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.     

Reactive histiocytosis of the orbit and posterior segment in a dog

We present a case of reactive histiocytic disease involving the orbit, optic nerve, retina, and choroid in a Border Collie dog initially presenting for vision loss. Long-term partial return of vision has been achieved with systemic immunosuppression. Anterior segment and ocular surface manifestations of reactive histiocytic disease in dogs are relatively common. Posterior segment and orbital involvement, however, are minimally documented in the existing literature. To the authors' knowledge, this is the first report of disease confined to the orbit and posterior segment as well as the first report of vision loss as a presenting complaint for reactive histiocytic disease. Clinical, magnetic resonance imaging, cytologic, and histopathologic findings are reviewed.     

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.     

Cerebrospinal fluid from a 10-year-old dog with a single seizure episode

A cerebrospinal fluid sample collected from the cerebellomedullary cistern of a 10-year-old Shetland Sheepdog with a recent history of seizures was submitted for fluid analysis and cytologic examination. Key findings included a total nucleated cell count of 520/microL (reference interval 0-5 cells/microL), with a predominance of mononuclear cells, a protein concentration of 51.8 mg/dL (reference interval 0-35 mg/dL), and a glucose concentration of 44.7 mg/dL (reference interval 52-105 mg/dL). There was marked atypia of the mononuclear cells, with abundant eosinophilic cytoplasm, marked anisocytosis and anisokaryosis, occasional binucleated cells, mitotic figures, and rare erythrophagia. The cytologic interpretation was marked, monocytoid-rich, mixed cell pleocytosis with cellular atypia worrisome for neoplasia. In addition to histiocytic neoplasia, differentials included granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, and granulomatous inflammation. The dog did not respond to anti-inflammatory and anticonvulsive therapy. At necropsy, a mass involving the meninges and subtending the neuropil of the right temporal lobe of the cerebrum was found. Histologically, the mass was composed of large, bizarre histiocytic cells with multinucleated forms and numerous mitotic figures. Using immunochemistry on cytologic and histologic samples, the pleomorphic histiocytic cells were positive for CD1c, CD11ad, CD45, lysozyme, and vimentin, and were negative for CD3, CD4, CD79a, CD90, and pancytokeratin. These findings supported a diagnosis of primary CNS malignant histiocytosis of dendritic antigen-presenting cell (CD1c+) origin. To our knowledge, this is only the third reported case of primary CNS histiocytic sarcoma in dogs, and the first to demonstrate strong immunochemical evidence for dendritic antigen-presenting cell origin.     

MR IMAGING OF HISTIOCYTIC SARCOMA OF THE CANINE BRAIN

Histiocytic sarcomas are characterized by proliferation and/or infiltration of neoplastic histiocytes localized to specific organs, unlike malignant histiocytosis which involves many organ systems. Only a few cranial histiocytic sarcomas have been reported. Here we describe four dogs that presented with neurological deficits referable to the forebrain, and were diagnosed histologically as having histiocytic sarcoma. Using magnetic resonance (MR) imaging, the tumors were characterized by a T2-hyperintense and T1-isointense mass in one dog, T2- and T1-isointense extraaxial masses in two dogs, and a diffuse T2-hyperintense lesion over the left cerebral cortex in one dog. All tumors had contrast enhancement. MRI features in three of the four dogs were similar to that of meningioma, supported by the observation of a dural tail in two of these three dogs, and a broad base of attachment in the other. In the other dog the imaging findings were similar to those of encephalitis. Intracranial histiocytic sarcoma does not appear to have specific MR imaging features and can be confused with meningioma or encephalitis.     

Malignant histiocytosis in a domestic cat: cytomorphologic and immunohistochemical features

Malignant histiocytosis (MH) was diagnosed in a 13-year-old neutered male Domestic Shorthair cat on the basis of light microscopic and immunohistochemical findings. Thoracic fluid analysis showed a modified transudate which contained a very few atypical discrete cells. Cytologic and histologic evaluation of mediastinal and splenic masses revealed a pleomorphic population of large, discrete, round cells 10 to 30 micrometers in diameter with marked cellular atypia. Nuclei were oval to reniform, often with prominent, bizarre nucleoli. Multinucleated cells and mitotic figures were commonly seen. Erythro- and leucocytophagia were noted. Immunohistochemistry indicated a scattered positive staining pattern with the histiocytic antigenic marker Mac387 and a minor population of cells showing positive reactivity for lysozyme. This report describes the characterization of MH in a cat and emphasizes that MH should be considered as a differential diagnosis in proliferative disorders of discrete-cells in this species.     

Dendritic cell leukemia in a Golden Retriever

An 8-year-old castrated male Golden Retriever was evaluated for decreased appetite, lethargy, and labored breathing of 1-week duration. Bilateral pulmonary infiltrates, hepatomegaly, and splenomegaly were present. Results of a CBC revealed marked leukocytosis (62,600/microL; reference interval 4000-15,500/microL) and large numbers of atypical cells (30,700/microL) with abundant cytoplasm. There was no concurrent anemia, neutropenia, or thrombocytopenia. Morphology of the atypical cells was most consistent with a histiocytic origin. Similar cells were identified in bone marrow aspirates, and were morphologically suggestive of the macrophage variant of disseminated histiocytic sarcoma. However, flow cytometry of the abnormal circulating cells revealed CD1c, CD11c, and major histocompatibility complex (MHC) Class II expression without expression of CD11d or lymphoid markers, consistent with myeloid dendritic antigen-presenting cells. At necropsy, the splenic architecture was effaced by neoplastic histiocytes that were also infiltrating lung, liver, an abdominal lymph node, myocardium, an bone marrow. Immunohistochemistry of the splenic neoplastic cells confirmed dendritic cell origin (CD1c+, CD11c+, MHC II+, no expression of CD11d and lymphoid markers). To the authors' knowledge, this is the first report of canine dendritic cell leukemia-in this instance accompanied by marked tissue infiltration.     

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.     

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.     

Histiocytic Sarcoma with Central Nervous System Involvement in Dogs: 19 Cases (2006–2012)

Background

Reports of histiocytic sarcoma (HS) involving the central nervous system (CNS) are sparse and consist mainly of case reports describing 1–3 animals.

Objective

The objective of this study was to report the signalments, clinical signs, clinicopathologic and diagnostic imaging findings, treatment, and outcome of a series of dogs with HS and CNS involvement.

Animals

Nineteen dogs with HS examined at veterinary referral hospitals.

Methods

Retrospective case series. Medical records were reviewed and cases with a histopathological diagnosis of CNS HS were included in the study. Diagnostic imaging studies of the CNS were evaluated and histopathologic samples were reviewed to confirm the diagnosis.

Results

Retrievers and Pembroke Welsh Corgis were overrepresented in this cohort of dogs. Tumors involved the brain in 14 dogs and the spinal cord in 5. In 4 dogs, HS was part of a disseminated, multiorgan process whereas it appeared confined to the CNS in 15 dogs. Diagnostic imaging had variable appearances although extraaxial masses predominated in the brain. There was meningeal enhancement in all dogs that was often profound and remote from the primary mass lesion. Pleocytosis was present in all dogs with CSF evaluation. Median survival was 3 days.

Conclusions and Clinical Importance

Breed predispositions appear to vary from reports of HS in other organ systems. Some unique imaging and clinicopathologic characteristics, particularly brain herniation, profound meningeal enhancement, and pleocytosis in combination with 1 or more mass lesions, might help to differentiate this neoplasm from others involving the CNS, although this requires further study.