STARR


Starr is a 4-year-old German Shorthaired Pointer used for hunting and stud purposes. His owner brings him in with a festering wound on his shoulder. They were hunting two weekends before and Starr got caught up in some thick thorny underbrush: he had a few cuts and scrapes but otherwise seemed fine. About three days ago a lump appeared over his shoulder and this morning the owner found that it had ruptured, oozing a thick, pus-like exudate down Starr's leg.

Starr is alert but a little depressed. He has a temperature of 103 degrees and is slightly tachypneic. Upon auscultation you hear some fluid crackling in his lungs. Palpation of the foreleg produces some pain. You can feel numerous swellings along the lymphatics and the axillary lymph nodes are quite firm and swollen. You take a blood sample and a fine needle aspirate of an unruptured lymph node. Starr is started on a course of antibiotics and sent home. Blood serum chemistry and CBC are ordered: you also send out aspirate fluid for a culture and aspirate with Gram's stain.

Starr comes back three days later, worse despite his antibiotics. His forelimb lymphatics are quite swollen and several locations have become draining tracts. He's depressed and lethargic and has a noticeable rasp when breathing. You decide to switch medications but the culture has not yet come back from the lab. A technician calls the lab and learns that your sample was plated out....but that nothing has grown on any of the media used. Like the dog that didn't bark in the nightime, the absence of a positive culture for bacteria is the clue that you needed to make the diagnosis.


DIAGNOSIS

Starr does have an infection, but it's not bacterial. He has blastomycosis ("Blasto") a condition caused by a fungus: Blastomyces dermatitidis. B. dermatiditis causes diffuse pyogranulomatous lesions in tissues throughout the body. Blastomyces can be quite difficult to culture and requires special media for growth in the laboratory. A typical mistake is for a clinician not to indicate to the laboratory that the specimen may be Blastomyces, resulting in the lab using a bacteria culture media that won't support the fungus.

The fungus enters the body either through the respiratory tract or through skin wounds, with respiratory infection and subsequent dissemination to other tissues being the most common form of the disease. It's present in the environment as a mold producing reproductive spores. if the spores gain entry into an animal (or a human), they adapt to the warm, moist environment, taking on the yeast form, which disseminates throughout the body causing a vigorous mononucleocytic immune response. The response to the fungus is prolonged because it's very difficult for the immune system to clear, so what occurs is the formation of diffuse granulomas. A "granuloma" is a small, persistent nodular inflammatory response that's usually associated with long-standing insult. Granulomas are firm to the touch and microscopically contain large numbers of macrophages and giant cells. In a B. dermtiditis infection they can appear anywhere in the body (the yeast travels via the lymphatic system and the bloodstream) but most common sites for granulomas are the lungs and the cutaneous lymphatics.

The condition described in this case is another example of caseous necrosis. Caseous necrosis can be thought of as a combination of coagulation and liquefaction, and it's most characteristic of granulomatous lesions. Granulomatous lesions are typically associate with stubborn, persistent infections with hard to kill organisms, most especially including the mycobacterial ones.

Dogs, especially dogs that spend a lot of time in the outdoors, are particularly predisposed to blastomycosis. Any outdoor dog presenting with respiratory distress and lymphadenopathy should be examined for blastomycosis. Diagnosis can be made by finding Blastomyces in the granulomas or the lymph nodes. Fine needle aspirate can be useful but sometimes a full lymph node biopsy is needed for definitive diagnosis.

Treatment can be quite prolonged in severe cases. The current preferred drug is amphotericin B, an effective but expensive antimycotic agent. Treatment is often ineffective in disseminated cases and recurrence of the fungal infection or even secondary bacterial infection may occur.


HISTOPATHOLOGY

This is the prescapular lymph node of a similar specimen. The area of caseous necrosis is pretty obvious in the gross specimens as a cottage-cheese-like semi-solid material. In the microscope this appears as cell-free whorled areas, usually srrounded by an inflammatory collar (INF) of macrophages, also shown at higher magnification, below.

The lymph node architecture has been badly disrupted. Infiltrates of mixed inflammatory cells, macrophages and disseminated hemorrhage are visible. Macrophages and giant cells are present within the necrotic area as are many large, nonstaining, round inclusions. These are the blastomyces organisms that have infected the node.

At left is a field of the granuloma in which one of the giant cells is present. The giant cell is a multi-nucleated syncytial aggregation with phagocytic capability. In essence it's a sort of super-macrophage, derived from the fusion of mononuclear precursors. Giant cells are characteristic of caseous granulomas, forming in response to the persistent and difficult-to-eradicate stimulus that's present. The inert polysaccharide capsule of the B. dermatiditis organism makes it very resistant to ingestion and destruction, resulting in an attempt to overpower it by brute phagocytic force, using giant cells. This tactic, unfortunately, isn't going to work.

 

 

At left you see two giant cells, the one on the right having ingested one of the fungal invaders. Notice that the capsule of the fungus has protected it entirely from the lytic enzymes, and it's as undisturbed as if it had never been engulfed in the first place. This resistance to digestion is the reason that fungal infections of this type are so hard to treat and why granuloma formation is the likely result of an infection with them.

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