JPC SYSTEMIC PATHOLOGY
Signalment (JPC # 2731574): Age and breed unspecified dog
HISTORY: Solitary dermal mass protruding from the lip
HISTOPATHOLOGIC DESCRIPTION: SLIDE A: Haired skin, lip: Expanding the dermis, compressing surrounding dermal collagen and adnexa, elevating the overlying minimally hyperplastic epidermis, and extending to a single deep border is an unencapsulated, well demarcated, densely cellular neoplasm which is separated from the overlying epidermis by a narrow zone of dermal collagen which is devoid of neoplastic cells (Grenz zone). The neoplasm is composed of round cells arranged in sheets, nests and packets separated by a fine fibrovascular stroma. Neoplastic cells have variably distinct cell borders and moderate amounts of eosinophilic, granular cytoplasm, and toward the periphery of the neoplasm, few cells have a perinuclear pale area (hof). Nuclei are irregularly round with variability in chromatin pattern, which range from finely stippled to dense with one usually indistinct nucleolus. Mitotic figures average 1 per HPF. Within the neoplasm, there is mild anisokaryosis, few scattered multinucleate cells with up to 5 nuclei, occasional single cell necrosis, and few foci of hemorrhage. Within the superficial dermis there is minimal pigmentary incontinence and few scattered lymphocytes.
MORPHOLOGIC DIAGNOSIS: Haired skin, lip: Plasmacytoma, breed unspecified, canine
Signalment (JPC #4076145): Husky, age unspecified.
HISTORY: Mass, right mandible near lip
HISTOPATHOLOGIC DESCRIPTION: SLIDE B: Expanding the dermis and compressing adnexa, elevating the epidermis, and extending into the subcutis and to cut borders is an unencapsulated, well-demarcated, poorly circumscribed, moderately cellular neoplasm composed of round cells arranged in sheets on a fine fibrovascular stroma, surrounded and separated by lakes of amorphous, smudgy, extracellular eosinophilic material (amyloid). Neoplastic cells have distinct cell borders, a moderate amount of eosinophilic, often vacuolated cytoplasm which often contains a perinuclear pale area (hof), a round to irregular shaped nucleus with coarsely stippled chromatin and 1-2 indistinct nucleoli. Anisocytosis and anisokaryosis are moderate; mitoses average 3 per 10 HPF. 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. The neoplasm is separated from the epidermis by a prominent area of dermal collagen measuring up to 200 um (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.
SLIDE C (Congo red): Lakes of eosinophilic, amorphous extracellular material diffusely stain orange-red (congophilic), and exhibit apple-green birefringence under polarized light (amyloid).
MORPHOLOGIC DIAGNOSIS: Haired skin, subcutis and skeletal muscle, right mandible near lip: Plasmacytoma, with amyloid, husky, canine.
CONDITION: Cutaneous extramedullary plasmacytoma (EMP); Plasma cell tumor
- 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: 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
- Associated with areas of chronic immune cell stimulation: Gingiva (periodontal disease); pinna (otitis externa); chin and paws (chronic allergic dermatitis)
- May be associated with chronic, prolonged B-cell recruitment and cytokine stimulation, particularly in gingiva (periodontal disease), pinna (otitis externa), and chin and paw pads (chronic allergic dermatitis)
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
- Although rare, they have been reported in aged cats
- Surgical excision is curative; local recurrence and metastases are rare
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 and packed nests
- 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 course 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 chondrous metaplasia can develop in the deposited amyloid
- 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:
- Positive on immunohistochemistry for vimentin, CD79a, CD20, CD18, immunoglobulin kappa light chains, MUM1/IRF4
- Most amyloid stains with thioflavine-T
- Methyl green pyronine stains cytoplasmic ribonucleic acid magenta
Gross: Similar to benign cutaneous histiocytoma
- Amelanotic epithelioid melanoma: Finely granular pale cytoplasm, prominent nucleoli, junctional activity, and positive Fontana-Masson or S-100 stain
- Histiocytoma: Cords of cells perpendicular to skin surface, lymphocytic infiltrates, no tumor giant cells
- Mast cell tumor: Granular cytoplasm, stromal collagen, positive toluidine blue and Giemsa, granules stain orange-brown with methyl green pyronine
- Cutaneous lymphoma: Rare, most often multiple, recur after surgical excision
- Reported in cats as occurring in the skin, gastrointestinal tract, retroperitoneal space, upper lip, gingival, orbit, and cerebrum
- One report in sheep
- Two cases of extramedullary plasmacytoma in the salivary gland of 2 Syrian hamsters
- One report of an intracerebral plasmacytoma in a mule deer
- Clancy CS, Roug A, Armien AG, Van Wettere AJ. Intracerebral malignant plasmacytoma in a mule deer. J Comp Pathol. 2016;154(2-3):268-71.
- Goldschmidt MH, Hendrick MJ. Tumors of the skin and soft tissues. In: Meuten DJ, ed. Tumors in Domestic Animals. 4th ed. Ames, IA: Iowa State Press; 2002: 113-115.
- Greenberg MJ, Schatzberg SJ, deLahunta A, Stokol T, Summers BA. Intracerebral plasma cell tumor in a cat: A case report and literature review. J Vet Intern Med. 2004;18:581-585.
- Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat, Clinical and Histopathologic Diagnosis. 2nd ed. Oxford, UK: Blackwell Science; 2005:866-872.
- Majzoub M, Breuer W, Platz SJ, Linke RP, Hermanns W. Histopathologic and immunophenotypic characterization of extramedullary plasmacytomas in nine cats. Vet Pathol. 2003;40:249-253.
- Platz SJ, Breuer W, Pfleghaar S, Minkus G, Hermanns W. Prognostic value of histopathological grading in canine extramedullary plasmacytomas. Vet Pathol. 1999;36: 23-27.
- Ramos-Vara JA, Miller MA, Valli VEO. Immunohistochemical detection of multiple myeloma 1/interferon regulatory factor 4 (MUM1IRF-4) in canine plasmacytoma: comparison with CD79a and CD20. Vet Pathol. 2007;44:875-884.
- Valli VE, Jacobs RM, Parodi AL, Vernau W, Moore PF. WHO Histological Classification of Hematopoietic Tumors of Domestic Animals, 2nd series, vol. VIII. Washington, DC: Armed Forces Institute of Pathology; 2002: 34-35.
- 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: 226-8.
- Wettere AJ, Linder KE, Suter SE, Olby NJ. Solitary intracerebral plasmacytoma in a dog: Microscopic, immunohistochemical, and molecular features. Vet Pathol. 2009;46:949-951.