JPC SYSTEMIC PATHOLOGY

HEMOLYMPHATIC SYSTEM

February 2024

H-F01

 

Signalment (JPC# 1535256): Pacific white-sided dolphin (Lagenorhynchus obliquidens).

 

HISTORY: Tissue from a dolphin, which had been in captivity for three years.

 

HISTOPATHOLOGIC DESCRIPTION: H-F01a: Lymph node: Diffusely effacing normal lymphoid architecture within the cortex and paracortical areas and extending into the medulla are numerous macrophages, viable and necrotic neutrophils, fewer lymphocytes and plasma cells, fibrosis, abundant eosinophilic fibrillar material (fibrin), and clear space (edema). Multifocally there are large areas of eosinophilic cellular and karyorrhectic debris (lytic necrosis) and hemorrhage, fibrin, and edema. Admixed are numerous 2 x 6 µm, round to oval to elongate (cigar-shaped), intrahistiocytic and extracellular yeasts that are surrounded by a 1 - 3 µm clear halo. Rarely, individual yeasts are encircled by numerous eosinophilic radiating spicules of Splendore-Hoeppli material (asteroid bodies). Diffusely, the lymph node capsule is expanded by neutrophils, macrophages, and fewer lymphocytes and plasma cells admixed with fibrin, edema, hemorrhage and cellular and karyorrhectic debris (capsulitis).

 

H-F01b: Lymph node (GMS): Diffusely there are numerous intrahistiocytic and extracellular round to oval to elongate, 2 x 6 µm (cigar shaped) yeasts, often with multiple buds. Admixed are many fungal hyphae that are 4-6 um thick with parallel cell walls, irregular septation and right angle and dichotomous branching (postmortem overgrowth).

 

MORPHOLOGIC DIAGNOSIS: Lymph node: Lymphadenitis and capsulitis, pyogranulomatous and necrotizing, diffuse, severe, with intrahistiocytic and extracellular yeast, Pacific white-sided dolphin (Lagenorhynchus obliquidens), cetacean.

 

ETIOLOGY: Sporothrix schenckii

 

ETIOLOGIC DIAGNOSIS: Sporothricotic lymphadenitis

 

GENERAL DISCUSION:  

• Most common in cats, dogs, horses, humans
• Dimorphic, saprophytic fungus that usually lives in soil and decaying organic matter (sphagnum moss, stored hay bales documented sources) 
• Opportunistic pathogen; infection often follows a penetrating wound
• Zoonotic; scratches and bites from infected cats are a significant public health risk
• Three clinical forms (see gross findings)

 

PATHOGENESIS: 

• Infection acquired via wound contamination or inoculation into tissue by puncture wounds (thorns, wood splinters, bites, scratches)
• Primary cutaneous form: Thought to result from high host immunity
  1. Infection localized at point of entry into skin
  2. Cats, dogs, horses
• Cutaneous-lymphatic form: Most common presentation in horses, humans, and dogs
  1. Forms localized cutaneous infection that spreads along lymphatic vessels
• Extracutaneous / Disseminated form: Develops as a sequela to the cutaneous-lymphatic form or is inhaled
  1. Occurs most frequently in cats (usually no underlying immunosuppression)

 

TYPICAL CLINICAL FINDINGS:  

• Primary cutaneous form: 
  1. Multiple ulcerated skin nodules 
• Cutaneous-lymphatic form:
  1. Multiple nodules arranged in lines following thickened lymphatic vessels
• Extracutaneous / Disseminated form:
  1. Fever, lethargy, anorexia
  2. +/- cutaneous lesions, lymphadenopathy
  3. Affected cats are often not immunosuppressed

 

TYPICAL GROSS FINDINGS:  

• Primary cutaneous form:  
  1. Multiple raised alopecic, ulcerated, crusted nodules or plaques
• Cutaneous-lymphatic form:  
  1. Firm, round nodules (usually on extremity or head)
  2. Thick cords with secondary nodules form along lymphatics
  3. May develop deep cavitating lesions that expose muscle +/- bone
• Extracutaneous / Disseminated form:
  1. Tan to red nodules in affected organs with or without cutaneous and lymphatic involvement

        

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Nodular to diffuse pyogranulomatous or granulomatous dermatitis, panniculitis, lymphadenitis
• Variable necrosis and fibrosis
• Intrahistiocytic or extracellular round, oval, or cigar-shaped yeasts that measure at least 2 - 6 µm in diameter (round to oval forms) or up to 3 x 10 µm (cigar form)
  1. Generally found in high numbers in lesions from cats and rare in tissues from dogs and horses
  2. Cigar shape is characteristic, but not always present
  3. Refractile cell walls
  4. Artifactual capsule may be present (cytoplasm shrinks away from cell walls during processing)
• Asteroid bodies: Central yeast surrounded by radiating eosinophilic spicules (Splendore-Hoeppli material) 
  1. Not observed in all cases

 

ADDITIONAL DIAGNOSTIC TESTS:  

• GMS or PAS stains
• Fungal culture 
• Cytology of exudate
• Fluorescent antibody
• Serology of limited use; only indicates exposure

 

DIFFERENTIAL DIAGNOSIS: 

• Histoplasma capsulatum: 2‑4 µm diameter, intrahistiocytic yeast, with single narrow‑based budding (hourglass appearance)
• Cryptococcus neoformans (I-F08): 2-20 µm diameter yeast with thick, mucin-positive, 2 µm thick capsule; forms single or multiple narrow‑based buds; capsule stains well with mucicarmine
• Blastomyces dermatitidis (I-F06): 8‑25 µm diameter, round, multinucleated yeast with double contoured, thick walls, with broad‑based budding
• Cutaneous leishmaniasis (I-P15): Chronic ulcerative dermatitis with 2 µm intrahistiocytic protozoal amastigotes with a vesiculate nucleus and kinetoplast

 

COMPARATIVE PATHOLOGY:  

• Can affect a wide range of species
  • Equids: Cutaneous-lymphatic form predominates with nodular lesions on distal extremities
    • DDX for cutaneous lymphangitis in horses:
      • Glanders – Burkholderia mallei
      • Melioidosis – Burkholderia pseudomallei
      • Epizootic lymphangitis – Histoplasma capsulatum subsp. farciminosum
      • Ulcerative lymphangitis – Corynebacterium pseudotuberculosis
      • Strangles – Streptococcus equi
      • Pythiosis - Pythium insidiosum
• Cats: All three forms observed in cats; grooming often will inoculate into other distant locations; early cutaneous-lymphatic wounds are grossly similar to bite wounds
  • Recent study in Brazil found extracutaneous lesions in 74/102 feline cases, including rhinitis or rhinosinusitis, lymphadenitis, pneumonia, meningitis, periorchitis, conjunctivitis, and glossitis (Santos, Vet Pathol 2024)
• Dolphin: Differential diagnosis: other systemic dimorphic fungi & Lacazia loboi
• NHPs: Lesions usually confined to the skin, subcutaneous tissues, and lymphatics; rare reports of disseminated disease involving bone, lungs, other viscera. Reported in a chimpanzee (multiple nodules and pustules on the face, enlarged sublingual and submaxillary lymph nodes); Experimentally induced in rhesus monkeys by implanting infected thorns in fingers
• Bilby: Disseminated infection involving multiple organs with a cutaneous lesion described
• Rodents: Cutaneous disease reported in several rodent species with dermatitis ranging from suppurative and necrotizing to granulomatous and fibrosing, depending on chronicity

 

REFERENCES:

1. Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2nd ed. San Diego, CA: Elsevier; 2012: 153-154, 574.
2. Boes KM. Respiratory System. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:189, 221-222. 
3. Coiacetto F, Arthur I, et al. Disseminated sporotrichosis in a bilby (Macrotis lagotis). J Comp Pathol. 2019; 170:74-77.
4. Delaney MA, Treuting PM, Rothenburger JL. Rodentia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 512.
5. Fisher DJ. Cutaneous and Subcutaneous Lesions. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:80.
6. Lane LV, Yang PJ, Cowell RL. Selected Infectious Agents. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:48-49.
7. Mätz-Rensing K, Lowenstine LJ. New World and Old World Monkeys. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 364, 368.e7-e8.
8. Mauldin EA, Peters-Kennedy J.  Integumentary System.  In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6^th ed. St. Louis, MO: Elsevier; 2016: 655-657.
9. Raskin RE, Conrado FO. Integumentary System. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4^th ed. St. Louis, MO: Elsevier; 2023:56-57.
10. Santos AF, Azevedo MI, Amaral CI, et al. Feline sporotricosis: Characterization of cutaneous and extracutaneous lesions using different diagnostic methods. Vet Pathol. 2024;61(2):221-231.
11. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1177.
12. Wellman ML, Radin MJ. Nasal Exudates and Masses. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:125.

 

Click the slide to view.

---