AFIP Wednesday Slide Conference - No. 17

19 February 1997

Conference Moderator: MAJ Mark Mense
Diplomate, ACVP
Division of Pathology
Walter Reed Army Institute of Research
Washington, DC 20307-5100

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Case I - 94-7089 (AFIP 2548771)

Signalment: 2-year-old, female, rainbow trout (Salmo gairdneri ) from a commercial production facility.

History: This asymptomatic 2-year-old female rainbow trout was killed during a routine harvest of fish for commercial sale.

Gross Pathology: During processing and inspection, a 6 cm. diameter, firm, tan mass was found filling the caudal aspect of the body cavity, firmly attached to the renal tissue subjacent to the vertebral column. Portions of the mass were fixed in 10% formalin for histologic examination.

Contributor's Diagnosis and Comments: Nephroblastoma (embryonal nephroma).

The mass consists of a neoplastic proliferation of primitive cells with varied differentiation. There are multiple foci composed of elongate mesenchymal cells arranged in interweaving bundles forming solid stromal sheets, which are separated by bands of connective tissue and remnants of normal renal tissue. Randomly distributed throughout the mesenchymal component, as well as within the connective tissue bands, are tubules, lined by single to multiple layers of neoplastic epithelial cells. Within some of these tubular structures are glomerulus-like invaginations of epithelial cells. These pleomorphic histologic features are typical of nephroblastoma (embryonal nephroma).

Nephroblastoma is a common spontaneous tumor in farmed rainbow trout. Affected fish may be asymptomatic, or present with distended abdomens and skeletal abnormalities. Experimentally, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), administered in a water bath to trout embryos, can result in nephroblastomas in greater than 50% of the animals by 9 month of age.

Some sections possess multiple renal granulomas with foci of mineralization in addition to the tumor.

AFIP Diagnosis:
1. Kidney: Nephroblastoma, rainbow trout (Salmo gairdneri), piscine.
2. Kidney: Nephritis, interstitial, chronic, multifocal, moderate, with multifocal glomerulosclerosis and periglomerular fibrosis.

Conference Note: As noted by the contributor above, granulomas were noted in some of the sections examined. We were unable to determine the cause.

The rainbow trout is a very good alternate animal model for environmental carcinogenesis research. Its strengths as an animal model include low rearing costs, sensitivity to many classes of carcinogens, well described tumor pathology, and responsiveness to tumor promoters and inhibitors. The most common neoplasms of the rainbow trout include mixed hepatocellular/cholangiocellular adenomas and carcinomas, hepatocellular carcinoma, nephroblastoma, adenopapilloma of the swim bladder and adenopapilloma of the stomach.

Contributor: Veterinary Diagnostic laboratory, Oregon State University, P.O. Box 429, Corvallis, OR 97339-0429.

1. Bruno, DW and TT Poppe: A color atlas of salmonid diseases; Academic Press, pp. 110, 1996.
2. Hayes, MA and FW Ferguson: Neoplasia in fish. In: Systemic pathology of fish; Iowa State University Press, pp. 240, 1989.
3. Hendricks, JD: The use of rainbow trout (Salmo gairdneri) in carcinogen bioassay, with special emphasis on embryonic exposure. In : Phyletic approaches to cancer, CJ Dawe et al (eds.); Japan Science Society Press, Tokyo: pp. 227-240; 1981.
4. Bailey GS, et al: Fish models for environmental carcinogenesis: the rainbow trout. Environ Health Perspect Mar;104 suppl 1:5-21, 1996.

International Veterinary Pathology Slide Bank: None.

Case II - PA 3301-2 (AFIP 2550841)

Signalment: 6-year-old, spayed, female, Himalayan cat.

History: The cat presented with a 3 cm diameter, firm mass on the inner aspect of the left thigh. The lesion failed to respond to antibiotic treatment, and was excised surgically and submitted for histopathological evaluation.

Contributor's Diagnosis and Comments: Dermatitis and panniculitis, granulomatous, diffuse, marked, with multifocal granules comprised of pleomorphic fungal hyphal aggregates.

Etiology: Consistent with feline dermatophytic mycetoma. This case not cultured, but this lesion is generally associated with Microsporum canis.

This lesion, generally seen in Persian cats, may result from traumatic implantation of Microsporum organisms from colonized hair into the dermis and subcutis. Large granules comprised of amorphous aggregates of refractile appearing pleomorphic fungal hyphae (with associated bulbous sporiform dilatation) are present. Despite the morphological dissimilarity to follicular dermatophytes, most cases where fungal cultures are performed have isolated Microsporum canis. Such cats may have dermatophyte positive cultures from normal appearing coat areas adjacent to the mycetomas, suggesting that inapparent Microsporum carriers may develop this condition in association with traumatic implantation into deeper regions. The breed predilection has led to speculation that a selective immunodeficiency may play a role in the pathogenesis of this lesion.

AFIP Diagnosis: Haired skin: Dermatitis and panniculitis, pyogranulomatous, focally extensive, severe, with mycelial pseudo-granules, and abundant intrahistiocytic debris, Himalayan cat, feline.

Conference Note: The conference participants agreed with the contributor's diagnosis. There was some debate about whether to consider this lesion a mycetoma or pseudomycetoma, because of conflicting reports in the literature. We elected to call it a pseudomycetoma. According to Ajello, Kaplan and Chandler, there are fundamental differences between the granules of the eumycotic mycetomas and the mycelial aggregates formed by the dermatophytes. The salient points of difference are summarized:

1. "General absence of a development sequence of granule formation in the eumycotic mycetomas in contrast to a sequential development ranging from individual mycelial filaments to small clusters of filaments, and, finally, to large aggregates of mycelium in pseudogranules produced by the dermatophytes. [Sequential development of granules in mycetomas has not been reported in the mycetoma literature.]"
2. "Striking and abundant Splendore-Hoeppli reaction material which surrounds the pseudogranules in all stages of development in contrast to varying amounts or absence of such precipitate in the eumycotic granules."
3. "Mycelium of the pseudogranules is less abundant and not as intricately interwoven and compact as in the eumycotic granules."
4. "Cement is not present in the pseudogranules; it may or may not, depending upon the etiologic agent, be present in the granules of the eumycotic mycetomas."
5. "The pseudogranules of the dermatophytes appear to have an endogenous origin with mycelial elements entering the dermis through a break in the follicular epithelium."

The three most common dermatophytes to infect cats are Microsporum canis, Trichophyton mentagrophytes, and Microsporum gypseum, with M. canis responsible for 99% of the infections.

Contributor: Department of Laboratory Animal Resources, S-1040 BST, University of Pittsburgh, Pittsburgh, PA 15261.

1. Gross TL (ed): Veterinary Dermatopathology, Feline Dermatophytic Mycetoma, Diseases of Dermis, part II, pp. 172-174.
2. Miller WH, Goldschmidt MH: Mycetomas in the cat caused by a dermatophyte, a case report. JAAHA, 27:255-260, 1986.
3. Tuttle PA, Chandler FW: Deep dermatophytosis in a cat, JAVMA 183:1106- 1108, 1983.
4. Yager JA, et al: Mycetoma-like granuloma in a cat caused by Microsporum canis. J Comp Pathol 96:171-175, 1986.
5. Ajello L, Kaplan W, Chandler FW: Dermatophyte mycetomas: fact or fiction?, In: Proceedings. 5th International Conference on Mycoses, Pan Am Health Organ Sci Publ 396:135-140, 1980.

International Veterinary Pathology Slide Bank: None.

Case III - 94-414 (AFIP 2549632)

Signalment: A 20-month-old, male, castrated, Cocker Spaniel.

History: The dog was submitted to the University of Pennsylvania, School of Veterinary Medicine with a two month history of inappetence, weight loss, and slight abdominal distention. Physical examination revealed persistent tachycardia that was independent of activity. Radiographs indicated microhepatica, and abdominal ultrasound revealed a small, hyperechoic liver.

Gross Pathology: The liver weight 356.3 g (2.12% of body weight; normal 3- 3.5%), was firm, light tan, and had a diffusely micronodular surface. Approximately 400 ml of serosanguineous fluid was recovered from the abdominal cavity, and multiple portocaval shunts were present.

Laboratory Results:

Albumin 1.8 g/dk (2.7-3.6) Total Protein 4.6 g/dl (5.7-7.0)
Bilirubin 1.8 g/dl (0.0-1.0) ALT 81 U/L (13-57)
Resting ammonia 113 mol/L (11-35)
Post prandial ammonia 138 mol/L (11-35)
PT and PTT twice normal controls. FSP > 40 (less than 10)

Contributor's Diagnosis and Comments: Liver: hepatitis, lobular dissecting, diffuse, severe, characterized by hepatocellular dissociation and individualization, and dissecting fibrosis with intracanalicular bile stasis, Cocker Spaniel, canine.

Lobular dissecting hepatitis is a rare cause of chronic liver failure in young dogs. In all of the twenty eight cases that have been previously described, dogs were less than 5 years of age. There was no predisposition based on sex, and early reports suggest a slight predisposition in the standard poodle. In each case, dogs showed clinical evidence of chronic liver failure. The most significant gross findings were micronodular microhepatica, ascites, and numerous porto-systemic shunts. Microscopically, the hepatic architecture was completely disrupted by collagen and reticulin fibers that separated the hepatic lobules into individual and small clusters of cells. Hepatocytes were multifocally swollen, lightly eosinophilic, and some were binucleated or (rarely) multinucleated. Scattered necrotic hepatocyes and occasional inflammatory cells were seen. Regenerative nodules were not consistent finding, and when present, were small. Copper accumulation was not a consistent or prominent feature in any of these cases.

An underlying etiologic agent has not been identified, but infectious agents, toxins, and metabolic abnormalities, such as those that result in the development of chronic active hepatitis and cirrhosis, should be considered. In one report, the pattern of dissecting fibrosis was compared to a similar histologic lesion in Indian childhood cirrhosis. This disease is associated with induction of a specific reactive pattern in the neonatal or juvenile liver. The author suggests a similar process in these young dogs.

AFIP Diagnosis: Liver: Hepatitis, chronic, diffuse, severe, with lobular dissecting fibrosis, canalicular cholestasis, mild biliary hyperplasia, multifocal intrahistiocytic pigment, hepatocellular vacuolar degeneration, and individual cell necrosis, Cocker Spaniel, canine.

Conference Note: The conference participants agreed with the contributor's diagnosis. This lesion is distinct from classic cirrhosis in which there is prominent portal bridging fibrosis, bile duct reduplication, and multifocal nodular regeneration. This disease process should be regarded as a specific reaction pattern in the liver of the neonatal and juvenile dog, comparable to neonatal hepatitis in humans. The differential diagnosis for this lesion would include copper toxicity, copper storage disease, aflatoxicosis, and infectious diseases such as those caused by canine adenovirus 1 and Leptospira spp.

Contributor: University of Pennsylvania - School of Veterinary Medicine, Department of Pathology, 3800 Spruce Street, Philadelphia, PA 19104.

1. Van den Ingh TS, Routhuizen J: Lobular dissecting hepatitis in juvenile and young adult dogs. J Vet Int Med 8(3):217-22, 1994
2. Bennett AM, Davies JD, Gaskell CJ, Lucke VM: Lobular dissecting hepatitis in the dog. Vet Pathol. 20(2): 179-188, 1983.
3. Jensen AL, Nielson OL: Chronic hepatitis in three young standard poodles. Zentralblatt Fur Veterinarymediazin k- Reihe A 38(3):194-197, 1991.

International Veterinary Pathology Slide Bank: None.

Case IV - 92-324 (AFIP 2550441)

Signalment: A third trimester abortus and placenta from a 2-year-old Holstein cow.

Gross Pathology: The cotyledons were mottled red and yellow-gray and were sometimes surrounded by a thin rim of edema. The abortus had moderate accumulation of serosanguinous fluid in all cavities and no other significant findings.

Laboratory Results: Candida parapsilosis and Streptococcus dysgalactieaewere isolated from lung, liver, kidney and placenta.

Contributor's Diagnosis and Comments: Acute, necrosuppurative placentitis with intralesional yeast (Candida parapsilosis).

Mycotic placentitis is one of the more common infectious causes of bovine abortion. Abortions ordinarily are sporadic and the incidence within a herd seldom reaches 10% of pregnant cows. Approximately 75% of mycotic abortions are attributed to Aspergillus sp., while the remaining 25% comprise zygomycotic and candida infections. The route of infection is presumed to be hematogenous.

Foley and Schlafer reported four cases of bovine abortion due to Candida parapsilosis. All four cases involved Holstein cows at five to six months gestation. Necrotizing placentitis with phagocytized yeast in trophoblasts, macrophages and neutrophils were observed and systemic infections were documented in all four fetuses. This fetus had also had a few yeast in the lung associated with mild bronchiolitis and a rare yeast was identified in the liver.

AFIP Diagnosis: Placenta: Placentitis, necrotizing, subacute, diffuse, severe, with intracellular and extracellular yeast and pseudohyphae, etiology consistent with Candida sp., Holstein, bovine

Conference Note: Many of the conference participants favored a protozoal infection with Toxoplasma gondii or Neospora caninum. The differential diagnosis also included Candida sp., Histoplasma capsulatum, and Sarcocystis cruzi. Positive staining with GMS and the presence of occasional pseudohyphae confirm the contributor's diagnosis.

Candida spp. belong to the Fungi Imperfectii. They are dimorphic, with a yeast and mycelial phase. In fluid media, the yeast stage predominates, while in tissue, there is a mixed mycelial population. Tissue invasion is often associated with the appearance of mycelial elements. Candida spp. are opportunistic fungi, occurring as normal inhabitants of the digestive tract, oral cavity, and vagina of humans and many domestic animals. Fungal invasion has often been associated with prolonged antibiotic or glucocorticoid use.

In cows, it is considered unlikely that a fungal infection would cross the bovine cervix and the route of entry of Candida into the gravid uterus is assumed to be hematogenous .

Candida organisms have numerous surface molecules that mediate adherence to host tissues, including (1) a receptor homologous to human CR3 which binds C3bi, fibrinogen, fibronectin, and laminin; (2) a lectin that binds sugars on epithelial cells; and (3) a second lectin that binds mannose-containing proteins on epithelial cells. Secreted virulence factors include an aspartyl proteinase that can degrade extracellular matrix proteins, and adenosine, which blocks neutrophil oxygen radical production and degranulation.

Contributor: Department of Biomedical Sciences & Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0442.

1. Foley, GL; Schlafer, DH, Candida Abortion in Cattle. Vet Path 24:532-536, 1987.
2. Cotran RS, Kumar V, Robbins SL (eds): Robbins, Pathologic basis of disease, 5th ed., WB Saunders Co., pp. 354-355, 1994.
3. Jubb KVF, Kennedy PC, Palmer N (eds): Pathology of Domestic Animals, Fourth ed., Vol 2, Academic Press, pp. 256-257, 1993.

International Veterinary Pathology Slide Bank: None.

Lance Batey
Captain, VC, USA
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615

* The American Veterinary Medical Association and the American College of Veterinary Pathologists are co-sponsors of the Registry of Veterinary Pathology. The C.L. Davis Foundation also provides substantial support for the Registry.

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