A femorotibial joint swelling with popliteal lymph node enlargement in a Rottweiler

A 9-year-old male Rottweiler was presented to the Veterinary Medical Hospital Montenegro, Porto, Portugal with a large mass medial to the left stifle and radiographic signs of bone lysis involving the proximal tibia, fibula, and distal femur. A fine-needle aspiration was obtained from left popliteal lymph node, which was markedly enlarged. Cytologic examination revealed a highly cellular sample consisting of pleomorphic cells with marked anisocytosis and anisokaryosis and other criteria of malignancy. Some cells contained intracytoplasmic, granular, dark brown material, consistent with hemosiderin. Histologic evaluation of the surgically-excised lymph node revealed a neoplastic proliferation of histiocytic cells, with marked pleomorphism; occasional cells were erythrophagocytic. Mitotic figures were frequently observed, and many were atypical. Histologic findings were consistent with malignant histiocytosis. Necropsy examination confirmed the diagnosis of malignant histiocytosis with systemic involvement affecting most organs examined. This case of malignant histiocytosis case had an atypical clinical presentation, mimicking a musculoskeletal disorder. It underlines the importance of cytology as a simple, inexpensive, rapid and noninvasive complementary exam in routine clinical practice that can permit early diagnosis of the disease and timely selection of the most adequate therapy.     

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.     

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.     

Neutropenia associated with osteomyelitis due to Hepatozoon canis infection in a dog

A 4-year-old, intact male Shiba dog was referred to Yamaguchi University Animal Medical Center, Yamaguchi, Japan, for the following complaints: anorexia, lethargy, intermittent fever, gingival bleeding and abdominal purpura. The dog presented with persistent neutropenia. Histopathological examination of a bone marrow sample revealed round to oval structures that resembled Hepatozoon micromerozoites and formed a "wheel-spoke" pattern. Furthermore, mature neutrophils were observed around these structures. PCR and sequencing using bone marrow aspirate confirmed Hepatozoon canis (H. canis) infection. These findings suggest that the neutropenia observed in this case was associated with osteomyelitis due to H. canis infection. This is the first report of neutropenia associated with H. canis infection. H. canis infection can be included in the differential diagnosis in canine cases of neutropenia in areas where the disease is endemic.     

Oestrogen-induced bone marrow aplasia in a dog with a Sertoli cell tumour

A 10-year-old male Drahthaar dog with unilateral cryptorchidism was examined because of feminisation and myelotoxicity. Radiography and ultrasonography revealed an abdominal mass which was surgically removed. The mass was identified as a Sertoli cell tumour on histological examination. Findings on bone marrow examination were compatible with aplasia due to the oestrogens secreted by the tumoral cells. Treatment with fluids, antibiotics, whole blood transfusions, corticosteroids and lithium carbonate was unsuccessful. Survival time was 22 days after surgery.     

Mammary gland carcinoma in a dog with peripheral blood and bone marrow involvement associated with disseminated intravascular coagulation

A 7-year-old female Leonberger dog was referred to the National Veterinary School of Lyon Teaching Hospital with a 2-day history of anorexia and bleeding. A mammary mass had been removed 7 months earlier, but histologic examination was not performed. On physical examination, the dog was depressed and had pale mucous membranes and numerous petechiae and hematomas. Significant laboratory findings were moderate thrombocytopenia, prolonged prothrombin, activated partial thromboplastin, and thrombin times, hypofibrinogenemia, and increased concentration of fibrin(ogen) degradation products. A peripheral blood smear, buffy coat preparation, and bone marrow aspirate contained low numbers of large atypical cells that had moderate nuclear:cytoplasmic ratios, oval nuclei with multiple prominent nuclei, and basophilic cytoplasm with villous projections. A small nodule was found in the left inguinal mammary gland, and a fine-needle aspirate contained cells similar to those in blood and bone marrow. In samples of blood, bone marrow, and the mammary mass, the neoplastic cells were immunoreactive for cytokeratin. The diagnosis was mammary carcinoma with secondary disseminated intravascular coagulation (DIC) and disseminated tumor cells in bone marrow and circulating tumor cells in blood; this diagnosis was not confirmed by histopathologic examination. Owing to clinical deterioration and the poor prognosis, the dog was euthanized and a necropsy was not performed. This is the first report of a canine mammary carcinoma with circulating tumor cells and secondary DIC.     

Malignant histiocytosis in four dogs

The clinical and pathologic features of 4 dogs with malignant histiocytosis were evaluated. The most common clinical signs were weight loss, lethargy, lymphadenopathy, hepatosplenomegaly, and anemia. Neoplastic histiocytic infiltrates most commonly were found in the spleen, bone marrow, liver, or lymph nodes. Malignant histiocytosis was considered as a differential diagnosis for anemic dogs with lymphadenopathy and/or hepatosplenomegaly.     

Bone marrow necrosis in a cat infected with feline leukemia virus

A one-year old castrated male cat was admitted to the hospital with vomiting and diarrhea. Laboratory examination revealed pancytopenia and positive for FeLV antigen. A bone marrow examination indicated necrosis of the nucleated cells. Based on these findings, the cat was diagnosed as bone marrow necrosis. Pancytopenia was effectively treated with corticosteroids. Re-examination of the bone marrow confirmed a recovery of normal hematopoietic cells with a infiltration of many macrophages. It is strongly suspected that the bone marrow necrosis in this case could be associated with a bone marrow suppression due to FeLV infection.     

Bone Marrow Cytological Findings in 4 Dogs and a Cat With Hemophagocytic Syndrome

Hemophagocytic syndrome or hemophagic histiocytosis was diagnosed in 4 dogs and 1 cat by evaluation of bone marrow aspirate smears. One of the dogs had a suspected infection with canine parvovirus and a confirmed infection with Salmonella spp, 2 dogs had presumptive diagnoses of myeloproliferative and lymphoproliferative disease, respectively, and 1 dog died without a diagnosis. The cat had hepatic lipidosis and lesions compatible with feline calicivirus infection. All animals had cytopenias involving 2 or more cell lines, and fragmented erythrocytes in the blood, along with mild to moderate increases in the number of macro-phages in the bone marrow. Numerous marrow macro-phages contained phagocytized hematopoietic cells. Other cytological features of the bone marrow were variable in each patient, but the degree of response in the blood was inadequate, even in those with bone marrow hyperplasia. The phagocytosis of hematopoietic elements did not appear to be caused by a primary immune disorder, but rather by the inappropriate activation of normal macrophages secondary to infectious, neoplastic, or metabolic diseases. These findings suggest that hemophagocytic syndrome may be an important factor in the development of cytopenias; the data also support the cytological evaluation of bone marrow aspirates as an aid in the diagnosis of hemophagocytic syndrome. J Vet Intern Med 1996;10:7–14. Copyright © 7996 by the American College of Veterinary Internal Medicine .     

A retrospective study of the incidence and the classification of bone marrow disorders in the dog at a veterinary teaching hospital (1996-2004)

BACKGROUND: An 8-year retrospective study was conducted to evaluate the prevalence and the classification of canine bone marrow disorders in a clinical pathology service at a university referral hospital. ANIMALS: Dogs evaluated for bone marrow disorders at a veterinary teaching hospital. HYPOTHESIS: A better understanding of the spectrum and the prevalence of canine bone marrow disorders can be achieved with a multiyear retrospective study. METHODS: Bone marrow aspirate smears, core biopsy specimens, and case records from 717 dogs were reviewed. RESULTS: Bone marrow specimens were first categorized based on the presence or the absence of a primary bone marrow disorder. Nondysplastic and nonmalignant pathologic changes were placed into 14 subcategories. Frequently observed pathologic disorders included nonregenerative immune-mediated anemia, pure red cell aplasia, bone marrow necrosis, myelofibrosis, and hemophagocytic syndrome. Dysmyelopoiesis (n = 61) was subcategorized into myelodysplastic syndromes (n = 27), and congenital (n = 1) and secondary (n = 33) dysmyelopoiesis. One hundred twenty-six cases of neoplasia were divided into acute leukemia (n = 46), chronic leukemia (n = 7), stage 5 malignant lymphoma (n = 28), multiple myeloma (n = 25), malignant histiocytosis (n = 11), metastatic mast-cell tumor (n = 3), sarcoma (n = 5), and carcinoma (n = 1). CONCLUSIONS AND CLINICAL IMPORTANCE: This study provides a general indication of the spectrum and the prevalence of canine bone marrow disorders at a referral center in North America.     

Malignant mesenchymoma with widespread metastasis including bone marrow involvement in a dog

A male castrated Golden Retriever was presented for evaluation of a large mass over the left shoulder extending to the lower part of the neck that had been present for an extended period of time, but had a recent history of rapid growth. Previous aspirates of the mass were consistent with a lipoma. The mass was surgically excised and was diagnosed as an extraskeletal osteosarcoma based on histopathology. After surgery, the dog was initiated on a chemotherapy protocol with carboplatin and metronomic cyclophosphamide. He became neutropenic, anemic, and thrombocytopenic 14 days after the carboplatin treatment was administered. The neutropenia resolved, but the anemia and thrombocytopenia progressed. A bone marrow aspirate revealed erythroid hypoplasia, myeloid hyperplasia with a predominance of early precursors, and a subset of cells that made up 20% of the total population that were reported as bizarre and unclassifiable. These cells were discrete in nature and were thought to be hematopoietic in origin. The dog was euthanized due to deterioration of the clinical condition. On postmortem examination, widespread metastasis involving the lungs, liver, kidney, heart, and bone marrow was found. Histopathology of the tumor lesions determined 2 distinct malignant populations of liposarcoma and osteosarcoma, consistent with malignant mesenchymoma. However, the possibility of 2 separate neoplastic processes cannot be definitively excluded. This is the first report of bone marrow metastasis of a malignant mesenchymoma in a dog.     

Thymic lymphosarcoma of T cell lineage in a koala (Phascolarctos cinereus)

Objective To diagnose and characterise thymic lymphosarcoma in a koala.
Design A pathological case.  

Animal

Seven-year-old female koala.
Procedure The neoplastic process was investigated macroscopically, haematologically, histologically and immunohistologically.
Results The koala had difficulty swallowing because of a medial swelling in the lower neck. Biopsy of this mass and blood examination revealed lymphosarcoma with a leukaemic manifestation; necropsy and histopathological examination showed the mass to be thymus. Palatine tonsils, cervical, axillary and mesenteric lymph nodes, spleen, liver, gut, bronchi, genitalia and bone marrow were infiltrated by neoplastic cells. Immunohistological staining of the thymic mass, cervical and mesenteric lymph nodes, bone marrow, spleen and gut revealed the neoplastic cells to be of T lymphocyte origin (positive for both anti-human CD3 and CD5).  

Conclusions

It is speculated that the neoplastic process originated in the thymus and was disseminated by bloodborne neoplastic cells: This first report of thymic lymphosarcoma in a marsupial confirms that antibodies raised originally to investigate human lymphoid neoplasia can cross-react with neoplastic lymphocytes in koalas.     

Diagnosis and treatment of chronic T-lymphocytic leukemia in a spotted hyena (Crocuta crocuta).

Physical examination of an asymptomatic 20-yr-old intact female spotted hyena (Crocuta crocuta) revealed a midabdominal mass. A complete blood count (CBC) revealed peripheral lymphocytosis. Abdominal ultrasonography and laparoscopy confirmed severe splenomegaly. Cytologic examination of a bone-marrow core and histologic examination of spleen and liver biopsy samples revealed neoplastic small lymphocytes. Immunohistochemical staining of liver and spleen samples with the use of leukocyte-specific monoclonal antibodies showed that the neoplastic lymphocytes were immunoreactive to T-lymphocyte CD3 receptor and immunonegative to B-lymphocyte CD79a receptor. The morphology and distribution of neoplastic T-lymphocytes within the spleen, liver, peripheral blood, and bone marrow was most consistent with chronic T-lymphocytic leukemia. Treatment with chlorambucil and prednisone effectively decreased the lymphocyte count, but was associated with thrombocytopenia, which resolved after chlorambucil treatment was temporarily discontinued. Chemotherapy was resumed with a single dose of L-asparaginase, followed by a lower dosage of chlorambucil and continued prednisone. Two years after initial diagnosis, the hyena developed a hemoabdomen and was euthanized. Neoplastic T-lymphocytes were present in spleen, liver, visceral and peripheral lymph nodes, lungs, heart, kidney, adrenal glands, mesentery, intestines, pancreas, brain, and bone marrow.     

Bone marrow hypoplasia in a feminized dog with an interstitial cell tumor.

Bone marrow hypoplasia and feminization developed in a 10-year-old male German Shepherd Dog with interstitial cell tumor. Clinical abnormalities included pyrexia, pale mucous membranes, signs of abdominal pain, large left testis, atrophied right testis, and feminization. Abnormal laboratory findings included pancytopenia, bacteremia, bacteriuria, and pyuria. Results of cytologic examination of a bone marrow aspirate were consistent with aplastic anemia. Serum estradiol concentration was high, and serum testosterone concentration was low, compared with normal values for male dogs. The left testicular mass was identified as an interstitial cell tumor. Other causes of the aplastic anemia or feminization were not found.     

Biclonal gammopathy associated with immunoglobulin A in a dog with multiple myeloma

A 10-year-old neutered male Airedale Terrier was evaluated for inappetance, weight loss, and lameness. Multiple myeloma was diagnosed based on bone marrow plasmacytosis, multiple lytic bone lesions, and hyperglobulinemia with a clonal gammopathy on serum protein electrophoresis. Splenic plasmacytosis, and retinal lesions consistent with hyperviscosity syndrome also were found. Temporary responses to 2 different chemotherapy protocols (melphalan and prednisone, and cyclophosphamide and prednisone) were seen, with remission of clinical signs and a decrease in the biclonal gammopathy but no resolution of the splenic mass. Eventual return of clinical signs led to euthanasia at 175 days postdiagnosis. Necropsy examination confirmed multiple myeloma involving bone marrow and spleen, and glomerulonephritis. An immunoglobulin-A (IgA) gammopathy was demonstrated by immunoelectrophoresis; biclonality was ascertained by immunofixation electrophoresis. The clonal components consisted of intact Ig with a heavy chain of the a class and a light chain of undetermined class. To our knowledge, this is the first report of undimerized biclonal gammopathy in a dog caused by a single heavy chain class involving IgA.     

Erythrocytosis and pleural effusion associated with a hepatoblastoma in a Thoroughbred yearling

A 10-month-old Thoroughbred filly was presented with a 2-month history of recurrent fever and pleural effusion. Major clinical findings were pyrexia and congested mucous membranes. Clinical pathology tests revealed an erythrocytosis, hyperfibrinogenaemia and hyperglobulinaemia. Pleural fluid was seen on ultrasonographic examination of the thorax and analysis of a thoracocentesis sample indicated a lymphocytic, modified transudate. A transtracheal aspirate was normal. The erythrocytosis persisted despite IV fluid therapy. Arterial blood gas analysis and bone marrow aspirate were normal. These findings were indicative of secondary inappropriate erythrocytosis. Ultrasonographic examination of the abdomen showed a large encapsulated heterogeneous mass in the left lobe of the liver. Histopathological evaluation of a biopsy of the mass was indicative of a hepatic carcinoma. The filly was euthanased and necropsy confirmed the presence of a hepatic tumour with no evidence of systemic metastasis. Further histopathological evaluation confirmed the tumour to be an embryonal macrotrabecular epithelial-type hepatoblastoma, a type of hepatoblastoma that has not previously been reported in a horse.     

Immunocytological confirmation of bone marrow metastases in a dog with cholangiocarcinoma

The case history of a four-year-old, male Bernese mountain dog is presented. Carcinoma cells were detected in the liver by ultrasound-guided fine-needle aspiration. Bone marrow aspirated from the iliac crest and the left femur showed a distinct infiltration by carcinoma cells. Immunocytological examination of the liver and bone marrow metastases showed a negative staining result for large spectrum cytokeratin (CK) KL1, a strong positive result for CK7 and a focal weak positive result for CK20. The dog was euthanased due to the grave prognosis. Histopathological examination revealed metastatic cholangiocarcinoma. The authors conclude that cytological and immunocytological examination of bone marrow aspirates should be used more frequently for the detection of distant metastases of carcinomas in small animal medicine.     

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.     

Myelophthisic pancytopenia in a pony mare

Myelophthisic pancytopenia was diagnosed in a 10-year-old pony mare with a history of recurring colic and anemia. Physical findings were unremarkable, with the exception of pale mucous membranes. Hematologic analysis revealed nonregenerative pancytopenia. Testing for equine infectious anemia and antiglobulin (Coombs) yielded negative results. The mare was treated with antibiotics, boldenone undecylenate, and corticosteroids, but a regenerative bone marrow response was not seen. Postmortem examination revealed severe myelofibrosis and multiple sites of extramedullary hematopoiesis. Myelophthisic pancytopenia develops when a space-occupying lesion destroys sufficient bone marrow or disturbs marrow architecture, resulting in decreased production capacity. Pancytopenia in the pony of this report resulted from inadequate production of blood cellular components secondary to replacement of the bone marrow by myelofibrosis. Cause of the myelofibrosis was not identified.     

Bone marrow necrosis and myelophthisis: manifestations of T‐cell lymphoma in a horse

Abstract: A 14‐year‐old spayed American Paint mare was evaluated for mild colic, anorexia, pyrexia, and pancytopenia. Physical examination revealed mild tachycardia, tachypnea, and pale mucous membranes. Serial laboratory analyses revealed progressive pancytopenia, hyperfibrinogenemia, and hyperglobulinemia. A few large atypical cells were observed in peripheral blood smears. Results of tests for equine infectious anemia and antipenicillin antibody were negative. Serum protein electrophoresis indicated a polyclonal gammopathy. Smears of bone marrow aspirates contained hypercellular particles, but cell lines could not be identified because the cells were karyolytic, with pale basophilic smudged nuclei and lack of cellular detail. A diagnosis of bone marrow necrosis was made. Treatment consisted of antimicrobials, nonsteroidal anti‐inflammatory drugs, and corticosteroids. The pyrexia resolved; however, the pancytopenia progressively worsened and petechiation and epistaxis developed. The horse was humanely euthanized. Postmortem examination revealed a diffuse round cell neoplasm infiltrating the kidneys, spleen, lymph nodes, lungs, and bone marrow. Immunophenotyping results (CD3+, CD79α−) indicated the neoplastic cells were of T‐cell lineage. Infiltration of lymphoma cells into the bone marrow appeared to have resulted in severe myelophthisis and bone marrow necrosis. Bone marrow necrosis has been associated previously with lymphoma in humans and dogs. To our knowledge, this is the first reported case of lymphoma resulting in bone marrow necrosis in a horse.