JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2025

I-N23B

SLIDE A

Signalment (JPC # 2731574): Age and breed unspecified dog

HISTORY: Solitary dermal mass protruding from the lip

HISTOPATHOLOGIC DESCRIPTION: Haired skin, lip (per contributor): Expanding the dermis, compressing surrounding dermal collagen and adnexa, elevating the overlying minimally hyperplastic and hyperkeratotic epidermis, and extending to the deep border is an unencapsulated, well demarcated, densely cellular neoplasm which is separated from the overlying epidermis by a narrow zone of dermal collagen devoid of neoplastic cells (Grenz zone). The neoplasm is composed of round cells arranged in sheets and indistinct nests and packets on a preexisting collagenous stroma. Neoplastic cells have variably distinct cell borders and moderate amounts of eosinophilic, granular cytoplasm. Occasional cells, often toward the periphery of the neoplasm, have a pale perinuclear hof (Golgi zone). Nuclei are irregular with finely stippled to dense chromatin with one variably prominent nucleolus. Anisocytosis and anisokaryosis is moderate. Mitotic figures average 1 per HPF. There are few scattered multinucleate neoplastic cells with up to 5 nuclei, occasional single cell necrosis, and few foci of hemorrhage, fibrin, and edema. Within the superficial dermis there is minimal pigmentary incontinence and few scattered lymphocytes.

MORPHOLOGIC DIAGNOSIS: Haired skin: Plasmacytoma, breed unspecified, canine

SLIDE B

Signalment (JPC #4076145): 12yo F/S Husky.

HISTORY: Mass, right mandible near lip

HISTOPATHOLOGIC DESCRIPTION: Haired skin, lip (per contributor): Expanding the dermis, compressing adnexa, elevating the epidermis, and extending into the subcutis and to surgical margins is an unencapsulated, well-demarcated, poorly circumscribed, moderately cellular neoplasm composed of round cells arranged in sheets on a preexisting collagenous stroma, surrounded and separated by lakes of amorphous, smudgy, extracellular, eosinophilic hyaline material (amyloid). Neoplastic cells have distinct cell borders, a moderate amount of eosinophilic cytoplasm which often contains a pale perinuclear hof (Golgi zone), and a round to irregular nucleus with coarsely stippled chromatin and 1-3 variably prominent nucleoli. Anisocytosis and anisokaryosis are moderate; mitoses average 3 per 2.37 mm². There are occasional multinucleated neoplastic cells with up to 3 nuclei, and rare intranuclear cytoplasmic invagination. Within the neoplasm are multifocal infiltrates of lymphocytes and areas of hemorrhage, fibrin, and edema. There are scattered macrophages that contain granular brown intracytoplasmic pigment (hemosiderin). The neoplasm is separated from the epidermis by a broad, up to 200µm wide, dermal band devoid of neoplastic cells (Grenz zone). Within and surrounding the lakes of amyloid are infiltrates of epithelioid macrophages and multinucleated giant cells with up to 27 nuclei, both Langhans type with peripheral nuclei and foreign body type with central nuclei.

Congo red: Lakes of eosinophilic, amorphous extracellular material are diffusely orange-red (congophilic), and exhibit apple-green birefringence under polarized light (amyloid).

MUM1: Within the external control (canine lymph node) there is moderate, multifocal, intranuclear immunoreactivity of paracortical and medullary plasma cells. Within the section of interest, there are occasional non-neoplastic plasma cells within the dermis with moderate intranuclear immunoreactivity (internal control). Neoplastic cells demonstrate diffuse, strong intranuclear immunoreactivity.

MORPHOLOGIC DIAGNOSIS: Haired skin, lip: Plasmacytoma with amyloid, husky, canine.

SYNONYMS: Cutaneous extramedullary plasmacytoma (EMP); Plasma cell tumor

GENERAL DISCUSSION:

• Cutaneous extramedullary plasmactyomas occur commonly in the dermis of middle aged or older dogs, and are rare in cats
• Originate from variably differentiated plasma cells
• Plasmacytic tumors:
  • Extramedullary plasmacytomas (D-N10): Solitary or rarely multiple tumors arising in soft tissues
  • Solitary osseous plasmacytoma: Single tumor arising in bone
  • Multiple myeloma: Involving bone marrow of multiple bones, plasma cells comprise over 30% of marrow, monoclonal gammopathy, Bence-Jones proteinuria, radiographic evidence of osteolysis
• Extramedullary plasmactyoma, especially in the oral cavity and the skin, tend to be benign; whereas, osseous lesions tend to progress to systemic multiple myeloma
• Extramedullary plasmactyoma of the esophagus, stomach, intestine, and rectal area tend to be more aggressive lesions that metastasize to regional lymph nodes
• Rarely, cutaneous plasmacytomas may precede or be present simultaneously with multiple myeloma
• Attempts have been made to develop grading systems, but are of little prognostic value

PATHOGENESIS:

• Unknown
• Amyloid is a pathogenic proteinaceous substance composed of polypeptides arranged in beta-pleated sheets; amyloid associated with plasma cell tumors is AL, amyloid light chain; derived from plasma cells; contains immunoglobulin light chains (either λ light chains or κ light chains)

TYPICAL CLINICAL FINDINGS:

• Average age of dogs is 10 years with no sex predilection; Cocker Spaniels may be predisposed
• Commonly present on digits, around the mouth (lips and chin), and ears
• Solitary; may be polypoid when associated with the ear canal; rarely multiple
• Tumors of digits are often ulcerated and hemorrhagic
• Surgical excision is curative; local recurrence and metastases are rare
• Bence-Jones proteinuria with multiple myeloma
• Hyperviscosity syndrome with high [Ig]
• Monoclonal gammopathy (narrow globulin spike on serum protein electrophoresis)

TYPICAL GROSS FINDINGS:

• Tumors are usually 1 to 2 cm, raised, smooth, well circumscribed, firm to soft, and pink to red

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Round cells arranged in sheets
• Cells are either well differentiated or atypical and pleomorphic
• Some cells may retain a Golgi zone or perinuclear hof
• Nuclei are round or crescentic (helmet cells), often eccentrically placed and vesiculate, with coarse chromatin forming a “clockface” pattern or finely stippled/hyperchromatic
• Approximately 10% may contain amyloid, more frequently found in feline EMP, which is often accompanied by granulomatous inflammation; occasionally, multifocal cartilaginous metaplasia can develop in the deposited amyloid

ULTRASTRUCTURAL FINDINGS:

• Oval to round, eccentric nucleus with marginated chromatin described as “cartwheel” or “clockface”
• Ample cytoplasm with abundant rough endoplasmic reticulum and a well-developed perinuclear Golgi apparatus

ADDITIONAL DIAGNOSTIC TESTS:

• Cytology: Aspirates tend to be moderately to highly cellular with discrete round cells that have abundant blue cytoplasm that may have a perinuclear clearing (golgi zone), a large, round nucleus, which is typically eccentric, chromatin is coarsely reticulated to stippled, and indistinct nucleoli; moderate anisocytosis and anisokaryosis, binucleate and multinucleate cells are typically found; may have an extracellular pink fibrillar material (amyloid); rarely rod-shaped to spiculated granules in the tumor cells
• Immunohistochemistry: Plasma cells are immunoreactive for: vimentin, CD79a, CD20, CD18, IHC or CISH for lambda/kappa light chains, MUM1/IRF4
  • Combination of IHCs for MUM1 and Ig light chains has superior sensitivity for diagnosing plasmacytomas compared to a combination of MUM1 and CD79 (Santos et al., 2025)
• Most normal and neoplastic plasma cells are lambda light chain positive (9:1 lambda to kappa)
• Can often be positive for Melan-A Red (need additional IHCs to differentiate from amelanotic melanocytic neoplasms) (Schuwerk et al., 2024)

• Histochemistry:
  • Amyloid stains with Congo red (congophilic)
  • Most amyloid stains with thioflavine-T, a fluorescent dye
  • Methyl green pyronine stains cytoplasmic ribonucleic acid magenta

DIFFERENTIAL DIAGNOSIS:

• Gross: Similar to canine cutaneous histiocytoma (I-N22)
• Microscopic:
  • Amelanotic epithelioid melanoma (I-N24): Finely granular, pale cytoplasm; prominent nucleoli; junctional activity; and positive Fontana-Masson, Melan-A, and/or S-100 stains; can also be positive for MUM1 (Mendes et al., 2024; Schuwerk et al., 2024)
  • Histiocytoma (I-N22): Cords of cells perpendicular to skin surface, lymphocytic infiltrates, no tumor giant cells
  • Mast cell tumor (I-N21): Granular cytoplasm, stromal collagen, positive toluidine blue and Giemsa, granules stain orange-brown with methyl green pyronine
  • Cutaneous lymphoma (I-N25, I-N26): Rare, most often multiple, recur after surgical excision

COMPARATIVE PATHOLOGY:

• Feline myeloma-related disorders (8): including cutaneous extramedullary plasmacytoma, multiple myeloma, noncutaneous extramedullary plasmacytoma, solitary plasmacytoma of bone, IgM macroglobulinemia, immunoglobulin-secreting lymphoma, immunoglobulin-secreting leukemia, and plasma cell leukemia
  • Periarticular plasma cell tumors in cats can have low cellularity, abundant amyloid, and more aggressive behavior (Craig; Vet Pathol; 2022)
• Psittacine birds get round cell tumors, of 38 studied cases: B-cell lymphoma 50%, T-cell lymphoma 16%, Plasma cell tumor 8%, B-and T- cell IHC markers 8% (Gibson, Vet Pathol 2021)
• Rarely erythrophagocytic multiple myeloma (Romanelli; J Vet Diagn Invest; 2022) and laryngotracheal plasma cell tumors (Mulka et al, 2025) are reported
• Plasmacytomas reported in Chinook salmon, collared peccary (extramedullary plasmacytoma), suids
• Inducible tumor of mice with pristane injection, retrovirus infection, or in BALB/c and NZB strains of mice
• Hamsters: develop ascites with plasmacytomas
• Rhesus macaque: plasmacytomas are accompanied by anemia

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016:110, 186.
2. Craig LE, Lieske DE. Periarticular plasma cell tumors in cats. Vet Pathol. 2022;59(2):264-268.
3. Durham AC, Boes KM. Bone marrow, blood cells, and the lymphoid/lymphatic system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:842-843, 869.
4. 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; 2020:90-91.
5. Gibson DJ, Nemeth NM, Beaufrère H, Varga C, Garner MM, Susta L. Lymphoma in Psittacine Birds: A Histological and Immunohistochemical Assessment. Vet Pathol. 2021;58(4):663-673.
6. Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier Saunders; 2015:256-262.
7. 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; 2016:735.
8. Mendes RE, Tolbert RH, Thorn CE, Rissi DR. Dermal melanoma with plasmacytoid differentiation in a dog. J Vet Diagn Invest. 2024 Nov;36(6):941-944.
9. Mulka KR, Gillette D, Durham AC, Mauldin EA. Canine laryngotracheal plasma cell tumors: Ten cases and literature review. Vet Pathol. 2025.
10. Raskin RE, Conrado FO. Integumentary system. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:108-112.
11. Romanelli P, Recordati C, Rigamonti P, Bertazzolo W. Erythrophagocytic multiple myeloma in a dog. J Vet Diagn Invest. 2022;34(4):718-722.
12. Santos BBN, Peixoto PV, Peleteiro MC, Rissi DR, Carvalho S, França TN. Histologic spectrum of canine extramedullary plasmacytomas: Diagnostic challenges and immunohistochemical differentiation from cutaneous histiocytomas. Vet Pathol. 2025
13. Schuwerk L, Ulianytska A, Baumgärtner W, Reineking W. Melan-A immunolabeling in canine extramedullary plasmacytomas. Veterinary Pathology. 2024;61(6):904-911.
14. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013: 383-385.
15. Terio KA, Mcaloose D, Leger JS, et al. Suidae and Tayassuidae. In: Pathology of Wildlife and Zoo Animals. Saint Louis: Elsevier Science & Technology; 2018:209, 226.
16. Terio K, Mcaloose D, Leger J, et al. Osteichthyes. In: Pathology of Wildlife and Zoo Animals. Saint Louis, MO: Elsevier Science & Technology; 2018:965.
17. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6^th ed. St. Louis, MO: Elsevier; 2016:27-28.
18. Valli VEO, Kiupel M, Bienzle D. Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:226-228.

Click the slide to view.

---