Tissue Histiocytes Research Articles

Orbital histiocytosis; From A to Z.

Histiocytosis is one of the most challenging diseases in medical practice. Because of the broad spectrum of clinical manifestations, systemic involvements, unknown etiology, and complex management, different types of histiocytosis are still a big question mark for us. Orbital histiocytosis is characterized by the abnormal proliferation of histiocytes in orbital tissues. It could affect the orbit, eyelid, conjunctiva, and uveal tract. Orbital histiocytosis can cause limited eye movement, proptosis, decreased visual acuity, and epiphora. In this study, we review the novel findings regarding the pathophysiology, diagnosis, and treatment of different types of histiocytosis, focusing on their orbital manifestations. This review was performed based on a search of the PubMed, Scopus, and Embase databases or relevant published papers regarding orbital histiocytosis on October 9th, 2023. No time restriction was proposed, and articles were excluded if they were not referenced in English. 391 articles were screened, most of them being case reports. The pathophysiology of histiocytosis is still unclear. However, different mutations are found to be prevalent in most of the patients. The diagnostic path can be different based on various factors such as age, lesion site, type of histiocytosis, and the stage of the disease. Some modalities, such as corticosteroids and surgery, are used widely for treatment. On the other hand, based on some specific etiological factors for each type, alternative treatments have been proposed. Significant progress has been made in the detection of somatic molecular changes. Many case studies describe various disease patterns influencing the biological perspectives on different types of histiocytosis. It is necessary to continue investigating and clustering data from a broad range of patients with histiocytosis in children and adults to define the best ways to diagnose and treat these patients.

Melatonin Level and Activity of Nucleolar Organizer Regions in the Prognosis of Infertility in Women with Ovarian Endometriosis

Introduction. Endometriosis is a multifactorial disease, affecting about 10 % of women of reproductive age. The purpose of the work is predicting the development of infertility in women with ovarian endometriosis by determining urine melatonin levels and activity indicators of nucleolar organizer regions in endometrioid ovarian heterotopias.Materials and methods. In the Clinic of South Ural State Medical University from 2018 to 2020, 2 groups of women with ovarian endometriosis were studied: group 1 — with infertility (n = 22); group 2 — without it (n = 27). The level of urinary 6-SMT and the activity of ribosomal synthesis were determined.Results. The level of 6-SMT is reduced in patients with stage I ovarian endometriosis. At stagesII and III, the level of 6-SMTis lower in women with infertility than without it: Stage II — (38.82±1.49) ng/ml and (93.04±3.64) ng/ml (p < 0.001); Stage III — (42.84±1.85) ng/ml and (58.06±1.65) ng/ml (p = 0.340). The activity of ribosomal synthesis in epithelial cells of endometrioid heterotopias increases at stage III. In fibroblasts of the stroma of endometrioid heterotopias, the activity of ribosomal synthesis is higherin women with stage III infertility, and in histiocytes— in women with stage II infertility. A logistic stepwise regression analysis was carried out and the most important predictors influencing the development of infertility were identified.Discussion. The decrease in melatonin in women with ovarian endometriosis, suffering from infertility, as well as in stage I ovarian endometriosis is consistent with the research of M. I. Yarmolinskaya et al. (2019). In the presence of infertility, activation of connective tissue histiocytes begins in the early stages. The results obtained may reflect the immunomodulatory effect of melatonin, which is expressed inincreased functional activity of connective tissue histiocytes and fibroblasts.Conclusion. Using mathematical analysis, the most important indicators that influence the reproductive prognosis in women with ovarian endometriosis (activity of nucleolar organizer regions, urine 6-SMT level) were determined, which makes it possible to create a model for calculating an individual reproductive prognosis.

The use of topical Rapamycin in successfully treating non-Langerhans cell histiocytosis in a pediatric patient

Non-Langerhans cell histiocytosis (non-LCH) refers to a collection of medical conditions distinguished by the excessive growth of histiocytes in bodily tissues. It is important to note that these conditions do not meet the established diagnostic criteria for Langerhans cell histiocytosis (LCH). Juvenile xanthogranuloma (JXG) and benign cephalic histiocytosis (BCH) represent the prevailing forms of cutaneous non-LCH. We present a case of JXG which responded to topical treatment with a 0.1% topical ointment of Rapamycin. Rapamycin, an immunosuppressive and antineoplastic agent, can thus be a viable alternative non-invasive topical modality for managing JXG. However, it is imperative to conduct prolonged observations to evaluate the efficacy and potential adverse reactions.

Multimodal Management With Immunotherapy, Radiation, and Surgery of Histiocytic Sarcoma Following Acute Lymphoblastic Leukemia: An Unusual Presentation of a Rare Disease.

Histiocytic sarcoma (HS) is a rare neoplasm with no known cause. This sarcoma is characterized by morphology similar to that demonstrated by mature tissue histiocytes and mostly afflicts adults. HSs typically have a poor prognosis due to a rapidly progressive clinical course. Our patient's case was unique due to its presentation four years after completion of treatment for B-cell acute lymphoblastic leukemia. The patient experienced progression with initial therapy for HS. With dual immunotherapy and radiation, however, the patient has remained clinically stable without detectable disease. Immunotherapy may be a successful and tolerable therapeutic option for histiocytic disease.

Identifying the potential origin of mucin in primary cutaneous mucinoses-A retrospective study and analysis using histopathology and multiplex fluorescence staining.

Primary cutaneous mucinoses (PCM) are rare diseases characterized by dermal or follicular mucin deposits. A retrospective study characterizing PCM to compare dermal with follicular mucin to identify its potential origin on a single-cell level. Patients diagnosed with PCM between 2010 and 2020 at our department were included in this study. Biopsy specimens were stained using conventional mucin stains (Alcian blue, PAS) and MUC1 immunohistochemical staining. Multiplex fluorescence staining (MFS) was used to investigate which cells were associated with MUC1 expression in select cases. Thirty-one patients with PCM were included, 14 with follicular mucinosis (FM), 8 with reticular erythematous mucinosis, 2 with scleredema, 6 with pretibial myxedema and one patient with lichen myxedematosus. In all 31 specimens, mucin stained positive for Alcian blue and negative for PAS. In FM, mucin deposition was exclusively found in hair follicles and sebaceous glands. None of the other entities showed mucin deposits in follicular epithelial structures. Using MFS, all cases showed CD4+ and CD8+ T cells, tissue histiocytes, fibroblasts and pan-cytokeratin+ cells. These cells expressed MUC1 at different intensities. MUC1 expression in tissue histiocytes, fibroblasts, CD4+ and CD8+ T cells, and follicular epithelial cells of FM was significantly higher than the same cell types in the dermal mucinoses (p < 0.001). CD8+ T cells were significantly more involved in expression of MUC1 than all other analysed cell types in FM. This finding was also significant in comparison with dermal mucinoses. Various cell types seem to contribute to mucin production in PCM. Using MFS, we showed that CD8+ T cells seem to be more involved in the production of mucin in FM than in dermal mucinoses, which could indicate that mucin in dermal and follicular epithelial mucinoses have different origins.

Neurology and the histiocytoses: a case of Rosai-Dorfman-Destombes disease.

The histiocytoses are a group of rare disorders characterised by the accumulation of neoplastic or non-neoplastic activated histiocytes in various tissues. Phenotypes vary widely from cutaneous lesions or lymphadenopathy that regress spontaneously to disseminated disease with poor prognosis. Neurological symptoms can be a presenting feature or appear during the course of disease. We present a challenging diagnostic and management case of Rosai-Dorfman-Destombes disease in a 48-year-old woman with a relapsing, partially steroid-responsive syndrome comprising patchy, non-length-dependent radiculoneuropathy with diffuse pachymeningitis and widespread systemic disease, and recent dramatic response to novel mitogen-activated kinase pathway inhibition. We discuss the clinical characteristics, diagnosis, recent breakthroughs in pathogenesis and emerging treatment options for Rosai-Dorfman disease and for the histiocytoses with neurological sequelae, including Langerhans cell histiocytosis and Erdheim-Chester disease.

Profound systemic alteration of the immune phenotype and an immunoglobulin switch in Erdheim-Chester disease in 78 patients from a single center

Erdheim-Chester disease (ECD) is a rare, systemic, non-Langerhans cell histiocytosis neoplasm, which is characterized by the infiltration of CD63+ CD1a- histiocytes in multiple tissues. The BRAFV600E mutation is frequently present in individuals with ECD and has been detected in hematopoietic stem cells and immune cells from the myeloid and systemic compartments. Immune cells and pro-inflammatory cytokines are present in lesions, suggesting that ECD involves immune cell recruitment. Although a systemic cytokine T-helper-1-oriented signature has been reported in ECD, the immune cell network orchestrating the immune response in ECD has yet to be described. To address this issue, the phenotypes of circulating leukocytes were investigated in a large, single-center cohort of 78 patients with ECD and compared with those of a group of 21 control individuals. Major perturbations in the abundance of systemic immune cells were detected in patients with ECD, with decreases in circulating plasmacytoid, myeloid 1, and myeloid 2 dendritic cells, mostly in BRAFV600E carriers, in comparison with individuals in the control group. Similarly, marked decreases in blood T-helper, cytotoxic, and B-lymphocyte numbers were observed in patients with ECD, relative to the control group. Measurement of circulating immunoglobulin concentrations revealed an immunoglobulin G switch, from IgG1 to IgG4 subclasses, which are more frequently associated with the BRAF mutation. First-line therapies, including pegylated interferon-a and vemurafenib, were able to correct most of these alterations. This study reveals a profound disturbance in the systemic immune phenotype in patients with ECD, providing important new information, helping to understand the physiopathological mechanisms involved in this rare disease and improving the therapeutic management of patients.

Abstract 829: Genetic risk factors for histiocytic sarcoma in a canine disease model

Abstract Histiocytic sarcoma is a rare, aggressive hematopoietic malignancy of mature tissue histiocytes with a poorly understood etiology in humans. A histologically and clinically similar counterpart in dogs affects two breeds at unusually high frequency, with 20-25% of Flatcoated Retrievers and Bernese Mountain Dogs developing histiocytic sarcoma, while the disease is extremely rare in other breeds. In this study, we leveraged the canine model system to investigate genetic risk factors for histiocytic sarcoma in the Flatcoated Retriever. Population bottlenecks and artificial selection during breed formation within last 200 years have created the unique breed structure in dogs, characterized by long linkage disequilibrium and low within-breed genetic diversity. This allows for the identification of disease-associated traits with relatively few markers and individuals. We conducted multiple genome-wide association studies in Flatcoated Retrievers in which we identified two loci conferring risk for histiocytic sarcoma (177 cases and 132 controls, total). The first locus, on canine chromosome (CFA) 5, also colocalizes with previously identified risk for hemangiosarcoma and B-cell lymphoma, two hematopoietic malignancies in the closely related golden retriever breed. The second locus is unique to the Flatcoated Retriever and increases risk for histiocytic sarcoma in combination with CFA5. There have been multiple reports of human histiocytic sarcoma diagnosis concurrent with other hematological cancers, including lymphoma, suggested to be the result of transdifferentiation or a common neoplastic progenitor. Here we link germline predisposition for histiocytic sarcoma and B-cell lymphoma to the same locus in retrievers. Subsequent whole genome, transcriptome, and ChIP sequencing, highlighted candidate genes at each locus with roles in cell migration, as well as candidate regulatory variants with predicted impact on transcription factor binding. This comprehensive, multi-omics approach has been previously largely unexplored in the canine model. Here we advance our knowledge of the biology of histiocytic sarcoma, which will have direct impact on canine health and elucidate the genetic mechanisms underlying a rare human cancer. Citation Format: Jacquelyn M. Evans, Heidi G. Parker, Jocelyn Plassais, Gerard R. Rutteman, Elaine A. Ostrander. Genetic risk factors for histiocytic sarcoma in a canine disease model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 829.

Multi-omics approach identifies germline regulatory variants associated with hematopoietic malignancies in retriever dog breeds.

Histiocytic sarcoma is an aggressive hematopoietic malignancy of mature tissue histiocytes with a poorly understood etiology in humans. A histologically and clinically similar counterpart affects flat-coated retrievers (FCRs) at unusually high frequency, with 20% developing the lethal disease. The similar clinical presentation combined with the closed population structure of dogs, leading to high genetic homogeneity, makes dogs an excellent model for genetic studies of cancer susceptibility. To determine the genetic risk factors underlying histiocytic sarcoma in FCRs, we conducted multiple genome-wide association studies (GWASs), identifying two loci that confer significant risk on canine chromosomes (CFA) 5 (Pwald = 4.83x10-9) and 19 (Pwald = 2.25x10-7). We subsequently undertook a multi-omics approach that has been largely unexplored in the canine model to interrogate these regions, generating whole genome, transcriptome, and chromatin immunoprecipitation sequencing. These data highlight the PI3K pathway gene PIK3R6 on CFA5, and proximal candidate regulatory variants that are strongly associated with histiocytic sarcoma and predicted to impact transcription factor binding. The CFA5 association colocalizes with susceptibility loci for two hematopoietic malignancies, hemangiosarcoma and B-cell lymphoma, in the closely related golden retriever breed, revealing the risk contribution this single locus makes to multiple hematological cancers. By comparison, the CFA19 locus is unique to the FCR and harbors risk alleles associated with upregulation of TNFAIP6, which itself affects cell migration and metastasis. Together, these loci explain ~35% of disease risk, an exceptionally high value that demonstrates the advantages of domestic dogs for complex trait mapping and genetic studies of cancer susceptibility.

Langerhans Cell Histiocytosis in Paediatric Zygoma Swelling.

Langerhans cell histiocytosis (LCH) is a rare neoplasm characterized by accumulation of histiocytes in various tissues. It has a wide clinical spectrum and its presentation may mimic clinical features of common diseases. High level of suspicion is required for early diagnosis. Here is a rare case of a rapidly aggressive LCH which first presented with right zygomatic swelling.

Nodal histiocytic sarcoma with prominent eosinophilic infiltration: expression of eotaxin-2 on tumor cells

BackgroundHistiocytic sarcoma (HS) is a rare neoplasm showing morphological and immunophenotypic features of mature tissue histiocytes. We report a patient with nodal HS exhibiting prominent reactive eosinophilic infiltration.Case presentationA 68-year-old man presented with intermittent left lower abdominal pain and weight loss over 3 months. A computed tomography scan revealed multiple abdominal nodules. Open biopsy of the mesenteric tumors was performed for definitive diagnosis. Histologically, the tumor was comprised of a diffuse noncohesive proliferation of pleomorphic large cells, including multinucleated cells. Neoplastic cells were positive for histiocytic markers (CD68, CD163, and LIGHT) and PD-L1 but lacked markers of Langerhans cells, follicular dendritic cells, and epithelial cells. Frequent reactive inflammatory cells were intermingled in the background. Interestingly, prominent eosinophilic infiltration was also noted. Spindle neoplastic cells were prone to be present around areas with little to no eosinophilic infiltration and exhibiting fibrosis and lymphatic vessel proliferation. Conversely, polygonal neoplastic cells were prone to be present around areas with relatively large amounts of eosinophilic infiltration without fibrosis or lymphatic vessel proliferation. Immunohistochemically, the tumor cells and reactive eosinophils expressed eotaxin-2 and eotaxin-3, respectively.ConclusionWe revealed that eotaxins induced the selective migration of eosinophils into tissues in this case. These eosinophils may affect the tumor remodeling and tumor biology characteristics of HS, such as fibrosis and lymphatic vessel proliferation.

Primary Histiocytic Sarcoma, an Extremely Rare Neoplasm: Report of a Case Presenting as a Skin Lesion

: Histiocytic sarcoma (HS) is a very rare neoplasm of hematopoietic origin characterized by the proliferation of malignant cells that have the morphological and immunohistochemical features of mature tissue histiocytes, with only a few cases reported. Most patients with symptoms of the unilateral or multichannel disease are more involved with the intestines, skin, and soft tissues, palpable mass lesions, and compressions of adjacent organs, such as intestinal obstruction, or constitutional symptoms (e.g., fever and weight loss). In this study, we reported a 56-year-old man with a six-month history of a cutaneous plaque lesion on the left arm’s posterior surface. He underwent skin lesion biopsy, histopathologic examination, and immunohistochemistry that was compatible with histiocytic sarcoma. Since surgical resection not deemed appropriate, our patient underwent aggressive multiagent chemotherapy with six cycles of ICE (ifosfamide, mesna, carboplatin, and etoposide) regimen and radiotherapy. After the completion of chemoradiotherapy, the skin lesion was completely disappeared. The patient is currently coming to us for the follow-up without any recurrence of the disease.

Carnivore Protoparvovirus-1 Associated With an Outbreak of Hemorrhagic Gastroenteritis in Small Indian Civets.

Carnivore protoparvovirus-1 (CPPV-1) infection has been reported frequently in both domestic and wildlife species including wild carnivores. Fifty-five captive small Indian civets (Viverricula indica), farmed for perfume production in Eastern Thailand, showed clinical signs of acute bloody diarrhea, anorexia, vomiting, circling, and seizures. The disease spread within the farm and resulted in the death of 38 of the 55 civets (69% mortality) within a month. Fecal swabs were collected from the 17 surviving civets, and necropsy was performed on 7 of the dead civets. Pathologic findings were severe hemorrhagic gastroenteritis with generalized lymphadenopathy. CPPV-1 was identified in both fecal swabs and postmortem samples by species-specific polymerase chain reaction. Further whole-gene sequencing and restriction fragment length polymorphism analysis suggested feline panleukopenia virus (FPV) as the causative agent. The viral tropism and tissue distribution were confirmed by immunohistochemistry, with immunolabeling in the cytoplasm and nucleus of small intestinal crypt epithelial cells, villous enterocytes, histiocytes in lymphoid tissues, myenteric nerve plexuses, and cerebral and cerebellar neurons. Phylogenetic analysis of civet-derived CPPV-1 indicated a genetic similarity close to the FPV HH-1/86 strain detected in a jaguar (Panthera onca) in China. To our knowledge, this mass die-off of civets is the first evidence of disease associated with CPPV-1 infection in the subfamily Viverrinae. These findings support the multi-host range of parvovirus infection and raises awareness for CPPV-1 disease outbreaks in wildlife species.

Histiocytic sarcoma transformed from a low grade B lymphoproliferative disorder – A case report

Histiocytic sarcoma (HS) is a rare and aggressive lympho-hematopoietic malignancy that represents less than 1% of all non-Hodgkin lymphomas with poor response to therapy. According to the World Health Organization classification it is defined on the basis of morphological and immune-histochemical properties of mature tissue histiocytes.1 It can occur sporadically or in association with other haematological neoplasms such low-grade lymphomas (follicular lymphoma or chronic lymphocytic leukaemia among others).2 Patients can present with either localised or disseminated disease involving organs such as the skin, central nervous system, spleen, gastrointestinal system, lymph nodes and the bone marrow. The pathogenesis of HS remains unclear and the presence of characteristic cytogenetic abnormalities such as PTEN, p14ARF and p16INK4A are currently non-contributory in the management or prognostication of the disease.3 As a result of the rarity of the disease and lack of clinical trials, treatment strategies remain a challenge due to limited therapeutic options which are largely based on case studies. We report a case of a 65-year-old woman presenting with histioctytic sarcoma, transformed from a low-grade B lymphoproliferative disorder (LPD). This case aims to highlight the heterogeneity of this disease, aggressive course and the limited treatment options available.

The Novel Tumor Suppressor SAMHD1 Is Differentially Expressed and Partly Regulated By MYC in Peripheral T-Cell Lymphomas (PTCL)

Introduction: The SAM domain and HD domain 1 (SAMHD1) protein is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, which has been initially described to restrict human immunodeficiency virus type 1 (HIV-1) in certain cell types through depletion of intracellular dNTP substrates required for HIV-1 reverse transcription. Mutations of SAMHD1 gene have been linked to Aicardi-Goutières syndrome (AGS) and have been identified as putative drivers of chronic lymphocytic leukemia resulting in decreased SAMHD1 mRNA and protein levels. More recently, SAMHD1 mutations have been reported in T-prolymphocytic leukemia (T-PLL). Based on these findings and the fact that SAMHD1 limits the dNTP pool in the cell, it may play a role in oncogenesis as a tumor suppressor. In addition, SAMHD1 may confer resistance to nucleoside-based chemotherapies by hydrolysing their active triphosphate metabolites, with cytarabine in acute myeloid leukemia being an example (Herold et al, Nat Med 2017; 23(2):256-263). The expression patterns and the potential role of SAMHD1 in the pathogenesis of peripheral T-cell lymphomas (PTCL) are not yet known.Methods: The patient cohort included 64 PTCLs of various histologic types which were diagnosed and treated at Karolinska University Hospital (Sweden). A control group of 4 reactive lymph nodes and 2 reactive tonsils was included in the study for comparison. All tissue samples were obtained prior to therapy. SAMHD1 expression was assessed by immunohistochemistry performed on a PTCL tissue microarray (TMA) with duplicate tumor cores from each case or full tissue sections using dual immunostaining (SAMHD1 / CD68) and a monoclonal antibody against SAMHD1 (Bethyl Laboratories, San Antonio, TX). At least 500 lymphoma cells were counted to calculate the percentage of SAMHD1-positive tumor cells. Overall survival (OS) was defined as time from diagnosis to death or last follow-up. Event-free survival (EFS) was defined as time from diagnosis to relapse, death, or last follow-up. Survival analyses were performed using the Kaplan-Meier method (log-rank test) and Cox regression models. Two T-cell lymphomas cell lines (Mac1, Mac2A) were used as an in vitro system. As our preliminary findings from in silico analysis revealed potential binding sites for MYC on the SAMHD1 gene promoter, we hypothesized that MYC might regulate SAMHD1 expression. Therefore, the T-cell lymphoma cell lines were treated with the selective BET / MYC inhibitor JQ-1 or transiently transfected with a MYC-overexpressing plasmid or MYC gene-specific siRNA constructs, respectively. Western blot analysis was used to assess the protein levels.Results: SAMHD1 protein was expressed in reactive T-cells and histiocytes (CD68+) in all reactive lymphoid tissues (lymph nodes and tonsils) with strong staining intensity. SAMHD was differentially expressed among PTCL subtypes generally with weaker staining intensity as compared to normal T-cells and histiocytes, thus being positive in all (100%) angioimmunoblastic T-cell lymphomas (AILT), 67% PTCL-NOS, 45% ALK+ ALCL, 20% of ALK+ ALCL, and none (0%) of T-lymphoblastic lymphomas (p=0.0017, chi-square test). Among the SAMHD1- positive cases, the percentage of positive lymphoma cells ranged from 0 to 100% and its highest median was observed in AILT. SAMHD1 expression inversely correlated with CD30 expression (% CD30+ positive lymphoma cells) (p=0.0025, Mann-Whitney test). No significant associations between SAMHD1 levels and other clinicopathologic parameters or clinical outcome (EFS or OS) were found, however, the number of patients analyzed in each histologic subtype was limited. Inhibition of MYC activity by JQ-1 or MYC gene silencing with specific siRNA resulted in a substantial increase in the SAMHD1 protein level in T-cell lymphoma cell lines. Inversely, transient transfection of the cell lines with a MYC overexpressing plasmid resulted in decreased levels of SAMHD1. Taken together, the in vitro data suggest a possible MYC-associated regulation (repression) of SAMHD1 gene expression in T-cell lymphoma.Conclusions: SAMHD1 is shown for the first time to be differentially expressed among PTCL types and its regulation may involve MYC. Preliminary survival analysis shows no significant associations of SAMHD1 expression with EFS and OS in this cohort of PTCL, however, analysis of a larger PTCL study group is underway to draw definite conclusions. DisclosuresÖsterborg:Gilead: Consultancy, Research Funding; Beigene: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Abbvie: Research Funding.

Histiocyticneoplasia in the heart

Introduction: Histiocytic sarcomas are malignant proliferation of cell showing morphological and immunophenotypic characteristics of mature tissue histiocytes. Objective : Is to report 3 years old girl presented with pyrexia of unknown origin and after echocardiography, MSCT on heart and MRI heart, the case was reported to have cardiac mass then after excisional biopsy of the mass and immunohistochemisrtry,histiocysticneoplasia was diagnosed. Conclusion: Cardiac tumor should be excluded in the case of pyrexia of unknown origin.

A retrospective histopathological, immunohistochemical and molecular study of the presence of Leishmania spp. in the skin of cats with head and neck ulcerative dermatitis.

Head and neck ulcers in cats can arise from allergic and nonallergic disorders, including feline leishmaniosis (FeL). It is important to rule out this aetiological agent in regions that are endemic for canine leishmaniosis, because the drugs used to treat immune-mediated disorders of cats can be contraindicated in the setting of infection. The aim of this study was to evaluate the skin of cats with ulcerative dermatitis of the head or neck for evidence of Leishmania infection using combined immunohistochemistry (IHC) and Polymerase Chain Reaction (PCR). An IHC for tissue histiocytes was also utilized because leishmaniosis may provoke a histiocytic inflammatory response. Twenty seven cats with head and/or neck ulcers. Skin biopsy specimens were examined for the presence of Leishmania spp. by routine histopathological evaluation and IHC using a polyclonal anti-Leishmania antibody, and by quantitative PCR (qPCR). The ionized calcium-binding adapter molecule-1 (IBA-1) antibody was used to immunolocalize histiocytes. Selected history and clinical data were recorded. All specimens showed a superficial mid-perivascular mixed inflammatory infiltrate. The presence of histiocytes was confirmed in 23 of 27 cases with the IBA-1 antibody. Immunohistochemistry and qPCR techniques confirmed the absence of Leishmania in all cases. Leishmania did not seem to play a role in the pathogenesis of feline ulcerative dermatitis of the head and neck in the subjects studied, despite a lifestyle potentially associated with infection. Histiocytic infiltration of tissue is not a specific marker for Leishmania infection in this population.

Juvenile Xanthogranuloma

The histiocytoses are a heterogenous group of diseases that are characterized by the accumulation of reactive or neoplastic histiocytes in various tissues. Juvenile Xanthogranuloma is a member of the non-Langerhans cell group of histiocytic proliferative disorders. This present case report describes a juvenile xanthogranuloma in a twenty-month old male baby.Nepal Journal of Dermatology, Venereology &amp; Leprology, Vol.14(1) 2016, pp.56-58

Canine Circovirus 1 (CaCV-1) and Canine Parvovirus 2 (CPV-2): Recurrent Dual Infections in a Papillon Breeding Colony.

Recurrent outbreaks of sudden death and bloody diarrhea were reported in March 2013 and February 2014 in a breeding colony of Papillon dogs. During the first outbreak, 1 adult dog and 2 eight-month-old puppies died. During the second outbreak, 2 ten-week-old puppies died. One puppy from the first outbreak and 2 puppies from the second outbreak were examined at necropsy. Histologically, all 3 puppies had severe segmental crypt necrosis of the small intestine and marked lymphoid follicle depletion in the spleen and Peyer's patches. Real-time (RT) polymerase chain reaction (PCR) demonstrated abundant canine parvovirus (CPV-2) DNA (Ct<15) in the affected small intestine, and immunohistochemistry detected large amounts of CPV-2 antigen in intestinal crypt epithelium and Kupffer cells but few positive macrophages in lymphoid organs. All puppies had marked sinusoidal histiocytosis and multifocal granulomatous inflammation in mesenteric lymph nodes and spleen, prompting additional RT-PCR testing for canine circovirus 1 (CaCV-1). Very high levels of CaCV-1 DNA (Ct<13) were detected in small intestine, lymph nodes, and spleen. In situ hybridization for CaCV-1 detected rare positive nuclei of regenerating crypt epithelium but abundant amounts of CaCV-1 nucleic acid in the cytoplasm and nuclei of histiocytes in all lymphoid tissues, including granulomatous inflammatory foci and hepatic Kupffer cells. Significant levels of CaCV-1 DNA were detected in blood and serum (Ct as low as 13) but not feces from 3 surviving dogs at 2 months or 1 year after the outbreak, respectively. We hypothesize that CPV-2 infection predisposed dogs to CaCV-1 infection and ultimately resulted in more severe clinical disease.

Sarcoma histiocítico en intestino delgado: estudio y discusión de un caso con reordenamiento clonal linfoide B

Histiocytic sarcoma is a rare malignant tumour of unknown pathogenesis characterized by proliferation of neoplastic cells morphologically and immunophenotypically similar to mature tissue histiocytes. There are only a few reported cases, but they have been described in both males and females of all ages and with nodal and extranodal involvement. A close relationship has often been observed with other haematolymphoid neoplasms which might provide clues to its etiology and pathogenesis. To date, diagnosis is by exclusion of other entities. The clinical course usually progresses rapidly and an effective therapeutic regime has not yet been established. We report a case in an 82year old male who had suffered a perforation of the jejunal loop and was found to have a malignant tumour infiltrating the wall of the small bowel. The tumour was positive only for CD68, CD45RO, CD163, lysozyme and vimentin and showed a Blymphoid clonal rearrangement with little amplification.