Pathology in Practice

Amélie Ménard Groupe de Recherche sur les Maladies Infectieuses en Production Animale (GREMIP), Faculté de Médecine Vétérinaire, Département de Pathologie et Microbiologie, Université de Montréal, St-Hyacinthe, Québec, Canada

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 DVM, MSc
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Dominique Fournier Laboratoire de Santé Animale Québec, MAPAQ, Québec, Québec, Canada

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 DVM, MVSc
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Marie-Odile Benoit-Biancamano Groupe de Recherche sur les Maladies Infectieuses en Production Animale (GREMIP), Faculté de Médecine Vétérinaire, Département de Pathologie et Microbiologie, Université de Montréal, St-Hyacinthe, Québec, Canada

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 DVM, PhD

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History

An 18-year-old 688-kg Belgian gelding was presented for chronic weight loss and a recent deterioration of its general condition.

Clinical and Gross Findings

On initial assessment, the horse had a rectal temperature of 39.0 °C (reference range, 37.2 to 38.3 °C), heart rate of 100 beats/min (reference range, 28 to 44 beats/min), and shallow respirations with clinically normal bronchovesicular sounds. Intestinal sounds were also clinically normal. There was frothy discharge from the oral cavity, and feces were slightly liquid. Ceftiofur (6.6 mg/kg, IM, q 96 h), moxidectin-praziquantel (dose not reported, PO), and flunixin meglumine (1.1 mg/kg, IV) were initially administered. The horse was examined 4 days later for worsening of its general condition. Rectal temperature was 38.9 °C, heart rate was 100 beats/min, and dyspnea was still present with a respiratory rate of 44 breaths/min. Intestinal sounds were decreased compared to what was noted on the first visit. On transrectal examination, the spleen was displaced medially, and there was a mild tension band on the right side. There was no evidence of colonic entrapment or intestinal dilatation. Passage of a nasogastric tube was attempted; however, the stomach could not be reached. A second dose of flunixin meglumine was administered. The horse died on the following night.

On necropsy (Figure 1), the horse was in relatively good body condition. There were multiple 0.5-cm-diameter gingival erosions. There was abundant turbid serosanguineous fluid in the thoracic cavity and pericardial sac (approx 1 L). The walls of the pulmonary artery and aorta were severely thickened (2 to 3 cm in thickness) by white to yellow smooth tissue. Multiple irregular yellowish foci thickened the epicardial surface of the atria. The spleen was displaced into the pelvis, the liver was pushed to the right side, and the stomach was severely displaced caudally and to the left. There was a 0.2-cm-thick segmental thickening of the small intestine wall by whitish and smooth tissue over 30 cm of its length. The base of the cecum was strangulated by a white to yellow, 7-cm-diameter pedunculated nodule. On the abdominal wall, there were several smooth, pale-yellow nodules measuring up to 5 cm in diameter.

Figure 1
Figure 1

Necropsy photographs of the inferior labial mucosa (A), heart (B), intestinal wall (C), and a mesenteric mass (D) of an 18-year-old 688-kg Belgian gelding that died shortly after having been evaluated for chronic weight loss and a recent deterioration of general condition A—Multiple irregular erosions of approximately 5 mm in diameter are seen on the labial mucosa. B—There is a moderate white to yellowish thickening of the left atrial wall seen on the transverse section. C—Notice the thickening of the intestinal wall (white arrow) by a focally extensive white infiltration. D—The cecum has been strangulated by a yellowish, pedunculated mass of 7 cm in diameter (black arrow).

Citation: Journal of the American Veterinary Medical Association 260, 10; 10.2460/javma.20.06.0320

Histopathologic Findings

On microscopic examination, multiple organs were extensively infiltrated by a population of neoplastic lymphoid cells organized in dense sheets effacing the normal architecture (Figure 2). Multiple tissues were multifocally infiltrated by the neoplastic cells: pituitary gland, cerebral leptomeninges, choroid plexus, tongue, myocardium, spleen, intestinal wall, portal areas in the liver, cortex and medulla of both kidneys, and walls of large vessels at the base of the heart. Most of the cells, approximately two-thirds of the population, had scant, poorly defined basophilic cytoplasm and a small, approximately 7 μm in diameter, dense, round to oval nucleus. Fewer large lymphoid cells, approximately one-third of the population, were scattered in the infiltrate and showed moderate atypia. This subpopulation had abundant, agranular basophilic cytoplasm. Their nuclei were pale, round, and large (range, 10 to 25 μm in diameter) and contained slightly clumped chromatin and 1 to 3 basophilic nucleoli. The nucleus was central to eccentric in some of these cells, and rare binucleated cells were observed. Anisocytosis and anisokaryosis were moderate, and there were 7 mitotic figures/10 hpfs (400X) examined. Plasma cells were also scattered throughout the infiltrate. Extensive vascular invasion by the neoplastic cells was present in the myocardium, lungs, kidneys, and skeletal muscles. Nodules found on the inner abdominal wall and the pedunculated abdominal mass were composed of the same neoplastic lymphoid cell population.

Figure 2
Figure 2

Photomicrographs of the white to yellowish infiltrate found in the kidney (A, C, and D) and the mesenteric mass (B) from the horse described in Figure 1. A—Notice the well-demarcated, extensive infiltration of lymphoid cells in the renal parenchyma (cortex and medulla). Hematoxylin phloxine saffron stain; bar = 300 μm. B—The mesenteric mass is composed of dense sheets of neoplastic lymphoid cells (approx 33%) and cells that appear as normal lymphocytes (approx 67%). Rare binucleated cells (arrows) and multiple plasma cells (arrowheads) can be observed. Hematoxylin phloxine saffron stain; bar = 50 μm.C—Some of the large atypical lymphoid cells and smaller lymphocytes have positive staining for the B-cell marker, cluster of differentiation (CD) 20, are scattered in the lymphoid population, and account for < 50% of the cells. Immunohistochemical staining for CD20 (CD20 polyclonal antibody [PA5-16701], Invitrogen, dilution 1/200); bar = 50 μm. D—Cells with positive staining for the T-cell marker, CD3, are generally small mature lymphocytes scattered individually or in aggregates through the infiltrate. The proportion of CD3-positive cells in panel D is similar to that of CD20-positive cells in panel C. Immunohistochemical staining for CD3 (Monoclonal mouse anti-human CD3 [clone F7.2.38]; Agilent; dilution 1/50); bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 260, 10; 10.2460/javma.20.06.0320

Immunohistochemistry staining was used on tumor sections to characterize the lymphoid phenotype. Cells with cluster of differentiation (CD) 20 (CD20; B-cell marker) were scattered throughout the infiltrate. The cytoplasmic staining was irregular and varied from weak to strong. Some of the larger atypical cells described earlier as well as smaller, round lymphocytes were immunolabeled by the anti-CD20 antibody. The proportion of cells that expressed CD3 (T-cell marker) varied greatly (minimal to almost 50% of cells). The CD3-positive cells were generally small, round, mature-looking lymphocytes and had a strong and uniform cytoplasmic staining. They were scattered individually or in aggregates through the infiltrate. The number of CD20-positive cells was similar to that of CD3-positive cells. Many cells were neither labeled with CD20 nor CD3.

Interpretation and Case Summary

Interpretation: disseminated T-cell-rich–large B-cell lymphoma (TCRLBCL) with caecal strangulation by a pedunculated mesenteric lymphomatous mass.

Case summary: multicentric TCRLBCL in a horse.

Comments

The most probable diagnosis, based on the clinical presentation and gross findings, was a generalized neoplastic process because of the multisystemic involvement and the macroscopic appearance of the infiltrate. In horses, the most common multicentric tumors are lymphomas, mostly TCRLBCL (34% [28/83]1) of multicentric lymphomas), peripheral T-cell lymphoma, and diffuse large B-cell lymphoma.1 Generalized mast cell tumors have also been reported, but they are extremely rare, and their metastases tend to be more nodular.2 Other metastatic tumors such as intestinal adenocarcinoma3 or malignant peripheral nerve sheath tumor4 can only be excluded with microscopic examination. The histopathologic and immunohistochemical evaluation of the infiltrate confirmed a diagnosis of TCRLBCL in this case.

T-cell-rich large B-cell lymphoma is defined as a variant of the large B-cell lymphoma in the World Health Organization classification system. Equine TCRLBCL can be cutaneous, multicentric, gastrointestinal, or extranodal. The cutaneous form is the most prevalent and often presents as multiple subcutaneous nodules.5 According to the limited epidemiological data available, TCRLBCL seems to affect more females than males (3 or 4:1),6 and there is no clear breed predisposition. The mean age of horses at diagnosis is 10 years, and the incidence tends to increase with age1; however, TCRLBC can occur at any age. It was proposed that equine herpesvirus-5 could be involved in the neoplastic process, but evidence is still lacking.7 In cats, TCRLBCLs represented 7.5% (56/751) of lymphomas in a study,6 and frequently appear as an enlarged lymph node in the neck area. T-cell-rich large B-cell lymphoma is generally rare in other domestic species.6

In our case, the lymphoma was multicentric. Reported tumor progression is relatively slow, and clinical signs are nonspecific (eg, weight loss, decreased appetite, lethargy, recurrent fever, ventral edema) until advanced stages, when they reflect the organs involved,8 making it a diagnostic challenge for equine practitioners. Cytologic, histological, and immunohistochemical analyses are required to identify the immunophenotype, which is an important factor to consider to establish an adequate treatment plan and prognosis. T-cell–rich large B-cell lymphoma has a unique histological appearance characterized by a mixed population of small benign T cells (CD3-positive cells) and large atypical neoplastic B cells (CD20-positive cells).5 In this case, there was a non-negligible proportion of cells that were negative for both CD3 and CD20; we hypothesized that they represented plasma cells and less differentiated neoplastic cells that no longer expressed CD20. A study9 based on human TCRLBCL suggested that the presence of T cells is caused by the production of interleukin-4 by the neoplastic cells or infiltrating histiocytes.

Multicentric TCRLBCLs have poor prognoses and are usually advanced at the time of diagnosis. With a localized tumor, surgical excision can be curative. In a retrospective study,10 9 of 16 (56%) horses with cutaneous TCRLBCL had no recurrence following excision. For the horse of the present report, the condition was very advanced, and the most likely cause of death was either heart failure associated with the tumor in the heart and large vessels at the base of the heart or shock following strangulation of the intestine.

To the authors’ knowledge, this was the first report to describe a case of intestinal strangulation associated with a pedunculated lymphoma in a horse, a pheno-menon classically observed with mesenteric lipomas.11 There are reported cases of intestinal TCRLBCLs manifesting as intestinal impaction or intussusception.12 Therefore, lymphomas should be kept in mind as a differential diagnosis for colic in horses.

Acknowledgments

No third-party funding or support was received in connection with this case report or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.

The authors thank the referring veterinarian, Dr. Samuel Morin, for his important contribution to the history and clinical findings sections.

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