Primary periocular basal cell carcinoma: recurrence, risk factors and follow-up^☆

Dear Editor,

Primary basal cell carcinoma (BCC) is the most common periocular malignant tumor.¹ Periocular tumors present therapeutic challenges due to the need for radical surgical excision while preserving eyelid function and facial aesthet-ics.

Although established guidelines recommend long-term follow-up for patients diagnosed with BCC due to the high risk of developing new lesions,¹ Brazil lacks a national registry for skin or periocular cancers. Available data are derived from small hospital-based studies, and national guidelines do not include standardized long-term follow-up protocols, leaving monitoring decisions to individual clini-cians.

To propose a tailored follow-up strategy for the Brazilian context, we retrospectively reviewed patients with pri-mary periocular BCC who underwent surgical excision at our university hospital between March 2012 and December 2019 (Ethics approval: 39820420.1.0000.5411). All included patients who had complete excision of primary periocular BCC, confirmed histological subtype, documented margin status, and at least 12-months of follow-up. Non-periocular BCCs, recurrent tumors, prior radiotherapy or cryotherapy, immunosuppression, Gorlin-Goltz syndrome, and incom-plete records were excluded.

We analyzed 135 histologically confirmed periocular BCC lesions from 116 patients, averaging 19.28 lesions treated annually. Periocular BCC predominantly affected elderly individuals, with a mean age of 69.47 ± 12.16 years old (range: 37-93) and a median age of 72. This trend likely reflects cumulative sun exposure, reduced DNA repair capacity, and age-related decline in immune response.²

Of the patients, 63 (54.31%) were female, with no sig-nificant gender difference in the occurrence of BCC. A higher incidence of periocular BCC in women has already been reported.³ The vast majority of patients (111/95.69%) had phototypes I or II, reinforcing the established link between BCC and lighter pigmentation, especially in indi-viduals chronically exposed to sunlight. In contrast, darker skin provides greater UV protection and is associated with lower BCC risk.⁴

The mean tumor size was 7.23 ± 4.96 mm (range: 2-40 mm; median: 8 mm). The lower eyelid was the most affected site (110/81.48%), followed by the medial can-thus (11/8.15%), upper eyelid (7/5.19%), lateral canthus (6/4.44%), and eyebrow (1/0.74%), consistent with previous studies.⁵,⁶ The lower eyelid and medial canthus are more exposed to UV radiation and inflammatory agents such as tear components. The upper eyelid, protected by the brow and orbital anatomy, showed a lower frequency. No signif-icant laterality effect was noted, although some studies suggest a higher incidence on the side of the face more exposed during driving.⁷

Tumors were generally conventionally excised under local anesthesia with 2-5 mm safety margins, depending on lesion size, consistent with other reports.⁸ Wider excision is recom-mended for aggressive subtypes of tumors (sclerodermiform, mixed), though it may compromise cosmetic and functional outcomes.⁹

In our clinic, frozen section or surgical excision with a safety margin is reserved for lesions with indistinct borders. This differs from other approaches that use frozen sections routinely or opt for wide local excision or Mohs surgery.¹

The most common histological subtype was nodular (59/43.70%), followed by mixed (52/38.52%) (Table 1). Perineural invasion occurred in only one case (1/0.74%), consistent with other studies.⁵,⁶,¹⁰

Table 1
Histological classification and surgical margins of periocular BCC treated at Faculty of Medicine - UNESP, 2025.

Variable Frequency	%
Histological classification
Nodular 59	43.70
Mixed 52	38.52
Sclerodermiform 7	5.19
Multifocal 2	1.48
Othera 2	1.48
No information 13	9.63
Perineural involvement
No 130	96.3
Yes 1	0.74
No information 4	2.96
Committed margins
No 110	81.48
Yes 14	10.37
No information 3	2.22
Committed margins and locationb
Deep 11	42.31
Lateral 10	38.46
Nasal 2	7.69
Upper 2	7.69
Lower 1	3.85

• ^a
  Others: Micronodular, multifocal, infiltrative, fibroepithelial, basosquamous, plexiform, keratotic and metatypy (WHO, 2006).
• ^b
  More than one margin can be affected (Total = 26).

We observed nine recurrences: 6 (66.67%) occurred in lesions with clear margins, underscoring that nega-tive margins do not eliminate recurrence risk; 3 (33.33%) recurrences were from lesions with compromised margins. Of the 14 cases with involved margins, only 3 (21.43%) recurred. Reported recurrence rates for positive margins vary widely,⁵,⁸,⁹ depending on histological subtype, surgical excision type, and follow-up duration.¹

Recurrences in our cohort were significantly associated with histological subtype (p = 0.037), being more frequent in nodular (3/33.33%), mixed (2/22.22%), and sclerodermi-form (2/22.22%) subtypes. While nodular BCC is generally well-defined and amenable to complete excision, its recurrence rate in our sample likely reflects its high prevalence rather than intrinsic aggressiveness. In mixed BCC, the lesion may be composed of either high-risk or low-risk subtypes, making it important for the histological report to specify which subtypes are present in the lesion. Conversely, aggres-sive subtypes such as sclerodermiform are known to pose greater risks of incomplete excision and recurrence. Most recurrences occurred in the lower eyelid (8/88.89%) or in the medial canthus (1/11.11%), which were also the most com-mon tumor locations. No significant association was found between recurrence and tumor size or margin status. Tumor-free surgical margins were achieved in 110 (81.48%) lesions, while compromised margins were identified in 14 (10.37%) cases. Twelve (8.89%) cases had indefinite margins; a known possibility related to the quality of some specimens.

The most frequently affected margin was the deep plane (11/42.31%), like other reports.¹ Although BCC typically exhibits limited depth invasion, meticulous excision of the deep portion remains essential. In the medial canthus, erro-neous efforts to preserve the lacrimal drainage system may inadvertently result in incomplete excision. Nevertheless, complete removal must remain the surgical goal to prevent orbital invasion and associated morbidity.

The mean follow-up duration was 3.41 ± 2.68 years (median: 2.84). Most patients’ lesions (88/75.86%) remained in follow-up, 39 (28.89%) were lost to follow-up after two years, four (2.96%) died from unrelated causes, and four lesions (2.96%) were from patients without disposable data on the records. No BCC metastases were reported. Table 2 presents recurrence according to histological subtype, com-mitted margins and time to observe lesion recurrence. Mean time to recurrence was 2.92 ± 2.37 years (range: 1.09-6.25; median: 1.39-years).

Table 2
Recurrence after exeresis according to histological subtype and years.

Histological subtype	Committed margins	Reccurrence (years)
Mixed	No	1,23
No information	No	1,68
Mixed	Yes	1,39
Sclerodermiform	No	1,09
Others	Yes	1,34
Nodular	Yes	1,34
Sclerodermiform	No	6,64
Nodular	No	6,25
Nodular	No	5,18

According to other studies, periocular BCC recurrence rates are influenced by tumor location, size, histological subtype (more aggressive subtypes include micronodu-lar, infiltrative, sclerosing, and morphea), margin status, immune function, systemic diseases, prior recurrences, and adjuvant treatments.⁶,¹⁰

The approach to incomplete excision of BCC remains controversial. Since not all cases of low-risk tumors will recur,⁹ we recommend that re-excision should be evaluated on a case-by-case basis, considering factors such as high-risk anatomical location, involvement of deep or lateral margins, and the patient’s ability to adhere to follow-up.

Histologically compromised margins or incomplete lesion removal are not definitive predictors of recurrence. Recur-rence may not occur even after several years, and clinical observation may be appropriate. Possible explanations for the absence of recurrence include devitalization of resid-ual tumor cells by postoperative inflammation, containment within excision margins, differences in tumor biology, sur-gical technique, clinical management, or other biological mechanisms not yet fully understood. However, although re-excision is not necessary in all cases, it is strongly recommended for positive margins, particularly in high-risk histological subtypes, with meticulous excision of the affected margin.

Postoperative follow-up of excised periocular BCCs repre-sents a significant workload for clinicians, and institutional protocols vary. For completely excised nodular BCC, recur-rence risk is low, and follow-up for at least one year is recommended.

For aggressive subtypes, follow-up should extend to a minimum of five years, while recurrent tumors require indef-inite surveillance. Approximately 30% of recurrences occur within the first year, and up to 82% within five years, rein-forcing this period as the critical window for monitoring.

However, the purpose of follow-up is not only to detect local recurrence but also to identify new BCCs. Individuals who have already had one carry a 30%-40% risk of developing another,⁹ and therefore the patient requires close surveil-lance.

Limitations and strengths

The limitations of this study include its retrospective design, which inherently involves incomplete information in medi-cal records, the involvement of multiple surgeons, and histopathological evaluations performed by doctors in train-ing - factors that may affect the external validity and reproducibility of the findings. Another study limitation is that surgical margin assessment was not specified in 100% of the margins; such a comprehensive evaluation could have provided additional data to strengthen the conclu-sions. Notable strengths include the relatively large number of lesions analyzed, which contributes to the statistical robustness of the data. Additionally, all surgical proce-dures and histopathological evaluations were conducted under the supervision of a senior ophthalmologist and a dermatopathologist, enhancing diagnostic accuracy and classification reliability.

Recommendations

• • Early diagnosis, timely treatment, and consistent follow-up of periocular BCC are essential to reduce morbidity and mortality.

• • Because patients with a history of BCC have an increased risk of developing additional tumors, follow-up should monitor both recurrence and the emergence of new lesions.

• • Patient education on self-surveillance and sun protection is critical for early detection and prevention.

• • Complete excision of low-risk lesions carries a low recur-rence risk; such patients may be monitored for one year.

• • Recurrences occurred on average three years post-surgery, with earlier recurrences (around one year) often associated with positive margins. Patients with compromised margins or confirmed recurrence should remain under annual follow-up, including routine dermatological assessments, for at least five years, regardless of subtype. After five years, patients may transition to primary care follow-up, provided that primary care teams are trained in lesion surveillance.

• ☆
  Study conducted at the Faculty of Medicine, Universidade Estad-ual Paulista, Botucatu, SP, Brazil.
• Financial support
  None declared.

Research data availability

The entire dataset supporting the results of this study was published in this article.

References

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• ³ Tavares GT, Morato IB, Wainstein AJA. 90-degree incision in Mohs micrographic surgery for eyelid margin tumors - is there a ben-efit? An Bras Dermatol. 2024;99:111-7.
• ⁴ Gupta P, Gupta R, Khan L. Profile of eyelid malignancy in a tertiary health care center in North India. J Cancer Res Ther. 2017;13:484-6.
• ⁵ Al Wohaib M, Al Ahmadi R, Al Essa D, Maktabbi A, Khandekar R, Al Sharif E, et al. Characteristics and factors related to eyelid basal cell carcinoma in Saudi Arabia. Middle East Afr J Ophthalmol. 2018;25:96-102.
• ⁶ Furdova A, Kapitanova K, Kollarova A, Sekac J. Periocular basal cell carcinoma - clinical perspectives. Oncol Ver. 2020;14:420.
• ⁷ Simon GJB, Lukovetsky S, Lavinsky F, Rosen N, Rosner M. Histo-logical and clinical features of primary and recurrent periocular basal cell carcinoma. ISRN Ophthalmol. 2012;2012:354829.
• ⁸ Koelblinger P, Lang R. New developments in the treatment of basal cell carcinoma: update on current and emerging treat-ment options with a focus on vismodegib. OncoTargets Ther. 2018;11:8327-40.
• ⁹ Fidelis MC, Stelini RF, Staffa LP, Moraes AM, Magalhães RF. Basal cell carcinoma with compromised margins: retrospective study of management, evolution, and prognosis. An Bras Dermatol. 2021;96:17-26.
• ¹⁰ Galindo-Ferreiro A, Sanchez-Tocino H, Diez-Montero C, Belani-Raju M, García-Sanz R, Diego-Alonso M, et al. Characteristics and recurrence of primary eyelid basal cell carcinoma in central Spain. J Curr Ophthalmol. 2020;32:183-8.

Edited by

• Editor
  Sílvio Alencar Marques.

Publication Dates

• Publication in this collection
  27 July 2026
• Date of issue
  2026

History

• Received
  16 July 2025
• Accepted
  08 Dec 2025
• Published
  20 Apr 2026