RESUMO
Histiocytic sarcoma (HS) is a rare hematopoietic neoplasm with an aggressive clinical course and a poor response to conventional chemotherapy. Currently, no standard treatment paradigms are available. Herein, we present a case of de novo HS treated with pembrolizumab combined with a GDP regimen (gemcitabine, cisplatin, and dexamethasone) that resulted in sustained complete remission with progression-free survival exceeding 4 years. Immunohistochemical analysis demonstrated significant overexpression of programmed death ligand 1 (PD-L1) on biopsy samples. Additionally, fluorescence in situ hybridization (FISH) with a JAK-2 probe indicated 9p24.1 amplification, suggesting reliance on the JAK-STAT pathway. Polymerase chain reaction (PCR) analysis did not reveal any BRAF-V600 mutations. Consequently, an immune checkpoint inhibitor (ICI) was administered alongside chemotherapy, resulting in sustained complete remission and progression-free survival for over 4 years. Our findings suggest that a combination of ICI and chemotherapy could represent a promising therapeutic approach for HS.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Desoxicitidina , Dexametasona , Gencitabina , Sarcoma Histiocítico , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Indução de Remissão , Masculino , Inibidores de Checkpoint Imunológico/uso terapêutico , Pessoa de Meia-Idade , Intervalo Livre de Progressão , FemininoRESUMO
Histiocytic sarcoma (HS) is a rare and highly aggressive cancer in humans and dogs. In dogs, it has a high prevalence in certain breeds, such as Bernese mountain dogs (BMDs) and flat-coated retrievers. Hemophagocytic histiocytic sarcoma (HHS) is a unique form of HS that presents with erythrophagocytosis. Due to its rareness, the study of HHS is very limited, and mutations in canine HHS patients have not been studied to date. In previous work, our research group identified two major PTPN11/SHP2 driver mutations, E76K and G503V, in HS in dogs. Here, we report additional mutations located in exon 3 of PTPN11/SHP2 in both HS and HHS cases, further supporting that this area is a mutational hotspot in dogs and that mutations in tumors and liquid biopsies should be evaluated utilizing comprehensive methods such as Sanger and NextGen sequencing. The overall prevalence of PTPN11/SHP2 mutations was 55.8% in HS and 46.2% in HHS. In addition, we identified mutations in KRAS, in about 3% of HS and 4% of HHS cases. These findings point to the shared molecular pathology of activation of the MAPK pathway in HS and HHS cases. We evaluated the efficacy of the highly specific MEK inhibitor, cobimetinib, in canine HS and HHS cell lines. We found that the IC50 values ranged from 74 to 372 nM, which are within the achievable and tolerable ranges for cobimetinib. This finding positions cobimetinib as a promising potential candidate for future canine clinical trials and enhances our understanding of the molecular defects in these challenging cancers.
Assuntos
Azetidinas , Sarcoma Histiocítico , Mutação , Piperidinas , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Proteínas Proto-Oncogênicas p21(ras) , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Piperidinas/farmacologia , Cães , Animais , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/veterinária , Sarcoma Histiocítico/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Azetidinas/farmacologia , Doenças do Cão/genética , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular TumoralRESUMO
Oncolytic viruses and morbilliviruses in particular, represent an interesting therapeutic approach for tumors with a poor prognosis and frequent resistance to conventional therapies. Canine histiocytic sarcomas (HS) exemplify such a neoplasm in need for new curative approaches. Previous investigations demonstrated a limited success of an acute intratumoral application of canine distemper virus (CDV) on xenotransplanted canine histiocytic sarcoma cells (DH82 cells), while persistently CDV-infected DH82 cell transplants exhibited a complete spontaneous regression. Therefore, the present study focuses on an intratumoral application of persistently CDV vaccine strain Onderstepoort-infected DH82 (DH82 Ond p.i.) cells into non-infected subcutaneous DH82 cell transplants in a murine model. DH82 cell transplants that received 10 applications, two days apart, showed a transient growth retardation as well as larger areas of intratumoral necrosis, lower mitotic rates, and a decreased intratumoral vascularization compared to controls. Viral mRNA was detected in all neoplasms following application of DH82 Ond p.i. cells until 66 days after the last injection. Furthermore, infectious virus was present until 62 days after the last injection. Although complete regression was not achieved, the present application regimen provides promising results as a basis for further treatments, particularly with genetically modified viruses, to enhance the observed effects.
Assuntos
Vírus da Cinomose Canina , Sarcoma Histiocítico , Terapia Viral Oncolítica , Animais , Vírus da Cinomose Canina/patogenicidade , Vírus da Cinomose Canina/genética , Cães , Sarcoma Histiocítico/virologia , Camundongos , Terapia Viral Oncolítica/métodos , Linhagem Celular Tumoral , Cinomose/virologia , Vírus Oncolíticos/genética , Vírus Oncolíticos/fisiologiaRESUMO
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
Histiocytic sarcoma (HS) is an extremely rare but aggressive hematopoietic malignancy, and the prognosis has been reported to be rather unfavorable with a median overall survival of merely 6 months. We presented a 58-year-old female patient complaining of abdominal pain and fever, who was admitted to our institution in September 2021. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scan showed enlargement of generalized multiple lymph nodes. Subsequently, laparoscopic retroperitoneal lesion biopsy and bone marrow aspiration were performed. The pathological findings indicated the diagnosis of HS concurrent with follicular lymphoma. The immunohistochemistry (IHC) staining of the tumor lesion revealed a high expression of CD38 and PD-L1 proteins. Furthermore, KRAS gene mutation was identified by means of next-generation sequencing. The patient exhibited poor treatment response to both first- and second-line cytotoxic chemotherapies. Therefore, she underwent six cycles of Daratumumab (anti-CD38 monoclonal antibody), Pazopanib (multi-target receptor tyrosine kinases inhibitor) combined with third-line chemotherapy, followed by involved-site radiotherapy and maintenance therapy with the PD-1 inhibitor Tislelizumab. Long-term partial remission was finally achieved after multi-modality treatment. Duration of remission and overall survival reached 22 and 32 months, respectively. Our case indicated that immuno-targeted treatment coupled with chemotherapy and radiotherapy might constitute a potential therapeutic option for HS.
Assuntos
Sarcoma Histiocítico , Linfoma Folicular , Humanos , Feminino , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/terapia , Linfoma Folicular/patologia , Pessoa de Meia-Idade , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/patologia , Sarcoma Histiocítico/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Indução de RemissãoRESUMO
The African pygmy hedgehog (Atelerix albiventris) is known to have a high incidence of tumor. However, investigating the tumors of this species has been constrained by the limited availability of research materials such as cell lines and genome information. In this study, we successfully established a novel cell line from a histiocytic sarcoma (HS) of an African pygmy hedgehog, allowing us to conduct a drug screening. We investigated using FDA-approved drug library screening to determine which anticancer drug this tumor cell line is sensitive to, and as a result of apoptosis experiments, bortezomib among the three proteasome inhibitors was found to induce cell death of cancer cells by significantly increasing caspase-3 cleavage (P<0.01). Thus, we elucidated that the proteasome inhibitors, particularly bortezomib, exhibit anti-tumor effects on a cell line derived from an HS in an African pygmy hedgehog through a mechanism comparable to that described in human tumors. This study reports the first characterized cell line from the African pygmy hedgehog and also highlights the potential utility of bortezomib as an anti-tumor treatment for HS in this species.
Assuntos
Antineoplásicos , Bortezomib , Ouriços , Sarcoma Histiocítico , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/veterinária , Apoptose/efeitos dos fármacosRESUMO
The precise cause of HS/DCS is still unknown. The relatively low incidence in humans urges for an animal model with a high incidence to accelerate knowledge about genetics and optimal treatment of HS/DCS. Namely, until now, the therapies targeting genetic variants are still more experimental and sparsely used, while consensus is missing. In addition, the literature about variants and possible mutation-targeted therapies in humans and dogs consists mainly of case reports scattered throughout the literature. Therefore, an overview is provided of all currently known genetic variants in humans and dogs with HS/DCS and its subtypes, their possible mutation-targeted therapies, their efficacy, and a contemplation about the future. Several genetic variants have already been discovered in HS/DCS, of which many are shared between canine and human HS/DCS, but unique variants exist as well. Unfortunately, none of these already found variants seem to be specifically causal for HS/DCS, and the puzzle of its landscape of genetic variation is far from complete. The use of mutation-targeted therapies, including MAPK-/MEK-inhibitors and the future use of PTPN11-, CDK4/6- and PD-1-inhibitors, seems to be promising for these specific variants, but clearly, clinical trials are needed to determine optimal inhibitors and standardised protocols for all variants. It can be concluded that molecular analysis for variants and subsequent mutation-targeted therapy are an essential addition to cancer diagnostics and therapy. A joint effort of humans and dogs in research is urgently needed and will undoubtedly increase knowledge and survival of this devastating disease in dogs and humans.
Assuntos
Doenças do Cão , Variação Genética , Cães , Doenças do Cão/genética , Doenças do Cão/tratamento farmacológico , Animais , Humanos , Saúde Única , Sarcoma Histiocítico/veterinária , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma/veterinária , Sarcoma/genética , Sarcoma/tratamento farmacológico , Sarcoma/terapia , Células DendríticasRESUMO
Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course and poor response to treatment. Primary gastric histiocytic sarcoma is rarer and just reported sporadically.Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course and poor response to treatment. Primary gastric histiocytic sarcoma is rarer and just reported sporadically. A case of a 71-year-old female admitted with a one-year history of upper abdominal pain exacerbated after meals. After CT scans revealed a bulged mass at the lesser curvature of the gastric body, the patient underwent endoscopic submucosal dissection. Microscopically, non-cohesive neoplastic cells diffusely infiltrated lamina propria and submucosa, and diffusely expressed LCA, CD4, CD163, CD68 (KP1), Cyclin D1, Lysozyme, and Vimentin. PD-L1 (22CS) expression evaluated as CPS 60. The final pathological diagnosis was gastric histiocytic sarcoma. Subsequently, next-generation sequencing identified a nonsense mutation in exon 21 of NF1 gene [c.2446C > T (p.R816*)] and the TUBB3 gene amplification (copy number: 4.55). The patient refused further treatment and died of the tumor half a year later. This case broadens the spectrum of differential diagnosis of gastric cancer and emphasizes the value of immunohistochemical and molecular tests in the accurate diagnosis of histiocytic sarcoma. Furthermore, we performed literature review of 11 cases of gastric histiocytic sarcoma so as to strengthen the understanding of the clinicopathologic features, treatment, and prognosis.
Assuntos
Sarcoma Histiocítico , Neurofibromina 1 , Neoplasias Gástricas , Tubulina (Proteína) , Humanos , Feminino , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/patologia , Sarcoma Histiocítico/cirurgia , Idoso , Neurofibromina 1/genética , Tubulina (Proteína)/genética , Amplificação de Genes , Mutação , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
A 7-year-and-8-month-old, male degu (Octodon degus) with anorexia, depression, and labored breathing was found to have a thoracic effusion and enlargement of the right testis on radiographic examination. Despite treatment, the animal died. At necropsy, hepatomegaly, splenomegaly, and multifocal nodules on the intestinal serosa and mesentery were observed. Histologically, the foci were densely cellular invasive neoplasms composed of sheets of round to polygonal cells, with occasional multinucleated giant cells. Immunohistochemically, the neoplastic cells were immunopositive for ionized calcium-binding adapter molecule 1, human leukocyte antigen-DR, and CD204. These findings were consistent with disseminated histiocytic sarcoma.
Assuntos
Sarcoma Histiocítico , Octodon , Animais , Sarcoma Histiocítico/veterinária , Sarcoma Histiocítico/patologia , Masculino , Evolução FatalRESUMO
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
Histiocytic sarcoma is an aggressive haematopoietic malignancy accounting for less than 1% of haematolymphoid neoplasms with a diagnosis based on morphology and immunophenotype of tissue biopsies with a very poor prognosis. Here, we report a 45-year-old man who was diagnosed with primary pulmonary histiocytic sarcoma with systemic metastases, with partial remission (PR) treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but it relapsed soon after therapy above. Tests demonstrated that TMB was 21 Muts/Mb PD-L1 expression was 90% positive, and the disease has been well-controlled over 3 years using immune checkpoint inhibitors (nivolumab and pembrolizumab). Bioinformatic pan-cancer analysis verified that there was the highest genetic alteration frequency of PD-L1 in which amplification accounted for the majority of sarcoma tumour samples. Following that, we found that the genetic alteration of PD-L1 was associated with poor prognosis in sarcoma patients in terms of overall survival (OS) (p = 1.51 × 10-4 ), progress-free survival (PFS) (p = 4.90 × 10-2 ) and disease-specific survival (DSS) (p = 4.90 × 10-2 ). To our knowledge, this may be the first reported case with high PD-L1 expression in primary pulmonary histiocytic sarcoma who may benefit from immunotherapy such as nivolumab and pembrolizumab significantly and safely.
Assuntos
Sarcoma Histiocítico , Neoplasias Pulmonares , Sarcoma , Masculino , Humanos , Pessoa de Meia-Idade , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/genética , Antígeno B7-H1/genética , Nivolumabe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Imunoterapia , Biologia ComputacionalRESUMO
Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC). The median age at diagnosis was 61 years (range, 3-83). Thirty-three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8-50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first-line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.
Assuntos
Sarcoma Histiocítico , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/terapia , Sarcoma Histiocítico/patologia , Macrófagos/patologia , Medula Óssea/patologia , Prognóstico , Fígado/patologiaRESUMO
ABSTRACT: Histiocytic disorders mostly occur as de-novo nodal or extranodal benign masses with rare secondary malignant transformation. A 10-year-old female presented with 10-cm cervical swelling since 9 months associated with fever. Computed tomography revealed left cervical lymphadenopathy and bilateral lung nodules. Lymph node excision biopsy showed effacement of architecture by atypical histiocytes with marked nuclear pleomorphism and frequent mitosis. Focal areas showed mature histiocytes with emperipolesis. The cells were immunopositive for CD68, CD163, and S100 (focal), whereas they were negative for Langerin and CD1a. The Ki67 proliferative index was 30%. A diagnosis of histiocytic sarcoma in a background of Rosai-Dorfman disease was made.
Assuntos
Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Sarcoma Histiocítico , Histiocitose Sinusal , Imuno-Histoquímica , Tomografia Computadorizada por Raios X , Humanos , Feminino , Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/patologia , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/patologia , Criança , Antígenos CD/análise , Proteínas S100/análise , Histiócitos/patologia , Linfonodos/patologia , Biópsia , Histocitoquímica , Transformação Celular Neoplásica , Microscopia , Receptores de Superfície Celular/genética , Linfadenopatia/patologia , Molécula CD68RESUMO
An 11-year-old male Schnauzer dog was referred for investigation of cough and regurgitation of one month duration and gradual hyporexia for the previous five months. Complete blood count showed severe leukocytosis. On ventrodorsal and lateral thoracic radiographs a soft tissue mass was visible in the craniodorsal mediastinum. Endoscopy showed esophageal dilatation and an irregular, nodular, friable, exophytic mass in the thoracic esophagus, which was invasive, vascularized and had ulcerated areas. The mass occluded approximately 90% of the esophageal lumen. The mucosa in the orad portion of the thoracic esophagus was pale and the aborad portion was hyperemic (red) with hemorrhages. The mucosa of the cervical and abdominal esophagus was macroscopically unremarkeble. Multiple biopsies using endoscopic cup biopsy forceps were taken from the mass for histopathologic analysis and a percutaneous endoscopic gastrostomy was performed. Histopathologic analysis of the biopsy samples was inconclusive due to the marked necrosis. The poor clinical condition of the dog precluded a more invasive approach, and palliative and supportive treatment was continued. After 100 days of follow-up, clinical signs worsened, and that day the dog had a fatal cardiac arrest due to aspiration pneumonia and sepsis. Postmortem examination showed a multilobulated mass in the esophageal wall with infiltration into the overlying esophageal mucosa and pulmonary and renal metastases. Histological examination revealed a poorly differentiated sarcoma. On immunohistochemical examination, the neoplastic cells showed marked cytoplasmic staining for vimentin and Iba-1. The proliferative rate was approximately 30% by Ki-67. Histological and immunohistochemical examination revealed the esophageal mass to be a primary histiocytic sarcoma. Histiocytic sarcoma is an extremely rare primary esophageal neoplasm in humans, and so far, there is no description in dogs. To the best of the authors knowledge this is the first case of primary esophageal histiocytic sarcoma in dogs. The clinical information reported here should improve recognition and aid in diagnosis of future cases.
Assuntos
Doenças do Cão , Neoplasias Esofágicas , Sarcoma Histiocítico , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Masculino , Cães , Animais , Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/patologia , Sarcoma Histiocítico/veterinária , Sarcoma/veterinária , Neoplasias Esofágicas/veterinária , Neoplasias de Tecidos Moles/veterinária , Doenças do Cão/diagnósticoRESUMO
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
ABSTRACT: Histiocytic sarcoma is a tumor of the lymphohematopoietic system characterized by macrophage morphology and immunophenotype. Here, we report FDG PET/CT images of a 50-year-old man with coexisting histiocytic sarcoma of the liver and spleen. Images showed multiple enhanced uptake lesions of FDG in both the liver and spleen. Ultimately, histiocytic sarcoma was confirmed by the biopsy histopathology.
Assuntos
Sarcoma Histiocítico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Masculino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Sarcoma Histiocítico/diagnóstico por imagem , Fluordesoxiglucose F18 , Baço/diagnóstico por imagem , Baço/patologia , Fígado/diagnóstico por imagem , Fígado/patologiaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Sarcoma Histiocítico , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Sarcoma Histiocítico/diagnóstico , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Rituximab/uso terapêutico , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Development of secondary tumor after CART treatment is not well investigated. We report a pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient who developed histiocytic sarcoma shortly after CART therapy. CASE REPORT: A 9-year-old boy diagnosed with relapsed B-ALL presenting the KRAS A146T mutation received autologous mouse-derived CD19 and CD22 chimeric antigen receptor T-cell therapy at our center (Chinese Clinical Trial Registry: ChiCTR2000032211). Thirty days post-CART therapy, the bone marrow showed complete remission. At 85 days post-CART therapy, the boy presented with fever and chills. An abdominal CT scan showed massive hepatomegaly with multiple low-density lesions in the liver. At 130 days post-CART therapy, a bone marrow smear showed abnormal proliferation of macrophages, some of which exhibited phagocytosis. On day 136 post-CART therapy, laparoscopic liver biopsy was performed, revealing multiple yellow-white lesions on the surface of the liver. Microscopically, multifocal lesions were observed, predominantly composed of cells with abundant cytoplasm. Immunohistochemical staining indicated histiocytic origin. Based on the immunohistochemical results, histiocytic sarcoma was diagnosed. The same cytogenetic markers were identified in histiocytic sarcoma. CONCLUSION: Our case illustrates a rare complication after CART therapy. The diagnosis and treatment of histiocytic sarcoma pose many challenges.
Assuntos
Sarcoma Histiocítico , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Masculino , Humanos , Criança , Animais , Camundongos , Imunoterapia Adotiva/métodos , Sarcoma Histiocítico/etiologia , Sarcoma Histiocítico/terapia , Antígenos CD19 , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Medula Óssea/patologiaRESUMO
A 7-month-old intact female bearded collie dog was admitted after a 2-week history of progressive cough, inappetence, and lethargy, with no response to previous treatment with doxycycline and steroids. Mild attenuation of lung sounds in the right middle hemithorax was the only abnormality detected on physical examination. Abdominal ultrasound and thoracic radiographs were performed and revealed multifocally distributed nodules and masses, well-circumscribed and of variable size in the kidneys and pulmonary parenchyma. Ultrasound-guided fine needle aspirates of the renal and pulmonary masses were taken. A cytologic evaluation of these lesions pointed towards a malignant mesenchymal neoplasia. Euthanasia was elected due to the poor prognosis and rapid progression. The post-mortem histopathology, a positive result to IBA1 immunoperoxidase staining, and a lack of detection of infectious agents, and negative E-cadherin immunostaining enabled the final diagnosis of a disseminated histiocytic sarcoma. We report an atypical form, both in breed and age, of canine disseminated histiocytic sarcoma. While all breeds can be affected, there is a clear predisposition in some, and no cases have been previously described in bearded collies. Moreover, to the authors' knowledge, this is the youngest dog with this histiocytic disorder described to date. Disseminated histiocytic sarcoma should be considered as a differential diagnosis of multinodular tumors in dogs, regardless of the anatomic location and age of the dogs, even in puppies.