JPC SYSTEMIC PATHOLOGY
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 separated by a fine network of capillaries. Neoplastic cells have variably distinct cell borders and moderate amounts of eosinophilic, granular cytoplasm. Nuclei are eccentrically located, irregularly round to oval, occasionally indented with finely clumped chromatin and have one variably prominent nucleolus. Nuclei often contain cytoplasmic invaginations. There is moderate anisocytosis and anisokaryosis with occasional megalokaryosis and rare binucleate cells. Mitotic figures average 3 per 10 HPF. Admixed with neoplastic cells are multiple foci of hemorrhage, fibrin, edema and fibrosis, and single cell necrosis. The overlying mucosa is eroded with multifocal dilated crypts and a focally extensive area (5mm) of ulceration that is replaced by hemorrhage, fibrin, and edema and many neutrophils. Multifocally, the lamina propria is expanded by moderate numbers of plasma cells and neutrophils along with mild hemorrhage, fibrin, and edema. Adjacent submucosa contains hemorrhage, fibrin, and edema with moderate numbers of plasma cells, fewer lymphocytes and hemosiderin-laden macrophages, and rare neutrophils.
MORPHOLOGIC DIAGNOSIS: Rectum: Plasmacytoma, mixed breed dog, canine.
CONDITION: Extramedullary plasmacytoma (EMP)
SYNONYM: Plasma cell tumor; Plasmacytoma
- Extramedullary plasmacytomas (EMP) are benign neoplasms of older dogs (rarely cats), with a low Ki67 index; complete surgical excision is curative.
- EMP a single tumor without paraproteinemia; Multiple myeloma (MM) is in bone marrow, has multiple osteolytic lesions, and paraproteinemia present
- Malignant variants occur but incidence is <10%
- EMPs 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, cocker spaniels; increased incidence in older male cats
- Cutaneous EMPs in dogs and cats have three morphologic subtypes: lymphoid, histiocytic, and pleomorphic. This classification has not been applied to intestinal EMPs
TYPICAL CLINICAL FINDINGS:
- Hematochezia, tenesmus, and rectal prolapse may be reported
- Rarely causes GI obstruction
TYPICAL GROSS FINDINGS:
- Usually solitary, red, raised and smooth, rapidly growing nodules that may protrude into the lumen
- Up to 5cm in size
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Well circumscribed, unencapsulated mass within the submucosa, usually not affecting the overlying mucosa
- Densely cellular
- Can see well-differentiated to pleomorphic cells within the same neoplasm.
- Variable amounts of eosinophilic, granular cytoplasm; more differentiated cells may have perinuclear clear zone (Golgi complex) and amphophilic cytoplasm
- Arranged in cords and single files with a fine reticular stromal network of capillaries separating the neoplastic cells; sometimes are vaguely packeted by a fine, fibrovascular stroma
- Binucleate, multinucleate and karyomegalic cells are frequent
- Nuclei are round to oval, eccentrically placed, and often indented
- Variable chromatin pattern; more differentiated cells at periphery with a "clock-face" pattern
- One or more prominent nucleoli
- Mitotic rate is usually low (0-1/HPF)
- Occasional Russell bodies: Large intracytoplasmic eosinophilic globules of immunoglobulin
- Submucosal, perivascular, and intracellular amyloid (lambda light chains) is rarely present; often find macrophages and foreign-body giant cells associated with amyloid
Features of plasma cells:
- 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:
- Mum-1/IRF4 is particularly sensitive and specific for plasma cell neoplasms
- Other labels include CD79a, CD20, and CD45RA
- Frequently are vimentin positive
- IHC indicates the tumor 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
- Plasma cell hyperplasia: Seen with chronic diseases such as canine leishmaniasis; mixed cell population, no mass affect
- Mast cell tumor: Positive for Toluidine blue, Giemsa, and Luna Mast
- Melanoma: Staining of melanin granules for S-l00 protein, Melan-A and Fontana-Masson
- 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 see an infrequent monoclonal gammopathy with canine ehrlichiosis).
- Anemia: Due to (1) myelophthisis or (2) relative blood dilution due to increased plasma oncotic pressure or (3) shortened RBC lifespan due to their coating with a paraprotein resulting in subsequent phagocytosis by macrophages
- Thrombocytopenia and neutropenia also develop with progressive myelophthisis
- Hypercalcemia due to the production of an osteoclast – activating factor
- May observe: Renal disease, hyperviscosity, and compensatory hyperglobulinemia
- Two of the following four criteria are required for diagnosis:
- Radiographic evidence of osteolysis
- Plasma cells in the bone marrow; 15-20 %
- Monoclonal gammopathy
- 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
- Electrophoresis: observe a narrow- based discrete band or peak, in the “beta” or “gamma” regions
- Has been reported in the cat, horse, sheep, African hedgehog, Syrian hamster, mule deer
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- Ehrensing G, Craig LE. Intravascular neoplastic cells in canine cutaneous plasmacytomas. J Vet Diag Invest. 2018; 30(2):329-332.
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- Sykes SE, Byfield V, Sullivan L, et al. Feline respiratory extramedullary plasmacytoma with lymph node metastasis and intrahistiocytic amyloid. J Comp Path. 2017; 156:173-177.
- 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.
- 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.