Predictive factors for the recurrence of surgically excised basal cell carcinomas: A retrospective clinical and immunopathological pilot study

Abstract

Basal cell carcinoma (BCC) is the most frequent form of skin cancer and is not a tumor with a lethal outcome if diagnosed and treated adequately. The gold standard for treatment is surgical excision with histologically safe margins. Even so, tumors excised with free margins may recur after a period of time. The identification of predictive factors for the recurrence of BCCs besides the localization, size and aggressive histology may be useful for the clinician. The aim of the present study was to identify clinical and pathological factors associated with recurrence in tumors with histologically free margins and assess via immunohistochemical staining, the expression of glioma-associated oncogene homolog 1 (GLI1), yes-associated protein (YAP), connective tissue growth factor (CTGF) and E-cadherin as they are involved in the development of BCCs, in the hope of identifying markers that are predictive for recurrence. In total, 8 recurrent BCCs and 38 non-recurrent tumors were analyzed. A Breslow index >2 (Se 100.0%, Sp 67.5%, P=0.008), Clark level >3 (Se 100.0%, Sp 47.5%, P<0.001), and excision margins both lateral (Se 87.5%, Sp 60.0%, P=0.04) and deep (Se 75.0%, Sp 82.5%, P<0.001) free from tumoral cells ≤1 mm proved to be predictive for recurrence in the present study. Recurrence may appear even after more than 3 years since the initial excision (Se 87.50%, Sp 70.0%, P<0.001). The expression levels of GLI1, YAP and E-cadherin were not different in the recurrent vs. non-recurrent BCCs. However, the low expression of CTGF may indicate a tumor with a higher aggressiveness. In conclusion, close follow-up of patients with excised BCCs at least annually is recommended and re-excision should be taken into consideration for locally advanced tumors especially if they are located in high-risk areas or those with histologically free margins <1 mm.

The Immunohistochemical Expression of the Serine and Arginine-Rich Splicing Factor 1 (SRSF1) Is a Predictive Factor of the Recurrence of Basal Cell Carcinoma: A Preliminary Study on a Series of 52 Cases

“…Although BCC is classically considered a malignant tumor, it is characterized by slow growth and an extremely low metastatic potential [1,2]. A surgical excision with tumor-free histological margins is considered the treatment of choice [9][10][11]. However, it is estimated that 2-8% of radically-excised BCCs tend to locally recur after 5 years postsurgical treatment [11].…”

“…A surgical excision with tumor-free histological margins is considered the treatment of choice [9][10][11]. However, it is estimated that 2-8% of radically-excised BCCs tend to locally recur after 5 years postsurgical treatment [11]. The tumor size, location, and some histological parameters have been identified as being involved in the recurrence of this neoplasm [11,20].…”

“…Histologically, BCCs are composed of islands/nests of basaloid cells with scant cytoplasm, hyperchromatic nuclei, and peripheral nuclear palisading; neoplastic cells are often surrounded by a fibro-myxoid stroma that induces Medicina 2022, 58, 139 2 of 8 tumor retraction [8]. Although the therapeutic gold standard is the surgical excision with tumor-free histological margins, a percentage of surgically-excised BCCs tend to recur even in the presence of safe histological margins [9][10][11]. Numerous clinical and histological parameters have been classically associated with the recurrence of BCC [10,11]: (i) its localization, (ii) the tumor size, (iii) the histological subtypes, (iv) the histological evidence of an invasion of the reticular dermis and/or subcutis, and (v) the histological presence of a vascular/perineural invasion.…”

“…Although the therapeutic gold standard is the surgical excision with tumor-free histological margins, a percentage of surgically-excised BCCs tend to recur even in the presence of safe histological margins [9][10][11]. Numerous clinical and histological parameters have been classically associated with the recurrence of BCC [10,11]: (i) its localization, (ii) the tumor size, (iii) the histological subtypes, (iv) the histological evidence of an invasion of the reticular dermis and/or subcutis, and (v) the histological presence of a vascular/perineural invasion. Based on the histology, BCCs are distinguished into lowrisk and high-risk subtypes [8].…”

“…The former includes the nodular, superficial, pigmented, infundibulo-cystic, and fibroepithelial variants; the latter includes the basosquamous, sclerosing/morphoeic, infiltrating, micronodular, and sarcomatoid variants. However, despite the above-mentioned predictive factors of local relapse, the reason why approximately 2-8% of surgically-excised BCCs with tumor-free margins locally recur at 5 years after surgery is still not clear [11]. Accordingly, it has been hypothesized that additional factors may contribute to the recurrence of this tumor.…”