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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
J Med Primatol. Author manuscript; available in PMC 2010 August 10.
Published in final edited form as:
PMCID: PMC2919327

Spontaneous Squamous Cell Carcinomas in 13 Baboons, a First Report in a Spider Monkey, and a Review of the Nonhuman Primate Literature



Squamous cell carcinoma (SCC) is a neoplastic proliferation of epithelial cells undergoing squamous differentiation and represents a diagnostic challenge in nonhuman primates (NHP), especially in baboons with perineal SCC.


Fourteen SCC (13 baboons, 1 spider monkey) were identified over a 20-year period. A literature search identified 86 additional published cases of spontaneous NHP SCC.


SCC was most commonly reported in macaques, baboons, marmosets, and squirrel monkeys. Metastasis occurred in 23%, of NHP. The most frequently reported primary locations were the oral cavity, integument, esophagus, and cervix-uterus. Perineal SCC occurred mainly in baboons. All reported SCC in marmosets occurred in the head. Nasal cavity SCC was only reported in male marmosets. All reported pulmonary SCC occurred in males, mostly in tree shrews.


SCC is a common neoplasm in NHP and exhibits species differences. NHPs may provide a useful SCC animal model.

Keywords: Cancer, neoplasm, Papio, skin, oral cavity, esophagus


Squamous cell carcinoma (SCC) is a neoplastic proliferation of epithelial cells undergoing squamous differentiation, and is a common tumor in nonhuman primates (NHP). SCC is the most common neoplasm of the oral cavity [5,13,14,39], esophagus [5] or skin and perineum [5,14] in several reviews, and was commonly reported in a survey of 11 zoos and NHP facilities [43]. Grossly, SCC typically appears as nodular and irregular proliferations of firm tissue, frequently with ulceration, local invasion into adjacent soft tissues and bone, or occasional metastasis to regional lymph nodes. Histologically, keratin pearls, intercellular bridges, cytokeratin positivity and invasiveness are characteristics of SCC.

Predisposing factors for the development of SCC include sun exposure and chronic irritation [1,53]. An association between SCC and papillomavirus infection has also been reported in humans [16], NHP [71,72], and cats [1]. SCC has been induced by carcinogen exposure in the trachea, lungs and esophagus in NHP [7,73].

We evaluated 14 spontaneous cases of SCC (13 baboon, 1 spider monkey) in NHP identified over a 20-year period and review 86 additional published cases of spontaneous NHP SCC. NHPs may be a useful animal model for studying SCC.

Materials and Methods


The baboon colony population averaged approximately 3275 animals (37% male) during the 20-year period. Baboons were occasionally added to the colony for genetic diversity and special projects. Baboons were housed in two 6-acre outdoor corrals, outdoor metal and concrete gang cages, and indoor-outdoor cages. For variable periods of time, baboons were housed inside various buildings individually or in groups for research or other special purposes. The baboons ate a diet of commercial monkey chow supplemented with grains, fruits and vegetables. Water was supplied ad libitum. All animal care and procedures were approved by the Southwest Foundation for Biomedical Research Institutional Animal Care and Use Committee. None of the baboons reported in this paper were used in research projects that would have an impact on their likelihood of acquiring SCC.


All baboons that died or were euthanized were necropsied and appropriate tissue samples were taken for histologic evaluation. Biopsy specimens taken as an antemortem diagnostic tool were counted with necropsy results from the same animal as one case. All tissues were fixed in 10% neutral buffered formalin, processed conventionally, embedded in paraffin, cut at 5 microns, stained with hematoxylin and eosin, and evaluated by light microscopy by at least one board-certified veterinary pathologist. If deemed necessary, cases were referred to the Armed Forces Institute of Pathology (AFIP) or other individual pathologists for consultation.

Records Review

Pathology records were reviewed for 7578 (4058 female, 3250 male) baboons (Papio spp.) necropsied over a 20-year period at the Southwest National Primate Research Center at the Southwest Foundation for Biomedical Research (SFBR). Thirteen cases (11 female, 2 male) of SCC were identified and the original hard-copy medical records, gross necropsy reports, histopathology reports, and histologic slides were obtained. When no hardcopy medical record was available, a computerized version of the medical record was reviewed instead. For each baboon, the following information was obtained: species, age, sex, tumor location, tumor behavior, presenting complaint, and length of treatment. Nine of the 13 cases had been previously reported [13]. Twelve baboons (92.3%) were over 18 years of age and the average age across all 13 baboons was 21.8 years.

Literature review

We performed a literature search for all published cases of spontaneous NHP SCC. Cases of experimentally induced SCC were excluded. We did not include neoplasia that was not specifically listed in a published article. Where discrepancies were seen between reports, the data from the original publication of the case was utilized. Six cases of SCC in macaques from a survey across multiple facilities [43] were excluded as it was not possible to determine if they were duplications of other published cases. Cases were organized by species and assessed by organ system and location in order of decreasing occurrence and the following information recorded: age at diagnosis, sex, and tumor behavior.



The retrospective baboon data is shown in Table 1. The 13 SCC involved the oral cavity (n = 6; 46.2%), perineum and vulva (n = 5; 38.5%), trachea (n = 1; 7.7%), and axillary lymph node (n = 1; 7.7%). This is the first known case of spontaneous tracheal SCC reported in a NHP.

Table 1
SCC in thirteen SFBR baboons.a

All baboon SCC were locally invasive with the exception of the one in the axillary lymph node; a primary site was not identified. Six cases (46.2%) had bone involvement. Five of these involved the oral cavity (4 mandible; 1 maxilla); the other involved the perineum. Five cases (38.5%) had lymph node involvement; these included SCC that originated from the perineum (2), oral cavity (1), trachea (1), and the case where no primary tumor was found; it is unclear whether that tumor arrived at the lymph node by metastasis from an unidentified primary site or if it originated in the lymph node.

SCC of the oral cavity, perineum and vulva presented as proliferative and ulcerative lesions (Figure 1, a–b). The tracheal and axillary lymph node SCC were firm, lobulated masses. All except the vulvar SCC displayed the typical proliferation of neoplastic epithelial cells with the characteristic keratin pearls and intercellular bridges (Figure 1, c–d). Variable numbers of mitotic figures were present and a mixed inflammatory infiltrate was often associated with areas of ulceration or necrosis. The vulvar SCC was a densely cellular unencapsulated mass composed of wide trabeculae of neoplastic cells that infiltrated into the adjacent tissue, had a high mitotic index, and were strongly and diffusely positive with cytokeratin immunohistochemistry.

Figure 1
Gross and histological presentation of squamous cell carcinoma in the baboon. A, Oral cavity. Note the expansile and ulcerative mass involving the rostral mandible and the loss of teeth, B, Perineum. The baboon is laying on it's left side with extensive ...

Clinical presentation

Baboons with oral cavity SCC had irregular soft tissue swelling of the gingiva and buccal mucosa with variable necrosis or ulceration of the oral soft tissues, loose or broken teeth, fracture of the jaw, or abscess formation. Two baboons received treatment. One tumor was surgically excised, but recurred within 5 months. The other baboon received intralesional chemotherapy, but the baboon died during the course of treatment.

Baboons with perineal SCC presented with non-healing, ulcerated and necrotic lesions of the sex skin, vulva, or ischial pads. These cases presented a diagnostic challenge as four of the five were initially diagnosed as trauma and treated. The lesions tended to heal partially, then worsen over time. The average treatment period was 6.1 months and all baboons were eventually euthanized.

Case report

During the course of the records review an additional case of SCC was identified involving the eye of an adult male black spider monkey (Ateles spp.). At necropsy, there was extensive local invasion of the periocular tissues, nasal sinus, maxilla, and pituitary. To the best of our knowledge, this is the first reported SCC in a spider monkey.

Literature review

Table 2 lists all NHP SCC in the published literature, and includes the baboon and spider monkey cases reported here. The most frequent NHP species reported with SCC in decreasing order (Table 3) were: macaques (n = 36), baboons (n = 21), marmosets (n = 18), squirrel monkeys (n = 11), tree shrews (n = 6), tamarins (n = 2), capuchin monkeys (n = 2), a black spider monkey (n = 1), a sooty mangeby (n = 1), a spectacled langur (n = 1), and an orangutan (n = 1).

Table 2
Reported squamous cell carcinoma in nonhuman primates.
Table 3
NHP species most commonly reported with SCC.

The most common reported locations of SCC in all NHP in decreasing order (Table 4) were: oral cavity (n = 38; gingiva, tongue, buccal mucosa), integument (n = 17; perineum, sex skin, skin), esophagus (n = 15), cervix-uterus (n = 8), lung (n = 6), nasal cavity (n = 3), and eye (n = 2). SCC was reported once each in the trachea and axillary lymph node. Nine reported cases of SCC involving the soft tissues of the head in marmosets were not identified to a specific location.

Table 4
Most common SCC locations in NHP.

The oral cavity was the most common site in all species with more than 2 reported cases, except for the tree shrew, which had no reported oral cavity SCC. Esophageal SCC was mainly seen in macaques and squirrel monkeys, with one case each in a tree shrew and an orangutan.

Baboons developed SCC later in life than macaques (p < 0.001); marmosets and tree shrews were diagnosed with SCC at younger ages. SCC in baboons was more common in females than males, while in other species there was generally similar incidence in males and females (p < 0.05). All but one case of perineal SCC was seen in female baboons (p < 0.001), the exception was a case in a 29-year-old male Macaca maurus.

All reported SCC in marmosets involved tissues of the head. SCC of the nasal cavity was only seen in male marmosets (p < 0.001). All pulmonary SCC occurred in males; four of the six were in tree shrews, and lung was the most common location for this species. Nasal cavity and pulmonary SCC occurred animals at a much younger age than SCC in other systems.

Metastasis occurred in 23% of NHP (23 of 100), but extensive local invasion was common and often led to the eventual euthanasia of the animal even following surgical excision. Although not statistically significant, there were 9 reports of SCC metastasis in M. mulatta, but none in M. fascicularis. SCC of the esophagus and oral cavity appeared most likely to metastasize, but also did not reach significance.


We reviewed 100 new and reported cases of SCC in NHP and report the first SCC in a spider monkey and the first naturally occurring tracheal SCC in a NHP. The macaque, baboon, and marmoset were the most common species reported; this is likely a reflection of their larger numbers in captivity and use in research rather than an increased species incidence of SCC.

The reason for the male predominance in nasal cavity and pulmonary SCC cases is unknown. The young age of diagnosis for these tumors was likely a result of their presence in species with a shorter lifespan (marmosets, tamarins, and tree shrews).

Baboons were the only species demonstrating a definite sex bias, with females affected overwhelmingly. This may be a result of the high prevalence of perineal neoplasms and a general population bias towards females, particularly among older animals. Although 8 of the 9 reported marmoset cases with known sex were male, the fact that an additional 9 cases were reported without sex information makes any conclusions concerning sex in this species speculative.

Perineal SCC was observed only in females and all but one case were seen in baboons. Several factors may account for this. Increased sunlight exposure is likely a factor: 5 of the 8 reported cases are from SFBR, where the baboons are housed outdoors. Possible contributors in the SFBR colony include sunlight exposure [1,53] trauma to the sex skin [53], and the effects of chronic herpes papio 2 infection [44], or Histoplasmosis duboisii infection of the sex skin [12]. SCC in this location often appeared similar to traumatic lesions resulting in delayed diagnosis. Definitive diagnosis by biopsy should be attempted early in the presentation of ulcerative lesions involving the perineum in baboons in order to avoid long ineffective treatment periods.


The authors acknowledge Marie Silva, Michaelle Hohmann and Denise Trejo for pathology support and the expert assistance of the Technical Publications personnel.

This work was supported by NIH NCRR grant P51 RR013986 to the Southwest National Primate Research Center.


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