Benign nodal epithelial inclusions may mimic metastasis in macaques

A case report in Veterinary Pathology is putting a small but important diagnostic trap on the radar for veterinary pathologists: benign epithelial inclusions in renal hilar lymph nodes of a cynomolgus monkey. The lesion, which would ordinarily raise concern for metastatic carcinoma, was found in an animal with severe renal damage but no evidence of neoplasia, underscoring how easily epithelial cell clusters in lymph nodes can be overinterpreted if morphology is assessed without clinical and anatomic context. (pathologyjournal.rcpa.edu.au)

That matters because epithelial inclusions in lymph nodes are a well-established source of confusion in human pathology, even if they remain uncommon. Reviews and case reports describe benign nodal inclusions from several tissue types, including salivary, thyroid, Müllerian, breast, mesothelial, and squamous epithelium, and emphasize that they can mimic metastatic deposits. In renal-associated nodes specifically, benign renal tubular epithelial inclusions have been documented only rarely, making the monkey case notable as a comparative and diagnostic reference point. (pmc.ncbi.nlm.nih.gov)

According to the abstract provided by the journal, the epithelial inclusions in this macaque were located in the subcapsular sinuses of renal hilar lymph nodes and were positive for cytokeratin. The monkey also had severe renal damage, but the report found no neoplastic lesion to explain the nodal epithelial cells as metastasis. That pattern aligns with prior human literature suggesting that renal tubular-type epithelial inclusions may be associated with damaged kidney tissue and lymphatic transport of benign epithelial elements, rather than malignant dissemination. One earlier human series described benign renal tubular epithelial inclusions in perinephric hilar lymph nodes, including a case with a severely atrophic kidney and enlarged hilar nodes. (sciencedirect.com)

The broader pathology literature helps explain why this distinction is so important. In human oncology practice, benign epithelial inclusions in sentinel or regional lymph nodes have been mistaken for metastatic carcinoma, sometimes leading to unnecessary additional surgery or altered staging. Reviews note that these inclusions often sit near the capsule or in subcapsular locations, can be solitary, and may require immunohistochemistry plus correlation with the primary site to separate them from true metastases. (pubmed.ncbi.nlm.nih.gov)

Direct expert reaction to this specific monkey report was limited in publicly accessible sources, but the consensus from the pathology literature is clear: benign nodal inclusions are a diagnostic pitfall, not a curiosity to dismiss. Authors across multiple human case reports and reviews stress that awareness of these lesions can prevent overtreatment and misclassification. That same caution likely applies in veterinary and preclinical settings, where incidental findings in nonhuman primates may otherwise be interpreted as evidence of systemic malignancy or test article-related change. This is an inference based on the human and comparative pathology literature, rather than a direct quote about the present case. (ascopubs.org)

Why it matters: For veterinary professionals, the practical takeaway is less about prevalence and more about pattern recognition. In a research, diagnostic, or toxicologic pathology setting, epithelial cells in a lymph node usually trigger concern for metastasis. This case broadens the differential diagnosis in cynomolgus monkeys and suggests that severe renal injury, lesion location within the node, and epithelial marker staining should all be weighed before concluding malignancy. It also reinforces the value of complete necropsy correlation and careful review of the kidney when renal hilar nodes contain epithelial structures. (sciencedirect.com)

The report also fits into a larger body of literature showing that unusual lymph node lesions do occur in cynomolgus monkeys and may be incidental. For example, Toxicologic Pathology has previously published rare intranodal lesions in this species, including an angiomyomatous hamartoma found in a control animal and considered to have no clinical or toxicologic significance. That precedent doesn’t make the lesions equivalent, but it does support a familiar message for veterinary pathologists: rare nodal findings in nonhuman primates need disciplined differential diagnosis, not reflex attribution to malignancy or study effect. (journals.sagepub.com)

What to watch: The next step will be whether additional case reports, conference abstracts, or review articles in veterinary pathology build on this finding and formalize how benign epithelial inclusions in nonhuman primate lymph nodes should be worked up, particularly in renal-associated lesions and safety assessment studies. (e-century.us)