RESUMO
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.
Assuntos
Classe I de Fosfatidilinositol 3-Quinases , Sarcoma Histiocítico , Imuno-Histoquímica , Neoplasias Bucais , Mutação , Proteínas Proto-Oncogênicas B-raf , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Masculino , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/patologia , Feminino , Pessoa de Meia-Idade , Classe I de Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Adulto , Biomarcadores Tumorais/genética , Idoso , Reação em Cadeia da PolimeraseRESUMO
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.
Assuntos
Sarcoma Histiocítico , Linfoma Anaplásico de Células Grandes , Humanos , Feminino , Pessoa de Meia-Idade , Sarcoma Histiocítico/patologia , Sarcoma Histiocítico/genética , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico de Células Grandes/diagnóstico , Quinase do Linfoma Anaplásico/genética , Diagnóstico Diferencial , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Neoplasias Torácicas/patologia , Neoplasias Torácicas/genéticaRESUMO
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.
Assuntos
Sarcoma Histiocítico , Neoplasias Cutâneas , Tumores Venéreos Veterinários , Feminino , Masculino , Cães , Animais , Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/veterinária , Vimentina , Tumores Venéreos Veterinários/patologia , Imuno-Histoquímica , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/veterinária , Neoplasias Cutâneas/patologia , Caderinas/metabolismoRESUMO
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.
Assuntos
Doenças do Cão , Hemangiossarcoma , Sarcoma Histiocítico , Linfoma , Animais , Cães , Humanos , NF-kappa B/metabolismo , Sarcoma Histiocítico/veterinária , Hemangiossarcoma/veterinária , Mastócitos , Subunidade p52 de NF-kappa B/metabolismo , Linfoma/veterináriaRESUMO
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)
Assuntos
Animais , Doenças do Cão , Sarcoma Histiocítico/veterinária , Hemangiossarcoma/diagnóstico , CãesRESUMO
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.
Assuntos
Caniformia , Otárias , Herpesviridae , Sarcoma Histiocítico , Animais , Brasil/epidemiologia , Sarcoma Histiocítico/veterináriaRESUMO
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.
Assuntos
Sarcoma Histiocítico , Linfo-Histiocitose Hemofagocítica , Adulto , Sequenciamento de Nucleotídeos em Larga Escala , Histiócitos/patologia , Sarcoma Histiocítico/complicações , Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/genética , Humanos , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Masculino , Mutação , Receptor Notch2/genética , Baço/patologia , Baço/cirurgia , Tirosina Quinase 3 Semelhante a fmsRESUMO
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.
Assuntos
Humanos , Trichosporon , Sarcoma Histiocítico/tratamento farmacológico , Tricosporonose/diagnóstico , Tricosporonose/tratamento farmacológico , Basidiomycota , Antifúngicos/uso terapêuticoRESUMO
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.