Basal Cell Carcinoma Recurrence after Excision in a Patient with Complex Cardiac history: A Case Report
Introduction
We present a case report of a 79-year-old man with
previously excised basal cell carcinoma over the subcutaneous border of the
right leg 20 months ago (Figure 1) who has now presented with recurrence
of BCC on the lateral canthus of his right ocular region (Figure 2) and
anterior scalp (Figure 3). The patient had symptomatic bradycardia
awaiting cardiac pacemaker insertion at the hospital. Previous Histology
Findings from excised BCC showed that on Microscopy, a diagnosis of
Infiltrative basal cell carcinoma was made with the following tissue Thickness
of 1.7mm, Clark level IV, Stage: pT1, Peripheral margin distance measured 3.3mm
and Deep margin distance measuring 3.5mm. There was no Perineural invasion and
squamous differentiation. Risk status was high risk. All standard advice
following prevention of UV radiation (wearing wide hats) was duly followed by
the patient. However, there was no strict adherence to wearing of creams with
sun protection factor SPF.
Figure 1: Small erosions on
right lower leg subcutaneous border
Figure 2: Papule with rolled
up borders on Lateral canthus of right ocular area
Figure 3: Papule with
pearly(transparent) border on anterior scalp
Background
Skin cancer is the most common cancer in the USA. It is five times more common than breast or prostate cancer1. Despite the widespread use of Mohs micrographic surgery (MMS) for periocular basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) - together called keratinocyte carcinoma (KC) - follow-up data regarding recurrences are limited2. Due to the specialized character of Mohs micrographic surgery (MMS) for periocular Keratinocyte cancers, A retrospective cohort study by F. Weesie et al. identified the need for a multidisciplinary approach between Mohs surgeons and oculoplastic surgeons is made available in a center of expertise, especially in case of previously incompletely treated, recurrent or aggressive tumors. This collaboration leads to combining the best of both worlds, specifically combining knowledge and skills and further adding complex reconstructions to the benefits of MMS2.
Approximately 1/4 of periocular Keratinocyte cancers are incompletely removed after standard excision, with histopathologically aggressive tumors and localization in the medial canthus having the highest risk3,4. Common Anatomy locations of BCC predominantly implicate sun-exposed skin areas, with the head and neck region accounting for most cases. Within the periocular region, the lower eyelid is most affected, followed by the medial canthus, which carries higher risks of incomplete excision and recurrence due to its anatomical complexity. Additionally, the periocular area lies within the high-risk facial "H-zone," encompassing the nose, nasolabial folds and periorbital regions. Lesions in these areas tend to recur more frequently due to the presence of complex underlying anatomical structures such as orbital fat, muscles and the lacrimal drainage system3. It is estimated that 30-50% of incompletely excised KCs result in a recurrence5-7. This case underscores the importance of multidisciplinary collaboration in managing recurrent periocular BCC to optimize the best Patient outcomes, especially in complex cases which may require orbital exenteration to prevent recurrence.
Discussion
Pathophysiology
Although the exact etiology
of BCC is unknown, there exists a well-established relationship between BCC and
the Pilo-sebaceous unit and it is currently thought to originate from
pluri-potential cells in the basal layer of the epidermis or the follicle. The
patched/hedgehog intracellular signaling pathway plays a central role in both
sporadic BCCs and nevoid BCC syndrome (Gorlin syndrome). The sonic hedgehog
protein is the most relevant to Basal cell carcinoma; nevertheless, the Patched
(PTCH) protein receptor is the ligand-binding component of the hedgehog
receptor complex in the cell membrane. The UV-specific nucleotide changes in
the tumor suppressor genes, TP53 and mutations in PTCH1, have also been
implicated in the development of Basal cell carcinoma8.
Basal cell carcinoma is the most common skin cancer globally and recurrence represents a notable clinical challenge, especially when it occurs in anatomically sensitive areas such as the periocular region. Recurrences typically arise from incomplete surgical excision, aggressive histological subtypes or tumor localization within high-risk anatomical sites, particularly the medial canthus9-11. Although systemic complications from BCC are relatively uncommon, they can develop if the tumor invades deeper tissues or adjacent anatomical structures. Perineural invasion, while more characteristic of squamous cell carcinoma (SCC), can also occur in aggressive subtypes of BCC and is associated with higher recurrence and morbidity rates12. Genetic mutations affecting the PTCH1 gene within the Hedgehog signaling pathway play a pivotal role in BCC pathogenesis, particularly in genetic conditions such as Gorlin syndrome. These genetic alterations lead to uncontrolled cell proliferation, increasing susceptibility to recurrent lesions. Risk factors have a causative role in the susceptibility of Basal cell carcinoma.
Several established risk factors contribute significantly to the development and recurrence of BCC. These include chronic Ultraviolet radiation exposure, fair skin phenotype, older age, male sex, history of prior skin cancers, immunosuppression, exposure to ionizing radiation, genetic predispositions such as Gorlin syndrome and aggressive histologic subtypes. Positive surgical margins, inadequate postoperative follow-up and patient noncompliance further elevate recurrence risk. An accurate diagnosis of BCC involves conducting a clinical evaluation and dermatoscopy followed by confirmatory testing with a biopsy. A classic presentation of BCC is a smooth, shiny bump with arborizing telangiectasias on the surface and pearly borders that appear rolled. This unique appearance of BCC allows for a clinical evaluation to be made. To help clinicians further distinguish BCC from other skin lesions, dermatoscopy can also be performed. This non-invasive technique can showcase the dermatoscopic features of BCC, including small erosions, blue-gray ovoid nests and arborizing vessels13. Therefore, dermatoscopy can help facilitate an accurate diagnosis of BCC. To confirm the clinical diagnosis, a biopsy of the skin lesion is performed. Histopathological examination assesses for key characteristics and growth patterns of BCC, which aids in both confirming the clinical evaluation and diagnosing the suspected skin lesion. (Figure 4) shows the histopathological characteristics of BCC which includes groups of basaloid cells and peripheral palisading of tumor nuclei, retraction artifacts and mucin deposition are also common findings in slides.
Figure 4: Peripheral palisading of tumor nuclei, groups of basaloid cells
What is the overall Rate of
Recurrence?
The rate of recurrence of BCC
can be greatly influenced by treatment modality. As highlighted in a study
supported by the American Society for Dermatologic Surgery, for primary BCC,
Mohs surgery has a 5-year recurrence rate of 1.0%, while non-Mohs surgery
methods have a 5-year recurrence rate of 8.7%. Additionally, standard surgical
excision has a 5-year recurrence rate of 10.1%. Curettage and
electrodesiccation have a 5-year recurrence rate of 7.7% and radiation therapy
and cryosurgery have 5-year recurrence rates of 8.7% and 7.5%, respectively14.
Associations between diet
and Bcc
There are various studies
that have explored dietary components that may contribute to the development of
BCC. In a nested case-control study conducted by Leone A et al., the greatest
adherence to the Mediterranean diet was associated with a 72% relative
reduction in the odds of BCC. Adherence to the Dietary Approaches to Stop
Hypertension diet was associated with a 68% relative reduction in the odds of
BCC. In this study, it was also found that greater intake of fruit and low-fat
dairy products was associated with a reduced risk of BCC15. The association between these dietary
patterns and the lower risk of BCC could be influenced by polyphenols present
in plant-derived foods. The photo-protective effects of these bioactive
compounds may contribute to the inhibition of carcinogenesis16. Additionally, in a systematic review of
epidemiological studies conducted by Hezaveh E, et al., it was reported that
greater consumption of folate, citrus and alcohol corresponded to a higher risk
of BCC. It was also found in this study that caffeine consumption was
associated with a reduced risk of BCC17.
Although these findings suggest that there are certain dietary components that
can either protect against or potentially contribute to the risk of BCC,
further studies need to be conducted to better understand definitive, causal
relationships and specific dietary factors that may be involved in modulating
the risk of BCC. Results gathered from a prospective study done in men
identified that a diet of monounsaturated fat was associated with a lower risk
of BCC, saturated and polyunsaturated fat were not associated with BCC risk.
Folate intake was associated with a slightly higher risk of BCC with (RR:
1.19), whereas α-carotene was associated with a slightly lower risk (RR: 0.88).
Intakes of long-chain n-3 fatty acids, retinol, vitamin C, vitamin D or vitamin
E were not materially related to BCC risk18.
Conclusion
A recurrent tumor may require
larger resections and if a tumor in this region invades the ocular muscles or
post septal space, exenteration is usually the only option to prevent the tumor
from invading the sinuses and brain19.
Exenteration is the complete surgical removal of the contents of a bodily
cavity, especially the eye socket, usually in cases of malignant cancer. Taking
a comprehensive medical history is pertinent prior to these surgeries such as
this case study where the patient has a complex cardiac history. Therefore, on
consultation with the cardiology registrar, the patient was advised to have his
cardiac pacemaker device fitted weeks prior to having his surgery for BCC
removal. A collaborative multidisciplinary approach between the tertiary care
physicians; oculoplastic surgeon, dermatologist and primary care physician
increases greater chance of success in these surgeries.
Acknowledgements
The North Midlands and
Cheshire Pathology Service, Dermlink scholars. Abiola Z. Odeyinka M.D. was
responsible for design conceptualization, data collection, collection of
patient photographs, consent and patient’s histopathology. Abiola Z. Odeyinka
critically revised the manuscript. All authors read and approved the integrity
and accuracy of the manuscript. Andres D. Parga B.S., Toan N. Vu B.S were
equally responsible for writing sections of the manuscript. Histopathology
photo source: Not index patient (usmle-Rx.com)® Kelly M. Frasier is the senior
author who supervised the manuscript draft.
Conflicts of Interest
The authors declare no
conflicts of interest.
Funding Statement
None declared.
References
3. Wolf DJ, Zitelli JA. Surgical margins for
basal cell carcinoma. Arch Dermatol 1987;123:340-344.
13. Silverman N. What’s New in Eyelid Tumors. Asia Pac J Ophthalmol (Phila)
2017.