|
|
CASE I – 2241590 (AFIP 2741248)
Signalment: Rainbow trout (Salmo gairdneri), age and sex unknown
History: A renal mass was discovered during sampling for whirling disease and viral surveillance.
Gross Pathology: The mass was indicated to be in the renal region, but was not described grossly. Gross photos were obtained at the time of sectioning for histopathology.
Laboratory Results: The causative organism of whirling disease and viral agents were not found.
Contributor’s Diagnosis and Comment: The mass consisted of large numbers of well-developed renal tubules with many primitive glomeruli. The mass also contained scattered mesenchymal tissue and increased hematopoietic tissue in a few regions. There was no evidence of inflammation.
Morphologic Diagnosis: Spontaneous nephroblastoma, rainbow trout.
Nephroblastomas have been described in rainbow trout by Roberts, in the Japanese eel (Anguilla japonica), and in a Japanese dace (ugui) (Tribolobon hakonensis). Spontaneous renal neoplasia is extremely rare in teleosts. Finding this spontaneous tumor in this fish was fortuitous. A genetic predisposition for these tumors in man and other species has been described. Rainbow trout have been indicated to be potential models for environmental carcinogenesis.
AFIP Diagnosis: Kidney: Nephroblastoma, rainbow trout.
Conference Comment: Spontaneous primary renal tumors are uncommon in all domestic animal species. Nephroblastoma, or Wilms’ tumor as it is called in humans, is a neoplasm of young children and also occurs in many animal species. In chickens, nephroblastoma is induced by the myeloblastosis-associated avian retroviruses. It has been proposed that the intradural extramedullary thoracolumbar tumor of young dogs is an extrarenal nephroblastoma because of its histological appearance and the discovery of the WT1 gene mutation in these dogs. WT1 is a tumor-suppressor gene considered essential for kidney, testis and ovary development. Tumor-suppressor genes function by regulating cell growth in the nucleus. Mutation of the WT1 gene is found in approximately 10% of Wilms’ tumors. The biological pathways leading to the development of Wilms’ tumor are considered complex and likely to involve several genetic loci.
Contributor: Animal Health Diagnostic Laboratory, P.O. Box 30076, Lansing, MI 48909-7576
References: 1. Bailey GS, Williams DE, Hendricks JD: Fish models for environmental carcinogenesis: the rainbow trout. Environ Health Perspect 104(1):5-21, 1996
2. Masahito P, Ishikawa T, Okamoto N, Sugano H: Nephroblastomas in the Japanese eel, Anguilla japonica Temmink and Schlegel. Cancer Res 52(9):2575-2579
3. Masahito P, Ishikawa T, Takayama S, Sugimura H: Gonadal neoplasms in largemouth bass, Micropterus salmoides and Japanese dace (ugui), Tribolodon hakonensis. 75(9):776-783, 1984
4. Nakatsuru Y, Minami K, Yoshikawa A, Zhu J, Oda H, Masahito P, Okamoto N, Nakamura Y, Ishikawa T: Eel WT1 sequence and expression in spontaneous nephroblastomas in Japanese eel. Gene 245(2):245-251, 2000
5. Roberts RJ: Neoplasia of teleosts, In: Fish Pathology, p. 113. Bailliere Tindall, London, England, 1978
6. Schofield D, Cotran RS: Diseases of infancy and childhood. In: Pathologic Basis of Disease, ed. Cotran RS, Kumar V, Collins T, 6th ed., pp. 286-287, 487-489. WB Saunders Co., Philadelphia, PA, 1999
CASE II – DHC (AFIP 2752919)
Signalment: 16-year-old, neutered male, Siamese mix, Felis catus, domestic cat.
History: This indoor/outdoor cat presented post-ictal to the referring veterinarian following a single grand mal-type seizure of two minutes duration. There was no prior history of seizures. Other clinical signs reported by the owner included recent episodes of vomiting and diarrhea, weight loss, and polyuria/polydipsia of long-term duration. Physical examination findings at presentation included severe dehydration, thinness, and an inability to stand or ambulate. Over the next few days, seizure activity was observed to correlate with subnormal serum glucose levels, and recovery was consistently facilitated by intravenous glucose administration. Six days following presentation the owners elected to euthanize this cat due to persistent hypoglycemia, continued intermittent seizures, and prognostic considerations.
Gross Pathology: A necropsy was performed by the referring veterinarian. An approximately 8-9 mm diameter, dark pink nodule was observed at the tip of the pancreas. Whitish flecks presumed to represent calcification/saponification surrounded the nodule. There was no macroscopic evidence of neoplastic metastasis to other viscera.
Laboratory Results: At presentation, serum glucose was 24 mg/dl (reference range: 7-145 mg/dl). Further serum glucose values varied from 0 to 65 mg/dl. Other initial abnormalities included a mild normocytic/normochromic anemia (thought to represent anemia of chronic disease) and a serum amylase of 2333 IU (reference range: 500-1500 IU). An insulin:glucose ratio was performed; however, the results of this test had not returned by the date of euthanasia and were not recorded.
Contributor’s Diagnoses and Comment: 1. Pancreatic islet cell carcinoma.
2. Endocrine pancreas: Islet atrophy.
3. Exocrine pancreas: Regional acinar atrophy.
4. Peri-pancreatic adipose tissue: Fat necrosis with mineralization, and mild chronic-active focal steatitis.
Situated adjacent to the pancreas is a large, encapsulated neoplasm consisting of irregular nests and cords of monomorphic polygonal cells that are packeted by a fine fibrovascular stroma (neuroendocrine pattern). In some areas of the mass, single layers of palisading tumor cells form fluid- or blood-filled cysts and duct-like structures. The tumor cells have eccentric, medium-sized, uniform round nuclei with stippled chromatin, and abundant finely granular pale eosinophilic cytoplasm. Mitotic figures are uncommon. In a subset of the submitted sections, nodules of neoplastic tissue are present within and external to the tumor capsule, suggesting invasion. In some regions of the main tumor, the stroma is variably expanded by globular to amorphous, pale pink material. Infrequent, irregular accumulations of similar material are also present within the neighboring non-neoplastic pancreas. Within the pancreas, normal islet tissue is either severely diminished or essentially lacking, depending on the section examined. Proximate to the neoplasm are multiple, irregular to ovoid nodules of poorly organized ductular tissue associated with mild lymphocytic infiltrates; such nodules are probably clusters of atrophic pancreatic acini.
Pancreatic islet cell tumors in domestic cats are considered to be rare. In one survey of data from American and Canadian veterinary medical colleges, 29 of approximately 10,500 domestic animal tumors were of islet cell origin, and only two of these occurred in cats. The signalment and history of the current submission are remarkably similar to data from three previous case reports of islet cell tumors in cats. Each case involved a 12 to 17-year-old male Siamese cat that presented with a history of late-onset episodic neurologic impairment. Additionally, common features of these reports were clinical and laboratory evidence of hypoglycemia and/or hyperinsulinemia, the discovery of a single, 1-2 cm pancreatic mass, no gross indication of tumor metastasis upon initial inspection, and a diagnosis of malignancy based upon local invasiveness or eventual evidence of metastasis.
Ancillary tests to further define the origin and behavior of feline islet cell tumors have included intravenous glucose or glucagon tolerance assays and immunocytochemical staining for insulin, glucagon, gastrin, pancreatic polypeptide, islet amyloid polypeptide, somatostatin, neuron specific enolase, and chromogranin A. In one cat, amyloid deposits were identified within the islet cell tumor and also within residual pancreatic islets, as confirmed by Congo red staining. In the present case, materials suspected to be amyloid were surprisingly not Congo red-positive, nor did they display apple-green birefringence under polarized light.
Treatment modalities for feline islet cell tumors have included surgical excision, or dietary management plus glucocorticoid therapy for instances in which the tumor recurred or metastasized. Post-presentation survival in such cases ranged from several weeks to two years.
In this case, blood insulin levels were not available and tumor insulin immunoreactivity was not performed; however, documentation of persistent hypoglycemia and glucose-responsive neurologic signs suggest that this cat’s islet cell tumor had a functional beta-cell component (insulinoma). The designation of malignancy was based upon histologic evidence of capsular invasion.
AFIP Diagnoses: 1. Pancreas: Islet cell tumor, with amyloid deposits, Siamese mix, feline.
2. Pancreas: Lobular atrophy, multifocal, moderate, with ductular hyperplasia.
3. Peripancreatic adipose tissue: Steatitis, necrotizing, subacute, focally extensive, moderate.
4. Pancreas, islets of Langerhans: Amyloidosis, diffuse, severe.
Conference Comment: Determination of the biological potential of single or multiple pancreatic islet cell tumors, based on histomorphology, can be difficult. In dogs, the tumors are often malignant and frequently metastasize to regional lymph nodes and liver. In humans and ferrets, the tumors are usually benign. Islet cell tumors may secrete a variety of peptide hormones in addition to insulin.
Only a few cases of insulin-producing islet cell tumors have been reported in cats. Cats generally present with a history of hypoglycemia, and weakness or seizures that respond to oral or intravenous glucose. In human medicine, this clinical history constitutes Whipple’s triad. Underlying diabetes mellitus, occasionally found in older cats with islet cell tumors, can complicate the clinical picture; surgical removal of the hyper-secreting islet cell tumor can result in severe hyperglycemia.
Gastrin-producing islet cell tumors produce the Zollinger-Ellison syndrome in man, and have been reported in the dog and cat. Animals present with diarrhea and gastrointestinal ulceration due to extreme gastric acid secretion stimulated by the gastrinoma.
A Congo red stain performed at the AFIP stained material in the islet cell tumor and in islets of the adjacent pancreas red; "apple-green" birefringence was produced under polarized light.
Contributor: Experimental Pathology Laboratories, Inc., P.0. Box 12766, Research Triangle Park, NC 27709
References: 1. Hawks D, Petersen ME, Hawkins KL, Rosebury WS: Insulin-secreting pancreatic (islet cell) carcinoma in a cat. J Vet Int Med 6(3):193-196, 1992
2. McMillan FD, Barr B, Feldman EC: Functional pancreatic islet cell tumor in a cat. J Am Anim Hosp Assoc 21:741-746, 1985
3. Myers NC III, Andrews GA, Chard-Bergstrom C: Chromogranin A plasma concentration and expression in pancreatic islet cell tumors of dogs and cats. Am J Vet Res 58(6):615-620, 1997
4. O’Brien TD, Norton F, Turner TM, Johnson KH: Pancreatic endocrine tumor in a cat: clinical, pathological, and immunohistochemical evaluation. J Am Anim Hosp Assoc 26:453-457, 1990
5. Priester WA: Pancreatic islet cell tumors in domestic animals. Data from 11 colleges of veterinary medicine in the United States and Canada. J National Cancer Inst 53(1):227-229, 1974
CASE III – 00-2048 (AFIP 2736176)
Signalment: 2-year-old, female, mixed breed, equine
History: This pony had an 8-month history of intermittent anorexia, diarrhea and general unthriftiness.
Gross Pathology: The horse is in poor body condition with markedly reduced fat and muscle stores. Approximately 2 L of clear yellow tinged fluid is in the peritoneal cavity. There is a watermelon sized (40x52x60 cm) mass involving the cranial flexure of the ventral colon that extends into the mesentery and encompasses the mesenteric lymph nodes. The mass extends through the wall of the colon and there is a cystic center that is continuous with the gut lumen forming a large cystic diverticulum. The cut surface is pale and smooth. Neighboring mesenteric lymph nodes are moderately enlarged (golf ball-sized to baseball-sized), but other systemic lymph nodes appear normal. There are no adhesions to the mass.
Laboratory Results: Streptococcus zooepidemicus and Pythium spp. were isolated. Pythium was identified based on characteristic zoosporangia formation in culture.
Contributor’s Diagnosis and Comment: Colitis, pyogranulomatous, proliferative, severe with fungal-like hyphae and vasculitis, lymphadenitis, pyogranulomatous, severe with fungal-like hyphae.
Etiology: Pythium insidiosum
The gross appearance of the mass in this horse was suggestive of lymphosarcoma and the initial imprint cytology of the cut surface of the mass demonstrated many lymphocytes. Histologically, the multifocal abscesses and the pyogranulomas that contained 7-10 m m hyphae with nonparallel walls, no septation and irregular branches were typical of mycotic colitis. Most of the mass consisted of densely packed proliferative fibrous connective tissue with severe infiltrates of lymphocytes, histiocytes, eosinophils and neutrophils. Differential included pythiosis or possibly zygomycosis. Using a recommended technique1, infected tissue was washed and put on Sabouraud’s dextrose agar media, then incubated for 48 hours at 37° C. Boiled blades of grass were added to induce sporangia development following additional 24 hours incubation at 37° C in dilute saline. The zoospores found were consistent with Pythium insidiosum. Given the tremendous size of this mass and the vascular and nodal involvement, it is surprising that the horse lived for many months with the infection. Some sections contain embedded plant material. We interpreted the many lymphocytes and lymphoblasts to be remnants of the effaced lymph nodes.
AFIP Diagnosis: Colon: Colitis, eosinophilic and granulomatous, transmural, diffuse, severe, with extensive granulation tissue and hyphae, mixed breed horse, equine.
Conference Comment: Pythium insidiosum is classified as a protist, and not a fungus, based on morphology and the presence of sexual reproductive structures. Infection by zoospores usually occurs through invasion of damaged tissue, penetrating wounds, or ingestion of contaminated water. Necrotic tissue has been shown to be chemotactic for Pythium zoospores, with spread of infection via the lymphatics. The invasive, granulomatous and eosinophilic reaction is characteristic. The granular, yellow-gray "kunkers" often found in Pythium lesions are thought to represent vascular sequestra or necrotic cores. Grossly, cutaneous pythiosis may resemble malignant edema, exuberant granulation tissue, sarcoid, and severe habronemiasis.
Contributor: University of Georgia, Veterinary Diagnostic & Investigational Lab, P.O. Box 1389, Tifton, GA 31793
References: 1. Hungerford LL, Campbell CL, Smith AR: Veterinary Mycology Laboratory Manual, p. 55. Iowa State University Press, Ames, IA, 1998
2. Purcell KL, Johnson PJ, Kreeger JM, Wilson DA: Jejunal obstruction caused by a Pythium insidiosum granuloma in a mare. J Am Vet Assoc 205:337-339, 1994
3. Morton LD, Morton DG, Baker GJ, Gelberg HB: Chronic eosinophilic enteritis attributed to Pythium sp. in a horse. Vet Pathol 28:542-544, 1991
CASE IV – N2989/B2964 (AFIP 2741898)
Signalment: 7-year-old, female capuchin (Cebus sp.)
History: This monkey came from a private facility where she was housed in an indoor/outdoor enclosure within an enclosed group of the same species. She had a 5-6 day history of lethargy and anorexia and a 1-day history of increased respiratory effort. On presentation, the monkey was slightly cyanotic with increased respiratory effort, elevated temperature, tachycardia and tachypnea (RR>100). No ocular or nasal discharge was noted. Heart sounds were muffled. Inguinal and axillary lymph nodes were slightly enlarged. Thoracic radiographs revealed complete consolidation of the left lung with a slight left mediastinal shift and hyperinflation of the right lung. A left-sided thoracotomy with a complete left lung lobectomy was performed and the lung was submitted for biopsy and culture. Subsequently, the capuchin was euthanized and a necropsy was performed.
Gross Pathology: A left lung lobe biopsy (99B2964) was diffusely tan to light pink and failed to collapse. On cut section, it had multiple consolidated, dry, tan, firm areas. At necropsy, the remaining lung lobes (99N2989) contained multiple variably sized tan, firm, raised nodules throughout the parenchyma. The accessory lung lobe was collapsed and tan to dark red. The trachea contained a moderate amount of thick, tan mucous. Multiple lymph nodes (left axillary, hilar, inguinal, and peripancreatic) were slightly enlarged. The liver was slightly enlarged and the adrenal glands had hemorrhage at the corticomedullary junction.
Laboratory Results: An antemortem transtracheal wash and bronchoalveolar lavage revealed intact neutrophils and macrophages. A mixed population of bacteria was cultured and interpreted to be contaminants. Tuberculin skin testing, PCR for Mycobacterium spp., and acid fast stains of tracheal wash samples were negative. Serologic assays for Coccidioides, Blastomyces, Cryptococcus neoformans, and Histoplasma were also negative. CBC and chemistry profile indicated a neutrophilic leukocytosis, thrombocytopenia, hyperfibrinogenemia, hypoproteinemia, and metabolic acidosis. Type B Francisella tularensis was isolated from the postmortem sample.
Contributor’s Diagnosis and Comment: Lung: Severe, chronic, multifocal to coalescing, histiocytic and suppurative pneumonia with massive alveolar histiocytosis and type II pneumocyte hyperplasia (Francisella tularensis, type B).
Examination of H&E-stained sections reveals multiple foci of pulmonary parenchyma expanded by large numbers of macrophages and variable numbers of neutrophils (99N2989). In one section (99B2964), the sample is completely consolidated by the inflammatory cells. Alveolar walls are thickened and prominent due to hyperplasia of type II pneumocytes. Some bronchioles are effaced by inflammatory cells and a small amount of immature fibrous connective tissue with collapse of the air space. There are also multiple areas of coagulative necrosis associated with vascular thrombi. The pleural surface is covered by a thick layer of fibrin with entrapped cellular debris, macrophages, and neutrophils.
Francisella tularensis is a highly infectious, small, pleomorphic, gram-negative intracellular coccobacillus, and a well-known zoonotic agent. The primary reservoir hosts of F. tularensis are thought to be rodents and lagomorphs. There are two biotypes, A and B. Type A is present only in North America and is associated with 70-90% of all human cases, while type B is found throughout the Northern hemisphere and has lower virulence for humans. It is typically transmitted to humans by infected ticks or direct contact with infected animals.
Tularemia is an uncommon infection in humans with approximately 200 cases reported annually in the United States. Six classic forms of tularemia have been described, to include glandular, ulceroglandular, oculoglandular, oropharyngeal, typhoidal, and primary pulmonary.
Tularemia has been reported in New and Old World nonhuman primates and lemurs. Affected animals had either the typhoidal or ulceroglandular forms of tularemia. In one report, type B F. tularensis was identified. This case is unusual in that the capuchin appears to have had primary pulmonary tularemia, with clinical presentation and pathologic findings similar to those in humans with that form of the disease. The source of infection in this case was not determined. None of the other animals housed with this capuchin had positive titers to F. tularensis, nor was there seroconversion in any of the veterinary hospital staff who were exposed to the animal.
AFIP Diagnosis: Lung: Bronchopneumonia, histiocytic and neutrophilic, subacute, diffuse, severe, with type II pneumocyte hyperplasia and fibrinous pleuritis, capuchin monkey (Cebus sp.).
Conference Comment: The histologic appearance of the bronchopneumonia, while non-specific, suggests a severe bacterial infection. Brown and Hopps tissue Gram stain and a modified silver technique did not demonstrate bacteria.
There are five subspecies of Francisella tularensis, but only F. tularensis biovar tularensis (or type A) causes significant human disease in North America. Infected rabbits are the principle reservoir host, with ticks and deer flies acting as vectors. F. tularensis biovar palearctica (or type B) has a rodent reservoir host, with mosquitoes acting as a vector to complete the lifecycle. F. tularensis biovar novicida rarely causes disease in man or animals. F. tularensis biovar palearctica mediasiatica is found in Central Asia and F. tularensis biovar palearctica japonica in Japan.
Contributor: University of California, Davis, Veterinary Medical Teaching Hospital, Department of Veterinary Pathology, 1 Garrod Drive, Davis, California 95616
References: 1. Calle PP, Bowerman DL, Pape J: Nonhuman primate tularemia (Francisella tularensis) epizootic in a zoological park. J Zoo and Wildl Med 24:459-468, 1993
2. Gill V, Cunha BA: Tularemia pneumonia. Sem Resp Infect 12:61-67, 1997
3. Nayar GPS, Crawshaw GJ, Neufeld JL: Tularemia in a group of nonhuman primates. J Am Vet Med Assoc 175:962-963,1979
4. Posthaus H, Welle M, Morner T, Nocilet J, Kuhnert P: Tularemia
in a common marmoset (Callithrix jacchus) diagnosed by
16s rRNA sequencing. Vet Microbiol 61:145-150, 1998
*Sponsored by the American Veterinary Medical Association, the American College of Veterinary Pathologists and the C. L. Davis Foundation.
 |
