Renal cell carcinoma (RCC), arising from renal tubular epithelial cells, is one of the most malignant forms of urogenital cancer and the sixth most common form of cancer in human males [1]. RCC is usually asymptomatic; hematuria, flank pain, and a palpable abdominal mass are seen infrequently [1, 2]. In 20–30% of RCC human patients, the cancer metastasizes most often to the brain, bones, and lungs [2]. RCC is common in humans and is reported in several nonhuman primates (NHP), but has not been reported in marmosets.

A seven-year old, female common marmoset (Callithrix jacchus) was humanely euthanized for chronic anemia and a very low hematocrit (patient: 12.6%, Reference range: 37–53%). A complete necropsy was performed and appropriate tissue samples were taken for histologic evaluation. All tissues were fixed in 10% neutral buffered formalin, processed conventionally, embedded in paraffin, cut at 5 micrometers, stained with hematoxylin and eosin and evaluated by board-certified veterinary pathologists. All animal care and procedures were approved by the Texas Biomedical Research Institute Institutional Animal Care and Use Committee. The lifetime records for the animal were retrieved and reviewed for clinical history and research-use.

At necropsy, the kidneys were bilaterally enlarged, firm, irregularly shaped, and pale to yellow-red. Histologically, bilaterally, the renal cortex was replaced by extensive areas of interstitial fibrosis, degeneration and regeneration of tubular epithelium, ectasia and loss of tubules, glomerular sclerosis, and infiltrates of lymphocytes, plasma cells, and erythroid and myeloid precursors, and megakaryocytes (chronic renal disease and extramedullary hematopoiesis) (Figure 1A, 1B). Additionally, there were two, well demarcated, masses in one kidney. The larger mass contained a central cavitated area filled with hemorrhage, cell debris, and macrophages (Figure 1C, 1D). The smaller mass contained scattered cholesterol clefts (Figure 1E, 1F). Both masses were composed of clusters and rare tubules of polygonal cells supported by a fine fibrovascular stroma (Figure 1D, 1F). The neoplastic cells had distinct cell borders, abundant pale, eosinophilic granular to vacuolated cytoplasm and irregular nuclei with lightly stippled chromatin and 1–2 basophilic nucleoli (Figure 1D, 1F). There were scattered multinucleate cells. Mitoses averaged 1 per 10 HPF. The neoplastic cells in the smaller mass were more pleomorphic (Figure 1F). Immunohistochemistry with markers PAX8, and CD10 was performed. The neoplastic cells of the kidney showed strong positive immunoreactivity to CD10 (Mouse anti-human, Monoclonal antibody, Ventana Cat # 760–2531), (Figure 1G) and PAX8 (Rabbit anti-human, Monoclonal antibody, Ventana, Cat # 790–4341) (Figure 1H),

A literature search for all published cases of spontaneous NHP renal tumors was performed. Cases of experimentally induced renal tumors were excluded. Where discrepancies were seen between reports, the data from the original publication of the case was utilized.

Pathology records were reviewed for 26,937 (13,549 female, 12,340 males, 1,048 unknown) NHP necropsied over a 41-year period (1983–2024) at the Southwest National Primate Research Center at the Texas Biomedical Research Institute. Cases from animals in a research study were excluded. Fifteen cases (8 female, 7 male) of renal tumors were identified and the original medical records, gross necropsy, and histopathology reports were reviewed. For each NHP, the following information was obtained: species, age, sex, and tumor type. Four of the 15 had been previously reported (two nephroblastomas, one metastatic adrenal carcinoma, and one metastatic hepatocellular carcinoma) [3–5].

Table 1 lists all 115 renal tumors in 114 NHPs, 104 reported in the published literature and 11 identified in the SNPRC pathology database. Cases were arranged by species including detailed case information, such as age, sex, and tumor type. Aging classification in macaques and baboons were determined according to published age classification [6]. One NHP had two tumors, a papillary renal adenoma and a transitional cell carcinoma.

Primary malignant renal neoplasms (n = 68, 64.8%) were more common than benign tumors (n = 37, 35.2%) in NHPs and were found to be more common in older animals (total=105); two tumors were of unspecified type. There were eight cases of secondary neoplasms (metastatic to the kidney). Overall, the most frequent tumors (total= 115) were carcinomas (n = 54, 47.0%), adenomas (n = 33, 28.7%), nephroblastomas (n = 9, 7.8%) and lymphomas (n = 6, 5.2%). The most common carcinomas were undifferentiated renal carcinomas (n = 20), papillary renal carcinomas (n = 13), renal adenocarcinomas (n = 6), and renal tubulopapillary carcinomas (n = 5). The most common adenomas were undifferentiated renal adenomas (n = 18) and renal tubular adenomas (n = 6). One of the nephroblastomas was a cystic variant. Five of the six lymphomas were multicentric, precluding determination of the tissue of origin.

Metastasis of primary renal neoplasia was uncommon, reported in 11.9% (8 of the 67 malignant neoplasms). Secondary renal neoplasia (metastatic neoplasms to the kidney) included hepatocellular carcinoma, and adrenal carcinoma, and likely lymphoma.

The most frequent NHPs reported with renal tumors in decreasing order were: macaques (n = 51), baboons (n = 26), prosimians (n = 16), marmosets (n = 6), and chimpanzees (n = 3).

In macaques (Macaca spp.), cases of renal carcinomas (n = 10), papillary renal carcinomas (n = 8), and renal tubular adenomas (n = 6) were most commonly reported. The average age overall was 14.33 years. Adult (n = 25) and geriatric (n = 20) macaques were affected most.

Baboons (Papio spp.) were the only species demonstrating a sex bias, with males (n = 14) more often affected than females (n = 6). Baboons were also unique in that they had more renal adenomas (n = 11) than carcinomas (n = 5); however, they had the highest rate of nephroblastoma (n = 4). The most common renal tumors reported in baboons included renal adenomas (n = 9), nephroblastomas (n = 4), and lymphomas (n = 2). Fourteen baboons (53.85%) were over the age of fifteen and the overall age of incidence in baboons was 16.51 years. Geriatric (n = 12) baboons were most affected.

Prosimians (Cheirogaleus spp., Eulemur spp., Lemur spp., Loris spp., Microcebus spp., Mirza spp., Nycticebus spp., and Perodicticus spp.) were most commonly reported with carcinomas including renal adenocarcinomas (n = 4) and renal carcinomas (n = 3). Marmosets (Callithrix spp.) had a variety of renal tumors, with no predominance of any specific tumor. Chimpanzees (Pan spp.) only had reported cases of renal carcinomas (n = 3).

The marmoset’s presentation for anemia was likely due to the kidney’s reduced function and ability to produce erythropoietin secondary to the chronic nephritis. The RCC was an incidental finding.

Although different subtypes of primary renal neoplasms are not clearly identified in NHP, in humans, they can be classified histologically into many types. The most common types of RCC are clear cell, papillary, chromophobe, and collecting-duct RCC [2]. Features of clear cell RCC include a low nuclear to cytoplasmic ratio, high vascularity, centrally or eccentrically-placed nuclei, prominent nucleoli, high pleomorphism, and wispy, granular, or vacuolated cytoplasm [7]. Features of papillary RCC include papillary or tubulopapillary growth patterns, long, branching papillae, and surrounding tumor cells arranged in tight clusters/spherules [7]. Papillary RCC are often multifocal and commonly seen in cases of chronic renal disease [8]. Both clear cell and papillary RCC often contain hemorrhage, necrosis, or cystic degeneration [8]. In chromophobe RCC, tumor cells are typically single or in loosely-cohesive groups. The cells have central nuclei with dark chromatin and abundant cytoplasm. Binucleation and nuclear pleomorphism can also be consistent with chromophobe RCC [7]. Collecting-duct RCC is a rare type of renal cell carcinoma arising from collecting ducts in the renal medulla. In 80% of collecting-duct RCC cases, there is metastasis to lymph nodes [7]. Although the presence of multifocal masses in a chronically diseased kidney can be features of papillary RCC, the absence of papillary structures and the cytomorphology of the tumor cells in this case are most consistent with a clear cell RCC.

CD10 (also known as neprilysin) is a membrane-bound zinc-dependent metalloprotease that is highly expressed in renal tissue. It is notably useful in distinguishing between different subtypes of renal cell carcinoma (RCC). It is expressed in clear cell RCC and certain other renal tumors but is absent or weak in other RCC subtypes, such as papillary RCC or chromophobe RCC. In addition, CD10 is useful in identifying renal oncocytoma, a benign tumor, and is also seen in collecting duct carcinomas. Higher CD10 expression in certain tumors may correlate with a more aggressive phenotype and worse prognosis, particularly in clear cell RCC. Pax8 (Paired box gene 8) Pax8 is a transcription factor that is expressed in the epithelial cells of the kidney and is a key marker for renal differentiation. Pax8 is highly sensitive and specific for renal tumors, including RCC and renal oncocytoma. It is also expressed in tumors that arise from the renal collecting ducts. [9–12]

Across all NHPs, malignant renal neoplasms were more frequent than benign; however, this may represent a reporting bias. There appears to be a sex predilection for renal tumors in baboons, with an increased incidence in males.

In conclusion, this is the first report of a renal cell carcinoma in the common marmoset (Callithrix jacchus). Although neoplasia is uncommon in marmosets, they have several naturally occurring cancers [13].