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Background: Histiocytic sarcoma originates in various tissues, including the skin, lymph nodes, gastrointestinal tract, lungs, bone marrow, and central nervous system. Primary central nervous system histiocytic sarcoma (PCNSHS) is exceptionally rare, known for its aggressive behavior and poor prognosis. This report describes a case of PCNSHS in the cerebellum treated with surgery and radiotherapy. Case presentation: A 30-year-old woman presented with progressive dizziness and headache. Magnetic resonance imaging scans showed right cerebellar neoplastic lesions approximately 3.6 cm*3.0 cm with cerebral edema and fourth ventricle and brainstem compression. The patient underwent surgical debulking, and the pathological diagnosis was PCNSHS. Two months after the surgery, the patient underwent adjuvant radiotherapy at a dose of 60 Gy. No tumor progression has been observed during the one-year follow-up period. Conclusions: This case report provides an example of effective central nervous system control using resection and radiation therapy. A review of the literature confirms that surgery alone or combined concurrent or sequential treatment of radiotherapy and chemotherapy is often used; however, the best treatment plan remains unclear. Moreover, the prognosis is poor, with a median survival of six months. Thus, ongoing research aims to better understand the biology of histiocytic sarcomas and find more effective strategies. [ABSTRACT FROM AUTHOR]

The purpose of this review is to clarify the terminology, possible cells of origin, and expected behavior of the most common synovial tumors in dogs. The synovial lining consists of 2 cell types, type A and type B. Type A synoviocytes are histiocytes of bone marrow origin that are immunoreactive with antibodies against typical markers of histiocyte origin, such as CD18, Iba-1, and CD204. Certain breeds and dogs with previous injury to a joint, especially cranial cruciate ligament rupture, are predisposed to synovial histiocytic sarcoma. Type B synoviocytes are mesenchymal cells that produce synovial fluid. There are no specific markers of type B synoviocytes, but based on their gross and microscopic appearance, synovial myxosarcomas (previously considered synovial myxomas) are presumed to be of type B synoviocyte origin. These can infiltrate into surrounding tissues, but are slow-growing and rarely metastasize, and then only to regional lymph nodes. Synovial histiocytic sarcomas and myxosarcomas can cause lysis in multiple bones surrounding the joint, but they have different prognoses and require histopathology and sometimes immunohistochemistry to diagnose them. Synovial sarcoma and synovial cell sarcoma are terms used in the human medical literature for a tumor that is not of synovial origin; these terms should not be used in veterinary medicine. [ABSTRACT FROM AUTHOR]

Canine cutaneous histiocytoma (CCH) is a tumor that originates from dermal Langerhans cells and affects particularly young dogs. The common spontaneous regression of CCH makes it an interesting model in comparative oncology research. Previous studies have indicated that anti-tumor immune responses may be involved, but details remain speculative to date. Here, we asked which specific immuno-oncological dynamics underlie spontaneous regression of CCH on mRNA and protein levels. QuantSeq 3′ mRNA sequencing with functional over-representation analysis and an nCounter RNA hybridization assay were employed on 21 formalin-fixed, paraffin-embedded CCH samples representing three different tumor stages (dataset information: GSE261387 —Immuno-Oncologic Profiling by Stage-Dependent Transcriptome and Proteome Analyses of Spontaneously Regressing Canine Cutaneous Histiocytoma—OmicsDI). Nine additional samples were subjected to matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Surprisingly, only minor stage-specific differences were found. When we investigated expression of B7 family ligands and CD28 family receptors holding co-stimulatory and -inhibitory functions, respectively, we found a higher abundance of CD80, CD86, CTLA4 and CD28, which may trigger a balanced activation of lymphocyte-mediated immune responses. CD80 and CD86 expressing cells were further quantified by in situ hybridization and compared with data from three cases of canine histiocytic sarcoma (HS), a malignant tumor variant originating from antigen-presenting interstitial dendritic cells. A stage-specific increase of CD80 expressing cells was recorded in CCH from the tumor bottom to the top, while CD86 was continuously and homogenously expressed at high levels. Overall expression of CD80 in CCH was similar to that in HS (73.3 ± 37.4% vs 62.1 ± 46.4%), while significantly more CD86 expressing tumor cells were found in CCH (94.7 ± 10.3%) when compared to HS (57.6 ± 11.0%). Our data suggest that major immuno-oncological pathways are not regulated during regression of CCH on the mRNA or protein levels as detectable by the methods used. Instead, our data provide further evidence supporting previous hypotheses towards a role of immune stimulatory B7 family ligands and CD28 family receptors in the regression of CCH. [ABSTRACT FROM AUTHOR]

Histiocytic neoplasms (HNs) in adults have been reported to be associated with a high prevalence of coexisting haematological and solid malignancies. While a proportion of coexisting HNs and haematological malignancies share identical genetic alterations, the genetic association between HNs and solid malignancies has scarcely been reported. We report a case of Rosai–Dorfman disease (RDD) complicated by coexisting clear cell sarcoma (CCS). RDD is a rare HN. CCS is an ultrarare soft tissue sarcoma with a poor prognosis. Mutation analysis with whole‐exome sequencing revealed six shared somatic alterations including NRAS p.G12S and TP53 c.559+1G>A in both the RDD and CCS tissue. This is the first evidence of a clonal relationship between RDD and solid malignancies using mutational analysis. We hypothesise that neural crest cells, which originate in CCS, are likely the common cells of origin for RDD and CCS. This case helps to unravel the underlying clinicopathological mechanisms of increased association of solid malignancies in HNs. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma (HS) is a rare yet lethal malignancy with no established standard of care therapies. A lack of pre-clinical models limits our understanding of HS pathogenesis and identification of therapeutic targets. Canine HS shares multiple clinical and genetic similarities with human HS, supporting its use as a unique translational model. Prior studies have investigated the immunogenicity of HS. Although increased tumor infiltrating lymphocyte (TIL) density is associated with favorable outcomes in canine HS, virtually all canine patients eventually succumb to progressive disease consistent with ultimate failure of anti-tumor immunity. To investigate potential regulators of the immune tumor microenvironment (TME), we undertook a comparative transcriptional approach of three long-lived cases of canine pulmonary HS with heavy T cell infiltrate and three short-lived cases of splenic HS that lacked significant T cell inflammation and compared these data to corresponding grossly normal tissues from dogs undergoing necropsy. This comparison identified PDCD1, encoding the immune checkpoint PD-1, and SPP1, encoding the secreted pro-tumorigenic protein osteopontin, as positive differentially expressed genes (DEGs) in canine HS. TXNIP, encoding the tumor suppressor TXNIP, was the most significant negative DEG. Comparative transcriptomic studies revealed conservation of enriched (including SPP1) and depleted (including TXNIP) DEGs between canine and human HS patients. Immunohistochemistry demonstrated osteopontin in the TMEs of canine and human HS. Collectively, we uncover PD-1, osteopontin, and TXNIP as putative actionable targets in HS and further establish canine HS as a preclinical platform to screen novel immunotherapeutic approaches for this deadly disease. [ABSTRACT FROM AUTHOR]

Background: Intracranial histiocytic sarcoma (HS) is uncommon in dogs, and no standard treatment has yet been defined for this disease. Herein, we describe a case of intracranial HS that responded favorably to nimustine treatment. Case Description: A 9-year-old, castrated Welsh Corgi Pembroke presented with a 2-month history of quadriplegia. Intracranial disease was suspected on neurological examination, and magnetic resonance imaging (MRI) revealed a contrast-enhanced mass in the left frontal lobe. Following tissue biopsy, the patient received intravenous nimustine (ACNU) treatment. The patient's neurological symptoms partially improved, and a reduction in tumor volume was observed on MRI on day 99. After three administrations of ACNU, tumor regrowth was confirmed on day 124, and temozolomide was subsequently administered. The patient subsequently showed no major changes in clinical symptoms, but subsequently died suddenly on day 195. Conclusion: In this case, administration of ACNU provided temporary symptom improvement and tumor reduction. Therefore, ACNU monotherapy may be a therapeutic option for canine intracranial HS. [ABSTRACT FROM AUTHOR]

Based on Type-I generalized progressive hybrid censored samples (GPHCSs), the parameter estimate for the unit-half logistic-geometry (UHLG) distribution is investigated in this work. Using maximum likelihood estimation (MLE) and Bayesian estimation, the parameters, reliability, and hazard functions of the UHLG distribution under GPHCSs have been assessed. Likewise, the computation is carried out for the asymptotic confidence intervals (ACIs). Furthermore, two bootstrap CIs, bootstrap-p and bootstrap-t, are mentioned. For symmetric loss functions, like squared error loss (SEL), and asymmetric loss functions, such as linear exponential loss (LL) and general entropy loss (GEL), there are specific Bayesian approximations. The Metropolis–Hastings samplers methodology were used to construct the credible intervals (CRIs). In conclusion, a genuine data set measuring the mortality statistics of a group of male mice with reticulum cell sarcoma is regarded as an application of the methods given. [ABSTRACT FROM AUTHOR]

Canine histiocytic sarcoma (CHS) is a malignant tumor derived from macrophages and dendritic cells. Since effective chemotherapy is needed for CHS cases, we conducted this prospective study to evaluate the efficacy and adverse events of vincristine treatment as a rescue therapy for this disease. We administered vincristine to nine CHS cases that acquired resistance to lomustine or nimustine. Complete remission was achieved in one dog, partial remission in two dogs, stable disease in five dogs, and progressive disease in one dog. The median progression-free survival was 21 days (range: 7-71 days). Severe adverse effect was observed in one dog (Grade 3 thrombocytopenia). It is essential to establish novel effective treatments for CHS. [ABSTRACT FROM AUTHOR]

A 4-year 9-month-old Amami spiny rat reared in a zoo died following a history of anorexia, weight loss, and respiratory distress. At necropsy, neoplastic tissues were found along the pleura and adhered to the thoracic wall, heart, and lungs. Histologically, the tumor was composed of diffuse, patternless sheets of large round to polygonal neoplastic cells with abundant eosinophilic cytoplasm, and multinucleated giant cells were often present. Metastatic lesions were observed in the abdominal lymph nodes. Neoplastic cells were immunopositive for vimentin, Iba-1, and CD204, and negative for E-cadherin and S100. Based on these findings, the tumor was diagnosed as histiocytic sarcoma. Compression of the lungs by the tumor may have caused respiratory failure and led to death. [ABSTRACT FROM AUTHOR]

Rosai–Dorfman disease (RDD), a rare histiocytic disorder, typically manifests as widespread lymphadenopathy. We present a unique case of extranodal RDD in a 14-year-old with a solitary maxillary lesion and mild bilateral submandibular lymphadenopathy. Clinical, radiological, and histopathological assessments confirmed RDD, highlighting the importance of a comprehensive approach. Immunohistochemistry, including CD68, CD45, CD 1a, and S100, played a crucial role in diagnosis. Differential diagnoses encompassed Langerhans cell histiocytosis, Erdheim–Chester disease, lymphomas, and histiocytic sarcoma, necessitating meticulous evaluation. Surgical excision was performed due to bone involvement, leading to successful healing in six months. Our case underscores the significance of a multidisciplinary and scientific approach for accurate RDD diagnosis and management, especially in atypical intraoral presentations. [ABSTRACT FROM AUTHOR]

Background: Malignant (intra-) nasal tumors (NTs) are the most common cause of chronic nasal discharge in dogs. Besides radiation therapy, palliative therapy is necessary in some dogs. Therefore, studies on receptor expression have supported the utility of tyrosine kinase inhibitors (TKI) in dogs with nasal carcinomas. However, studies on receptor expression in nasal sarcomas are lacking. Materials and methods: This study evaluated the expression of vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor (EGFR), cyclooxigenase-2 (COX-2), Ki-67, survivin and E-cadherin in nasal carcinomas and sarcomas and compared it with tumor (T) categories based on computed tomography (CT). Results: In 26 dogs with NTs, cross sectional imaging and upper airway endoscopy with guided biopsy collection were performed, followed by histopathological examination of NTs, revealing 19 epithelial and 7 mesenchymal tumors. While EGFR and E-cadherin were only expressed by carcinomas, the following markers were expressed by both carcinomas and sarcomas without significant differences between tumor types and T-categories: VEGFR-2 (carcinomas and sarcomas 100%), COX-2 (carcinomas 63%, sarcomas 57%), survivin (carcinomas 100%, sarcomas 86%) and Ki-67 (median expression of 28.5% in carcinomas and 17.3% in sarcomas). Conclusion: Based on similarities in marker expression between canine carcinomas and sarcomas, clinical studies should further elucidate the use of TKI or COX-2 inhibitors as additional therapy in dogs with nasal sarcomas. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course and poor response to treatment. Primary gastric histiocytic sarcoma is rarer and just reported sporadically.Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course and poor response to treatment. Primary gastric histiocytic sarcoma is rarer and just reported sporadically. A case of a 71-year-old female admitted with a one-year history of upper abdominal pain exacerbated after meals. After CT scans revealed a bulged mass at the lesser curvature of the gastric body, the patient underwent endoscopic submucosal dissection. Microscopically, non-cohesive neoplastic cells diffusely infiltrated lamina propria and submucosa, and diffusely expressed LCA, CD4, CD163, CD68 (KP1), Cyclin D1, Lysozyme, and Vimentin. PD-L1 (22CS) expression evaluated as CPS 60. The final pathological diagnosis was gastric histiocytic sarcoma. Subsequently, next-generation sequencing identified a nonsense mutation in exon 21 of NF1 gene [c.2446C > T (p.R816*)] and the TUBB3 gene amplification (copy number: 4.55). The patient refused further treatment and died of the tumor half a year later. This case broadens the spectrum of differential diagnosis of gastric cancer and emphasizes the value of immunohistochemical and molecular tests in the accurate diagnosis of histiocytic sarcoma. Furthermore, we performed literature review of 11 cases of gastric histiocytic sarcoma so as to strengthen the understanding of the clinicopathologic features, treatment, and prognosis. [ABSTRACT FROM AUTHOR]

MAPK has been reported as a key oncogenic pathway for canine histiocytic sarcoma, which can be pharmacologically targeted with trametinib, a small inhibitor of MEK1/2. Preliminary data showed promising antitumor activity in in vitro and in vivo models and represented a proof of concept to translate the findings from bench to bedside. In this phase I, dose escalating study using a 3 + 3 cohort design, trametinib was evaluated in 18 dogs with cancer. Adverse events were graded according to VCOG‐CTCAE v2. Blood samples and tumour biopsies were collected for pharmacokinetic and pharmacodynamic assessment. Trametinib was well tolerated with a maximum tolerated dose of 0.5 mg/m2/day, PO. Dose‐limiting toxicities included systemic hypertension, proteinuria, lethargy and elevated ALP, and were all Grade 3. The drug exposures increased more than linearly with dose since the elimination of trametinib was saturable. At a dose of 500 μg Q24h (0.5 mg/m2/day in a 30 kg dog), approximately 70% of dogs had an average steady‐state concentration of 10 ng/mL, achieved after approximately 2 weeks. This threshold was associated with clinical efficacy in humans. Target engagement was not observed in biospecimens collected on Days 0 and 7. In conclusion, trametinib was considered safe in dogs with cancer, and the dose of 0.5 mg/m2/day was the recommended dose for phase II studies. [ABSTRACT FROM AUTHOR]

The precise cause of HS/DCS is still unknown. The relatively low incidence in humans urges for an animal model with a high incidence to accelerate knowledge about genetics and optimal treatment of HS/DCS. Namely, until now, the therapies targeting genetic variants are still more experimental and sparsely used, while consensus is missing. In addition, the literature about variants and possible mutation‐targeted therapies in humans and dogs consists mainly of case reports scattered throughout the literature. Therefore, an overview is provided of all currently known genetic variants in humans and dogs with HS/DCS and its subtypes, their possible mutation‐targeted therapies, their efficacy, and a contemplation about the future. Several genetic variants have already been discovered in HS/DCS, of which many are shared between canine and human HS/DCS, but unique variants exist as well. Unfortunately, none of these already found variants seem to be specifically causal for HS/DCS, and the puzzle of its landscape of genetic variation is far from complete. The use of mutation‐targeted therapies, including MAPK‐/MEK‐inhibitors and the future use of PTPN11‐, CDK4/6‐ and PD‐1‐inhibitors, seems to be promising for these specific variants, but clearly, clinical trials are needed to determine optimal inhibitors and standardised protocols for all variants. It can be concluded that molecular analysis for variants and subsequent mutation‐targeted therapy are an essential addition to cancer diagnostics and therapy. A joint effort of humans and dogs in research is urgently needed and will undoubtedly increase knowledge and survival of this devastating disease in dogs and humans. [ABSTRACT FROM AUTHOR]

Feline histiocytic diseases are uncommon and rarely reported. Feline progressive histiocytosis (FPH) is the most common histiocytic disease in cats, predominantly affecting middle-aged animals. The most common presentation is the cutaneous form with solitary or multiple cutaneous nodules. A female, mixed-breed 6-year-old cat was presented with a 9-month history of a nodule in the nasal planum and was diagnosed by histopathology with histiocytic proliferation. At the time of diagnosis, new nodules were discovered on the lower lip, digit, and two lesions in the tail region, with the largest measuring 1.5 cm. Supplementary immunohistochemistry, showed immunolabeling for Iba-1 that in combination with the clinical course of the disease, confirmed the diagnosis of FPH. No response to chemotherapy treatment with lomustine alternated with doxorubicin was achieved. Toceranib phosphate resulted in a transient response and, stable disease for a short period (6 weeks). Electrochemotherapy with bleomycin was initiated and resulted in partial remission. Later on, chlorambucil was also started. Ultimately, the combination of all three treatments led to a complete response and disappearance of all the lesions. FPH is considered a disease resistant to various treatments, and effective treatments have not been reported. In this case report, we describe a successful multimodal therapeutic approach that resulted in complete resolution of the FPH and long-term survival (460 days without external lesions at the time of death). Further studies are necessary to confirm the efficacy of this therapeutic approach. [ABSTRACT FROM AUTHOR]

The article discusses the evaluation of neurofilament light chain (NfL) as a biomarker for central nervous system (CNS) involvement in histiocytic neoplasms. Topics include the use of contrast-enhanced MRI for monitoring CNS disease, the potential clinical utility of NfL in assessing disease activity, and the methodology for testing and analyzing NfL levels in patients with histiocytic disorders.

A 7‐year‐old female spayed Bernese Mountain dog was presented for evaluation of hematuria. Incidentally, a right stifle sarcoma was diagnosed via cytology, which raised concern for histiocytic sarcoma (given the patient's signalment) versus another joint‐associated sarcoma. Histopathology and immunohistochemistry revealed a CD18‐negative, non‐histiocytic origin cell population. Findings were consistent with a joint‐associated grade II soft tissue sarcoma (STS). The patient's hematuria was progressive over 5 months, and urinary bladder transitional cell carcinoma (TCC) was diagnosed via cystoscopy and histopathology. An enlarged right medial iliac lymph node was identified on routine restaging via abdominal ultrasound 3 months later. Cytology of the lymph node revealed a markedly pleomorphic cell population, again raising concern for histiocytic sarcoma (HS). Other differentials included an anaplastic metastatic population from the joint‐associated STS or the TCC. Immunocytochemistry revealed a cytokeratin‐positive, CD18‐, CD204‐, and vimentin‐negative cell population, consistent with a carcinoma. DNA was extracted from cytology slides to sequence cells for BRAF mutation status. Sequencing revealed a homozygous V596E (transcript ENSCAFT00845055173.1) BRAF mutation, consistent with the known biology of TCC. In neither case was HS truly present in this patient, but immunocytochemistry provided information that helped to optimize the patient's chemotherapy recommendations. [ABSTRACT FROM AUTHOR]

Histiocytic Sarcoma (HS) is an extremely rare haematolymphoid neoplasm that exhibits morphological and immunophenotypic features indicative of histiocytic differentiation. In most cases, it is misdiagnosed as Diffuse Large B-Cell Lymphoma (DLBCL) or anaplastic large cell lymphoma. HS is a diagnosis of exclusion, necessitating extensive immunophenotypic analysis to finalise the diagnosis. Hereby, authors present a case series of five cases diagnosed as HS based on histomorphology and an extensive Immunohistochemistry (IHC) panel. A total of five cases reported as HS over a five-year period (2018 to 2023) were diagnosed at the Department of Pathology. All demographic and clinical data, as well as treatment history, were collected from the patients and their family members. Paraffin-embedded blocks were retrieved from the archive, and routine Haematoxylin and Eosin (H&E) and special stains like Periodic Acid-Schiff (PAS) were performed. Microscopy revealed sheets of round to oval tumour cells with small round nuclei, inconspicuous nucleoli, and moderately microvacuolated cytoplasm. An extended IHC panel was applied to confirm the microscopic findings. All five cases exhibited intense immunoreactivity for Leukocyte Common Antigen (LCA) and showed strong positivity for the histiocytic marker CD68, while CD163 demonstrated variable cytoplasmic positivity. Dako R antibody at a dilution of 1:100 was used for the IHC analysis. This case series aims to highlight the importance of clinical, radiological, histological, and immunohistochemical properties of this rare neoplasm for early diagnosis and proper management. [ABSTRACT FROM AUTHOR]

Oncolytic viruses and morbilliviruses in particular, represent an interesting therapeutic approach for tumors with a poor prognosis and frequent resistance to conventional therapies. Canine histiocytic sarcomas (HS) exemplify such a neoplasm in need for new curative approaches. Previous investigations demonstrated a limited success of an acute intratumoral application of canine distemper virus (CDV) on xenotransplanted canine histiocytic sarcoma cells (DH82 cells), while persistently CDV-infected DH82 cell transplants exhibited a complete spontaneous regression. Therefore, the present study focuses on an intratumoral application of persistently CDV vaccine strain Onderstepoort-infected DH82 (DH82 Ond p.i.) cells into non-infected subcutaneous DH82 cell transplants in a murine model. DH82 cell transplants that received 10 applications, two days apart, showed a transient growth retardation as well as larger areas of intratumoral necrosis, lower mitotic rates, and a decreased intratumoral vascularization compared to controls. Viral mRNA was detected in all neoplasms following application of DH82 Ond p.i. cells until 66 days after the last injection. Furthermore, infectious virus was present until 62 days after the last injection. Although complete regression was not achieved, the present application regimen provides promising results as a basis for further treatments, particularly with genetically modified viruses, to enhance the observed effects. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma (HS) is a rare and highly aggressive cancer in humans and dogs. In dogs, it has a high prevalence in certain breeds, such as Bernese mountain dogs (BMDs) and flat-coated retrievers. Hemophagocytic histiocytic sarcoma (HHS) is a unique form of HS that presents with erythrophagocytosis. Due to its rareness, the study of HHS is very limited, and mutations in canine HHS patients have not been studied to date. In previous work, our research group identified two major PTPN11/SHP2 driver mutations, E76K and G503V, in HS in dogs. Here, we report additional mutations located in exon 3 of PTPN11/SHP2 in both HS and HHS cases, further supporting that this area is a mutational hotspot in dogs and that mutations in tumors and liquid biopsies should be evaluated utilizing comprehensive methods such as Sanger and NextGen sequencing. The overall prevalence of PTPN11/SHP2 mutations was 55.8% in HS and 46.2% in HHS. In addition, we identified mutations in KRAS, in about 3% of HS and 4% of HHS cases. These findings point to the shared molecular pathology of activation of the MAPK pathway in HS and HHS cases. We evaluated the efficacy of the highly specific MEK inhibitor, cobimetinib, in canine HS and HHS cell lines. We found that the IC50 values ranged from 74 to 372 nM, which are within the achievable and tolerable ranges for cobimetinib. This finding positions cobimetinib as a promising potential candidate for future canine clinical trials and enhances our understanding of the molecular defects in these challenging cancers. [ABSTRACT FROM AUTHOR]

The article discusses a case of ocular mass in the anterior chamber of a 9-year-old male Golden Retriever, diagnosed as intraocular histiocytic sarcoma. The patient presented with symptoms such as edema, inflammation, and blindness, leading to enucleation and subsequent euthanasia due to hemoabdomen. The article highlights the challenges in diagnosing histiocytic sarcoma and differentiating it from ocular melanoma, emphasizing the importance of immunohistochemical stains for accurate diagnosis and prognosis. [Extracted from the article]

A 55-year-old man presented with dizziness and left lower limb weakness, leading to the discovery of a cerebral mass in his left frontal lobe. The mass was diagnosed as histiocytic sarcoma (HS), an exceedingly rare and aggressive hematopoietic tumor that primarily affects various parts of the body. The diagnosis was confirmed through histological examination, immunohistochemistry, and exclusion of other potential tumor lineages. The study highlights the importance of accurate diagnosis and potential therapeutic targets for HS. [Extracted from the article]

We report a histiocytic sarcoma originating from the epididymis observed in a 110-week-old male CD-1 mouse in a carcinogenicity study. At necropsy, no lesions were observed in the epididymis. Histologically, a neoplastic lesion was observed in the cauda of the epididymis that was well demarcated from the surrounding tissues. The lesion mainly consisted of spindle-shaped tumor cells with oval to elongated nuclei and abundant eosinophilic or foamy cytoplasm. The tumor cells were arranged in a fascicular pattern, interlacing bundles, or a whorl pattern. The nuclei showed mild atypia with irregular shapes and varied sizes, whereas few mitotic figures and no typical multinucleated cells were observed. The epididymal ducts remained within the neoplastic lesion, and the tumor cells invaded between the epithelium and the smooth muscle layer of the epididymal duct. Immunohistochemically, the tumor cells were positive for vimentin and macrophage markers (Iba1, CD204, F4/80, and Mac-2) but negative for cytokeratin and other mesenchymal cell (a-smooth muscle actin, desmin, CD31, and platelet-derived growth factor receptor-ß), neural cell (S-100 and nestin), or Leydig cell markers (calretinin). Proliferating cell nuclear antigen-positive tumor cells were sporadically observed in the lesion. Based on these results, the tumor was diagnosed as a histiocytic sarcoma originating from the epididymis. This report provides additional histopathological evidence of spontaneous histiocytic sarcomas originating from the epididymis of aged mice. [ABSTRACT FROM AUTHOR]

Summary: Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai–Dorfman–Destombes disease (RDD) and Erdheim–Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy‐proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty‐seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non‐V600‐BRAF, RAF1 and a BICD2‐BRAF fusion. A repeated‐measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19–137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03–0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma (HS) is an extremely rare but aggressive hematopoietic malignancy, and the prognosis has been reported to be rather unfavorable with a median overall survival of merely 6 months. We presented a 58-year-old female patient complaining of abdominal pain and fever, who was admitted to our institution in September 2021. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) scan showed enlargement of generalized multiple lymph nodes. Subsequently, laparoscopic retroperitoneal lesion biopsy and bone marrow aspiration were performed. The pathological findings indicated the diagnosis of HS concurrent with follicular lymphoma. The immunohistochemistry (IHC) staining of the tumor lesion revealed a high expression of CD38 and PD-L1 proteins. Furthermore, KRAS gene mutation was identified by means of next-generation sequencing. The patient exhibited poor treatment response to both first- and second-line cytotoxic chemotherapies. Therefore, she underwent six cycles of Daratumumab (anti-CD38 monoclonal antibody), Pazopanib (multi-target receptor tyrosine kinases inhibitor) combined with third-line chemotherapy, followed by involved-site radiotherapy and maintenance therapy with the PD-1 inhibitor Tislelizumab. Long-term partial remission was finally achieved after multi-modality treatment. Duration of remission and overall survival reached 22 and 32 months, respectively. Our case indicated that immuno-targeted treatment coupled with chemotherapy and radiotherapy might constitute a potential therapeutic option for HS. [ABSTRACT FROM AUTHOR]

Purpose: To determine and report the underlying cause of local inflammation causing recurrent neuropathy and multiple operations in a patient with a Barricaid® device. Methods: After removal of this patient's Barricaid® device, we sent local inflammatory tissue to pathology for histochemical analysis. Upon discovery of giant cells formation with polarizable foreign bodies, we performed a literature review regarding the Barricaid® device and its elements. Results: After two previous operations and three trials of conservative management, the presented patient underwent an L5/S1 TLIF with removal of her previously installed Barricaid® device. There were no signs of device instability/failure nor were there obvious signs of infection. Inflamed tissue proximal to the Barricaid® device was discovered, debrided, and sample sent to pathology. Removal of the Barricaid® device led to subsequent and durable relief of her symptoms. During review of this case, we discovered the polyethylene terephthalate (PET) weave used in the Barricaid® device is known to induce foreign body reactions, and this precise finding was seen in the majority of animal data submitted to the FDA for the device's acceptance. Conclusion: Given the constellation of this patient's symptoms, imaging, intraoperative, and pathology findings, previously published reports, and pre-approval data submitted to the FDA, we conclude that the inflammatory response to the PET weave in this patient's Barricaid® device was the ultimate cause of her continued neuropathy despite multiple prior surgical interventions. [ABSTRACT FROM AUTHOR]

Rosai-Dorfman Disease (RDD) is a rare, benign, idiopathic histiocytic proliferative disorder, with its occurrence in the cranial bones being particularly uncommon and prone to misdiagnosis in preoperative radiological examinations. This article reports a case of RDD in the left temporal bone. The radiological presentation of intraosseous RDD includes osteolytic bone destruction, infrequent periosteal reaction, clearly defined tumor margins, and marked uniform enhancement on contrast-enhanced scans. However, these radiological features lack specificity, highlighting the necessity of histopathological examination for a definitive diagnosis, especially for the rarer extranodal subtypes of RDD. Surgical excision of the lesion can lead to favorable therapeutic outcomes. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive analysis of primary nervous system histiocytic neoplasms, focusing on Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman disease (RDD). The study found that isolated nervous system involvement was observed in 5% of adult patients with histiocytic neoplasms, with each disease exhibiting different clinical manifestations and age ranges. The article discusses treatment options and outcomes, emphasizing the importance of considering a histiocytic neoplasm in cases of specific symptoms and imaging findings. The authors recommend long-term surveillance imaging due to the potential for systemic involvement. [Extracted from the article]

Background: A xanthoma is a rare bone condition consisting of a predominant collection of lipid-rich, foamy histiocytes. The central xanthoma of the jaws is a unique benign tumor. Case report: A 15-year-old Caucasian male has been presented to our department. He had radiological changes in the area of the left mandibular angle, with an area of diffuse osteolysis of 3.0 cm by 2.0 cm. Computed tomography reveals an area of diffuse osteolysis that starts from the distal root of the lower second molar and reaches the ascending process. A bone biopsy was performed, which revealed a benign proliferative process composed of histiocytic cells involving and infiltrating trabecular bone in a background of loose fibrous connective tissue devoid of any other significant inflammatory infiltrate. The size of the formation was 2.9 cm by 2.0 cm. Immunohistochemical staining for CD68 was strongly positive and negative for S-100 and CD1a. From routine blood tests, cholesterol, triglycerides, and blood sugar are within normal values, which excludes systemic metabolic disease. Subsequent to the surgical intervention, the patient underwent postoperative assessments at intervals of 14, 30, 60 days, and a year later, revealing the absence of any discernible complications during the aforementioned observation periods. Conclusion: The diagnosis of primary xanthoma of the mandible is rare and can often be confused with other histiocytic lesions. A differential diagnosis should be made with nonossifying fibroma and Langerhans cell histiocytosis, as in our case. In these cases, immunohistochemistry with CD 68, S-100, and CD1a, as well as blood parameters, are crucial for the diagnosis. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, and liver involvement in LCH is rare. This retrospective study reported the clinical features and prognosis of patients with hepatic LCH. Liver involvement was defined by histopathological findings, liver dysfunction or abnormalities, or ultrasound imaging. A total of 130 patients (14.5%) with hepatic LCH out of 899 in the LCH population were enrolled. Patients with liver involvement had greater frequencies of skin, lung, hearing system, and haematologic system involvement, and hemophagocytic lymphohistiocytosis (P<0.001, 0.001, 0.002, 0.009, and <0.001, respectively). Overall survival and progression-free survival were lower in LCH patients with liver involvement than in those without liver involvement (P<0.001 and <0.001). In patients with liver involvement, the overall survival (OS) and progression-free survival (PFS) rates were lower in patients with cholangitis than in those without cholangitis (P<0.020 and 0.030). For the treatment response, the response rate of hepatic LCH patients to initial first-line therapy (n=89) was 22.5%. However, there was no significant difference in the response rate or recurrence rate between patients who shifted from first-line treatment to second-line treatment (n=29) or to targeted therapy (n=13) (P=0.453 and 1.000). The response rate of hepatic LCH patients who received initial second-line therapy (n=13) was 38.5%. Two of these patients subsequently experienced bone recurrence. The response rate of hepatic LCH patients who received initial targeted therapy (n=16) was 75.0%. Three patients subsequently experienced recurrence, including 2 in the bone and 1 in the liver and skin. A total of 39.3% of patients who received second-line treatment had severe myelosuppression (grade III-IV), and 50.8% had varying degrees of gastrointestinal events, whereas there was no severe toxicity in patients who received first-line treatment and targeted therapy. Four patients underwent liver transplantation because of liver cirrhosis. The patients' liver disease improved within a follow-up period of 18-79 months. This study demonstrated that LCH with liver involvement, especially cholangitis, indicates a poor prognosis. Targeted therapy provides a good treatment response and less toxicity. However, it may relapse after withdrawal. Liver transplantation is still a reliable salvage option for patients with end-stage liver disease. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of secondary histiocytic sarcoma (HS) that developed rapidly following chimeric antigen receptor T-cell (CAR-T) therapy for relapsed diffuse large B-cell lymphoma (DLBCL). The patient initially presented with DLBCL and underwent various treatments, including CAR-T therapy, which resulted in a partial remission. However, PET/CT scans later revealed progression of the disease, and biopsies confirmed the presence of HS. Genetic testing showed a clonal relationship between the DLBCL and HS, supporting the hypothesis of divergent evolution. The article suggests that CAR-T therapy may have played a role in the development of HS, although further research is needed to confirm this. [Extracted from the article]

OBJECTIVE To validate the performance of a novel, integrated test for canine cancer screening that combines cell-free DNA quantification with next-generation sequencing (NGS) analysis. SAMPLE Retrospective data from a total of 1,947 cancer-diagnosed and presumably cancer-free dogs were used to validate test performance for the detection of 7 predefined cancer types (Iymphoma, hemangiosarcoma, osteosarcoma, leukernia, histiocytic sarcoma, primary lung tumors, and urothelial carcinoma), using independent training and testing sets. METHODS Cell-free DNA quantification data from all samples were analyzed using a proprietary machine learning algorithm to determine a Cancer Probability Index (High, Moderate, or Low). High and Low Probability of Cancer were final result classifications. Moderate cases were additionally analyzed by NGS to arrive at a final classification of High Probability of Cancer (Cancer Signal Detected) or Low Probability of Cancer (Cancer Signal Not Detected). RESULTS Of the 595 dogs in the testing set, 89% (n = 530) received a High or Low Probability result based on the machine learning algorithm; 11% (65) were Moderate Probability, and NGS results were used to assign a final classification. Overall, 87 of 122 dogs with the 7 predefined cancer types were classified as High Probability and 467 of 473 presumably cancer-free dogs were classified as Low Probability, corresponding to a sensitivity of 71.3% for the predefined cancer types at a specificity of 98.7%. CLINICAL RELEVANCE This integrated test offers a novel option to screen for cancer types that may be difficult to detect by physical examination at a dog's wellness visit. [ABSTRACT FROM AUTHOR]

Disease monitoring of amphibian assurance populations is an important buffer against ongoing global extinctions. This study documents a high incidence of neoplasia in a zoo-managed assurance population of Puerto Rican crested toads (Peltophryne lemur ; PRCTs). Over 5 years, neoplasia was diagnosed in 17/49 (35%) submitted adult PRCTs and was the cause of death or euthanasia in 13/17 (72%). Most toads were male (16/17; 94%) and 6 to 11-years-old (average 8.1 years). Notably, seven toads (41%) had multiple neoplasms. Of the 29 neoplasms identified, 17 (59%) were cutaneous or subcutaneous. The most common neoplasms included mast cell tumors (MCTs; 8/29; 28%), histiocytic sarcomas (6/29; 21%), lymphoma/leukemia (4/29; 14%), and squamous cell carcinomas (3/29; 10%). Distant metastases were documented in 6/8 (75%) toads with MCTs. Causes for neoplasia in this population were not determined though may include genetic or environmental factors. Continued investigations of managed endangered amphibians will help elucidate mechanisms of carcinogenesis. [ABSTRACT FROM AUTHOR]

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Background and aims: X lymphoproliferative syndrome type 1 (XLP1) is a rare inborn error of immunity due to mutations of SH2D1A, encoding for slamassociated protein (SAP). The clinical phenotype includes severe mononucleosis, hemophagocytic lymphohistiocytosis (HLH), and Bcell lymphomas. Methods: We report the case of a child affected with XLP1 who presented with an incomplete HLH, triggered by Epstein-Barr virus (EBV) and treated with rituximab, involving orbits and paranasal sinuses. Results: The lesion was indistinguishable from lymphoma, complicating diagnosis and treatment. In addition, considering the high incidence of lymphoma in patients with XLP1, histology helped define its nature, driving therapeutic choices. Conclusion: We described an unusual presentation of incomplete HLH in a patient affected with XLP1: an EBV-driven infiltration of the orbits and paranasal sinuses. This led us to a challenging differential diagnosis of lymphoma-associated hemophagocytic syndrome, which can be frequently observed in patients with XLP1. Considering the extremely poor prognosis of this clinical finding, we sought for a prompt diagnosis and managed to obtain it and to immediately establish the right treatment on the basis of the pathological finding. [ABSTRACT FROM AUTHOR]

Aims: The discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics and additional haematologic cancers of patients diagnosed with histiocytic disorders in The Netherlands. Methods and results: We retrieved data on histiocytosis patients from the Dutch Nationwide Pathology Databank (Palga). During 1993 to 2022, more than 4000 patients with a pathologist‐assigned diagnosis of a histiocytic disorder were registered in Palga. Xanthogranulomas were the most common subtype, challenging the prevailing assumption that Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. LCH and juvenile xanthogranuloma (JXG) had a peak incidence in the first years of life; males were overrepresented among all histiocytosis subgroups. 118 patients had a histiocytic disorder and an additional haematologic malignancy, including 107 (91%) adults at the time of histiocytosis diagnosis. In 16/118 patients, both entities had been analysed for the same genetic alteration(s). In 11 of these 16 patients, identical genetic alterations had been detected in both haematologic neoplasms. This included two patients with PAX5 p.P80R mutated B cell acute lymphoblastic leukaemia and secondary histiocytic sarcoma, further supporting that PAX5 alterations may predispose (precursor) B cells to differentiate into the myeloid lineage. All 4/11 patients with myeloid neoplasms as their additional haematologic malignancy had shared N/KRAS mutations. Conclusions: This population‐based study highlights the frequency of xanthogranulomas. Furthermore, our data add to the growing evidence supporting clonal relationships between histiocytic/dendritic cell neoplasms and additional myeloid or lymphoid malignancies. Particularly adult histiocytosis patients should be carefully evaluated for the development of these associated haematologic cancers. [ABSTRACT FROM AUTHOR]

Here we report a case series of two dogs diagnosed as renal interstitial cell tumor (RICT) accompanied by elevated serum erythropoietin level and marked polycythemia. RICT is a rare tumor in dogs, originating from renal interstitial cells. While several renal tumors such as renal lymphoma, adenocarcinoma, carcinoma, sarcoma, fibrosarcoma and nephroblastoma may cause polycythemia, polycythemia caused by RICT has never been reported in dogs. The tumors in both dogs were solitary and lied within cortex or cortico-medullary junction. Histopathology revealed spindle-shaped cells suggesting mesenchymal origin, with no mitotic figures suggesting that the tumors in both dogs were benign. Following surgical removal of the affected kidney, serum erythropoietin level and polycythemia normalized in both dogs. [ABSTRACT FROM AUTHOR]

Introduction: Erdheim-Chester disease (ECD) is a rare disease that belongs to the group of Dendritic and histiocytic neoplasms. Only 2000 cases have been reported worldwide. It can present with a wide range of symptoms, making a differential diagnosis especially difficult. The primary and most important diagnostic tool is a biopsy of the affected organ/tissue. Nowadays the analysis of different mutations affecting the BRAF and MAPK pathways makes it possible to use targeted treatments, such as vemurafenib, dabrafenib, or cobimetinib. Objective: Our aim is to present the results of three male patients treated in our hematology department. Results: Our BRAF mutation-positive patient presented with retroperitoneal tissue proliferation and diabetes insipidus. The initial therapy of choice was dabrafenib. After 3 months of treatment, 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) scans showed regression, and after 2 years of treatment, no disease activity was detected. In our second patient, a recurrent febrile state (not explained by other reasons) and diabetes insipidus suggested the diagnosis. A femoral bone biopsy confirmed BRAF-negative ECD. The first-line therapy was interferon-alpha. After 3 months of treatment, no response was observed on 18FDG-PET/CT, and treatment with cobimetinib was started. The control 18FDG-PET/CT imaging was negative. Our third patient was evaluated for dyspnea, and a CT scan showed fibrosis with hilar lymphadenomegaly. A lung biopsy confirmed BRAF-negative ECD. We started treatment with interferon-alpha, but unfortunately, no improvement was observed. Second-line treatment with cobimetinib resulted in a partial metabolic response (PMR) according to control 18FDG-PET/CT. Conclusions: Our results demonstrate that an appropriately chosen treatment can lead to a good therapeutic response, but dose reduction may be necessary due to side effects. With advanced targeted therapeutic treatment options, survival and quality of life are significantly improved. [ABSTRACT FROM AUTHOR]

Simple Summary: Histiocytic sarcoma (HS), a rare and highly aggressive cancer of histiocytic origin, has been identified across various animal species, including sporadic cases in non-human primates. This research presents the initial documented instance of disseminated HS in a captive orangutan. The clinical presentation closely resembled symptoms observed in human HS cases. A thorough examination of tissue samples revealed typical features of this cancer through histopathology, and the diagnosis was confirmed using immunohistochemistry, employing markers such as Iba-1 and HLA-DR. Notably, the lack of expression of CD163 and CD204 challenges their effectiveness as diagnostic indicators in non-human primates. This investigation contributes to our comprehension of diagnosing HS in non-human primates, emphasizing the importance of standardized markers and diagnostic procedures. Histiocytic sarcoma (HS), an infrequent highly aggressive hematopoietic tumor, has been observed in diverse animal species, with isolated occurrences in non-human primates. This study describes the first case of disseminated HS in a 45-year-old female hybrid captive orangutan. The clinical profile mirrored symptoms seen in human HS cases, encompassing anorexia and ascites. Detailed histopathological examination demonstrated characteristic features of this tumor and immunohistochemistry, using markers such as Iba-1 and HLA-DR, confirmed the diagnosis. Significantly, the absence of CD163 and CD204 expression challenges their diagnostic utility in non-human primates. This investigation enhances our understanding of HS diagnosis in non-human primates, underscoring the necessity for standardized markers and diagnostic protocols. [ABSTRACT FROM AUTHOR]

Background: Spinal cord tumors present a challenge in diagnosis and treatment due to their varied histopathological characteristics. While Ewing sarcoma is a rare malignant tumor typically originating from skeletal bone, cases of primary intradural extraskeletal Ewing sarcoma are exceptionally rare. The similarity of its presentation to other spinal tumors further complicates its identification and management. Case presentation: We report a case of a 58-year-old Palestinian male with intradural extraskeletal lumbar Ewing sarcoma. The patient initially presented with lower back pain and bilateral S1 radiculopathy, with more severe symptoms on the left side. Magnetic resonance imaging revealed a 7 cm oval-shaped mass with homogeneous contrast enhancement, obstructing the spinal canal from L3/L4 to L5/S1 levels. Initially, a myxopapillary ependymoma was suspected, but the patient's sensory and motor functions suddenly deteriorated during hospitalization. Repeat magnetic resonance imaging indicated heterogeneous contrast enhancement, indicating acute intratumoral hemorrhage. Consequently, the patient underwent emergent L3–L5 laminotomy, with successful gross total resection of the tumor. Histopathological and immunohistochemical analyses confirmed the diagnosis of intradural extraskeletal Ewing sarcoma. Adjuvant therapy was administered to minimize the risk of local recurrence or distant metastasis. A systematic review of relevant literature, along with retrospective analysis of medical records, operative reports, radiological studies, and histopathological findings of similar cases, was also conducted. Conclusions: Intradural extraskeletal Ewing sarcoma is an infrequently encountered condition in adult patients, emphasizing the importance of considering it in the differential diagnosis of spinal tumors. Surgeons must possess a comprehensive understanding of this rare entity to ensure accurate staging and optimal management, particularly in the early stages when prompt intervention may improve prognosis. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma is an aggressive haematopoietic malignancy accounting for less than 1% of haematolymphoid neoplasms with a diagnosis based on morphology and immunophenotype of tissue biopsies with a very poor prognosis. Here, we report a 45‐year‐old man who was diagnosed with primary pulmonary histiocytic sarcoma with systemic metastases, with partial remission (PR) treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but it relapsed soon after therapy above. Tests demonstrated that TMB was 21 Muts/Mb PD‐L1 expression was 90% positive, and the disease has been well‐controlled over 3 years using immune checkpoint inhibitors (nivolumab and pembrolizumab). Bioinformatic pan‐cancer analysis verified that there was the highest genetic alteration frequency of PD‐L1 in which amplification accounted for the majority of sarcoma tumour samples. Following that, we found that the genetic alteration of PD‐L1 was associated with poor prognosis in sarcoma patients in terms of overall survival (OS) (p = 1.51 × 10−4), progress‐free survival (PFS) (p = 4.90 × 10−2) and disease‐specific survival (DSS) (p = 4.90 × 10−2). To our knowledge, this may be the first reported case with high PD‐L1 expression in primary pulmonary histiocytic sarcoma who may benefit from immunotherapy such as nivolumab and pembrolizumab significantly and safely. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma (HS) is a common tumour in flat coat retrievers (FCRs) often affecting periarticular tissues and joints. Palliative‐intent radiotherapy, seeks to achieve local tumour control, pain relief and improve limb function. However, the effect of palliative‐intent radiotherapy on analgesic levels of dogs with localised HS has not been studied. We hypothesised that palliative‐intent radiotherapy could improve lameness in dogs affected by localised HS. This study aimed to assess the impact of palliative‐intent radiotherapy on lameness of FCRs with localised HS. A retrospective cohort single institution study was performed. Medical records of FCR dogs with HS that received external beam radiotherapy between 2003 and 2022 were reviewed and included demographic, staging, severity of baseline lameness, therapeutic management and outcome data. Descriptive statistics, McNemar's chi‐squared test, Fisher's exact test and Kaplan–Meier analysis were used for statistical analysis. Thirty‐nine dogs were included with a median age of 7.2 years, 25 were male and 14 were female. HS was most commonly located in the forelimb (29 dogs, 74.3%), affecting the shoulder joint (19 dogs, 48.7%). Staging was performed in all 39 dogs with 22 (56.4%) dogs having localised HS, six (15.3%) dogs had localised HS with node metastasis and 11 (28.2%) dogs had localised HS with systemic metastasis. All dogs received palliative‐intent hypo‐fractionated radiation therapy, 32 (82%) dogs showed improvement in lameness. In conclusion, palliative intent radiation treatment has an analgesic effect reducing lameness or clinical signs associated with affected tumour‐bearing joints. [ABSTRACT FROM AUTHOR]

Purpose: This review primarily aims to review the epidemiology, clinical characteristics, imaging, pathology, immunohistochemistry, diagnosis, differential diagnosis, treatment, and prognosis of Primary pulmonary myxoid sarcoma (PPMS) with EWS RNA binding protein 1::cAMP response element binding protein 1 (EWSR1::CREB1) fusion. It provides reference for the diagnosis and treatment of this disease. Methods: Retrospectively collected the literature about PPMS with EWSR1::CREB1 fusion, its clinical, radiology, histology, molecular characteristics and current treatment strategies were collated and analyzed. This review provides a detailed differential diagnosis of the disease. Results: PPMS is an exceptionally rare, low-grade malignant tumor of the lung. This tumor commonly infiltrates lung tissue and develops within bronchial passages. It is identified by a genetic rearrangement involving the EWSR1 gene and a distinct chromosomal translocation t(2; 22)(q33; q12). Variants include EWSR1::CREB1 fusion and EWS RNA binding protein 1::activating transcription factors (EWSR1::ATF1) fusion. PPMS with EWSR1::CREB1 fusion is more prevalent among middle-aged individuals and affects both sexes almost equally. Clinical symptoms are relatively non-specific, primarily including cough, hemoptysis, and weight loss. Most patients undergo surgery and experience a favorable prognosis. Further research is required to validate the effectiveness of alternative treatments for PPMS with EWSR1::CREB1 fusion. Conclusion: EWSR1 rearrangement and EWSR1::CREB1 fusion are crucial genetic features of PPMS and serve as important diagnostic markers. Immunohistochemically, PPMS tests positive for EMA. In terms of treatment, surgery has been the primary approach in recent years. Therefore, the efficacy of other treatments still requires further investigation. [ABSTRACT FROM AUTHOR]

Immunotherapy has emerged as a promising treatment approach in oncology, as it is specifically designed to boost the strength and accuracy of the immune system, allowing it to target tumor cells but spare non-tumor tissue. This treatment not only demonstrates potential for improved clinical outcomes but may also be associated with fewer adverse effects compared to traditional therapies. Despite its early success, the application of immunotherapy has largely been limited to adult cancer patients, with slow adoption noted in the treatment of pediatric cancer patients. Our objective is to demonstrate a single institution's experience with immunotherapy in pediatric cancer patients and to discuss the use of these treatment modalities in this unique patient population. We performed a retrospective chart review and identified patients who received immune checkpoint inhibitors (ICIs) and/or underwent immunohistochemistry (IHC) testing for programmed death ligand 1 (PD-L1), quantification of tumor mutational burden (TMB), and classification of microsatellite instability (MSI) status. In total, we identified seven pediatric cancer patients who received therapy with ICIs. Four of these patients demonstrated positive PD-L1 expression, high TMB, and/or MSI-high status. These patients were treated with nivolumab alone or in combination with ipilimumab or brentuximab. The diagnoses included: multifocal epithelioid and spindle cell hemangioma (n = 1); metastatic melanoma (n = 2); histiocytic sarcoma (n = 1); rectal adenocarcinoma in the setting of constitutional mismatch repair deficiency syndrome (CMMRD) (n = 1); and Hodgkin lymphoma (n = 2). The patients received between four and nineteen cycles of immunotherapy. Immunotherapy-related adverse events included: mild allergic reaction; prodromal symptoms; anemia; neutropenia; transaminitis; endocrinopathies; and self-limiting neuritis. Of the seven patients, three are still being treated with immunotherapy (the patients with rectal adenocarcinoma, metastatic melanoma, and multifocal epithelioid and spindle cell hemangioma) with positive treatment responses observed on imaging, one is being treated with other modalities (the patient with Hodgkin lymphoma), two have achieved remission (the patients with metastatic melanoma and Hodgkin lymphoma), and one has relapsed (the patient with histiocytic sarcoma). The three patients who completed their immunotherapy regimens have been followed for 1 month, 4 months, and 10 months, respectively. This report of a single-institution experience with immunotherapy in pediatric cancer patients highlights the positive impact immunotherapy can have, especially when utilized to treat relapsed/refractory malignancies, as tumor regression or stabilization of disease burden was achieved in six of the patients described (CR = 2; PR = 4). Further research is needed to accurately identify pediatric oncology patients who could benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

A 7‐month‐old intact female bearded collie dog was admitted after a 2‐week history of progressive cough, inappetence, and lethargy, with no response to previous treatment with doxycycline and steroids. Mild attenuation of lung sounds in the right middle hemithorax was the only abnormality detected on physical examination. Abdominal ultrasound and thoracic radiographs were performed and revealed multifocally distributed nodules and masses, well‐circumscribed and of variable size in the kidneys and pulmonary parenchyma. Ultrasound‐guided fine needle aspirates of the renal and pulmonary masses were taken. A cytologic evaluation of these lesions pointed towards a malignant mesenchymal neoplasia. Euthanasia was elected due to the poor prognosis and rapid progression. The post‐mortem histopathology, a positive result to IBA1 immunoperoxidase staining, and a lack of detection of infectious agents, and negative E‐cadherin immunostaining enabled the final diagnosis of a disseminated histiocytic sarcoma. We report an atypical form, both in breed and age, of canine disseminated histiocytic sarcoma. While all breeds can be affected, there is a clear predisposition in some, and no cases have been previously described in bearded collies. Moreover, to the authors' knowledge, this is the youngest dog with this histiocytic disorder described to date. Disseminated histiocytic sarcoma should be considered as a differential diagnosis of multinodular tumors in dogs, regardless of the anatomic location and age of the dogs, even in puppies. [ABSTRACT FROM AUTHOR]

Purpose: To study the epidemiological profile of various pediatric orbital tumors and determine their clinicopathological correlation over 20 years. Methods: A retrospective analysis of all pediatric patients with orbital tumors from the medical records between 1995 and 2015 was done. Tumors were categorized based on their cellular origin. Demographic details, clinical and histopathological diagnoses, frequency, and clinicopathological correlation were studied. Results: A total of 265 pediatric patients with orbital tumors were analyzed, of which 145 (54.7%) patients were males and 120 (45.3%) were females. The mean age was 7 years (median: 6 years; range: 10 days–16 years). The distribution of lesions in each group was as follows: vasculogenic, 76 (28.7%); lipogenic and myxoid, 66 (25%); myogenic, 31 (11.7%); optic nerve and meningeal, 22 (8.3%); lymphoid and lymphoproliferative, 18 (6.8%); secondary orbital tumors, 14 (5.2%); histiocytic, 9 (3.4%); miscellaneous, 9 (3.4%), lacrimal gland, 8 (3%); mesenchymal with neural differentiation, 6 (2%); osseous, 4 (1.5%), and fibrocystic, 2 (0.8%). The most common benign and malignant pediatric orbital tumors were dermoid cysts (65, 24.5%) and rhabdomyosarcoma (31, 11.7%). A statistically significant (P < 0.0001) clinicopathological correlation was observed in 208 (83.2%) out of 250 biopsy-proven cases. Conclusion: Pediatric orbital neoplasms include a broad spectrum of benign and malignant lesions. Vasculogenic tumors constitute the majority of them, followed by lipogenic and myxoid tumors. A thorough knowledge of the incidence, clinical profile, imaging features, and histopathology of specific orbital tumors aids in accurate diagnosis and their successful management. [ABSTRACT FROM AUTHOR]

This editorial provides a comprehensive review of canine soft tissue sarcomas, discussing their classification, clinical characteristics, and treatment options. It highlights recent research on new diagnostic and therapeutic approaches, such as dynamic contrast-enhanced ultrasound and microbrachytherapy. The article also presents findings on electroporation-based treatments for oral tumors, which have shown to be safe and effective but require further standardization. Additionally, the text explores canine extraskeletal osteosarcoma and suggests potential diagnostic markers for osteosarcoma. The editorial concludes by emphasizing the importance of interdisciplinary collaboration and the need for further research in veterinary oncology. [Extracted from the article]

The Journal of Cancer Research & Therapeutics published several articles on rare cases of lymphoma and hematological malignancies. One case discussed secondary cutaneous histiocytic sarcoma in a patient with B-cell acute lymphoblastic leukemia, highlighting the need for accurate diagnosis and treatment. Another case focused on intravascular large B-cell lymphoma presenting as panniculitis, emphasizing the importance of early detection due to its varied presentation. Additionally, a study explored the use of flattening filter-free beams in total body irradiation treatment planning, showing promising results in dose homogeneity and treatment efficiency. These articles underscore the complexities of diagnosing and treating rare hematological malignancies, emphasizing the need for personalized and effective treatment approaches. [Extracted from the article]

Increased or constitutive activation of nuclear factor kappa B (NF-kB) is a feature of many chronic disease processes, including cancer. While NF-kB overactivation has been documented extensively in human oncology, there is a relative paucity of data documenting the same phenomenon in veterinary medicine. To assess NF-kB activity, antibodies to p65 and p100/p52, which are components of NF-kB heterodimers, were first validated for specificity and canine cross-reactivity via Western blot and labeling of immortalized cell pellets. Then, nuclear labeling for these antibodies was assessed via QuPath software in over 200 tumor tissue samples (10 hemangiosarcomas, 94 histiocytic sarcomas, 71 lymphomas, and 28 mast cell tumors) and compared to immunolabeling in appropriate normal tissue counterparts. Greater than 70% of spontaneous canine tumors evaluated in this study had more nuclear p65 and p100/p52 immunoreactivity than was observed in comparable normal cell populations. Specifically, 144/204 (70.58%) of tumors evaluated had positive p65 nuclear labeling and 179/195 (91.79%) had positive p100/p52 nuclear labeling. Surprisingly, greater nuclear p100/p52 reactivity was associated with a longer progression-free survival (PFS) and overall survival (OS) in canine lymphomas. These results provide support and preliminary data to investigate the role of NF-kB signaling in different types of canine cancer. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma is a malignant proliferation of cells that exhibit morphological and immunophenotypic features of mature histiocytes. Owing to its rarity, its clinical features and standard treatment have not yet been established. This report describes a case of histiocytic sarcoma of the palate that developed in a 76-year-old man, the first report of an intraoral histiocytic sarcoma. An extended resection was performed; however, establishing the excision line was extremely difficult because assessing the tumour boundary on imaging was challenging and the tumour underwent dynamic gross morphological changes following biopsy. Complete resection is required to obtain a favourable prognosis for high-grade tumours with indistinct borders. In this case, an intraoperative rapid examination with frozen section analysis was performed along the planned excision line to completely resect the tumours exhibiting such behaviour. At 28 months postoperatively, the patient demonstrated no recurrence or metastasis; however, he is under careful monitoring. [ABSTRACT FROM AUTHOR]