Case Of Histiocytic Sarcoma Research Articles

PTPN11 mutations in canine and human disseminated histiocytic sarcoma.

In humans, histiocytic sarcoma (HS) is an aggressive cancer involving histiocytes. Its rarity and heterogeneity explain that treatment remains a challenge. Sharing high clinical and histopathological similarities with human HS, the canine HS is conversely frequent in specific breeds and thus constitutes a unique spontaneous model for human HS to decipher the genetic bases and to explore therapeutic options. We identified sequence alterations in the MAPK pathway in at least 63.9% (71/111) of HS cases with mutually exclusive BRAF (0.9%; 1/111), KRAS (7.2%; 8/111) and PTPN11 (56.75%; 63/111) mutations concentrated at hotspots common to human cancers. Recurrent PTPN11 mutations are associated to visceral disseminated HS subtype in dogs, the most aggressive clinical presentation. We then identified PTPN11 mutations in 3/19 (15.7%) human HS patients. Thus, we propose PTPN11 mutations as key events for a specific subset of human and canine HS: the visceral disseminated form. Finally, by testing drugs targeting the MAPK pathway in eight canine HS cell lines, we identified a better anti-proliferation activity of MEK inhibitors than PTPN11 inhibitors in canine HS neoplastic cells. In combination, these results illustrate the relevance of naturally affected dogs in deciphering genetic mechanisms and selecting efficient targeted therapies for such rare and aggressive cancers in humans.

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.

Hematolymphoid Neoplasms Rarely Mimic Undifferentiated Pleomorphic Sarcoma of Soft Tissue.

Undifferentiated pleomorphic sarcoma (UPS) of soft tissue is defined as a sarcoma with no recognizable line of differentiation. During the past few decades, advances in ancillary studies and review of prior UPS diagnoses have narrowed the category of UPS by excluding more-specific malignancies. However, few of those studies have specifically targeted pleomorphic hematolymphoid neoplasms. To determine what fraction of UPS cases are misclassified pleomorphic hematolymphoid neoplasms, such as anaplastic large cell lymphoma, diffuse large B-cell lymphoma, histiocytic sarcoma (HS), myeloid sarcoma, and follicular dendritic cell sarcoma. Sixty-one UPS cases were screened by tissue microarray and an immunostain panel with subsequent analysis on whole block sections for suspicious cases. Five of 61 tumors (8%) were suggestive of HS based on the screening panel and were further evaluated with additional immunostains (PU.1, CD45, CD163) using whole sections. The 5 candidate HS cases were only focally positive for at most one stain with most staining in smaller, less-pleomorphic cells. Ultimately, no UPS met criteria for anaplastic large cell lymphoma, diffuse large B-cell lymphoma, myeloid sarcoma, follicular dendritic cell sarcoma, or HS. Our results suggest that a UPS of somatic soft tissue is unlikely to represent a misclassified hematopoietic malignancy. Exclusion of HS is most challenging, but immunostaining for PU.1, a nuclear transcription factor, may be easier to interpret in this context.

Histiocytic sarcoma: An encounter with a rarity

Histiocytic sarcoma is a rare hematolymphoid neoplasm originating from histiocytic cell clones. The lesions can occur in nodal or extranodal sites. A minority of cases present as unique cutaneous lesions. The definitive diagnosis is made by immunohistochemistry. The treatment depends on the severity of the disease. Herein, we report a case of histiocytic sarcoma in a 65-year-old female presenting with subcutaneous swellings and ulcerated coalescing nodules on the forearms and thighs with metastasis to the lung and treated with systemic chemotherapy.

Comprehensive Genomic Profiling of 104 Rare Histiocytic and Dendritic Cell Neoplasms Reveals Shared and Distinct Targetable Genomic Alterations

Introduction: Histiocytic and dendritic neoplasms are a diverse group of uncommon hematologic tumors arising from monocytic or dendritic cell lineage. While genomic profiles for the more common entities Langerhans cell histiocytosis and Erdheim-Chester disease are established, less common neoplasms in this broad category are poorly characterized. In the current study, we assessed the genomic landscape of these often aggressive histiocytic and dendritic cell neoplasms to identify distinct mutational signatures for each subtype in the current WHO classification system. Methods: 104 histiocytic and dendritic cell neoplasmswere tested during routine clinical care by hybridization capture of 406 cancer-related genes to detect base substitutions, small indels, amplifications (amp), deletions, and rearrangements. Tumor mutational burden (TMB, mutations/Mb) was determined on ~1.1 Mbp of sequenced DNA. Review of pathology reports, histopathology, and patient clinical data was performed. Cases included 48 follicular dendritic cell sarcoma (FDCS), 37 histiocytic sarcoma (HS), 8 interdigitating dendritic cell sarcoma (IDCS), 5 Langerhans cell sarcoma (LCS), 4 indeterminate cell histiocytosis (ICH), 1 fibroblastic reticular cell tumor (FRCT), and 1 inflammatory pseudotumor-like follicular/fibroblastic dendritic cell sarcoma (FDC/FRCS). Results: Pathogenic or likely-pathogenic genomic alterations (GAs) in the four most common sarcoma subgroups are summarized in the Table. CDKN2A and TP53 pathogenic mutations were the most frequent GAs observed in the cohort, present in 27% and 20% of the cases, respectively. Compared to the rest of the cohort, FDCS showed significantly more cases harboring a pathogenic GA in genes involved with NFkB pathway regulation (58% vs. 18%, p<0.0001). Other relevant alterations in FDCS included NTRK1 (2 cases; 1 NTRK1-PDIA3 fusion and 1 amp), NTRK3 (1 case), FGFR3 (1 amp), STAT3 (3 cases) and PTEN (3 cases). Compared to the rest of the cohort, HS showed significantly more cases with pathogenic GAs in the MAPK pathway (59% vs. 19%, p<0.0001), including 3 cases with BRAF fusions. Other relevant alterations in HS included PTEN (3 cases), PDGFRA (2 amp), MET (2 amp), 2 IGH-BCL2 fusions, and 1 IGH-BCL6 fusion. IDCS cases showed pathogenic MAPK GAs in 88% (7/8), and TET2 mutations were identified in 50% (4/8). A single NTRK1-TPR fusion was identified. LCS cases demonstrated GAs in both MAPK and NFkB pathways (4/5 and 3/5 cases, respectively). 2/4 cases of ICH demonstrated NCOA2-ETV3 fusions; TET2 mutations were present in the remaining two cases. The FRCT case contained an NRAS GA, and the FDC/FRCS cases had EBV (HHV-4) sequence reads. Conclusions: Our findings provide a comprehensive view of the shared and distinct genomic features among these rare histiocytic and dendritic cell neoplasms. The frequent inactivation of CDKN2A, which normally encodes an endogenous CDK inhibitor, suggests possible effectiveness of pharmacologic CDK4/6 inhibitors in treatment of this subset of cases. There are significant differences in the molecular profiles of different diseases: 58% of FDCS cases contain at least one pathogenic alteration in the NFkB pathway, while 59% and 88% of HS and IDCS cases contain potentially-actionable MAPK pathway mutations, respectively. LCS cases show frequent mutations in both pathways. Potentially-actionable molecular alterations are identified in 63/104 (61%) histiocytic and dendritic tumors in our cohort. These results illustrate the importance of performing comprehensive genomic profiling to define treatment strategies, including clinical trial "molecular eligibility" and more fully inform personalized therapeutic options. Disclosures Hasserjian: Jazz Pharmaceuticals: Consultancy; Promedior, Inc.: Consultancy. Montesion:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Sokol:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Pavlick:F. Hoffman La Roche, Ltd.: Equity Ownership; Foundation Medicine, Inc.: Employment. Shah:F. Hoffman La Roche, Ltd.: Equity Ownership; Foundation Medicine, Inc.: Employment. Danziger:F. Hoffman La Roche, Ltd.: Equity Ownership; Foundation Medicine, Inc.: Employment. Killian:F. Hoffman La Roche, Ltd.: Equity Ownership; Foundation Medicine, Inc.: Employment. Severson:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Duncan:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Elvin:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Miller:F. Hoffman La Roche, Ltd.: Equity Ownership; Foundation Medicine, Inc.: Employment. Ross:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Vergilio:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Williams:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership.

Canine histiocytic sarcoma cell lines with SHP2 p.Glu76Gln or p.Glu76Ala mutations are sensitive to allosteric SHP2 inhibitor SHP099.

Some canine cases of histiocytic sarcoma (HS) carry an activating mutation in the src homology two domain-containing phosphatase 2 (SHP2) encoded by PTPN11. SHP099 is an allosteric inhibitor of SHP2 that stabilizes SHP2 in a folded, auto-inhibited conformation. Here, we examined the expression and mutation status of SHP2 in five canine HS cell lines and evaluated the growth inhibitory properties of SHP099 against these cell lines. All five of the canine HS cell lines expressed SHP2, with three of the lines each harbouring a distinct mutation in PTPN11/SHP2 (p.Glu76Gln, p.Glu76Ala and p.Gly503Val). In silico analysis suggested that p.Glu76Gln and p.Glu76Ala, but not p.Gly503Val, promote shifting of the SHP2 conformation from folded to open-active state. SHP099 potently suppressed the growth of two of the mutant cell lines (harbouring SHP2 p.Glu76Gln or p.Glu76Ala) but not that of the other three cell lines. In addition, SHP099 suppressed ERK activation in the cell line harbouring the SHP2 p.Glu76Ala mutation. The SHP2 p.Glu76Gln and p.Glu76Ala mutations are considered to be activating mutations, and the signal from SHP2 p.Glu76Ala is inferred to be transduced primarily via the ERK pathway. Moreover, SHP099-sensitive HS cells, including those with SHP2 p.Glu76Gln or p.Glu76Ala mutations, may depend on these mutations for growth. Therefore, targeting cells harbouring SHP2 p.Glu76Gln and p.Glu76Ala with SHP099 may be an approach for the treatment of canine HS.

Activating Mutations in PTPN11 and KRAS in Canine Histiocytic Sarcomas.

While the genetic contributions to the predisposition of Bernese mountain dogs (BMDs) to histiocytic sarcoma (HS) remains unclear, some insights into key genetic drivers have been gained. Our group recently reported a mutation in the PTPN11 gene (E76K). We have now identified a second missense mutation in PTPN11 (G503V), and a mutation in KRAS (Q61H) present in HS cell lines. These mutations are associated with malignancies in humans, and known to be gain-of-function mutations that result in activation of the mitogen-activated protein kinase (MAPK) pathway. The goal of the present study was to evaluate the prevalence of these mutations in a large sample of HS cases from BMDs and golden retrievers, and in lymphoma cases, from a cohort of BMDs. Mutations in PTPN11 were present in HS in 41/96 (43%) BMDs, and in 3/13 (23%) golden retrievers. PTPN11 mutations E76K and G503V did not coexist in the same neoplasm. The KRAS mutation was much less frequent, with a prevalence of 3.1% (3/96). We did not identify either PTPN11 nor KRAS mutations in any of the lymphoma samples. These results point out the potential relevance of PTPN11 and KRAS mutations as activators of the oncogenic MAPK pathway for canine HS, particularly in BMDs.

Identification of diverse activating mutations of the RAS-MAPK pathway in histiocytic sarcoma

Recent studies have demonstrated recurrent activating mutations involving the classical MAPK and PI3K signaling pathways in a large proportion of histiocytic neoplasms, such as Langerhans cell histiocytosis. However, very little is known about the molecular genetics of histiocytic sarcoma, a rare aggressive malignant neoplasm that shows pathologic characteristics of mature macrophages. Here we report the genomic characteristics of a large cohort of histiocytic sarcomas (n = 28) using a targeted next-generation sequencing approach to identify driver alterations. We identified recurrent mutations involving the RAS-MAPK signaling pathway (MAP2K1, KRAS, NRAS, BRAF, PTPN11, NF1, CBL) in a majority (57%) of histiocytic sarcoma cases and report a clinical response to a MEK inhibitor (Cobimetinib) in a patient with a NF1-mutated histiocytic sarcoma. A smaller subset of cases (21%) also showed mutations resulting in activation of the PI3K signaling pathway (PTEN, MTOR, PIK3R1, PIK3CA). In addition, the tumor-suppressor gene CDKN2A was the most frequently altered gene (46%). Further, a subset of histiocytic sarcoma cases shows striking molecular genetic similarities to B cell lymphomas, supporting a clonal relationship between B cell neoplasms and a subset of histiocytic sarcomas. These findings support a cooperative role for MAPK, PI3K, and cyclin-CDK4/6-INK4 signaling in the pathogenesis of histiocytic sarcoma and provide a rational basis for targeting these pathways.

Establishment and characterization of a cell line from a feline histiocytic sarcoma

Feline histiocytic sarcoma (HS) is an aggressive and uncommon tumor originating from dendritic cells/macrophages. Here, a feline HS cell line, FHS-1, was established from a case of feline HS and characterized. Immunohistochemically, FHS-1 cells were positive for vimentin and Iba-1, and negative for MHC class II and CD163. FHS-1 cells were positive for α-naphthyl butyrate esterase staining, which was clearly inhibited by sodium fluoride. FHS-1 cells had phagocytic and antigen uptake/processing activities. Moreover, FHS-1 cells were tested for susceptibility to feline infectious peritonitis virus (FIPV) strain 79-1146; however, this cell line was not susceptible to this viral strain. Although FHS-1 cells lost the expression of MHC class II and CD163, our findings indicate that FHS-1 is a feline HS cell line that retains functional properties of dendritic cells/macrophages in terms of phagocytic and antigen uptake/processing activities. While FHS-1 cells are not suitable for in vitro study of FIP using strain 79-1146, they may be applicable for studies aimed at developing new diagnostic and therapeutic strategies for feline HS.

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.

Clinicopathologic analysis of 7 cases of histiocytic sarcoma

Clinicopathologic analysis of 7 cases of histiocytic sarcoma

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.

Multifocal Gastric Histiocytic Sarcoma Presenting as Gastrointestinal Bleeding

Histiocytic sarcoma is a rare malignancy that accounts for less than 1% of hematologic neoplasms, and shows morphologic and immunophenotypic non-Langerhans histiocytic differentiation. Commonly presents with nodal involvement, however extranodal sites are involved in 1/2 of cases. The skin and gastrointestinal (GI) tract are commonly involved. GI involvement manifests as abdominal mass, pain, intestinal obstruction, lower GI bleeding, or weight loss. We present case of histiocytic sarcoma manifesting as upper GI bleeding from innumerable synchronous gastric polyps. A 76 y/o female with CAD requiring multiple coronary stents, CABG, and AICD on dual antiplatelet therapy presented with melena and hematemesis. EGD revealed innumerable sessile and pedunculated polyps in the gastric body, fundus, and antrum. Two oozing polyps up to 5.3cm in diameter required polypectomy. Pathology showed histiocytic sarcoma. CT-scan was negative for metastases. 4 days post-discharge she developed further GI bleeding that required total gastrectomy with Roux-en-Y reconstruction for hemostasis. Intra-operatively no metastases were seen and negative margins were obtained. Two months later, the patient had recurrent hematemesis. CT scan showed small bowel obstruction and an intraluminal lesion, confirmed to be recurrent histiocytic sarcoma on endoscopic biopsies. The patient was discharged with plans for outpatient treatment, but sadly expired one month later. Although histiocytic sarcoma has been described throughout the GI tract, tumor confined to the stomach has only been described in 10 cases. Upon literature review, these have been mainly described in Asian populations and associated with H. pylori infection. Histiocytic sarcoma may present as a unifocal or multifocal tumor. Disease course is difficult to predict due to scarcity of reports, but aggressive behavior has been described. Our case illustrates the propensity for multifocal histiocytic sarcoma to behave aggressively despite complete resection with negative margins. Despite complete resection, distal recurrence has been described in 50% of cases and local recurrence in 20% of the cases. Multifocal disease confers a poor prognosis and is associated with poor response to chemotherapy. Our case represents an unusual case of multifocal disease limited to one organ. Complete margin-negative resection was possible, but the tumor recurred regionally in the jejunum, reflecting propensity to recur distantly rather than locally.Figure. 56: mm oozing pedunculated polyp seen on proximal gastric body on EGD at initial presentation.Figure: Innumerable gastric polyps throughout the fundus and body of the stomach.Figure: Jejunal polyp representing recurrence after margin negative total resection with gastrectomy.

An extremely rare neoplasm, histiocytic sarcoma: A report of two cases with an aggressive clinical course

Abstract Histiocytic sarcoma (HS) is an extremely rare malignant neoplasm accounting for less than 1% of all hemato-lymphoid neoplasms. Sixty percent of all cases are metastatic at presentation and the prognosis is poor. Two cases of HS with an aggressive clinical course are presented. The first case was a 58-year-old man admitted to our hospital with back pain and paresthesia of the lower extremities. Magnetic resonance imaging (MRI) of the thoracic spine revealed a mass measuring 48 × 15 mm between the T2‒T5 paravertebral area, entering the spinal channel via the neural foramen and compressing the spinal cord. The mass was completely resected and pathological and immunohistochemical staining confirmed the diagnosis of HS. After three cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and two cycles of carboplatin/paclitaxel, the patient died due to disease progression after 9 months. The second case is a 48-year-old man who presented with fever and weight loss, and complained of back pain for 2 months. Thoracic vertebral MRI revealed a lesion destructing the T6, T7 and T9 vertebral corpus and a mass measuring 2.5 × 2 cm near the T6‒T7 transverse process. Total-body fluorodeoxyglucose positron emission tomography (FDG-PET) imaging revealed bilateral inguinal hypermetabolic lymph nodes measuring 10 × 14 mm and osteolytic destructive bone lesions on the vertebral colon and pelvic bones. Pathological and immunohistochemical staining of bone marrow aspirate confirmed the diagnosis of HS. After three cycles of ifosfamide, carboplatin, etoposide (ICE) chemotherapy, the patient died due to disease progression after 3 months. Conclusions HS is an extremely rare malignant neoplasm of the monocytic/macrophage lineage, with no standardized chemotherapy regimen for multisystemic disease. Metastatic patients have a more aggressive clinical course than those with unifocal disease.

BRAFV600E expression in histiocytic sarcoma associated with splenic marginal zone lymphoma: a case report

BackgroundHistiocytic sarcoma is a rare histiocytic neoplasm of unknown etiology that constitutes less than 1% of hematologic malignancies. A few cases of histiocytic sarcoma harboring the BRAFV600E mutation have been reported, but this finding has not been confirmed in all studies.Case presentationWe report the case of a 63-year-old white woman with a history of splenic marginal zone lymphoma who presented with 2 weeks of right-sided neck swelling. Positron emission tomography revealed an intensely hypermetabolic and destructive soft tissue mass in her right skull base. A bone marrow biopsy was performed, which revealed an infiltrate of malignant cells characterized as large pleomorphic cells with frequent folded/irregular nuclei, variably prominent nucleoli, fine chromatin, and abundant amounts of eosinophilic cytoplasm. The malignant cells were positive for CD163, CD68 (granular), lysozyme (granular), CD4, and CD45 (partial). Based on the biopsy findings, she was diagnosed as having histiocytic sarcoma. The malignant cells tested positive for the BRAFV600E protein using immunohistochemistry. Before treatment of her histiocytic sarcoma could be initiated, she developed disseminated intravascular coagulation and acute hypoxemic respiratory failure secondary to non-cardiogenic pulmonary edema. She decided to pursue comfort care and died in our hospital 2 weeks following admission.ConclusionsOur case illustrates the aggressive nature of histiocytic sarcoma, and provides rare evidence that histiocytic sarcoma associated with indolent lymphomas may harbor the BRAFV600E mutation. Further research is needed to clarify the role of targeted therapies such as vemurafenib in the treatment of patients with this disorder.

Histiocytic sarcoma with bladder involvement: Case report and literature review

We report an unusual case of histiocytic sarcoma with bladder involvement. An 80 year-old man with a previous history of diffuse large B-cell malignant lymphoma presented with hematuria and back pain. Serial urine cytologies revealed no urothelial malignant cells, but cystoscopy showed a large intravesical mass. The patient underwent transurethral resection (TUR) of the tumor. The bladder TUR specimen showed a widely infiltrating epithelioid neoplasm, with intense immunohistochemical positivity for CD45 and histiocytic markers (CD68, lysozime and fascin). Histopathological diagnosis was histiocytic sarcoma. As the patient's condition was progressively deteriorating, only palliative care was indicated and he died one month after TUR. Although histiocytic sarcoma can often be widespread at the time of diagnosis, to our knowledge, this is the first report of a case presenting with urinary symptoms. Histiocytic sarcoma can mimic many other malignant lesions, and only immunohistochemistry can define the tumor cells, allowing correct therapy. We discuss the differential diagnosis and possible associations.

A histiocytic twist in a tale of GIST

Histiocytic sarcoma (HS) is a rare, non-Langerhan’s, malignant histiocytic neoplasm that occurs in lymph nodes and extranodal sites mainly the skin and intestine. Amidst the cases reported so far; majority of the cases previously diagnosed as HS have been Primary T cell lymphomas (PTCL). Cases primarily involving the extranodal sites are rare, with a confusing clinical picture and thus, are often misdiagnosed. Here we report a rare case of extranodal HS in a 54-year-old man, a previously treated case of gastrointestinal stromal tumor (GIST) of the stomach, who now presented with abdominal pain. On imaging, a growth was detected in the small bowel without accompanying lymphadenopathy.

Somatic mutations in histiocytic sarcoma identified by next generation sequencing.

Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 "Hotspot" oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6%] and G466R (VF of 29.6%) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4%), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities.

A Case of Histiocytic Sarcoma Arising in Head and Neck Region with Rhabdoid Differentiation

A Case of Histiocytic Sarcoma Arising in Head and Neck Region with Rhabdoid Differentiation

Histiocytic Sarcoma in a Kidney Transplant Patient: A Case Report and Review of the Literature.

Objective. Histiocytic sarcoma (HS) is an aggressive neoplasm with only limited number of reported series of cases and rare case reports of occurrence as a posttransplant neoplastic disorder. The etiology and pathogenesis of the disease is unknown and the optimal treatment is still under investigation. We describe an unusual case of HS in a patient with a remote history of kidney transplant. Method and Results. A 54-year-old male with a remote history of renal transplantation under maintenance immunosuppression presented with features of sepsis. CT abdomen revealed multiple heterogeneous masses in bilateral native kidneys and liver and enlarged abdominal and retroperitoneal lymph nodes. Viral serology work-up was negative. Needle core biopsy revealed a highly undifferentiated neoplasm comprised of highly atypical large cells with eosinophilic to vacuolated cytoplasm and hemophagocytosis. Extended panel of immunohistochemistry proved histiocytic lineage for the tumor cells. The patient expired 2 weeks following the diagnosis. Conclusion. Our case along with three previously published case reports raised the possibility of HS as a treatment-related neoplasm or a posttransplantation neoplastic disorder in solid organ transplant recipients.