Hypercalcemia and parathyroid hormone‐related peptide expression in a dog with thyroid carcinoma and histiocytic sarcoma

A 9.5‐year‐old, male castrated Walker Hound was presented for evaluation of progressive weakness, anorexia, and weight loss. Imaging revealed multiple abdominal and thoracic masses and ascites; fine‐needle aspirates of mesenteric and splenic masses confirmed malignancy, most likely histiocytic sarcoma. Laboratory analyses revealed increased ionized calcium and parathyroid hormone‐related peptide (PTH‐rP) concentrations, and concurrent low–normal parathyroid hormone concentration, consistent with humoral hypercalcemia of malignancy. Necropsy was performed after euthanasia. The dog had disseminated histiocytic sarcoma, including sarcomatosis, as well as bilateral thyroid carcinoma. PTH‐rP immunostaining was positive in the thyroid carcinoma but negative in the histiocytic neoplasm. These results suggest that thyroid carcinoma‐associated hypercalcemia can be caused by tumor secretion of PTH‐rP.     

Pulmonary histiocytic sarcoma in a rabbit

An approximately 8‐year‐old male castrated Dutch rabbit was evaluated for a 6‐day history of respiratory signs, which began as sneezing and progressed to tachypnea with anorexia. On physical examination, tachypnea and pale mucous membranes were noted. Thoracic radiographs revealed a soft tissue pulmonary mass, fine‐needle aspirates of which confirmed a neoplasia with malignant features suspicious for a histiocytic sarcoma. The rabbit was discharged and due to a rapidly deteriorating condition, the owner declined chemotherapy with Lomustine and elected euthanasia of the rabbit. The affected lung was submitted for histopathology. Histologic sections of the lung were characterized by clusters of histiocytic cells and multinucleated giant cells with occasional invasion of blood and lymphatic vessels. The histologic diagnosis was histiocytic sarcoma. To the authors' knowledge, this is the first case report of histiocytic sarcoma in a rabbit. Based on the clinical and radiologic findings in this case, histiocytic sarcoma should be included in the list of differentials for rabbits presenting with respiratory signs and evidence of a pulmonary mass.     

Unique cytologic and histologic features of a suspected cutaneous xanthoma in a dog

A 4‐year‐old spayed female American Staffordshire Terrier presented to the U‐Vet Animal Hospital, Werribee, Australia, with a cutaneous mass that had been slowly growing over 12 months. Cytologic evaluation showed cohesive to individualized, vacuolated spindled cells often arranged in a perivascular pattern. The mass was completely excised, and the histopathologic examination demonstrated sheets of vacuolated spindled to round cells expanding the full thickness of the dermis. The cells demonstrated both Iba1 and CD18 antibody binding, leading to an initial interpretation of histiocytic sarcoma. Given the discordance with the clinical presentation, further immunohistochemistry (IHC) was performed. The cells demonstrated strong CD204 antibody binding and did not bind E‐cadherin antibody, consistent with a dermal macrophage origin. Ki‐67 antibody binding was regionally variable from <5% to 25%, with more regions that had low Ki‐67 expression. A fasted serum biochemistry panel revealed hypertriglyceridemia and persistent hypercholesterolemia. Based on clinical, microscopic, biochemical, and IHC results, the final interpretation was an indolent dermal histiocytic proliferation of macrophage origin, with a preference for cutaneous xanthoma or reactive dermal fibrohistiocytoma.     

Invasive histiocytic sarcoma of the lumbar spine in a ferret (Mustela putorius furo)

This report describes the history, clinical examination and histopathology of a histiocytic sarcoma in a domestic ferret. Clinical signs were acute paraplegia and dysuria. Physical examination revealed a firm, smooth, touch‐sensitive mass in and around the lumbar vertebral column. Neurologic examination was consistent with a lesion between spinal cord segments T3 and L3. Magnetic resonance images revealed bone lesions of L2 and L3 combined with compression of the spinal cord due to a homogenous, isointense mass that was diagnosed as a malignant round cell tumour and the ferret was euthanased. Histopathology confirmed the diagnosis of an infiltrative histiocytic sarcoma.     

Multifocal cutaneous histiocytic sarcoma in a young dog and review of histiocytic cell immunophenotyping

A 9‐month‐old male Great Dane had progressive generalized nodular dermatopathy for several months. There were > 100 raised, alopecic, firm, painful nodules throughout the skin. Aspirates from several lesions yielded moderate numbers of irregularly round or polygonal to spindle‐shaped cells with mild to moderate anisocytosis and few inflammatory cells, and the cytologic interpretation was proliferation of mesenchymal or histiocytic cells. On histopathologic examination, nodules were composed of densely packed sheets of round to spindle‐shaped cells with mild anisokaryosis and low mitotic activity. Multifocal histiocytic sarcoma with a spindle‐cell pattern was diagnosed based on morphologic features and intense expression of CD18. Additional immunophenotypic analysis on frozen sections of tissue confirmed the diagnosis of histiocytic sarcoma; expression of CD18, CD45, CD1a, CD11b, and CD11c, limited expression of Thy‐1 (CD90) and CD80, and lack of expression of CD4, CD11d, and CD86 indicated that the cells were likely interstitial dendritic cells; a review of reactive and neoplastic dendritic cells is provided. Based on staging, internal organs were not affected. Sequential treatment with lomustine and doxorubicin failed to prevent progression of the cutaneous lesions, and the dog died 3 months after initial diagnosis. At necropsy, a focus of neoplastic cells was present in one lymph node, but except for skin other organs were not involved. The clinical presentation of histiocytic sarcoma may be unusual, and neoplastic cells may lack overt features of malignancy on cytologic and histopathologic examination. In some instances, immunophenotyping is required to differentiate histiocytic sarcoma from other histiocytic disorders.     

IMAGING DIAGNOSIS—SPINAL CORD HISTIOCYTIC SARCOMA IN A DOG

A 12‐year‐old mixed breed dog was presented for evaluation of progressive paraparesis and ataxia. Magnetic resonance (MR) imaging was performed and identified multifocal intradural spinal cord mass lesions. The lesions were hyperintense in T2‐weighted sequences, isointense to mildly hyperintense in T1‐weighted sequences with strong contrast enhancement of the intradural lesions and spinal cord meninges. Spinal cord neoplasia was suspected. A diagnosis of intramedullary spinal cord histiocytic sarcoma, confined to the central nervous system, was confirmed histopathologically. Spinal cord histiocytic sarcoma is a rare neoplasm, but should be included in the differential diagnosis for dogs with clinical signs of myelopathy.     

Histiocytic sarcoma in the tarsus of a cat

A 12-year-old Persian cat was examined for a firm swelling of the right tarsal region and enlargement of the corresponding right popliteal lymph node. Cytologic evaluation demonstrated a population of malignant cells consistent with large cell lymphoma. Necropsy revealed a multi-lobulated subcutaneous mass involving the tarsus with some extension into adjacent deep muscular tissue. Histologically, the mass was composed of round cells with eosinophilic cytoplasm and pleomorphic anisokaryotic nuclei. Evidence of articular and nodal infiltration by these cells was observed. Differential diagnoses included synovial sarcoma and histiocytic sarcoma. Neoplastic cells were negative for cytokeratin, CD79a, and CD3 and positive for CD18, vimentin, lysozyme, and alpha-1-antitrypsin, most consistent with a diagnosis of histiocytic sarcoma. This is the first report of a histiocytic sarcoma involving a joint of a cat. The final diagnosis was based on the light microscopic appearance in combination with the immunohistochemical stains.     

Canine inflamed nonepitheliotropic cutaneous T‐cell lymphoma: a diagnostic conundrum

Background –  Cutaneous T‐cell lymphoma (CTCL) in dogs is a heterogeneous disease complex, which consists of nonepitheliotropic (NE) and epitheliotropic forms. These lymphomas are readily recognized by the presence of dominant populations of cytologically atypical lymphocytes. Objective –  The objective of this study was to introduce the key features of inflamed NE‐CTCL, which is easily confused with reactive, inflammatory histiocytic disease. Animals –  Twenty‐four dogs (mean age 7.5 years) presented with inflamed NE‐CTCL. Lesions presented as nodules, plaques or masses. An initial diagnosis of cutaneous reactive histiocytosis (11 dogs) or histiocytic neoplasia (three dogs) was made by primary pathologists. Methods –  Lesions were assessed by histology and immunohistochemistry to detect canine leukocyte antigens. Lesional genomic DNA was extracted and gene rearrangement analysis of the T‐cell receptor γ locus was assessed. Results –  The cutaneous lesions consisted of pleocellular infiltration of the dermis with variable extension into the subcutis. The lesions often surrounded vessels and adnexae. Epitheliotropism was minimal or lacking. Small lymphocytes, plasma cells and intermediate to large, cytologically atypical lymphocytes were scattered between prominent histiocytic infiltrates. Atypical lymphocytes often had marked variation in the intensity of CD3 expression. Molecular clonality analysis of the T‐cell receptor γ locus revealed clonal expansion of T cells in 22 of 23 dogs tested. Conclusion –  The recognition of inflamed NE‐CTCL and its differentiation from cutaneous reactive histiocytosis depends on careful assessment of lymphocyte morphology and immunostaining patterns. Confirmation of the diagnosis is best accomplished by T‐cell antigen receptor gene rearrangement analysis.     

Histiocytic sarcoma of the spleen in flat-coated retrievers with regenerative anaemia and hypoproteinaemia

Three flat-coated retrievers with a regenerative anaemia were examined. They were hypoproteinaemic suggesting that the anaemia might be due to blood loss, but it was not possible to identify a site of haemorrhage. All three had splenomegaly with splenic abnormalities apparent on ultrasonography. Ultimately all three animals were shown to have a histiocytic sarcoma involving the spleen and other tissues. A fourth flat-coated retriever with anaemia, hypoproteinaemia and an abdominal mass was also diagnosed with a histiocytic sarcoma of the spleen following splenectomy. It is postulated that the dogs' anaemia was due to erythrophagocytosis, either directly by neoplastic cells or by reactive macrophages.     

SKELETAL LESIONS OF HISTIOCYTIC SARCOMA IN NINETEEN DOGS

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

Anti‐tumour activity of oncolytic reovirus against canine histiocytic sarcoma cells

Canine histiocytic sarcoma is an aggressive, fatal neoplastic disease with a poor prognosis. Lomustine is generally accepted as the first‐line systemic therapy, although this compound does not provide complete regression. Therefore, research into a novel approach against canine histiocytic sarcoma is needed. However, anti‐tumour effects of oncolytic therapy using reovirus against histiocytic sarcoma are unknown. Here, we showed that reovirus has oncolytic activity in canine histiocytic sarcoma cell lines in vitro and in vivo. We found that reovirus can replicate and induce caspase‐dependent apoptosis in canine histiocytic sarcoma cell lines. A single intra‐tumoural injection of reovirus completely suppressed the growth of subcutaneously grafted tumours in NOD/SCID mice. Additionally, we demonstrated that susceptibility to reovirus‐induced cell death was attributable to the extent of expression of type I interferons induced by reovirus infection in vitro. In conclusion, oncolytic reovirus appears to be an effective treatment option for histiocytic sarcoma, and therefore warrants further investigation in early clinical trials.     

Carcinosarcoma mimicking a feline injection‐site sarcoma in a cat

A 15‐year‐old spayed female domestic short‐haired cat with cutaneous/subcutaneous well‐circumscribed, alopecic mass approximately 25 × 30 mm in diameter, localized to the left shoulder region was brought to the veterinary surgery department. Despite the suggestive location and macroscopic appearance, feline injection‐site sarcoma was not suspected based on the cytologic examination of fine‐needle aspirates. The tumor was surgically resected, and tissue sections were evaluated microscopically. The tumor was found to be nonencapsulated with a distinct border between the neoplastic parenchyma and surrounding connective tissue. The neoplastic tissue consisted of 2 cell populations: elongated to spindle‐shaped cells arranged in bands and cords and malignant epithelial‐like cells. Both populations showed microscopic features of malignancy. Multinucleate giant cells with irregular cytoplasm were scattered among the neoplastic cells. The spindle‐shaped cells strongly expressed vimentin but did not express α‐smooth muscle actin (α‐SMA) or cytokeratin. Desmin was strongly expressed in about 0‐5% of cells. Epithelial‐like cells expressed cytokeratin, but not vimentin, desmin, or α‐SMA. Multinucleate giant cells expressed vimentin, but did not α‐SMA, desmin, or cytokeratin. Based on microscopic observations and IHC results, the final diagnosis was carcinosarcoma with histologic features compatible with feline injection‐site sarcoma, but without the clinical aggressiveness of this tumor.     

SONOGRAPHIC FEATURES OF HISTIOCYTIC NEOPLASMS IN THE CANINE ABDOMEN

The purpose of this retrospective study was to describe the ultrasonographic features of malignant histiocytosis (MH), malignant fibrous histiocytoma, and histiocytic sarcoma in abdominal organs of dogs. The medical records of 18 dogs that had undergone abdominal sonography and had a histopathologic diagnosis of abdominal MH, malignant fibrous histiocytoma, and histiocytic sarcoma were reviewed. The organ most commonly affected was the spleen. MH was the most common followed by histiocytic sarcoma and malignant fibrous histiocytoma. In the spleen there were often multiple hypoechoic nodules with well-defined borders. In one dog, without focal lesions, the spleen was enlarged and hypoechoic. The liver was the second most commonly affected organ. MH was most common followed by histiocytic sarcomas and malignant fibrous histiocytoma. The most common sonographic feature in the liver was the presence of multiple hypoechoic nodules with well-defined borders. One dog without hepatic nodules had a liver that was ultrasonographically enlarged and hypoechoic. MH in the abdominal lymph nodes resulted in hypoechoic lymphadenopathy. Malignant fibrous histiocytoma was the only neoplastic type in the kidneys appearing as a single heteroechoic renal mass with well-defined borders. MH was observed in the stomach of one dog. Sonographically there was a single well circumscribed hypoechoic mass with well-defined borders and abnormal stomach layers. In this study it was not possible to differentiate between MH, malignant fibrous histiocytoma, and histiocytic sarcoma using sonography.     

Phagocytic plasmacytoma in a dog

A 4-year-old neutered male Golden Retriever was presented to the oncology service of the North Carolina State University Veterinary Teaching Hospital for staging of a histiocytic sarcoma of the left forelimb, diagnosed on the basis of biopsies submitted by the referring veterinarian. Cytologic assessment of aspirates of 2 splenic nodules identified on ultrasonographic examination of the abdomen revealed a highly phagocytic population of neoplastic round cells morphologically suggestive of plasma cells. Histologic assessment of the forelimb mass after amputation of the limb revealed a neoplastic round cell population demonstrating extensive cytophagia and erythrophagia. Immunohistochemical analysis of the tumor population revealed it to be negative for BLA.36 with sporadic positivity for lysozyme and CD79a. Immunofluorescent evaluation revealed weak tumor cell positivity for immunoglobulin (Ig) A and IgM, but extensive strong positivity for IgG, confirming the plasma cell origin of the tumor. Although extensive phagocytic activity may strongly suggest histiocytic origin, plasma cell origin must also be considered among the differential diagnoses for phagocytic round cell tumors.     

Comparisons among MRI signs,apparent diffusion coefficient,and fractional anisotropy in dogs with a solitary intracranial meningioma or histiocytic sarcoma

Although MRI has become widely used in small animal practice, little is known about the validity of advanced MRI techniques such as diffusion‐weighted imaging and diffusion tensor imaging. The aim of this retrospective analytical observational study was to investigate the characteristics of diffusion parameters, that is the apparent diffusion coefficient and fractional anisotropy, in dogs with a solitary intracranial meningioma or histiocytic sarcoma. Dogs were included based on the performance of diffusion MRI and histological confirmation. Statistical analyses were performed to compare apparent diffusion coefficient and fractional anisotropy for the two types of tumor in the intra‐ and peritumoral regions. Eleven cases with meningioma and six with histiocytic sarcoma satisfied the inclusion criteria. Significant differences in apparent diffusion coefficient value (× 10^?3 mm²/s) between meningioma vs. histiocytic sarcoma were recognized in intratumoral small (1.07 vs. 0.76) and large (1.04 vs. 0.77) regions of interest, in the peritumoral margin (0.93 vs. 1.08), and in the T2 high region (1.21 vs. 1.41). Significant differences in fractional anisotropy values were found in the peritumoral margin (0.29 vs. 0.24) and the T2 high region (0.24 vs. 0.17). The current study identified differences in measurements of apparent diffusion coefficient and fractional anisotropy for meningioma and histiocytic sarcoma in a small sample of dogs. In addition, we observed that all cases of intracranial histiocytic sarcoma showed leptomeningeal enhancement and/or mass formation invading into the sulci in the contrast study. Future studies are needed to determine the sensitivity of these imaging characteristics for differentiating between these tumor types.     

Disseminated histiocytic sarcoma with peripheral blood involvement in a Bernese Mountain dog

Abstract: A 6‐year‐old Bernese Mountain dog was presented with a history of lethargy and weight loss of 2 weeks duration. On physical examination the dog had pale mucous membranes and tachypnea. Ultrasound examination revealed hepatomegaly, splenomegaly, and mesenteric lymphadenomegaly. Results of a CBC included marked normocytic normochromic nonregenerative anemia, marked thrombocytopenia, and moderate leukocytosis with mild neutrophilia and a large population of unclassified round cells (6.2 × 10³/μL). The unclassified cells occasionally were bi‐ or multinucleated and had variably abundant pale basophilic cytoplasm that contained multiple irregular clear vacuoles and occasionally erythrocytes. Fine needle aspirate specimens of the mesenteric lymph nodes and spleen were composed of a population of round pleomorphic cells with the same features as the circulating cells. On flow cytometric analysis of peripheral blood, the unclassified cells expressed CD18, CD45, CD11c, CD1c, and CD14; immunocytochemical analysis of blood smears also indicated the cells were positive for CD1c, CD1a, and CD11c. The dog died a few hours after referral. The histologic interpretation of samples collected from spleen, liver, and lymph nodes was malignant neoplasia of histiocytic origin. Immunohistochemical staining yielded negative results for CD11d, a marker of red‐pulp macrophages, ruling out hemophagocytic histiocytic sarcoma. Based on clinical and pathologic findings, the final diagnosis was disseminated histiocytic sarcoma (DHS) with peripheral blood involvement. To our knowledge, DHS in a dog with evidence and immunophenotyping of neoplastic cells in peripheral blood has been reported only rarely.     

Surgical treatment of a large congenital cavernous haemangioma on the thorax of a foal

A 3‐day‐old male foal was presented with a fluctuant 25 × 15 cm mass on the thorax. The mass had increased in size since birth. The mass did not respond to conservative treatment consisting of aspiration of serohaemorrhagic contents and compression bandages, and it was therefore surgically removed when the foal was approximately 2½ weeks. A histopathological diagnosis of cavernous haemangioma was made. Healing progressed without complications despite a large surgical wound left to heal by second intention. Recurrence was not observed during the 1.5‐year follow‐up period.