Cytologic evaluation of benign and malignant hemophagocytic disorders in canine bone marrow

Abstract: Canine hemophagocytic disorders were studied to better understand the cytologic features that differentiate benign and malignant disease. Of 286 canine clinical bone marrow reports evaluated retrospectively, 13 (4.5%) noted at least 3% hemophagocytic macrophages. Macrophages comprised between 6% and 44% of nucleated bone marrow cells. Clinical diagnoses for dogs with hemophagocytic disorders included malignant histiocytosis (n = 2), myelodysplastic syndromes (n = 4), round cell neoplasia (n = 2), immune-mediated disorders (n = 2), and idiopathic hemophagocytic syndrome (n = 3). Differentiation of benign and malignant forms of histiocytosis was problematic. Two dogs with a diagnosis of hemophagocytic syndrome had macrophages with atypical features similar to those described for malignant histiocytosis. Furthermore, only 2 of 11 dogs with presumably benign hemophagocytic disorders had exclusively mature macrophages in bone marrow. Other dogs had variable numbers of large reticular-type cells characterized by lacy chromatin, anisocytosis, anisokaryosis, and prominent and/or multiple nucleoli. On the basis of these results, cytomorphologic evaluation of bone marrow alone may not be adequate to consistently differentiate benign and malignant forms of hemophagocytic disorders.     

Hemophagocytic syndrome in dogs: 24 cases (1996-2005)

OBJECTIVE: To determine the frequency, potential causes, and clinical and clinicopathologic features of hemophagocytic syndrome in dogs. DESIGN: Retrospective study. ANIMALS: 24 client-owned dogs. PROCEDURES: Records for dogs in which diagnostic bone marrow specimens (including an aspiration smear and core biopsy material) were obtained from 1996 to 2005 were reviewed. Inclusion criteria were presence of bicytopenia or pancytopenia in the blood and > 2% hemophagocytic macrophages in the bone marrow aspirate. RESULTS: Of 617 bone marrow specimens evaluated, evidence of hemophagocytic syndrome was detected in 24 (3.9%). The Tibetan Terrier breed was overrepresented among dogs with hemophagocytic syndrome. Clinical signs associated with hemophagocytic syndrome included fever, icterus, splenomegaly, hepatomegaly, and diarrhea. Hemophagocytic syndrome was associated with immune-mediated, infectious, and neoplastic-myelodysplastic conditions and also occurred as an idiopathic condition. Overall, dogs with infection-associated hemophagocytic syndrome had better 1-month survival rates than dogs with immune-associated and idiopathic hemophagocytic syndrome. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that hemophagocytic syndrome may occur more frequently in dogs than has previously been suspected on the basis of the paucity of reported cases. Although most dogs had definable underlying disease conditions, idiopathic hemophagocytic syndrome was also identified. Hemophagocytic syndrome of any cause is potentially life-threatening; however, the prognosis should be adjusted on the basis of the associated disease process and potential for successful treatment.     

Flow cytometric evaluation of hemophagocytic disorders in canine

Background — Hemophagocytic macrophages in canine bone marrow are observed in malignant histiocytosis as well as benign hemophagocytic histiocytosis. Cytomorphologic evaluation alone may be inadequate to consistently differentiate between benign and malignant forms of hemophagocytic disorders. Objective — The purpose of this study was to evaluate the ability of flow cytometry and immunophenotyping to differentiate between benign and malignant types of hemophagocytic disorders in dogs. Methods — Blood smears and bone marrow differential cell counts were evaluated for 10 dogs with hemophagocytic disorders. Bone marrow samples were labeled with monoclonal antibodies to CD18, MCH class‐II, Thy‐1, CD14, CD3, and CD21. Using flow cytometry, forward‐angle versus side‐angle light scatter plots were analyzed and immunophenotypes were determined. Results — Scatter plots from 3 dogs with a necropsy diagnosis of malignant histiocytosis revealed 2 atypical cell clusters. One cluster contained cells of similar size or larger than immature myeloid cells and metamyelocytes. Cells in the other cluster were highly granular, with granularity similar to or greater than that of metamyelocytes. In bone marrow from dogs with malignant histiocytosis that was labeled with anti‐CD14 antibody, macrophages represented 29–48% of nucleated cells. Seven dogs had a clinical or histopathologic diagnosis of benign hemophagocytic syndrome. Three of the dogs had normal cell distribution in scatter plots. Two dogs had 2 abnormal cell clusters: 1 within the immature myeloid and metamyelocyte gates and the other with granularity similar to or greater than that of metamyelocytes. The remaining 2 dogs had an atypical cell population, mostly within the immature myeloid gate. For dogs with benign hemophagocytic syndromes, 6–17% of cells in the bone marrow were CD14 positive. Conclusions — The cellular distribution in scatter plots and the total number of macrophages in bone marrow may be useful in differentiating malignant histiocytosis from benign hemophagocytic syndromes in dogs.     

Cytologic evaluation of primary and secondary myelodysplastic syndromes in the dog

Myelodysplastic syndromes are a heterogeneous group of acquired primary and secondary alterations of hematopoietic stem cells that result in cytopenias in blood and cytologic features of dysplasia in blood and/or bone marrow. To better understand the cytologic features that would permit differentiation of primary and secondary forms of myelodysplasia, we reviewed 267 consecutive bone marrow reports from dogs. These reports indicated that 34 dogs (12.7%) had dysgranulopoiesis, dyserythropoiesis, and/or dysthrombopoiesis in >10% of granulopoietic cells, erythroid cells, and/or megakaryocytes, respectively. Thirteen dogs had primary myelodysplastic syndromes, and 21 had secondary myelodysplastic syndromes. Of the 13 dogs with primary myelodysplasia, 4 were subclassified as myelodysplastic syndrome with refractory anemia (MDS-RA), and 9 were subclassified as myelodysplastic syndrome with excess blasts (MDS-EB). Secondary conditions associated with dysplasia in the bone marrow included malignant lymphoma (n = 5), myelofibrosis (n = 3), immune-mediated thrombocytopenia (n = 4), immune-mediated hemolytic anemia (n = 5), multiple myeloma with melphalan administration (n = 1), pyometra with estrogen administration (n = 1), polycythemia vera (n = 1), and thrombopathia (n = 1). MDS-RA was characterized by <5% myeloblasts in bone marrow, normal granulocyte maturation ratio, increased erythroid maturation ratio, and dysplastic changes in >15% of erythroid cells. MSD-EB was characterized by >/=5% myeloblasts in bone marrow, high granulocyte maturation and erythroid maturation ratios, >/=32% dysplastic granulocytes, and the presence of small atypical immature myeloid cells. Secondary myelodysplastic syndromes were characterized by <5% myeloblasts in bone marrow, variable granulocyte maturation and erythroid maturation ratios, and variable dysplastic features. These results indicate that morphology alone cannot be used to distinguish primary and secondary myelodysplastic syndromes in dogs.     

New insights into the physiology and treatment of acquired myelodysplastic syndromes and aplastic pancytopenia.

MDS are a diverse group of primary and secondary bone marrow disorders that are characterized by cytopenias in blood, prominent dysplastic features in blood or bone marrow, and normal or hypercellular bone marrow. MDS in cats are typically associated with FeLV infection. Dogs with MDS-RC and MDS-Er seem to respond to erythropoietin administration and have prolonged survival. Dogs with MDS-EB respond poorly to present treatments, and survival is short. Prognosis and probability of progression to acute myelogenous leukemia can be predicted based on the percentage of myeloblasts in bone marrow. Several experimental therapeutic modalities in human beings have been described that may be useful in treating MDS-EB in dogs and cats. Aplastic pancytopenia is a relatively rare disorder in dogs and cats. Causes include Ehrlichia spp, Parvovirus, and FeLV infections; sepsis; chronic renal failure; drug and toxin exposure; and idiopathic causes. Diagnosis is based on identification of multiple cytopenias in the blood and hypoplastic/aplastic bone marrow, with the marrow space replaced by adipose tissue. Treatment and outcome are dependent on determining the underlying cause of the bone marrow failure.     

Diagnostic use of cytologic examination of bone marrow from dogs with thrombocytopenia: 58 cases (1994-2004)

OBJECTIVE: To determine the diagnostic use of cytologic examination of bone marrow from dogs with thrombocytopenia. DESIGN: Retrospective case series. ANIMALS: 58 dogs with thrombocytopenia. PROCEDURES: Medical records were searched and reviewed for dogs with thrombocytopenia. Dogs that had thrombocytopenia and cytologic examination of bone marrow were included in the study. Dogs with other hematologic abnormalities, with a previous diagnosis of hematopoietic neoplasia, or that had previous treatment with cytotoxic drugs were excluded. Bone marrow cytologic findings were reviewed. Results were compared between dogs with severe thrombocytopenia (< 20,000 platelets/microL) and dogs with mild to moderate thrombocytopenia (20,000 to 200,000 platelets/microL). RESULTS: 58 dogs met the inclusion criteria. Of 55 dogs with diagnostic bone marrow aspirates, 36 had severe thrombocytopenia. Cytologic evaluation of bone marrow did not reveal substantial nonmegakaryocytic bone marrow abnormalities or result in a definitive diagnosis in any of these dogs. Nineteen dogs with mild to moderate thrombocytopenia had diagnostic bone marrow aspirates. Bone marrow cytologic findings revealed nonmegakaryocytic abnormalities in 4 of these dogs. Significantly fewer dogs with severe thrombocytopenia had abnormalities identified on cytologic examination of bone marrow, compared with dogs with mild to moderate thrombocytopenia. CONCLUSIONS AND CLINICAL RELEVANCE: Cytologic examination of bone marrow is unlikely to provide specific diagnostic or prognostic information in dogs with severe thrombocytopenia.     

Blood smear from a cat: features to "dys"cover

A 4-year-old, spayed female, domestic shorthair cat was presented for lethargy, nonregenerative anemia, and inappetence. Results of a CBC included macrocytic, normochromic, nonregenerative anemia and a glucocorticoid-associated leukogram. On blood smear examination, neutrophils had abnormal features including hyposegmentation and a diffuse chromatin pattern with nuclear filament formation and nuclear blebbing. Microscopic examination of a roll preparation of bone marrow revealed hypolobulated megakaryocytes with asynchronous maturation of nuclei. The granulocytic to erythrocyte (G:E) ratio was 76. Segmented neutrophils had asynchronous maturation and dysplastic features. The entire erythroid lineage was markedly decreased for the degree of anemia and rare dysplastic features were noted in erythroid precursor cells. The interpretation of bone marrow findings was erythroid hypoplasia, megakaryocytic dysplasia, and granulocytic hyperplasia with dysplasia. Histopathologic examination of a bone marrow core sample also revealed myeloid hyperplasia and erythroid hypoplasia. The result of a direct immunofluorescence assay for FeLV performed on the bone marrow roll preparation was positive. A diagnosis of dysmyelopoiesis associated with FeLV infection was made. This case was unique in that the dysplastic changes occurred in cell lines that did not have associated cytopenias. The dysmyelopoiesis most closely resembled myelodysplastic syndrome with refractory cytopenia (MDS-RC); however, secondary dysmyelopoiesis could not be ruled out.     

An appraisal of bone marrow biopsy in assessment of sick dogs.

Dogs were classified into a number of disease categories according to hematological, cytological and serochemical changes. Aspiration and core bone marrow biopsies were examined in 128 dogs in the various disease categories and compared to marrow samples in 36 dogs which appeared clinically normal. Differential cell counts on bone marrow smears were examined in relation to the blood variables in all animals. Blood and bone marrow data (group means) were compared among the normal and disease groups. Anemia, responsive and poorly responsive was the most frequent blood abnormality. Most dogs in the thrombocytopenia group had increased numbers of megakaryocytes in the marrow but two dogs had a marked decrease. The frequency of serious alteration of marrow production of the erythroid, myeloid and megakaryocytic series was less than anticipated. Marrow hemopoiesis was not significantly compromised in dogs with lymphoma or in dogs with other types of cancer. Bone marrow examination was necessary for the diagnosis of myelofibrosis and pancytopenia and was very helpful in the groups with insufficient change in the blood to permit a definitive diagnosis to be made. The myeloid-erythroid ratio was a useful indicator of marrow response while the erythroid maturation index and the myeloid maturation index were useful for identification of altered patterns of maturation (ineffective hemopoiesis). The reticulocyte response in absolute numbers is the most efficient and clinically relevant measure of erythroid response.     

Prospective Hematologic and Clinicopathologic Study of Asymptomatic Cats With Naturally Acquired Feline Immunodeficiency Virus Infection

Prospective studies were performed over a 28- to 77-month period (median, 66 months) on 5 cats with naturally acquired feline immunodeficiency virus (FIV) infection in an attempt to correlate hematologic and Clinicopathologic changes with the emergence of clinical disease. On presentation, all cats were asymptomatic; free of opportunistic infections; and had normal complete blood counts, bone marrow morphologies, marrow progenitor frequencies, and progenitor in vitro growth characteristics. During study, 2 cats remained healthy, 2 cats showed mild clinical signs, and 1 cat developed a malignant neoplasm (ie, bronchiolar-alveolar adenocarcinoma). Although persistent hematologic abnormalities were not observed, intermittent peripheral leukopenias were common. In 3 of 5 FlV-seropositive cats, lymphopenia (< 1,500 lymphs/μL; normal reference range, 1,500 to 7,000 lymphs/μL) was a frequent finding and the absolute lymphocyte counts had a tendency to progressively decline. One of the other 2 cats had consistently low to low-normal absolute neutrophil counts (1,300 to 4,800 segs/μL; mean, 2,730 segs/μL; normal reference range, 2,500 to 12,500 segs/μL), and the remaining cat had consistently normal leukograms, except for a transient period (ie, 11 months) of benign lymphocytosis (7,200 to 13,430 lymphs/μL) early in the study. Periodic examinations of bone marrow aspirates revealed normal to slightly depressed myeloid-to-erythroid ratios with normal cellular morphology and maturation. Bone marrow abnormalities observed late in the study included mild dysmor-phic changes (ie, megaloblastic features) in 2 cats, and a significant decrease (60% of controls, P < .001) in the frequencies of burst-forming units erythroid (BFU-E) in marrow cultures of FIV-seropositive cats compared with uninfected control cats. Serum biochemical profiles were unremarkable throughout the study, with the exception of hyperglobulinemia (ie, polyclonal gammopathy) in 2 of 5 cats. Peripheral blood and bone marrow findings were of no apparent prognostic value. These results confirm the long latency between natural FIV infection and the development of life-threatening clinical disease. Chronic FIV infection, like infection with human immunodeficiency virus, can be associated with derangements in peripheral blood cell counts, as well as pertubations in marrow cell morphologies and hematopoietic progenitor frequencies before the terminal symptomatic stages of retroviral disease, when persistent cytopenias are prominent.     

Ultrasound-Guided Cytology of Spleen and Liver: A Prognostic Tool in Canine Cutaneous Mast Cell Tumor

Background: In the clinical staging of cutaneous mast cell tumors (cMCT), the diagnosis of metastasis is controversial based on cytological examination of lymph nodes, spleen, liver, bone marrow, and blood.
Objectives: To define the prognostic role of ultrasound-guided cytology of spleen and liver in cMCT. The results of cytological evaluation were compared in relation with survival time.
Animals: Fifty-two client-owned dogs with a diagnosis of cMCT.
Methods: Selection of cases was based on cytological evaluation of liver and spleen to detect infiltration at distant sites. The Kaplan Meier method was used to compare survival in dogs with and without infiltration of spleen and liver (log-rank test P < .05).
Results: Ten dogs with cMCT had mast cell infiltration of spleen, liver, or both and 4 of these dogs had involvement of the regional lymph nodes. The majority of dogs had 2 or more ultrasonographically abnormal findings simultaneously in spleen and liver. Nine dogs had grade II cMCT, and 1 had grade III cMCT. Dogs with positive evidence of mast cell infiltration to spleen, liver, or both had shorter survival times (34 versus 733 days) compared with dogs negative for mast cell infiltration at distant sites.
Conclusion and Clinical Importance: Dogs with evidence of mast cell infiltration at distant sites have a shorter survival times than dogs without evidence of infiltration at distant sites. This study suggests that cytology of spleen and liver is indicated either for ultrasonographically normal or for ultrasonographically abnormal spleen and liver in dogs with cMCT.     

Evaluation of dysmyelopoiesis in cats: 34 cases (1996-2005)

OBJECTIVE: To further classify dysmyelopoiesis as diagnosed by use of a general classification scheme and to determine clinical features and laboratory test results that could be used to differentiate between the various forms of dysmyelopoiesis in cats. DESIGN: Retrospective case series. Sample Population-Bone marrow slides from 34 cats. PROCEDURES: Medical records of cats in which dysmyelopoiesis was diagnosed on the basis of blood and bone marrow analyses from 1996 to 2005 were reviewed. Criteria for inclusion in the study were findings of > 10% dysplastic cells in 1 or more hematologic cell lines in the bone marrow and concurrent cytopenias in the blood. Cats that met these criteria were classified into subcategories of myelodysplastic syndromes or secondary dysmyelopoiesis on the basis of reevaluation of slides. RESULTS: Of 189 bone marrow slides reviewed, 34 (14.9%) had > 10% dysplastic cells in 1 or more cell lines. Cats were subcategorized as having myelodysplastic syndrome with excessive numbers of blast cells (n = 13), myelodysplastic syndrome with refractory cytopenias (8), a variant form of myelodysplastic syndrome (1), and secondary dysmyelopoiesis (12). Findings of dysmyelopoiesis and autoagglutination in cats with myelodysplastic syndrome and in those with immune-mediated anemia complicated differentiating between the 2 conditions. CONCLUSIONS AND CLINICAL RELEVANCE: Differentiating cats with myelodysplastic syndromes from cats with immune-mediated hemolytic anemia was difficult because severe anemia and autoagglutination may be concurrent findings in both conditions. Differentiating between myelodysplastic syndrome with excessive numbers of blast cells and myelodysplastic syndrome with refractory cytopenias was useful in predicting clinical outcome.     

Hemophagocytosis and Histoplasma‐like fungal infection in 32 cats

Histoplasmosis is one of the most common systemic fungal diseases in cats from the United States. It commonly causes respiratory or disseminated disease and is often associated with one or more cytopenias. Here, we describe 32 cats in which a Histoplasma‐like fungal infection was associated with concurrent hemophagia in at least one sample site, commonly spleen, bone marrow, liver, and/or lymph node. The degree of hemophagia was characterized as moderate or marked in the majority of cases, and in all cases, there was a predominance of phagocytized mature erythrocytes. A few cases also had macrophages with phagocytized erythroid precursors, platelets, and/or neutrophils. Complete blood count results were available for 25 cats, and cytopenias were common (20/25), including solitary anemia (10), anemia and thrombocytopenia (5), solitary neutropenia (2), pancytopenia (2), and anemia and neutropenia (1). Bone marrow samples were only available in a small subset of cases, preventing the further assessment of the causes of the cytopenias. Hemophagocytosis has been previously reported in cats with neoplastic diseases and a cat with calicivirus infection, and likely occurs with other conditions as well, such as hemorrhage or hemolysis. Results of this report suggest that systemic fungal disease is an additional differential to consider when there is hemophagia in a feline cytology sample.     

Role of Latent Feline Leukemia Virus Infection in Nonregenerative Cytopenias of Cats

Background: Nonregenerative cytopenias such as nonregenerative anemia, neutropenia, and thrombocytopenia in cats with feline leukemia virus (FeLV) antigen are assumed to be caused by the underlying FeLV infection. In addition, cats with negative FeLV antigen-test results that have cytopenias of unknown etiology often are suspected to suffer from latent FeLV infection that is responsible for the nonregenerative cytopenias.
Objective: The purpose of this study was to assess the role of latent FeLV infection by polymerase chain reaction (PCR) in bone marrow of cats with nonregenerative cytopenias that had negative FeLV antigen test results in blood.
Animals: Thirty-seven cats were included in the patient group. Inclusion criteria were (1) nonregenerative cytopenia of unknown origin and (2) negative FeLV antigen test result. Antigenemia was determined by detection of free FeLV p27 antigen by ELISA in serum. Furthermore, 7 cats with positive antigen test results with nonregenerative cytopenia were included as control group I, and 30 cats with negative antigen test results without nonregenerative cytopenia were included as control group II.
Methods: Whole blood and bone marrow samples were tested by 2 different PCR assays detecting sequences of the envelope or long terminal repeat genes. FeLV immunohistochemistry was performed in bone marrow samples.
Results: Two of the 37 cats (5.4%) in the patient group were positive on the bone marrow PCR results and thus were latently infected with FeLV.
Conclusions and Clinical Importance: The findings of this study suggest that FeLV latency is rare in cats with nonregenerative cytopenias.     

Peripheral blood abnormalities and bone marrow infiltration in canine large B‐cell lymphoma: is there a link?

Official guidelines do not consider bone marrow (BM) assessment mandatory in staging canine lymphoma unless blood cytopenias are present. The aim of this study was to find out if blood abnormalities can predict marrow involvement in canine large B‐cell lymphoma. BM infiltration was assessed via flow cytometry. No difference was found between dogs without haematological abnormalities and dogs with at least one. However, the degree of infiltration was significantly higher in dogs with thrombocytopenia, leucocytosis or lymphocytosis and was negatively correlated to platelet count and positively to blood infiltration. Our results suggest that blood abnormalities are not always predictive of marrow involvement, even if thrombocytopenia, leucocytosis or lymphocytosis could suggest a higher infiltration. BM evaluation should therefore be included in routine staging in order not to miss infiltrated samples and to improve classification. However, its clinical relevance and prognostic value are still not defined and further studies are needed.     

Evaluation of proliferative disorders in canine bone marrow by use of flow cytometric scatter plots and monoclonal antibodies

The combination of flow cytometric scatterplot analysis and specific monoclonal antibodies was used to evaluate the lineage of cells from six dogs with proliferative disorders of bone marrow. Scatterplot analysis was used to identify mature and immature myeloid and erythroid cells. The immunophenotype of cells in the immature myeloid gate was determined by labeling cells with four monoclonal antibodies. These results were compared to results of cytologic and cytochemical evaluation. The immunophenotype of a dog with a diagnosis of myelogenous leukemia was a cluster of differentiation-18 (CD-18) positive, CD-14 negative, Thy-1 negative, and a major histocompatibility complex (MHC) class II negative. The immunophenotype of a dog with a diagnosis of myelomonocytic leukemia was CD-18 positive, CD-14 positive, Thy-1 positive, and MHC class II positive. Although this phenotype clearly differentiated myelomonocytic leukemia from myelogenous leukemia, it was similar to the immunophenotype of dogs with a diagnosis of malignant histiocytosis or hemophagocytic syndrome. The immunophenotype of two dogs with myelodysplastic syndrome was CD-18 positive and CD-14 negative. Results for Thy-1 and MHC class II were variable. As additional lineage-specific monoclonal antibodies become available, immunophenotyping should become a valuable tool for determination of the lineage of cells in canine myeloproliferative disorders.     

A dog with myelodysplastic syndrome: chronic myelomonocytic leukemia

An eleven-year-old female pug was referred to Yamaguchi University Animal Hospital for evaluation of anemia and thrombocytopenia. The cytological examination of the peripheral blood showed some giant monocytic lineage blast cells. A few granulocytes and platelets had dysplastic features. On day 7, in addition to increasing the monocytic lineage cells, the dysplastic features of the blood had also increased compared to the initial examination. We performed bone marrow aspiration upon her death. The bone marrow revealed dysplastic features in all three hematopoietic cell lines, and an increase in the monocytic cell line. Based on the features of the bone marrow and the peripheral blood, this case was confirmed to be myelodysplastic syndrome--Chronic myelomonocytic leukaemia (MDS-CMML).     

Histiocytic sarcoma of macrophage origin in a cat: case report with a literature review of feline histiocytic malignancies and comparison with canine hemophagocytic histiocytic sarcoma

Mild nonregenerative anemia was detected in a 9-year-old neutered male domestic shorthair cat during a routine examination. Bone marrow core biopsy revealed erythroid hyperplasia; however, a specific cause was not identified. Over the next 8 months the anemia progressed, eventually becoming mildly regenerative, and moderate thrombocytopenia developed. On ultrasonographic examination, marked splenomegaly, mild hepatomegaly, and abdominal lymphadenopathy were found. Cytologic evaluation of splenic aspirates revealed increased numbers of mildly to moderately pleomorphic histiocytes that frequently had phagocytosed RBCs, leukocytes, and occasionally platelets. Histopathologic examination of the spleen and liver revealed effacement of splenic architecture by a histiocytic sarcoma (HS), and neoplastic histiocytes in hepatic sinusoids. A second bone marrow aspirate revealed neoplastic infiltration by similar cells. The histiocytes in all tissues were mildly to moderately pleomorphic and markedly erythrophagocytic. The immunophenotype of histiocytes in the spleen was CD1c(-)/CD11b(+)/CD18(+)/MHC-II(+), supporting a macrophage cell lineage. The clinical, pathologic, and immunophenotypic findings in this cat were similar to those in hemophagocytic HSs in dogs. To our knowledge, this is the first report of a HS of purported macrophage phenotype in a cat.     

Hemophagocytic syndrome in a cat with multiple myeloma

An 11‐year‐old, castrated male, Domestic Medium Hair cat was presented to the University of Florida Small Animal Hospital with a 2‐week history of upper respiratory infection and increased serum globulins, as reported by the referring veterinarian. Physical examination was unremarkable other than melanosis of the left iris, with no evidence of ocular, nasal, or respiratory disease. Laboratory abnormalities included moderate nonregenerative anemia, mild leukopenia, mild hyperfibrinogenemia, severe hyperglobulinemia, mild hypoalbuminemia, and hypocholesterolemia. Abdominal radiographs and ultrasonographic examination revealed mild splenomegaly with no other abnormalities. Thoracic radiographs revealed no abnormalities. Cytologic evaluation of fine‐needle aspirates from the spleen, liver, and bone marrow revealed numerous plasma cells and many vacuolated macrophages exhibiting marked phagocytosis of mature erythrocytes and platelets, occasionally metarubricytes and leukocytes, and rarely plasma cells. The cytologic interpretation was multiple myeloma and associated hemophagocytic syndrome (HPS). Serum protein electrophoresis revealed a monoclonal gammopathy, providing further evidence for a multiple myeloma. To the authors' knowledge, this is the first report of HPS secondary to neoplasia in a cat.     

Hematopathology in dogs experimentally infected with a Swedish granulocytic Ehrlichia species

Seven, adult, female beagles were inoculated with a Swedish granulocytic Ehrlichia organism closely related to Ehrlichia equi and E. phagocytophila. Blood and bone marrow changes were evaluated throughout the acute phase of infection. All dogs developed moderate to severe thrombocytopenia during the parasitemic period. The mean platelet volume and platelet distribution width increased, and large platelets were seen on blood smears when platelet numbers were low. In bone marrow, absolute numbers of megakaryocytes and immature megakaryocytes were increased. These results suggested the thrombocytopenia was caused by increased platelet destruction. The dogs also developed mild, normocytic, normochromic anemia, with simultaneous decreases in serum iron concentration and total iron-binding capacity that resembled the anemia of inflammation. In bone marrow, there was a slight increase in immature erythroid cells and no erythroid hypoplasia; iron stores were normal to increased. Myeloid hyperplasia was seen in all infected dogs, despite neutropenia in peripheral blood. Lymphopenia occurred early in the parasitemic period, but lymphocytes responded strongly and numbers increased above baseline levels by the end of parasitemia. Blast-transformed lymphocytes (5% to 20%) were seen in peripheral blood for a few days. Experimentally-induced canine granulocytic ehrlichiosis caused cytopenias of short duration, coincident with the appearance of ehrlichial inclusions in neutrophils.