AFIP Wednesday Slide Conference - No. 25

April 23 1997
Conference Moderator: Dr. Michael H. Goldschmidt
Diplomate, ACVP
Laboratory of Pathology
School of Veterinary Medicine
University of Pennsylvania
Philadelphia, PA 10104
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Case I - 95-4002 (AFIP 2551548), 1 photo

Signalment: 5-year-old red ruffed lemur.
History: The lemur was a zoo resident for its entire life. There was no significant medical history until 2 months prior to death. At that time, the lemur was found lethargic and shaking and with diarrhea. A leukocytosis with left shift and elevated BUN and creatinine were present. Signs resolved with symptomatic treatment. Two weeks later, sign re-appeared and palpable bone lesions were present. The serum alkaline phosphatase was 724 IU/L (normal 400) which rose to 1574 IU/L 2 weeks later. BUN and creatinine were not significantly elevated. The illness waxed and waned over the next month. The lemur was anesthetized for magnetic resonance imaging but became hyperthermic and died.
Gross Pathology: Significant gross lesions were limited to periosteal proliferation on long bones.
Laboratory Results: See above.
Contributor's Diagnosis and Comments: Ulna: Marked chronic periosteal hyperostosis with cancellization (osteopenia) of underlying cortex.
Proliferative bone disease in primates is a rare condition. Junge reported periarticular hyperostosis and renal disease in six black lemurs (Junge, 1994), and diaphyseal hyperostosis was noted in two ruffed lemurs in 1994 (personal communication, Martha Weber). Familial infantile cortical hyperostosis (Caffey's disease) has been described in rhesus monkeys with bilaterally symmetrical subperiosteal hyperostosis of the diaphyses of the long bones and in the mandible, but without the inflammation which is sometimes noted in this disease (Snook, 1989). The lesions in the case presented here represent chronic periosteal new bone formation with involvement of the diaphyseal, metaphyseal, and periarticular regions. The new bone formation resembles that seen in hypertrophic osteopathy, except that the lesions are more widespread. The cancellization of the underlying cortex likely represents stress shielding of the cortical bone by the periosteal new bone. The lemur in this case was also found to have membranous glomerulonephritis and chronic interstitial nephritis but BUN and creatinine were not elevated. No thoracic or abdominal lesions was found, as might be associated with hypertrophic osteopathy. The cause of the proliferative bone lesions seen here and reported in other lemurs is undetermined.
AFIP Diagnosis: Bone, ulna: Hyperostosis, periosteal, chronic, focally extensive, severe, with cortical osteopenia, ruffed lemur (Varecia variegata), primate.
Conference Note: The conference participants agreed with the contributor's diagnosis and comments. The cause of this lesion remains to be demonstrated.
Proliferative periosteal disease with formation of new bone can develop in human beings and animals in association with various conditions, including traumatic injuries, infections, inflammation, neoplasms, and metabolic disease. Additionally, there are several idiopathic skeletal disorders associated with periosteal proliferation. In dogs, such conditions include hypertrophic osteodystrophy and panosteitis. A third idiopathic condition, hypertrophic osteopathy, is a proliferative periosteal disease of many domestic and non-domestic animals species, which typically affects the diaphyses of long bones and usually is associated with chronic lesions in the thoracic cavity. Weber and Heriot described an idiopathic proliferative bone disease in ruffed lemurs that was very similar to Paget's disease in humans.
Contributor: Ohio State University, Dept of Veterinary Biosciences, 1925 Coffey Rd, Columbus, OH 43210.
1. Junge RE, et al. Periarticular hyperostosis and renal diseases in six black lemurs of two family groups. Journal of the American Veterinary Medical Association 205(7):1024-1029, 1994.
2. Snook SS, King NW: Familial infantile cortical hyperostosis (Caffey's disease) in rhesus monkeys (Macaca mulatta). Vet Pathol 26:274-277, 1989.
3. Weber M, Heriot K: An idiopathic proliferative disease of bone in two subspecies of ruffed lemur (Varecia variegata variegata and Varecia variegata rubra), Proceedings of the joint conference of the AAZV, WDA and AAWV, pg. 268, 1995.
International Veterinary Pathology Slide Bank: None.

Case II - 96-6444 (AFIP 2550475)

Signalment: 1-year-old Columbian ewe.
History: This ewe was the only one of a flock of 50 that was involved. She was unable to swallow and was separated from the flock one evening. The next morning, the ewe was recumbent and paddling and was euthanized. The head was submitted to the diagnostic laboratory with a request to check for scrapie.
Gross Pathology: No gross lesions were observed by the practitioner that necropsied the ewe. No gross lesions were observed in the brain upon removal.
Laboratory Results: Listeria monocytogenes was isolated from the brain stem.
Contributor's Diagnosis and Comments: 1. Brain stem: Encephalitis, multifocally extensive, suppurative, acute, marked with intralesional bacteria.
2. Encephalitis, perivascular, lymphohistiocytic, multifocal.
Etiology: Listeria monocytogenes.
Listeria monocytogenes was isolated from the brain of this ewe on the fourth weekly subculture from cold enrichment broth, but not from earlier subcultures or direct culture of the brain. The organisms can be identified in most H&E sections in this case, as tangled to filamentous organisms within and bordering the microabscesses. Organisms were gram-positive on stains of tissue sections. The degree of perivascular infiltrates of lymphocytes and macrophages varies and is minimal in some sections.
Several months after this ewe died, the owner indicated that it was the only case that occurred, and that ewes at the time were in a drylot being fed hay; silage had never been fed. Outbreaks of listeriosis often are associated with silage with a pH of 5.5 or greater. The organism is commonly found in the intestinal tract of normal ruminants; L. monocytogenes is considered to be a facultative intracellular organism. Stress-related factors probably allow the development of bacteremia.
Listeriosis occurs in 3 distinct syndromes: 1) abortions, 2) septicemia with visceral abscesses, and 3) encephalitis. Abortion in ruminants usually occurs in late gestation, and is not associated with illness of the dam. Septicemic disease with visceral abscessation is recognized in neonatal ruminants. Encephalitic listeriosis occurs mostly in adult ruminants, although younger ewes are at higher risk than aged ewes. In encephalitic listeriosis, the organism has marked affinity for the brain stem, primarily the pons and medulla, as was present in this case. There is evidence that the organism gains entrance to the brain via cranial nerves, particularly the trigeminal, rather than via a hematogenous route.
In this case, positive identification of organisms by cold-enrichment culture techniques required approximately 4 weeks. Immunoperoxidase methods have been developed for detection of L. monocytogenes in tissue sections, which allow for more rapid confirmation, and a definitive result in cases that are culture-negative.
AFIP Diagnosis: Brain, brain stem: Meningoencephalitis, subacute, multifocal, moderate, with microabcesses, neuronal necrosis, and numerous bacteria, Columbian ewe, ovine.
Conference Note: A Gram stained section examined at the conference contains numerous gram-positive bacilli in and around microabcesses and multifocally within neurons. The bacilli are approximately 1 x 2 µm and tend to occur in short chains. Rare coccoid forms were noted. The morphology of the bacteria is consistent with that of Listeria monocytogenes.
Listeria monocytogenes is a gram-positive, facultative, anaerobic bacillus. It is ubiquitous in the environment, particularly in temperate zones, and has been isolated from fish, birds and mammals. The species name was coined due to the monocytosis that occurs in sublethally infected rabbits, guinea pigs and dogs; this is not a feature of infection in ruminants or swine.

The organism is resistant to harsh external environmental conditions; Listeriaspp. are able to survive in dried media for several months and in moist soil for up to 10 years and can survive high temperature pasteurization within leukocytes. The bacterium is psychrophilic and some of its virulence factors such as hemolysin are induced or enhanced at low temperature. Coupled with increased stress to ruminants in winter months, the psychrophilia is thought to be responsible for the increased number of cases seen during this time.

Listerial encephalitis is almost solely a disease of adult animals. Listeria has an affinity for the brain stem, the lesions being most severe in the medulla and pons and less severe anteriorly in the thalamus and posteriorly in the cervical parts of the spinal cord. The proposed route of infection is by entry through a defect in the oral mucous membrane, penetration into a nerve and centripetal spread to the CNS via the cranial nerves. The trigeminal nerve is particularly implicated. There is correlation between listerial encephalitis and trigeminal neuritis and between the severity of the trigeminal neuritis and ipsilateral lesions in the brain stem. L. monocytogenes has been demonstrated in myelinated axons of the trigeminal nerve and fiber tracts in the brain stem and in the cytoplasm of medullary neurons. Rhinitis is a common finding in encephalitic cases, but invasion of the brain by the olfactory nerve has not been verified by histology.
Microabscesses in the brain stem are characteristic. These lesions may arise from small foci of microglial reaction or clusters of neutrophils. Usually glial nodules are infiltrated by neutrophils, and the centers liquefy (although some nodules are predominantly histiocytic). The focal lesions rarely expand, but may form streaks in the white matter. The surrounding parenchyma is not severely affected, although there is often mild rarefaction of the white matter and infiltration by small numbers of neutrophils and hypertrophied microglia. Vasculitis with exudation of fibrin occurs in the white matter secondary to drainage of the microabscesses into the Virchow-Robin spaces; meningeal infiltrates are produced by the same process of drainage. The cranial nerves may have intrafascicular and perineural accumulations of inflammatory cells (lymphocytes, macrophages, plasma cells and neutrophils).

Contributor: Kansas Sate University, College of Veterinary Medicine, 1800 Denison Ave, Manhattan, KS 66506.
1. Jubb KVF, Huxtable CR: The Nervous System. In Pathology of Domestic Animals, 4th Ed., Vol 1, KVF Jubb, PC Kennedy, N Palmer, eds. pp. 393-397, 1993.
2. Johnson GC, Fales WH, Maddox CW, Ramov-Vara JA: Evaluation of laboratory tests for confirming the diagnosis of encephalitic listeriosis in ruminants. J Vet Diagn Invest 7:223-228, 1995.
3. WSC Conference - No. 1, Case II, 18 September 1991.
International Veterinary Pathology Slide Bank:
Laser disc frame #7478, 17045, 17046, 17047, 11774, 11777, 11780.

Case III - N94 2004 (AFIP 2549847)

Signalment: 8-year-old female American Shorthair cat.
History: This cat had a long history of inappetence, poor body condition, weakness, and was severely pruritic. The cat had open sores on head and neck and alopecia on head, forelimbs, neck and thorax. It had been treated with systemic antibiotics for several weeks prior to skin biopsy and euthanasia.
Gross Pathology: The cat was very emaciated and had extensive hair loss and cutaneous edema of especially the eyelids and frontal and occipital regions of the head. The subcutaneous tissues of the entire body, but especially the trunk and proximal forelimbs were slightly slimy, yellowish and studded with flat to miliary bodies lying free in the fascial planes. Similar lesions were present in the skeletal muscle, fascial planes of forelimbs, pelvic limbs and subscapular regions. The epicardial surface of the right ventricle and atrium of the heart were studded with yellow miliary streaks and nodules. White chalky flecks were visible in the anterior chamber of the eyes, and the pupils were irregular in shape bilaterally.
Laboratory Results: A Mycobacterium sp was isolated on special culture media but further identification of the organism has not been successful.
Contributor's Diagnosis and Comments: Panophthalmitis, optic neuritis, orbital cellulitis and myositis, granulomatous, diffuse, severe with intralesional acid fast bacteria.
The original diagnosis of Mycobacterium sp granulomatous dermatitis was made on cutaneous punch biopsies, in which masses of filamentous bacteria were present in large adipose tissue vacuoles throughout the dermis. The organisms were visible on H & E sections, were acid-fast and auramine-rhodamine positive, and very few organisms were gram-positive. A Mycobacterium sp grew after several weeks in special mycobacterium culture media.
Bacteria were present in all tissues of this cat, including bone marrow, brain and skeletal muscle. Other disease or infectious processes (including FIV and FELV) were not found to explain this disseminated and severe mycobacterial infection.
AFIP Diagnosis: Eye: Panophthalmitis, granulomatous, multifocal, moderate to severe, with periocular skeletal myositis, steatitis, optic neuritis, and myriad bacilli, American Shorthair, feline.
Conference Note: The conference participants agreed with the contributor's diagnosis. This case was also studied by the Department of Infectious and Parasitic Disease Pathology. Based on histomorphologic and epidemiologic findings, the organisms are most likely of the Mycobacterium avium-intracellulare complex (MAIC).
Ocular mycobacterial infections are rare and, as in this case, are usually associated with systemic disease. In cats, the most common strain associated with ocular lesions is Mycobacterium tuberculosis. In the cat, ocular tuberculosis may also occur as a keratoconjunctivitis without uveal involvement.
Refer to 1996/97 Wednesday Slide Conference No. 1, Case III, for a general discussion on MAIC in cats.
Contributor: Western College of Veterinary Medicine, 52 Campus Drive, University of Saskatchewan, Saskatoon, Saskatchewan Canada, S7N 5B4.
1. Formston C: Retinal detachment and bovine tuberculosis in cats. J Small Anim Pract 35:5-8, 1994.
2. Jordan HL, Cohn LA, Armstrong PJ: Disseminated Mycobacterium aviumcomplex infection in three Siamese cats. JAVMA, Vol 204(1):90-93, 1994.
3. Monroe WE et al: Atypical Mycobacterial Infections in Cats. Comp Cont Educ Vol 10(9):1044-1047, 1988.
4. Hines ME, et al: Mycobacterial infections of animals: pathology and pathogenesis, Lab Anim Sci 45(4):334-351, 1995.
International Veterinary Pathology Slide Bank:
Laser disc frame #5327, 9127, 21897.

Case IV - 95-1541 (AFIP 2507540)

Signalment: A female BALB/c mouse.
History: Presented with a 0.1 x 0.7 cm mass on the right ear; centrally, the mass contained fluid and white pus.
Contributor's Diagnosis and Comments: Haired skin: Myoepithelioma.
AFIP Diagnosis: Haired skin: Myoepithelioma, malignant, BALB/c mouse, rodent.
Conference Note: All conference participants agreed that this neoplasm is consistent with a myoepithelioma as described in the rodent pathology literature. Since the term "myoepithelioma" implies benignancy, we believe it is appropriate to indicate malignancy in the morphologic diagnosis of this tumor. The tumor has multiple features of malignancy including a high mitotic rate, cellular atypia, necrosis, and evidence of invasive growth.
Myoepitheliomas are frequently diagnosed in inbred laboratory mice, most often in the strains A and BALB/c as well as their F1 hybrids. Myoepitheliomas most frequently arise in the parotid and submaxillary salivary glands, and expand the subcutis of the ventral neck. They can also be associated with the mammary, Harderian, and preputial glands. These tumors can become very large, with cystic chambers containing a pink to brown serous fluid. This fluid is not secretory in nature, but forms through liquefaction of the neoplasm.
Myoepitheliomas are typically invasive, unencapsulated, and have foci of necrosis. As implied by the name, myoepitheliomas exhibit epithelial characteristics in some areas and features of smooth muscle cells in others. In viable areas, spindled cells palisade around vessels, or whirl around large rounded cells. According to Dawe, myoepitheliomas may have a squamous appearance in areas distant from vessels, but do not keratinize or form pearls. Mitoses are typically infrequent. Staining with PTAH reportedly allows visualization of cytoplasmic fibrils. Staining characteristics with a panel of specific antisera to mouse keratins and smooth muscle actin support origin from extraglandular ductular myoepithelial cells. In aging studies with BALB/c strains, myoepitheliomas may account for up to 10.5% of pulmonary metastases from various neoplasms. A curious feature is concomitant myeloid hyperplasia of bone marrow and spleen, apparently related to a secretory product of the tumor.
Contributor: Naval Medical Research Institute, Pathobiology (Code 21) 8901 Wisconsin Ave, Bethesda, MD 20889-5607.
1. Percy, DH, Barthold SW: Pathology of Laboratory Rodents and Rabbits, Iowa State University Press, Ames Iowa, p 68, 1993.
2. Sundberg JP, et al: Myoepitheliomas in Inbred Laboratory Mice. Vet Pathol 28:313-323, 1991.
3.. Burger GT, Frith CH, and Townsend JW: Myoepithelioma, salivary glands, mouse. In: Monographs On Pathology of Laboratory Animals: Digestive System, ed. Jones TC, Mohr U, and Hunt RD, pp. 185-189, Springer-Verlag, Heidelberg, Germany, 1985.
4. Delany WE: Transplantable murine salivary gland carcinoma (myoepithelioma). Biologic behavior and ultrastructural features. J Natl Can Inst 58:61- 65, 1977.
5. Dawe CJ: Tumours of the salivary and lachrymal glands, nasal fossa and maxillary sinuses. In: Turusov VS, Davis W (Eds.): Pathology of Tumours in Laboratory Animals, Volume II -- Tumours of The Mouse. IARC Scientific Publications No. 23, pp. 95-96, 1979.
6. Rehm S: Chemically induced mammary gland adenomyoepitheliomas and myoepithelial carcinomas of mice. Am J Pathol 136:575-584, 1990.

International Veterinary Pathology Slide Bank
Laser disc frame # 08417, 08418, 08435, 08485, 08486, 08527, 08528, 08719, 08720, 08728.
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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