Histiocytic Differentiation Research Articles

A Classical Case Of Histiocytic Sarcoma: A Rare Haematopoietic Neoplasm

Histiocytic sarcoma is a rare haematopoietic tumor of histiocytic differentiation. Generally they are concurrent to other neoplasms or morphologically similar to them. This is the reason why they are oftenly missed on diagnosis. Here in our case report we have discussed a case of a 61 year old man who presented with a nasal mass. A long list of differentials like lymphomas, sarcoma, melanoma, metastasis etc were kept in count. However after applying large panel of various immunohistochemical markers it was finally ruled out to be a case of histicoytic sarcoma which is an aggressive haematopoietic neoplasm

Atypical dermatofibroma simulating hansenoma

Introduction: dermatofibroma is a benign mesenchymal lesion of uncertain etiology, centered in the dermis, with fibroblastic and histiocytic differentiation. The atypical variant can mimic superficial sarcoma histologically. Objective: to describe the clinical and histopathological findings of atypical dermatofibroma in a patient undergoing treatment for leprosy with multiple therapeutic failures. Case Description: the report concerns a 39-year-old woman with multiple therapeutic failures for Virchowian leprosy, who developed an atypical dermatofibroma on the upper limb, which clinically resembled a leproma. Discussion: molecular analyses suggest dermatofibroma may be associated with a neoplastic process. However, several studies correlate it to trauma, insect bites, folliculitis, immunological changes, and treated or reactive leprosy. The association of dermatofibroma and leprosy, especially in the Virchowian pole, is documented in the literature. However, there are no reports of atypical dermatofibroma associated with leprosy. Final Considerations: this case adds to other studies regarding a possible association between the pathogenesis of dermatofibroma and the immunological aspects present in leprosy.

Histiocytic sarcoma affecting the oral cavity: a clinical, pathologic and molecular study

ObjectiveTo investigate the clinicopathological, immunohistochemical and molecular features of histiocytic sarcomas affecting the oral cavity. MethodsPathology files of two institutions were searched for cases of histiocytic sarcoma, and new H&E-stained slides and immunohistochemistry reactions evaluated for diagnosis confirmation. Molecular screening for KRAS and PIK3CA mutations was performed through polymerase chain reaction (PCR) followed by Sanger sequencing. BRAFp.V600E mutation was assessed by pyrosequencing. Clinical data regarding sex, age, tumor location, systemic manifestations, clinical presentation, follow-up time, treatment applied and status at last follow-up were collected from patients' pathology and medical files. ResultsThree cases were retrieved during the period investigated (2000-2023). Two females and one male were affected, with a wide age range, involving the tongue, palate and gingiva. Histopathologically, the neoplasms presented as highly pleomorphic atypical cells distributed diffusely with infiltration of normal structures. All cases demonstrated histiocytic differentiation expressing CD68 and CD163, and a high Ki67 expression. Genetic mutations were evaluated in two cases. One case harboured BRAF-V600E mutation, but not in KRAS and PIK3CA, while the second case did not show mutation in BRAF-V600E, KRAS and PI3KCA. One patient was lost, and two patients died after eight and four months of follow-up. ConclusionHistiocytic sarcomas involving the oral cavity are extremely rare, and may represent dissemination of a systemic condition. It has an aggressive biological behaviour with a poor overall prognosis.

Littoral cell angioma: An incidental finding in a traumatic spleen

Littoral cell angioma (LCA) of the spleen, a rare vascular tumor, is usually asymptomatic, often discovered incidentally and a majority of them are benign in nature. A 20-year-old boy with a history of blunt abdominal trauma, who underwent splenectomy showed the presence of a capsular tear and variegated outer surface on gross examination of the spleen. On the cut section, multiple nodular areas with areas of hemorrhage were noted. Microscopical examination revealed the proliferation of anastomosing, irregular, tortuous blood-filled channels with plenty of histiocytes in the splenic tissue and extensive areas of hemorrhage, inflammatory cell infiltration, and fibrinoid deposits. Immunohistochemistry revealed positivity for CD31 (endothelial differentiation), CD68, and lysozyme (histiocytic differentiation) but was negative for CD34. The final diagnosis was LCA in a case of ruptured spleen after ruling out angiosarcoma. The possibility of this benign entity to have contributed to the potentially fatal splenic injury cannot be overlooked.

Cutaneous and Nodal Histiocytic Sarcoma: A Series of Five Cases

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.

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.

Cutaneous involvement in Ph-negative myeloproliferative neoplasms: from extramedullary hematopoiesis to myeloid metastasis with histiocytic differentiation. A systematic review of the literature.

Myeloid neoplasms may metastasize to the skin, presenting a wide range of clinical-pathological features that often lead to a reduction in patients' survival. The presentation varies depending on the category of myeloid neoplasm and its prognostic significance. The literature has specifically focused on the features of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelomonocytic leukemia (CMML). In this article, we aimed to uncover the peculiarities of clonal skin proliferations in the course of Ph-negative myeloproliferative neoplasms (MPNs). We conducted a systematic review and statistical analysis of the literature data. MPN patients mainly exhibited cutaneous extramedullary hematopoiesis, while a minority displayed cutaneous histiocytic lesions. Furthermore, these patients showed lower survival rates compared to the median survival of MPN patients, especially when calculating survival from the appearance of cutaneous lesions. Our work highlights, for the first time, the prognostic relevance and histological heterogeneity of cutaneous lesions in MPN. Moreover, it emphasizes the importance of dermatological and histological examinations when cutaneous lesions are present.

Abstract 6749: Histiocytic sarcoma descriptors and clinicopathologic determinants of survival: Analysis of a pooled database

Abstract Background Histiocytic sarcoma (HS) is an aggressive, rare malignant neoplasm of cells with histiocytic differentiation. It can occur de novo or develop in the context of other malignant disorders. HS can present as disseminated or localized lesions in the skin, lymphatics, gastrointestinal tract, central nervous system, or other organs. Little is known about factors that impact HS clinical outcomes. We conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in this rare histiocytic entity. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 146 cases of HS. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results A total of 146 patients with confirmed HS were identified. The median age was 52, with bimodal peaks between 14-28 and 56-70 years. There was a male preponderance with M:F of 1.3. Primary sites of involvement were CNS (21%), GI(16%), soft tissues (12%), H&N and bones (9% each), skin (8%), liver (7%), spleen (5%), lung (4%), and breast (1%). Lymphadenopathy and bone marrow (BM) were involved in 21% and 42%, respectively. Constitutional symptoms were present in 6%. The median size of the HS tumor was 4.45cm. The median OS of the whole group was 16 months. Age younger than 55 had better median OS (NR vs. 6 months, p=0.038). The primary site of involvement also impacted the median OS, where soft tissues and visceral disease had longer OS than those with CNS and spleno-lymphatic disease (60 vs. 7 vs. 6 months, p=0.03). Stage 1 disease had better median OS than stages 2-4 (p=0.06). Furthermore, unifocal had better median OS than multifocal/multicentric disease (60 vs. 9 months, p=0.007). The presence of inflammatory background positively impacted OS (p=0.01). Compared to no treatment, localized therapies such as surgery (S) and radiation therapy (RT), and systemic combination chemotherapy (CT) were statistically superior, with a median OS of 1, 204, and 21 months, respectively (p=0.003). With HS not amenable to complete resection, CT and CT+S were superior to RT+S (15 vs. 60 vs. 7 months, p=0.008). While BM involvement and size >10 cm were associated with worse OS, the latter did not reach statistical significance. There was no difference in median OS with respect to sex. Conclusion This study presents updated clinicopathologic data from a pooled cohort of patients with HS. It identifies age, the primary site of the disease, stage and extent of the disease, the inflammatory background status, and treatment approach as key determinants of OS. Citation Format: Dinesh Keerty, Philip A. Haddad. Histiocytic sarcoma descriptors and clinicopathologic determinants of survival: Analysis of a pooled database. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6749.

Acute monocytic leukaemia with histiocytic differentiation and erythrophagocytosis

Acute monocytic leukaemia with histiocytic differentiation and erythrophagocytosis

TREATMENT OF A PATIENT DIAGNOSED WITH ERDHEIM CHESTER'S DISEASE IN COOPERATION WITH PLASTIC SURGERY AND HEMATOLOGY

Erdheim Chester disease (ECD) is a rare non-Langerhans histiocytic multisystem disorder. ECD is most commonly manifested as multifocal sclerotic long bone lesions. Orbital and intraocular manifestations are rare. We report an unusual bilateral orbital presentation as xanthomatous infiltration of ECD. A 56-year-old male was admitted due to papular lesions on both eyelids. Eyelid tissue histology showed histiocytic infiltration consistent with ECD. BRAF V600E mutation (-). In the first year, PET-CT showed new lesions on the lymph node, eyelids, knees and elbows. Laboratory investigation was within normal apart of mild increased CRP. The disorder was unresponsive to pegylated interferon alfa. With cladribine of 3 courses and surgical intervention he achieved a nearly normal facial appearance. Uncontrolled cell survival, differentiation, and proliferation of histiocytes in ECD result in soft tissue thickening and progressed to chronic fibrotic disease which may be unresponsive to medical treatments and requires surgical interventions.

INTRAORAL PIGMENTED BENIGN FIBROUS HISTIOCYTOMA: AN UNUSUAL PRESENTATION

Benign fibrous histiocytoma (BFH) is a benign mesenchymal neoplasm that shows both fibroblastic and histiocytic differentiation. To date, about 65 oral BFH cases have been reported. Oral BFH most often affects middle-aged adults, with a female predilection. Several variants of BFH have been described, such as classical, aneurysmal, hemosiderotic, cellular, epithelioid, lipidized, clear cell, granular cell, myxoid, and signet-ring cell. A 56-year-old woman was referred for management of a painless lesion in the palate 6 years ago. After excisional biopsy, microscopic analysis showed a benign proliferation of spindle cells, arranged in a storiform pattern, associated with pigmented deposits, which were highlighted with Fontana-Masson and Perl's iron stains. Immunohistochemical analysis revealed positivity for vimentin, HLA-DR, CD68, CD163 and FXIIIa; pan-CK, EMA, α-SMA, GFAP, S-100, and CD34 were negative. Ki-67 highlighted scarce positive cells. The current case probably expands the microscopical spectrum of the hemosiderotic variant of BFH. Benign fibrous histiocytoma (BFH) is a benign mesenchymal neoplasm that shows both fibroblastic and histiocytic differentiation. To date, about 65 oral BFH cases have been reported. Oral BFH most often affects middle-aged adults, with a female predilection. Several variants of BFH have been described, such as classical, aneurysmal, hemosiderotic, cellular, epithelioid, lipidized, clear cell, granular cell, myxoid, and signet-ring cell. A 56-year-old woman was referred for management of a painless lesion in the palate 6 years ago. After excisional biopsy, microscopic analysis showed a benign proliferation of spindle cells, arranged in a storiform pattern, associated with pigmented deposits, which were highlighted with Fontana-Masson and Perl's iron stains. Immunohistochemical analysis revealed positivity for vimentin, HLA-DR, CD68, CD163 and FXIIIa; pan-CK, EMA, α-SMA, GFAP, S-100, and CD34 were negative. Ki-67 highlighted scarce positive cells. The current case probably expands the microscopical spectrum of the hemosiderotic variant of BFH.

Intraosseous Benign Fibrous Histiocytoma of the Mandible

<h3>Introduction</h3> Fibrous histiocytomas are a diverse group of tumors that exhibit fibroblastic and histiocytic differentiation and are considered to be a true neoplasm. Intrabony fibrous histiocytomas of the jaws are rare, with most cases being reported in the femur, tibia, pelvis and occasionally the skull bones. <h3>Material and Methods</h3> This report describes a case of 69 year old male patient who presented with pain in the area of tooth #18 (mandibular left second molar) and an endo-perio lesion that perforated through the cortical bone which appeared to be multilocular on radiographs. Clinically, there was a buccal swelling and when the buccal bifurcation was probed, a 10mm depth was revealed with a purulent exudate emanating from the pocket. The bridge was sectioned at the junction of #19 and 20 pontic followed by extraction of tooth #18. Reflection of the mucosa revealed a large bony lesion destroying the buccal plate of bone in the area of teeth #18 and 19. The purulent material was primarily associated with the tooth #18 and not the overall lesion. The majority of the lesion was enucleated and removed. <h3>Results</h3> Histopathological examination revealed fragments of mildly inflamed connective tissue that demonstrated a focus of spindle or mesenchymal cells proliferating in a whorling or storiform pattern. The tissue contained large scattered deposits of mineralized material and fragments of vital bone. Immunohistochemical stains for Desmin, SMA, CD34 and factor XIIIa were negative while diffusely positive for CD68. The positivity for CD68 demonstrated that the lesion was composed of histiocytic cells. <h3>Conclusions</h3> Benign fibrous histiocytomas of the soft tissues are well recognized entities, the rare intra-bony counterpart shares clinical, radiographic and histological features with odontogenic tumors, non-ossifying fibromas, osteoblastomas and fibrous dysplasia, and therefore should be considered in the differential diagnosis of these lesions.

Blurred lines – two cases of acute myeloid leukaemia with histiocytic differentiation

The unique morphological, immunophenotypic and functional features of histiocytes can be recapitulated in acute myeloid leukaemia (AML), particularly in monocytic/monoblastic subtypes.1–3 The spectrum of histiocytic differentiation in AML ranges from subtle morphological features to a relatively distinct syndrome with t(8;16) and erythrophagocytosis. Herein, we present two cases of AML with histiocytic differentiation.1,2

BCR::ABL1-positive histiocytic sarcoma of the small intestine in a patient with chronic myeloid leukaemia.

Histiocytic sarcoma (HS) is a rare myeloid-derived neoplasm with histiocytic differentiation and an aggressive clinical course. Recent studies suggest a common clonal origin between various haematolymphoid disorders. However, HS coexisting with chronic myeloid leukaemia (CML) without tyrosine kinase inhibitors (TKIs) has not been reported.

A unique case of classic pleomorphic sarcoma restricted to the toes

Over 50% of soft tissue sarcomas occurring in older adults are histologically pleomorphic and high grade. Most have traditionally been classified as malignant fibrous histiocytoma (MFH). MFH was originally defined as a malignant pleomorphic spindle cell neoplasm showing fibroblastic and histiocytic differentiation. More recently, pathologists have accepted that this morphology may be shared by a wide range of malignant neoplasms. Many sarcomas that were previously classified as pleomorphic MFH, on careful immunohistochemical and histopathologic analyses, revealed a specific line of differentiation and could be reclassified as myxofibrosarcoma (30%), myogenic sarcoma (30%), liposarcoma (4%), malignant peripheral nerve sheath tumor (2%), or soft tissue osteosarcoma (3%), whereas about 30% had no specific line of differentiation or were myofibroblastic. The term undifferentiated pleomorphic sarcoma (UPS) is now reserved for pleomorphic sarcomas that show no definable line of differentiation by current technology. The majority of extremity sarcomas occur in the lower extremity (74 vs. 26% in the upper limb). According to one of the studies conducted on 315 patients, non-metastatic soft tissue sarcoma of the lower extremity who were treated at one institution over a ten-year period. Sixty-six percent of the lesions were above the knee, and 60% were high grade. This case had a 3x3 cm ulcer at the 3rd toe in a 30-year-old male patient who subsequently underwent midfoot ampuatation.

Case report: Infrequent littoral cell angioma of the spleen.

Introduction and importanceLittoral cell angioma is a rare solid spleen tumor with uncertain malignant potential. It is usually asymptomatic; therefore, its diagnosis is usually incidental. There are approximately 150 cases reported in the medical literature, but none of them in the Hispanic population.Case presentationWe present a case of a 54-year-old woman who presented to our clinic with nonspecific abdominal pain. Imaging studies show a splenic mass with littoral cell angioma characteristics. The patient underwent an open splenectomy with subsequent histopathologic and immunohistochemical studies that confirmed the presence of a littoral cell angioma of a diameter of 8 × 4.5 × 3.5 cm. The patient was discharged after an uneventful postoperative recovery and was referred to the outpatient clinic for follow up.Clinical discussionThis case report highlights the close relationship between the littoral cell angioma, neoplasias, and autoimmune diseases. Even though LCA has a good prognosis, there is still the possibility of malignant transformation, especially when the spleen weighs 1500 g; our patient's sample pointed towards a benign pathology. LCA has a positive IHC for endothelial and histiocyte tissues. The IHC results of our patient were positive for CD34+ and CD68+, confirming the LCA diagnosis.ConclusionWithin red pulp spleen tumors, LCA should be highly considered as a differential diagnosis in all types of populations. In the case of a confirmed LCA, routine screening for neoplasias and autoimmune diseases should be performed.

Histiocytic and dendritic cell neoplasms of the mediastinum.

In this review, we discuss a logical approach to diagnosis of histiocytic and dendritic cell lesions of the mediastinum. We break down the differential diagnosis between true neoplasms of histiocytic and dendritic cells [Rosai-Dorfman disease (RDD), Langerhans cell histiocytosis (LCH), and follicular dendritic cell sarcoma (FDCS)] versus selected neoplasms of other lineages which frequently attract non-neoplastic histiocytes or resemble them morphologically (carcinoma, melanoma, sarcoma, germinoma, mesothelioma, and lymphoma). As neoplasms in the latter category are more common, they should be stringently excluded before diagnosing a lesion in the first group, particularly given enormous differences in clinical management. We also consider histiocytic sarcoma (HS), an extremely rare lesion which, in some cases is likely of intrinsic histiocytic differentiation, whereas in others represents clonal evolution from an underlying non-histiocytic neoplasm.

An Interesting Case of Lineage Switch to Histiocytic Sarcoma in a Case of Diffuse Large B Cell Lymphoma

Lineage switch involves change in the phenotypic characteristics from one type to another. It is a rare phenomenon described in mature lymphoid neoplasms which transform to histiocytic/dendritic cell tumor, more commonly described in low-grade lymphoma like follicular, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), wherein the neoplasm loses the phenotypic characteristics of non-Hodgkin lymphoma and acquires the markers of histiocytic differentiation. Here, we present a case of diffuse large B cell lymphoma transforming to histiocytic sarcoma post 6 months of start of therapy. Histiocytic sarcoma being a very aggressive tumor, the patient had a very rapid deteriorating course and succumbed to disease.

Multifocal Gastric Histiocytic Sarcoma Presenting as Gastrointestinal Bleeding

Histiocytic sarcoma is a rare malignancy that accounts for less than 1% of hematologic neoplasms, and shows morphologic and immunophenotypic non-Langerhans histiocytic differentiation. Commonly presents with nodal involvement, however extranodal sites are involved in 1/2 of cases. The skin and gastrointestinal (GI) tract are commonly involved. GI involvement manifests as abdominal mass, pain, intestinal obstruction, lower GI bleeding, or weight loss. We present case of histiocytic sarcoma manifesting as upper GI bleeding from innumerable synchronous gastric polyps. A 76 y/o female with CAD requiring multiple coronary stents, CABG, and AICD on dual antiplatelet therapy presented with melena and hematemesis. EGD revealed innumerable sessile and pedunculated polyps in the gastric body, fundus, and antrum. Two oozing polyps up to 5.3cm in diameter required polypectomy. Pathology showed histiocytic sarcoma. CT-scan was negative for metastases. 4 days post-discharge she developed further GI bleeding that required total gastrectomy with Roux-en-Y reconstruction for hemostasis. Intra-operatively no metastases were seen and negative margins were obtained. Two months later, the patient had recurrent hematemesis. CT scan showed small bowel obstruction and an intraluminal lesion, confirmed to be recurrent histiocytic sarcoma on endoscopic biopsies. The patient was discharged with plans for outpatient treatment, but sadly expired one month later. Although histiocytic sarcoma has been described throughout the GI tract, tumor confined to the stomach has only been described in 10 cases. Upon literature review, these have been mainly described in Asian populations and associated with H. pylori infection. Histiocytic sarcoma may present as a unifocal or multifocal tumor. Disease course is difficult to predict due to scarcity of reports, but aggressive behavior has been described. Our case illustrates the propensity for multifocal histiocytic sarcoma to behave aggressively despite complete resection with negative margins. Despite complete resection, distal recurrence has been described in 50% of cases and local recurrence in 20% of the cases. Multifocal disease confers a poor prognosis and is associated with poor response to chemotherapy. Our case represents an unusual case of multifocal disease limited to one organ. Complete margin-negative resection was possible, but the tumor recurred regionally in the jejunum, reflecting propensity to recur distantly rather than locally.Figure. 56: mm oozing pedunculated polyp seen on proximal gastric body on EGD at initial presentation.Figure: Innumerable gastric polyps throughout the fundus and body of the stomach.Figure: Jejunal polyp representing recurrence after margin negative total resection with gastrectomy.

Variations in Histiocytic Differentiation of Cell Lines From Canine Cerebral and Articular Histiocytic Sarcomas

Two newly established canine histiocytic sarcoma (HS) cell lines, designated as PWC-HS01 and FCR-HS02, were obtained from brain and articular tumors, respectively. These 2 HS cell lines had phagocytic ability and modal chromosome aberrations. Although morphologic features of both HS cells were similar, immunocytochemical examinations revealed that the PWC-HS01 cell line expressed both dendritic cell (ie, S100, CD208, CD1, and CD4) and macrophage (ie, CD68, CD163, and CD204) markers. In contrast, the FCR-HS02 cell line was immunonegative for CD204 and CD68 but consistently positive for the dendritic cell markers. Moreover, reverse transcription polymerase chain reaction analyses confirmed histiocytic differentiation of both HS cell lines. These results suggest that HS from the central nervous system may have a tendency to be more undifferentiated compared with cases from other organs. In addition, the 2 newly established HS cell lines were also tumorigenic and metastatic in immunodeficient mice, supporting that these cell lines can be used as new tumor models for investigating canine histiocytic diseases.