchromatic nuclei, small nucleoli and scant cytoplasm. Immunohistochemical analysis were immunoreactive to CD3, CD8 & TIA and negative to CD20, CD4 & CD56. Based on clinical findings, histopathology report and immunohistochemical analysis, the patient diagnosed with SPTCL. Hence, any suspicious maxillofacial swelling without obvious sign of infection and trauma shall be investigated until a final diagnosis is reached.

Cytogenetic Profile in Monoclonal Gammopathy of Undetermined Significance, Smoldering and Symptomatic Multiple Myeloma: A Study of 1087 Patients with Highly Purified Plasma Cells

The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p), MYC-rearrangement (MYC-R), del(1p), and tetraploidy. Elevated frequencies of high-risk cytogenetics (59%), 1q gain (44%), and del(17p) (23%), as well as the presence of subclones (48%), were particularly notable in RRMM cases. IGH::CCND1 was observed in 26% of the cases, with no apparent variations across races, ages, or disease groups. Concurrent chromosomal analysis with FISH revealed that the incidence of abnormal karyotypes was strongly correlated with the extent of neoplastic plasma cell infiltration, genomic complexity, and the presence of specific abnormalities like del(17p) and MYC-R. Approximately 98% of the cases with abnormal karyotypes were complex, with most featuring five or more abnormalities. Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort.

Initial Results from Summit: An Ongoing, 3-Part, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of Bezuclastinib in Adult Patients with Nonadvanced Systemic Mastocytosis (NonAdvSM)

Background: Systemic mastocytosis (SM) is a rare disease characterized by neoplastic mast cell infiltration of extracutaneous tissues and encompasses a spectrum of subtypes that can range from non-advanced to advanced disease. Nonadvanced SM (NonAdvSM) includes two variants of SM: indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM). NonAdvSM is often associated with debilitating symptoms which may significantly reduce health-related quality of life (HRQoL). In up to 95% of patients, SM is driven by the somatic KIT D816V gain of function mutation located in exon 17. Bezuclastinib (CGT9486) is an oral, potent, and selective type 1 tyrosine kinase inhibitor (TKI) with activity against KIT D816V. Preclinical studies demonstrate bezuclastinib inhibits KIT D816V with minimal brain penetration. Early results from Part 1 of a Phase 2 trial of patients with AdvSM demonstrate that bezuclastinib is well-tolerated and is associated with encouraging clinical activity. Bezuclastinib resulted in meaningful reductions in markers of disease burden including serum tryptase, bone marrow mast cell burden, and KIT D816V variant allele fraction (DeAngelo et al. [abstract] In: Blood (ASH) 2022; 140 (Supplement 1): 1512-13). These results support the investigation of bezuclastinib as a potential therapy in NonAdvSM. Study Design and Methods: Summit (NCT05186753) is a multi-center, Phase 2, randomized, double-blind, placebo-controlled, 3-part clinical trial of bezuclastinib in patients with NonAdvSM, including ISM and SSM, who have inadequate control of symptoms despite treatment with best supportive care (BSC). Patient-reported outcome measures (PROMs), including mastocytosis activity score (MAS) and mastocytosis quality of life (MC-QoL), are being used to assess treatment impact on symptoms and HRQoL. Approximately 48 patients will be enrolled in Part 1 of the trial with 1:1:1 randomization to one of two doses of bezuclastinib (100 or 200 mg QD for Part 1a; 100 or 150 mg QD for Part 1b) or placebo. Here we report initial data from Part 1a of the Summit trial. Results: Part 1a of Summit enrolled 20 patients; 18 patients had ISM and 2 patients had SSM. In Part 1a, a majority of patients were female (75%) and had an Eastern Cooperative Oncology Group Performance Status of 0-1 (90%) or 2 (10%). Mean age was 54. Patients utilized a median (range) of 3 (2 to 7) BSC medications, with 100% using H1 blockers, 95% using H2 blockers and 40% using leukotriene receptor antagonists. Enrolled patients had a median (range) serum tryptase of 74 (10 to 592) ng/mL and 85% of patients had a serum tryptase ≥20 ng/mL. 75% of patients were KIT D816V positive and median (range) KIT D816V variant allele fraction in whole blood was 0.5% (0 to 32). Median (range) percent bone marrow mast cell burden was 23% (1 to 80%). Utilizing MAS to assess baseline disease severity, a majority of patients self-reported severe disease with a median score of 43 (range 22-79). Patients also self-reported a mean score of 56+/- 19 on the MC-QOL, indicating moderate impact to their HRQoL. Conclusions: The Summit trial evaluating safety and efficacy of bezuclastinib enrolled 20 patients in Part 1a. The patients enrolled in Part 1a of the Summit trial are generally representative of the population of patients with moderate to severe nonadvanced systemic mastocytosis based on number of supportive care medications, symptom severity, and disease impact on HRQoL. Initial safety and efficacy results from Part 1a of the 3-part, randomized, double-blind, placebo-controlled Summit trial will be presented.

CTNI-56. FEASIBILITY AND EFFICACY OF AI-GUIDED PERSONALIZED PRECISION RADIATION THERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA: A MATCHED-CONTROL STUDY

Abstract PURPOSE The aim of this study was to evaluate the feasibility and efficacy of AI-guided personalized precision radiation therapy (PPRT) in improving outcomes for patients with newly diagnosed glioblastoma. METHODS In an open-label trial conducted at the University of Pennsylvania (NCT03477513), between August 2018 and April 2021, 17 patients with IDH-wildtype glioblastoma who underwent maximal safe resection were enrolled. They were matched with a cohort of glioblastoma patients based on age, sex, extent of resection (EOR), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation status, and IDH status. Propensity Score Matching (PSM) was employed to assess the impact of the intervention on the likelihood of survival, using logistic regression to estimate the propensity score. Four patients were disqualified based on exclusion criteria. The PPRT group received personalized radiation dose escalation guided by AI-based predictive modeling of recurrence, along with concomitant and maintenance temozolomide chemotherapy. The control group received standard-of-care chemoradiotherapy between 2012 and 2020. In this study, we utilized a previously published and evaluated (retrospectively and prospectively) predictive AI model, which accurately estimated neoplastic cell infiltration and predicted future tumor recurrence using preoperative, multi-parametric MRIs. RESULTS Median overall survival was 24.4 months in the PPRT-temozolomide group and 17.9 months in the standard-of-care treatment group (hazard ratio, 0.34; 95% CI: 0.15-0.77; p = 0.009). PPRT was well-tolerated, with low-grade adverse events during radiation. Radiation necrosis occurred in 54% of the PPRT-temozolomide group and 36% of the standard-of-care group. CONCLUSION AI-guided PPRT in newly diagnosed glioblastoma patients demonstrated feasibility in routine clinical practice and led to a statistically significant improvement in overall survival compared to matched controls receiving standard-of-care treatment. These findings highlight the potential of personalized precision radiation therapy, with focused dose escalation, in enhancing outcomes for glioblastoma patients and emphasize the need for prospective validation in a randomized controlled clinical trial.

T-cell lymphoma involving the rectum of a dog

A mediastinal mass was diagnosed in a 7-year-4-month-old neutered female mixed breed dog following a 3-week history of lethargy, hyporexia and pyrexia. Bi-cavitary imaging, needle aspirate cytology and flow cytometry confirmed WHO clinical stage IVb, intermediate to large T-cell lymphoma involving the mediastinum, liver and spleen. The dog initially responded to a multidrug chemotherapy protocol but clinical deterioration occurred 3 months later. The dog presented with anorexia, vomiting and diarrhoea, associated with marked faecal tenesmus and haematochezia, initially believed by the primary care practitioner to be related to chemotherapy toxicity. However, rectal examination revealed multiple sessile and pedunculated masses. Further diagnostic imaging, cytology and flow cytometry confirmed progressive disease, including T-cell lymphoma of the rectum. Histology and immunohistochemistry confirmed an infiltrate of intermediate-sized CD3-positive neoplastic cells that expanded the rectal mucosa. Rectal lymphoma is uncommon in dogs and previous cases have been B cell in origin. In this report we describe the clinical presentation and macro- and microscopic findings of a case of canine T-cell lymphoma involving the rectum.

Efficacy and safety of different thermal ablative therapies for desmoid-type fibromatosis: a systematic review and meta-analysis.

Desmoid-type fibromatosis (DF) is a locally aggressive tumor characterized by peripheral infiltration of neoplastic cells and remote metastasis disability. This systematic review examined the efficacy and safety of thermal ablative therapy for DF tumors. A literature search was conducted using PubMed, Web of Science, Cochrane Library, and Embase from January 1, 2000, to November 12, 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to guide literature selection. The inclusion criteria were the following: (I) the patients were diagnosed with aggressive fibromatosis pathologically, (II) the patients were treated by thermal ablations, and (III) a focus on treatment efficacy and safety. Meanwhile, the exclusion criteria were the following: (I) cohorts of patients with hypertrophic scar, Gardner fibroma, or nodular fasciitis; (II) conference abstracts, reviews, case reports, letters to editors, comments, or editorials; (III) number of patients <5; (IV) in vitro or animal experiments; and (V) non-English language articles. The inverse variance method with a random effects model was used to obtain the pooled data. Subgroup analyses were performed to identify treatment factors. Egger test was conducted to assess the risk of publication bias. After literature selection, 694 DF tumors were identified in 23 studies. In terms of modality, 13 studies used cryoablation, 9 studies used high-intensity focused ultrasound (HIFU), and 1 study used microwave ablation (MWA). The pooled symptom relief rate was 90% [95% confidence interval (CI): 80-97%], with that for HIFU being 100% (95% CI: 85-100%), that for cryoablation being 87% (95% CI: 74-97%), and that MWA being 89% (95% CI). The pooled major complication rate was 3% (95% CI: 1-7%), and that for each modality was as follows: HIFU =2% (95% CI: 0-6%), cryoablation =4% (95% CI: 1-8%), MWA =11%, ultrasound =6% (95% CI: 1-13%), computed tomography (CT) =2% (95% CI: 0-7%), and magnetic resonance imaging (MRI) =3% (95% CI: 0-14%). The pooled nonperfused volume rate (NPVR) was 76% (95% CI: 71-81%), and that for each modality was as follows: HIFU =77% (95% CI: 71-85%), cryoablation =74% (95% CI: 69-79%), ultrasound =75% (95% CI: 67-83%), CT =76% (95% CI: 67-87%), and MRI =78% (95% CI: 70-87%). The pooled local control rate was 88% (95% CI: 79-94%) and that for each modality was as follows: HIFU =99% (95% CI: 96-100%), cryoablation =80% (95% CI: 68-90%), and MWA =78%. The differences in major complication rate (P=0.77) and NPVR between imaging-guided modalities (P=0.40) were not significant, nor were the differences in symptom relief rate (P=0.32) and major complication rate (P=0.61) between ablative techniques; however, the differences in local control rate (P=0.01) were significant between ablative techniques. Imaging-guided thermal ablative therapies contribute to symptom relief with a duration of more than 6 months and a low major complication rate of DF tumors.

Breast cancer metastasis to endometrium: Case report and up-date of literature

Introduction: Breast cancer is the leading neoplasia metastasizing to genital organs. Uterine metastases are seldom reported and those limited to endometrium account for 3.8% of patients with uterine spread. We reported on a woman with breast cancer metastasizing to endometrium and up-date of literature. Presentation of case: In July 2022, a 59 years-old woman with breast cancer was referred to Gynecological consultation due to Positron Emission Tomography showing an enhanced signal to the endometrium. Throughout the four previous years, she underwent bilateral surgery due to metachronous lobular cancers and adjuvant therapies consisting of Letrozole, Exemestane, chemotherapy, and Tamoxifen. In May 2022, bony metastases were found and she shifted to Abemaciclib/Fulvestrant therapy. No gynecological complaints were recorded, and physical examination was uneventful while Transvaginal Ultrasound demonstrated an enhanced endometrial thickness as a unique abnormality. Hysteroscopy showed mucosal thickenings attributed to Tamoxifen-related cysts formation. The biopsy pathology reported stromal infiltration of neoplastic cells staining for Cytokeratins and GATA-3. Negative staining was reported for PAX-8 and CD-10. On these findings, a breast cancer metastasis was established. Four months later the patients died from metastatic brain progression. Discussion: Endometrial metastasis from breast cancer is anecdotal. The case described supports that uterine spread is a late event, often concurrent with extragenital metastases and mostly associated with lobular histology. A hysteroscopic view can be misleading and a careful pathological study is needed for a differential diagnosis against endometrial primitiveness. Conclusion: Endometrial abnormalities in breast cancer patients might be caused by metastasis. The management of these patients is challenging and must be tailored to the clinical background.

Apoptosis-mediated inhibition of human T-cell acute lymphoblastic leukemia upon treatment with Staphylococus Aureus enterotoxin-superantigen.

Patients with relapsed T cell acute lymphoblastic leukemia (T-ALL) have limited therapeutic options and poor prognosis. The finding of efficient strategies against this refractory neoplasm is a medical priority. Superantigens (SAgs) are viral and bacterial proteins that bind to major histocompatibility complex class II molecules as unprocessed proteins and subsequently interact with a high number of T cells expressing particular T cell receptor Vβ chains. Although on mature T cells, SAgs usually trigger massive cell proliferation producing deleterious effects on the organism, in contrast, on immature T cells, they may trigger their death by apoptosis. On this basis, it was hypothesized that SAgs could also induce apoptosis in neoplastic T cells that are usually immature cells that probably conserve their particular Vβ chains. In this work, we investigated the effect of the SAg Staphylococcus aureus enterotoxin E (SEE) (that specifically interacts with cells that express Vβ8 chain), on human Jurkat T- leukemia line, that expresses Vβ8 in its T receptor and it is a model of the highly aggressive recurrent T-ALL. Our results demonstrated that SEE could induce apoptosis in Jurkat cells in vitro. The induction of apoptosis was specific, correlated to the down regulation of surface Vβ8 TCR expression and was triggered, at least in part, through the Fas/FasL extrinsic pathway. The apoptotic effect induced by SEE on Jurkat cells was therapeutically relevant. In effect, upon transplantation of Jurkat cells in the highly immunodeficient NSG mice, SEE treatment reduced dramatically tumor growth, decreased the infiltration of neoplastic cells in the bloodstream, spleen and lymph nodes and, most importantly, increased significantly the survival of mice. Taken together, these results raise the possibility that this strategy can be, in the future, a useful option for the treatment of recurrent T-ALL.

AI-based pathologic biomarker for pathologic downstaging in patients with muscle-invasive bladder cancer undergoing cystectomy after neoadjuvant nivolumab, gemcitabine, and cisplatin: BLAAST-1 Trial.

e16566 Background: The BLASST-1 study is a multi-center phase II trial evaluating the combination of neoadjuvant nivolumab with gemcitabine-cisplatin (N+GC) for muscle-invasive bladder cancer (MIBC) patients undergoing radical cystectomy (RC). The primary endpoint was pathologic down staging (PaR; ≤pT1N0). We previously reported a PaR rate of 65.8% (Gupta S et al. ASCO GU 2020). Given the lack of validated and optimal biomarkers to predict PaR, we studied the association of an AI-based pathologic biomarker measuring pre-treatment morphological features with PaR. Methods: Forty-one patients with MIBC (cT2-T4a, N≤1, M0) and candidates for RC were enrolled between Feb 2018 and June 2019 (cT2N0 90%, cT3N0 7%, cT4N1 3%). Thirty-six patients had transurethral resection of bladder cancer (TURBT) with pre-treatment diagnostic specimens available for analysis. Patients received four cycles of N+GC followed by RC within 8 weeks. A board-certified pathologist selected diagnostic regions from TURBT-derived representative H&amp;E diagnostic slides for each patient. To compute the pathological biomarker, a proprietary deep-learning algorithm (Valar Labs, Palo Alto, CA) first segmented nuclei from digital whole-slide images of the H&amp;E specimens to extract quantitative histological features. The Valar pathologic biomarker was then computed from features associated with immune infiltration and morphological characteristics of neoplastic cells. The Valar biomarker was split based on unsupervised clustering into two groups: Valar-High was associated with PaR and Valar-Low with no PaR. PD-L1 cutoff of 1% was used for dichotomization. To compare the Valar biomarker with PD-L1, a subcohort of 33 patients with available PD-L1 scores were analyzed. T-tests and diagnostic performance metrics were used to distinguish between PaR response rates in each cluster group across tests. Results: Patients designated Valar-High (n=23) had higher PaR compared to no PaR in the Valar-Low (n=13) group (PAR 78.3% vs 38.4%, respectively, p&lt;0.008). Compared to PD-L1, the Valar biomarker had higher sensitivity (85.7 vs 57.1%), specificity (66.6 vs 66%), positive predictive value (81.8 vs 75.0%), negative predictive value (72.7 vs 47.0%), and accuracy (78.8 vs 60.6%) across both cohorts. The Valar biomarker was not correlated to PD-L1 (r^2=0.029) or sex (22 male, 14 female). The combined Valar-High or PD-L1 High test had a high sensitivity for PaR (95.2%). Conclusions: In this hypothesis-generating study, pre-treatment morphological features measured by the AI-based Valar pathologic biomarker identified responders to neoadjuvant N+GC in MIBC. Further prospective studies are needed to study the prognostic vs. predictive utility of this biomarker.

Natural Killer Cell Activity Test Helps to Suspect Aggressive Natural Killer Cell Leukemia - Diagnostic Challenge.

Aggressive natural killer cell leukemia (ANKL) is a rare disease with an aggressive clinical course. We aimed to assess the clinicopathological characteristics of the difficult to diagnose ANKL. During ten years, nine patients with ANKL were diagnosed. All the patients exhibited aggressive clinical course and underwent the BM study to rule out lymphoma and hemophagocytic lymphohistiocytosis (HLH). BM examination showed varying degrees of infiltration of neoplastic cells, which were mainly positive for CD2, CD56, cytoplasmic CD3 and EBV in situ hybridization. Five BM aspirates showed histiocytic proliferation with active heomphagocytosis. Normal or increased NK cell activity test results were obtained from 3 patients who were available for testing. Four had multiple BM studies until diagnosis. An aggressive clinical course and positive EBV in situ hybridization, often with associated secondary HLH, should raise the suspicion of an ANKL. Conducting additional supplementary tests such as NK cell activity and NK cell proportion would be helpful for the diagnosis of ANKL.

Summit: A 3-Part, Phase 2 Study of Bezuclastinib (CGT9486), an Oral, Selective, and Potent KIT D816V Inhibitor, in Adult Patients with Nonadvanced Systemic Mastocytosis (NonAdvSM)

Background: Systemic mastocytosis (SM) is characterized by neoplastic mast cell infiltration of extracutaneous tissues and encompasses a spectrum of subtypes that can range from non-advanced to advanced disease. NonAdvSM is characterized by the lack of mast cell-related organ damage (e.g., C-findings) and other features of advanced SM such as associated hematologic neoplasms. NonAdvSM includes two variants of SM: indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM). ISM affects nearly 85% of the general SM population and is characterized by symptoms related to mast cell degranulation/mediator release. SSM is characterized by higher mast cell burden in the absence of organ damage or an associated hematologic neoplasm. There are currently no approved therapies for the treatment of the underlying causes of ISM or SSM, and anti-mediator therapies are used for symptom control with variable efficacy and tolerability due to disease heterogeneity. In up to 95% of patients, SM is driven by the somatic KIT D816V gain of function mutation located in exon 17; therefore, agents targeting this mutated kinase have been used to treat advanced SM variants. However, off-target activity of these agents may lead to toxicities that limit dosing and thus efficacy in this population. Therefore, an unmet need remains for safe and effective treatments for patients with NonAdvSM. Bezuclastinib inhibits KIT D816V mutations with high potency and specificity while avoiding other kinases with potential off-target liabilities such as PDGFRα, PDGFRβ, VEGFR2, and CSF1R. Bezuclastinib has demonstrated minimal brain penetration and no central nervous system toxicities were observed in preclinical studies. In an ongoing Phase 2 study (Apex) of patients with AdvSM, early data indicate that bezuclastinib was generally well tolerated and is associated with a meaningful reductions in serum tryptase levels, bone marrow mast cell burden, and KIT D816V variant allele fraction. Additionally, bezuclastinib was safely administered in a completed phase 1/2 clinical study in patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumors (GIST), in which activating KIT mutations are found in a majority of patients. In that study, bezuclastinib led to a reduction in KIT exon 17 mutational burden, which was associated with a reduction in tumor burden. These results support the investigation of bezuclastinib as a potential therapy in GIST as well as AdvSM and NonAdvSM. Study Design and Methods: The Summit study (NCT05186753) is a multi-center, Phase 2, double-blind, placebo-controlled, 3-part clinical trial to evaluate the safety, efficacy, and biomarker correlates (e.g., bone marrow mast cell burden, serum tryptase level, and KIT D816V mutation burden) of bezuclastinib in patients with NonAdvSM. Patients diagnosed with ISM or SSM who have inadequate control of their symptoms despite treatment with at least 2 anti-mediator therapies will be included in this trial. Multiple patient-reported outcome measures (PROMs) will be used to follow symptom scores while on treatment. Part 1 of the study will assess the safety profile of bezuclastinib and will determine the recommended dose for Part 2 through the assessment of changes from baseline of a disease specific PROM. Part 2 will evaluate the efficacy of bezuclastinib at the selected dose as compared with placebo through the evaluation of the PROMs and changes in clinical activity markers such as serum tryptase, bone marrow mast cell burden, and KIT D816V mutation allele burden. All patients will continue to receive their baseline anti-mediator treatments throughout the trial. Serial photographic evaluation will assist in the determination of changes of disease in the skin. Part 3 allows patients who have completed treatment in Part 1 or Part 2 of the study, including those initially randomized to placebo, to participate in a long-term extension study and receive open label bezuclastinib. Conclusions: There are currently no approved therapies for patients with NonAdvSM. Data from the Summit study will support further development of bezuclastinib in SM.

Survival in patients with multiple myeloma: evaluation of possible associations with bone marrow fibrosis and investigation of factors independently associated with survival

BackgroundMultiple myeloma (MM) is characterized by infiltration of neoplastic plasma cells in the bone marrow. Although many novel agents have been developed in the last decade, MM remains a non-curable disease. The association between bone marrow fibrosis (BMF) and MM survival is unknown, and the considerable changes in patient survival during the last few decades necessitates new studies to examine survival and associated factors in patients with MM.ResultsA total of 72 patients with MM, 39 (54.17%) males and 33 (45.83%) females, were included in this retrospective study. Fifteen patients did not have BMF, 55 had BMF (grades 1–4); there were no significant differences between these groups in terms of any of the parameters examined. The 5-year overall survival (OS) rate was 56.5 ± 7.4%. Mean OS was 81.54 ± 7.01 months, mean progression-free survival (PFS) after first-line treatment was 14.07 ± 2.54 months, and mean PFS after autologous stem cell transplantation (ASCT) was 25.92 ± 3.66 months. Survival times or mortality risk were not found to be associated with BMF in any of the analyses (HR 1.208, [95% CI 0.408–3.578], p = 0.733). Mortality risk was increased by 8.163-fold in patients with hypercalcemia (HR 8.163, 95% CI 2.413–27.617, p = 0.001), while it was decreased by 0.243-fold in patients with favourable response to first-line treatment (HR 0.243, 95% CI 0.078–0.756, p = 0.015). Younger patients (< 60 years) had a 1.981-fold greater risk of progression after first-line treatment (HR 1.981, 95% CI 1.111–3.532, p = 0.021), while those with hypercalcemia had a 3.160-fold greater risk of progression after ASCT (HR 3.160, 95% CI 1.103–9.052, p = 0.032). Low haemoglobin levels were also associated with increased mortality risk (p = 0.024).ConclusionAlthough hypercalcemia, unfavourable treatment response, young age and a low haemoglobin level were found to be indicators of poor prognosis in patients with MM, no relationship was found between BMF and survival.

Intraepithelial cytotoxic lymphocytes are associated with a poor prognosis in feline intestinal T-cell lymphoma.

The expression of cytotoxic molecules in feline intestinal T-cell lymphoma cells was examined immunohistochemically using endoscopic samples of 50 cases. Cases included 14 large-cell lymphomas (LCLs) and 36 small-cell lymphomas (SCLs). Most LCL and some SCL exhibited marked erosion and villous atrophy. Clonal T-cell receptor (TCR) gene rearrangement was detected in 10/14 (71%) LCL cases and 33/36 (92%) SCL cases. No clonal immunoglobulin heavy chain (IgH) gene rearrangement was detected. Immunohistochemically, all cases were positive for CD3 and negative for CD79α, CD30, CD56, and Foxp3. LCLs were positive for CD8 in 13/14 cases (93%), T-cell intracellular antigen 1 (TIA1) in 14/14 cases (100%), and granzyme B in 6/14 cases (43%). SCLs were positive for CD8 in 28/36 cases (78%), TIA1 in 33/36 cases (92%), and granzyme B in 2/36 cases (6%). TIA1- and granzyme B-positive neoplastic lymphocytes were predominantly observed in the mucosal epithelium of 10/50 cases (20%) and 6/50 cases (12%), respectively. No significant differences in survival time were found based on cell size or epitheliotropism. However, cases with TIA1+ and/or granzyme B+ neoplastic lymphocytes predominantly in the mucosal epithelium had significantly shorter survival times (P < .05), suggesting that mucosal epithelium infiltration of neoplastic cells with a cytotoxic immunophenotype is a negative prognostic factor. Therefore, intraepithelial cytotoxic lymphocytes may be associated with mucosal injury and impaired intestinal function, leading to a poor prognosis in cats with intestinal T-cell lymphoma.

Basal cell carcinoma in an albino pindani (Chindongo socolofi) and a cobalt-zebra (Maylandia callainos): Diagnostic imaging, clinical and histopathological study.

A female albino pindani (Chindongo socolofi) and female cobalt-zebra (Maylandia callainos) were referred to the Ornamental Fish Clinic with a soft tissue mass on their upper jaw. Also, during clinical examination, an unencapsulated intraoral soft tissue mass was observed in the cobalt-zebra cichlid. Digital radiography showed soft tissue masses and osteolytic lesions. Computed tomography (CT) imaging confirmed that osteolytic lesions occurred in skull bones of cobalt-zebra. Also, soft tissue mass invaded to the intraoral space. Histopathologically, a non-encapsulated, multilobulated and densely cellular neoplastic mass was identified. Extensive infiltration of neoplastic cells to the dermis and subcutaneous tissue was observed in both cases. The masses were composed of multiple coalescing nests, sheets, lobules and trabeculae of neoplastic cells within a fibrovascular stroma. The palisading basaloid neoplastic cells were markedly extended from the basal cells of the epidermis into the dermis and subcutis. The majority of the neoplastic cells had scant amounts of eosinophilic cytoplasm with indistinct margins, round to ovoid nuclei and typically a single small basophilic nucleolus. There was invasion of basaloid neoplastic cells into the bone tissue that caused osteolytic lesions. Mitotic figures were three to seven per high-power field. Epidermal basement membrane was periodic acid-Schiff (PAS) positive and neoplastic cell extension into the dermis was identified by the PAS staining. Fibrovascular stroma of the mass was also stained blue with Masson's trichrome. Based on histopathological and histochemical findings, the masses were diagnosed as infiltrative type of basal cell carcinoma (BCC).

Primary nervous system lymphoma in cats.

Here we characterize the neuroanatomic distribution, neuropathology, and immunophenotype of 10 cases of primary nervous system lymphoma in cats. Cases were retrospectively searched from 2 academic institutions. Selected cases were reviewed and subjected to immunohistochemistry (IHC) for CD3, CD20, and Pax5. The mean age of affected cats was 9.1 y, and no sex or breed predilection was observed. The most common clinical sign was ataxia (8 cases). Gross changes reported in 8 cases consisted of white-to-tan masses (7 cases) or swelling (1 case) within the neuroparenchyma (5 cases) or epidural spaces (3 cases). Histologically, intraparenchymal lymphomas occurred in the gray and white matter or perivascular spaces (7 cases); extraparenchymal lymphomas (6 cases) consisted of neoplastic cell infiltration of the perivascular spaces in the leptomeninges, choroid plexus, or epidural spaces. Nerve lymphomas were diffusely infiltrative. Tumors occurred in the brain (4 cases), spinal cord and nerves (3 cases), spinal cord (2 cases), and brain, spinal cord, and nerves (1 case). IHC was consistent with a B-cell lymphoma in 5 cases and with a T-cell lymphoma in 5 cases.

Histopathology and Immunohistochemistry of tumors in animals attending veterinary teaching hospital

We aim in the current study to investigate the pathology and incidence of tumors that are excised surgically in Veterinary Teaching Hospital. This study collected the tissue samples from animals from 1 October 2020 until 1 April 2021. These samples were collected from animals that undergo surgical procedures to remove neoplastic growths in their body. After tissue grossing, samples were collected from tumor mass, then fixed in neutral buffered 10% formalin for 72 hours, then processed to embedded in paraffin wax. A routine Harris’s hematoxylin and eosin stain were also used, histochemical stains such as Masson’s trichrome and PAS techniques were used as needed. In exceptional cases, IHC protocol was used for diagnostic steps to some types of tumors included in the current study. The antibodies that were used are Vimentin for canine osteosarcoma, P53 for squamous cell carcinoma, Mdm2 for ovine pulmonary adenocarcinoma, and CD10 for neoplastic lymphocytes. The result of the current study showed that the prevalence of tumor recorded was Marek’s diseases 22.8%, squamous cell carcinoma 22.8%, ovine pulmonary adenocarcinoma 15.4%, third eyelid adenoma 15.4%, canine osteosarcomas 7.4%, venereal transmitting tumors 7.4%, and feline mammary gland tumor 7.4%. Histological examination of feline mammary gland tumor composed from server infiltration of neoplastic cells, these neoplastic cells identified as lymphocytes in a fibrous stroma. Third eyelid adenomas in cats and dogs were composed of well-demarcated nodules containing neoplastic sebaceous cells present in glandular form and combined by hyperplasia of epidermis extended inside the neoplastic mass. Venereal transmitting tumor in cat composed from cells with a round to oval shape and the cytoplasm is poorly defined by routine stain, with dense fibrous tissue. Osteosarcoma in a dog has a pleomorphic nature with an anaplastic form composed of islands of osteoid materials, and the tumor is composed of three types of osteoblast, chondroblast, and fibroblast. Pulmonary adenocarcinoma in sheep composed of a nodular formation containing dense collagen fiber deposition with transformation of cells lining alveoli into cuboidal or columnar cells can also be observed in other air passages. Squamous cell carcinomas are primarily found in skin lesions associated with the formation of pathognomic lesions known as keratin pearls. This lesion is composed of the acentric layer of keratin produced by neoplastic keratinocytes. Marek’s disease was observed in visceral organs such as liver, lung, kidney, intestines, and spleen composed from pleomorphic lymphocytes, diffusely proliferating small-to-medium-size lymphoblast. In conclusion, the incidence of tumor in animals that attending Veterinary Teaching Hospital belong to the College of Veterinary Medicine, the University of Mosul was in general high in comparison to other studies in Iraq and other countries, this high incidence should pay attention to the causes of these cancerous conditions and their relation to environmental etiology.

CT in the Differentiation of Gliomas from Brain Metastases: The Radiomics Analysis of the Peritumoral Zone.

Due to their similar imaging features, high-grade gliomas (HGGs) and solitary brain metastases (BMs) can be easily misclassified. The peritumoral zone (PZ) of HGGs develops neoplastic cell infiltration, while in BMs the PZ contains pure vasogenic edema. As the two PZs cannot be differentiated macroscopically, this study investigated whether computed tomography (CT)-based texture analysis (TA) of the PZ can reflect the histological difference between the two entities. Thirty-six patients with solitary brain tumors (HGGs, n = 17; BMs, n = 19) that underwent CT examinations were retrospectively included in this pilot study. TA of the PZ was analyzed using dedicated software (MaZda version 5). Univariate, multivariate, and receiver operating characteristics analyses were used to identify the best-suited parameters for distinguishing between the two groups. Seven texture parameters were able to differentiate between HGGs and BMs with variable sensitivity (56.67–96.67%) and specificity (69.23–100%) rates. Their combined ability successfully identified HGGs with 77.9–99.2% sensitivity and 75.3–100% specificity. In conclusion, the CT-based TA can be a useful tool for differentiating between primary and secondary malignancies. The TA features indicate a more heterogenous content of the HGGs’ PZ, possibly due to the local infiltration of neoplastic cells.

Morpheaform leukemia cutis in a case of b-cell acute lymphoblastic leukemia - A rare presentation

Leukemia cutis (LC) is the cutaneous infiltration of neoplastic cells rarely seen with acute lymphocytic leukemia. We report the case of a young female presenting with a morpheaform plaque on the face, subsequently diagnosed with B-cell acute lymphoblastic leukemia (ALL) and LC, on histopathology and immunohistochemistry. Among the limited cases of LC reported with B-cell ALL, such an atypical presentation has previously never been reported.

Ileocolic Intussusception Associated with a Multicentric Round Cell Tumor in a Red-Tailed Boa (Boa constrictor constrictor)

A 5-year-old, female red-tailed boa constrictor ( Boa constrictor constrictor ) was presented with hyporexia, regurgitation and progressive focal distention of the caudal coelom since two months. During physical examination a firm, well-demarcated and movable intracoelomic mass was detected halfway down the caudal coelom but no other abnormalities were noticed. Ultrasonographic examination showed the mass to consist of an intestinal intussusception. A complete blood cell count and serum biochemistry blood test results revealed mild anemia and leukocytosis as well as hyperuricemia and hyperphosphatemia with inversion of the calcium/phospohorus ratio. Explorative coeliotomy was performed and revealed anterograde invagination of the ileum into the colon through the ileocolic junction. Although the intussusception was surgically repositioned, the snake died three weeks post-operatively despite showing a good general condition and defecation following assisted feeding. During necropsy, a thickened wall of the caudal segment of the ileum that was previously involved in the intussusception was observed as well as the presence of multifocal, white nodules throughout the parenchyma of the liver, spleen and kidneys. Histopathological examination demonstrated a malignant round cell tumor of the ileum with infiltration of neoplastic round cells in the liver, spleen and kidneys. Immunohistochemical staining (CD3, CD20, MAC387, S100 and NSE) could not confirm the cell origin of the round cell tumor. The present case highlights the need to include round cell tumors as a differential diagnosis in the development of ileocolic intussusception in red-tailed boa constrictors.