JPC SYSTEMIC PATHOLOGY
SIGNALMENT (JPC # 1632089): An adult Vizsla dog
HISTORY: This dog presented with intractable diarrhea unresponsive to therapy.
HISTOPATHOLOGIC DESCRIPTION: DF03a: Colon: Multifocally and transmurally, there are many extracellular and intrahistiocytic, round to oval, 8-20 um diameter algal sporangium that have a clear 2-4 um thick wall, and contain either central granular amphophilic material or multiple (2-8 or more) wedge-shaped endospores. These are admixed with moderate numbers of macrophages and plasma cells, and rare lymphocytes and neutrophils that diffusely expand the lamina propria and extend through the muscularis mucosa and into the submucosa. The submucosa is expanded up to twice normal thickness by algae and a similar population of inflammatory cells admixed with small amounts of hemorrhage and edema, and inflammation also mildly infiltrates the tunica muscularis, and multifocally disrupt serosa and attached mesentery. Occasionally, the superficial mucosal epithelium is disrupted by eosinophilic cellular and karyorrhectic debris (necrosis) and the tunica muscularis has multifocal, mild myofiber degeneration and loss.
DF03b: Colon (PAS): The algal cell wall is PAS positive.
MORPHOLOGIC DIAGNOSIS: Colon: Colitis, histiocytic and plasmacytic, subacute, diffuse, moderate, with mesenteric steatitis and many extracellular and intrahistiocytic algae, Vizsla, canine.
ETIOLOGIC DIAGNOSIS: Protothecal colitis
CAUSE: Prototheca spp.
- Ubiquitous, saprophytic, colorless, unicellular, opportunistic algae that reproduce asexually by internal septation (endosporulation)
- Causes gastrointestinal or disseminated infections in dogs, cutaneous infections of cats and humans, and mastitis in cows.
- Three species cause disease: Prototheca zopfii, P. wickerhamii, P. salmonis
- Only P. zopfii & P. wickerhamii are pathogenic in humans and mammals
- P. wickerhamii: (5-12 mm) sporangium with compact round or cuboidal endospores
- P. zopfii: (10-25 mm) oval sporangium with larger, round to polyhedral endospores
- Probably a mutant achlorous form of green algae (genus Chlorella)
- Characteristic “morula” containing multiple wedge-shaped endospores, arranged radially around a central endospore
- Only the cell wall stains intensely with PAS
- Stains intensely with GMS, Gridley fungal, and Mucicarmine; gram positive
- Cell walls lack muramic acid and glucosamine, unlike fungi and bacteria
- Infections described in dogs, cats, cows, humans, deer, Atlantic salmon, fruit bats, beaver, rabbits, rats, mice, ferrets, and snakes
- Predisposing factors are poorly understood
- Cutaneous infections likely due to traumatic inoculation; alimentary tract infections secondary to existing mucosal lesions
- Collies and oxers may be over-represented, suggesting breed-related susceptibility or immunodeficiency
- Persistent shedding maintains infection in herds
- Underlying immune suppression may be a factor
TYPICAL CLINICAL FINDINGS:
- Dog: Hemorrhagic large bowel diarrhea, ocular disease (ophthalmitis, blindness involved in two-thirds of the cases), +/- CNS signs, polyuria/polydipsia, progressive weight loss, emesis, otitis, chronic nasal discharge, and deafness
TYPICAL GROSS FINDINGS:
- Kidney: Disseminated white to gray nodules or surface depressions, with pale foci within parenchyma and at corticomedullary junction; necrosis of the renal papilla
- Intestine: Small white to gray serosal nodules; friable, thickened corrugated colon/rectum; patchy hemorrhagic necroulcerative enterocolitis
- Liver: Enlarged lobulated; patchy yellow discoloration
- Eye: Exudate in anterior chamber; gray-white granular material in vitreous
- Serosa: Disseminated gray nodules (peritoneum, pericardium)
- Skin: Localized gray-white, subcutaneous or dermal lesions that extend deeply into fascia, tendons, vessels, and nerves
- Udder: Mastitis and regional lymphadenitis; massive necrosis of udder, with thrombosis and hemorrhage; regional lymph node enlargement
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Many extracellular and intrahistiocytic, round to oval, 8-20 um diameter algae that have a clear/refractile 2-4 um thick wall, and contain either central granular amphophilic material or multiple (2-8 or more) wedge-shaped endospores
- Varies from mild lymphocytic or lymphoplasmacytic to pyogranulomatous and granulomatous reactions with giant cells
- Hemorrhage and necrosis are often present
- “Mercedes-Benz” endospores – tripartite cell wall division
- Minimal internal structure evident; lacks chloroplasts
- Both Prototheca and Chlorella have starch granules, but Chlorella has them within chloroplasts
ADDITIONAL DIAGNOSTIC TESTS:
- Culture, cytology, fluorescent antibody test, EM
Organisms that reproduce by endosporulation (mnemonic CRCB):
- Chlorella : Algal organism reported in cattle, sheep, and beaver; granulomatous and necrotizing lesions with similar organisms containing intracytoplasmic starch granules and chloroplasts, which are PAS positive and anisotropic in unstained and H & E sections and evident on EM; green discoloration of unfixed tissue grossly
- Rhinosporidium seeberi: Nasal mucosa; large, mature sporangia 100-350 um diameter with numerous round, mature endospores 7-9 um diameter
- Coccidioides immitis: Larger (10‑60 um), with many endospores per sporangium
- Batrachochytrium dendrobatidis: Thalli with discharge papillae in the epidermis of amphibians
Granulomatous colitis in dogs:
- Histoplasma capsulatum: Ulcerative, granulomatous transmural colitis
- Trichuris vulpis (whip worms): Presence of intraluminal nematodes; usually affects cecum and proximal ascending colon; evolves into a granulomatous transmural condition
- Mycobacterium spp. (M. bovis, M. tuberculosis)
- Leishmania sp: Heavy mucosal infiltrate of macrophages and often plasma cells
- Cats: Single or multiple small gray-white or tan subcutaneous nodules on extremities; usually confined to dermis and subcutis +/- regional lymph nodes; dense infiltrations of macrophages and giant cells without discrete granulomas
- Bovine: Nodular (granulomatous) mastitis; enlarged and pale supramammary lymph node; giant cells and eosinophils common
- Man: Cutaneous protothecosis (most prevalent); olecranon bursitis; disseminated
- Salmon: Renal granulomatous disease
- Beribè F, Miglio A, Cassarani MP, Magi G, et al. What is your diagnosis? Systemic lymphadenopathy and blindness in a dog from Italy. Vet Clin Pathol. 2014; 43(4): 605-6.
- Cheville NF. Algae, fungi and other eukaryotes. In: Ultrastructural Pathology: The Comparative Cellular Basis of Disease. 2nd ed. Ames, IA: Wiley-Blackwell; 2009: 573-576.
- Gelberg HB. Alimentary System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017: 385-6.
- Greene CE, Rakich PM, Latimer KS. Protothecosis. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, MO: Saunders; 2012: 696-701.
- Huth N, Wenkel RF, Roschanski N, et al. Prototheca zopfii Genotype 2-induced Nasal Dermatitis in a Cat. J Comp Path. 2015; 152: 287-290.
- Moller A, Truyen U, Roesler U. Prototheca zopfii genotype 2-The causative agent of bovine protothecal mastitis?. Vet Microbiol. 2007;120(3-4):370-374.
- Schöniger S, Roschanski N, Rösler, et al. Prototheca species and Pithomyces chartarum as Causative Agents of Rhinitis and/or Sinusitis in Horses. J Comp Path. 2016; 155: 121-125.
- Uzal FA, Plattner BL, Hostetter JM. Alimentary System. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 2. St. Louis, MO: Elsevier; 2016: 203-204.
- Vince AR, Pinard C, Ogilvie AT, et al. Protothecosis in a dog. Can Vet J 2014; 55: 950-954.