Histiocytic sarcoma is a malignant neoplasm with cells showing morphologic and immunohistochemical features of histiocytes. The lung and stomach are rare sites of involvement, and few have been reported in the existing literature. We report a 72-year-old woman with primary histiocytic sarcoma involving the right lung, stomach, and bilateral adrenal glands. Computed tomography revealed a large heterogeneous mass in the upper lobe of the right lung, regional lymphadenopathy, and masses within the bilateral adrenal glands. Gastric involvement was discovered via polypectomy during a routine gastric endoscopy. Morphologically, the lung and stomach specimens showed sheets of large and spindle cells with increased mitotic figures. Immunohistochemical staining revealed CD163, CD68, and CD4 expression in the lung tumor and CD163 and CD4 in the gastric tumor. The patient deteriorated rapidly and died of a pulmonary infection two months after diagnosis. Surgical resection remains the most effective treatment. However, for those with advanced disease, systemic chemotherapy alone may be the only available option, but the outcomes are variable. Advancements in targeted therapy are needed to improve treatment outcomes for patients with multi-organ involvement of histiocytic sarcoma.

Viral infections in humans and animals are increasing, and retrospective studies using formalin-fixed, paraffin-embedded (FFPE) samples reveal recurring outbreaks over past decades. However, the impact of pre-analytical factors like fixation and autolysis on immunohistochemistry (IHC) remains insufficiently understood. To examine how autolysis, fixation duration (6–72 h) and formalin concentration (2.5–25%) influence histology and IHC of canine distemper virus (CDV, Morbillivirus canis), interferon-β (IFN-β), and selected IFN-stimulated genes (ISGs), the study was conducted using an in vitro model based on persistently CDV-infected and non-infected DH82 cells (canine histiocytic sarcoma cell line). Autolysis led to a progressive loss of cell morphology, whereas formalin fixation had minimal impact. CDV nucleoprotein, ISG15, and myxovirus resistance protein (Mx) showed stable immunohistochemical signals across all fixation conditions and remained detectable after prolonged autolysis. CDV infection upregulated ISG15 and Mx. In contrast, IFN-β and phosphorylated protein kinase R (pPKR) exhibited variable staining and did not distinguish infected from non-infected samples. Overall, autolysis had a stronger negative impact on IHC signal quality than fixation parameters. Despite the limitations of the in vitro model, the robustness of CDV, ISG15, and Mx under suboptimal conditions highlights their potential utility as virus-sensing markers in FFPE material.

To investigate the diagnostic value of Interferon regulatory factor 8 (IRF8) in blastic plasmacytoid dendritic cell neoplasm (BPDCN) and extranodal NK/T-cell lymphoma, nasal type (ENKTL). Immunohistochemistry staining was used to detect IRF8 expression in 19 cases of BPDCN and 59 cases of ENKTL. In addition, 21 cases of myeloid sarcoma, 30 of B-lymphoblastic leukemia/lymphoma (B-ALL/LBL), 30 of T-lymphoblastic leukemia/lymphoma (T-ALL/LBL), 10 of histiocytic sarcoma, 10 of Langerhans cell histiocytosis, and 9 of follicular dendritic cell sarcoma were also included. DNA sequencing detected IRF8 genetic variation in 6 cases of BPDCN and 20 cases of ENKTL. IRF8 expression was detected in 100.00% (19/19) of BPDCN, exhibiting a strong and uniform staining pattern, and in 91.53% (54/59) of ENKTL, with varying degrees of staining intensity. Weak and focal staining was detected in 33.33% (7/21) of myeloid sarcoma, 13.33% (4/30) of B-ALL/LBL, and 11.11% (1/9) of follicular dendritic cell sarcoma. No expression was found in T-ALL/LBL, histiocytic sarcoma, or Langerhans cell histiocytosis. The proportion of IRF8 positive expression was higher in BPDCN and ENKTL than in other hematolymphoid neoplasms. In ENKTL, the average IRF8 expression was higher in nasal cases than in extranasal cases and in cases with mitosis figures of more than 4/10 high-power field (HPF). Predominantly large transformed cell morphology and extranasal involvement site might serve as independent prognostic factors of two-year survival in ENKTL. IRF8 genetic point mutations were found in 33.33% (2/6) of BPDCN and 10.00% (2/20) of ENKTL. The study demonstrated the promising value of IRF8 in the diagnosis of BPDCN and ENKTL.

This report presents a case of esophageal and nodal metastasis in a primary pulmonary histiocytic sarcoma in a dog. Histiocytic sarcoma is a malignant neoplasm originating from histiocytic cells, characterized by its aggressive nature, high metastatic potential and high mortality rate. Pulmonary involvement occasionally results in pleural effusion and regional lymph node involvement, such as the tracheobronchial, sternal, and mediastinal lymph nodes. Thoracic radiography is the preferred complementary diagnostic test when respiratory disorders are suspected, as it can identify pulmonary masses and associated complications, such as pleural effusion. Similarly, ultrasonography can be used when pulmonary conditions are suspected, helping to differentiate lesions. A one-year-old, intact male mixed-breed dog weighing 18kg was referred for emergency clinical care due to severe inspiratory dyspnea. Thoracic radiography and ultrasonography revealed a large intrathoracic mass located in the mediastinum, displacing adjacent structures, along with associated pleural effusion. The primary diagnostic hypothesis was a neoplasm of cranial mediastinal origin. During the thoracocentesis procedure, the animal decompensated and died. Necropsy revealed a large, multilobulated tumor mass in the mediastinum, showing direct extension into the esophagus, as well as another nodule similar to the mediastinal mass in the left caudal lung lobe. Histopathological analysis supported the diagnosis of pulmonary histiocytic sarcoma with esophageal and nodal metastasis, confirmed through an immunohistochemical panel. The involvement of cranial mediastinal and tracheobronchial lymph nodes, as well as the presence of pleural effusion, are common features associated with HS. However, the occurrence of esophageal metastases is considered uncommon, highlighting the uniqueness of this case, as well as supporting the potential for its occurrence. Thoracic radiography and ultrasonography played a crucial role in the initial suspicion of neoplasia, emphasizing their importance in early diagnostic approaches.

Abstract Background Primary central nervous system histiocytic sarcoma (PCNSHS) is a rare malignant neoplasm of histiocytic origin. Its clinical features, optimal management, and outcomes remain poorly defined. Methods We systematically reviewed PubMed, MEDLINE, Web of Science, Scopus, and Cochrane Library. Thirty-nine studies (35 case reports, 4 case series) describing 47 patients with PCNSHS were included. Clinical presentation, imaging findings, treatment modalities, and outcomes were analyzed. Results The mean age at diagnosis was 43.6 years (range 17 months–84 years); 51% were male. Headache (38%), vomiting (23%), and gait instability (23%) were the most frequent presenting symptoms. Lesions were solitary in 55% and multifocal in 44%. Contrast enhancement was reported in 81%, and peritumoral edema in 34%. Surgery was performed in 26 patients (55%), with gross total resection (GTR) in 13 (28%). Chemotherapy and radiotherapy were administered in 51% and 53% of cases, respectively. Median overall survival (OS) was 7.5 months (range 1–70 months). GTR was associated with longer survival compared to non-GTR (median OS 16 vs. 6 months; HR 6.67, 95% CI 1.82–25.0; p = 0.004). Radiotherapy improved survival (8 vs. 4.6 months; HR 2.71, 95% CI 1.31–5.63; p = 0.007). Chemotherapy showed a nonsignificant trend toward benefit (8 vs. 5 months; HR 1.56, 95% CI 0.78–3.12; p = 0.205). Solitary lesions correlated with improved outcomes. Conclusion PCNSHS is an aggressive tumor with a poor prognosis (median OS 7.5 months). Accurate diagnosis requires comprehensive imaging and immunohistochemistry to exclude mimickers. Multimodal therapy—particularly GTR and radiotherapy- appears to prolong survival, underscoring the need for collaborative efforts and prospective studies.

The molecular landscape of patients with malignant histiocytosis

A fixed-duration, chemo-sparing approach in CLL: 8-year results of the phase 2 icll-07 filo trial

Abstract Introduction/Objective Histiocytic sarcoma (HS) is a rare hematolymphoid malignancy, accounting for less than 1% of all hematologic neoplasms. While most cases arise de novo, rare instances of HS have been reported as transformations from pre-existing B-cell lymphomas, particularly follicular lymphoma (FL). These transformations, though uncommon, illustrate lineage plasticity and are supported by molecular studies demonstrating clonal relationships between the original FL and subsequent HS. Transformation can occur metachronously, synchronously, or even within the same lymph node. The pathogenesis of this phenomenon is not fully understood but is thought to involve direct transdifferentiation, dedifferentiation followed by reprogramming, or evolution from a common progenitor clone. Epigenetic reprogramming and activation of the MAPK/ERK pathway have been implicated. Clinically, transformation often presents with rapid disease progression and extranodal involvement. Diagnosis requires careful histopathologic and immunophenotypic evaluation, often supplemented by molecular testing. HS can mimic other neoplasms such as myeloid sarcoma, adding to diagnostic complexity. Recognition of this rare transformation is critical, as HS carries a poor prognosis and requires intensive treatment strategies. We present a case of histiocytic sarcoma in a patient with a history of follicular lymphoma, with molecular studies confirming a clonal relationship between the two neoplasms. Methods/Case Report A 56-year-old man with a history of follicular lymphoma presented with an enlarged tonsil, lymphadenopathy, and a rapidly growing cervical mass. Imaging raised clinical suspicion for disease progression with transformation to diffuse large B-cell lymphoma (DLBCL). Tonsillar biopsy showed small atypical lymphoid cells in a nodular pattern, positive for CD20, PAX5, CD10, BCL6, and BCL2, and a low Ki67 proliferation index consistent with persistent low-grade follicular lymphoma. Due to ongoing concern for transformation, a cervical lymph node biopsy was performed. This revealed large, pleomorphic cells with amphophilic cytoplasm, negative for multiple B-cell markers (CD19, CD20, CD22, PAX5, CD79a). Additional immunohistochemical studies showed positivity for CD163, CD68, CD4, and lysozyme, and negativity for CD34, CD117, and myeloperoxidase, supporting a diagnosis of histiocytic sarcoma. FISH analysis detected t(14;18) in both the follicular lymphoma and histiocytic components, and clonality studies showed identical IGH gene rearrangements, establishing a clonal relationship and supporting transdifferentiation of follicular lymphoma to histiocytic sarcoma. Next-generation sequencing is underway to identify actionable mutations for potential future targeted therapies. Results NA Conclusion This case highlights a rare but clinically significant transformation of FL into HS, confirmed by molecular evidence of clonal relatedness. HS is an exceptionally rare malignancy with an aggressive clinical course and poor prognosis, even with intensive therapy. Diagnosis requires a high index of suspicion, especially in patients with a history of indolent B-cell lymphoma who present with rapid clinical progression or atypical extranodal disease. Management of HS remains challenging due to the absence of standardized treatment protocols. Current approaches often involve a combination of surgical resection and aggressive chemotherapy, although outcomes are generally poor. In cases where HS arises from FL, therapies typically used for B-cell lymphomas may offer clinical benefit. A case report demonstrated efficacy of rituximab and bendamustine, achieving durable remission in patient with HS transformed from FL. Establishing a clonal relationship between HS and the antecedent lymphoid neoplasm is not only diagnostically valuable but may also inform therapeutic decisions. This case underscores the importance of integrating clinical, histopathologic, immunophenotypic, and molecular data to accurately diagnose such cases and guide management in this rare and diagnostically challenging transformation.

Abstract Introduction/Objective Extra-nodal histiocytic sarcoma is an extremely rare neoplasm that has mostly polygonal cell morphology. It can remain localized to a single organ or become disseminated. Histiocytic sarcoma is not a true mesenchymal sarcoma but rather a hematopoietic neoplasm, due to characteristic mature tissue histiocytic differentiation. Cutaneous histiocytic sarcoma with spindle cell morphology has only been previously reported as a single case, showing predominant polygonal cells, with focal spindle cell morphology. Our case is unique in showing predominant spindle cell morphology, thereby mimicking mesenchymal sarcoma. Methods/Case Report A 37-year-old female presented for a rapidly-growing, fungating, ulcerated, soft tissue mass on the right anterior thigh, which was resected and submitted to surgical pathology. Results The tumor mass was demonstrated to be a spindle cell neoplasm with storiform pattern and infiltrative peripheral growth. The neoplasm showed diffuse sheets of spindle cells with eosinophilic cytoplasm and irregular, vesicular nuclei and prominent nucleoli. The tumor cells were stained positively for CD45(LCA), which is suggestive of hematopoietic origin, rather than mesenchymal neoplasm. Stains of tumor cells were positive for CD68, CD163, lysozyme, and vimentin, which is characteristic of mature tissue histiocytes. Ki-67 showed a proliferation index of 10-20%. Conclusion Histiocytic sarcoma is an extremely rare neoplasm that can be classified into two types: localized histiocytic sarcoma which involves single organs and is usually less aggressive and disseminated histiocytic sarcoma which involves multiples organs and is more aggressive. The most commonly involved organs are skin, soft tissue, and the gastrointestinal tract. Our case, which is cutaneous, mimics mesenchymal sarcoma, due to the predominant spindle cell storiform morphology. However, this is truly a hematopoietic neoplasm with mature tissue histiocyte differentiation. Since this is extremely rare, diagnosis of cutaneous histiocytic sarcoma requires a high index of suspicion, and immunohistochemistry is pivotal in diagnosing cutaneous histiocytic sarcoma with predominant spindle cell morphology.

We received a specimen of right hemicolectomy in a case of 35 years male, presented with persistent abdominal pain for last 6 months. Patient was admitted with sevre abdominal pain and frequent episodes of haematochezia for last 15 days. On gross examination of right hemicolectomy specimen, no obvious growth was found, only thickening of caecal wall was noted. Microscopical features showed atypical discohesive cells involving muscle fibers, serosal fat and subserosal lymph node. These discohesive cells having pleomorphic nuclei, nuclear grooving, prominent nucleoli surrounded by foamy to eosinophilic cytoplasm. Coagulative tumor necrosis was also present in the wall of the colon. Morphologically our initial diagnosis was non-Hodgkin’s lymphoma or poorly differentiated carcinoma or neuroendocrine tumor. Diagnosis of Histiocytic Sarcoma was confirmed by the immunohistochemistry study using CK, Chromogranin, Synaptophysin, CD20, CD3, S100, CD 45 and CD 68. In our case the tumor cells were diffusely positive for CD45 and CD 68. Tumor cells were CK, Chromogranin, Synaptophysin, CD20, CD3, and S100 negative.

Histiocytic sarcoma is an extremely rare and aggressive malignant neoplasm characterized by immunophenotypic features of mature histiocytes. The mechanisms underlying its malignant transformation remain poorly understood; consequently, the development of effective therapies remains limited. Resected histiocyticsarcoma specimens were cultured using a modified air-liquid interface organoid method, serially passaged, and xenografted into NOD-scid IL2Rgnull mice. Tumors formed by xenografted organoids retained histological and genetic similarities with the original tumor. Genomic analysis revealed the activation of the Sonic Hedgehog signaling pathway and amplification of Yes-associated protein 1, a key effector of the Hippo pathway. Accordingly, we evaluated the sensitivity of the organoids to the Sonic Hedgehog inhibitor vismodegib and Yes-associated protein 1 inhibitor verteporfin, both of which demonstrated potent in vitro antitumor activity in organoid cultures. This model offers a valuable preclinical platform for investigating the molecular pathology of this rare malignancy and accelerating the development of targeted therapies.

Histiocytic sarcoma (HS) is an extremely rare hematopoietic neoplasm derived from the monocytic/histiocytic/dendritic cell lineage. While sporadic cases of primary soft-tissue HS have been reported, its clinicopathological and molecular features remain incompletely characterized. This study investigates the clinicopathological features of two cases of soft-tissue HS and reviews the relevant literature. Microscopically, the tumor cells exhibited a diffuse growth pattern, with morphologic features varying from spindle-shaped sarcomatoid to epithelioid subtypes. Occasional bizarre cells were observed. Immunohistochemically, the tumor cells were positive for CD68, Lysozyme, S100, CD4, and CD163, but negative for a comprehensive panel of markers, including those for myeloid, Langerhans, follicular dendritic, lymphoid (T, B, NK), epithelial, vascular endothelial, and melanocytic lineages. Next-generation sequencing (NGS) revealed distinct mutational profiles: Case 1 harbored mutations in BRAF V600E, BRAF V600E, CDKN2A, and CIITA, while Case 2 exhibited mutations in CREBBP, INPP4B, RB1, PTEN, KMT2D, MSH2, and TP53, which may contribute to tumorigenesis and progression. Despite therapeutic efforts, both patients died within 6 and 9 months of follow-up, respectively. In conclusion, HS is a diagnostically challenging malignancy due to its rarity and morphological overlap with other soft tissue tumors. Immunohistochemical markers (CD68, Lysozyme, S100, CD4, CD163) are essential for diagnosis. Currently, no standard treatment exists. This study characterizes the molecular profiles of two extranodal HS cases, contributing to the understanding of their clinicopathological and genetic features.

ABSTRACTWe report a 31‐year‐old male patient repeatedly hospitalized for mimicking infectious symptoms. Following standardized anti‐infective and anti‐inflammatory treatment, clinical evolution was discordant, characterized by treatment non‐response and symptom exacerbation. Ultimately, the multidisciplinary team and repeated histopathological examinations diagnosed histiocytic sarcoma (HS). Unfortunately, the treatment opportunity was lost due to HS's high aggressiveness and rapid progression.

In vitro investigation of the oncolytic potential of two bovine herpesviruses in cultured canine osteosarcoma and histiocytic sarcoma cells

Transcriptomic changes of canine histiocytic sarcoma cells persistently infected with canine distemper virus maintained under different conditions

Histiocytic sarcoma (HS) is an ultra-rare hematopoietic neoplasm that frequently occurs in extranodal sites of adults. Clinically, HS demonstrates aggressive behavior and can arise de novo or in association with other hematological neoplasms. The median overall survival from the time of diagnosis is approximately six months. Histologically, HS is composed of sheets of large, round to oval cells with abundant eosinophilic cytoplasm and can be confused with a variety of benign and malignant conditions. Immunohistochemistry plays a crucial role in the diagnosis of HS, showing expression of CD163, CD68, lysozyme, and PU.1 and negative staining with follicular dendritic cell markers and myeloid cell markers. Recent studies have demonstrated a high rate of PD-L1 expression, suggesting a potential therapeutic target. Several genomic alterations have been identified in HS, including mutations involving the RAS/MAPK and PI3K/AKT/mTOR signaling pathways, CDKN2A mutations/deletions, and TP53 mutations. There is no standard protocol for the management of HS. Surgical resection with or without radiotherapy is the most common first-line treatment for unifocal/localized disease. The systemic treatment options for multifocal/disseminated disease are very limited. This review provides an overview of the current knowledge on the clinicoradiological features, histopathology, pathogenesis, and management of HS.

Research on cancer in wild animals provides important insights into the mechanisms of carcinogenesis. Histiocytic sarcomas comprise a rare malignant macrophage-dendritic cell lineage neoplasm in wildlife. This study reports a case of histiocytic sarcoma in the small intestine of a collared peccary (Pecari tajacu), describing its clinical, anatomopathological, and immunohistochemical aspects. A six-year-old male collared peccary maintained in captivity at a facility in Northeastern Brazil presented progressive weight loss, diarrhea, anorexia, dyspnea, lethargy, abdominal distension, bristled fur, and pale mucous membranes. A complete blood count indicated a mild degree of anemia and moderate leukocytosis. Treatment included anti-inflammatories and antibiotics; however, on the 18th day after initial presentation, the animal was found dead in its enclosure. An anatomopathological examination revealed that the animal exhibited poor body condition, scant body fat with a gelatinous appearance, hydrothorax, pulmonary edema, and ascites. Thickening of the duodenal wall was observed, along with the presence of a yellowish-white tumor. Histopathological examination of the affected intestinal segment revealed a neoplastic proliferation of round cells with large, hyperchromatic nuclei, prominent nucleoli, and a high mitotic index (20 mitoses per high-power field). Numerous multinucleated and binucleated giant cells were present. The neoplastic cells extensively infiltrated all layers of the intestinal wall, from the mucosa to the serosa. Immunohistochemical analysis showed strong positivity for macrophage/mononuclear phagocytic lineage markers (CD18, IBA-1, and lysozyme), while negative for T-cell (CD3), B-cell (CD79), and plasma cell (MUM1) markers. The proliferation index assessed by Ki-67 was approximately 60%. The histopathological and immunohistochemical findings confirmed the diagnosis of intestinal histiocytic sarcoma in a collared peccary, representing the first documented case of this neoplasm in this species.

Rosai-Dorfman disease is an uncommon histiocytic neoplasm that is often self-limiting; however, rarely, it exhibits aggressive behavior and may undergo biological transformation to histiocytic sarcoma. Pathogenic genetic drivers of Rosai-Dorfman disease include recurrent genetic abnormalities in KRAS, NRAS, ARAF, and MAP2K1. Mutation of BRAF is a well-known oncogenic driver in histiocytic neoplasms, including up to 50% of Langerhans cell histiocytosis lesions, Erdheim-Chester disease, and adult and juvenile xanthogranuloma. However, BRAF mutations have been documented in only 4 reported Rosai-Dorfman disease specimens, and none were rearrangements. Herein, we report the first instance of Rosai-Dorfman disease with OSBPL11::BRAF gene rearrangement, a unique gene fusion, and describe its clinicopathological features.

Recurrent Cerebral Infarctions Caused by Cardiac Histiocytic Sarcoma.

Canine histiocytic sarcoma (HS) is a rare tumor with a poor prognosis. Rapid tumor growth often causes central hypoxia and starvation, impacting tumor progression. In the present study, HS cells were cultured under hypoxia and starvation for 1 and 3 days, simulating intermediate and central tumor zones, respectively. Cells were counted at each time point, followed by RNAseq analysis. Only hypoxia significantly reduced the cell number (p < 0.05). Short-term hypoxia altered 1645 differentially expressed genes (DEGs). Upregulated genes belonged to vasculature development, and downregulated genes to cell cycle processes. Short-term starvation affected 157 genes, mainly involving responses to stimuli. Prolonged hypoxia and starvation induced 1301 and 836 DEGs, respectively. Prolonged hypoxia upregulated genes mainly involved in immune responses, response to stimulus, adhesion, and angiogenesis. Prolonged starvation upregulated genes associated with signaling, adhesion, circulatory system development, and response to stimulus. Lipid metabolism and cell cycle pathways were downregulated under prolonged hypoxia and starvation, respectively. KEGG "pathways in cancer" were enriched under all conditions (adjusted p-values < 0.05). These findings indicate that hypoxia and starvation significantly alter the expression of genes involved in tumor progression. Further studies, namely post-translational analyses, are needed to elucidate the functional impact of these changes and identify potential therapeutic targets.