JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

D-N10 (NP)

 

Signalment (JPC #2749934): 9-year-old mixed breed dog

 

HISTORY: Rectal mass 

 

HISTOPATHOLOGIC DESCRIPTION: Rectum: Expanding the submucosa and elevating the overlying ulcerated mucosa is a 1 cm diameter, unencapsulated, well-circumscribed, densely cellular neoplasm composed of sheets, packets and cords of round cells on a fine fibrovascular stroma. Neoplastic cells have distinct cell borders and a moderate amount of eosinophilic, granular cytoplasm. Nuclei are eccentrically located, irregularly round to oval, and occasionally indented, with finely clumped chromatin and one variably prominent nucleolus. Nuclei often contain cytoplasmic invaginations. There is moderate anisocytosis and anisokaryosis with occasional megalokaryosis and rare binucleate cells, and occasional single cell necrosis/death. The mitotic count averages 5 per 2.37mm². Within the neoplasm are multiple foci of hemorrhage, fibrin, edema, and fibrosis. The overlying mucosa is focally extensively (5-6mm) ulcerated with replacement by hemorrhage, fibrin, edema, and many neutrophils, is multifocally eroded, and there are multifocal dilated crypts. Multifocally, the lamina propria is expanded by moderate numbers of plasma cells and neutrophils, mild hemorrhage, fibrin, and edema. The submucosa contains hemorrhage, fibrin, edema, moderate numbers of plasma cells, fewer lymphocytes, hemosiderin-laden macrophages, and rare neutrophils.

 

MORPHOLOGIC DIAGNOSIS: Rectum: Plasmacytoma, mixed breed, canine.

 

SYNONYM: Plasma cell tumor; Plasmacytoma; Extramedullary plasmacytoma (EMP)

 

GENERAL DISCUSSION:

• Extramedullary plasmacytomas (EMP) are benign neoplasms that occur in older dogs and rarely cats; complete surgical excision is curative
• EMP is a single tumor without paraproteinemia; multiple myeloma (MM) is in bone marrow, has multiple osteolytic lesions, and has paraproteinemia 
• Malignant variants occur but incidence is <10%; may widely metastasize
• EMPs are most common in the skin (digits and ears), oral cavity, lips, chin, and colorectal mucosa in dogs, though they can be found in other visceral organs as well
• Occur in middle aged to older dogs; no sex predilection; suspected predisposition in terrier breeds (Yorkshire, Airedale, Kerry blue, and Scottish), cocker spaniels, and standard poodles

 

TYPICAL CLINICAL FINDINGS:

• Hematochezia, tenesmus, and rectal prolapse may be reported
• Rarely causes GI obstruction

 

TYPICAL GROSS FINDINGS:

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Well circumscribed, unencapsulated mass within the submucosa, usually does not affect the overlying mucosa 
• Densely cellular, arranged in cords and single files separated by a fine reticular stromal network of capillaries; sometimes exhibit vague packeting
• Variable amount of eosinophilic, granular cytoplasm; more differentiated cells may have perinuclear clear zone (Golgi complex) and amphophilic cytoplasm
• Binucleate, multinucleate and karyomegalic cells are frequent; may have well-differentiated to pleomorphic cells within the same neoplasm
• Nuclei are round to oval, eccentrically placed, often indented, with a variable chromatin pattern; more differentiated cells have a "clock-face" chromatin pattern; one or more prominent nucleoli
• Mitotic rate is usually low (0-1/HPF [0.237mm²])
• Occasional Russell bodies: Large, intracytoplasmic, eosinophilic globules of immunoglobulin
• Rarely, amyloid (AL; lambda light chains) may be present; may be submucosal, perivascular, and/or intracellular; amyloid often has associated macrophages and foreign-body giant cells
• Cutaneous EMPs in dogs and cats have three morphologic subtypes: lymphoid, histiocytic, and pleomorphic; this classification has not been applied to intestinal EMPs 

 

ULTRASTRUCTURE: 

 

ADDITIONAL DIAGNOSTIC TESTS:

• Immunohistochemistry:
  • Low Ki67 index
  • Mum-1/IRF4 is particularly sensitive and specific for plasma cell neoplasms; a recent report has shown that plasma cell neoplasms can be positive for melan-A (Schuwerk, Vet Pathol, 2024)
  • Neoplastic cells are monoclonal for IgG, IgM, or IgA and for either lambda or kappa light chain; IgG and lambda light chain most common and has been recently been reported in a canine gastric plasmacytoma (Hanari, J Comp Pathol, 2021); chromogenic ISH for lambda or kappa light chain has been shown in a recent report to be a useful diagnostic tool to identify poorly differentiated plasma cell tumors (Foiani, J Vet Diagn Invest, 2020)
• Amyloid (if present) is confirmed with Congo red or thioflavin T stains
• Cytology

• Round cells with distinct cell borders, basophilic cytoplasm, and nuclei that are small, round, eccentrically positioned, and contain fine chromatin and indistinct nucleoli, +/- perinuclear clearing
• Anisocytosis/anisokaryosis is often prominent, binucleation in common, multinucleation can occur
• Amyloid (eosinophilic amorphous material) is present in about 10% of cases.
• Mott cells are not always present, but a recent report has shown that they can predominate in plasmacytomas (Auch, J Vet Diagn Invest, 2024)
• No cytoplasmic fragments (as would be seen in lymphomas)

 

DIFFERENTIAL DIAGNOSIS: 

• Plasma cell hyperplasia: Seen with chronic diseases such as canine leishmaniasis; mixed cell population, no mass affect
• Mast cell tumor: Metachromatic granules highlighted with Toluidine blue, Giemsa, and Luna Mast histochemical stains
• Melanoma: Melanocytes immunoreactive S-100 and Melan-A; melanin granules stain with Fontana-Masson histochemical stain
• Lymphoma (non-epitheliotrophic): Sheets and clusters of neoplastic lymphocytes; neoplastic cells are often intermingled with normal lymphocytes, plasma cells, and histiocytes
• Plasma cell myeloma (multiple myeloma):

• Hallmarks of disease: Hyperproteinemia, hyperglobulinemia, and monoclonal gammopathy (may also infrequently see monoclonal gammopathy with canine ehrlichiosis). 
• Two of the following four criteria are required for diagnosis:

• Radiographic evidence of osteolysis
• Plasma cells in the bone marrow comprising at least 15-20% of the sample
• Monoclonal gammopathy: electrophoresis reveals a narrow-based discrete band or peak, in the “beta” or “gamma” regions
• Bence-Jones proteinuria: Free immunologlobulin light chains (Bence Jones proteins) are smaller than albumin; readily pass through the glomerulus into the urine; their concentration is higher in the urine than in the serum 

• Anemia: Due to (1) myelophthisis, (2) relative blood dilution due to increased plasma oncotic pressure, or (3) shortened RBC lifespan due to coating with a paraprotein à phagocytosis by macrophages
• Thrombocytopenia and neutropenia due to progressive myelophthisis
• Hypercalcemia due to the production of an osteoclast-activating factor
• +/- renal disease, hyperviscosity, compensatory hypoalbuminemia

 

COMPARATIVE PATHOLOGY:

• EMP has been reported in the cat (increased incidence in older males), horse, sheep, African hedgehog, Syrian hamster, mule deer
• Cats: Periarticular plasma cell tumors have been recently reported (Craig, Vet Pathol, 2022); most commonly found in the tarsus, frequently associated with abundant amyloid, and the presence of this abundant amyloid appeared to be correlated with malignancy
• Mice: Plasmacytomas are rare, but can be readily induced with intraperitoneal injections of pristine (tumors of the peritoneum) in some strains (BALB/c, NZB, or F1 crossed mice), or by infection with acutely transforming retroviruses; may be common in some types of genetically engineered mouse models (GEMs)
• Hamsters: One report references transplantable ascites-plasmacytoma with Encephalitozoon infection 
• Pigs: Plasmacytomas are infrequently described in suids 
• Chinook salmon: Benign and malignant plasmacytomas/plasmacytoid leukemia reported

 

REFERENCES:

1. Ángeles Jiménez Martínez M, Gasper DJ, del Carmen Carmona Muciño M, Terio KA. Suidae and Tayassuidae. In: Terio KA, McAloose D, Judy St. Leger J, ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA Academic Press; 2018: 209.
2. Auch CL, Michael A. Cutaneous plasmacytoma with Mott cell differentiation in a dog. J Vet Diagn Invest. 2024;36(4):564-568. 
3. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley & Sons; 2016: 110, 186.
4. Boes KM, Durham AC. Bone marrow, blood cells, and the lymphoid/lymphatic system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:795. 
5. Craig LE, Lieske DE. Periarticular plasma cell tumors in cats. Vet Pathol. 2021;59(2):264-268.
6. 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; 2022:869.
7. Foiani G, Zanardello C, Carminato A, Melchiotti E, Roccabianca P, Tecilla M, Vascellari M. Chromogenic in situ hybridization for the detection of lambda and kappa immunoglobulin light chains as a potential auxiliary diagnostic technique in canine plasmacytomas. J Vet Diagn Invest. 2020.
8. Frasca, Jr. S, Wolf JC, Kinsel MJ, Camus AC, Lombardini ED. Osteichthyes. In: Terio KA, McAloose D, Judy St. Leger J, ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA Academic Press; 2018: 965.
9. Hanari N, Nagashima T, Machida Y, et al. Gastric Plasmacytoma with Immunoglobulin Lambda Light Chain Deposition in a Dog. J Comp Pathol. 2021;187:7-10.
10. Meinkoth JK, Cowell RK, Tyler RD. Cell Types and Criteria of Malignancy. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:28. 
11. Munday JS, Lohr CV, Kiupel M. Tumors of the alimentary tract. In: Meuten D, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: John Wiley & Sons; 2017:171-172, 218-225,577.
12. 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; 2022:108.
13. Schuwerk L, Ulianytska A, Baumgärtner W, Reineking W. Melan-A immunolabeling in canine extramedullary plasmacytomas. Vet Pathol. 2024: doi: 10.1177/03009858241246979. 
14. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:27-28. 
15. Valli VEO, Kiupel M, Bienzle D et al. 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.

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