Commentary on: Refining prognostic assessment in eyelid sebaceous carcinoma after histologically complete excision

Sebaceous carcinoma (SC) of the eyelid is a potentially aggressive malignancy with a marked propensity for local recurrence, regional lymph node involvement, and distant metastasis. Despite advances in diagnostic modalities and surgical management, accurately identifying patients at increased risk of adverse outcomes remains a significant clinical challenge. The present study provides valuable long-term data from a large Japanese cohort and offers important insights into the clinicopathological factors associated with recurrence and metastasis following histologically complete excision of eyelid sebaceous carcinoma.

A major strength of this study is its focus on patients who underwent complete tumor excision with histologically negative margins. Previous studies have often included heterogeneous patient populations with positive margins, recurrent tumors, orbital extension, or adjuvant treatment, making interpretation of prognostic factors difficult.[1,2] Therefore, minimizing these potential confounding variables, the authors provide a more accurate assessment of the biological determinants of disease progression following apparently curative surgery.

The reported local recurrence rate of 4.8% and the metastasis rate of 7.5% are lower than those stated in previous series, where recurrence rates have ranged from 6% to 32.7% and metastatic rates from 3.1% to 28%.[3,4] These findings emphasize the importance of meticulous surgical excision with comprehensive histopathological margin assessment. Nevertheless, the recurrence and metastasis despite histologically negative margins suggest the presence of occult microscopic disease extending beyond clinically detectable tumor boundaries, thereby reinforcing the necessity for prolonged postoperative surveillance.

Among the most clinically significant findings is the strong association between pagetoid spread and both local recurrence and metastasis. Pagetoid spread is a well-recognized predictor of aggressive sebaceous carcinoma and represents intraepithelial dissemination of malignant cells beyond the clinically apparent tumor margins.[5] Such diffuse epithelial involvement may evade routine clinical detection and remain difficult to eradicate completely, even when histopathological margins appear negative. Previous studies have similarly identified pagetoid spread as an independent predictor of adverse outcomes, including local recurrence, regional lymph node metastasis, and tumor-related mortality.[6,7] The findings of the present study further strengthen the need for careful conjunctival mapping biopsies and vigilant postoperative follow-up in patients demonstrating this clinical feature.

An intriguing observation from this study is the association between female sex and increased local recurrence risk. Although sex has not consistently emerged as a prognostic factor in previous investigations, the finding is noteworthy and deserves further exploration. Hormonal influences may potentially contribute to differences in tumor biology, particularly considering that the meibomian glands are the most common site of origin of eyelid sebaceous carcinoma that express androgen, estrogen, and progesterone receptors.[8] However, future molecular and translational studies are required to elucidate whether sex-specific biological or hormonal mechanisms contribute to tumor aggressiveness or recurrence.

Furthermore, the identification of lower eyelid as a risk factor for metastasis also provides an unusual contribution to the literature. Conventionally, sebaceous carcinomas arising from the upper eyelid have received greater clinical attention owing to the higher density of meibomian glands and the perceived complexity of surgical management. However, the present study suggests that tumors involving the lower eyelid may exhibit greater metastatic potential. Anatomical differences in tarsal plate architecture, tissue barriers, and regional lymphatic drainage may partially explain this observation. If validated in future multicenter studies, tumor location could become an important parameter in postoperative risk stratification and surveillance planning.

Patients with tumors classified as AJCC T1c stage or higher exhibited a significantly increased risk of metastasis.[3,6] These findings further validate the prognostic utility of the AJCC 8^th edition staging system for risk stratification and support its role in identifying patients who may benefit from closer surveillance and more individualized postoperative follow-up strategies.

However, several limitations should be acknowledged. The retrospective design introduces the possibility of selection bias, and the relatively small number of recurrence and metastatic events limits statistical power. Additionally, multivariable analysis was not performed, making it difficult to determine whether the identified risk factors are independently associated with outcomes or influenced by confounding variables. Future multicenter prospective studies with larger patient populations and molecular profiling may help validate these findings and further refine prognostic models.

In conclusion, this study represents an important contribution to the understanding of eyelid sebaceous carcinoma. The findings demonstrate that pagetoid spread, female sex, higher AJCC stage, and lower eyelid location are associated with an increased risk of recurrence and metastasis despite histologically complete excision. These results highlight the importance of individualized risk assessment and support the development of tailored surveillance strategies for patients with high-risk disease.

Author’s contribution

MS: Definition of intellectual content, data acquisition and analysis, manuscript preparation and hold the overall responsibility for the manuscript. PS: Definition of intellectual content, literature search, data analysis and review. PG: Data acquisition, data analysis, editing and review of manuscript.