Pagetoid Intraepithelial Neoplasia Linked With Tumor-Related Mortality

Patients with pagetoid intraepithelial neoplasia, a form of eyelid sebaceous carcinoma (SC), have increased chances of tumor-related mortality, according to a study published in the British Journal of Ophthalmology. Nearly one-third of patients with eyelid SC have intraepithelial tumor growth, the study shows.

The researchers reviewed the medical history of 214 patients (median age 63 years at diagnosis, 124 women) with SC who were evaluated at a Chinese hospital between January 2000 and January 2019. They excluded patients who had intraepithelial SC without tumors.

The median diagnostic delay was 18 months, and 78 patients were previously misdiagnosed in response to the eyelid SC symptoms. Misdiagnoses included blepharitis (n=25) and squamous cell carcinoma (n=19).

The most frequently impacted area (n=107) was the upper lid, followed by the lower lid (n=70), caruncle (n=27), bulbar conjunctiva (n=20), and both lids (n=13). In 35 cases, orbital involvement was present from baseline and 15 cases had lymph node metastasis. Researchers discovered that 67 patients had intraepithelial invasion, including 34 with pagetoid, 27 with bowenoid, and 6 with papillary.

Intraepithelial invasion was linked with longer diagnostic delay (P =.04). 

When researchers analyzed solely patients with intraepithelial growth patterns, they found that women were more likely to have pagetoid growth pattern (74%) and men were more likely to have papillary growth pattern (83% P =.023).

Diagnostic delays were longest in the pagetoid group (31 months), followed by the papillary group (22.5 months) and bowenoid group (18 months P =.006). Patients with pagetoid intraepithelial spread experienced longer diagnostic delay (P =.001) and more frequent misdiagnosis with blepharitis (P =.035). Median follow-up time was 34 months.

Pagetoid intraepithelial invasion was somewhat associated with increased risk of distant metastasis (HR=2.57, P =.050). Thirty patients, including 22 with eyelid SC, died during follow-up after a median 36 months. Those who died included 15 without intraepithelial invasion, 6 with pagetoid and 1 with bowenoid. Patients with pagetoid intrapethlial growth had higher risk of cumulative tumor-related mortality (pagetoid vs non-intraepithelial: HR=2.75 P =.040; pagetoid vs non-pagetoid: HR=2.95 P =.026).

“From our observation, the pagetoid intraepithelial growth pattern was associated with increased chances of tumour-related mortality, whereas the bowenoid and papillary pattern did not alter the clinical outcomes in terms of recurrence, metastasis and mortality,” the investigators report. “The higher tumour-related mortality in patients with  pagetoid invasion is probably attributable to a delay in diagnosis and appropriate treatment.”

The researchers recommend ophthalmologists carefully examine patients with pagetoid invasion and determine whether those with SC have intraepithelial tumor growth.

Limitations include exclusion of cases with obscured epithelium, lack of multivariate analyses, and inability to establish causation.


Zhou C, Chai P, Xia W, et al. Intraepithelial growth pattern for eyelid sebaceous carcinoma: a cohort of 214 patients from a single institution. Br J Ophthalmol. Published online October 16, 2021. doi:10.1136/bjophthalmol-2021-319789