JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2021
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 and cords of round cells on a fine fibrovascular stroma.  Neoplastic cells have variably 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 10 HPF (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, and colorectal mucosa in dogs
• 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:

• Usually solitary, red, raised, smooth, rapidly growing nodules up to 5cm that may protrude into the lumen

 

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;
  • Recent report of cutaneous/mucocutaneous plasmacytomas with atypical histomorphology in dogs; neoplastic cells arranged in pseudoglandular structures with a central lumen resembling acini/epithelial neoplasia; neoplastic cells were strongly immunoreactive for MUM-1 and immunonegative for pancytokeratin AE1/AE3 (McHale, J Vet Diagn Invest. 2018)

 

ULTRASTRUCTURE: 

• Plasma cells have oval or round eccentric nuclei with marginated chromatin (clock-face nuclei), prominent rough endoplasmic reticulum (Golgi complex), and intracytoplasmic filaments (likely represent immunoglobulin)

 

ADDITIONAL DIAGNOSTIC TESTS:

• Immunohistochemistry:
  • Low Ki67 index
  • Mum-1/IRF4 is particularly sensitive and specific for plasma cell neoplasms; other immunolabels include CD79a, CD20, and CD45RA (Ehrensing, J Vet Diagn Invest, 2018)
  • Neoplastic cells are monoclonal for IgG, IgM, or IgA and for either lambda or kappa light chain; IgG and lambda light chain most common
• Amyloid (if present) is confirmed with Congo red or thioflavin T stains

 

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

• Plasma cell leukemia: Rare; recent report of a dog with primary plasma cell leukemia with plasmablastic morphology, plasmablasts comprised >20% of the circulating cells (Dagher, J Vet Diagn Invest, 2019)

 

COMPARATIVE PATHOLOGY:

• EMP has been reported in the cat (increased incidence in older males), horse, sheep, African hedgehog, Syrian hamster, mule deer
• A recent study evaluated the significance of intravascular neoplastic cells in 134 cutaneous plasmacytomas in 125 dogs; intravascular neoplastic cells were present in 16% of the patients but did not have a negative impact on prognosis (Ehrensing, J Vet Diagn Invest. 2018)
• Cats: Feline respiratory extramedullary plasmacytoma has been reported in numerous respiratory locations (frontal sinus, nasal cavity, soft palate larynx, trachea, lungs); patients had metastasis to multiple lymph nodes; there was granulomatous inflammation with extensive intrahistiocytic and extracellular amyloid (AL); neoplastic cells were immunoreactive for CD79a and MUM1- (Sykes, J Comp Pathol. 2017)
• 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. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley & Sons; 2016: 110, 186.
3. 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.
4. Clancy CS, Roug A, Armien AG, Van Wettere AJ. Intracerebral malignant plasmacytoma in a mule deer (Odocoileus hemionus). J Comp Pathol. 2016; 154:268-271.
5. Dagher E, Soetart N, Chocteau F, et al. Plasma cell leukemia with plasmablastic morphology in a dog. J Vet Diag Invest. 2019; 31(6)868-874.
6. Ehrensing G, Craig LE. Intravascular neoplastic cells in canine cutaneous plasmacytomas. J Vet Diag Invest. 2018; 30(2):329-332.
7. 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.
8. McHale B, Blas-Machado U, Oliveira FN, Rissi DR. A divergent pseudoglandular configuration of cutaneous plasmacytoma in dogs. J Vet Diag Invest. 2018; 30(2): 260-262.
9. 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.
10. Sykes SE, Byfield V, Sullivan L, et al. Feline respiratory extramedullary plasmacytoma with lymph node metastasis and intrahistiocytic amyloid. J Comp Pathol. 2017; 156:173-177.
11. 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.
12. 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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