Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis.

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.

Long-Term Remission with Novel Combined Immune-Targeted Treatment for Histiocytic Sarcoma Accompanied by Follicular Lymphoma: Case Report and Literature Review.

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.

NF1 mutation and TUBB3 amplification in gastric histiocytic sarcoma: a case report and literature review.

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.

Disseminated histiocytic sarcoma in a degu (Octodon degus).

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.

Atypical disseminated histiocytic sarcoma in a 7-month-old dog.

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.

First description of a primary esophageal histiocytic sarcoma in a dog.

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.

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.

A rare case of primary central nervous system histiocytic sarcoma harboring a novel ARHGAP45::BRAF fusion: a case report and literature review.

INTRODUCTION: Patients with histiocytic sarcoma occurring in the central nervous system (CNS) are rare and have a very poor prognosis. The increased use of molecular diagnostic approaches in solid tumors has brought more opportunities for the diagnosis and treatment of central nervous system histiocytic sarcoma (CNSHS). CASE DESCRIPTION: A 9-year-old girl was admitted to the hospital with pain in her head and neck, as well as vomiting. Imaging scans showed a prominent abnormality in the anterior falciform region, and histopathology revealed the presence of CD68 (+) and CD163 (+) cells, leading to a preliminary diagnosis of primary intracerebral CNSHS. Molecular profiling tests identified a new variant of ARHGAP45::BRAF fusion in this case, which has not been reported in any other tumor. The patient underwent surgical removal of the tumor and will require long-term monitoring. CONCLUSION: The presence of the BRAF point mutation, predominantly BRAF p.V600E, has been documented in prior literature of CNSHS. This is the first case of pediatric histiocytic sarcoma in the anterior falciform region who has a unique ARHGAP45::BRAF fusion. The findings of our study indicate that a broader range of molecular assays should be employed in the diagnosis of CNSHS and opens up new possibilities for the treatment of the patient.

Rosai Dorfman Disease with malignant transformation to Histiocytic Sarcoma: A diagnostic conundrum.

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.

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.

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.

Sarcoma histiocítico cutáneo: Reporte de un caso / Cutaneous histiocytic sarcoma: Report of one case

Histiocytic sarcoma (HS) is a rare hematologic malignancy with morphologic and immunophenotypic evidence of histiocytic differentiation. Previously known as "true histiocytic lymphoma", the tumor follows an aggressive clinical course. Involvement of lymph nodes, skin, and extranodal sites has been described. Among the latter, approximately 29 cases involving the skin have been reported. On pathology, the lesion shows a diffuse proliferation of large epitheloid histiocytes with marked pleomorphism. We report a 78 year-old male who presented with a nodular lesion in the forehead, involving the skin and son tissue. The pathological diagnosis was a HS. The patient waslost from follow up.

Sarcoma histiocítico de intestino delgado: Reporte de un caso y revisión de la literatura / Histiocytic sarcoma of the small intestine: Report of one case

Histiocytic sarcoma (HS) is a rare malignant neoplasm of the lymphohematopoietic system, that occurs in lymph nodes, skin and at extranodal sites, particularly the gastrointestinal tract. Although it shows characteristics histoiogical and immunohistochemical features, it may be misdiagnosed. We report a 67 year-old female patient presenting with colicky abdominal pain and vomiting. A CT sean of the abdomen revealed a tumor in the ileum, that was surgically removed. On pathology, the neoplastic cells displayed large abundant eosinophilic cytoplasm, with bizarre-shaped nuclei, that expressed CD 45, CD 68 and lisozyme. The diagnosis of HS requires the use of a panel of immunohistochemical markers and may be supported by ultrastructural findings .

Biopsia de Medula Osea. Patrones Morfologicos de las Hemopatias y Tumores Solidos en Pediatria / Bone marrow biopsy. Morphological patterns of hemopathies and solid tumours in pediatrics

Se presentan los resultados del estudio de 165 biopsias de medula osea realizadas a pacientes ingresados en el Hospital Pediatrico Docente "Juan Manuel Marques". Las distintas afecciones que motivaron las biopsias fueron: enfermedades hematologicas no malignas, 56 casos; leucemia linfoblastica aguda, 9 casos; leucemia mieloide cronica juvenil, 2 casos; histiocitosis maligna, 1 caso; linfoma no Hoggkin, 25 casos; enfermedad de Hodgkin, 31 casos; neuroblastoma, 13 casos; sarcoma de partes blandas, 11 casos; neuroblastoma, 13 casos; evaluacion del organo posquimioterapia, 17 casos. Se describen las caracteristicas morfologicas de la medula osea en diferentes hemopatias y los patrones de infiltracion de las leucemias y los tumores solidos mas frecuentes en el nino

Reticulosis medular histiocítica / Histiocytic medullary reticulosis

La Reticulosis Medular Histiocítica constituye una neoplasia maligna generalmente fatal en un período corto de tiempo. Los histiocitos atípicos invaden hueso, médula ósea, higado, bazo, intestino, meninges, piel agregando nosotros laringe, localización no referida en la bibliografia consultada. Las lesiones cutáneas constituyen el 10-13% del compromiso general; consisten en tumores queratósicos ulcerados, distribuidos en tronco y miembros. Los métodos inmunohistoquimicos (lisozima, alfa, antitripsina, S-100) son actualmente otro elemento importante de diagnóstico, siendo como en nuestro caso positivos tanto en laringe como piel. La evolución es mala, falleciendo en poco tiempo por sobreinfecciones o bien hemorragias. Nuestra paciente respondió satisfactoriamente a la quimioterapia instituida, en un período de dos años de control.

Sistema histiocítico- macrofágico, suas neoplasias e marcadores / Histiocyte-macrophage system, its neoplasm and tracers

O sistema histiocític-macrofágico é composto por células derivadas da célula primitiva da medula óssea, que se transforma em promonócitos e em monócitos. Nos tecidos, os histiócitos recebem nomes diferentes, como células de Kupffer, células de Langerhans da epiderme, macrófagos alveolares, células do sistema retículo-endotelial, osteoclastos, microglia, células epitelióides e células gigante multinucleadas. Estudos recentes, entretanto, têm demonstrado a heterogeneidade desse sistema, de acordo com a presença de fenótipos imunológicos diferentes. Os histiócitos de zonas T distribuem-se nos órgäos linfóides periféricos em regiöes de células T e compreendem as células de Langerhans da epiderme e células reticulares interdigitantes do linfonodos, baço e medula tímica. Estas células apresentam imunoexpressäo da proteína S-100 por técnicas imuno-histoquímicas. As neoplasias derivadas destas células compreendem as histiocitoses (granuloma eosinófilo, doença de Letterer-Siwe e doença de Hand-Schüller-Christian), assim como a reticulose histiocítica medular, linfo-histiocitose familial e histiocitose maciça sinusoidal. Os monócitos e macrófagos teciduais apresentam imunofenótipos diversos, com demonstraçäo de lisozima, alfa-1-antitripsina e alfa-1-antiquimotripsina por técnicas imuno-histoquímicas. A proteína S-100 é consistentemente negativa nestas células, assim como em neoplasias delas derivadas, correspondendo ao histiocitoma, à histocitose maligna e ao linfoma histiocítico verdadeiro, assim como ao fibro-histiocitoma. A pesquisa imuno-histoquímica de antígenos do sistema histiocític-macrofágico tem-se mostrado de grande valia na identificaçäo e na diferenciaçäo neoplasias deste sistema. As enzimas resistem à fixaçäo e ao processamento do tecido, permitindo estudos retrospectivos e prospectivos de material processado rotineiramente

A punçåo aspirativa no diagnóstico das linfadenopatias: citomorfologia e imunocitoquímica / Aspiration biopsy in the diagnosis of lymphadenopathies: cytomorphology and immunocytochemistry

A fim de avaliar a eficácia da punçåo aspirativa no diagnóstico das linfadenopatias, utilizando conjuntamente a citomorfologia e imunocitoquímica, foi examinado o material aspirado, com agulha fina, de lifonodos aumentados em 75 pacientes. Os resultados obtidos foram comparados com o estudo histológico e imunohistoquímica e descritos os aspectos citólogicos encontrados nas diversas linfadenopatias. A punçåo aspirativa fez o diagnóstico em 29 neoplasias metastáticas, 13 linfomas nåo Hodgkin, três casos de doença de Hodgkin, 10 linfadenites reacionais, 15 linfadenites granulomatosas e dois casos de doença de Rosai-Dorfman. Um caso de linfoma de células T, de baixo grau, e dois casos de doença de Rosai-Dorfman. Um caso de linfoma de células T, de baixo grau, e dois casos de histiocitoses maligna nåo foram diagnosticados. Obteve-se uma sensibilidade de 93 por cento e uma especificidade de 100 por cento. A associaçåo da citomorfologia com a imunocitoquímica melhorou a acurácia da punçåo aspirativa no diagnóstico das linfadenites reacionais e linfomas nåo Hodgkin. Conclui-se que a punçåo aspirativa pode contribuir para uma maior eficiência e rapidez de diagnóstico nas linfadenopatias, reduzindo a necessidade de biópsia e diminuindo os custos da avaliaçåo diagnóstica

Histiocitosis maligna en el niño / Malignant histiocytosis in children

Reportamos un caso de histiocitosis maligna en un niño de 2 años de edad. Las manifestaciones clínicas más importantes fueron fiebre, compromiso del estado general, adenopatías generalizadas y hepatoesplenomegalia. La biopsia ganglionar demostró proliferación de células de tipo histiocítico con marcadas atipias eritrofagocitosis y un patrón de infiltración de tipo sinusal. El compromiso hepático fue demostrado mediante biopsia hepática por punción. La evolución fue progresiva y fatal después de 6 meses de tratamiento quimioterápico

Histiocitosis maligna: reporte de un caso / Malignal hystiocytosis: report of a case

Reportamos un caso de histiocitosis maligna con compromiso fundamentalmente ganglionar, que comprometía las cadenas cervical y mediastínica y que llega a dar "edema en esclavina". Se revisan las características histológicas, citológicas, inmunológicas y bioquímicas que caracterizan a esta entidad, así como la bibliografía respectiva