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

OBJECTIVE: To investigate the clinicopathological, immunohistochemical and molecular features of histiocytic sarcomas affecting the oral cavity. METHODS: Pathology 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. RESULTS: Three 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. CONCLUSION: Histiocytic 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.

Anaplastic large cell lymphoma with ALK::ATIC fusion mimicking a histiocytic sarcoma debuting as an anterior thoracic soft tissue tumor with exceptional clinicopathological, morphological and molecular features.

A 56-year-old woman debuted with a palpable painless mass in the anterior thorax wall at the level of the second and third right parasternal intercostal space, which progressively increased in size over 5 months accompanied by localized skin rash, mild dyspnea and chest pain when changing position. Imaging studies showed a soft tissue mass measuring 75 × 62 mm and a density of 34 Hounsfield Units that had caused the lysis of the costal arches and grew expansively towards the anterior mediastinum, without identifying mediastinal adenopathies only by this imaging method. Core biopsy was performed, which was initially diagnosed as histiocytic sarcoma (HS); however, when the diagnostic panel was expanded to include molecular and NGS studies, the final diagnosis was anaplastic large cell lymphoma with ALK::ATIC fusion. Here, we report a very rare neoplasm with unusual clinical presentation, histopathology and molecular features.

Immunohistochemical expression of vimentin, E-cadherin, and CD45 in natural cases of canine cutaneous round tumors.

Round cell tumors are common cutaneous lesions in dogs, with increased occurrence percentages among different skin tumors. This study aimed to investigate the frequency as well as gross and pathological characteristics of round cell tumors in natural cases of tumorous dogs in relation to breed, sex, and age. Moreover, it aimed to evaluate the immunohistochemical expression of a panel of immunohistochemical stains, including vimentin, E-cadherin, and cluster of differentiation (CD45) as an adjunct technique for the differential diagnosis of cutaneous round cell neoplasm. Data were collected from 64 dogs of both sexes (36 females and 28 males), various breeds, and different ages (8 months to 7 years). The histopathological nature of neoplastic growth was reported, and neoplasm prevalence was classified using age, sex, breed, and site on the body. We observed 48 cases of transmissible venereal tumors, 12 cutaneous histiocytomas, and 4 histiocytic sarcoma. Immunohistochemical characterization revealed an intense positive immunoreactivity for vimentin in transmissible venereal tumor cells and moderate positive immunoreactivity for E-cadherin and CD45 in cutaneous histiocytoma and histiocytic sarcoma cells. In conclusion, the canine transmissible venereal tumor was the most frequent form of round cell tumor; thus, a definitive cutaneous neoplasm diagnosis should be based on histopathological morphology and immunohistochemical findings.

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.

Concomitant occurrence of multicentric hemangiosarcoma and histiocytic sarcoma in a dog

Histiocytic sarcoma (HS) is uncommon malignant neoplasia of round cells with marked predilection in Rottweiler and Bernese Mountain. The disseminated form, which mainly affects the spleen, lungs, lymph nodes, bone marrow, skin, and subcutis, presents a quick and aggressive clinical behavior. Hemangiosarcoma (HAS) is a malignant neoplasm of endothelial vessel cells commonly reported to affect the right atrium of dogs' hearts. A male Rottweiler, five years old, presented flaccid paraplegia and progressive muscular atrophy in the temporal, masseter, and limbs muscles; Due to the clinical stage of the animal, euthanasia was conducted. During the necroscopic examination, it was noticed that several masses presented different sizes; some were whitish, and others were reddish and spread in multiple organs (lungs, heart, spleen, stomach, kidneys, brain, medulla, skeletal muscle, and pre-scapular lymph node). Microscopically, in some organs such as the stomach, right ventricle, lungs, and medulla, it was noticed a proliferation of myeloid cells, highly cellular, with poor demarcation, no encapsulation, and with the infiltrative growth pattern of cells with high pleomorphism. Numerous tumoral emboli were observed in the spleen, brain, skeletal muscle, and lymph node. These cells were submitted for immunohistochemistry and were positive for CD18 (HS antibody). In the right atrium, liver, and kidney it was observed malignant and infiltrative endothelial proliferation (HSA) and emboli in the medulla. Therefore, we conclude that both neoplasms (HS and HSA) cause the animal's paraplegia due to their embolism and metastasis to the spinal cord and skeletal muscle.(AU)

Myeloid and histiocytic sarcomas in subantarctic fur seals Arctocephalus tropicalis, Brazil.

Histopathological and immunohistochemical methods were used to diagnose round cell tumors in 2 subantarctic fur seals Arctocephalus tropicalis with marked anemia. Although wild-born, both individuals were placed under human care while juveniles in a Brazilian aquarium. Both pinnipeds were PCR tested for herpesvirus, and 1 was infected with otariid gammaherpesvirus 5 (OtHV-5), previously described in a subantarctic fur seal stranded in Brazil. Although some gammaherpesviruses can cause sarcomas and other neoplasms, it was not possible to definitively associate OtHV-5 with the neoplasm. To our knowledge, these are the first neoplasm records in subantarctic fur seals.

Primary splenic histiocytic sarcoma associated with hemophagocytic lymphohistiocytosis: A case report and review of literature of next-generation sequencing involving FLT3, NOTCH2, and KMT2A mutations.

BACKGROUND: Histiocytic sarcoma is a very rare monocyte/macrophage-derived hematopoietic system tumor with a poor prognosis whose diagnosis is pathologically challenging due to its extreme rarity and histological overlap with various mimicking entities in which histiocytes also predominate. CASE: We report the case of a 33-year-old male patient with hemophagocytic lymphohistiocytosis, purpuric syndrome, and significant splenomegaly. The patient underwent splenectomy; subsequent macroscopic examination revealed a spleen weighing 2065 grams with hyperemic red pulp and multiple infarcts at the periphery. The histological and immunohistochemical study established a diagnosis of primary splenic histiocytic sarcoma with frequent hemophagocytosis. Next-generation sequencing demonstrated mutations in FLT3, NOTCH2, and KMT2A, microsatellite stability, and a tumor mutational burden of 2 mut/Mb. The patient's condition deteriorated clinically from the appearance of the first symptoms and he died 6 months later from multi-organ failure. CONCLUSION: Primary splenic histiocytic sarcoma is one of the rarest tumors of the hematopoietic system. We report the first case with mutations in FLT3, NOTCH2, and KMT2A, and associated hemophagocytic lymphohistiocytosis.

Disseminated mucocutaneous trichosporonosis in a patient with histiocytic sarcoma

Abstract Trichosporon asahii is the causal agent of trichosporonosis. Patients with immunosuppression or hematological malignancies are at higher risk of infection. Skin and mucosal involvement appear as fast-growing papulonodular lesions and necrotic ulcers. Internal organ dissemination is lethal. Therapeutic success depends on the underlying disease. Here, the authors present the first case of disseminated mucocutaneous trichosporonosis in a patient with a post-mortem diagnosis of histiocytic sarcoma, a rare and aggressive haematolymphoid neoplasm. Regretfully, death occurred despite treatment with liposomal amphotericin B and supportive measures, showcasing the fatality of both diseases.

Disseminated mucocutaneous trichosporonosis in a patient with histiocytic sarcoma.

Trichosporon asahii is the causal agent of trichosporonosis. Patients with immunosuppression or hematological malignancies are at higher risk of infection. Skin and mucosal involvement appear as fast-growing papulonodular lesions and necrotic ulcers. Internal organ dissemination is lethal. Therapeutic success depends on the underlying disease. Here, the authors present the first case of disseminated mucocutaneous trichosporonosis in a patient with a post-mortem diagnosis of histiocytic sarcoma, a rare and aggressive haematolymphoid neoplasm. Regretfully, death occurred despite treatment with liposomal amphotericin B and supportive measures, showcasing the fatality of both diseases.

Atypical spleen hemophagocytic histiocytic sarcoma in a dog

Background: The histiocytic sarcoma (HS) complex is a set of malignant neoplasms originating from interstitial dendritic cells or macrophages. When it involves macrophages of the splenic red pulp and bone marrow, it is referred to as hemophagocytic histiocytic sarcoma (HHS). HHS behaves more aggressively than HS and is usually fatal. HHS can be diagnosed by cytological and histopathological examination of neoplastic tissue. HHS is confirmed by immunohistochemistry using an anti-CD11d antibody. This neoplasm is often confused with immune-mediated hemolytic anemia or Evans syndrome due to erythrophagocytosis and platelet consumption. The clinical presentation of the animals progresses with evident anemia and thrombocytopenia, leading to signs such as prostration, inappetence, and pale mucosa, making diagnosis challenging and often late. This study aimed to report the clinic-pathological aspects of a canine with atypical hemophagocytic splenic HS. Case: A 4-year-old male Shih-Tzu canine was referred to the Veterinary Hospital with a history of prostration and anorexia. Pale mucous membranes were observed on physical examination. Blood tests revealed non-regenerative anemia, leukopenia, and thrombocytopenia. Serum protein levels were below the reference values for the species in biochemical examinations. Hemoparasitosis was suspected; however, the result of the polymerase chain reaction was negative. Abdominal ultrasound revealed a splenomegaly with heterogeneous parenchyma and a slightly irregular surface, but no visible mass in the spleen. Due to the difficulty of stabilizing the patient, even after successive transfusions, the animal underwent exploratory laparotomy with medial access and posterior splenectomy. Subsequently, the spleen was surgically removed, fixed in 10% buffered formalin, and processed routinely. Macroscopically, it had an irregular reddish-brown capsular surface. Histopathological examination of the spleen revealed a densely cellular neoplasm composed of round to spindle cells (histiocytes) arranged haphazardly in variably sized sheets separating the pre-existing spleen stroma. These histopathological findings were consistent with a histiocytic malignant neoplasm. Immunohistochemical analysis was performed to better define the origin of the histiocytic neoplasm. Neoplastic cells showed positive immunostaining of more than 80% of tumor cells for the CD11d antibody and weak immunostaining for CD11c and lysozyme. The patient survived for less than 30 days after the first hospital visit. Discussion: The diagnosis of HHS was based on the histological characteristics and positive immunostaining of more than 80% of the tumor cells for the CD11d antibody. HHS is an extremely aggressive and rare tumor that affects elderly dogs of any breed. In this study, HHS had atypical histologic characteristics, in which erythrophagocytosis and hemosiderin were not observed within macrophages. HHSs arise from macrophages of the red pulp of the spleen or bone marrow and express the b2 integrin, CD11d, and have low expression of CD1 and CD11c, which are predominantly expressed by non-hemophagocytic HS. The hematological and biochemical changes observed in this case were similar to those described in other dogs with HHS. Treatment of HHS is only palliative. Erlichia ewingii, E. canis, Anaplasma phagocytophilum, A. platys, Borrelia burgdorferi, Dirofilaria immitis, Leishmania infantum and immune-mediated hemolytic anemia are the main differential diagnoses because they cause anemia and thrombocytopenia accompanied by splenomegaly.

Hemophagocytic histiocytic sarcoma in dog

Background: Histiocytic sarcoma can present in a localized or disseminated form, being a malignant neoplasm derived from interstitial dendritic cells. Another form of the disease is called hemophagocytic histiocystic sarcoma (HHS), which originates from macrophages located in the splenic red pulp and bone marrow. HHS is a rare neoplasm with unknown etiology and rapid development. It mainly affects middle-aged to elderly animals. It primarily affects the spleen and bone marrow, with occurence of metastases in other organs. Some canine breeds are considered more predisposed to this neoplasia, among them the Rottweiler. The aim of this study was to report a case of HHS in a Rottweiler dog. Case: An 8-year-old Rottweiler suffering from hyporexia and progressive weight loss for a month was attended at the Veterinary Hospital of State University of Maringá. On physical examination, he only presented mild discomfort on abdominal palpation. Blood count was performed, which revealed mild thrombocytopenia (145,000/µL, reference value for the species 150,000-500,000/µL). The Polymerase Chain Reaction (PCR) exam was requested for babesiosis and ehrlichiosis, due to a history of ectoparasites. The animal was released with the prescription of Doxycycline at a dose of 10 mg/kg orally for 28 days. After 5 days, the condition worsened and the animal returned with emesis, apathy and hyporexia, being hospitalized. Abdominal ultrasound, blood count, urinalysis, serum urea and creatinine tests were requested. Among the hematological changes, thrombocytopenia (116,000/µL) and the appearing of regenerative anemia and atypical round cells with ample and slightly basophilic cytoplasm in the smear, similar to histiocytes, stood out. On ultrasound examination, splenomegaly was observed with hypoechogenic areas. Ultrasound-guided fine-needle aspiration cytology (FNAC) of the spleen was performed, which...(AU)

Pediatric multifocal histiocytic sarcoma- a fatal diagnosis not to miss!

Histiocytic sarcoma (HS) is a rare hematolymphoid malignant neoplasm with an aggressive clinical course. It can arise de novo or from low-grade B-cell lymphoma. We describe the case of a 16-year-old boy referred to our hospital with generalized lymphadenopathy, weight loss, and decreased appetite for one month. The patient died undiagnosed on the 7th day of hospitalization. Lymph node and bone marrow biopsies were performed one day before the patient died. The lymph node biopsy revealed an architectural effacement with a diffuse proliferation of large pleomorphic neoplastic cells containing large, multilobulated nuclei, coarse vesicular chromatin, prominent nucleoli, and a moderate amount of eosinophilic cytoplasm. The bone marrow aspiration smears and biopsy also showed evidence of infiltration by these above-mentioned cells. Based on the morphology, along with the exclusion of many differential diagnoses by an extensive panel of immunohistochemical markers, a diagnosis of HS was made. This case report aims at evaluating all the clinical and immunophenotypic features of a case of HS with multifocal presentation and an aggressive clinical course in order to give a correct and definite diagnosis at the proper time.

Hemophagocytic histiocytic sarcoma in dog

Background: Histiocytic sarcoma can present in a localized or disseminated form, being a malignant neoplasm derived from interstitial dendritic cells. Another form of the disease is called hemophagocytic histiocystic sarcoma (HHS), which originates from macrophages located in the splenic red pulp and bone marrow. HHS is a rare neoplasm with unknown etiology and rapid development. It mainly affects middle-aged to elderly animals. It primarily affects the spleen and bone marrow, with occurence of metastases in other organs. Some canine breeds are considered more predisposed to this neoplasia, among them the Rottweiler. The aim of this study was to report a case of HHS in a Rottweiler dog. Case: An 8-year-old Rottweiler suffering from hyporexia and progressive weight loss for a month was attended at the Veterinary Hospital of State University of Maringá. On physical examination, he only presented mild discomfort on abdominal palpation. Blood count was performed, which revealed mild thrombocytopenia (145,000/µL, reference value for the species 150,000-500,000/µL). The Polymerase Chain Reaction (PCR) exam was requested for babesiosis and ehrlichiosis, due to a history of ectoparasites. The animal was released with the prescription of Doxycycline at a dose of 10 mg/kg orally for 28 days. After 5 days, the condition worsened and the animal returned with emesis, apathy and hyporexia, being hospitalized. Abdominal ultrasound, blood count, urinalysis, serum urea and creatinine tests were requested. Among the hematological changes, thrombocytopenia (116,000/µL) and the appearing of regenerative anemia and atypical round cells with ample and slightly basophilic cytoplasm in the smear, similar to histiocytes, stood out. On ultrasound examination, splenomegaly was observed with hypoechogenic areas. Ultrasound-guided fine-needle aspiration cytology (FNAC) of the spleen was performed, which...

Estudio Observacional: Dermatofibrosarcoma Protuberans, Serie de casos / Observational Study: Dermatofibrosarcoma Protuberans, Case Series

Introducción: El dermatofibrosarcoma protuberans(DFSP), es uno de los tumores cutáneos menos frecuentes, se clasifica dentro de los sarcomas fibrohistociticos y está caracterizado por un crecimiento lento y progresivo. Métodos: Se realizó una serie de casos retrospectiva de los pacientes con DFSP atendidos en el Centro de la Piel (CEPI) entre 2010 y 2019, se tomó en cuenta la información demográfica, características clínicas, tratamiento y su evolución. Resultados: Seis pacientes fueron diagnosticados y tratados por DFSP en el período evaluado, existió un predominio de mujeres (4 mujeres, 2 hombres) con una media de edad de 58.2 (DE =19,6), tres de ellos presentaron lesiones en forma de placa indurada y los restantes presentaron nódulo único, la localización de las lesiones fueron en hombro, cuello e hipogastrio. El tratamiento más utilizado fue la escisión amplia, ninguno de los pacientes presentó recidivas al primer y quinto año del seguimiento. Conclusión: Es necesario el reconocimiento de las características clínicas típicas de DFSP ya que podría pasar como una tumoración benigna de piel, por lo cual se debe apoyar con el estudio histopatológico frente a la sospecha de este tipo de lesión

Introduction: Dermatofibrosarcoma protuberans (DFSP) is one of the rare tumors found in the fibrohistocytic sarcomas and it is characterized by slow and progressive growth. Methods:A retrospective study of six cases treated at the Skin Center (CEPI) between 2010 and 2019 was carried out. We have take into account demographic information, characteristics, treatment and evolution of the lesions. Results:Six patients were diagnosed and treated by DFSP. There was a predominance of women (4 women, 2 men) with a mean age of 58.2 (SD = 19.6), three of them presented lesions in the form of indurated plaque and the rest presented a unique nodule. The locations of the lesions were the shoulder, neck and hypogastrium. The most commonly used treatment was wide excision, none of the patients presented recurrences at the first and fifth year of follow-up. Conclusion:Recognition of the typical clinical characteristics of DFSP is necessary since it could be mistaken as a benign tumor of the skin. The diagnosis must be always done by histopathological confirmation

Disseminated histiocytic sarcoma in a Labrador retriever in Brazil

Histiocytic sarcoma (HS) refers to a rare neoplasm of round cells frequently presented in a disseminated form, affecting bones, joints, skin, and subcutaneous tissue. The objective of this study was to report a case of disseminated HS in a canine attended at HOVET-UFRPE, Recife, Brazil. Physical examination and complementary tests were performed; complete blood count and serum biochemistry were normal, but at thoracic radiography exam a neoformation was detected in the right lung. Cytopathological evaluation was suggestive of malignant epithelial neoplasia. At necropsy, there were disseminated nodules in the lungs, liver, spleen, kidneys, meninges and eye. The histopathological examination revealed proliferation of pleomorphic round cells, suggesting HS, which was confirmed by immunohistochemistry. From the obtained results, it becomes evident the importance of complementary exams to properly diagnose histiocytic diseases. This is one of the few reports of canine disseminated HS in Brazil.

Disseminated histiocytic sarcoma in a Labrador retriever in Brazil

Histiocytic sarcoma (HS) refers to a rare neoplasm of round cells frequently presented in a disseminated form, affecting bones, joints, skin, and subcutaneous tissue. The objective of this study was to report a case of disseminated HS in a canine attended at HOVET-UFRPE, Recife, Brazil. Physical examination and complementary tests were performed; complete blood count and serum biochemistry were normal, but at thoracic radiography exam a neoformation was detected in the right lung. Cytopathological evaluation was suggestive of malignant epithelial neoplasia. At necropsy, there were disseminated nodules in the lungs, liver, spleen, kidneys, meninges and eye. The histopathological examination revealed proliferation of pleomorphic round cells, suggesting HS, which was confirmed by immunohistochemistry. From the obtained results, it becomes evident the importance of complementary exams to properly diagnose histiocytic diseases. This is one of the few reports of canine disseminated HS in Brazil.(AU)

Bony Histiocytic Sarcoma of the Scapula: Case Report / Sarcoma histiocítico ósseo em escápula: relato de caso

Abstract Case report of a pediatric patient with a diagnosis of bony histiocytic sarcoma of the scapula, submitted to oncologic resection (Tikhoff-Linberg type II surgery), who returned to previous activities and was disease-free after 24 months of follow-up.

Resumo Relato de caso de paciente pediátrico com diagnóstico de sarcoma histiocítico ósseo em escápula, submetido à ressecção oncológica (cirurgia de Tikhoff-Linberg tipo II), com retorno às atividades prévias e livre de doença após 24 meses de seguimento.