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Cells Oct 2023Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide. In detail, basal cell carcinoma (BCC) is the most frequent malignancy in the... (Review)
Review
Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide. In detail, basal cell carcinoma (BCC) is the most frequent malignancy in the fair-skinned population. The incidence of BCC remains difficult to assess due to the poor registration practice; however, it has been increasing in the last few years. Approximately, 85% of sporadic BCCs carry mutations in Hedgehog pathway genes, especially in PTCH, SUFU and SMO genes, which lead to the aberrant activation of GLI transcriptional factors, typically silent in cells of adult individuals. The management of advanced BCC (aBCC), both metastatic (mBCC) and locally advanced BCC (laBCC), not candidates for surgical excision or radiotherapy, remains challenging. The discovery of mutations in the Hh signaling pathway has paved the way for the development of Hh pathway inhibiting agents, such as vismodegib and sonidegib, which have represented a breakthrough in the aBCC management. However, the use of these agents is limited by the frequent occurrence of adverse events or the development of drug resistance. In this review, we thoroughly describe the current knowledge regarding the available options for the pharmacological management of aBCCs and provide a forward-looking update on novel therapeutic strategies that could enrich the therapeutic armamentarium of BCC in the near future.
Topics: Adult; Humans; Skin Neoplasms; Hedgehog Proteins; Antineoplastic Agents; Carcinoma, Basal Cell; Signal Transduction
PubMed: 37947611
DOI: 10.3390/cells12212534 -
Current Oncology (Toronto, Ont.) Nov 2023Basal cell carcinoma (BCC) is the most common skin cancer, with a lifetime risk currently approaching up to 40% in Caucasians. Among these, some clinical and... (Review)
Review
Basal cell carcinoma (BCC) is the most common skin cancer, with a lifetime risk currently approaching up to 40% in Caucasians. Among these, some clinical and pathological BCC variants pose a higher risk due to their more aggressive biological behavior. Morpheaform BCC (morBCC), also known as sclerosing, fibrosing, or morpheic BCC, represents up to 5-10% of all BCC. Overall, morBCC carries a poorer prognosis due to late presentation, local tissue destruction, tumor recurrence, and higher frequency of metastasis. In this systematic review, we review the epidemiological, clinical, morphological, dermatoscopical, and molecular features of morBCC. After the title and abstract screening of 222 studies and the full-text review of 84 studies, a total of 54 studies met the inclusion criteria and were thus included in this review.
Topics: Humans; Neoplasm Recurrence, Local; Carcinoma, Basal Cell; Skin Neoplasms; Transcription Factors
PubMed: 37999140
DOI: 10.3390/curroncol30110720 -
Molecular Carcinogenesis Dec 2017Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits... (Review)
Review
Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10-100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs.
Topics: Carcinoma, Basal Cell; Cilia; Disease Progression; Hedgehog Proteins; Humans; Models, Genetic; Mutation; Signal Transduction; Skin Neoplasms
PubMed: 28574612
DOI: 10.1002/mc.22690 -
Clinical & Translational Oncology :... Jul 2015Despite that basal cell carcinoma (BCC) is curative in the vast majority of cases, some patients are at high risk of recurrence and, in a few patients, lesions can... (Review)
Review
Despite that basal cell carcinoma (BCC) is curative in the vast majority of cases, some patients are at high risk of recurrence and, in a few patients, lesions can progress to a point unsuitable for local therapy and prognosis is quite poor. The aim of the present work is to review clinical and pathologic characteristics as well as classical and new treatment options for high-risk, metastatic and locally advanced BCC. Surgery and radiotherapy remain the selected treatments for the majority of high-risk lesions. However, some patients are located on a blurry clinical boundary between high-risk and locally advanced BCC. Treatment of these patients is challenging and need an individualized and highly specialized approach. The treatment of locally advanced BCC, in which surgery or radiotherapy is unfeasible, inappropriate or contraindicated, and metastatic BCC has changed with new Hedgehog pathway inhibitors of which vismodegib is the first drug approved by FDA and EMA.
Topics: Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Dermatologic Surgical Procedures; Humans; Mohs Surgery; Pyridines; Radiotherapy; Skin Neoplasms
PubMed: 25643667
DOI: 10.1007/s12094-014-1272-9 -
Journal Der Deutschen Dermatologischen... Jul 2021Basal cell carcinoma (BCC) is the most common malignant tumor in light-skinned people and amounts to about 75 % of all cases of skin cancer. Increasing incidence rates...
Basal cell carcinoma (BCC) is the most common malignant tumor in light-skinned people and amounts to about 75 % of all cases of skin cancer. Increasing incidence rates have been reported for decades all over the world. The main risk factors include UV radiation, male sex, light skin type, advanced age, long-term immunosuppression, a positive individual or family history, and certain genodermatoses. BCC metastasizes only rarely, and its mortality is low, but it is associated with significant morbidity. Genetic mutations especially in the hedgehog pathway play an important role in BCC pathogenesis. Non-invasive procedures such as optical coherence tomography or confocal laser scan microscopy are increasingly utilized for diagnostics in addition to visual inspection and dermatoscopy, but only in exceptional cases can histological confirmation of the diagnosis be dispensed with. Various clinical and histological subtypes have been defined. Differentiating between BCC with high and low risk of recurrence has a significant influence on the choice of treatment. Most BCC can be treated effectively and safely with standard surgery, or in selected cases with topical treatment. Locally advanced and metastasized BCC must be treated with radiation or systemic therapy. Radiation is also an option for older patients with contraindications for surgery. The hedgehog inhibitors vismodegib and sonidegib are currently approved for systemic therapy of BCC in Europe. Approval for the PD1 inhibitor cemiplimab as second-line therapy is expected in the near future.
Topics: Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Hedgehog Proteins; Humans; Male; Neoplasm Recurrence, Local; Skin Neoplasms
PubMed: 34288482
DOI: 10.1111/ddg.14580 -
Radiation Research Mar 2016This commentary summarizes studies showing risk of basal cell carcinoma (BCC) development in relationship to environmental, occupational and therapeutic exposure to... (Review)
Review
This commentary summarizes studies showing risk of basal cell carcinoma (BCC) development in relationship to environmental, occupational and therapeutic exposure to ionizing radiation (IR). BCC, the most common type of human cancer, is driven by the aberrant activation of hedgehog (Hh) signaling. Ptch, a tumor suppressor gene of Hh signaling pathway, and Smoothened play a key role in the development of radiation-induced BCCs in animal models. Epidemiological studies provide evidence that humans exposed to radiation as observed among the long-term, large scale cohorts of atomic bomb survivors, bone marrow transplant recipients, patients with tinea capitis and radiologic workers enhances risk of BCCs. Overall, this risk is higher in Caucasians than other races. People who were exposed early in life develop more BCCs. The enhanced IR correlation with BCC and not other common cutaneous malignancies is intriguing. The mechanism underlying these observations remains undefined. Understanding interactions between radiation-induced signaling pathways and those which drive BCC development may be important in unraveling the mechanism associated with this enhanced risk. Recent studies showed that Vismodegib, a Smoothened inhibitor, is effective in treating radiation-induced BCCs in humans, suggesting that common strategies are required for the intervention of BCCs development irrespective of their etiology.
Topics: Anilides; Animals; Carcinoma, Basal Cell; Chernobyl Nuclear Accident; Hedgehog Proteins; Humans; Neoplasms, Radiation-Induced; Nuclear Weapons; Pyridines; Radiation Exposure; Radiation, Ionizing; Signal Transduction; Skin Neoplasms; Survivors
PubMed: 26930381
DOI: 10.1667/RR4284.S1 -
Anais Brasileiros de Dermatologia 2021Non-melanoma skin cancer is the most common type of malignancy in the Western world, and surgical excision is the preferred approach. The approach adopted in the face of...
BACKGROUND
Non-melanoma skin cancer is the most common type of malignancy in the Western world, and surgical excision is the preferred approach. The approach adopted in the face of incomplete excisions of basal cell carcinoma is still controversial.
OBJECTIVES
To compare the number of tumor recurrences after treatment for incompletely excised basal cell carcinoma.
METHODS
Selection and statistical analysis of medical records of patients who had compromised margins after excision of basal cell carcinoma in a tertiary hospital from 2008 to 2013.
RESULTS
A total of 120 medical records were analyzed; the mean age was 69.6 years, and 50% of the patients were female. The most prevalent histological type was nodular; the mean size was 1.1 cm, and the tumor location with the highest incidence was the nose. The lateral margin was the most frequently positive. Clinical follow-up was more widely adopted; only 40 patients underwent a second surgery. The total number of patients who had tumor recurrence was 34 (28.3%). Only the malar location significantly influenced the incidence of recurrence (p = 0.02). The mean follow-up time was 29.54 months, with no significant difference between the follow-ups, although 32.9% of the patients followed-up clinically showed recurrence, against only 20% of those who underwent a second surgery.
STUDY LIMITATIONS
Mean follow-up time of less than five years and sample size.
CONCLUSIONS
The presence of compromised margins does not necessarily imply recurrence. Location, tumor size, histological subtype, previous epithelial tumors, and clinical conditions of the patient must be considered when choosing the best treatment option.
Topics: Aged; Carcinoma, Basal Cell; Female; Humans; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Skin Neoplasms
PubMed: 33288370
DOI: 10.1016/j.abd.2020.11.001 -
American Journal of Clinical Pathology Nov 2019Diagnosis of metastatic basal cell carcinoma (BCC) remains challenging, in part due to its rarity. With the advent of molecularly targeted therapies, recognition of this...
OBJECTIVES
Diagnosis of metastatic basal cell carcinoma (BCC) remains challenging, in part due to its rarity. With the advent of molecularly targeted therapies, recognition of this entity is more important than ever.
METHODS
We identified 11 cases of metastatic BCC over a 13-year period. We analyzed these tumors in conjunction with their respective primary tumors by histomorphologic, immunohistochemical, and molecular genetic analyses.
RESULTS
We identified three morphologic patterns of metastasis in BCC. The most common (seven cases) was characterized by completely typical features of BCC. Two cases showed marked squamous differentiation within BCC. The final two cases showed exclusively features of a poorly differentiated carcinoma. One of these was definitively classified by molecular analysis, as both the primary and metastatic tumors harbored the same inactivating PTCH1 mutation.
CONCLUSIONS
This study illustrates multiple distinct morphologic patterns in metastatic BCC and highlights the utility of ancillary molecular testing for accurate diagnosis.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Skin Neoplasms
PubMed: 31355851
DOI: 10.1093/ajcp/aqz089 -
Actas Dermo-sifiliograficas May 2022As one of the most common malignancies, basal cell carcinoma (BCC) has evolved as a global burden with incidence annually rising, especially in the older population.... (Review)
Review
As one of the most common malignancies, basal cell carcinoma (BCC) has evolved as a global burden with incidence annually rising, especially in the older population. Even though the condition is mostly localized, the nature of the disease is destructive and can evolve as either locally advanced BCC (laBCC) or even more rarely as metastatic BCC (mBCC). There are well-established conventional treatment options for these cases, including surgeries and radiotherapy. However, not all cases are eligible for conventional treatments. Recently, biologic treatment has gained a lot of attention and research. This has led to the development of targeted treatment involving the hedgehog pathway inhibitor (HPI), a key pathogenesis in laBCC and mBCC. There are currently two approved HPIs, vismodegib and sonidegib to treat inoperable laBCC and mBCC. This review seeks to explore the pathophysiology of hedgehog pathway behind the development of BCC, and the current update of the efficacy as well as pharmacokinetics properties of HPIs that led to the ideal treatment for laBCC or mBCC, either as monotherapy or in combination with other conventional therapies.
Topics: Anilides; Antineoplastic Agents; Biphenyl Compounds; Carcinoma, Basal Cell; Hedgehog Proteins; Humans; Pyridines; Skin Neoplasms
PubMed: 35697404
DOI: 10.1016/j.ad.2022.01.005 -
BMC Ophthalmology Jun 2022To report tumour pathology, surgical procedure, complication rates and overall outcome of periocular basal cell carcinoma (BCC) in the Department of Ophthalmology at...
BACKGROUND
To report tumour pathology, surgical procedure, complication rates and overall outcome of periocular basal cell carcinoma (BCC) in the Department of Ophthalmology at Sygehus Lillebaelt, Southern Denmark Region over a 5-year period.
METHODS
Medical records for all patients who underwent surgery for periocular BCC between January 2016 and December 2020 were reviewed. All tumours were excised with a 3 mm margin beyond the clinically apparent delimitation of the tumour and analysed by frozen section histological examination. Paraffin sections were subsequently examined for a final histopathological diagnosis. Patient age, gender, date of resection, former cancer history, referring unit and follow-up time were recorded. Furthermore, histological subtypes identified from biopsy and resection, lesion location, lesion diameter, free margin after the first operation, lacrimal punctum involvement, reconstructive techniques and complications were also recorded.
RESULTS
A total of 242 surgical excisions from 237 patients were recorded. The mean age was 69.7 ± 12.6 with women significantly predominant compared to men (1.8:1, p < 0.0001, binomial test). The mean tumour diameter was 4.29 mm (range 0.5-20 mm). The most common location and histological subtype was the lower eyelid and nodular BCC respectively (64.9% and 74.0% of cases). In 17.4% of the patients, the initial resection margin on the frozen section histology was not free of tumour cells and the risk was significantly greater for BCC subtypes considered aggressive in terms of growth pattern (morphea form, infiltrative and micronodular features) as compared to non-aggressive BCC subtypes (nodular and superficial) (p = 0.002, X). In 239 (98.8%) of the patients, the BCC was found to be radically removed after final histopathological examination. The sensitivity of identification of aggressive subtypes of periocular BCC in biopsies was 47.7%. No recurrences were found during the 5-year period.
CONCLUSION
This study demonstrated a tendency towards more women than men being diagnosed with periocular BCC. The initial biopsy performed for all patients underestimated the aggressiveness of BCC in almost half of the cases while aggressive BCC subtypes were more likely to need further resection after frozen section compared to non-aggressive subtypes.
Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Denmark; Eyelid Neoplasms; Female; Humans; Male; Middle Aged; Retrospective Studies; Skin Neoplasms; Treatment Outcome
PubMed: 35761210
DOI: 10.1186/s12886-022-02494-9