Histiocytic Sarcoma Research Articles

Two sides of the same coin: transdifferentiation from Burkitt lymphoma to histiocytic sarcoma

Two sides of the same coin: transdifferentiation from Burkitt lymphoma to histiocytic sarcoma

Prevalence of malignancy and factors affecting outcome of cats undergoing splenectomy.

To determine the prevalence of splenic malignancy in cats undergoing splenectomy and to investigate possible factors associated with post-operative outcome. 62 client-owned cats that underwent splenectomy. Medical records of 4 UK-based referral hospitals were searched and data reviewed retrospectively over 17 years. Factors associated with outcomes post-splenectomy were analyzed. 50 out of 62 cats (81%) were diagnosed with splenic neoplasia. Mast cell tumor ([MCT], 42%), hemangiosarcoma ([HSA], 40%), lymphoma and histiocytic sarcoma (6% each) were the most common tumor types. Fifteen cats (24%) presented with spontaneous hemoabdomen and were all diagnosed with splenic neoplasia. The diagnostic accuracy of cytology to detect splenic malignant lesions was 73% (100% for MCTs and 54% for mesenchymal tumors). Median survival time for cats with nonneoplastic splenic lesions was 715 days (IQR, 18 to 1,368) and 136 days for cats with splenic neoplasia (IQR, 35 to 348); median survival time was longer for cats with splenic MCT when compared to cats with HSA (348 vs 94 days; P < .001). Presence of metastatic disease and anemia (PCV < 24%) at diagnosis were associated with a poorer survival when considering all cats. Presence of anemia, a splenic mass on imaging or spontaneous hemoabdomen were associated with a diagnosis of HSA (P < .001). Benign splenic lesions were uncommon in this cohort of cats. Spontaneous hemoabdomen should prompt the clinician to suspect neoplasia in cats with splenic disease. Anemia and evidence of metastasis at diagnosis were poor prognostic factors regardless of the final diagnosis.

Cutaneous Histiocytic Sarcoma with Giant Cells in a Free-ranging Brush Rabbit (Sylvilagus bachmani).

A cutaneous mass in a free-ranging brush rabbit (Sylvilagus bachmani) was composed of neoplastic spindle to polygonal cells with multinucleated giant cells, which were positive for CD204 and negative for smooth muscle actin and desmin. Histiocytic sarcoma with giant cells was diagnosed; this neoplasm has not been reported previously in free-ranging lagomorphs.

Cutaneous Manifestations of Myeloid Neoplasms Exhibit Broad and Divergent Morphologic and Immunophenotypic Features but Share Ancestral Clonal Mutations With Bone Marrow

In this study, we performed a comprehensive molecular analysis of paired skin and peripheral blood/bone marrow (BM) samples from 17 patients with cutaneous myeloid or cutaneous histiocytic-dendritic neoplasms. The cutaneous manifestations included 10 patients with cutaneous acute myeloid leukemia (c-AML), 2 patients with full or partial Langerhans cell differentiation, 2 patients with blastic plasmacytoid dendritic cell neoplasms (BPDCN), 1 patient with both Langerhans cell differentiation and BPDCN, and 2 patients with full or partial indeterminate dendritic cell differentiation. Seven of the 10 c-AML patients (70%) exhibited concurrent or subsequent marrow involvement by acute myeloid leukemia, with all 7 cases (100%) demonstrating shared clonal mutations in both the skin and BM. However, clonal relatedness was documented in one additional case that never had any BM involvement. Nevertheless, NPM1 mutations were identified in 7 of the 10 (70%) of these c-AML cases while one had KMT2A rearrangement and one showed inv(16). All 3 patients (100%) with Langerhans cell neoplasms, 2 patients with BPDCN (100%), and one of the 2 patients (50%) with other cutaneous dendritic cell neoplasms also demonstrated shared mutations between the skin and concurrent or subsequent myeloid neoplasms. Both BM and c-AML shared identical founding drivers, with a predominance of NPM1, DNMT3A, and translocations associated with monocytic differentiation, with common cutaneous-only mutations involving genes in the signal transduction and epigenetic pathways. Cutaneous histiocytic-dendritic neoplasms shared founding drivers in ASXL1, TET2, and/or SRSF2. However, in the Langerhans cell histiocytosis or histiocytic sarcoma cases, there exist recurrent secondary RAS pathway hits, whereas cutaneous BPDCN cases exhibit copy number or structural variants. These results enrich and broaden our understanding of clonally related cutaneous manifestations of myeloid neoplasms and further illuminate the highly diverse spectrum of morphologic and immunophenotypic features they exhibit.

Enhanced Computed Tomography and 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Uncommon Histiocytic Sarcoma of Small Intestine Arising after Gastric Large B-Cell Lymphoma.

Histiocytic sarcoma (HS) is an extremely rare and aggressive malignant neoplasm of hematopoietic origin that shows morphologic and immunophenotypic evidence of histiocytic differentiation. In approximately 25% of the cases, presumed transdifferentiation of a preexisting hematolymphoid disorder can be demonstrated. Various extranodal sites, particularly the gastrointestinal tract, soft tissue, skin, and spleen, can be involved. Enhanced CT and FDG PET/CT findings of extranodal histiocytic sarcoma have been barely reported. We present a case with extranodal HS originating in the small intestine after gastric large B-cell lymphoma, mistaken for prostate cancer metastasis in a 76-year-old man.

THU107 A Case Of Primary Histiocytic Sarcoma Of Pituitary Gland Presenting With Central Diabetes Insipidus

Abstract Disclosure: S. Ahn: None. Y. Kim: None. Y. Cho: None. D. Seo: None. S. Kim: None. J. Cho: None. S. Choi: None. K. Kim: None. E. Kim: None. S. Hong: None. Introduction: Histiocytic sarcoma is a rare and aggressive hematopoietic neoplasm derived from non-Langerhans histiocytic cells of the monocyte/macrophage system. Here, we reported the first case of primary histiocytic sarcoma involving pituitary gland. Methods: Medical records were reviewed. Results: A 53 years old Korean men presented with general weakness, polydipsia, polyuria, and abnormal thyroid function test suspicious for secondary hypothyroidism. Laboratory examinations showed growth hormone deficiency, hypogonadotropic hypogonadism, and central diabetes insipidus. The magnetic resonance imaging showed a well-enhanced mass involving entire posterior pituitary gland with stalk thickening. The biopsy of pituitary mass was identified as a malignant tumor consistent with histiocytic sarcoma. This malignant tumor inoperably increased within a short duration and hormone deficiency such as secondary hypothyroidism and adrenal insufficiency additionally developed. Therefore, the patient started radiation therapy with desmopressin, levothyroxine, and hydrocortisone replacement. Conclusion: The biopsy is not regarded as the mandatory procedure for diagnosing patients with central diabetes insipidus with posterior pituitary lesion since in many cases, this is the result of hypophysitis. However, since there is still the possibility of primary malignancy and metastasis involving pituitary gland, an appropriate decision for performing biopsy should be made according to the patient’s clinical situations. Presentation: Thursday, June 15, 2023

Histiocytic sarcoma in renal transplant patients: a literature review

BackgroundHistiocytic sarcoma (HS) is defined as neoplasm resembling morphological and immunophenotypic characteristics of mature histiocytes. It is a rare form of lymphoid neoplasms. Despite advances in treatment and diagnosis of histiocytic sarcoma, majority of cases had poor prognosis due to progressive nature of the disease. In the following article, all reported cases of histiocytic sarcoma in renal transplant patients are reviewed.MethodsIn our literature review, all relevant reports were collected electronically by entering the necessary keywords. A Boolean approach using Medical Subject Heading (MeSH) keywords was implemented. After establishing the inclusion/exclusion criteria, article titles and abstracts were evaluated by Systematic Reviews and Meta-Analyses (PRISMA) standards for 2020. All cases of histiocytic sarcoma in renal transplant patients were included.ResultBased on our inclusion and exclusion criteria 4 case reports were yielded in this review. Two were males and 2 were females with the mean age of 42.25 years. Fever was the most common symptom. Although tumor originated from the native kidney on one patient, the site of the primary tumor was thorax, oropharynx, and transplanted kidney in the rest. Metastasis was detected in all cases. Prednisone was used for all cases. EBV was positive in 2 cases and negative in one of them. Histology was diagnostic and similar in all cases. Immunohistochemistry was done for 3 cases. Although chemotherapy was done for 3 patients, all 4 cases ended in mortality.ConclusionDespite the fact that neoplasms are post renal transplant complications, histiocytic sarcoma is a scarce and fatal entity in such patients. Histological and immunohistochemistry tests are the corner stone in diagnosis of histiocytic sarcoma.

Multimodal Management With Immunotherapy, Radiation, and Surgery of Histiocytic Sarcoma Following Acute Lymphoblastic Leukemia: An Unusual Presentation of a Rare Disease.

Histiocytic sarcoma (HS) is a rare neoplasm with no known cause. This sarcoma is characterized by morphology similar to that demonstrated by mature tissue histiocytes and mostly afflicts adults. HSs typically have a poor prognosis due to a rapidly progressive clinical course. Our patient's case was unique due to its presentation four years after completion of treatment for B-cell acute lymphoblastic leukemia. The patient experienced progression with initial therapy for HS. With dual immunotherapy and radiation, however, the patient has remained clinically stable without detectable disease. Immunotherapy may be a successful and tolerable therapeutic option for histiocytic disease.

IBCL-078 Histiocytic Sarcoma Presenting as Nodular Skin Lesion on the Anterior Chest In a 38-Year-Old Woman: A Case Report

IBCL-078 Histiocytic Sarcoma Presenting as Nodular Skin Lesion on the Anterior Chest In a 38-Year-Old Woman: A Case Report

Alternative Lengthening of Telomeres Is Rare in Canine Histiocytic Sarcoma.

Cancer cells activate telomere maintenance mechanisms (TMMs) to overcome senescence and thus are targets for TMM-specific therapies. Telomerase-independent alternative lengthening of telomeres (ALT) is frequently utilized as a TMM in human sarcoma subtypes. Histiocytic sarcoma (HS) is a rare but aggressive tumor of hematopoietic origin with unknown ALT incidence in humans. ALT has been identified in canine HS, a tumor type comparable to human HS that occurs with high rates in certain canine breeds such as Bernese mountain dogs (BMDs). This retrospective study characterized the frequency of ALT in BMD and non-BMD patients diagnosed with HS as surrogates for humans. Formalin-fixed paraffin-embedded tumor samples from 63 dogs at two centers, including 47 BMDs, were evaluated for their ALT activity and relative telomere content (TC) using a radiolabel C-circle assay (CCA). Known ALT-positive samples served as controls. CCA-positive cases were validated via FISH. Two BMD samples showed ALT activity of 1-14% compared to controls. All other samples were ALT-negative. The TC did not correlate with the CCA results. ALT positivity was validated by the appearance of ultrabright telomere foci. Low ALT activity was present in 4% of BMDs with HS and therefore does not appear to be a common target for therapeutic approaches but can have diagnostic value.

Utility of the second-generation curcumin analogue RL71 in canine histiocytic sarcoma.

Canine histiocytic sarcoma is an aggressive cancer, with a high rate of metastasis. Thus, novel therapeutic approaches are needed. Synthetic analogues of curcumin have elicited potent anti-cancer activity in multiple in vitro and in vivo models of human cancer. Furthermore, the compound 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71) has recently exhibited potent cell cycle arrest and apoptotic induction in a canine osteosarcoma cell line. To determine its potency in canine histiocytic sarcoma cells, cell viability of DH82 and Nike cells was measured using the sulforhodamine B assay. Flow cytometry was then used to analyse both cell cycle distribution and apoptosis. Of the five curcumin analogues examined, RL71, had the highest potency with EC50 values of 0.66 ± 0.057 µM and 0.79 ± 0.13 µM in the DH82 and Nike cell lines, respectively. Furthermore, RL71 at the 1x EC50 concentration increased G2/M cell cycle arrest 2-fold, and at the 2x EC50 concentration increased the number of apoptotic cells 4-fold. These findings are consistent with previous work using RL71 in both canine and human cancer cell lines. Future research should be directed on time-dependent changes, and mechanistic investigation in greater detail to elucidate RL71 mechanisms of action.

Primary intracranial histiocytic sarcomas: a report of six cases and a pooled analysis of individual patient data.

Primary intracranial histiocytic sarcomas (PIHSs) are extremely rare with limited reported cases, making their prognostic factors and management uncertain. This study aims to describe the clinical characteristics of PIHSs and propose a treatment protocol for this entity. Clinical data were collected from six patients diagnosed with PIHSs at Beijing Tiantan Hospital between March 2011 and October 2022. Additionally, a comprehensive search of the PubMed database was conducted using the keywords "primary intracranial" or "primary central nervous system" combined with "histiocytic sarcoma" or "histiocytic sarcomas" between 1996 and 2022, identifying 24 cases. A pooled analysis of individual patient data was performed to assess risk factors for overall survival (OS). The six cases included four males and two females, with a mean age of 42.2 ± 13.3years. In total, 24 cases of PIHSs were identified from previous studies. Multivariate Cox regression analysis revealed that gross total resection (GTR) was the only factor predicting a longer OS (p = 0.027). Kaplan-Meier analysis demonstrated that GTR (p = 0.0013), solitary lesions (p = 0.0048), and radiotherapy (p = 0.0492) were associated with a longer OS. PIHSs are rare brain tumors with poor clinical prognosis. Patients with solitary lesions have a longer OS than those with multifocal lesions. Gross total resection must be the first choice. Radiotherapy may bring benefits for these patients, but chemotherapy may not be useful. Further studies involving larger cohorts are necessary to validate these findings.

Malignant Histiocytosis Comprises a Phenotypic Spectrum That Parallels the Lineage Differentiation of Monocytes, Macrophages, Dendritic Cells, and Langerhans Cells

Malignant histiocytoses (MHs), or the ‘M group’ of the Histiocyte Society classification, are characterized by neoplastic histiocytes with large pleomorphic nuclei. MH encompasses the diagnoses of histiocytic sarcoma, interdigitating dendritic cell sarcoma, and Langerhans cell sarcoma. We aimed to define the phenotypic spectrum of MH and examine the genotypic features across this spectrum. Using immunohistochemistry, we arranged the 22 cases into 4 subtypes that correspond to the lines of differentiation from monocytic and dendritic cell precursors as follows: (1) macrophage (n = 5): CD68+, CD163+, CD14+, and Factor 13a+; (2) monocyte-macrophage (n = 5): CD68+, CD163+, CD14+, S100+, and OCT2+; (3) dendritic cell (n = 6): CD68+, CD11c+, S100+, lysozyme+, ZBTB46+, and CD1a/langerin < 5%; and (4) Langerhans cell (n = 6): CD68+, CD11c+, S100+, ZBTB46+, CD1a+, and langerin+. The phenotypic subtypes align with those seen in low-grade histiocytic neoplasms as follows: MH-macrophage type correlates with Erdheim-Chester disease phenotype; MH-monocyte-macrophage type with Rosai-Dorfman disease phenotype, and MH-Langerhans cell type with Langerhans cell histiocytosis. Activating mutations in MAPK-pathway genes were identified in 80% of MH cases; 29% had mutations in the PI3k-AKT-mTOR pathway and 59% had mutations in epigenetic modulating genes. Strong expression of cyclin D1 was present in all cases, whereas p-ERK and p-AKT were not uniformly expressed. Eight of 22 (36%) MH cases were proven to be clonally related to a prior B-cell lymphoma. Defining the phenotypic spectrum of MH provides a guide to diagnosis and allows further exploration into the potential biological and clinical significance.

Renal histiocytic sarcoma in a cat undergoing nephrectomy and adjuvant chemotherapy

AbstractA 6‐year‐old, male neutered, domestic shorthair cat was presented for further investigation of a right‐sided kidney mass. A contrast‐enhanced computed tomography scan of head, thorax and abdomen showed a right‐sided renal mass, with infiltration of the surrounding tissue, but no evidence of distant metastasis. Cytology was consistent with a poorly differentiated neoplasia, and nephrectomy was performed. Following surgery, the cat underwent multiple blood transfusions due to severe anaemia and developed tricavitary effusion compatible with a protein‐rich transudate. The tumour was confirmed to be a histiocytic sarcoma on histopathology and immunohistochemistry, and the patient received adjuvant chemotherapy with lomustine. Restaging procedures were performed 121 days following surgery and documented recurrence at the previous surgical site together with cutaneous metastasis, therefore a rescue protocol with single agent doxorubicin was started. The patient was euthanased after worsening of its clinical conditions, 152 days since nephrectomy was performed.

Functional Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Delivered by Canine Histiocytic Sarcoma Cells Persistently Infected with Engineered Attenuated Canine Distemper Virus.

The immune response plays a key role in the treatment of malignant tumors. One important molecule promoting humoral and cellular immunity is granulocyte-macrophage colony-stimulating factor (GM-CSF). Numerous successful trials have led to the approval of this immune-stimulating molecule for cancer therapy. However, besides immune stimulation, GM-CSF may also accelerate tumor cell proliferation, rendering this molecule a double-edged sword in cancer treatment. Therefore, detailed knowledge about the in vitro function of GM-CSF produced by infected tumor cells is urgently needed prior to investigations in an in vivo model. The aim of the present study was to functionally characterize a persistent infection of canine histiocytic sarcoma cells (DH82 cells) with the canine distemper virus strain Onderstepoort genetically engineered to express canine GM-CSF (CDV-Ondneon-GM-CSF). The investigations aimed (1) to prove the overall functionality of the virally induced production of GM-CSF and (2) to determine the effect of GM-CSF on the proliferation and motility of canine HS cells. Infected cells consistently produced high amounts of active, pH-stable GM-CSF, as demonstrated by increased proliferation of HeLa cells. By contrast, DH82 cells lacked increased proliferation and motility. The significantly increased secretion of GM-CSF by persistently CDV-Ondneon-GM-CSF-infected DH82 cells, the pH stability of this protein, and the lack of detrimental effects on DH82 cells renders this virus strain an interesting candidate for future studies aiming to enhance the oncolytic properties of CDV for the treatment of canine histiocytic sarcomas.

Immunohistochemical evidence of NF-kB activation in canine lymphomas, histiocytic sarcomas, hemangiosarcomas, and mast cell tumors.

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.

Hemolymphoreticular Neoplasias from the Ramazzini Institute Long-term Mice and Rat Studies on Aspartame.

Haemolymphoreticular neoplasias (HLRNs) from the Ramazzini Institute (RI) carcinogenicity studies on Aspartame (APM) in rats and mice were heterogeneously grouped over the years and different statistical methods were applied. We report all the detailed HLRN diagnoses of all the RI rats and mice studies on APM and the related statistics. Histological subtypes and lineage (myeloid or lymphoid) are reported in males (MM) and females (FF) in line with the International Harmonization of Nomenclature and Diagnostic Criteria for Lesions (INHAND) for rodents and the World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues. Statistical analyses included Fisher's Exact test and Cochran-Armitage trend test. Results from the post-natal bioassay on Sprague-Dawley (SD) rats (BT6008) showed statistically significant increases in lymphomas (all types) (MM, FF), leukemias (all types) (FF), immunoblastic lymphomas (MM, FF), total lymphoid tumours (MM, FF), monocytic leukemia (FF), myeloid leukemia (FF), histiocytic sarcoma (FF), and total myeloid tumours (FF). Results from the prenatal experiment on SD rats (BT6009), showed statistically significant increases in lymphomas (all types) (FF), leukemias (all types) (FF), total lymphoid tumours (FF), myeloid leukemia (FF), and total myeloid tumours (FF). Finally, results from the prenatal bioassay on Swiss mice (BT6010) showed statistically significant increases in leukemias (all types) (MM, FF), lymphoblastic leukemia (MM, FF), monocytic leukemia (MM) and total myeloid tumours (MM). Our analyses, performed in line with international recommended guidelines for statistics and pathology, confirm and reinforce our previous findings of statistically significant increases of HLRNs in rodents exposed to APM.

Dendritic/histiocytic cell sarcoma: The OSU experience.

e23552 Background: Dendritic and histiocytic cell sarcomas (DHCS) are ultra-rare malignant neoplasms with morphological and immunotypic features of histiocytes. Incidence rates are unknown, it is estimated to represent &lt; 1% of all soft tissue tumors. Diagnosis is often challenging due to histological variability and lack of a pathognomonic molecular marking. Currently, there is no well-defined standard of care for these patients. This study describes a single-center experience with and this is one of the largest cohorts reported in the medical literature. Methods: Patients evaluated at The Ohio State University James Comprehensive Cancer Center between January 1, 2010 and April 1, 2022, were included. Data collected included baseline demographic variables, pathologic and molecular features, treatment regimen, and outcomes. Due to a small cohort size, descriptive statistics were performed instead of formal power calculations. Results: 18 patients were identified. 8 were censored, as they did not receive treatment at our institution, or were lost to follow-up, out of the 10 evaluable patients. Nine (90%) were white, and 7 (70%) were male. The median age at diagnosis was 54 years (24-67). The most common anatomic location was the head and neck region (60%). The average size of the tumor was 4.8 cm. 4 out of 10 patients presented with localized disease, and 6 with metastatic disease. 8 patients received chemotherapy, 3 received radiation therapy, and 3 patients underwent surgery. The patients who received chemotherapy underwent a range of 2 to 6 cycles, utilizing a variety of regimens, most commonly cytotoxic chemotherapies. We analyzed the time to progression (TTP) for each line of treatment for each patient the shortest TTP for a chemotherapy line was 16 days for a patient who received single-agent Sirolimus. A patient who received Cyclophosphamide, Doxorubicin, and Vincristine had the longest TTP at 354 days (or 51 weeks). Due to the small sample size, progression rates were calculated instead of median TTP. Five of the 8 patients that received chemotherapy progressed (62.5%), while a third progressed (33.3%) if they had received radiation or surgery. Four of the 10 patients (40%) died from the disease within the dates studied. 7 of 18 patients underwent somatic NGS testing. 4 of the 18 had a TP53 mutation, and 5 of the 7 patients who received NGS testing had a positive PD-L1 expression level. The median tumor mutation burden was 4.75(3-127). Conclusions: We found that DHCS a has relatively unfavorable outcomes despite aggressive multi-modality treatment. Due to the limited sample size, we could not identify significant associations between clinicopathological factors and treatment outcomes. However, the descriptive data suggests multidisciplinary approach may lead to better outcomes. We recommend multi-institutional collaboration to design clinical trials and define optimal treatment strategies for patients with this ultra-rare sarcoma.

Whole exome and transcriptome analysis revealed the activation of ERK and Akt signaling pathway in canine histiocytic sarcoma

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients.

The many faces of mouse histiocytic sarcoma in C57BL/6J mice.

Histiocytic sarcoma is a tumor of the hematopoietic system considered to be derived from macrophages. Although rare in humans, it occurs frequently in mice. Histiocytic sarcoma can be a difficult tumor to diagnose due to its diverse cellular morphologies, growth patterns, and organ distributions. The varying morphology of histiocytic sarcomas makes it easy to confuse them with other types of neoplasia, including hepatic hemangiosarcoma, uterine schwannoma, leiomyosarcoma, uterine stromal cell tumor, intramedullary osteosarcoma, and myeloid leukemia. As such, immunohistochemistry (IHC) is often needed to differentiate histiocytic sarcomas from other common tumors in mice that they can morphologically mimic. The goal of this article is to present a broader perspective of the diverse cellular morphologies, growth patterns, organ distributions, and IHC labeling of histiocytic sarcomas encountered by the authors. This article describes these features in a set of 62 mouse histiocytic sarcomas, including the IHC characterization of the tumors using a panel of markers for the macrophage antigens F4/80, IBA1, MAC2, CD163, CD68, and lysozyme, and describes differentiating features of histiocytic sarcomas from other morphologically similar tumors. The genetic changes underlying the pathogenesis of histiocytic sarcoma in humans are beginning to be elucidated, but this is difficult due to its rarity. The higher prevalence of this tumor in mice provides opportunities to investigate mechanisms of its development and to test potential treatments.