Diagnosis Of Histiocytic Sarcoma Research Articles

Histiocytic Sarcoma

Histiocytic sarcoma is a rare and frequently missed diagnosis. With unusual and varied presentations, it typically indicates a rapid patient decline and poor outcomes. The diagnosis requires a high degree of clinical suspicion. In this case, we explore the progression of illness in a 56-year-old white male who initially presented with a 2-week history of soft-tissue nodules scattered throughout his head, neck, torso, and limbs, as well as shortness of breath and knee pain. After a thorough workup including computed tomography imaging of the neck, chest, and lower extremity, as well as a biopsy of a nodule with immunoperoxidase staining, a diagnosis of histiocytic sarcoma was established. Due to the severity of his malignancy, his hospital course was complicated by a deep vein thrombosis. Clinicians should be mindful of the risk of acute decompensation in such cases and can employ the various tenets of osteopathic theory to improve patient quality of life. Depending on the severity of illness, physicians may proceed to facilitate end-of-life measures with grace and dignity.

Co-Occurrence of Clonally Related Follicular Lymphoma and Histiocytic Sarcoma

Histiocytic sarcoma (HS) is an extremely rare and aggressive malignancy thought to be derived from mononuclear phagocytic cells. HS may occur as primary tumor or may be clonally related to a hematologic malignancy. Rare cases of HS have been reported in patients with follicular lymphoma (FL). Prior reports have demonstrated a common clonal origin of FL and HS in many cases via demonstration of identical BCL2/IGH [t(14;18)] translocations in both malignancies. As this is likely the earliest event in FL pathogenesis, the mechanisms by which HL may arise from FL remain unknown. A greater understanding of how a B cell malignancy can transdifferentiate into a myeloid one would yield insights into the fundamental underlying biology. From a patient with long-standing history of FL and subsequent diagnosis of HS, we collected tumor biopsies from a tumor site harboring both FL and HS. Tumor biopsies were subjected to standard histopathological assays, as well as targeted hybrid-capture DNA sequencing of 164 genes commonly mutated in hematologic malignancies and cytogenetic assays for the BCL2 rearrangement (Figure 1). Additionally, we performed single cell RNA sequencing (scRNA-seq) using the 10X chromium followed by single cell long read sequencing using Nanopore Oxford Technologies (Figure 1). Two tumor populations were evident in the scRNAseq data - FL tumor cells, identified by homogeneity of BCR light chain variable gene expression and expression of FL marker genes, and a separate cluster of cells expressing CD68, CD163 and S100A8, characteristic for HS cells. Gene expression profiles of the two tumor populations revealed high expression of the targetable “don´t eat me” signal CD47 on both populations. HS also expressed BCL2, hinting at a common clonal origin of FL and HS neoplasms. Indeed, fluorescent in situ hybridization (FISH) studies demonstrated the presence of t(14;18) in both the FL and HS tumor cells. To understand if similar transcription factors (TFs) were active in the two malignancies, we inferred the top 10 enriched TF for each tumor subpopulation and found that while TFs like IRF8 and REL were enriched in FL cells, HS cells showed a higher expression of MYC, STAT2 and CEBPD. Bulk targeted hybrid-capture DNA sequencing of the tumor sample revealed mutations in genes frequently altered in FL ( e.g.CREBBP, BIRC3, and PIM1) as well as in a gene commonly mutated in HS ( MAP2K1). To gain deeper insight into the clonal relationship between the two malignancies within the same tumor, we conducted long read sequencing on the barcoded single cell-cDNA. We are currently analyzing the data in two ways. First, we are searching for the mutations identified in bulk sequencing now in the single cell long read data from the FL and HS cells, using microenvironmental immune cells from the same tumor as a negative control. We have confirmed that these genes are all expressed in the FL, HS, and immune cells, providing transcripts for us to analyze for mutations. Second, we are employing an unbiased approach for identifying genetic variants, again comparing FL and HS cells. This data will be available by the annual meeting. By applying single cell genomics analyses to a combined FL/HS biopsy, our study aims to understand the evolutionary relationship of HS arising from FL, particularly whether the HS arose from an early dormant clone (branched evolution) or from a late, prevalent Fl clone (linear evolution). Evidence of the former would strengthen the view that common progenitor cells (CPCs) in FL are capable of differentiating into myeloid and lymphoid malignancies.

Histiocytic sarcoma in renal transplant patients: a literature review

BackgroundHistiocytic sarcoma (HS) is defined as neoplasm resembling morphological and immunophenotypic characteristics of mature histiocytes. It is a rare form of lymphoid neoplasms. Despite advances in treatment and diagnosis of histiocytic sarcoma, majority of cases had poor prognosis due to progressive nature of the disease. In the following article, all reported cases of histiocytic sarcoma in renal transplant patients are reviewed.MethodsIn our literature review, all relevant reports were collected electronically by entering the necessary keywords. A Boolean approach using Medical Subject Heading (MeSH) keywords was implemented. After establishing the inclusion/exclusion criteria, article titles and abstracts were evaluated by Systematic Reviews and Meta-Analyses (PRISMA) standards for 2020. All cases of histiocytic sarcoma in renal transplant patients were included.ResultBased on our inclusion and exclusion criteria 4 case reports were yielded in this review. Two were males and 2 were females with the mean age of 42.25 years. Fever was the most common symptom. Although tumor originated from the native kidney on one patient, the site of the primary tumor was thorax, oropharynx, and transplanted kidney in the rest. Metastasis was detected in all cases. Prednisone was used for all cases. EBV was positive in 2 cases and negative in one of them. Histology was diagnostic and similar in all cases. Immunohistochemistry was done for 3 cases. Although chemotherapy was done for 3 patients, all 4 cases ended in mortality.ConclusionDespite the fact that neoplasms are post renal transplant complications, histiocytic sarcoma is a scarce and fatal entity in such patients. Histological and immunohistochemistry tests are the corner stone in diagnosis of histiocytic sarcoma.

Two Sides of the Same Transdifferentiated Coin: A Case Vignette and Review of the Literature Exploring the Relationship between B Cell Non-Hodgkin Lymphoma, Histiocytic Sarcoma and Interdigitating Dendritic Cell Sarcoma

WHO classifies Histiocytic Sarcoma (HS) and Interdigitating Dendritic Cell Sarcoma (IDCS) as separate, unrelated, entities under histiocytic/dendritic cell neoplasms. We do not fully understand the pathogenesis of HS and IDCS, yet both have been shown to transdifferentiate from B cell non-Hodgkin lymphomas. Diagnosis is challenging and requires application of a wide variety of immunohistochemical studies, flow cytometry and molecular analysis. We present a case of HS which evolved from CLL/SLL and presented as a diagnostic challenge due to unusual features overlapping with what is typically seen in IDCS. An 82-year-old male with a history of CLL/SLL presented with right infiltrative tonsillar mass and cervical lymphadenopathy. Biopsy of the lymph node revealed two abnormal populations of cells : Twenty percent of cells were consistent with CD20+ kappa surface light chain restricted CLL/SLL cells. Eighty percent of cells were histiocytic cells with an abnormal immunophenotype showing expression of CD4, CD43, fascin, HLA-DR, PU.1, (weak) S100 and CD1a without CD163, lysozyme, CD34, CD117, CD21, CD23 or CD14. Expert consultation favored the diagnosis of HS with transdifferentiation from CLL/SLL. PCR for IgH gene rearrangement, performed on separate HS-rich and CLL-rich areas of the biopsy detected identical clonal peaks. Next generation sequencing detected pathogenic KRAS mutations (p.G12D, p.A146P) and likely pathogenic BCOR (p.K839fs*17) and FBXW7 (p.R465S) mutations. While HS was the favored diagnosis, some immunophenotypic features were unusual, including diffuse fascin immunoreactivity, weak S100, and CD1a immunoreactivity which raised the possibility of so-called IDCS. While clonal evolution of HS and IDCS from B cell Non-Hodgkin lymphomas has been reported, there is a paucity of literature on these entities. We suggest that there may be a pathogenic relationship between these two neoplasms that has yet to be elucidated due to their rarity and diagnostic challenge. Few clinical laboratories can perform the breadth of markers required for diagnosis. Both neoplasms have varied clinical presentations with nodal or extranodal involvement and portend poor prognosis. Review of the literature shows significant overlap in immunophenotypic and genomic characteristics of IDCS and HS, suggesting they may be related manifestations of the same neoplasm. A case report has described the initial presentation of IDCS that subsequently developed into HS, although sampling may have been an issue. We identified 11 cases, including our case in the literature presenting with positive histiocytic and dendritic cell markers referred as hybrid dendritic-histiocytic sarcomas or histiocytic sarcoma with interdigitating dendritic cell differentiation. Immunohistochemical analysis of these cases showed positivity rates of S100 (100%), lysozyme (82%) and CD1a (18%). One case in the literature described fascin immunoreactivity, as was observed in our case. Four of six cases had CD163 immunoreactivity. A hybrid neoplasm with overlapping features of follicular and interdigitating dendritic cells has also been reported, further confounding our understanding of these neoplasms. Large studies analyzing genomic features of these neoplasms have shown recurrent mutations in RAS-MAPK pathway, as was seen in our case. Further studies of the relationship between HS, IDCS should include gene expression profiling of these entities which may also yield therapy targets. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Lymph node recurrence and re-excision after primary tumor resection of a histiocytic sarcoma of duodenal origin: a case report

BackgroundHistiocytic sarcoma is a rare malignant tumor that is similar in characteristics to a mature histiocyte/macrophage and is a relatively new disease entity. In approximately one-third of cases, the site of origin is a lymph node; development from the gastrointestinal tract, spleen, soft tissue, and skin has further been reported. The tumor characteristics are not well-understood as reports on its clinical presentation and treatment are limited. We report a case of duodenal primary histiocytic sarcoma.Case presentationAn elevated lesion in the second part of the duodenum was detected in a 70-year-old woman during routine examination using upper gastrointestinal tract endoscopy. Blood biochemistry findings were normal for tumor markers. No abnormal findings were observed in the blood count and biochemical examination. Upper gastrointestinal endoscopy revealed a 20-mm elevated lesion with a slight depression in the center, opposite to the papilla of the descending duodenum. The biopsy showed erosions of the mucosal epithelium and inflammatory cell infiltration, but no evidence of malignancy. Ultrasound-guided endoscopy revealed an ischemic tumor of submucosal origin, and bowel biopsy suggested a histiocytic sarcoma. Distant metastasis and lymph node enlargement were absent on abdominal sonography, computed tomography, and magnetic resonance imaging. Duodenal segmental resection was performed. Immunostaining of the excised lesion was positive for CD68, CD163, CD4, CD5, CD15, and CD45 and negative for CD1a, CD21, CD34, MPO, and S-100 protein. Ki-67 positivity was approximately 20%. Based on these findings, the diagnosis of histiocytic sarcoma was confirmed. Ten months after the surgery, a lymph node recurrence in the dorsum of the pancreatic uncus was observed. No evidence of recurrence was found in any other part; hence, we performed pancreaticoduodenectomy. Pathological findings of the excised lymph node confirmed the recurrence of histiocytic sarcoma in the lymph node.ConclusionsThis is the first reported case of a duodenal primary histiocytic sarcoma with recurrence in the lymph node after the primary resection. The patient was treated for recurrence by lymph node excision and pancreaticoduodenectomy.

A case of primary histiocytic sarcoma arising from a neck lymph node.

Histiocytic sarcoma (HS) is an aggressive and rare hematological malignancy. Its treatment has not been established, and most patients die within 2years of diagnosis. Resection can provide a favorable prognosis for solitary lesions. We present the case of an 80-year-old Japanese man with HS. He presented a history of a slow-growing painless mass in the lower part of his right jaw. Ultrasonography showed a swollen lymph node in the vicinity of the right submandibular gland. Contrast-enhanced computed tomography revealed a heterogeneous, low-contrast mass on the right of the neck. Magnetic resonance imaging revealed a heterogeneously enhanced mass in gadolinium-enhanced T1-weighted images. The fine needle biopsy showed spindle-shaped cells and HS was suspected. Fluorodeoxyglucose positron emission tomography revealed uptake by the tumor alone. The patient underwent right upper neck dissection and resection of the submandibular salivary glands. No postoperative adjuvant treatment was administered, but 2-year survival was achieved. Histopathological examination showed proliferation of large, pleomorphic atypical cells without differentiation into lymphocytes, which proved their differentiation into histiocytes. A bone marrow biopsy showed no evidence of monocytic leukemia. Thus, a diagnosis of HS was made. With local treatment alone, our patient achieved long-term survival, maintaining his quality of life.

A rare primary localized extranodal histiocytic sarcoma of oral mucosa: a case report

<h3>Background</h3> Histiocytic sarcoma is a rare hematopoietic malignancy which typically involves extranodal sites, mainly of the gastrointestinal tract. Of the small number of reported cases in the head and neck region, only one case was localized to the oral cavity. The disease may present as a solitary lesion or disseminated process secondary to other hematopoietic malignancies. Histopathologically, the tumors can be mistaken for other lymphoprolifera- tive disorders. Immunohistochemistry shows tumor cells expressing one or more of the histiocytic markers CD163, CD68, or lysozyme. Surgery with or without chemotherapy or radiotherapy are the mainstays of treatment. Even though histiocytic sarcoma has clinically aggressive behavior with poor response to therapy, studies show that a subset of the patients with localized disease and small tumor size have more favorable outcome with surgery alone. We present a case with localized extranodal histiocytic sarcoma of oral mucosa. <h3>Case Description</h3> A 31-year-old, fe- male with onemonth duration of a 10 × 8 × 2 mm smooth-surfaced, well circumscribed, firm soft tissue enlargement at buccal vestibule of #11/12. Biopsy shows a diffuse population of pleomorphic cells with atypical mitoses and fine granular cytoplasm within fibrocollagenous connective tissue. Immunohistochemical studies demonstrated tumor cells positive to CD163, CD68, CD45, CD43, CD4, muramidase, SOX10, S100, NSE and vimentin with a diagnosis of his- tiocytic sarcoma. Surgical excision with uninvolved margins was performed. The diagnosis of histiocytic sarcoma was confirmed with hematopathology consultation. There was no evidence of tumor recurrence after 3 months fol- low up. <h3>Conclusion</h3> To the best of our knowledge, this is the second case of primary localized extranodal histiocytic sarcoma of oral cavity. Surgery alone was the treatment modality for our case. However, due to the rarity/limited number of reported cases, treatment outcomes of a localized disease is limited. The treatment protocol may become more evident as newer studies emerge.

Progressive respiratory distress caused by a laryngeal histiocytic sarcoma in a European rabbit (Oryctolagus cuniculus)

Histiocytic sarcoma (HS) represents a rare type of malignant disease, characterized by neoplastic proliferation of interstitial dendritic cells (iDCs). In rabbits, there are only two previous reports of HS with pulmonary and cutaneous primary localizations. A 2-year-old, male, European rabbit (Oryctolagus cuniculus) with a clinical history of chronic respiratory distress and progressive weight loss was necropsied. Postmortem examination revealed a gray-white, well-demarcated ovoid mass that deformed the ventral region of the larynx. Similar nodules were identified in both lungs. Histologically, the laryngeal mass and pulmonary nodules were composed of dense sheets of neoplastic histiocytes with marked atypia and multinucleated neoplastic cells. Immunohistochemically, the neoplastic cells were intensely positive for Iba1, CD1a, and vimentin, occasionally for E-cadherin, and negative for multi-cytokeratin. A diagnosis of laryngeal HS with multiple pulmonary metastases was made. To the authors' knowledge, laryngeal histiocytic tumor has not been previously reported in rabbits.

First reported case of a histiocytic sarcoma in an Armenian hamster (Cricetulus migratorius).

A 14-month-old male Armenian hamster (Cricetulus migratorius) presented with a spontaneous, subcutaneous, firm mass (4.0 × 2.0 × 1.5 cm) on the ventral neck extending towards the cheek pouch causing multifocal small oral ulcerations. This animal was immunized subcutaneously on the dorsal neck for the development of monoclonal antibodies seven months before presentation. The animal was euthanized and necropsy was performed. Histopathology of the mass showed a well demarcated, multilobulated, unencapsulated, highly cellular, neoplastic mass composed of spindle cells arranged in interlacing streams and bundles, with a moderate amount of fibrovascular stroma. The neoplastic cells exhibited indistinct cell borders and a moderate to large amount of eosinophilic, fibrillar cytoplasm, marked anisocytosis and anisokaryosis, binucleated and multinucleated cells, and high mitotic rate. Based on the histomorphologic features of the mass, and the presence of renal tubular hyaline globules and myeloid hyperplasia in the bone marrow, a diagnosis of histiocytic sarcoma was made. The presumptive diagnosis was confirmed by immunohistochemistry, upon which the neoplastic cells showed strong immunoreactivity for the histiocytic cell markers Iba1 and CD11b. Histiocytic sarcomas have been reported in Syrian (Mesocricetus auratus) and Siberian dwarf (Phodopus sungorus) hamsters but, to our knowledge, the current report represents the first case of histiocytic sarcoma described in an Armenian hamster. It is plausible to consider the animal's experimental immunization history and the development of the histiocytic sarcoma to be related. An association between adjuvanted vaccines and soft-tissue sarcomas has been described in cats and referred to as feline injection-site sarcomas.

Histiocytic sarcoma arising from a lymph node: a diagnostic conundrum

Histiocytic Sarcoma (HS) is extremely rare, with only a few hundred cases reported in the literature. The majority of patients present with symptoms due to unifocal or multifocal extra-nodal disease. Less than 20% of these cases show solitary involvement of a lymph node. We report a case of a solitary HS in a 53-year-old woman presenting with a 2.7-cm right groin mass arising from an inguinal lymph node. The initial cytologic examination of the tissue showed a high-grade spindle-shaped morphology with high-grade mitotic activity. A high-grade sarcoma was initially considered considering the absence of normal lymphoid aggregate and the presence of high-grade cytologic features in the cells. To evaluate the tumor in its entirety, the mass was surgically excised. A histological examination of the tumor showed focal rimming of the lymphoid tissue at the periphery and a centrally located stellate necrotic focus. The tumor cells had an epithelioid to spindle cell morphology along with large uniform nuclei and prominent nucleoli. A high mitotic index was present. Immunohistochemistry (IHC) stains showed strong positivity for CD68, CD163, and Vimentin, and were weakly positive for SMA and CD45. Based on the histologic and clinical examination, a diagnosis of HS was made. Multiple malignancies can mimic HS histopathology and the rarity of this tumor makes the diagnosis more challenging. No fine-needle aspiration (FNA) criteria for its diagnosis have been recognized. Herein, we report a rare case of an isolated HS involving a lymph node which resembled high-grade sarcoma on the FNA biopsy to raise awareness among our surgical pathologist colleagues.

Histiocytic sarcoma of paranasal sinus; report of the first case with emphasis on potential diagnostic pitfalls and differential diagnosis

Introduction: Histiocytic sarcoma is a very rare hematopoietic malignancy of mature histiocytes with an aggressive clinical course, arising as a primary neoplasm or less commonly as a secondary neoplasm from pre-existing indolent lymphoma or rarely after therapy for other neoplasms. Most patients present at advanced stage with metastasis and hence have poor prognosis. Case Report: A 70 year old female presented with difficulty in breathing and epistaxis. There was no pain, fever, weight loss and other systemic manifestations. On examination, there was a tumour in the nasopharynx. Based on the characteristic morphological features and an extensive panel of Immunohistochemistry markers, a diagnosis of histiocytic sarcoma was rendered. Discussion: It usually occurs in extra nodal sites and the most common locations being the gastrointestinal tract, skin, various soft tissue sites, liver and spleen. To the best of our knowledge, rare case arising in nasal cavity has been reported, but tumour from paranasal sinus has not been reported in literature, so far. We report the first case of Histiocytic sarcoma arising from Ethmoid in an elderly female, also discuss the differential diagnosis, potential pitfalls and highlight the importance of immunohistochemistry. Keywords: Differential diagnosis, Ethmoid sinus, Histiocytic sarcoma, Immunohistochemistry.

Imprint cytology of histiocytic sarcoma manifesting as a retroperitoneal mass: A valuable aid for frozen section diagnosis

Histiocytic sarcoma (HS) is a comparatively rare hematolymphoid neoplasm. Differential diagnosis of this entity has generally been proven to be so difficult that extensive immunohistochemical staining is required to confirm its presence. We herein present a case of HS manifesting as a retroperitoneal mass in which imprint cytology (IC) contributed to the diagnosis. A 77-year-old man was referred for the evaluation of a colonic tubulovillous polypoid lesion. Preoperative imaging revealed a 3 cm-sized polypoid lesion in the transverse colon. Incidentally, a retroperitoneal mass of 8 cm in the left para-aortic region was also detected. Diff-Quik stained IC slides were prepared as an adjunct to intraoperative pathology consultation. The smear exhibited moderate cellularity involving loosely cohesive cell clusters with intervening delicate vasculature. Most of the tumor cells consisted of large single cells with abundant eosinophilic cytoplasm that was vacuolated and foamy. The nuclei were predominantly large and eccentrically located. Mitotic figures were minimal in number and finely granular brown pigments were occasionally observed. A frozen section diagnosis was reported as a malignant neoplasm, and a histologic diagnosis of HS was confirmed by conducting a battery of immunohistochemical stains: negative for pan-cytokeratin, EMA, CD117, HMB45, Melan A, CD30, PAX5, CD20, S-100, and CD23 but strong positive for vimentin and CD68. This entity is rarely described in terms of cytopathologic features. This case study highlights how cytopathologists should be aware of HS as a retroperitoneal lesion and should become familiar with cytomorphologic features.

Histiocytic Sarcoma in the Kidney: A Rare Presentation

Abstract Background Histiocytic sarcoma is a rare neoplasm of mature histiocytes with a wide range of clinical presentations and manifestations. The heterogeneity of this neoplasm can cause difficulty in both diagnosis and treatment. It is a diagnosis of exclusion, requiring verification of the histiocytic lineage and the exclusion of other B-cell related malignancies. Although cases of postrenal transplant histiocytic sarcoma have been reported, incidences in a native kidney are rare. Case Report We present the case of a 70-year-old male with a history of colorectal adenocarcinoma, status post chemotherapy, with an incidental exophytic renal mass found on imaging, which was determined to be a sarcomatoid renal cell cancer on biopsy. Radical nephrectomy was performed, revealing a 4.5 × 3.5 × 3.2-cm mass invading the renal pelvis and fat. Microscopic examination of the tumor showed large, poorly cohesive neoplastic cells with abundant pale, eosinophilic cytoplasm that stained positive for vimentin, CD4, CD163, and CD68 and weakly/focally positive for lysozyme. Negative immunostains included PAX-8, pan-CK, AE1/AE3, HMB45, S100, CD34, CD30, ALK1, CD1a, myeloperoxidase, CD138, myo-D1, SMA, and CD21. A diagnosis of histiocytic sarcoma, grade 4 was made based on these findings. Discussion Histiocytic sarcoma is a disease of unknown etiology accounting for less than 1% of all hematolymphoid neoplasms. Our literature review revealed no other cases arising de novo in the kidney, but several cases were reported in postrenal transplant patients. Diagnosis of histiocytic sarcoma is difficult as it is a diagnosis of exclusion. The immunohistochemical profile most often expresses lysosome-related markers, such as CD68, CD163, or lysozyme. Additionally, negative staining is expected for markers related to B cells, T cells, and melanocytes. The cells are often large with eosinophilic cytoplasm, well-defined borders, and vesicular chromatin. Although there are numerous differentials, distinct morphologic and immunohistochemical features allow for accurate diagnosis.

Clinical features, molecular aberrations, treatments, and outcomes in histiocytic sarcoma.

7020 Background: Histiocytic sarcoma (HS) is a rare and aggressive malignancy of the monocyte/macrophage lineage. There is a paucity of data on treatments and outcomes in HS. Methods: This is a retrospective study of patients with histologically confirmed diagnosis of HS from 2000-2018. Kaplan-Meier and log-rank tests were used to perform overall survival (OS) analyses. Hazard ratios (HR) with confidence intervals (CI) were calculated using Cox-proportional hazards. Results: There were 27 patients in the study (median age 59; range 3-83) and 63% were males. Nine had unifocal involvement and 18 had multifocal disease. Common sites involved were lymph node (50%), soft tissue (40%), bone (36%), and bone marrow (22%). Two of 8 patients had the BRAF-V600E mutation. Next-generation sequencing was performed on 8 patients and showed ≥1 oncogenic alterations (DNMT3A, FLT4, KRAS, NRAS, NUP98, PTCH1, PTPN11, TP53, TSC1, PDGFR, or BRAF genes) as well as a CLIP2-BRAF fusion. The median OS for the cohort was 12 months. Factors associated with worse OS included multifocal disease (OS 10 vs. 125 months, p = 0.03; HR 5.0, CI 1.1-21.8) and marrow involvement (OS 3 vs. 43 months, p = 0.003; HR 8.9, CI 1.7-45.0). Twelve (44%) had surgery with median OS of 42 months (range 1-125). Fifteen had chemotherapy with median OS of 12 months (range 2-67; Table). Conclusions: HS is an aggressive neoplasm, with multifocal disease and bone marrow involvement portending worse outcomes. Most patients have somatic oncogenic alterations involving the MAPK-ERK pathway and other genes. Chemotherapeutic regimens have variable response rates but are not durable. More studies on targeted kinase inhibitors in HS are needed to improve outcomes. [Table: see text]

HISTIOCYTIC SARCOMA: A CASE SERIES OF EXTRANODAL AND NODAL PRESENTATIONS

Introduction: Histiocytic sarcoma is an aggressive malignancy of mature histocytes which often carries a poor prognosis. Histiocytic sarcoma is defined in the World Health Organisation (WHO) classification of histiocytic and dendritic cell neoplasms. Case Presentation: Case 1 depicts a 42 year old Malay gentleman with no premorbids presented to the haematology unit with a three month history of fever, night sweats, unintentional weight loss, left axillary and bilateral inguinal swellings which were progressively enlarging.  Physical examination revealed a medium built gentleman with left axilla, bilateral inguinal lymphadenopathies and hepatosplenomegaly. Excision biopsies of the left axillary and inguinal lymph nodes were compatible with histiocytic sarcoma. He did not have any bone marrow infiltration. He was treated with 6 cycles of CHOP (Cyclophosphamide, doxorubicin, vincristine, prednisolone) polychemotherapy but he subsequently succumbed to severe hemophagocytic syndrome shortly after his 6 th CHOP chemotherapy. Case 2 describes a 55 year old previously healthy Malay gentleman who presented with perianal swelling and weight loss for two months. Physical examination revealed a large perianal swelling measuring 10 cm with bilateral inguinal lymphadenopathies. Anorectal tissue histology was compatible with the diagnosis of histiocytic sarcoma. He underwent  a transverse colostomy which was subsequently reversed post chemotherapy. He completed 6 cycles of CHOP chemotherapy followed by upfront consolidation autologous stem cell transplant. He is currently 9 months in complete remission. Conclusion: Histiocytic sarcoma remains a disease with poor treatment outcomes and high mortality. Understanding the pathogenesis and pathobiology of the disease will provide future to the development of novel therapies.

Histiocytic Sarcoma: A Case Series of Extranodal and Nodal Presentations

Introduction: Histiocytic sarcoma is an aggressive malignancy of mature histocytes which often carries a poor prognosis. Histiocytic sarcoma is defined in the World Health Organisation (WHO) classification of histiocytic and dendritic cell neoplasms. Case Presentation: Case 1 depicts a 42 year old Malay gentleman with no premorbids presented to the haematology unit with a three month history of fever, night sweats, unintentional weight loss, left axillary and bilateral inguinal swellings which were progressively enlarging.  Physical examination revealed a medium built gentleman with left axilla, bilateral inguinal lymphadenopathies and hepatosplenomegaly. Excision biopsies of the left axillary and inguinal lymph nodes were compatible with histiocytic sarcoma. He did not have any bone marrow infiltration. He was treated with 6 cycles of CHOP (Cyclophosphamide, doxorubicin, vincristine, prednisolone) polychemotherapy but he subsequently succumbed to severe hemophagocytic syndrome shortly after his 6th CHOP chemotherapy. Case 2 describes a 55-year-old previously healthy Malay gentleman who presented with perianal swelling and weight loss for two months. Physical examination revealed a large perianal swelling measuring 10 cm with bilateral inguinal lymphadenopathies. Anorectal tissue histology was compatible with the diagnosis of histiocytic sarcoma. He underwent a transverse colostomy which was subsequently reversed post-chemotherapy. He completed 6 cycles of CHOP chemotherapy followed by upfront consolidation autologous stem cell transplant. He is currently 9 months in complete remission. Conclusion: Histiocytic sarcoma remains a disease with poor treatment outcomes and high mortality. Understanding the pathogenesis and pathobiology of the disease will provide a future to the development of novel therapies.

Histiocytic sarcoma of the neck: A case report.

Histiocytic sarcoma (HS) is a term used to describe malignant hyperplasia of cells exhibiting morphological and immunophenotypical characteristics similar to those of mature cells, with expression of one or more tissue cell markers, excluding acute monocytic leukemia and primitive monocytic sarcoma. We herein describe a case of histiocytic sarcoma of the neck supported by histopathological and immunohistological evidence. A 53-year-old female patient of Chinese descent presented with a rapidly enlarging right neck mass. Imaging studies revealed multiple right cervical lymphadenectases with right jugular vein involvement. The tumor was composed of diffusely distributed large non-cohesive tumor cells, round or oval and focally spindle-shaped. The tumor cells were immunopositive for macrophage-associated antigen CD68 and lysosomes, mostly consistent with a diagnosis of HS. HS is very prone to systemic metastasis; therefore, early diagnosis and timely treatment are crucial.

Morphological Distinction of Histiocytic Sarcoma from Other Tumor Types in Bernese Mountain Dogs and Flatcoated Retrievers.

Histiocytic sarcoma (HS) represents a group of malignant canine tumors to which Bernese Mountain Dogs (BMD) and Flatcoated Retrievers (FCR) are predisposed. The differential diagnosis for HS is broad, encompassing round cell tumors, sarcomas and other histiocytic diseases. The aim of this study was to establish morphological and immunohistochemical criteria for routine use on formalin-fixed, paraffin-embedded samples and cytological smears for the recognition and differentiation of canine HS and its subtypes. Retrospectively, tumor sections were reviewed from 449 BMD and 380 FCR with confirmed or suspected HS, other histiocytic conditions, or a disease of the differential diagnosis of HS. In a large proportion of cases, 47.5% for histology and for 46.3% cytology, the initial diagnosis was changed after the revision process. A large variation in morphological features of HS was observed in this study, making the existence of several subtypes in dogs also very likely. Furthermore, the different percentage of morphological features between BMD and FCR indicates the different mixture of cell type origins resulting possibly from genetic or environmental differences at the onset of HS in those breeds. This study stresses the value of a strictly applied and standardized scoring system for microscopic evaluation of tumor sections and smears, and the implementation of review and revision of pathological diagnoses.

Fas-ligand and caspase-3 positivity in three cases of histiocytic sarcoma: a different etiopathogenic pathway?

Histiocytic sarcoma (HS) is a rare malignant neoplasia of hematopoietic origin and unknown etiology. We studied three patients with histiocytic sarcoma reviewing the morphological and immunohistochemical aspects. We evaluated in particular, if apoptosis may be unbalanced in this disease. All cases have morphological and immunohistochemical features consistent with the diagnosis of histiocytic sarcoma. The markers CD163, CD68, vimentin, lysozyme, and S-100 were positive in all cases. Similarly, the three samples were positive for Fas-ligand and Caspase-3. It is well-known that neoplasms may induce increased levels of Fas-ligand with the blockade of the apoptosis process. In the context of HS, the increased Fas-ligand expression represents a new area for research. Indeed, it is linked to proinflammatory stimulus and, maybe with the association of an infection.

Prior joint disease is associated with increased risk of periarticular histiocytic sarcoma in dogs.

Periarticular histiocytic sarcoma (PAHS) is the most common synovial tumour in dogs and is characterized by aggressive local disease with a high rate of distant metastasis. Previously, an association between PAHS and prior joint disease has been demonstrated in the Bernese Mountain Dog breed and suggested in the Rottweiler. We hypothesized that this association would be present in other breeds and investigated this via a retrospective, case-controlled analysis. Cases were dogs diagnosed with PAHS of the stifle or elbow. Controls were age, breed and sex-matched dogs without a diagnosis of histiocytic sarcoma. Diagnosis of prior joint disease was determined based on review of medical records and direct veterinarian and owner communications. Data were evaluated using logistic regression, 2-sampled t tests, and chi-squared analysis. Our study population consisted of 28 cases and 46 controls, including Flat-Coated, Golden and Labrador Retrievers, Rottweilers, English Bulldogs, Shih Tzus, Australian Shepherds, Staffordshire Terriers and mixed breed dogs. Dogs with PAHS were more likely to have prior joint disease in the tumour-affected joint compared with the control population (odds ratio [OR] = 13.42, P < .0001, 95% confidence interval [CI] = 4.33-48.63). A total of 88.2% of dogs with stifle PAHS had prior joint disease in their tumour-affected joint, most commonly cranial cruciate ligament rupture. This study confirms that the previously noted association between prior joint disease and PAHS in Bernese Mountain Dogs also applies to other breeds. Additional studies are needed to further investigate for a causal relationship.