Descriptive Analysis of Histiocytic and Dendritic Cell Neoplasms: A Single-Institution Experience.

PURPOSE: Histiocytic and dendritic cell neoplasms are rare hematologic tumors. This study aimed to describe the epidemiologic features of the entire spectrum of histiocytic and dendritic cell neoplasms, including clinicopathological variables and patient outcomes. MATERIALS AND METHODS: We comprehensively reviewed 274 patients who were diagnosed with histiocytic and dendritic neoplasms at Severance Hospital, Seoul, South Korea between 1995 and 2018. RESULTS: The most common neoplasm was Langerhans cell histiocytosis (LCH), followed by dermal xanthogranuloma. Among non-LCH sarcomas, histiocytic sarcoma (HS) showed a relatively high prevalence, followed by follicular dendritic cell sarcoma (FDCS). Disseminated juvenile xanthogranuloma (DJG), Erdheim-Chester disease (ECD), indeterminate dendritic cell tumor (IDCT), and interdigitating dendritic cell sarcoma (IDCS) rarely occurred. Generally, these tumors presented in childhood, although the non-LCH sarcoma (HS/FDCS/IDCS/IDCT) group of tumors and ECD occurred in late adulthood. Multiorgan involvement and advanced Ann-Arbor stage, as well as recurrence and death of disease, were not uncommon. The non-LCH sarcoma group had the worst overall survival, compared to the DJG, ECD, and LCH groups. CONCLUSION: Our findings indicate that histiocytic and dendritic cell neoplasms exhibit heterogeneous epidemiologic characteristics and that some patients may have unfavorable outcomes, especially those with non-LCH sarcoma.

A retrospective survey on canine intracranial tumors between 2007 and 2017.

To clarify the prevalence of canine intracranial tumors in Japan, a retrospective study was performed using data on 186 canine intracranial tumors. Of 186 cases, 159 cases (85.5%) were primary and 27 cases (14.5%) were secondary intracranial tumors. Among primary intracranial tumors, meningioma (50.9%) was the most common, followed by glial tumors (21.4%) and primary intracranial histiocytic sarcoma (12.6%). These 3 tumors were most frequently found in middle-aged to elderly dogs without any sex predilection. Regarding glial tumors, the incidence of oligodendroglial tumors (79.4%) was higher than that of astrocytic tumors (17.6%). A significant breed predisposition (P<0.05) was observed for meningioma in Rough Collie, Golden Retriever, Miniature Schnauzer, and Scottish Terrier; for glial tumors in Bouvier de Flandres, French Bulldog, Newfoundland, Bulldog, and Boxer; for primary intracranial histiocytic sarcoma in Pembroke Welsh Corgi, Siberian Husky, and Miniature Schnauzer. The high incidence of oligodendroglial tumors in dogs and the breed predisposition for primary intracranial histiocytic sarcoma in Pembroke Welsh Corgi have not been reported in previous epidemiological studies on canine tumors. Since the incidence of intracranial tumors was vary among dog breeds, the present results demonstrate the uniqueness of the canine breed population in Japan.

Histiocytic sarcoma in 14 miniature schnauzers - a new breed predisposition?

OBJECTIVES: To describe a series of miniature schnauzers diagnosed with histiocytic sarcoma and assess for possible breed predisposition. MATERIALS AND METHODS: Medical records of miniature schnauzers with a diagnosis of histiocytic sarcoma between January 2008 and April 2015 were reviewed. Data collected included signalment, body weight, presenting complaint, date of diagnosis, clinicopathologic and diagnostic imaging findings, treatment, therapeutic response, date of death or last follow-up and necropsy findings. Breed predisposition was assessed with odds ratios, using breed-matched dogs without histiocytic sarcoma admitted during the study period as controls. Pedigree analysis was performed for dogs with available registration information. RESULTS: Fourteen miniature schnauzers were diagnosed with histiocytic sarcoma during the study period, making them over-represented among the hospital population (odds ratio=4·8, P=0·0009). Disease was considered localised in ten dogs and disseminated in four. Of the dogs with localised disease, nine were diagnosed with primary pulmonary histiocytic sarcoma based on the presence of a large pulmonary mass with (n=7) or without (n=2) evidence of intra-thoracic metastasis, and one had gastric histiocytic sarcoma with nodal metastasis. Treatments varied, but an aggressive clinical course was found in most patients. Pedigree analysis revealed a recent common ancestor for a subset of the dogs assessed. CLINICAL SIGNIFICANCE: Miniature schnauzers were over-represented among dogs with histiocytic sarcoma in this patient population. Pedigree analysis supports an inherited risk factor, which has not previously been suggested in the breed. Primary pulmonary involvement with or without intra-thoracic metastasis was common in this cohort.

Risk Factors Associated with Development of Histiocytic Sarcoma in Bernese Mountain Dogs.

BACKGROUND: Histiocytic sarcoma (HS) is a rare but aggressive malignancy in humans that is poorly responsive to existing treatments. Although rare in most breeds of dogs, HS is common in Bernese mountain dogs (BMDs). OBJECTIVE: Determine risk factors associated with development of HS in BMD. ANIMALS: A total of 216 BMD were registered with the Berner-Garde Foundation. METHODS: An internet-based cross-sectional survey was used to collect information from owners of BMD diagnosed with HS and owners of disease-free littermates of dogs with HS. Mixed-effects logistic regression (MELR) and conditional logistic regression (CLR) were used in parallel to examine associations between potential risk factors and the occurrence of HS. RESULTS: When controlling for litter as a marker of relatedness, dogs diagnosed with orthopedic conditions were found to be more likely to develop HS (MELR, OR: 2.5, 95% CI: 1.5, 5.2; CLR, OR: 2.81, 95% CI: 1.1, 7.3), whereas dogs receiving prescription anti-inflammatory medications were found to be at considerably lower risk of developing HS (MELR, OR: 0.42, 95% CI: 0.2, 0.8; CLR, OR: 0.32, 95% CI: 0.1, 0.8). CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest inflammation may be a modifiable risk factor for the development of HS in BMD.

Histiocytic sarcoma as a secondary malignancy: pathobiology, diagnosis, and treatment.

Histiocytic sarcoma (HS) is an extremely rare non-Langerhans cell disorder with an aggressive course and limited treatment options. Recent advances in molecular/genetic sequencing have suggested a common clonal origin between various hematolymphoid disorders and cases of secondary HS. Deriving conclusions from previously reported cases of HS arising secondarily to certain hematolymphoid disorders, here we have tried to provide insight into the mechanisms influencing this evolution. We also discuss a clinical case of a 72-year-old man with a diagnosis of chronic myeloid leukemia (CML), presenting subsequently with a heterogeneous liver mass positive with a diagnosis of HS. The liver mass showed a retained BCR-ABL1 translocation suggesting clonality between the CML and HS. As seen in our case and other reported cases of HS derived secondarily, the concurrent expression of immunoglobulin heavy (IGH)-/light-chain rearrangements or cytogenetic markers common to the primary malignancy suggests an evolutionary mechanism involving lineage switching that could potentially be influenced by genetic or epigenetic cues which may occur at the level of a progenitor or the malignant cell itself.

Causes of death and the impact of histiocytic sarcoma on the life expectancy of the Dutch population of Bernese mountain dogs and Flat-coated retrievers.

Bernese mountain dogs and Flat-coated retrievers are predisposed to hereditary oncological diseases. Since 1986 several authors have reported a high prevalence of tumours in both breeds, especially malignant histiocytosis/histiocytic sarcoma, which has a negative influence on life expectancy. However, many earlier reports included relatively low numbers of dogs, distributed over a small number of broad categories, often using outdated disease criteria. The aim of this study was to provide new data on causes of death, and the relative role of tumours, especially histiocytic sarcoma, collected and verified in a large number of dogs of both breeds in co-operation with dog owners and veterinarians. The study demonstrates that the death of at least 55.1% of Bernese mountain dogs and 63.8% of Flat-coated retrievers is associated with malignant tumours. In addition, it appears that over 1/7 of all Bernese mountain dogs and Flat-coated retrievers die because of histiocytic sarcoma. This emphasises the need for further research on tumours, especially histiocytic sarcoma.

Thalidomide therapy for aggressive histiocytic lesions in the pediatric population.

Aggressive histiocytic lesions are uncommon in the pediatric population. These neoplasms occur in isolation or after therapy for other types of hematopoietic malignancy such as T-cell acute lymphoblastic leukemia. The etiology of these lesions is poorly understood, and no definitive standard of care has been established for patients with these diagnoses. Here, we report the success of thalidomide treatment for 2 subtypes of histiocytic proliferation--metastatic histiocytic sarcoma and extracutaneous juvenile xanthogranuloma--in pediatric patients. Our findings highlight the importance of considering thalidomide therapy in this unique and difficult to treat patient population.

Tumors associated with avian leukosis virus subgroup J in layer hens during 2007 to 2009 in China.

In the 3 years leading up to November 2009, 6 different types of naturally occurring neoplasms associated with avian leukosis virus subgroup J (ALV-J) were diagnosed by histopathology, polymerase chain reaction (PCR) and immunohistochemistry (IHC) in 140 layer hens out of approximately 100,000. The most prevalent tumor type was hemangioma (50%) in commercial layer flocks; the second most prevalent neoplasm type was myelocytoma (38.6%); a small number of ALV-J positive lymphomas (4.3%) that were not associated with Marek's disease (MD) or lymphoid leukosis (LL) was observed. Histiocytic sarcomas (2.1%) were found mainly in the spleen, liver and kidney. Fibrosarcomas (2.8%) presented as metastatic thigh, liver, lung and kidney neoplasms. Three cases of intestinal adenocarcinoma (2.1%) were found associated with ALV-J. Chickens with multiple tumors were a common phenomenon. Usually, hemangiomas plus myelocytomas (8.6%), myelocytomas plus histiocytic sarcomas (2.1%), hemangioma plus myelocytoma and lymphoma (3.6%) were found in various viscera organs. The present report describes the occurrence of multiple neoplasms associated with ALV-J in field layer hens.

Epidemiology, pathology, and genetics of histiocytic sarcoma in the Bernese mountain dog breed.

Histiocytic sarcoma (HS) refers to a highly aggressive and frequently disseminated neoplastic disease belonging to the class of canine histiocytic proliferative disorders. Disseminated HS (previously called malignant histiocytosis) is highly breed specific, with Bernese mountain dogs (BMDs), rottweilers, and retrievers having a high prevalence with a frequency of approximately 25% in the BMD breed. We collected DNA samples and clinical information from 800 BMDs, of which 200 are affected by HS. To better characterize the physiopathology and epidemiology, an in-depth analysis of 89 BMD cases has been performed. The mean age of onset was 6.5 years, males and females being equally affected. The clinical features, biochemical parameters, and pathological features have been determined. The life span after diagnosis has been estimated to be 49 days. A large BMD pedigree of 327 dogs, 121 of which are affected, was assembled. Using a subset of 160 BMDs, encompassing 21 complete sibships, we now propose an oligogenic transmission mode of the disease. Whole-genome linkage scans as well as association studies using a case/control analysis, in parallel with expression profiling of neoplastic versus normal histiocytes, are all underway. Altogether, these complementary approaches are expected to localize the genes for HS in the BMD, leading to advances in our knowledge of histiocyte diseases in dogs and humans.

Skeletal lesions of histiocytic sarcoma in nineteen dogs.

The purpose of this study was to describe the clinical and radiographic findings in dogs with bone lesions secondary to histiocytic sarcoma. Nineteen dogs with radiographically identified bone lesions that were histologically diagnosed as histiocytic sarcoma were assessed. The medical records, all available radiographs and histologic sections were reviewed retrospectively. Dogs were subcategorized into localized or disseminated histiocytic sarcoma groups. Golden Retrievers or Rottweilers greater than 5 years of age, with a history of lameness or neurologic deficits localized to the spinal cord was the most common presentation. Fifteen of 19 dogs had a radiographically detectable soft tissue mass associated with bone destruction. The bone lesions had aggressive characteristics and the sites of involvement included periarticular bones (n = 11), vertebrae (n = 6), proximal humerus (n = 5), and rib (n = 2). Fifteen of 19 dogs had disseminated histiocytic sarcoma, and four had localized histiocytic sarcoma. All Rottweilers had disseminated histiocytic sarcoma. Histiocytic sarcoma should be considered as a differential diagnosis for aggressive periarticular, vertebral, or proximal humeral bone lesions identified on radiographs. The index of suspicion should be increased in greater than 5-year-old Golden Retrievers and Rottweilers when a soft tissue mass is associated with the bone lesion on radiographs or myelography. Bone involvement with histiocytic sarcoma, and the Rottweiler breed, was associated with the disseminated form of the disease.

Malignant histiocytosis: a reassessment of cases formerly classified as histiocytic neoplasms and review of the literature.

Malignant histiocytosis (MH) and true histiocytic lymphoma (THL) are hematopoietic malignancies of the mononuclear phagocytic system distinguished from each other by clinical presentation and presumed cell of origin. THL present as a localized mass derived from the fixed tissue histiocyte which may or may not disseminate. MH originates from the circulating monocyte or tissue macrophage and is characterized by a syndrome of systemic symptoms, pancytopenia, adenopathy, hepatosplenomegaly, and wasting. The distinction between MH and THL is at times arbitrary and overlap exists between these syndromes. The clinicopathologic studies that defined these entities were performed prior to the development of immunophenotyping and other molecular techniques currently used to ensure proper classification of hematopoietic malignancies. Nine patients from the University of Minnesota originally diagnosed with MH were retrospectively analyzed using a panel of antibodies reactive against T cell, B cell, and myelomonocytic antigens. Only one patient was reclassified as a possible histiocytic malignancy after reevaluation. Similar immunophenotyping studies have also shown cases previously diagnosed as MH or THL express lymphoid antigens, and would now be classified as Ki-1 positive anaplastic large cell lymphoma (ALCL) or some other hematopoietic neoplasm. These results indicate true histiocytic neoplasms are extremely rare, and previous concepts concerning clinical presentation and therapeutic outcome of the entities are inaccurate. In this paper we summarize the results of multiple retrospective analyses of cases previously diagnosed as MH or THL, including our experience at University of Minnesota, to illustrate the overall rarity of these entities. The current literature on malignant histiocytic disorders is reviewed, and the clinical presentation of patients determined to have histiocytic malignancies using contemporary analytical techniques is discussed.

Histiocytic neoplasias: immunohistochemical evaluation of their frequencies among malignant lymphoma and related conditions in Japan.

Through histologic review of 1,766 cases with malignant lymphoma and related conditions, 35 cases (2%) were selected as probable histiocytic neoplasias. Proliferating cells in these cases had voluminous, granulated cytoplasm, and round to irregularly shaped nuclei often with bi- or multinucleated forms showing monomorphous or polymorphous proliferation accompanying small lymphocytes, plasma cells, and, less frequently, eosinophils. Cases showing proliferation of convoluted cells with numerous benign-appearing histiocytes or large cells with clear cytoplasm were excluded under a diagnosis of T-cell lymphoma. To evaluate the immunologic character of proliferating cells, immunohistochemistry using antibodies Mx-Pan B, MB-1, MT-1, UCHL-1, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 alpha, S-100 beta, Leu M1, epithelial membrane antigen, and Ki-1 were carried out in 23 cases. Naphthol-ASD-chloracetate reaction and toluidine blue stain were also performed. These procedures revealed that 12 cases (52%) were B-cell type, three cases (13%) T-cell type, six cases (26%) true histiocytic type, and two cases null type. Therefore, the frequency of cases with true histiocytic neoplasias among cases with malignant lymphoma and related conditions in Japan may be 0.5%.

[Histiocytosis syndrome in children]. / Histiocytosesyndromer hos børn.

The recommended classification of the histiocytosis syndromes in children is as follows: 1. Langerhans' cell histiocytoses. 2. histiocytoses of mononuclear phagocytes. 3. neoplastic histiocytoses. The previous term, histiocytosis X, including eosinophilic granuloma of bone, the Hand-Schüller-Christian syndrome and Letterer-Siwe's disease, is now more correctly called Langerhans' cell histiocytosis (LCH) since the infiltrating cell in histiocytosis X both histologically and immunophenotypically is identified as the Langerhans' cell. Local and generalized LCH differmarkedly with respect to treatment and outcome. It is therefore necessary to perform an extensive investigation at the time of the initial evaluation of the patient. The most common mononuclear phagocytic syndromes are the familial erythrophagocytic lymphohistiocytosis and infection-associated or reactive hemophagocytic syndromes. The pathognomonic cell in familial erythrophagocytic lymphohistiocytosis is possibly a hybrid phenotype sharing characteristics of the two main types the mononuclear phagocyte system - i.e. the Langerhans' cells and phagocytic macrophages. Malignant histiocytosis is rarely seen in children and is a form of the Ki-1 positive anaplastic cell lymphoma.