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NEOPLASIA AND PROLIFERATIVE LESIONS IN FREE- RANGING MOUNTAIN AND GRAUER’S GORILLAS (GORILLA BERINGEI)
Authors: Iyer, Maya L., Gilardi, Kirsten V., Cranfield, Michael R., Corner, Sarah M., Syaluha, Eddy Kambale, et al.
Source: Journal of Zoo and Wildlife Medicine, 56(2) : 208-216
Published By: American Association of Zoo Veterinarians URL: https://doi.org/10.1638/2024-0080
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NEOPLASIA AND PROLIFERATIVE LESIONS IN FREE-RANGING MOUNTAIN AND GRAUER’S GORILLAS (GORILLA BERINGEI)
Maya L. Iyer, DVM, Kirsten V. Gilardi, DVM, DACZM, Michael R. Cranfield, DVM, Sarah M. Corner, DVM, MS, PhD, DACVP, Eddy Kambale Syaluha, DVM, MSc, Jean Bosco Noheri, DVM, MSc, MBA, Benard Ssebide, DVM, MSc, Jean Felix Kinani, DVM, MSc, Fred Nizeyimana, DVM, MSc, Ricky Okwir Okello, BVM, MSc, Julius Nziza, DVM, MSc, Martin Kabuyaya, DVM, Methode Bahizi, DVM, Richard Muvunyi, MS, Elisabeth Nyirakaragire, Tierra Smiley Evans, DVM, PhD, and Linda J. Lowenstine, DVM, PhD, DACVP
Abstract: There are no published data on the occurrence of neoplasia in wild great apes of any species. The aim of this study was to utilize postmortem and histopathology reports collected from wild human- habituated mountain gorillas (Gorilla beringei beringei) and Grauer’s gorillas (Gorilla beringei graueri) to deter- mine both the incidence and types of spontaneous neoplasms and proliferative lesions that occur in these species. Pathology records of 194 mountain gorillas and 12 Grauer’s gorillas necropsied from 1985 to 2020 were examined for all cases of neoplasia or hyperplastic/proliferative disease. Slides and/or scanned images were reviewed to confirm morphologic diagnoses. Data were collected on comorbidities that may have con- tributed to neoplastic/proliferative transformation. A total of nine malignant neoplasms were identified: large cell anaplastic B-cell lymphoma, gastric adenocarcinoma (two cases), gastric carcinoid, oral mucocuta- neous malignant melanoma, gastric carcinoma in situ (two cases), squamous cell carcinoma of the lip, and renal adenocarcinoma. Benign lesions included pheochromocytoma, adrenocortical adenoma (two cases), parathyroid adenoma, mandibular fibroma with gingival hyperplasia, and uterine hemangioma. Proliferative gastritis was commonly identified secondary to gastrointestinal parasitism (n = 35); chronic inflammation from nematodiasis may have led to neoplastic transformation of hyperplastic mucosal epithelium. Other hyperplastic lesions included nodular hyperplasia of the adrenal cortex (n = 9), adrenal medulla (n = 7) and thyroid glands (n = 3), pulmonary reactive lymphoid hyperplasia in infants and juveniles (n = 16), as well as nodular splenic siderofibrosis (n = 5) that may be associated with parasite migration. These findings demon- strate that free-ranging mountain and Grauer’s gorillas in a natural environment develop neoplasia and pro- liferative disease.
INTRODUCTION
Neoplasia (cancer) and proliferative disorders in great apes (gorillas, chimpanzees, orangutans, and bonobos) are reported to be rare, especially
From the Karen C. Drayer Wildlife Health Center, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA (Iyer, Gilardi, Cranfield, Smiley Evans); MGVP, Inc., Goma, DR Congo, Kampala, Uganda, Musanze, Rwanda and Davis, CA, USA (Gilardi, Cranfield, Syaluha, Noheri, Ssebide, Kinani, Nizeyimana, Okwir Okello, Nziza, Kabuyaya, Bahizi, Nyirakaragire, Smiley Evans); Veterinary Diagnostic Laboratory, Michigan State University College of Veterinary Medicine, East Lansing, MI, USA (Corner); One Health Approach for Conservation (OHAC)-Gorilla Health, Kigali, Rwanda (Kinani); Rwanda Development Board, Kigali, Rwanda (Muvunyi); Depart- ment of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA (Lowenstine). Correspondence should be directed to Maya Iyer (mayaiyerdvm@gmail.com) and Linda Lowenstine (ljlowenstine@ucdavis.edu).
Note: This article contains supplemental material found in the online version only.
in comparison to the prevalence of such lesions in humans and Old World monkeys.26,29,39 How- ever, all of these data were obtained from captive great apes and monkeys, and the assumption that neoplasia is rare is largely based on a comparison to the incidence of similar cancers in humans and domestic animals. Studies of neoplasia in zoo- housed chimpanzees, orangutans, and western low- land gorillas and lab-housed chimpanzees describe lethal neoplasms only.5,27,29,39 As a result, the inci- dence of neoplasia and proliferative disorders in captive great apes is likely underreported. The apparent rarity of neoplasia in free-ranging great apes could be attributed to a lack of available data on wild apes (especially older animals), a lack of exposure to carcinogens in a pristine natural envi- ronment, or a shortened life span in the wild com- pared to captivity.25
Mountain gorillas (Gorilla beringei beringei) are endangered and Grauer’s gorillas (Gorilla beringei graueri) are critically endangered.15,34 There are an estimated 1,063 mountain gorillas in the wild over- all and an estimated 5,252 Grauer’s gorillas within their known range in eastern Democratic Republic of Congo (DR Congo).16,17,33 Understanding the
incidence and risk factors for neoplasia in these subspecies can help wildlife managers provide best achievable veterinary care to individual goril- las, aiding conservation. Cancer in wildlife is understudied overall but can provide insight into mechanisms of oncogenesis and infectious/toxic etiologies of tumor development in humans and animals.32
At present, there are no published data on the prevalence of neoplasia in any species of wild great ape. Postmortem and histopathology reports collected from populations of wild human-habitu- ated mountain and Grauer’s gorillas inhabiting the Virunga Massif of Rwanda, Uganda, and DR Congo, and the Bwindi Impenetrable Forest in Uganda can be used to determine the occurrence and types of such lesions. With necropsy records from 206 eastern gorillas, Gorilla Doctors maintains the largest available database of histopathology from wild apes. Clinical records and histopathol- ogy reports can reveal potential comorbidities that may suggest potentially infectious etiologies for neoplastic/hyperplastic lesions, such as onco- genic viruses (e.g., mountain gorilla lymphocrypto- virus12) or chronic inflammation due to persistent bacterial/parasitic infections.
The goal of this study was to evaluate the types of neoplasms and proliferative lesions that occur in wild mountain and Grauer’s gorillas, using diagnostic pathology as a research tool, to under- stand neoplasms in long-lived great apes in the wild better. Because of the lack of published data on infectious and toxic etiologies of cancer in apes, a secondary aim of this project was to investigate if neoplasms or hyperplastic lesions diagnosed in wild gorillas are associated with known pathogens, specifically common endopar- asites like gastrointestinal nematodes.
MATERIALS AND METHODS
The study population for this investigation included wild human-habituated mountain gorillas inhabiting the Virunga Massif (spanning the bor- ders of Rwanda, Uganda, and DR Congo) and Bwindi Impenetrable National Park in Uganda, as well as Grauer’s gorillas inhabiting Kahuzi-Biega National Park and Mount Tshiaberimu (Virunga National Park) in DR Congo. Human-habituated family groups inhabiting these regions are rou- tinely monitored for signs of illness and injury by Gorilla Doctors, and veterinary interventions are conducted in the field as needed. Additionally, orphaned Grauer’s gorillas housed at the Gorilla Rehabilitation and Conservation Education center
in Kasugho, DR Congo were included in the study population.
Gorilla Doctors perform necropsies on all deceased habituated and unhabituated gorillas that can be recovered from their landscape. Gross necropsy records and histopathology com- piled by Gorilla Doctors from all 194 mountain gorillas and 12 Grauer’s gorillas that died between 1985 and 2020 were examined. For necropsies completed between 1985 and 2014, tissues were submitted in 10% neutral buffered formalin for his- topathologic examination at the University of Cal- ifornia, Davis, William R. Pritchard Veterinary Medical Teaching Hospital. Tissues were embed- ded in paraffin, sectioned at 5 um, and stained with hematoxylin-eosin for review by a board-cer- tified veterinary pathologist (LJL). Tissues col- lected from 2014 to 2020 were processed in range countries and read either by veterinary patholo- gists at Makerere University in Uganda, by visit- ing U.S. pathologists, or remotely (by LJL or SC).
Morphologic diagnoses from necropsy reports were confirmed by re-examination of histopa- thology by a board-certified veterinary patholo- gist (LJL). For cases in which the diagnosis was not definitive, and for which tissues were archived at UC Davis, special stains and immunohisto- chemistry (IHC) were performed to characterize the lesions better. Immunohistochemistry with primary antibodies against pan-cytokeratin, chro- mogranin A, synaptophysin, CD20, CD3, CD86, and CD4 was performed using previously estab- lished and routinely used methods (Supplemental Table 1).38 Special stains included myeloperoxi- dase and Masson’s trichrome stains. Animals for which tissue samples or histopathology were not available for re-examination were evaluated based on gross postmortem findings. All lesions were categorized by tissue of origin, malignancy (to identify those implicated in mortality), and demo- graphic factors such as species, age, sex, family group, and forest location.
The clinical records of all mountain and Gra- uer’s gorillas with diagnoses of benign or malig- nant neoplasia or hyperplasia on postmortem examination were examined. Histopathology and gross postmortem reports of gorillas with docu- mented neoplasms were reviewed for any concur- rent disease conditions. Data were collected on concurrent infectious agents, as well as covariate data on inflammatory processes, such as high parasite loads.
Associations between neoplasia or other prolif- erative disorders and demographic factors such as age, sex, location, and family group were evaluated
by multivariable analyses. The effects of age were evaluated by dividing gorillas into the following age classes: less than 1 mon of age (neonate), 1 mon-3 yr (infants), 4-8 yr (juvenile), 9-13 yr (sub- adult), 14-29 yr (adult), and 30 yr or older (aged). Age or age class was estimated at the time of nec- ropsy for animals with an unknown date of birth based on previous monitoring data since habitua- tion. Multivariable logistic regression was then used to assess the association of risk factors with neoplasia or proliferative lesions for variables that were significant on bivariate analysis (P < 0.1); these included age, sex, and location. Separate logistic models were generated for all neoplasia and specific neoplasms of the gastrointestinal sys- tem to account for variation in etiologies. Vari- ables were included if they significantly improved model fit, based on the likelihood ratio test (P < 0.1), while minimizing the Akaike information cri- terion. Overall model fit was assessed using the Hosmer-Lemeschow goodness-of-fit test. The log odds of developing neoplasia was predicted by the use of the following logistic model:
ln P(x) 1 P(x)
5 4.6 + 1.71(S) +2.01(A) + 1.95(VNP),
where P(x) denotes the probability of a gorilla developing neoplasia (Hosmer-Lemeshow model goodness-of-fit (x2 = 4.47; P = 0.346), S denotes sex, A denotes age, and VNP denotes Virunga National Park). All statistical analyses were per- formed using Stata/SE 16 (StataCorp).
RESULTS
Neoplasia
A total of 206 gorillas (194 mountain gorillas and 12 Grauer’s gorillas) that died between 1985 and 2020 received complete postmortem (gross and histopathologic) examinations. The study popula- tion included animals ranging from neonates to aged adults (Table 1). Neoplasia was detected in 15 mountain gorillas total (7.28%; Table 2), includ- ing 12 females and 3 males. Neoplasia was speci- fied as the cause of death in five of these cases. Eight neoplasms were diagnosed in aged adults and seven were found in adults. Malignant neo- plasms were diagnosed in nine mountain gorillas, four of which were found to have distant metastatic disease upon necropsy and histopathology. No neoplasms were identified in necropsies from the 12 Grauer’s gorillas examined.
| Age class | Age range | Gorilla beringei beringei | Gorilla beringei graueri |
|---|---|---|---|
| Neonate | <1 mon | 16 | 1 |
| Infant | ≥1 mon-3 yr | 61 | 2 |
| Juvenile | ≥4-8 yr | 13 | 2 |
| Subadult | ≥9-13 yr | 9 | 0 |
| Adult | ≥14-29 yr | 68 | 4 |
| Aged adult | ≥30 yr | 27 | 3 |
| Total | 194 | 12 |
One aged adult female mountain gorilla was diag- nosed with large cell anaplastic B-cell lymphoma affecting several thoracic lymph nodes, in addi- tion to severe fibrinopurulent constrictive peri- carditis due to a secondary bacterial infection. Affected lymph nodes, as well as a fibrotic mass at the base of the heart, were made up of a pleo- morphic population of cells, including large and bizarre binucleate and multinucleate cells, which were strongly positive with CD20 immu- nohistochemical staining (Fig. 1). There was apparent induction of fibroblasts by the neoplas- tic population. Differentials include Hodgkin- like lymphoma.
Metastatic melanoma was identified in one aged adult female;20 the nonencapsulated, infiltrative neoplasm was located at the mucocutaneous junc- tion of the lip and was composed of both round and spindloid cells containing large amounts of black pigment (melanin) (Fig. 2). Metastases were present in regional lymph nodes, lung, liver, and kidney.
Five mountain gorillas were diagnosed with gastric neoplasms. One case of metastatic carci- noid (Fig. 3E) originating at the junction between the pylorus and proximal duodenum in an aged adult female was confirmed via strongly positive immunohistochemical labeling for chromogranin A (Fig. 3F). Other gastric neo- plasms included a widely metastatic schirrous gastric adenocarcinoma (Fig. 3C), a gastric mucin- ous adenocarcinoma, as well as two cases of carci- noma in situ showing glandular and nuclear atypia and lamina proprial invasion. Another epithelial cancer was a renal adenocarcinoma that consisted of a single, fairly well-circumscribed tumor nod- ule found incidentally (Fig. 3D). Squamous cell carcinoma of the lip was identified in an aged female and led to severe disfiguration of the face.
| Case | Diagnosis | Malignancy | Subspecies | Sex | Age (yr) | Location |
|---|---|---|---|---|---|---|
| 1 | Large cell anaplastic B-cell lymphoma | Metastaticb | Gbb | F | 39 | Rwanda |
| 2 | Mucocutaneous melanoma | Metastatic | Gbb | F | Adult | DR Congo |
| 3 | Schirrous gastric adenocarcinoma | Metastatic | Gbb | F | 17 | Rwanda |
| 4 | Gastric carcinoid | Metastatic | Gbb | F | 35 | DR Congo |
| 5 | Gastric adenocarcinoma in situ | Malignantb | Gbb | M | 17 | Rwanda |
| 6 | Gastric carcinoma in situ | Malignant | Gbb | M | 25 | Rwanda |
| 7 | Gastric mucinous adenocarcinoma | Malignant | Gbb | F | 35 | DR Congo |
| 8 | Squamous cell carcinoma (lip) | Malignant | Gbb | F | 34 | DR Congo |
| 9 | Renal adenocarcinoma | Malignant | Gbb | F | 32 | Rwanda |
| 10 | Pheochromocytoma | Benign | Gbb | F | Adult | Uganda |
| 11 | Adrenocortical adenoma | Benign | Gbb | F | 24 | Rwanda |
| 12 | Adrenocortical adenoma | Benign | Gbb | F | 42 | Rwanda |
| 13 | Parathyroid adenoma | Benign | Gbb | F | 40 | DR Congo |
| 14 | Mandibular fibroma with gingival hyperplasia | Benign | Gbb | M | 26 | DR Congo |
| 15 | Uterine hemangioma | Benign | Gbb | F | 37 | Rwanda |
a Gbb, Gorilla beringei beringei; F, female; M, male.
b Metastatic refers to animals diagnosed with metastases distant to the primary lesion at the time of postmortem exam; malig- nant refers to neoplasms with metastatic potential that were not found to have distant lesions on necropsy.
Benign neoplasms were identified in six moun- tain gorillas. Endocrine lesions included two adre- nocortical adenomas diagnosed in aged adult females (Fig. 3A), a parathyroid adenoma in an aged adult female with chronic renal disease, and a unilateral pheochromocytoma in an adult female (Fig. 3B). In the latter case, vascular changes in the heart and kidney of this animal were sugges- tive of chronic hypertension possibly secondary to the pheochromocytoma. A mandibular fibroma with gingival hyperplasia was diagnosed in an adult male with a history of facial trauma. The large, hollow mandibular mass showed excessive dense connective tissue and atypical epithelial hyperplasia. Finally, a small uterine hemangioma was identified in an aged female.
Gross nodules or masses were identified in three additional mountain gorillas, but histopathology
was not performed to confirm morphologic diag- noses. These included periorbital and caudal abdominal masses in an adult female; an adult female with gross nodules on the liver, kidney, and lung; and an adult male with a renal nodule. Because of the lack of histopathology available for definitive diagnosis, these cases were not included in statistical analyses.
There were no significant associations between the occurrence of neoplasia and family group. Results of our multivariable model showed that males were 5.5 times more likely to develop neopla- sia than females (95% confidence interval [CI]: 1.3- 22.2; P = 0.016), adults and aged adults were 7.5 times more likely to develop neoplasia compared to younger age classes (95% CI: 2.2-25.6; P = 0.001), and gorillas within Virunga National Park were 7.1 times more likely to develop neoplasia compared to
A
B
C
100 um
20 pm
20 um
A
B
gorillas in other parks (95% CI: 1.8-27.1; P = 0.005).
Proliferative lesions
Proliferative lesions were detected in 74 of 206 (35.92%) gorillas necropsied between 1985 and 2020, and included hyperplasia of gastric mucosa, lymphoid tissue, adrenal cortex, adrenal
medulla, spleen, and thyroid gland (Table 3). Chronic proliferative gastritis was observed in 34 mountain gorillas. Nematodes were identified in the gastric mucosa or lumen of 16 out of 34 ani- mals with chronic proliferative gastritis, and intra- lesional nematodes were identified histologically by the presence of longitudinal ridges to be of family Trichostrongylidae in 10 of these cases.7 Gorillas in which chronic proliferative gastritis
A
C
E
1.0 mm
200 pm
200 jam
B
D
F
50.0
um
200 pm
100 μm
| Diagnosis | Number of affected animals | |
|---|---|---|
| Gorilla beringei beringei | Gorilla beringei graueri | |
| Proliferative gastritis | 34 | 0 |
| Pulmonary reactive lymphoid | 16 | 0 |
| hyperplasia | ||
| Adrenocortical nodular | 8 | 0 |
| hyperplasia | ||
| Adrenal medullary hyperplasia | 7 | 0 |
| Splenic nodular siderofibrosis | 5 | 0 |
| Thyroid nodular hyperplasia | 2 | 0 |
was identified were 8.2 times more likely to have a neoplasia of gastrointestinal origin also identified (95% CI: 1.32-51.26; P = 0.024).
Pulmonary reactive lymphoid hyperplasia (PRLH), consisting of lymphocytic interstitial pneumonia and follicular bronchitis, was identified in 15 infant mountain gorillas and one juvenile mountain gorilla. Nodular splenic siderofibrosis was identi- fied in five mountain gorillas (one adult female and four aged adult females) and was described as a mass composed of dense fibrous connective tis- sue with extensive mineralization. These ranged in size from 1.5 to 5 cm diameter.
DISCUSSION
Cancer is the second leading cause of death in humans, accounting for approximately 9.6 million deaths globally in 2018.4 Comparatively, spontane- ous neoplasms in apes are reported infrequently in published literature and have been documented in captive great apes only.25,27 In particular, studies of captive chimpanzees report the rarity of carcino- mas, a group of malignancies that is diagnosed in one in three humans in developed countries.39
In this first study documenting the occurrence of neoplasia in a wild great ape of any species, we observed neoplasms in 15 of 206 (7.28%) mountain and Grauer’s gorillas necropsied between 1985 and 2020. This study demonstrates that wild mountain gorillas spontaneously develop neoplasia. Besides the inequality in sample sizes, there are several pos- sible explanations for the disparity in occurrence of neoplasia between humans and gorillas. Wild mountain gorillas have a shorter life expectancy than humans, with the oldest animal in the Gorilla Doctors database achieving approximately 50 yr of age. Longer life spans allow for more time to
accrue mutations that may lead to neoplastic transformation, as well as decreased tumor sur- veillance due to immunosenescence. Despite their high degree of genetic similarity, human cells also display reduced apoptotic function compared to chimpanzee cells,2 which may provide a biological basis for the increased incidence of cancer in humans, as compared to great apes.3
Additionally, approximately 75% of cancers in humans are caused by environmental and lifestyle factors, such as tobacco, carcinogen exposure, diet (specifically heavy red meat consumption and food additives), and obesity.1 In this study, one gorilla was diagnosed with squamous cell carcinoma of the lip in this population; in humans, major risk factors for development of squamous cell carci- noma include tobacco use and chronic UV exposure (either from solar damage or cosmetic tanning).1 Though use of tobacco and tanning beds are clearly not risk factors in a free-ranging gorilla, chronic UV exposure could contribute to neoplastic transforma- tion. Similarly, obesity and diet factors like red meat consumption and food additives are unlikely to cause oncogenesis in free-ranging mountain and Grauer’s gorillas, as they are herbivorous. However, diet could play a role through the ingestion of natu- rally occurring carcinogens.
This study also found that gorillas within Virunga National Park were more likely to develop neopla- sia than gorillas in other parks. Though only a small number of neoplasms were identified in this study overall and most necropsy reports were from gorillas in Virunga National Park, the significant correlation between location and neoplasia could suggest either a genetic or environmental factor contributing to development of neoplasia for gorillas in this park.
In addition to neoplasms, mountain and Gra- uer’s gorillas examined in this study developed several proliferative disorders. The most common hyperplastic lesion (34 of 206) was nodular prolif- erative gastritis, associated, in 10 cases, with intralesional trichostrongylid nematodes. Mortal- ity due to gastroenteritis has been reported to be uncommon in this gorilla population, but gastric nematodiasis has been found to be significantly associated with chronic and proliferative or ulcer- ative gastritis in mountain gorillas.3º Although establishing causality is beyond the scope of this study, the three cases of gastric carcinoma or ade- nocarcinoma documented in this mountain gorilla population were identified in individuals that were also suffering from chronic gastritis. Neopla- sia of gastrointestinal origin overall was also highly correlated with chronic gastritis.
Chronic inflammation is a known mechanism by which pathogens drive oncogenic transformation; inflammation is especially relevant to wildlife can- cers, as free-ranging animals are more likely to have prolonged, untreated infections and be exposed to a high macroparasite burden.32 Repetitive cell dam- age and repair due to gastric nematodiasis may lead to neoplastic transformation of mucosal epithelial cells. Inflammation can play a key role in carcino- genesis via increased cell proliferation, free radical production, and epithelial cell death.14 For exam- ple, Helicobacter pylori infection has been shown to increase the risk of gastric carcinogenesis in humans significantly.10,14 Nonhuman primate and rodent models suggest that sustained H. pylori infections induce chronic atrophic gastritis and p53 mutations, leading to the development of gastric carcinoma.22 Helicobacter pylori and other gastric spirochetes have not been identified in eastern gorillas and were not specifically tested for in this study. The link between chronic atrophic gastritis and gastric carcinoid tumors or adenocarcinomas is well established in humans, but the association between gastritis and similar tumors in gorillas has not been studied.10,36,37 Nematodiasis has also been implicated in carcinoma development via similar mechanisms; gastric adenocarcinoma was reported in a Persian cat with chronic proliferative gastritis with intralesional nematodes.9 Strongyloi- des infection has also been diagnosed in a man with early gastric adenocarcinoma, with both eggs and adult nematodes identified within the neoplasm.35
Certain neoplastic and proliferative lesions have also been linked to viral pathogens in nonhuman primates.25,28 Specifically, gamma-1 lymphocryp- toviruses (LCV) infect apes, including mountain gorillas, and show similarities to human Epstein- Barr virus (EBV), an oncogenic virus linked with lymphoproliferative disorders.12,27 Mountain gorilla LCV is suspected to be associated with oro-esopha- geal leukoplakia and follicular hyperplasia in the tonsils and lymph nodes of adults, in addition to EBV-like pathology in infant gorillas.12,13,25 A previous study of infant gorillas in this study pop- ulation detected the presence of mountain gorilla LCV in animals with lymphoproliferative lesions.12 Pulmonary reactive lymphoid hyperplasia (consist- ing of lymphocytic interstitial pneumonia and lym- phofollicular bronchitis) was identified in 16 of 63 infant mountain gorillas necropsied during the study period. EBV is known to cause a similar lym- phoid hyperplasia in human pediatric patients and has been associated with malignancies including diffuse large B-cell lymphoma, nasopharyngeal car- cinoma, and Burkitt lymphoma.6
Lymphoma is among the most common malig- nancies in monkeys and apes, and LCV has been linked to the development of non-Hodgkin lympho- mas in rhesus macaques experimentally infected with simian immunodeficiency virus.27,28 However, the association between LCV and lymphoma has not yet been proven in any species of ape.25 The adult female mountain gorilla diagnosed with large cell anaplastic B-cell lymphoma in this study tested positive for mountain gorilla LCV by PCR on blood collected at necropsy.
Other proliferative lesions included nodular hyperplasia of the adrenal and thyroid glands. Focal nodular hyperplasia of the adrenal cortex is common in older humans and may be due to a loss of the proliferative capacity of cells in the adrenal cortex secondary to aging. Though adre- nocortical tumors can develop in humans, nodu- lar hyperplasia due to cellular senescence is not pathologic, and a similar process may be occur- ring in gorillas with these changes.11,18 Adrenal medullary hyperplasia (AMH) was identified in 7 of 206 gorillas. Unlike adrenocortical nodular hyperplasia, AMH is regarded as a precursor of pheochromocytoma in humans.23,24 The etiology of splenic nodular siderofibrosis identified in some gorillas is unknown, but similar lesions have been described in cynomolgus macaques with filariasis.31 Although parasites were not identified in any of these lesions, they may be caused by vascular damage from microfilaria migration.
Naturally occurring carcinogens like phyto- chemicals have also been associated with neopla- sia. Consumption of plants containing hepatotoxic pyrrolizidine alkaloids (HPAs) has been identified as a potential source of hepatic lesions in a popula- tion of Grauer’s gorillas inhabiting the Mount Tshiaberimu forest.19 However, no hepatic neo- plasms or proliferative disorders were identified in Grauer’s gorillas necropsied during the study period.
Overall, these findings demonstrate that wild mountain gorillas in a natural environment develop neoplasia and proliferative disorders. Knowledge of the occurrence of neoplasia in great apes can inform diagnosis and treatment of wild human- habituated mountain and Grauer’s gorillas, aiding in the conservation of these critically endangered subspecies, as well as captive apes.
Acknowledgments: The authors are thankful to the many veterinarians involved in postmortem exams and histopathologic evaluation, including Dawn Zimmerman, Jan Ramer, Chris Whittier,
Lucy Spelman, Susanne Abildgaard, Jacques Iyanya, Jennifer Luff, Elizabeth Macfie, and Gla- dys Kalema.
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Accepted for publication 26 December 2024