Concurrent pancreatic exocrine hyperplasia and adenomas in a Eurasian otter with pleuropneumonia and urolithiasis

Abstract

The Eurasian otter (Lutra lutra) is a semi-aquatic mammal classified as near-threatened by the International Union for Conservation of Nature. There have been few reports on their diseases, especially neoplasms. Here we describe exocrine nodular hyperplasia and adenomas in the pancreas, along with suppurative pleuropneumonia and urolithiasis, in an aged captive Eurasian otter. Pancreatic adenomas are rare in animals, and coexistence of adenoma and nodular hyperplasia in the pancreas has not been reported previously in veterinary medicine, to our knowledge.

The Eurasian otter (Lutra lutra), a semi-aquatic mammal in the family Mustelidae, is distributed widely across Europe, Asia, and parts of northern Africa. ¹² Despite their broad range, populations of the otter species have significantly declined due to water pollution, loss of habitat, and hunting. ¹² As a result, the International Union for Conservation of Nature (IUCN) classifies the Eurasian otter as a “near-threatened (NT)” animal. ¹² In the past, the limited population of otter species, including the Eurasian otter, led to few reports on their diseases, especially spontaneous neoplasms; a study of 145 autopsies in free-living otters included only 2 cases of enlarged spleen or splenic tumor, and 1 case of a small intestinal tumor. ¹⁴ However, as part of conservation efforts, otters are often raised in zoos or wildlife shelters.^6,12 Therefore, reports of neoplasms in captive otters have been increasing. In Eurasian otters, cases of hepatocellular adenoma, ¹ sustentacular (Sertoli) cell tumor, ⁶ intestinal lymphoma, ³ malignant melanoma, ⁷ trichoblastoma, ⁷ and mammary gland adenoma ⁷ have been documented. Lymphangiosarcoma ²⁰ and thyroid gland carcinoma ¹⁰ were diagnosed in small-clawed otters (Aonyx cinereus). Additionally, pancreatic adenocarcinoma was reported in a giant otter (Pteronura brasiliensis) ¹⁹ and pancreatic endocrine adenoma in a river otter (Lontra canadensis). ⁸

Nodular hyperplasia of the exocrine pancreas is a common incidental finding in older domestic animals, such as dogs, cats, and cattle. ¹⁷ On the other hand, pancreatic exocrine adenoma, a benign tumor, is uncommon in animals.^15,17 Histologically, nodular hyperplasia and adenoma of the pancreas are very similar, and although some guidance for distinction exists, those divisions are somewhat arbitrary.^9,15 It has been suggested that nodular hyperplasia in old animals is an age-related change rather than a response to previous injury or predisposition to neoplasia.^15,17 Furthermore, pancreatic exocrine hyperplasia may not be a pre-neoplastic lesion but rather an idiopathic change because common concurrent lesions with hyperplastic pancreatic nodules are fibrosis, atrophy, and/or mild lymphocytic inflammation. ¹⁸ Notably, we found concurrent lesions of nodular hyperplasia and adenoma in the pancreas of an aged captive Eurasian otter. Here we describe pancreatic exocrine nodular hyperplasia and adenomas, as well as suppurative pleuropneumonia and urolithiasis, in an aged captive Eurasian otter.

A male Eurasian otter was rescued and kept at a wildlife shelter; he was estimated to have been 1- or 2-y-old at time of rescue. The otter had been kept at the shelter for ~13 y due to its inability to adapt to the wild. Its environment was an indoor space with water, and its daily diet consisted mainly of live catfish and chicken meat. He had a seizure episode and dyspnea, with hypotension noted during a physical examination. Radiographic examination confirmed pleural effusion, and blood analysis revealed severe azotemia, hyponatremia, hypochloremia, hyperglycemia, and leukopenia. Despite first aid, including fluid therapy and oxygen supplementation, vital signs remained unstable with no signs of improvement. Consequently, the otter died and was submitted to the veterinary pathology laboratory for postmortem examination.

At autopsy, a large amount of blood-tinged and turbid pleural effusion was found in the thoracic cavity (Fig. 1A). Purulent exudate was loosely attached to the lung surface and pleura. The lungs were diffusely atelectatic. The pancreas was markedly enlarged, and numerous small beige-white nodules were scattered randomly throughout the pancreas (Fig. 1B). Both kidneys were enlarged and irregular (Fig. 1C). The right kidney had more remarkable changes; the renal capsule was severely thinned. On the cut surface of the kidneys, the expanded lobes were severely hydronephrotic (Fig. 1D). Numerous calculi were present in the expanded lobes and pelvis. Renal calculi were fine sand–like in the right kidney, and irregularly shaped, yellow-green stones in the left kidney. The remaining organs were within normal limits.

Figure 1.

Gross lesions in a male Eurasian otter. A. Large amount of blood-tinged and turbid pleural effusion in the thoracic cavity, with exudate loosely attached to the visceral and parietal pleura. The lungs are atelectatic. B. The pancreas is enlarged by pale-beige to white nodules. C. Both kidneys are enlarged with expanded lobes, and the material within the right kidney (on the left) is visible through the thinned renal capsule. D. Sagittal section of both kidneys. Severe cystic changes, enlargement of renal pelvises, and loss of parenchyma with numerous calculi. The right kidney (on the left) is collapsed after the leakage of its internal fluid component.

Tissue samples were fixed in 10% neutral-buffered formalin, processed routinely, sectioned at 4 μm, and stained with H&E and Masson trichrome stains. The pleural exudate was cultured on blood agar plates. Colonies obtained from the plates were isolated and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS; Biotyper 3.0, Bucker). PCR assay and electrophoresis were performed to confirm the reliability of bacterial identification by MALDI-TOF MS and to differentiate the serogroup of the bacteria. ¹⁶

Microscopically, the parietal pleura was covered with a layer of abundant neutrophils, macrophages, and cellular debris, and the cuboidal mesothelial cells of the parietal pleura were moderately hypertrophic. A few inflammatory cells also infiltrated the parietal pleura and the superficial layer of the thoracic wall (Suppl. Fig. 1A). The pulmonary alveolar spaces were generally collapsed (Suppl. Fig. 1B). Cuboidal mesothelial cells of the visceral pleura were also moderately hypertrophic, with prominent infiltration of the lung parenchyma by macrophages, lymphocytes, and plasma cells (Suppl. Fig. 1C). Localized fibrotic changes were seen in the peripheral lung parenchyma (Suppl. Fig. 1D). Marked renal fibrosis was confirmed, with mineralization of some renal corpuscles (Suppl. Fig. 2A, 2B), but no inflammation in the renal parenchyma.

In the pancreas, 2 types of nodules (0.5–6-mm diameter) were observed; most were well demarcated and unencapsulated (Fig. 2A). The acinar cells in the unencapsulated nodules were similar to normal pancreatic cells, but nuclei were more crowded, and cells were in a tubuloglandular pattern of elongated acinar units with hypereosinophilic zymogen granules, consistent with hyperplasia. Mitotic figures were not seen in 2.37 mm² (Fig. 2B). Some other large nodules with prominent fibrous capsules compressed the adjacent parenchyma (Fig. 2C). The acinar cells in the encapsulated nodules had prominent nucleoli and a more solid arrangement pattern rather than a tubuloglandular pattern, which was considered adenomatous. Mitotic figures were also not seen in 2.37 mm² (Fig. 2D). There was no evidence of tumor invasion or metastasis to adjacent tissues or other organs.

Figure 2.

Histologic sections of the pancreas from a Eurasian otter. H&E. A. Well-circumscribed unencapsulated nodules of acinar hyperplasia (arrows). B. Acinar hyperplasia (H) is distinguished from the normal pancreatic parenchyma (N) by more crowding of nuclei and elongated tubuloglandular units with increased eosinophilic zymogen granules. C. Some adenomas are well circumscribed by prominent fibrous capsules (arrow), compressing the adjacent pancreatic parenchyma. These nodules are composed of acinar cells and do not include islets of Langerhans. D. The acinar cells in the adenoma are more crowded, are basophilic, and have prominent nucleoli.

In the identification of the bacterial pleuropneumonia, Pasteurella multocida type A was confirmed through the electrophoresis of PCR products derived from bacterial colonies isolated from the pleural exudate (Suppl. Fig. 3). Based on the pathology findings and bacterial cultures, we concluded that the otter died due to suppurative pleuropneumonia caused by P. multocida, potentially exacerbated by uremia secondary to chronic kidney disease. Pancreatic nodular hyperplasia and adenomas were considered to be concurrent lesions unrelated to the bacterial infection.

Bacterial infections were identified as the most common cause of death in a study of 24 autopsies of captive otters; 15 cases were attributed to bacterial infections. ⁶ P. multocida was isolated from 2 of 15 otters that died from pleuropneumonia and fibrinopurulent pleuritis; P. multocida infection may have occurred via bite wounds or the intake of contaminated food. ⁶ P. multocida is a commensal microbe of the oropharynx of mammals and is also one of the most common secondary pathogens causing suppurative pneumonia in domestic animals in immunocompromised states or in those with pulmonary diseases. ¹⁵ The strains of P. multocida are classified into 5 serogroups (A, B, D–F) based on capsule antigens. ²¹ Among them, types A and D have been detected frequently from a variety of infections in animals.^16,21 Notably, type A, which was identified in our case, is the prevalent capsular type of P. multocida in various animals, including cattle, swine, poultry, and rabbits, and also has been isolated from an otter. ¹⁶ Furthermore, uremia, the clinical manifestation of severe azotemia, can compromise immune function and lead to various pathologic conditions, including neurologic and pulmonary complications.^2,13 In our case, uremia resulting from severe renal urolithiasis in the otter may have induced immune suppression and contributed to the seizure, a neurologic sign. However, given that kidney damage was severe in the otter, the possibility of uremic pneumopathy should also be considered. Uremic pneumopathy is a severe pulmonary complication observed in humans and dogs with uremia and is designated as a special form of uremic pulmonary edema.^4,11 Kidney injury induces pulmonary capillary damage and subsequent interstitial and alveolar edema, widespread atelectasis, alveolar hemorrhages, and fibrin-rich pulmonary hyaline membranes. ⁴ The otter in our case did not have typical features of uremic pneumopathy.

Captive otters are reported to have a higher incidence of urolithiasis (64.7%) than free-ranging wild otters (23.4%). ⁵ This significant difference may be caused by several factors, including diet, genetic factors, and stress. ⁵ Although we could not analyze renal calculi due to their dissolution in formalin, according to a previous report in Europe, the main component of calculi in Eurasian otters was ammonium acid urate. ⁵

In the pancreas, distinguishing exocrine adenoma, a rare lesion, from nodular hyperplasia is challenging, as both lesions have similar histologic features. An adenoma occurs as a single encapsulated mass, whereas nodular hyperplasia occurs as foci of various sizes without a capsule. ¹⁵ The size of the adenoma can be one of the distinguishing criteria, as adenomas tend to be 5–10-mm diameter with compression of the adjacent parenchyma.^9,15 Interestingly, we found coexisting exocrine adenoma and nodular hyperplasia in the pancreas in our case. Some of the pancreatic nodules in our case had obvious encapsulation, whereas others did not. Notably, even the largest nodules lacked encapsulation; some smaller nodules were encapsulated. The encapsulated nodules partially compressed the adjacent pancreatic parenchyma, and the cells within the encapsulated nodules had prominent nucleoli and were slightly more solid than a tubuloglandular pattern.

To the best of our knowledge, based on our search in PubMed, Google Scholar, Scopus, and other databases using the search terms “pancreatic adenoma”, “Eurasian otter”, “pancreatic adenoma and hyperplasia”, “animals”, and various related terms, spontaneous pancreatic adenoma has not been reported in Eurasian otters, and the combination of pancreatic exocrine adenoma and nodular hyperplasia has not been reported previously in veterinary medicine. The development of spontaneous nodular hyperplasia in the pancreas has not been considered a pre-neoplastic lesion in domestic animals to date. ¹⁸ Furthermore, because spontaneous pancreatic adenoma has been reported to occur as a solitary mass, it has sometimes been diagnosed as nodular hyperplasia without microscopic examination when widespread foci were observed grossly in the pancreas. Therefore, histologic examination should be performed for a definitive diagnosis of pancreatic lesions.

Supplemental Material

sj-pdf-1-vdi-10.1177_10406387251338327 – Supplemental material for Concurrent pancreatic exocrine hyperplasia and adenomas in a Eurasian otter with pleuropneumonia and urolithiasis

Supplemental material, sj-pdf-1-vdi-10.1177_10406387251338327 for Concurrent pancreatic exocrine hyperplasia and adenomas in a Eurasian otter with pleuropneumonia and urolithiasis by Jeong-Eun Yeom, Min-Gyeong Seo, Kook-Young Han, Sang-Hyun Kim, Eun-Joo Lee, Kyu-Shik Jeong and Il-Hwa Hong in Journal of Veterinary Diagnostic Investigation