JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2025

I-M32

Signalment (JPC 2614951): Nine-year-old domestic shorthair cat

HISTORY: This cat had a swollen, soft, discolored footpad.

HISTOPATHOLOGIC DESCRIPTION: Skin, footpad: Infiltrating the dermis, separating and surrounding footpad adipose tissue and collagen bundles, and surrounding adjacent adnexa are multifocal to coalescing clusters of numerous plasma cells and fewer lymphocytes and neutrophils. Frequently, plasma cells contain numerous globular, eosinophilic, intracytoplasmic vacuoles (Russell bodies within Mott cells). There is increased dermal clear space separating collagen fibers as well as ectatic lymphatics (edema) that occasionally contain clusters of lymphocytes. There is mild multifocal increased intercellular clear space and accentuation of intercellular bridges (spongiosis).

MORPHOLOGIC DIAGNOSIS: Skin, footpad: Pododermatitis, plasmacytic, multifocal to coalescing, marked, domestic shorthair, feline.

CAUSE: Unknown

CONDITION: Feline plasma cell pododermatitis (“pillow foot”)

GENERAL DISCUSSION:

• Rare skin disease of cats; rarer in dogs
• No breed predilection, typically affects cats 6-months to 12-years of age, neutered males are possibly predisposed
• A minority of affected cats also have plasma cell stomatitis, immune-mediated glomerulonephritis, or renal amyloidosis; may have concurrent indolent ulcers or eosinophilic granulomas
• Both medical and surgical treatment is curative
• Recent report suggests this may be a predisposing factor for the formation of silica-associated (cat litter) granulomas in the paw (Agrawal et al., 2025).

PATHOGENESIS:

• Pathogenesis is unknown
• Likely a purely immune-mediated because of the following features:
  • Persistent hypergammaglobulinemia
  • Plasma cell infiltrate
  • Positive response to glucocorticoid and immunomodulatory (i.e. doxycycline) treatment
  • Immunohistochemistry and PCR studies have not revealed any infectious agents, though some cases are responsive to doxycycline treatment
• Recurrence in warm weather supports an allergenic origin

TYPICAL CLINICAL FINDINGS:

• Pain and associated lameness variable

TYPICAL GROSS FINDINGS:

• Gross appearance is diagnostic
• Commonly affects multiple pads on multiple feet; larger metacarpal and metatarsal pads are most commonly affected
• Uniform swelling with a doughy consistency on palpation that does not disturb normal pad architecture with web-like, cross-hatched appearance (“striae”) to the pad surface
• Ulceration is common

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Cutaneous lesions:

• Histologic features are diagnostic
• Early, superficial and deep plasmacytic vasculitis that progresses to diffuse dermal plasma cell infiltrate that obscures normal architecture
• Plasma cells containing Russell bodies (Mott cells) can be frequent
• Leukocytoclastic vasculitis is rare
• Epidermal acanthosis, erosion, or ulceration
• Variable number of neutrophils independent of ulceration
• Suppurative to pyogranulomatous inflammation secondary to ulceration/proliferation

Other lesions:

• +/- Renal lesions:
• Renal amyloidosis
• Immune complex glomerulonephritis with positive direct immunofluorescence indicating immunoglobulin deposits within the basement membrane zone
• +/- Oral lesions: Plasma cell stomatitis
• Secondary bacterial infection

ADDITIONAL DIAGNOSTIC TESTS:

• Cytology: Aspiration cytology reveals predominately plasma cells; in combination with classic clinical appearance, biopsy may not be necessary
• Serum immunoelectrophoresis: hypergammaglobulinemia
• Clinical pathology: Hypergammaglobulinemia; +/- positive antinuclear antibody (ANA), Coombs positive anemia, polyclonal gammopathy

DIFFERENTIAL DIAGNOSIS:

• Eosinophilic granuloma: Features eosinophils and collagen degradation; will not usually involve multiple foot pads
• Nocardiosis: Swelling of foot pads with pyogranulomatous inflammation
• Neoplasia: Eccrine carcinoma, metastatic pulmonary bronchioloalveolar carcinoma (multiple feet), plasmacytoma (typically only one foot)
• Infectious or sterile granuloma
• Foreign body
• Insect bites

REFERENCES:

1. Agrawal A, Garuba W, Dunn N, Rissi DR, Schneider SM, Sharma B, LoBato D. Cutaneous silica-associated (cat litter) granulomas in the paws of 13 domestic cats. Vet Pathol. 2025.
2. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Ltd. 2016:613-614.
3. Raskin RE, Conrado FO. Chapter 3: Integumentary System. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:43.
4. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1259-1260.

Click the slide to view.

---