JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

November 2025

I-P16

Signalment (JPC# 1647900): Cardinal tetra (Paracheirodon axelrodi)

HISTORY: This is one of ten Cardinal tetras obtained from a pet store. Nine days later, multiple raised, pinpoint to 3 mm white spots appeared. Within days, all ten tetras were dead.

MICROSCOPIC DESCRIPTION: Head and rostral body, parasagittal section: Multifocally within the epidermis, gill epithelium, and oral mucosa, there are nodular foci of hyperplastic epithelium that measure up to 500 µm in length and pile up to 8 cell layers thick. Hyperplastic epithelial cells are occasionally markedly hypertrophied and contain an intracytoplasmic, up to 175µm diameter, irregularly round, single‑celled protozoal cysts with a 1‑2 µm thick hyaline wall, abundant, finely granular to vacuolated, basophilic cytoplasm that contains abundant membrane-bound, phagocytosed material; and a 30 µm x 100 µm, crescent-shaped, deeply basophilic macronucleus (trophont). Multifocally, there is mild hyperplasia of gill and oral epithelium with blunting and fusion of secondary lamellae in addition to the numerous previously described intraepithelial protozoa.

MORPHOLOGIC DIAGNOSIS: Skin, oral cavity, and gills: Epithelial hyperplasia, nodular, multifocal, moderate, with numerous protozoal cysts, Cardinal tetra (Paracheirodon axelrodi), piscine.

ETIOLOGY: Ichthyophthirius multifilis

ETIOLOGIC DIAGNOSIS: Cutaneous, oral, and branchial ichthyophthiriosis

CONDITION: Ich

CONDITION SYNONYMS: Freshwater white spot disease

GENERAL:

• One of the most common parasitic protozoans of freshwater fish worldwide
  • Less pathogenic for cold water species (e.g. salmon)
  • Scaleless fish are especially vulnerable: Catfish, sunfish
• Economically important ectoparasite of captive commercial fish
• Infected fish can develop immunity to re-infection that can last for several months
• Cryptocaryon irritans is saltwater equivalent.

LIFE CYCLE:

• Adult ciliated protozoa (theronts) adheres to epithelium > burrows into epithelium (trophont) > nodular epithelial hyperplasia around the trophont > trophont erupts through the epithelium, drops off host, forms a capsule (tomont) adhering in environment > undergoes binary fission > producing hundreds to thousands of tomites
  • Theront: Free-swimming, non-feeding, infective stage
  • Trophont/trophozoite: Host (fish)-feeding stage
  • Tomont: Encysted, dividing stage
  • Tomite: Daughter cells produced by a tomont
• Duration of life cycle and number of tomites produced is temperature dependent
  • Warmer water (59 – 77 ° F) improves proliferation

PATHOGENESIS:

• Encysting protozoans (such as I. multifilis) induce focal epidermal hyperplasia and hypertrophy at attachment sites due to burrowing and/or encysting
• Protozoa penetrates the epithelium > entering and exiting of the epithelium results in erosions and ulceration > prone to secondary bacterial infections
• Parasites cause intense pruritus leading to additional epidermal injury from self trauma
• Severe gill hyperplasia leads to hypoxia and possibly respiratory compromise
• Can be fatal if severe; epithelial destruction leads to osmoregulatory failure

TYPICAL GROSS FINDINGS:

• Small 1.0 mm grayish-white raised multifocal to coalescing nodules on the surface of the body, fins and gills with epidermal hyperplasia
• In advanced severe cases, cysts coalesce and form mucoid masses
• Epithelial erosion and ulceration
• Often cause behavioral changes such hyperactivity and chronic irritation

TYPICAL MICROSCOPIC FINDINGS:

• Ciliate encysted within the host epithelium is pathognomonic; cilia of Ichthyophthirius are evenly distributed over entire body surface (“holotrich”)
• Protozoa have a small circular mouth opening at one end, numerous small contractile vacuoles throughout the body, opaque granules, and an oval, C-shaped, or horseshoe-shaped macronucleus
• Heavy infestations have lymphocytic, plasmacytic and neutrophilic inflammation
  • Chronic inflammation: Macrophages
    • Potential mechanism for hiding from immune response (Araújo 2024)

DIFFERENTIAL DIAGNOSIS:

• Protozoan:
• Non-encysting protozoan cause epidermal hyperplasia and hypertrophy due to feeding activity: Trichodina spp., Chilodonella spp., Ichthyobodo spp.
  • Trichodina spp. (Trichodinosis): Non-encysting protozoan that infects marine or freshwater fish; causing mild disease similar to Ichthyophthirius multifiliis; wet mount identification of ‘scooting’ protozoan on affected tissue surfaces
  • Ichthyobodo spp. (Ichthyobodosis, costiosis, Ichthyobodo necator complex): smallest ectoparasite of fish (approximately the size of red blood cell) ; infects immunosuppressed and young fish; primary freshwater disease yet can infect saltwater; two forms: detached and mobile; grossly causes epithelial hyperplasia with increased mucus production, giving fish a bluish cast (slime)
• Encysting protozoans induce focal epidermal hyperplasia and hypertrophy at attachment sites due to burrowing and/or encysting: Ichthyophthirius spp., Cryptocaryon spp., Amyloodinium spp., Piscinoodinium spp
  • Cryptocaryon irritans (‘Marine Ich’): Penetrates the epithelium; same life cycle and same gross lesions in saltwater fish; readily diagnosed when seen under the skin or gills Chilodonella spp. (Chilodonellosis): Similar same life cycle and gross pathology as Ichthyophthirius multifiliis; yet more insidious often with severe tissue damage due to strong cellular response. Is smaller in diameter compared to Ichthyophthirius (up to 450 um)
  • Amyloodinium spp. (amyloodiniosis, marine velvet disease, marine oodinium disease, oodiniosis): One of the most important diseases of warm water marine fish affecting elasmobranches (sharks, rays) and teleost (ray fin fish); highly adapted dinoflagellate with similar life cycle and gross pathology as Ichthyophthirius multifiliis; primarily affects gills and can infect skin and eyes; diagnosis base on larger 50 to 350 µm trophonts
  • Piscinoodinium spp. (freshwater velvet disease, rust disease, gold dust disease, Pillularis disease, freshwater Oodinium): Freshwater analogue of Amyloodiniosis with same life cycle and gross pathology
• Fungal / Algae:
  • Saprolegniales (typical water mold infection, winter kill): One of the most common freshwater infections of fish (especially estuarine tropical fish); causes cottony, proliferative growth on the skin or gills
• Bacterial:
  • Epitheliocystis (Mucophilosis): Common gill disease of marine and freshwater fish; intracellular, Gram-negative, Chlamydia­-related bacteria that causes dermal and gill epithelial cell enlargement up to 400 µm in diameter
• Viral:
  • Lymphocystis disease (I-V15, piscine iridovirus): Similar gross appearance; variably sized, hypertrophied fibroblasts with basophilic intracytoplasmic inclusions on histology

REFERENCES:

1. Araújo BL, Serantoni Moyses CR, Spadacci-Morena DD, Xavier JG, Lallo MA. White spots amidst the gold: ultrastructural and histological aspects of the chronic inflammatory response of goldfish with ichthyophthiriasis. J Comp Pathol. 2024;211:21-25.
2. Frasca S, Wolf JC, Kinsel MJ, et al. Osteichthyes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsev

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