History
A 16-year-old sexually intact male Cocker Spaniel was referred for fluoroscopy and esophagogastroduodenoscopy to investigate a 6-week history of ptyalism and regurgitation. Gastrointestinal tract obstruction was suspected.
Clinical, Gross, and Cytologic Findings
At the referral evaluation, the dog was responsive and in good body condition (body condition score, 5/9). Two orthogonal radiographic views obtained by the referring veterinarian revealed a radiodense, well-demarcated, space-occupying mass within the cranial aspect of the thorax at the level of the T2-T4 vertebrae. The dog was anesthetized to perform fluoroscopic and upper GI endoscopic examination. The presence of a 4.1 × 2.5 × 3.1-cm, well-demarcated, smooth contoured, pale-pink, broad-based, firm, and markedly vascularized mass protruding from the esophageal wall and markedly obstructing the lumen was confirmed (Figure 1). Laser ablation was performed during the endoscopic examination by means of a 10-W diode laser combined with high-frequency monopolar snare for extraction of larger mass fragments. After removal, fine-needle aspirate specimens of the mass were obtained for in-clinic cytologic examination. The aspirate specimens were moderately cellular with a predominant monomorphic population of round cells in a background containing moderate numbers of erythrocytes. Most round cells each had a moderately distinct cell border and a moderate amount of pale blue cytoplasm containing 1 eccentric, round, large nucleus. Binucleated and trinucleated cells were common. Anisokaryosis and anisocytosis were moderate to marked, and the nuclear-to-cytoplasmic ratio was usually high. Mitotic figures were also frequently observed. Samples of the mass were fixed in neutral-buffered 10% formalin and routinely processed for histologic examination.
Endoscopic view (A) and fine-needle aspirate specimen (B) of an esophageal mass in a 16-year-old Cocker Spaniel that had a history of chronic regurgitation and ptyalism. In the endoscopic view, a large, firm, pedunculated, pink, highly vascularized mass protrudes from the esophageal wall and obstructs the esophageal lumen. In the fine-needle aspirate specimen of the mass, notice a population of round cells that have moderate anisokaryosis and anisocytosis. Some multinucleated cells are visible, and a binucleated cell has 1 prominent mitotic figure. Rare inflammatory cells and erythrocytes form the cellular background. Romanowsky stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 257, 7; 10.2460/javma.257.7.719
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic Findings
Sections of the removed esophageal mass were examined microscopically. The submucosa was focally expansively effaced and replaced by a well-demarcated, unencapsulated, multilobulated, moderately cellular, highly vascularized, and infiltrative round cell neoplasm (Figure 2). Neoplastic cells were variably arranged in densely packed sheets or cords supported by a moderate amount of fibrovascular connective tissue that had occasional areas of hyalinization. Each cell had a moderately distinct cell border, a moderate amount of eosinophilic cytoplasm, and a large, irregularly round nucleus. Cell nuclei each had coarsely stippled chromatin and a magenta nucleolus. There were frequent binucleated cells and trinucleated cells; occasionally, very bizarre giant multinucleated cells were noted. Anisokaryosis and anisocytosis were moderate, and there were 6 mitoses in 10 hpf (400X). Scattered within the neoplasm were multifocal to coalescing lakes of brightly eosinophilic, homogeneous, extracellular, acellular material. Intermingled with the neoplastic cells were moderate numbers of hemosiderin-laden macrophages. Clusters of neoplastic cells infiltrated the surgical margins in all the planes examined.
Photomicrographs of sections of the firm mass removed from the dog in Figure 1. A—The submucosa is expanded by a monomorphic proliferation of plasma cells accompanied by large lakes of eosinophilic material. H&E stain; bar = 100 μm. B—In the section next in series from that in panel A, notice that much of the extracellular material is congophilic, consistent with amyloid. Congo red stain; bar = 100 μm. Inset—Under polarized light, the extracellular material has apple-green birefringence; bar = 50 μm. C—In this section, notice the monomorphic population of plasma cells. Moderate anisokaryosis and anisocytosis, multinucleated cells, and mitoses (arrowheads) are present. H&E stain; bar = 20 μm. D—The cytoplasm of neoplastic plasma cells is diffusely and strongly positive for CD79α. Anti-CD79α immunohistochemical reaction with hematoxylin counterstain; bar = 20 μm. Inset—The cytoplasm of the neoplastic plasma cells and the amyloid are diffusely and strongly positive for λ light chain. Anti-λ light chain immunohistochemical reaction with hematoxylin counterstain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 257, 7; 10.2460/javma.257.7.719
Congo red staining of additional tissue sections revealed that the extracellular material was congophilic with apple-green birefringence under polarized light. The overlying mucosa was focally ulcerated, and the superficial blood vessels were multifocally markedly dilated and congested. Immunohistochemical analysis of tissue sections revealed that the neoplastic cells were diffusely and strongly positive for CD79α and λ light chain and negative for CD20, CD3, and κ chain. Findings of serum protein electrophoresis, hematologic and serum biochemical analyses, and urinalysis were within reference limits. Assessment of multiple radiographic views of the axial and appendicular bones revealed no abnormalities. A subtotal excision of the esophageal mass was achieved, which cleared the esophageal lumen and provided total remission of the clinical signs. At 30 days after surgery, endoscopic examination revealed that the esophageal mucosa was healed although there was a focal area of elevation of the mucosa, which was macroscopically consistent with recurrence of the mass. The owner declined follow-up examination of the dog at 60 days after surgery, but the dog was presented at 180 days after surgery because of recurrence of the clinical signs. Endoscopy confirmed the presence of a mass of similar appearance and size as that of the removed mass at the site of the previous excision. The owner declined resection of the mass by thoracotomy, and the dog underwent endoscopic resection. The dog developed ventricular arrhythmias and was euthanized 5 days after the second endoscopic resection. Postmortem examination of the dog was not permitted.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: primary, extramedullary plasmacytoma (EP) with marked amyloidosis and focally severe esophageal ulceration.
Case summary: esophageal plasmacytoma in a dog.
Comments
Plasmacytoma is a relatively common, extranodal lymphoid neoplasm of differentiated B cells that is characterized by production of a particular immunoglobulin light chain. Two other neoplastic entities, plasmablastic lymphoma and lymphoplasmacytic lymphoma, which involve plasma cell differentiation and affect lymph nodes, organs, or both, are uncommon tumors in dogs and are associated with a poor prognosis.1 Multiple myeloma is a primary tumor of bone that involves clonal proliferation of malignant plasma cells arising from within the bone marrow and is associated with monoclonal gammopathy, hypercalcemia, and multiple painful, osteolytic lesions.2,3 Plasmacytomas are solitary masses and can originate within the bone marrow (solitary plasmacytoma of bone) or be extramedullary.4,5 Solitary plasmacytoma of bone frequently evolves toward multiple myeloma.4 Among dogs, extramedullary plasmacytomas typically develop in adults, and a predisposition among terriers, Cocker Spaniels, and Standard Poodles has been reported.5
Extramedullary plasmacytoma is primarily a tumor of the skin and the oral region; typically, it is benign and complete surgical excision is usually curative. Nevertheless, distant metastases from cutaneous and oral EPs have been reported.1,5 Within the gastrointestinal tract (excluding the oral cavity), EPs occasionally develop in the colon and rectum, followed in frequency by locations in the stomach and intestines.1 Colorectal EP is associated with hematochezia, intussusception, tenesmus, and rectal prolapse. However, complete excision of gastric and intestinal EPs is also considered curative.1,6 Extramedullary plasmacytomas are very rarely associated with monoclonal gammopathy or Bence-Jones proteinuria.1,4,5,7
Primary tumors of the esophagus are rare in dogs and may represent just 0.08% of all canine neoplasms.1 This prevalence (up to 0.8%) is much higher in tropical countries where Spirocerca lupi infestation is common. Spirocerca lupi–associated sarcomas are most commonly osteosarcomas (60%) followed by fibrosarcomas (35%); undifferentiated sarcomas also have been reported. Mesenchymal neoplasms in S lupi-negative dogs are also uncommon. Leiomyomas and leiomyosarcomas in dogs between 8 and 17 years old have been occasionally reported, but metastatic disease in S lupi-negative animals with leiomyosarcomas has not been documented.1 In domestic animals, epithelial esophageal neoplasms are much less common and in dogs they include squamous cell carcinoma and adenocarcinoma.1 In humans, only 5 esophageal EPs have been reported, and this is only the second case of an esophageal EP in the veterinary medical literature, to the authors’ knowledge.2,7–10 In contrast to the characteristics of esophageal EPs in humans7 and in the other reported canine case,9 the mass in the dog of the present report had large lakes of amyloid. In EPs, the amyloid is immunoglobulin derived (primary amyloidosis) and composed of λ light chains, and its production is an uncommon but helpful diagnostic feature.1,5 Extramedullary plasmacytomas have distinctive cytologic and histologic characteristics, and diagnosis of EPs is usually straightforward. Undifferentiated plasmacytomas may need to be differentiated from histiocytic sarcomas and other round cell tumors on the basis of the results of immunohistochemical testing with a panel of markers for CD79α, MUM1, λ light chain, κ light chain, and CD138 (results expected to be positive) and CD20 and CD3 (results expected to be negative).1,2,7,9 The dog with esophageal EP described in the previous report9 was cured following complete resection of the mass during thoracic surgery. However, this treatment option was not acceptable to the owner of the dog of the present report. The dog underwent endoscopic resection of the mass, and incomplete removal of the tumor resulted in its re-growth; a second endoscopic surgery was required, which presumably led to thermal injury to the vagus nerve and postoperative development of cardiac arrhythmias. Given the outcome in this case, treatment options other than those used for the dog of the present report should be considered for dogs with EPs of the esophagus.
Acknowledgments
This report was self-funded. The main author (ASB) was supported by a Clinical Training Scholarship (Residency) funded by the Horserace Betting Levy Board (HBLB) at the Royal Veterinary College. The authors thank Samanta da Silva Fonseca and Dr. Caroline Thaung of the University College London, Institute of Ophthalmology for technical assistance.
References
1. Munday JS, Löhr CV, Kiupel M. Tumors of the alimentary tract. In: Meuten DJ, ed. Tumors of domestic animals. 5th ed. Ames, Iowa: Wiley-Blackwell, 2017;499–601.
2. Rimmer C, Hazra A, Gulli VM, et al. Esophageal plasmacytoma diagnosed in a patient presenting with cardiac symptoms: a novel case. Case Rep Gastrointest Med 2013;2013:121670.
3. Thompson KG, Dittmer KE. Tumors of bone. In: Meuten DJ, ed. Tumors of domestic animals. 5th ed. Ames, Iowa: Wiley-Black well, 2017;412–414.
4. Adelman L, Larson V, Sissener T, et al. Extramedullary plasmacytoma in the lung of a Doberman Pinscher dog. Can Vet J 2014;55:1237–1240.
5. Gross TL, Ihrke PJ, Walder EJ, et al. Lymphocytic tumors. In: Gross TL, Ihrke PJ, Walder EJ, et al., eds. Skin diseases of the dog and cat. 2nd ed. Ames, Iowa: Blackwell, 2005;866–893.
6. Bellezza E, Bianchini E, Pettinelli S, et al. Intestinal plasmacytoma causing colocolic double intussusception in an adult dog. J Small Anim Pract 2016;57:718.
7. Chetty R, Bramdev A, Reddy AD. Primary extramedullary plasmacytoma of the esophagus. Ann Diagn Pathol 2003;7:174–179.
8. Ahmed N, Ramos S, Sika J, et al. Primary extramedullary esophageal plasmacytoma: first case report. Cancer 1976;38:943–947.
9. Hamilton TA, Carpenter JL. Esophageal plasmacytoma in a dog. J Am Vet Med Assoc 1994;204:1210–1211.
10. Zhou Y, Xu X, Xu L, et al. Treatment of primary isolated extramedullary plasmacytoma of esophagus with endoscopic submucosal dissection. Clin Gastroenterol Hepatol 2012;10:e21–e22.
