AFIP Wednesday Slide Conference - No. 3
16 September 1998

Conference Moderator:
COL Nancy Jaax, Diplomate, ACVP
Pathology Division
U.S. Army Medical Research Institute of Infectious Disease
Ft. Detrick, Frederick, MD 21702-5011

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Case I - 9735768 (AFIP 2639843)

Signalment: Eleven-year-old, male, domestic shorthair, feline.
History: One large focal mass was noticed within the skin and underlying subcutaneous tissues of the caudal dorsal midline by the owner. An excisional biopsy was performed by the referring veterinarian.
Gross Pathology: One large focal tan mass, approximately 2.5 cm in diameter, was submitted for histologic examination.
Laboratory Results: Cultures of the mass were positive for Blastomyces dermatitidis.
Contributor's Diagnosis and Comments: Severe focal ulcerative pyogranulomatous mycotic dermatitis, cellulitis, and myositis (blastomycosis), caudal dorsal midline.
Etiology: Blastomyces dermatitidis.
The histologic appearance of the section of skin and underlying tissues is characterized by severe epidermal ulceration and large accumulations of neutrophils intermixed with macrophages, plasma cells, lymphocytes and epithelioid cells within the dermal and subcutaneous tissues which extend into the underlying skeletal musculature. Numerous spherical to slightly ovoid, thick, double contoured walled organisms are also evident within the inflammatory cell accumulations. Occasional organisms displaying broad based, single budding are noted in some sections. Large, multifocal to coalescing areas of necrosis are also evident scattered throughout the tissues. The lesions extend to the edges of many of the sections.
Blastomycosis is primarily a disease of humans and dogs but can be seen in other animals, including the cat and horse. Blastomyces dermatitidis, the causative agent of North American blastomycosis, is a dimorphic fungus which produces a mycelial growth at room temperature and yeast-like forms in tissue and culture at 37 degrees Celsius. The organism reproduces by budding and can be found free or within macrophages in affected tissues. Although the lung is considered the most common site of primary involvement, primary cutaneous infections can also occur. The pulmonary form of the disease has a chronic course characterized by exercise intolerance and coughing. Systemic dissemination can occur with lesions found within the lymph nodes, skin, eyes, central nervous system, subcutaneous tissues, bones, joints, urogenital system and other organs. Cutaneous lesions begin as small papules and progressively develop into granulomas or pyogranulomas.
20x obj. GMS 40x obj.
Case 3-1. Haired skin. Diffusely (here, Left, 20x obj) replacing normal dermal elements, there is an cellular infiltrate composed of high numbers of neutrophils, fewer epithelioid macrophages, lymphocytes, and plasma cells with rare foreign body type giant cells (lower left). There are rare 15-20u diameter oval yeast bodies with a basophilic central zone surrounded by a clear eccentric halo (upper right). Gomori Methenamine Silver (Right, GMS 40x obj) staining highlights yeast bodies which are occasionally forming broad based buds.
AFIP Diagnosis: Haired skin and subcutis: Dermatitis and panniculitis, pyogranulomatous, diffuse, severe, with ulceration, acanthosis, furunculosis, and yeast-like organisms, Domestic Shorthair, feline, etiology consistent with Blastomyces dermatitidis.
Conference Note: Blastomycosis is usually acquired by inhalation of spores from the environment. The organism establishes a primary infection in the lung, and becomes disseminated most commonly to the lymph nodes, skin, eyes, bone, subcutaneous tissues, external nares, brain and testes via the vascular and lymphatic system. Less commonly, dissemination may occur to nasal passages, mouth, prostate, liver, mammary gland, vulva, and heart. Occasionally, primary cutaneous infection may occur from a puncture wound in the skin. Such skin lesions begin as papules and develop into abscesses. As the abscesses expand, the center undergoes cicatrization. Because skin lesions more commonly result from disseminated infection, cutaneous blastomycosis should arouse suspicion of systemic disease. Lung lesions sometimes resolve by the time the sites of disseminated infection become apparent.
Soil is thought to be the reservoir for B. dermatitidis. Four key environmental factors have been epidemiologically associated with infection. These are moisture; sandy, acidic soil with organic debris; disruption of the soil; and the presence of wildlife. Most cases of blastomycosis occur along waterways. Many infections are associated with sandy, acidic soil and organic debris, and the disruption of soil may be caused by earth moving equipment or landscaping. The presence of wildlife, particularly beavers and waterfowl and their excreta, is also believed to play a part in the occurrence of disease. In these environments, the organism grows as a saprophytic mycelial form that produces infective spores. At body temperatures, the organism transforms from the mycelial form to the yeast form under the control of its bys-1 gene.
As noted by the contributor, blastomycosis is most common in dogs and people, but cats, horses, sea lions, wolves, ferrets, dolphins and polar bears have also developed the disease. In cats, pulmonary, cutaneous, and systemic forms occur. There does not seem to be breed, age, or sex predisposition. In dogs, however, sex and breed predispositions have been noted. Male dogs are more frequently infected than females, and a greater percentage of females with equally severe disease survive treatment. Sporting dogs and hounds are at greater risk, probably due to more frequent outdoor activity than other breeds. In general, young (one to five-year-old), male, large breed dogs are most commonly infected. In the southeast United States, occurrence is not seasonal, but in other areas of the U.S., most cases occur from the late spring through late autumn.
A differential diagnosis that included cryptococcosis, histoplasmosis, aspergillosis, coccidiomycosis, African histoplasmosis and South American blastomycosis was considered by the conference attendees. In tissue, Blastomyces dermatitidis occurs as 8-15 micron diameter, spherical to oval, multinucleate, yeast-like cells, with thick, doubly contoured, refractile walls and single, broad-based buds. Coccidiodes immitis is larger, and reproduces by endosporulation rather than budding. Histoplasma capsulatum is much smaller than Blastomyces, and has narrow-based budding. Histoplasma capsulatum var. duboisii (African histoplasmosis) may be confused with Blastomyces dermatitidis, but the former has narrow-based buds and do not contain multiple nuclei. Cryptococcus neoformans is characterized by a wide, carminophilic capsule. Aspergillus organisms often occur as radiating hyphae that branch dichotomously at acute angles. Paracoccidiodes braziliensis, the cause of South American blastomycosis, reproduces in tissue by multiple budding.
Contributor: Animal Diagnostic Laboratory, Pennsylvania State University, University Park, PA 16802.
1. Cote E, Barr SC, Allen C, Eaglefeather E: Blastomycosis in six dogs in New York
state. J Amer Vet Med Assoc 210(4):502-504, 1997.
2. Jubb KVF, Kennedy PC, Palmer N: The respiratory system. In: Pathology of
Domestic Animals, 4th ed., vol. 2, pp. 667, Academic Press, 1993.
3. Carter GR, Cole Jr. JR: In: Diagnostic Procedures in Veterinary Bacteriology and Mycology. 5th ed., pp. 442-446, Academic Press, 1990.
4. Breider MA, Walker TL, Legendre AM, van Ee RT: Blastomycosis in cats: five cases (1979-1986). J Amer Vet Med Assoc 193(5):570-572, 1988.
5. Nasisse MP, van Ee RT, Wright B: Ocular changes in a cat with disseminated blastomycosis. J Amer Vet Med Assoc 187(6):629-631, 1985.
6. Legendre AM: Blastomycosis. In: Infectious Diseases of the Dog and Cat, 2nd ed., pp. 371-377, WB Saunders Co., 1998.
7. Jones TC, Hunt RD, King NW: Diseases caused by fungi. In: Veterinary Pathology, 6th ed., pp. 505-547, Williams and Wilkins, 1997.
International Veterinary Pathology Slide Bank:
Laser disc frame #'s 12365-12367.

Case II - A96359034 (AFIP 2639019)

Signalment: Two-week-old, female Labrador Retriever.
History: Two puppies from a litter of seven became acutely ill with diarrhea ranging from bloody to mucoid. In one of the puppies, there was severe abdominal cramping.
Gross Pathology: Acute pulmonary congestion and edema. Ileal serosal petechiation.

Laboratory Results:

Bacterial cultures:
1. Bitch's milk: Staphylococcus intermedius.
2. Puppy lung & intestine: E. coli.
Virology: Electron microscopy of puppy intestinal contents positive for parvovirus.

Contributor's Diagnosis and Comments: Enteritis, acute, necrotizing with enterocyte intranuclear inclusions. Etiology: Minute virus of canines (parvovirus).
Additional lesions present in the puppy were multifocal hepatic necrosis and interstitial pneumonia with intravascular colonies of small gram-negative bacilli suggesting an acute superimposed bacteremia. Lymphoid necrosis in Peyer's patches and mesenteric lymph nodes was attributed to the viral infection.

Two distinct parvoviruses are known to infect dogs. Canine parvovirus-type 1 (minute virus of canines) infection seems to be fairly widespread, but clinical disease is uncommon. Canine parvovirus-type 2 infection, first recognized in 1978, is also widespread, and infection commonly results in severe disease with high mortality. The viruses differ in antigenicity and tissue tropism.

Clinical disease due to CPV-1 can result from in utero infection early in gestation with embryonic/fetal death. In utero infection late in gestation results in the birth of normal puppies. Infection in puppies generally less than three weeks of age can result in clinical disease, but factors relating to clinical disease versus inapparent infection are unknown. Clinically, the disease is manifest as vomiting, diarrhea, crying, and dyspnea. Histologically, the lesions affect primarily small intestine and lymphoid tissues. In the small intestine, intranuclear inclusion bodies occur at or near the villous tips with sloughing but minimal necrosis of epithelial cells. Hyperplasia of crypt and villous epithelium may also be noted. Necrosis and/or depletion of lymphocytes occur in lymphoid tissues. According to one report, the Walter Reed canine cell line is the only one that supports replication of the CPV-1.
40x obj.
Case 3-2. Small intestine. Demonstrates villous fusion, swelling of mucosal epithelial cells, and multiple brick-shaped amphophilic intranuclear inclusions.
20x obj.
Case 3-2. Lymph node. There is lymphoid depletion of the paracortex, loss of follicular definition, and scattered karyorrhexis of lymphoid cell nuclei (necrosis).
40x obj.
Case 3-2. Pancreas. Multifocally within a blood vessel there are clusters of small bacilli.
AFIP Diagnosis:
1. Small intestine: Enteritis, subacute, diffuse, mild, with multifocal villar fusion, multifocal epithelial necrosis, and numerous, villar tip, epithelial intranuclear inclusions, Labrador Retriever, canine.
2. Lymph node; Peyer's patches: Lymphoid necrosis, diffuse.
3. Pancreas: Bacilli, intravascular and multifocal.
Conference Note: Canine parvoviruses are small (20 nm diameter), nonenveloped, single-stranded DNA viruses that require rapidly dividing cells, such as bone marrow cells, intestinal epithelium, and lymphoid cells, for replication. Parvoviruses are extremely stable and resistant to both adverse environmental conditions and most common detergents and disinfectants, with the exception of sodium hypochlorite (household bleach).
The domestic dog is the only proven host for CPV-1, although other canids are probably susceptible. Serologic evidence suggests that it has a widespread distribution in the dog population, but clinical disease is generally restricted to pups less than three weeks old. Natural disease develops in these young pups through oronasal exposure or in utero infection and causes enteritis, mild pneumonia, and occasional myocarditis or sudden death. Because of the limited number of reported cases, the clinical importance of CPV-1 infection is not completely known.

Histologically, the intestinal lesions produced by CPV-1 infection are remarkably different from those of CPV-2 enteritis. CPV-2 infection results in loss of normal villar architecture, collapse of the mucosa, extensive blunting and fusion of villi, and often severe crypt epithelial necrosis. Epithelial intranuclear inclusions are uncommonly observed. In contrast, relatively normal villar architecture is maintained in CPV-1 infection, and there is crypt epithelial hyperplasia. Villar epithelial cells are often vacuolated and contain numerous intranuclear inclusions, and there may be a mild inflammatory infiltrate.
Several other histologic lesions may occur in parvoviral infections. Varying degrees of lymphoid necrosis and depletion, both within Peyer's patches and lymph nodes, are described in both types of parvovirus infection. Interstitial pneumonia, bronchitis, pneumonitis, and the presence of intranuclear inclusions within the bronchiolar epithelium can occur with CPV-1, and are especially associated with experimental infections. Infrequently, a nonsuppurative myocarditis may occur in CPV-1 infection, and varying histologic lesions have been described including interstitial edema, infiltration by mononuclear inflammatory cells, myocardial necrosis and mineralization, and occasionally the presence of intranuclear inclusions within myocardiocytes.
Gross lesions in infected puppies are often mild. In experimental infections, lesions noted included red-gray consolidation of ventral and hilar areas of the apical and cardiac lobes of the lung, and bronchial and mediastinal lymphadenopathy. Lesions in natural infections vary and include enlarged lymph nodes, streaking of the myocardium, atelectatic lungs, and soft, pasty stools in the intestinal tract. The disease may cause stillbirths or the birth of weak pups in infected bitches.
Minute virus of canines may cause spontaneous disease in young pups. Failure to subject stillborn or neonatal pups to pathologic study may be the cause for the lack of reports. Pneumonia and enteritis, and occasionally myocarditis, characterize the pathological finidings in CPV-1 infection. The virus may provoke only mild or vague signs, and fatal cases may be diagnosed as "fading pups". Minute virus of canines should be considered in the differential diagnosis for pups that die when less than three weeks of age and in cases of failure to conceive or fetal death.

1. Barker IK, van Dreumel AA, Palmer N: The alimentary system. In: Pathology of Domestic Animals, 4th ed., Jubb, Kennedy, Palmer eds., vol. 2, pp. 141-199, Academic Press, 1993.
2. Carmichael LE, Schlafer DH, Hashimoto A: Pathogenicity of minute virus of canines (MVC) for the canine fetus. Cornell Vet 81:151-171, 1991.
3. Harrison LR, Styer EL, Pursell AR, Carmichael LE, Nietfeld JC: Fatal disease in nursing puppies associated with minute virus of canines. J Vet Diag Invest 4:19-22, 1992.
4. Macartney L, et. al.: Characterization of minute virus of canines (MVC) and its pathogenicity for pups. Cornell Vet 78:131-145, 1988.
5. Hoskins JD: Canine viral enteritis. In: Infectious Diseases of the Dog and Cat, 2nd ed., pp. 40-46, WB Saunders Co., 1998.
Contributor: Texas Veterinary Medical Diagnostic Lab, P.O. Box 3200, Amarillo, Texas 79116-3200.

Case III - D96 3803 (AFIP 2642051 [corrected])

Signalment: Eleven-year-old, male, neutered Domestic Longhaired cat.
History: This cat had fever of 105.8 and did not respond to enrofloxacin or dexamethasone. He then became lethargic, shocky and died.
Gross Pathology: None described.

Laboratory Results: None.

Contributor's Diagnosis and Comments: Splenitis, histiocytic, diffuse, severe, with numerous intracellular protozoal organisms, characteristic of Cytauxzoon.
Etiology: Cytauxzoon felis.

There are many intravascular and extravascular macrophages in the spleen filled with schizonts characteristic of Cytauxzoon felis infection. Cytauxzoon felis is classified in the family Theileriidae. It is transmitted by ixodid ticks and is not contagious by direct contact exposure. The bobcat is a natural host. Cats infected with Cytauxzoon felis develop signs of anemia, icterus, pyrexia, and depression. Early diagnosis of this disease can be achieved by examination of peripheral blood for erythroparasitemia. Cytauxzoon felis trophozoites are ring-forms and present within the cytoplasm of erythrocytes. This differs from feline infectious anemia caused by Hemobartonella felis in which the organisms are coccoid and present on the surface of red blood cells. Cytauxzoonosis is fatal in cats, and so far there is no drug available for the treatment of this disease.
10x obj.
Case 3-3. Spleen. There is little white pulp, and here it is predominantly around a small arteriole. Multifocally within the red pulp and vascular sinuses, there are abundant ill defined large granular basophilic cells (interpreted as macrophages).
20x obj.
Case 3-3. Spleenic artery. Within the splenic arteries there are abundant large 20-30u cells with granular cytoplasm, open faced nuclei and a single prominant nuclei (interpreted as macrophages containing protozoal organisms). Similar macrophages are scattered around the artery in the red pulp.
AFIP Diagnosis: Spleen: Histiocytosis, intravascular and diffuse, moderate, with intrahistiocytic protozoal schizonts, Domestic Longhair, feline, etiology consistent with Cytauxzoon felis.
Conference Note: Most conference participants preferred the diagnosis of splenic histiocytosis over splenitis based upon the lack of histological changes associated with inflammation. The lesion is characterized by an infiltrate composed almost entirely of histiocytes that are filled with basophilic organisms (schizonts), but there is lack of other inflammatory cells and vascular changes that normally characterize an inflammatory process.

Cytauxzoon is classified in the order Piroplasmida and family Theileriidae. This family has both an erythrocytic and a tissue (leukocytic) phase. Large schizonts of C. felis develop in macrophages, whereas in Theileria the exoerythrocytic stage occurs primarily within lymphocytes. The Babesiidae, a related family, is characterized by having a primarily erythrocytic phase in the mammalian host, and its morphological features are indistinguishable from the erythrocytic form of Cytauxzoon. Cytauxzoon felis, B. equi, and B. rodhaini have been linked to both the babesias and theilerias by RNA gene sequence analysis, and it has been suggested that these organisms be reclassified within a separate family.
Ticks are implicated as the natural vector for Cytauxzoon, because most cases of infection have been associated with the presence of these parasites on the hosts. Experimentally, Dermacentor variabilis can transmit the organism from bobcats to domestic cats. In a white tiger that developed a natural, fatal infection in Florida, two female Lone Star ticks (Amblyomma americanum) were present on the inguinal skin. In the life cycle of C. felis, schizonts develop within mononuclear phagocytes, initially as indistinct vesicular structures and later as large, distinct nucleated schizonts that actively undergo division by true schizogony and binary fission. Later in the course of the disease, schizonts develop buds (merozoites) that separate and eventually fill the entire host cell. The host cell probably ruptures, releasing merozoites into the tissue fluid and blood. Merozoites are then believed to enter erythrocytes to form the intraerythrocytic stage. Merozoites appear in macrophages one to three days before they are observed in erythrocytes.
Clinically, the disease in cats is characterized by fever, depression, dyspnea, anorexia, lymphadenopathy, anemia, and icterus leading to death in three to six days. Gross findings include pale or icteric mucous membranes, petechiae and ecchymoses in the lung, heart, lymph nodes and on mucous membranes, splenomegaly, lymphadenomegaly, and hydropericardium. Microscopically, numerous large schizonts are present within the cytoplasm of endothelial-associated macrophages. Infected macrophages become markedly enlarged (up to 75 micrometers) and may occlude the lumens of numerous vessels of many tissues, especially the lungs. Minimal inflammatory reaction is present in tissues.
Each schizont may contain numerous merozoites. Ultrastructurally, schizonts lack a parasitophorous vacuole, and individual merozoites possess rhoptries. Merozoites within erythrocytes, best seen on peripheral blood or tissue impressions, are variable in morphology and can occur as round, oval, or signet ring-shaped bodies 1-5 micrometers in diameter with a small, peripherally placed basophilic nucleus.
Organisms that must be distinguished from the intraerythrocytic phase of C. felis include Babesia and Hemobartonella, because the blood stage may appear similar to the ring forms of Hemobartonella and to the piriforms of Babesia. Unlike Cytauxzoon, however, babesiosis and hemobartonellosis do not have a tissue stage of infection. Differential diagnosis for the tissue phase of cytauxzoonosis includes other small (less than 5 m), intrahistiocytic organisms such as Toxoplasma, Leishmania, and Histoplasma.
1. Cowell RL, Panciera RJ, Fox JC, Tyler RD: Feline cytauxzoonosis. Compend Cont Ed Pract Vet 10:731-735, 1988.
2. Garner MM, Lung NP, Citino S, Greiner EC, Harvey JW, Homer BL: Fatal cytauxzoonosis in a captive-reared white tiger (Panthera tigris). Vet Pathol 33:82-86, 1996.
3. Kier AB, Greene CE: Cytauxzoonosis. In: Infectious Diseases of the Dog and Cat, 2nd ed., pp. 470-473, WB Saunders Co., 1998.
4. Jones TC, Hunt RD, King NW: Diseases due to protozoa. In: Veterinary Pathology, 6th ed., pp. 599-600, Williams and Wilkins, 1997.
Contributor: PAL-PATH, Inc., 1277 Record Crossing Road, Dallas, TX 75235.
International Veterinary Pathology Slide Bank:
Laser disc frame #'s 5298-5300, 5829-5831, 7986, 14300, 9642.

Case IV - 97-26234 (AFIP 2642418 [corrected])

Signalment: Four-year-old, female, spayed, Pug, canine.
History: The dog was originally presented for peripheral lymphadenopathy which was diagnosed via excisional lymph node biopsy as granulomatous lymphadenitis secondary to mycobacteriosis. Lymph node culture revealed Mycobacterium avium. The dog did well for two years on a multiantibiotic treatment regimen. Regularly scheduled appointments to monitor the disease included serum chemistries and palpation of peripheral lymph nodes which initially regressed in size. Two years after diagnosis, the lymph nodes began to enlarge again, and since the dog was shedding M. avium in the feces as confirmed by culture, she was euthanized at that time.
Gross Pathology: The spleen was greatly enlarged (2800 g; 30x6x4 cm). It was meaty in texture and was mottled cream-colored to yellow throughout the parenchyma. The mesenteric and cecocolic lymph nodes were enlarged and uniformly cream-colored to tan on cut section.
Laboratory Results: Blood chemistries: Hypoalbuminemia, hypocholesterolemia, decreased BUN.
Contributor's Diagnosis and Comments: Disseminated granulomatous disease, mycobacteriosis, Mycobacterium avium.
Although gross changes were confined to the spleen and intestinal lymph nodes, there were multifocal infiltrates of macrophages in the lungs, liver, kidneys, thyroid gland, bone marrow, intestines, and other lymph nodes. Acid-fast stains of sections revealed numerous acid-fast bacteria in macrophages in all tissues examined. Splenic architecture was effaced by sheets of macrophages with binucleate and multinucleate forms and epithelioid macrophages with a few foci of residual lymphoid cells. The bone marrow was almost completely effaced by macrophages, although some myeloid and erythroid cells remained. Perivascular infiltrates of macrophages were present throughout the lungs and liver and in the lamina propria of multiple intestinal sections.
Mycobacteriosis in dogs is uncommon in the U.S. since the effort to eradicate tuberculosis in domestic animals has been largely successful. The dog is experimentally equally susceptible to Mycobacterium tuberculosis and M. bovis, but is considered resistant to M. avium. Infection is generally via inhalation of aerosols or ingestion of infected material. The size of the inoculum, the number of times an animal is exposed to the organism, and the immune status of the individual all determine whether an active mycobacterial infection becomes established.
While a route of exposure to M. avium was not determined for this dog, a possibility that remains is that the dog frequently visited a location that was adjacent to a major waterfowl staging area. The dog had a habit of being a "garbage hound" and would always ingest things it found on the ground or floor. If this dog was ingesting M. avium-infected waterfowl droppings or inhaling infected aerosols repeatedly, the cumulative exposure to M. avium could have been great enough for infection to occur. There was no indication given in the record regarding the immune status of this dog.
40x obj.
Case 3-4. Liver. Demonstrates focus of epithelioid macrophages replacing normal hepatic cords. These cells are filled with ill defined rod shaped structures.
40x obj.
Case 3-4. Lung. Similar clusters of epithelioid macrophages and lymphocytes expand alveolar septa near moderate sized blood vessels. Macrophages contain granular to rod shaped material.
40x obj. Zeil-Neilson
Case 3-4. Lung. Cell clusters adjacent to vessels like those described above contain myriad acid fast bacilli.
AFIP Diagnosis:
1. Liver: Hepatitis, granulomatous, portal, central, and multifocal, moderate, with numerous intrahistiocytic bacilli.
2. Lung: Pneumonia, granulomatous, perivascular, multifocal, moderate, with numerous intrahistiocytic bacilli.
3. Lung: Congestion, diffuse, moderate, with abundant alveolar edema.
Conference Note: Mycobacterial infections in man and animals are caused by bacteria belonging to the family Mycobacteriaceae, order Actinomycetales. Mycobacterium is a genus compromising morphologically similar, aerobic, gram- positive, non-spore forming, and non-motile bacilli with wide variations in host affinity. They have the unique property of being acid-fast due to the high lipid content of mycolic acid in the cell wall.
The bacteria have been subdivided into several groups and individual species based on biochemical and culture characteristics. The species causing "classic" tuberculosis are termed the M. tuberculosis complex (MTC) and include M. bovis, M. tuberculosis, M. africanum (rare cause of human TB in Africa), and M. microti (a rodent pathogen that has been reported to infect cats). Those species grouped together causing the syndrome of M. avium complex (MAC), sometimes referred to as "avian mycobacteriosis", include Mycobacterium avium-intracellulare and M. avium susp. paratuberculosis. The latter, which is the cause of Johne's disease in ruminants (ruminant paratuberculosis), can infect monogastric animals and produces lesions in stump-tailed macaques that are very similar to Crohn's disease in man, thus implicating this bacteria as a potential etiology for the human disease. Another separate group of myocobacterial infections is caused by M. leprae and called either leprosy or Hansen's disease, while feline and murine leprosy is caused by M. lepraemurium. The final group, termed "atypical mycobacteriosis", can be described as the localized opportunistic skin and subcutaneous infections caused by saprophytic and rapidly growing mycobacteria, e.g. M. fortuitum, M. chelonae, etc.
Classic tuberculosis in immunocompetent humans results in the formation lumps or nodules called tubercles (from the Latin word "tuberculum"), and histologically consists of well-formed granulomas composed of epithelioid macrophages, Langhans-type multinucleate macrophages, and lymphocytes. Acid-fast mycobacteria are few and difficult to find. Granuloma formation, which fundamentally requires sufficient numbers of functioning macrophages and T helper-1 lymphocytes, is often absent in humans and nonhuman primates that are immunocompromised due to concurrent infection with immunodeficiency viruses.
Instead, these individuals and animals develop disseminated disease with diffuse granulomatous inflammatory infiltrates and contain more abundant acid-fast organisms.
In dogs and cats, MAC infections are uncommon; in humans MAC organisms are of low virulence in immunocompetent individuals, but cause infections in 15 to 24% of patients with HIV infections that become severely immunocompromised (less than 60 CD4+ cells per cubic mm). Most infections in all three species are caused by M. avium-intracellulare, often originate in the gastrointestinal tract via oral ingestion, and become widely disseminated to the liver, spleen, lung, and lymph nodes. Spread to skin, bone, cervical vertebrae, mammary gland, and serous surfaces may also occur in animals.
Histologically, MAC infections in most mammals, including humans, are characterized by a diffuse granulomatous, inflammatory reaction containing large numbers of epithelioid macrophages without necrosis, fibrosis, or calcification. Macrophages are packed with high numbers of acid-fast bacilli, which may appear as "negative images" in hematoxylin and eosin stained sections. Langhans-type multinucleated macrophages may be present, but not always. There is little lymphocytic response. In dogs and cats, lesions are multifocal and coalescing to diffuse, and the inflammatory cells often displace or replace affected tissues creating a "sarcomatous" appearance.
The histological similarities of MAC infections in cats and dogs to immunocompromised humans infected with MAC suggest that innate immunodeficiency may predispose these small animals to the disease. Histologically, the character of the inflammation in immunodeficient humans concurrently infected with classic tuberculosis more closely resembles MAC infections in dogs and cats than the character of classic tuberculosis in immunocompetent individuals, further supporting the theory of a deficiency in cell-mediated immunity in these animals. Finally, there is evidence that a genetic predisposition to MAC infections may exist in basset hounds, miniature schnauzers, and Siamese cats.
1. Feldman WH: The pathogenicity for dogs of bacilli of avian tuberculosis. J Am Vet Med Assoc 76:399-419, 1930.
2. Francis J: Tuberculosis in small animals. Mod Vet Pract 39-42, 1961.
3. Snider WR: Tuberculosis in canine and feline populations. Am Rev Resp Dis 104:877-887, 1971.
4. Liu S: Canine tuberculosis. J Am Vet Med Assoc 177:164-167, 1980.
5. Thoen C O, Himes E M: Mycobacterium. In: Pathogenesis of Bacterial Infections in Animals, pp. 26-37, Iowa State University Press, 1986.
6. Carpenter J L, et al.: Tuberculosis in five Bassett Hounds. J Am Vet Med Assoc 192:1563-1568, 1988.
7. Shackelford CC, Reed WM: Disseminated Mycobacterium avium infection in a dog. J Vet Diagn Invest 1:273-275, 1989.
8. Clercs C, et al.: Tuberculosis in dogs: A case report and review of the literature. J Am Anim Hosp Assoc 28:207-211, 1992.
9. Eggers JS, et al.: Disseminated Mycobacterium avium infection in three miniature schnauzer litter mates. J Vet Diagn Invest 9:424-427, 1997.
Contributor: University of Minnesota, Veterinary Diagnostic Laboratory, College of Veterinary Medicine, 1333 Gortner Avenue, St. Paul, MN 55108.
International Veterinary Pathology Slide Bank:
Laser disc frame #'s 21897, 9127, 9926.
Ed Stevens, DVM
Captain, United States Army
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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