Conference 14 - 2016 Case: 3 20170111

Signalment:

Nine-year-old, female, golden retriever, (Canis familiaris).The dog was brought to the clinic with a history of intermittent rectal prolapse. Clinical examination revealed a rectal mass (5 cm cranial from the anus), and the dog was referred to the surgical excision of the mass.

Gross Description:

Rectal mass: an oval 3x5 cm mass, on cross section light brown in color and firm consistency.

Histopathologic Description:

Rectum: Expanding the submucosa and elevating the overlying ulcerated mucosa is a well circumscribed, partially encapsulated, densely cellular neoplasm composed of sheets and packets of round cells separated by a fine fibrous stroma. Neoplastic cells have variably distinct cell borders and moderate amounts of eosinophilic granular cytoplasm. Nuclei are round, rarely oval, usually eccentrically located with finely stippled to finely clumped chromatin and usually one indistinct nucleolus. There is moderate anisokaryosis, multifocal karyo-megaly and a moderate number of multinucleate cells. Mitotic figures average 10 per 10 HPF. Multifocally between neoplastic cells or at the periphery of the tumor are variably sized and shaped, extracellular deposits of amorphous, homogenous, eosinophilic material (amyloid) with multifocal islands of cartilage formation (cartilaginous metaplasia) that is occasionally mineralized.

Morphologic Diagnosis:

>Rectum: Plasmacytoma (or Extramedullary Plasmacytoma), golden retriever, canine.

Lab Results:

Immunohisto-chemistry antibodies against CD 3, CD79 and MUM1 were applied. The tumor was CD79 and MUM1 positive, and CD3 negative. Congo red stain revealed amyloid deposits at the periphery of the tumor.

Condition:

Extramedullary plasmacytoma

Contributor Comment:

Extramedullary plasmacytoma (EMP) is a relatively common tumor in older dogs and occur most frequently on the skin and mucous membranes, but has been reported in other areas such as the brainstem, spinal cord, lymph nodes, abdominal viscera, genitalia, and eyes.^2,9

Plasmacytomas of the lower gastrointestinal tract are uncommon neoplasms in dogs, and rare in cats and other species. They are encountered most frequently in the submucosa of the distal colon and rectum of dogs, where they are associated with signs of large bowel diarrhea and bleeding⁵. Gastrointestinal EMP has also been reported in other sites, including the esophagus, stomach and small intestine.¹⁰

Histologically they resemble plasmacytomas of the skin, oral cavity or larynx. The tumor is formed by solid packets of pleomorphic round cells with various degrees of plasmacytoid maturation, especially at the periphery of the tumor. There is a frequent nuclear hyperchromasia and convolution. The cells are typically arranged in solid endocrine-like packets and there may be AL amyloid deposition among the tumor cells. The majority of the tumor growth is submucosal. A small proportion exhibit more aggressive behavior, including invasion of tunica muscularis, and some spread to regional lymph nodes and spleen.⁹ Canine EMP histological typing system has been established and is helpful diagnostic tool, although the types cannot be used for a tumor grading system.⁴

An unusual finding in plasmacytomas is the presence of cartilage and bone in close association with amyloid deposits. Meta-plastic bone and cartilage have been described in two canine intestinal EMPs⁵ and in human amyloidosis of tongue¹¹ and myelomas.¹ The exact pathogenesis of chondroid metaplasia in amyloidosis is not clearly described. Ramos Vara and colleagues hypothesized that in amyloidosis the inducing stimulus for bone formation is the amyloid deposits, with resultant stimulation of mesenchymal precursor cells to differentiate into cartilage- and bone-forming cells under the influence of soluble factors liberated by histiocytic and other cells.⁵

JPC Diagnosis:

Colon: Plasmacytoma, extramedullary, golden retriever, Canis familiaris.

Conference Comment:

The contributor provides a great example of a relatively common neoplasm in the skin or mucus membrane of dogs in an uncommon location within the abdominal viscera. Extra-medullary plasmacytomas of the lower gastrointestinal tract have been reported in dogs to occur most frequently in the submucosa of the distal colon and rectum, as in this case, and are considered a benign neoplastic proliferation of monoclonal B cells.⁹ Rectal and colonic plasmacytomas represent only 4% of all extramedullary plasmacytomas in dogs.⁶ Despite the uncommon location, conference participants identified solid packets of pleomorphic plasmacytoid round cells with a perinuclear clearing (Golgi complex) admixed with abundant homogenous smudgy material recognized as amyloid, commonly deposited in plasma cell tumors. The contributor confirmed the presence of amyloid via Congo-red staining and apple-green birefringence with polarized light. The conference moderator also pointed out the distinctive clumping pattern of the hetero-chromatin, giving the neoplastic cells the classic clock face histomorphology of plasma cells.⁹

The most striking feature of this case is the prominent streaks of amyloid within and surrounding the neoplasm, often admixed with foci of chondroid metaplasia. Amyloid is a proteinaceous substance composed of polypeptides arranged in beta-pleated sheets and is deposited in tissues in response to a number of pathogenic processes. Primary systemic or immunoglobulin associated amyloid (AL) is associated with light chains derived from plasma cells in monoclonal B cell proliferations of extramedullary plasmacytomas or multiple myelomas. The light chains are then converted to amyloid fibrils by proteolytic enzymes in macro-phages and deposited within tissues.⁸ As mentioned by the contributor, chondroid metaplasia has been uncommonly reported to occur with amyloidosis secondary to a variety of conditions, although the exact pathogenesis is currently unknown.^3,11

Another type of amyloid is formed secondary to a variety of chronic inflammatory conditions inciting excessive release of serum amyloid associated (AA) acute phase protein, predominantly by the liver under the influence of interleukin-6 (IL-6) and IL-1. AA is then deposited in multiple organs including the spleen, pancreas, intestinal lamina propria, lymph nodes, kidneys and liver.^7,8,9 Amyloid-beta (AB) has been found in cerebral plaques of aging humans and rhesus macaques and is associated with Alzheimers disease. Interestingly, neurofibrillary tangles, another feature of Alzheimers disease in humans, have not been found in aging rhesus macaques.⁷

References:

1. Karasick DV, Schweitzer ME, Miettinen M, OHara BJ. Osseous metaplasia associated with amyloid-producing plasmacytoma of bone: A report of two cases. Skeletal Radiol. 1996; 25:263267.
2. Jacobs JM, Messick JB, Valli VE. Lymphoid Tumors. In: Meuten DJ, ed. Tumors in Domestic Animals. 4^th ed. Iowa State Press; Blackwell Publishing; 2002: 163.
3. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. 2nd ed. Ames, IA: Blackwell; 2005: 870-871.
4. Platz SJ, Breuer W, Pfleghaar S, Minkus G, Hermanns W. Prognostic value of histopathological grading in canine extramedullary plasma-cytomas. Vet Pathol. 1999; 36: 23-27.
5. Ramos-Vara JA, Miller MA, Pace LW, Linke RP, Common RS, Watson GL. Intestinal multinodular AL deposition associated with extramedullary plasmacytoma in three dogs: Clinicopathological and immunohistochemical Studies. J Comp Path. 1998; 119: 239-249.
6. Rannou B, Helie P, Bedard C. Rectal plasmacytoma with intracellular hemosiderin in a dog. Vet Pathol. 2009; 46:1181-1184.
7. Simmons HA. Age-associated pathology in rhesus macaques (Macaca mulatta). Vet Pathol. 2016; 53(2):399-416.
8. Snyder PW. Diseases of immunity. In: McGavin MD, Zachary JF, ed. Pathologic Basis of Veterinary Disease, 6th ed. St Louis, MO: Elsevier Mosby; 2017:285.
9. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. 6th ed. Vol 2. St. Louis, MO: Elsevier; 2016:109.
10. Vail DM. Plasma Cell Neoplasms. In: Withrow SJ, Vail DM, eds. Small Animal Clinical Oncology. 4^th ed. Philadelphia, PA: Elsevier Saunders; 2007: 769-784.
11. Vasudevan JA, Somanathan T, Patil SA, Kattoor J. Primary systemic amyloidosis of tongue with chondroid metaplasia. J Oral Maxillofac Pathol. 2013; 17(2): 266-268.