Diagnosis of aggressive subtypes of eyelid basal cell carcinoma by 2-mm punch biopsy: prospective and comparative study. We compared the biopsy results to the gold standard pathology of the surgical specimen. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Kappa coefficient to determine the level of agreement in both groups. The agreement was There was no significant difference between the groups regarding the distribution of quantitative and qualitative variables gender, age, disease duration, tumor larger diameter, area and commitment of margins.
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Basal cell carcinoma BCC is a common malignant tumor throughout the world. One of the known risk factors of BCC is intense exposure to ultraviolet radiation.
The gold standard of diagnosis of BCC is histopathology. Treatment options for BCC consist of surgery, vismodegib, radiotherapy and imiquimod. Surgical excision using Mohs micrographic surgery or wide surgical excision with frozen section margin control is the first consideration for treatment of periocular BCC.
Eyelid reconstruction should be carefully considered as both function and esthetic outcome in patients are important after clear excision of tumors. Exenteration is considered in the case of extensive orbital invasion or high-risk aggressive tumors in order to reduce the rate of recurrence.
Basal cell carcinoma BCC is the most common cancer in the world. Although metastasis is rare, BCC of the eyelids has a high risk of recurrence. Recurrent BCCs are often associated with primary tumors of an aggressive subtype, and they usually have a worse overall prognosis than the primary tumor.
BCC is usually not fatal, but if it is not diagnosed for a long time, the function and the appearance of the eyelid will be destroyed. The incidence of BCC is higher in more equatorial latitudes than in polar latitudes. UVB radiation damages DNA and its repair system, and changes the immune system resulting in progressive genetic alterations that lead to the formation of neoplasms. The mutations which play a significant role in cutaneous carcinogenesis activate hedgehog intercellular signaling pathway genes, including patched Ptch , sonic hedgehog and smoothened.
Ptch-1 mutations promote the development of eyelid BCC. Lim et al found that a high incidence of BCC and a larger BCC size were associated with a low socioeconomic status, which corresponds to studies in the UK, Ireland and the Netherlands showing that patients living in areas of socioeconomic deprivation are more likely to have BCC. Since early and small BCCs are usually easily managed with a good prognosis, prevention is preferable to treatment.
People living in economically deprived areas should be informed that simple measures like avoiding extensive sun exposure or the long-term use of hats with brims can reduce the incidence of periocular skin cancers. Other factors such as chemical or physical irritation of tears may do more harm to the lower lid.
BCC arises from basal cells of the epidermis. It is characterized by a pearly edge and a pink color. Sometimes, it can present as ulceration and bleeding. The tumor size is positively correlated with age. The distance to the center of the tumor from the medial area is greater when the diameter is larger. Other common manifestations included mass fixation to orbital bone A visible or palpable mass was observed in only Other possible symptoms included immobile lids, epiphora secondary to canalicular or nasolacrimal sac involvement and ptosis.
Imaging examinations of patients with orbital invasion may find bone and soft tissue involvement. Computed tomography with bone windows can be used for visualizing bony destruction. Magnetic resonance imaging is a better option for visualizing soft tissue changes and rare perineural invasion.
A new noninvasive imaging technique, in vivo reflectance confocal microscopy IVCM , has sparked great interest for the diagnosis of eyelid tumors to avoid unnecessary surgical excisions.
IVCM can be used to examine both the skin and the conjunctiva, but more studies are needed to confirm the diagnostic capabilities of this imaging technique. As clinical symptoms can be variable, the final diagnosis of tumors must always be histological, and for that reason, a pathological examination is required.
Biopsy is recommended for all suspicious lesions. The histological types of BCC are superficial, infiltrating and nodular tumors, and those with adnexal differentiation. The nodular and superficial types of BCC are the most common which tend to be less aggressive. We provide a brief summary of different treatment options for BCC in Table 1. The first treatment option for BCC is surgery, including both Mohs micrographic surgery MMS and wide surgical excision with frozen section margin control.
Initial treatment with local excision or MMS should achieve negative resection margins in order to reduce the risk of local recurrence. The integrity of the eyelids is important for protecting and preserving the function of the globe. The distance of the tumor from the eyelid margin and the diameter of the tumor are important to estimate the prognosis and choose the best surgical technique.
When the tumor affects the margin of the eyelid, reconstruction with a flap based on the tumor size in the eyelid is necessary to preserve eyelid function and esthetics Figure 1. Smaller margins 2—3 mm may be taken in case of limited reconstructive options. The smaller the size of the tumor, the simpler the reconstruction, and better functional and esthetic results are obtained.
This research remains the remarkable randomized study suggesting the benefit of MMS and guiding medical decision making. Notes: A The appearance of the tumor before surgery. B One day after MMS surgery and reconstruction with a flap of upper lid. C Three months after surgery. Written informed consent for publication of photographs was obtained from the patient.
MMS is not usually recommended for deep orbital invasion because it is always difficult to obtain correctly oriented specimens from orbital soft tissues. Also, the risk of false-negative results with standard frozen section techniques is significant. Therefore, paraffin section histology remains the choice of margin control for BCCs with orbital invasion. Reconstruction of the exenterated orbit usually uses split-thickness skin grafts, temporalis muscle flaps or free flaps.
Ho et al conducted the largest series of BCC excisions with the non-Mohs rapid paraffin technique. They first performed excision with a 3 mm margin from the perceived edge of the lesions to obtain a rapid-turnaround paraffin section. The reconstruction was performed a few days after the histology results were available. If the margins were clear, reconstruction was performed. If the margins were involved, further excision was performed using frozen section or paraffin examination until a clear margin was obtained, followed by reconstruction.
Rapid fresh-frozen sections, which have been widely employed with proven efficacy, are used for margin control involving just one margin not of morpheaform, but are less accurate than paraffin sections.
The surgeon can repair the surgical defect after obtaining clear margins, resulting in a better long-term cure. Conway et al evaluated the recurrence of primary BCC infiltrating the eyelid margins after resection with and without intraoperative frozen section IFS control. There was no tumor relapse in group I compared with three 9.
Tumors of more aggressive histological subtypes are more likely to be incompletely excised, especially when unmonitored excision is performed. Exenteration is considered in cases of bulbar or extensive orbital invasion. It may be combined with adjunctive radiotherapy when margins are not clear or in high-risk aggressive tumors with perineural invasion. Final margins were clear in 18 of 20 patients, positive in one of 20 patients and unclear in one of 20 patients.
With a mean follow-up of 38 months, only one patient relapsed. This study showed that conservative non-exenterating surgery with careful planning and margin control in this highly selected group of patients was able to reduce the rate of disease recurrence. Vismodegib, a hedgehog pathway inhibitor, has been used as a medical or adjuvant therapy of periocular and orbital BCC to decrease tumor size. Vismodegib is also used to treat basal cell nevus syndrome Gorlin syndrome , which is not amenable to surgery and involves numerous cutaneous lesions of the periocular region and face.
The recommended dosage is mg per day. The hedgehog signal transduction pathway plays an important role in cell proliferation, and alterations in hedgehog signaling may transform a conjunctival intraepithelial neoplasia into invasive squamous cell carcinoma.
Many studies of patients with advanced periocular BCC have shown that vismodegib is effective, but the long-term results after stopping vismodegib are still unknown. Another two patients taking vismodegib as adjuvant therapies showed complete remission after a median of 7 months of therapy and no evidence of clinical recurrence after ceasing vismodegib for a median of 15 months. An additional two patients with extensive periocular involvement had complete clinical remission after a median of 14 months of oral treatment.
All seven cases had demonstrated recurrent tumors previously excised with controlled margins by frozen section or MMS. The mean follow-up duration of this study was 7. The periorbital tumor regressed after treated with vismodegib for 3 months but recurred after 9 months due to drug resistance and was finally treated with orbital exenteration.
Resistance to vismodegib does pose a challenge in the clinic. The first histopathological description of the effects of vismodegib treatment on BCC was described in a case by Kahana et al. After 5 months of treatment with vismodegib, residual squamous cells not only exhibited degenerative cytologic features, but the surgical specimen failed to show nuclear immunoreactivity for the proliferation marker Ki Side effects of vismodegib include muscle spasms, alopecia, dysgeusia, dysosmia, weight loss, fatigue, nausea, decreased appetite, diarrhea and even keratoacanthoma and squamous cell carcinoma.
Although some patients give up therapy with vismodegib because of these side effects, vismodegib is generally well tolerated with acceptable side effects.
Additional study will be required to better estimate the risks of treatment and to establish the treatment criteria. Radiotherapy is used as an adjunctive therapy to excision with clear margins, but may be followed by exenteration of high-risk aggressive BCC with perineural invasion or applied to residual inoperable tumors. It is also used for BCC patients who are unsuitable surgical candidates. Radiotherapy has side effects including dry eye, cataract formation, ectro-pion, stenosis of the lacrimal duct, neovascular glaucoma, radiation retinopathy and radiation optic neuropathy, and can even cause significant ocular morbidity or blindness.
He was treated with CyberKnife in stereotactic body radiation therapy modality alone. After the treatment, the patient enjoyed rapid tumor regression, with complete remission after 6 months without toxicity.
Although surgical excision is the gold standard for periocular nodular BCC PNBCC and is associated with the highest cure rates, for those for whom surgery is not possible, topical immunotherapy may be an alternative treatment for periocular BCC. IMQ is an immune modulator which stimulates innate and adaptive immunity and induces apoptosis in tumor cells. It is typically applied once per day, five times per week for 8—16 weeks depending on the patient situation.
The symptoms of periocular BCC, including conjunctival irritation, conjunctivitis, keratitis, foreign body sensation, lacrimation, low visual acuity, ectropion and discomfort with blinking, usually disappear when treatment ends. The histological clearance rate was In the IMQ group, all 15 patients had complete clinical clearance at 24 months of follow-up. Another 12 patients in the radiotherapy group, who received treatment two or three times per week for 5 weeks with a dose of cGy per session and a total administered dose of 4,—7, cGy, were in clinical remission at the final evaluation at 24 months.
Esthetic and functional results were superior in the IMQ group, but the treatments were tolerated better in the radiotherapy group. Most recurrences occur on the lower lid and in the medial canthus, possibly related to earlier deep extension. Aggressive histological forms of BCC are associated with a high risk of recurrence, usually because of incomplete excision of these lesions.
Basal cell carcinoma BCC is a common malignant tumor throughout the world. One of the known risk factors of BCC is intense exposure to ultraviolet radiation. The gold standard of diagnosis of BCC is histopathology. Treatment options for BCC consist of surgery, vismodegib, radiotherapy and imiquimod. Surgical excision using Mohs micrographic surgery or wide surgical excision with frozen section margin control is the first consideration for treatment of periocular BCC. Eyelid reconstruction should be carefully considered as both function and esthetic outcome in patients are important after clear excision of tumors. Exenteration is considered in the case of extensive orbital invasion or high-risk aggressive tumors in order to reduce the rate of recurrence.
2014, Number 1
BCC is a malignant epidermal carcinoma. As its names implies, BCC derives from cells of the epithelial basal cell layer. Histologically the tumor has an appearance similar to the normal epithelial basal cell layer Figure 1. BCC forms strands, cords, and islands of tumor. Palisading of the nuclei at the periphery of the islands of tumor is characteristic Figure 1. An additional distinguishing feature of the tumor is the clefts or separation artifact, which results from tissue processing.
Basal Cell Carcinoma
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Ocular basal cell carcinoma: a brief literature review of clinical diagnosis and treatment
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