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Counting mitotic figures (MF) in hematoxylin and eosin–stained histologic sections is an integral part of the diagnostic pathologist’s tumor evaluation. The mitotic count (MC) is used alone or as part of a grading scheme for assessment of prognosis and clinical decisions. Determining MCs is subjective, somewhat laborious, and has interobserver variation. Proposals for standardizing this parameter in the veterinary field are limited to terminology (use of the term MC) and area (MC is counted in an area measuring 2.37 mm2). Digital imaging techniques are now commonplace and widely used among veterinary pathologists, and field of view area can be easily calculated with digital imaging software. In addition to standardizing the methods of counting MF, the morphologic characteristics of MF and distinguishing atypical mitotic figures (AMF) versus mitotic-like figures (MLF) need to be defined. This article provides morphologic criteria for MF identification and for distinguishing normal phases of MF from AMF and MLF. Pertinent features of digital microscopy and application of computational pathology (CPATH) methods are discussed. Correct identification of MF will improve MC consistency, reproducibility, and accuracy obtained from manual (glass slide or whole-slide imaging) and CPATH approaches.

A primary intimal aortic angiosarcoma was diagnosed in a 4-year-old, spayed female German Shepherd that presented for complications of thromboembolic disease because of infarcts in multiple organs. On gross examination, aneurysmal dilatation of the aorta was associated with a friable, necrotic mass attached to the endothelial surface, which partially occluded the aortic lumen. On histologic examination, plump neoplastic spindle cells formed a plaque-like mass arising from the intima that merged with a large accumulation of fibrin and necrotic debris, and projected into the lumen. Neoplastic cells invaded periaortic vessels and were seen in some infarct-associated thromboemboli. Tumor cells expressed vimentin and CD31, with infrequent, patchy staining with factor VIII-related antigen; tumor cells were negative for cytokeratin and smooth-muscle actin. Aortic angiosarcoma is a rare malignancy in humans. This is the first description of a primary intimal aortic angiosarcoma in a dog, with immunohistochemical evidence of endothelial origin.

The elbow joint is one of the feline appendicular joints most commonly and severely affected by degenerative joint disease. The macroscopic and histopathological lesions of the elbow joints of 30 adult cats were evaluated immediately after euthanasia. Macroscopic evidence of degenerative joint disease was found in 22 of 30 cats (39 elbow joints) (73.33% cats; 65% elbow joints), and macroscopic cartilage erosion ranged from mild fibrillation to complete ulceration of the hyaline cartilage with exposure of the subchondral bone. Distribution of the lesions in the cartilage indicated the presence of medial compartment joint disease (most severe lesions located in the medial coronoid process of the ulna and medial humeral epicondyle). Synovitis scores were mild overall and correlated only weakly with macroscopic cartilage damage. Intra-articular osteochondral fragments either free or attached to the synovium were found in 10 joints. Macroscopic or histologic evidence of a fragmented coronoid process was not found even in those cases with intra-articular osteochondral fragments. Lesions observed in these animals are most consistent with synovial osteochondromatosis secondary to degenerative joint disease. The pathogenesis for the medial compartmentalization of these lesions has not been established, but a fragmented medial coronoid process or osteochondritis dissecans does not appear to play a role.

Morphologic and biologic features of five feline granulated round cell tumors were compared with those previously reported to be of globule leukocyte and large granular lymphocyte origin. The five cats ranged from 6 to 9 years of age and presented with nonspecific gastrointestinal signs. Four of the five cats were tested for feline leukemia virus and were negative by enzyme-linked immunosorbent assay. The neoplastic process involved the abdominal cavity in all cases, with a predilection for the distal small intestine and mesentery. The liver and peripheral and thoracic lymphoid tissues were also sporadically affected. Neoplastic round cells contained 0.5–1.5-μm eosinophilic cytoplasmic granules that were difficult to discern on casual observation with hematoxylin and eosin stain but were deep blue and easily visualized when stained with phosphotungstic acid-hematoxylin. In two cases, epithelium in the affected ileum and liver contained unusually large numbers of apparently normal globule leukocytes. Ultrastructurally, the tumor granules tended to cluster at one nuclear pole and were spindle to round in shape with variably dense contents. Some granules contained a dense “cap” at one end or internal crystalloid bars that distorted the granule membrane. The tumors reported herein are similar to all three of the previously reported feline granulated round cell tumors and probably have a common cellular origin.

The objectives of this study were to determine in horses 1) the ages at which viable cartilage canal vessels are present in the articular–epiphyseal cartilage complex of three predilection sites and one nonpredilection site of osteochondrosis (OC), 2) the prevalence of lesions of OC in these sites, and 3) whether there was an association of lesions of OC with necrotic cartilage canal blood vessels. The medial femoral condyle, lateral femoral trochlear ridge, and distal ends of the tibia and proximal phalanx were examined grossly, microradiographically, and histologically in 35 horses 18 months old or younger. Cartilage canals containing patent blood vessels were present in all sites examined in foals less than 3 weeks old and were absent from all sites by 7 months of age. The overall prevalence of lesions of OC at one or more of the sites examined was 12/35 (34%). Prevalence increased to 11/22 (50%) in horses 2 months old and older. These lesions occurred primarily in the medial condyle of the femur ( n = 5) and the intermediate ridge of the distal tibia ( n = 5). All lesions seen in horses between 3 weeks and 5 months of age were associated with necrotic cartilage canal blood vessels. In horses 7 months of age and older, lesions of OC were considered chronic because of extensive involvement of the subchondral bone and bone marrow. These results suggest that OC lesions develop prior to 7 months of age and that ischemic necrosis of cartilage secondary to a defect in vascular supply is an important factor in the pathogenesis of this disease in horses.

Lipogranulomatous lymphangitis of the intestine occurred in four dogs with intestinal lymphangiectasia. All four presented with chronic diarrhea; three had ascites and two had hypoalbuminemia. Lipogranulomas appeared in lymphatics, often at the point of mesenteric attachment, of small intestine, ileum, or ileum and colon. Mesenteric lymphatics were obstructed and villous lacteals were distended. Mesenteric lymph nodes of one dog contained large lipid spaces and that same animal had a solitary subcapsular lipogranuloma of the liver. This disorder is one of several that result in protein-losing enteropathy in dogs.

Multinucleated syncytial cells consisting of clusters of closely apposed, darkly staining nuclei and densely eosinophilic cytoplasm were present in parathyroid glands from 25 of 36 dogs (69%). They were most often located either peripherally in the parathyroid gland or adjacent to blood vessels. The numbers of nuclei per syncytial cell ranged from two to greater than 30. Syncytial cells had degenerative changes as suggested by vacuolated mitochondria, dilated rough endoplasmic reticulum, irregular nuclear outlines, and condensed nuclear chromatin. These ultrastructural changes contrasted sharply with adjacent chief cells that had well-preserved organelles. The presence of desmosomes and fragments of cell membranes between nuclei suggested that syncytial cells were derived from fusion of adjacent chief cells rather than nuclear division without cytokinesis. Syncytial cells were present in normal, hyperplastic, and inactive parathyroid glands from dogs. There were no significant correlations between the presence of multinucleated cells and age of dog, parathyroid histology, and changes in the concentrations of serum calcium, phosphorus, creatinine, or plasma parathyroid hormone. Syncytial cells occurred frequently in canine parathyroid glands regardless of the state of activity of the gland or the concentration of plasma parathyroid hormone or serum calcium.

Articular-epiphyseal cartilage complexes from the distal femur and humerus of five 3-month-old pigs were collected and preserved using either a conventional or a ruthenium hexammine trichloride (RHT)-supplemented fixation technique. Lesions were similar regardless of the fixation technique. Areas of necrosis were in epiphyseal but not articular cartilage from both sites of all pigs. Cartilage canals were confined to epiphyseal cartilage and contained vessels which had endothelial cells in varying stages of degeneration and necrosis. Areas of necrotic cartilage often were adjacent to or surrounded degenerate cartilage canals. Lipid emboli (up to 40.0 γm in diameter) were infrequently located in vessels within cartilage canals. Associated with the lipid emboli were leukocytes, erythrocytes, necrotic cell remnants, and flocculent material. Restriction of necrosis to epiphyseal cartilage and the association of these necrotic areas with degenerating vessels in cartilage canals strongly implicate a defect in cartilage canal blood supply in the pathogenesis of osteochondrosis. The RHT fixation technique resulted in excellent cellular detail at the light microscopic level, but ultrastructurally there was marked vacuolation of chondrocytes and matrix. The conventional technique caused shrinkage of all chondrocytes, resulting in a wide halo of pericellular matrix surrounding each cell.

Primary hyperparathyroidism was diagnosed in two German shepherd pups from a litter of four females. Clinical signs were apparent by two weeks of age and included stunted growth, muscular weakness, and polydipsia/polyuria. Radiography revealed diffuse reduction in bone density. Both pups had marked hypercalcemia, hypophosphatemia, increased plasma immunoreactive parathyroid hormone concentrations and increased fractional clearance of inorganic phosphate in the urine. Intravenous infusion of one affected pup with calcium gluconate failed to suppress the plasma concentration of immunoreactive parathyroid hormone, suggesting autonomous secretion of parathyroid hormone. Necropsy of the other pup at eight weeks of age revealed diffuse hyperplasia of parathyroid chief cells, nodular hyperplasia of thyroid C-cells, skeletal alterations consistent with fibrous osteodystrophy, hypercalcemic nephropathy, and extensive mineralization of the lungs and gastric mucosa. The dam and sire were half sibs. One male pup from a previous litter of six had developed similar clinical signs and radiographic lesions, suggesting autosomal recessive inheritance. This is the first report of hereditary primary hyperparathyroidism in domestic animals, a disease which may be analogous to hereditary neonatal primary hyperparathyroidism in children.

Three canine laryngeal tumors were diagnosed as oncocytomas by light microscopy, but were determined to be rhabdomyomas following ultrastructural and immunocytochemical examination. Tumors consisted of large eosinophilic cells interspersed with smaller dark cells. Large tumor cells had a granular, intensely eosinophilic cytoplasm. Scattered through the tumors were a few elongated cells with cytoplasmic cross striations and multiple nuclei. Tumor cells from all three dogs contained numerous mitochondria and bundles of myofibrils with electron-dense Z-lines typical of striated muscle cells. Intracellular myoglobin and desmin were detected in the tumors by immunocytochemistry. Comparisons are made with a previous report of canine laryngeal oncocytomas.

Rhinosporidiosis was diagnosed in six dogs from the southeastern United States. All six dogs had unilateral nasal polyps with multiple small white sporangia visible beneath the surface. Microscopically, the polyps consisted of organisms and fibrovascular tissue with a surface of columnar or squamous epithelium. Juvenile sporangia were unilamellar, 15-75 in diameter, nucleated, and accounted for about 65% of sporangia seen. Approximately 5% of the sporangia were in intermediate stages of maturation, were bilamellar, 100-150 μm in diameter, and contained immature endospores. Mature sporangia comprised about 30% of the total, were usually unilamellar, 100-400 μm in diameter, and contained a mixture of immature and mature endospores. The inner layer of the wall of the intermediate sporangia and the single wall of the mature sporangia were argyrophilic and carminophilic. Ultrastructurally. the earliest stage contained a nucleus and many ribosomes, lipid droplets, and phagolysosomes. Maturing sporangia contained discrete membrane-bound, round clevage products. These structures subsequently matured to spores, each of which had a wall and contained a nucleus and many lipid droplets. The organism from one dog was cultured and grown in vitro for 7 months and is the first successful cultivation of Rhinosporidium seeberi.

Clinical, gross, and light microscopic findings are described for 36 dogs, 33 females and three males, with adenocarcinomas arising from the apocrine glands of the anal sac. All tumors had light microscopic features of malignancy and 22 of 23 metastasized to iliac and lumbar lymph nodes. Nine dogs had disseminated metastases, but bone metastases were found in only one dog. Differentiated neoplasms formed secretory acini and tubules lined by tall columnar or cuboidal epithelium. Most neoplasms were histologically bimorphic, with glandular areas and solid nests. Parathyroid glands were atrophic. Hypercalcemia (mean = 16.1 mg/dl) was present in 20 of 22 dogs (90%) and hypophosphatemia (mean = 3.2 mg/dl) in 12 of 17 (71%). Remission of hypercalcemia by tumor ablation and recurrence of hypercalcemia with tumor regrowth suggested that the tumor produced a substance that caused hypercalcemia. This unique clinicopathologic syndrome is characterized by hypercalcemia in old. predominantly female, dogs with an adenocarcinoma arising from the apocrine glands of the anal sac.