Atypical Spleen Hemophagocytic Histiocytic Sarcoma in a Dog

Background: The histiocytic sarcoma (HS) complex is a set of malignant neoplasms originating from interstitial dendritic cells or macrophages. When it involves macrophages of the splenic red pulp and bone marrow, it is referred to as hemophagocytic histiocytic sarcoma (HHS). HHS behaves more aggressively than HS and is usually fatal. HHS can be diagnosed by cytological and histopathological examination of neoplastic tissue. HHS is confirmed by immunohistochemistry using an anti-CD11d antibody. This neoplasm is often confused with immune-mediated hemolytic anemia or Evans syndrome due to erythrophagocytosis and platelet consumption. The clinical presentation of the animals progresses with evident anemia and thrombocytopenia, leading to signs such as prostration, inappetence, and pale mucosa, making diagnosis challenging and often late. This study aimed to report the clinic-pathological aspects of a canine with atypical hemophagocytic splenic HS.Case: A 4-year-old male Shih-Tzu canine was referred to the Veterinary Hospital with a history of prostration and anorexia. Pale mucous membranes were observed on physical examination. Blood tests revealed non-regenerative anemia, leukopenia, and thrombocytopenia. Serum protein levels were below the reference values for the species in biochemical examinations. Hemoparasitosis was suspected; however, the result of the polymerase chain reaction was negative. Abdominal ultrasound revealed a splenomegaly with heterogeneous parenchyma and a slightly irregular surface, but no visible mass in the spleen. Due to the difficulty of stabilizing the patient, even after successive transfusions, the animal underwent exploratory laparotomy with medial access and posterior splenectomy. Subsequently, the spleen was surgically removed, fixed in 10% buffered formalin, and processed routinely. Macroscopically, it had an irregular reddish-brown capsular surface. Histopathological examination of the spleen revealed a densely cellular neoplasm composed of round to spindle cells (histiocytes) arranged haphazardly in variably sized sheets separating the pre-existing spleen stroma. These histopathological findings were consistent with a histiocytic malignant neoplasm. Immunohistochemical analysis was performed to better define the origin of the histiocytic neoplasm. Neoplastic cells showed positive immunostaining of more than 80% of tumor cells for the CD11d antibody and weak immunostaining for CD11c and lysozyme. The patient survived for less than 30 days after the first hospital visit.Discussion: The diagnosis of HHS was based on the histological characteristics and positive immunostaining of more than 80% of the tumor cells for the CD11d antibody. HHS is an extremely aggressive and rare tumor that affects elderly dogs of any breed. In this study, HHS had atypical histologic characteristics, in which erythrophagocytosis and hemosiderin were not observed within macrophages. HHSs arise from macrophages of the red pulp of the spleen or bone marrow and express the b2 integrin, CD11d, and have low expression of CD1 and CD11c, which are predominantly expressed by non-hemophagocytic HS. The hematological and biochemical changes observed in this case were similar to those described in other dogs with HHS. Treatment of HHS is only palliative. Erlichia ewingii, E. canis, Anaplasma phagocytophilum, A. platys, Borrelia burgdorferi, Dirofilaria immitis, Leishmania infantum and immune-mediated hemolytic anemia are the main differential diagnoses because they cause anemia and thrombocytopenia accompanied by splenomegaly.Keywords: histiocytic sarcoma, spleen, immunohistochemistry, splenectomy, erythrophagocytosis.

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Immune-mediated Hemolytic Anemia and Thrombocytopenia in a Cat after Bone Marrow Transplantation

Veterinary Pathology ◽

10.1177/030098588802500209 ◽

1988 ◽

Vol 25 (2) ◽

pp. 161-162 ◽

Cited By ~ 6

Author(s):

G. R. Cain ◽

J. L. Cain ◽

J. M. Turrel ◽

G. Theilen ◽

N. C. Jain

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Hemolytic Anemia ◽

Marrow Transplantation ◽

Immune Mediated

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Hemophagocytic Histiocytic Sarcoma in Dog

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.103774 ◽

2020 ◽

Vol 48 ◽

Author(s):

Juliana Das Chagas Goulart ◽

Felipe Jacques Sanches ◽

Natalie Bertelis Merlini ◽

Barbara Cristina Mazzucatto ◽

Beatriz Gasser ◽

...

Keyword(s):

Bone Marrow ◽

Blood Count ◽

Rapid Development ◽

Clinical Signs ◽

Malignant Neoplasm ◽

Reference Value ◽

Abdominal Ultrasound ◽

Needle Aspiration ◽

Histiocytic Sarcoma ◽

Unknown Etiology

Background: Histiocytic sarcoma can present in a localized or disseminated form, being a malignant neoplasm derived from interstitial dendritic cells. Another form of the disease is called hemophagocytic histiocystic sarcoma (HHS), which originates from macrophages located in the splenic red pulp and bone marrow. HHS is a rare neoplasm with unknown etiology and rapid development. It mainly affects middle-aged to elderly animals. It primarily affects the spleen and bone marrow, with occurence of metastases in other organs. Some canine breeds are considered more predisposed to this neoplasia, among them the Rottweiler. The aim of this study was to report a case of HHS in a Rottweiler dog.Case: An 8-year-old Rottweiler suffering from hyporexia and progressive weight loss for a month was attended at the Veterinary Hospital of State University of Maringá. On physical examination, he only presented mild discomfort on abdominal palpation. Blood count was performed, which revealed mild thrombocytopenia (145,000/µL, reference value for the species 150,000-500,000/µL). The Polymerase Chain Reaction (PCR) exam was requested for babesiosis and ehrlichiosis, due to a history of ectoparasites. The animal was released with the prescription of Doxycycline at a dose of 10 mg/kg orally for 28 days. After 5 days, the condition worsened and the animal returned with emesis, apathy and hyporexia, being hospitalized. Abdominal ultrasound, blood count, urinalysis, serum urea and creatinine tests were requested. Among the hematological changes, thrombocytopenia (116,000/µL) and the appearing of regenerative anemia and atypical round cells with ample and slightly basophilic cytoplasm in the smear, similar to histiocytes, stood out. On ultrasound examination, splenomegaly was observed with hypoechogenic areas. Ultrasound-guided fine-needle aspiration cytology (FNAC) of the spleen was performed, which revealed the presence of abundant cellularity consisting of round cells arranged individually and in small groups, with variable nucleus / cytoplasm ratio, slightly basophilic cytoplasm and, sometimes, vacuolized. Eccentric nucleus with chromatin ranging from loose to dense, with evident and often multiple nucleus. In addition, a large number of multinucleated giant cells, mitosis figures (sometimes atypical) and intense anisocytosis and anisocariosis were observed. Furthermore, it was possible to observe erythrophagocytic activity, alterations compatible with histiocytic sarcoma (HS). After 10 days of the first visit, the animal died. At necropsy, samples from altered areas of the spleen, lungs and lymph nodes were collected and sent for histopathological and immunohistochemical examination, in which the diagnosis of hemophagic histiocytic sarcoma was confirmed, in addition to lungs and lymph node metastasis.Discussion: The prognosis of HHS is the worst among histiocytic disorders, as it is associated with coagulopathies and severe anemia due to erythrophagocytic activity, as occurred in the case presented, with a maximum survival time between one to two months. The described animal died ten days after showing the first clinical signs. The immunohistochemistry technique using HLA-DR, CD18, CD163, and CD11d markers was essential to confirm the cell line. Positivity for CD11d marker was found, which allowed to classify the neoplasm as hemophagocytic HS. This report exposes the importance of cytological examination for screening and histopathological and immunohistochemical tests to confirm the diagnosis of this extremely aggressive neoplasm.

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Multiple Myeloma in a Feline

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.106859 ◽

2020 ◽

Vol 48 ◽

Author(s):

Taina Dos Santos Alberti ◽

Fabiano Da Rosa Venancio ◽

Rosimeri Zamboni ◽

Haide Valeska Scheid ◽

Carolina Buss Brunner ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Lymph Nodes ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Malignant Neoplasms ◽

Hemorrhagic Diathesis ◽

Chronic Infections ◽

Eosinophilic Cytoplasm ◽

Positive Immunostaining

Background: Multiple myelomas (MM) are malignant neoplasms originating in the bone marrow plasmacytes, and are characterized by the presence of persistent hyperglobulinemia. Although they are rarely found in domestic animals, the canine species is most affected. In felines, they represent less than 1% of hematopoietic neoplasms, and mainly occur in older animals aged 10-12 years. The aim of the present study was to report a case of multiple myeloma, with extramedullary plasmocytosis in a feline.Case: A 3-year-old feline, female, mixed breed, with a history of apathy, anorexia, halitosis, and vomiting was referred to the Laboratório Regional de Diagnóstico (LRD) at the Universidade Federal de Pelotas (UFPel). Oral examination revealed a cyanotic oral mucosa and ulcerative lesions on the gingiva. The necropsy showed generalized lymphadenomegaly, splenomegaly, and hemorrhagic diathesis. Organ fragments were collected and fixed in 10% buffered formalin. After 48 h, the samples were cleaved, embedded in paraffin, and stained using the routine hematoxylin and eosin technique. Selected sections were subjected to immunohistochemistry (IHC) using the streptavidin-biotin method. The CD79a, CD138, CD3, and MUM1 antibodies were used. Histopathological evaluation of the bone marrow revealed hypercellularity with predominant round pleomorphic cells (90%), which presented an eccentric basophilic nucleus and abundant eosinophilic cytoplasm. The same neoplastic cells infiltrated the gingival mucosa, lymph nodes, spleen, liver, kidneys, heart, lungs, and brain. The IHC showed positive immunostaining for MUM1 and CD138 antibodies.Discussion: The diagnosis of MM in the present study was based on histopathology and by IHC. According to the literature, the presence of neoplastic plasmocytes in the bone marrow (>20%), osteolytic lesions, monoclonal gammopathy, and Bence-Jones proteinuria should be investigated in suspected MM cases. The presence of two or more of these characteristics is necessary for confirmed diagnosis. However, studies show that only 50% of felines with MM have two or more of these characteristics, with cell morphology and neoplastic infiltration in other organs being important parameters for the definitive diagnosis of MM in them. For MM diagnosis by IHC, CD79a, CD138, and MUM1 can be used. In this report, there was positive immunostaining for MUM1 and CD138, which allowed the exclusion of other neoplasms of hematopoietic origins. The origin of MM is unknown, but chronic immune stimulation is believed to be involved in humans. In felines, although infection by the feline immunodeficiency virus (FIV) and feline leukemia (FeLV) is commonly associated with the occurrence of lymphomas, the same is not described for MM. This was corroborated in the present study, since the animal in this report tested negative for FIV and FeLV. In cats, MM has no apparent predilection for race or sex, and mainly affects older animals (average age, 10 years). Although MM is rare, it has been described not only in this case, but also in young cats. The infiltration of neoplastic plasmacytes in the extramedullary tissues (extramedullary plasmacytosis) is observed more frequently in felines than in canines, and mainly occurs in the lymph nodes, spleen, and liver. In this case, there was disseminated extramedullary plasmacytosis involving multiple organs, such as the brain, lungs, heart, and kidneys. Persistent hyperglobulinemia is the main clinical manifestation of MM observed in 87.7% of cats with this neoplasm. However, this variation can also be observed in other pathologies, such as chronic lymphocytic leukemia, B cell lymphoma, primary macroglobulinemia, and chronic infections (e.g., ehrlichiosis, leishmaniasis, and heartworm disease). Hence, MM should always be considered as differential diagnosis when diagnosing the aforementioned diseases.

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HISTOPATHOLOGICAL EXAMINATIONS PROFILE OF BLADDER DISEASES IN DR. SOETOMO GENERAL ACADEMIC HOSPITAL FROM JANUARY 2015 TO DECEMBER 2019

Indonesian Journal of Urology ◽

10.32421/juri.v29i1.761 ◽

2022 ◽

Vol 29 (1) ◽

Author(s):

Veronika Intan Krismaningrum ◽

Anny Setijo Rahaju ◽

Lilik Herawati ◽

Soetojo

Keyword(s):

Histopathological Examination ◽

Malignant Neoplasm ◽

Secondary Data ◽

Malignant Neoplasms ◽

Benign Neoplasms ◽

Academic Hospital ◽

Bladder Disease ◽

Bladder Diseases ◽

Bladder Abnormalities ◽

Male Patients

Objective: This study aimed to analyze the profile of bladder disease in Soetomo General Hospital based on histopathological examination. Material & Methods: This study was using secondary data. Histopathological examination data of patients with bladder disease were evaluated based on age, gender, and histopathological types. Results: There were 419 patients with bladder abnormalities. Non-neoplasm bladder diseases were found in 62 patients consisted of 56 patients (90.32%) with cystitis and 6 patients (9.67%) with glandular cystitis. Neoplastic bladder diseases were found in 357 patients and were divided into benign and malignant neoplasm. Benign neoplasms were found in 11 patients consisted of 5 patients (45.45%) with UP and 6 patients (54.54%) with IUP. Malignant neoplasms were found in 340 patients consisted of 300 patients (88.23%) with urothelial carcinoma, 26 patients (7.64%) with adenocarcinoma, 14 patients (4.12%) with SCC. Moreover, six male patients with PUNLMP were also reported. Conclusion: Histopathological examination in patients with bladder abnormalities shows that neoplastic bladder diseases (357/419, 85.20%) were more common than non-neoplastic bladder disease (62/419, 14.80%).

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Erythrocyte Volume Distribution Analysis and Hematologic Changes in Two Horses with Immune-mediated Hemolytic Anemia

Veterinary Pathology ◽

10.1177/030098588302000405 ◽

1983 ◽

Vol 20 (4) ◽

pp. 424-433 ◽

Cited By ~ 33

Author(s):

G. Weiser ◽

C. Kohn ◽

A. Vachon

Keyword(s):

Bone Marrow ◽

Hemolytic Anemia ◽

Packed Cell Volume ◽

Volume Distribution ◽

Distribution Analysis ◽

Erythrocyte Volume ◽

Erythroid Hyperplasia ◽

Immune Mediated ◽

Positive Direct ◽

Erythrocyte Fragility

Immune-mediated hemolytic anemia was diagnosed in two horses on the basis of regenerative anemia, increased erythrocyte fragility in hypotonic saline, auloagglutination, and a positive direct antiglobulin (Coomb's) test. During steroid therapy partial resolution of the anemia was indicated by rising packed cell volume, macrocytosis, and bone marrow erythroid hyperplasia. Using erythrocyte volume distribution histograms (erythrograms), the regenerative response was characterized by analysis of macrocytic and normocytic erythrocyte subpopulations. In both horses, a gradual net increase of about 2 × 106 macrocytes/μl occurred over a four- to five-week period. Over the same interval there was a gradual decrease in the number of normocytes. We suggest that the macrocytes remained large through this period rather than contributing to normocyte population growth. Erythrograms may provide an additional means of evaluating erythrocyte regeneration in horses.

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Histiocytic Sarcoma of Bone Marrow With Partial Cohesive Neoplastic Cells and Hemophagocytosis: a Case Report

10.21203/rs.3.rs-659174/v1 ◽

2021 ◽

Author(s):

Yang Liang ◽

Li Mao ◽

Yihua Chen ◽

Guangjie Wang

Keyword(s):

Bone Marrow ◽

Tumor Cells ◽

Hemophagocytic Syndrome ◽

Histiocytic Sarcoma ◽

Neoplastic Cells ◽

Case Presentation ◽

Barr Virus ◽

History Of ◽

Epstein Barr ◽

Aggressive Clinical Course

Abstract Background: Histiocytic sarcoma (HS) is a rare hematolymphoid neoplasms whose cells show morphologic and immunophenotypic features of mature tissue histiocytes. We herein report a HS case without nodules or lymphadenectasis confirmed with the help of immunohistochemistry (IHC) on bone marrow (BM) biopsy and smear.Case presentation: A 63-year-old female patient with a history of cerebral infarction presented with fever, retching and hypodynamic sign for three weeks. The peripheral blood examination showed aggressive pancytopenia accompanying with the positivity for Epstein-Barr virus (EBV) antibody. The computed tomography and abdomen ultrasound scan didn’t reveal any nodules or lymphadenectasis other than hypersplenotrophy. Significantly, the BM aspirate shows vast pleomorphic tumor cells atypically distributed in both forms of single diffuse and cohesive. The hemophagocyte phagocytized granulocytes on BM smear exhibited the lymphoma related hemophagocytic syndrome. Immunohistochemically, neoplastic cells were immunopositively for macrophage-associated antigen cluster of CD4, CD68, CD163, but negative for the T-cell, B-cell and myeloid lineage markers of CD15, CD20, PAX-5, CD5, CD30, CD3, CD56, CD38, CD138, ALK and MPO, confirming the hypothesis of HS in BM. Conclusion: The rare HS case of bone marrow with atypically partial cohesive pleomorphic tumor cells had the hemophagocytic syndrome, presented highly aggressive clinical course and challenged to the diagnoses.

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Thrombocyte indices and plateletcrit in dogs with primary immune-mediated hemolytic anemia

Medycyna Weterynaryjna ◽

10.21521/mw.6262 ◽

2019 ◽

Vol 75 (05) ◽

pp. 6262-2019

Author(s):

EKREM ÇAĞATAY ÇOLAKOĞLU ◽

ALI EVREN HAYDARDEDEOĞLU

Keyword(s):

Bone Marrow ◽

Hemolytic Anemia ◽

Reference Population ◽

Coombs Test ◽

Inclusion Criteria ◽

Platelet Volume ◽

Control Series ◽

Platelet Size ◽

Immune Mediated ◽

Healthy Dogs

Primary immune-mediated hemolytic anemia (IMHA) is one of the most common autoimmune disorders in dogs. Platelet indices in dogs with IMHA have not been commonly used in daily clinical practice. The purpose of this study was to evaluate trombocyte indices, including platelet count (PLT), mean platelet volume (MPW), platelet size deviation width (PDW), and plateletcrit (PCT) in dogs with primary IMHA and to compare them with the corresponding values in a control series of healthy dogs. This study was performed on 21 dogs diagnosed with primary IMHA and 11 healthy dogs. The inclusion criteria were the presence of a positive Coombs’ test, true agglutination, anemia with HCT <35 %, hyperbilirubinemia, bilirubinuria, hemoglobinemia, hemoglobinuria, and spherocytosis. MPV and PDW were significantly higher in the dogs with IMHA compared to the reference population. No significant differences were found in PLT and PCT between the groups. The use of MPV and PDW values in evaluating the bone marrow response would be helpful in dogs with primary IMHA.

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Clinic-Pathological Aspects of Spleen Hemophagocytic Histiocytic Sarcoma in a Dog

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.106173 ◽

2021 ◽

Vol 49 ◽

Author(s):

Thaynan Cunha Vieira ◽

Luiz Flávio Telles ◽

Karen Yumi Ribeiro Nakagaki ◽

Geovanni Dantas Cassali

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Splenic Vein ◽

Malignant Neoplasm ◽

Histiocytic Sarcoma ◽

Biological Behavior ◽

Clinical Aspects ◽

Histopathological Analysis ◽

Microscopic Evaluation ◽

Eosinophilic Cytoplasm

Background: Histiocytes are cells that differentiate into macrophages and dendritic cell lines from bone marrow CD34+ stem cells. The hemophagocytic histiocytic sarcoma (HHS) is the only malignant neoplasm originating from macrophage lineages, being a variation of histiocytic sarcoma (HS), originated from dendritic cells. In general, the HHS shows aggressive biological behavior, due to the erythrophagocytosis characteristic of this disease and overall average survival around seven weeks, affecting mainly Bernese Mountain Dog, Rottweiler and Golden Retriever breeds. Therefore, the objective of this work is to report the case of a dog with HHS, emphasizing the clinical aspects and its diagnostic method.Case: An 8-year-old bitch Rottweiler, was attended with history of inappetence and prostration. The complete blood count showed normochromic normocytic anemia, monocytosis and thrombocytopenia, with serum urea levels below the reference value for the specie in the biochemical examination. The abdominal ultrasound highlighted splenomegaly, with heterogeneous parenchyma and presence of a vascularized mass and an enlarged splenic vein. Thoracic radiographic examination showed multifocal and rounded radiopaque structures in the pulmonary parenchyma, suggesting metastatic formation. Rapid serological tests for detection of the main hemoparasitosis antibodies were negative, as well as negative Coombs test. The animal was submitted to exploratory laparotomy with medial line access and posterior splenectomy. The spleen microscopic evaluation revealed neoplastic proliferation cells in mantle arrangement and solid nests areas, supported by a fine fibrovascular stroma. The cells had broad and eosinophilic cytoplasm, round nuclei and some pleomorphism, rude chromatin and evident nucleoli. It was also observed the presence of marked anisocytosis and anisocariosis, hemophagocytic activity, and 27 mitoses in 10 fields (40 x). There were atypical mitoses and necrosis and extensive hemorrhaged areas. These histopathological findings suggested a histiocytic malignant neoplasia and immunohistochemical analysis was performed to define a better histiocytic neoplasm origin. The neoplastic cells showed positive imunostaining for CD11d and Iba1 and negative imunostaining for CD3 and CD20, as well as a proliferative index of 80%, supporting the diagnosis of HHS in the animal's spleen. The following hematological analyzes demonstrated persistence of anemia, worsening of thrombocytopenia, prolongation of activated partial thromboplastin time, hypoproteinemia with hypoalbuminemia, serum increase of creatinine, alkaline phosphatase and total bilirubin. Myelogram showed erythrocyte and granulocytic lineage hypoplasia, thrombocytic aplasia and more than 50% of macrophages in bone marrow cell population. The animal’s clinical condition worsened rapidly, after successive transfusions and administration of chemotherapy with lomustine, leading to death 14 days after the surgery.Discussion: HHS is the most serious clinical presentation among histiocytic disorders, conferring an extremely unfavorable prognosis. In addition, the scientific literature that specifically addresses the HHS is rare, with therapeutic extrapolations being performed for the treatment of HS from dendritic cells. The racial predisposition and clinical findings, associated with hematological changes, histopathological analysis and confirmation by immunohistochemistry allowed the diagnosis of HHS, a rare and underreported neoplasm, with aggressive biological behavior and with still inefficient treatment in veterinary medicine.

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