Positive markers
CK-PAN: Pan-cytokeratin. Indicates an epithelial tumor.
CK7: Cytokeratin 7. A glandular epithelial marker.
CD117: c-kit. Positive in oncocytoma.
P63: A basal cell marker. Positive.
Oncocytoma (oxyphilic cell tumor)
Key points at a glance
Section titled “Key points at a glance”1. What is oncocytoma (oxyphilic cell tumor)?
Section titled “1. What is oncocytoma (oxyphilic cell tumor)?”Oncocytoma (oxyphilic cell tumor) is a benign tumor composed of eosinophilic epithelial cells (oncocytes) rich in mitochondria. Oncocytoma of the ocular adnexa was first reported in the literature in 1941 as a lacrimal caruncle lesion.
Known sites of occurrence in the body include the thyroid gland, parathyroid glands, salivary glands, and kidneys, and in the salivary glands it accounts for 1% to 2% of all tumors. In the ocular adnexa, the incidence is extremely rare at 0.3 per 1 million people per year. In the ICD-10 classification, it falls under D31.
Frequency by site of occurrence
Section titled “Frequency by site of occurrence”The following shows the frequency of ocular adnexal oncocytoma by site of occurrence based on a review of 212 cases in the literature.
| Site of occurrence | Number of cases | Percentage |
|---|---|---|
| Lacrimal caruncle | 127 cases | 60% |
| Lacrimal sac | 40 cases | 19% |
| Conjunctiva | 20 cases | 10% |
| Eyelid | 15 cases | 6% |
| Lacrimal gland | 10 cases | 5% |
Reports of malignant forms (eosinophilic adenocarcinoma) are extremely rare, with only 3 cases in the lacrimal gland and 11 in the lacrimal sac.
Q
Which site is most common for ocular adnexal oncocytoma?
A
In a literature review of 212 cases, the lacrimal caruncle was the most common site, with 127 cases (60%). This was followed by the lacrimal sac (19%) and the conjunctiva (10%). Occurrence in the lacrimal gland and eyelid is relatively rare.
2. Main symptoms and clinical findings
Section titled “2. Main symptoms and clinical findings”Subjective symptoms
Section titled “Subjective symptoms”The most common symptom is the appearance of a mass (lump). It may also be accompanied by the following symptoms:
- Mass: Noticed as a painless mass in the ocular adnexa (lacrimal caruncle, conjunctiva, eyelid, lacrimal sac, lacrimal gland).
- Discomfort: Local discomfort or a foreign-body sensation may occur because of the mass.
- Tearing (epiphora): Occurs when the mass involves the lacrimal drainage system (lacrimal sac, lacrimal caruncle).
Clinical findings
Section titled “Clinical findings”Imaging evaluation with ultrasound biomicroscopy (UBM) and anterior segment optical coherence tomography (AS-OCT) is performed. In a study of 15 cases, the following findings were reported.
- Mixed solid-cystic appearance: On UBM/AS-OCT, both solid and cystic components are seen together.
- No scleral invasion: No signs of scleral invasion are seen, suggesting benign behavior.
Ultrasound biomicroscopy is a contact test that can obtain detailed cross-sectional images of the anterior segment at a resolution of 20–60 μm. Anterior segment optical coherence tomography is non-contact and can obtain high-resolution cross-sectional images, so it places less burden on the patient.
Q
What is seen on imaging studies of an oncocytoma?
A
Ultrasound biomicroscopy and anterior segment optical coherence tomography are characterized by mixed solid and cystic components. There are no signs of scleral invasion, and the imaging features are consistent with a benign tumor. This is a useful test for assessing the tumor extent before surgery.
3. Causes and risk factors
Section titled “3. Causes and risk factors”Pathophysiology
Section titled “Pathophysiology”Mitochondrial and somatic gene mutations are thought to be involved in the development of oncocytoma.
The mechanism is as follows.
- Failure of oxidative phosphorylation: Mitochondrial gene mutations impair oxidative phosphorylation.
- Reduced ATP production: ATP production within mitochondria decreases.
- Compensatory increase in mitochondria: To make up for reduced energy production, mitochondria are thought to accumulate within the cell.
- Formation of eosinophilic granular cytoplasm: The accumulation of mitochondria is seen under light microscopy as abundant eosinophilic granular cytoplasm.
Mutations in mitochondrial DNA (mtDNA) have been reported in salivary gland oncocytoma1). A similar molecular mechanism may also be involved in ocular adnexal oncocytoma.
4. Diagnosis and examination methods
Section titled “4. Diagnosis and examination methods”Pathological findings
Section titled “Pathological findings”Histopathological examination is essential for a definitive diagnosis.
- Macroscopic findings (cell morphology): Composed of enlarged polygonal to cuboidal epithelial cells with little atypia.
- Cytoplasm: Abundant and strongly eosinophilic, due to massive mitochondrial accumulation.
- Nuclei: Little atypia; benign nuclear features.
- Mitochondrial confirmation: PTAH (phosphotungstic acid hematoxylin) stain can be used to confirm mitochondria1).
Immunohistochemistry
Section titled “Immunohistochemistry”Based on data from salivary gland oncocytoma, the following immunostaining features are seen1). A similar staining pattern is suggested for ocular adnexal oncocytoma.
Negative markers
Ki-67: <2%, showing low proliferative activity and reflecting a benign tumor nature.
Vimentin・CD10: Mesenchymal and renal cell carcinoma markers. Negative.
S-100・SOX-10: Nerve and Schwann cell markers. Negative.
Imaging studies
Section titled “Imaging studies”- Ultrasound biomicroscopy (UBM): Useful for evaluating anterior segment tumors. Can visualize the ciliary body and the back surface of the iris. Contact examination.
- Anterior segment optical coherence tomography (AS-OCT): Non-contact, high-resolution cross-sectional imaging. Less burdensome for patients.
- On both tests, evaluate whether solid and cystic components are mixed and whether there is scleral invasion.
Differential diagnosis
Section titled “Differential diagnosis”The lacrimal caruncle is a site where many different lesions can occur, so pathological examination is essential for differential diagnosis. The following shows the frequency of each disease in a pathological review of 112 lacrimal caruncle cases.
| Lesion | Frequency |
|---|---|
| Nevi | 43% |
| Squamous papilloma | 13% |
| Sebaceous hyperplasia | 9% |
| Chronic inflammation | 5% |
| oncocytoma | 4% |
| epithelial inclusion cyst | 4% |
| foreign body granuloma | 3% |
| pyogenic granuloma | 3% |
| malignant melanoma | 2% |
| capillary hemangioma | 2% |
Other rare lesions such as lymphoma, basal cell carcinoma, and squamous cell carcinoma are also considered in the differential diagnosis.
Q
What is the most important lacrimal caruncle lesion to consider in the differential diagnosis of oncocytoma?
A
The most common lesion of the lacrimal caruncle is nevus (43%). Oncocytoma is rare at 4%, and it is difficult to distinguish them based on clinical findings alone. Definitive diagnosis requires histopathological examination of a biopsy or excised specimen.
5. Standard treatment
Section titled “5. Standard treatment”Benign cases (lacrimal caruncle/conjunctiva)
Section titled “Benign cases (lacrimal caruncle/conjunctiva)”The standard treatment for oncocytoma arising in the lacrimal caruncle or conjunctiva is complete excision (total resection).
- Prognosis after complete excision: No recurrences have been reported for lacrimal caruncle or conjunctival lesions after complete excision, and the prognosis is excellent.
- Follow-up: Regular follow-up should be performed after excision.
Recurrence risk by site of origin
Section titled “Recurrence risk by site of origin”Low recurrence risk
Lacrimal caruncle and conjunctiva: No recurrences have been reported after complete excision.
The clinical course is benign. Cure can be expected with complete excision.
Risk of recurrence
Eyelid, lacrimal sac, and lacrimal gland: Even after complete removal, recurrence can occur in rare cases.
Careful follow-up is needed.
Malignant cases (oncocytic adenocarcinoma)
Section titled “Malignant cases (oncocytic adenocarcinoma)”There have been 15 reported cases of oncocytic adenocarcinoma (malignant oncocytoma), and more aggressive management, including radiotherapy and chemotherapy, is needed.
Q
How high is the risk of recurrence after complete removal?
A
The risk of recurrence varies by site. There have been no reports of recurrence after complete removal in the caruncle or conjunctiva, and the prognosis is favorable. On the other hand, rare recurrences have been seen in the eyelid, lacrimal sac, and lacrimal gland, so regular follow-up is important.
6. Pathophysiology and detailed mechanism of onset
Section titled “6. Pathophysiology and detailed mechanism of onset”The molecular mechanism underlying the development of oncocytoma is thought to be as follows.
When mitochondrial DNA (mtDNA) mutations occur, oxidative phosphorylation is impaired through dysfunction of the electron transport chain. As a result, ATP production decreases and the cell becomes energy-depleted. As a compensatory response to this state, mitochondria accumulate abnormally within the cell. mtDNA mutations have been reported in salivary gland oncocytoma1), and a similar mechanism is thought to occur in the ocular adnexa as well.
Accumulated burnt-out mitochondria form the following pathologically characteristic findings.
- Eosinophilic granular cytoplasm: observed as granular cytoplasm that stains deep pink on H&E staining.
- Cell body enlargement: cells become markedly enlarged due to accumulation of mitochondria.
- Low proliferative activity: Ki-67 proliferation index is <2%, reflecting the slow growth of the tumor1).
7. Latest research and future prospects (reports at the research stage)
Section titled “7. Latest research and future prospects (reports at the research stage)”Because orbital adnexal oncocytoma is extremely rare, with an incidence of 0.3 cases per million people per year, there is no evidence from large prospective studies or randomized controlled trials. Current research trends are as follows.
- Genome and immunohistochemical analysis: Reports have described the characteristics of immunostaining panels such as CK-PAN, CK7, CD117, and P63 in salivary gland oncocytoma1). Extrapolating these findings to orbital adnexal oncocytoma remains a future challenge.
- Refinement of preoperative imaging assessment: Evidence is accumulating regarding the evaluation of solid and cystic components using ultrasound biomicroscopy/anterior segment optical coherence tomography and the exclusion of scleral invasion.
- Clarification of malignant transformation mechanisms: The molecular mechanism of malignant transformation into eosinophilic adenocarcinoma remains unclear, and further research is expected.
8. References
Section titled “8. References”- Zhu W, Zhang Y, Li F, Li G, Zhang P, Fang H, Bian L. Case of clear-cell oncocytoma of parotid gland and literature review. Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology. 2024;42(1):126-134. doi:10.7518/hxkq.2024.2023185. PMID:38475961; PMCID:PMC10965352.
- Williams GM, Lynch DT. Renal Oncocytoma. . 2026. PMID: 30725948.
- Mirkheshti N, Farrukh N, Legesse T, Rowe SP, Gordetsky J, Hussain A. Renal oncocytoma: a challenging diagnosis. Curr Opin Oncol. 2022;34(3):243-252. PMID: 35671122.