Features of basal cell carcinomas in basal cell nevus syndrome

Basal cell nevus syndrome (BCNS) is an autosomal dominant genodermatosis that is characterized by early onset basal cell carcinomas (BCCs) that define the disease and often lead to diagnosis of the underlying syndrome. The objective of this study was to investigate the anatomic location, subtypes, and impact of BCCs on a group of 61 individuals affected with BCNS attending a research colloquium. Fifty individuals had at least one prior BCC with 22 participants having over 100 lesions. The median age of syndrome diagnosis was 11 years and median age of first BCC was 16 years. Males had more lesions on the upper back, upper extremities, and M-zone of the face, while females had more lesions on the scalp, back, and lower extremities. Pigmented BCCs were concentrated on the neck, upper trunk, and extremities. Subjects with >100 lesions showed wider anatomic distribution. The number of BCCs did not correlate with any of the other major features of the syndrome. Eighty percent of affected individuals reported great concern related to BCCs, citing the limitations and morbidity of available treatments. Vigilant surveillance, which was found to be inconsistent for participants in this study, is warranted. Future work should include development of a consensus guideline on skin examinations and strategies to optimize therapy of BCCs in this syndrome.     

Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome.

PURPOSE: Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal-dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, calcification of the falx cerebri, and spine and rib anomalies. NBCCS is due to mutations in PTCH1, the human homologue of the Drosophila segment polarity gene patched. Mutations are detected in approximately 60% to 85% of individuals tested by sequencing of PTCH1; therefore, clinical examination and x-rays remain important in diagnosis of NBCCS. METHODS: We studied 82 NBCCS patients and 38 of their unaffected siblings at the NIH between 1985 and 1994. Chest, rib, spine, skull, hand and foot x-rays, brain MRI or CT, and pelvic ultrasound (in females) were obtained in the affected individuals and compared to their unaffected relatives. RESULTS: The following features were significantly more frequent in those with NBCCS: calcification of the falx cerebri, the most frequent radiological feature, was present in 79% of patients > 20 years and in 37% <20 years, calcification of the tentorium cerebellum was present in 20%, bridging of the sella in 68%, and abnormal frontal sinus aeration in 18% of affected individuals. Bifid ribs most often involving the third, fourth, and fifth ribs were seen in 26%; splayed, fused, and misshapen ribs in a further 16%, and widened ends of clavicles in 12%. Spine X-rays revealed calcification of the nuchal ligament in 18%, fusion of vertebrae in 10%, and hemivertebrae in 15%. Flame-shaped lucencies of the metacarpals and/or phalanges were present in 30%, modeling deformities of the phalanges in 14%, and polydactyly of the feet in 4%. The frequency of scoliosis, cervical ribs, absent or rudimentary ribs, spina bifida occulta, or short 4th metacarpal was not higher in the affected individuals as compared to their unaffected relatives. Except for falx calcification, the frequency of radiological manifestations was similar in different age groups. Cranial CT or MRI in 42 affected individuals revealed asymmetric or dilated ventricles in 24%, cerebral atrophy in 10%, cavum septum pellucidum in 19%, dysgenesis or agenesis of the corpus callosum in 10%, and meningioma in 5%. Ovarian fibromas were detected in 17% of females. CONCLUSIONS: This study reports the varied radiological manifestations of NBCCS. In the absence of major features such as basal cell carcinomas, jaw cysts, or falx calcification, which is often not evident until the teen years, other radiological manifestations of the disorder can permit early diagnosis of NBCCS in childhood. This will allow optimum surveillance for medulloblastoma and other neoplasms (cardiac fibromas and basal cell carcinomas) associated with NBCCS.     

Tenascin distribution in basal cell carcinomas

The distribution of tenascin, an extracellular matrix protein highly expressed in the stroma around sites of epithelial-mesenchymal interaction during morphogenesis and in malignant neoplasms, was assessed in cryostat sections of 17 basal cell carcinomas using a polyclonal antibody. There was marked staining of the vascularized stroma around neoplastic islands, usually as an intense, well-defined band, but being more widespread and diffuse in sclerosing, infiltrative areas. Apparently enhanced staining was seen in tumours showing retraction artefact, which may be related to the observation that tenascin interferes with the cell binding function of fibronectin. Reduced staining was seen in areas showing evidence of tumour regression. Tenascin is an important component of the epithelial-mesenchymal interactive process and further studies on its distribution in benign and malignant skin tumours are required.     

The management of basal cell carcinomas

The mortality and morbidity associated with basal cell carcinoma (BCC) is low. However, BCCs represent a significant burden to the health service due to their high and increasing incidence. This audit was designed to examine the management of BCCs by a dermatology department and to highlight deficiencies in the service offered to patients. The mean intervals between the first dermatology clinic visit and definitive treatment by the dermatology and the plastic surgery departments were 62 and 129 days respectively. Factors contributing to the delay included the frequent use of diagnostic incisional biopsies and the high referral rate from dermatology to the department of plastic and reconstructive surgery. In 90% of cases the dermatologist made an accurate clinical diagnosis. Despite this, diagnostic biopsies were performed in 72% of cases, often necessitating additional hospital visits. Forty three percent of cases were treated definitively by dermatology, whereas over 50% were referred to the department of plastic surgery. A number of changes are planned or are in process as a consequence of the audit.     

Parental origin of chromosome 9q22.3-q31 lost in basal cell carcinomas from basal cell nevus syndrome patients

The basal cell nevus syndrome is an autosomal dominant disease,one of the most prominent phenotypic features of which Is alarge number of cutaneous basal cell carcinomas. The gene whosemutation underlies this disease has been mapped to chromosome9q22. 3-q31, and basal cell carcinomas frequently have allellclosses including this site. We report here that the chromosome9q22. 3-q31 lost in 24 basal cell carcinomas from basal cellnevus syndrome patients was the one predicted by linkage tocontain the wild-type gene. Hence these data are compatiblewith the expectation that the product of the basal cell nevussyndrome gene acts as a tumor suppressor.     

Collision sebaceous and basal cell carcinomas of the eyelid

OBJECTIVE: To report a rare case of collision sebaceous and basal cell carcinomas of the eyelid. DESIGN: Interventional case report. METHODS: An 80-year-old woman presented with a nodular lesion at the center of the left lower eyelid. Small ulceration and madarosis were also present. RESULTS: The patient underwent excisional biopsy with frozen section control. Histopathology showed mixed sebaceous as well as basal cell carcinoma with uninvolved surgical margins. Oncologic survey did not disclose any other lesion. At 6-month follow-up, there was no evidence of recurrence, new lesions, or metastasis. CONCLUSION: Sebaceous and basal cell carcinomas can coexist in the eyelid within the same clinical lesion. Because of the potential risk of metastasis of sebaceous carcinoma, close follow-up of the patients is advisable.     

Nonrandom karyotypic features in basal cell carcinomas of the skin.

Cytogenetic analysis of short-term cultured 44 basal cell carcinomas (BCC) revealed clonal karyotypic abnormalities in 38 tumors. Relatively complex karyotypes (at least four structural and/or numerical changes per clone) with unbalanced structural as well as numerical aberrations were found in eight (approximately 21%) of the BCC, while the remaining BCC (79%) had simple karyotypes (1 to 3 aberrations per clone). Numerical changes only were found in 16 tumors, 15 BCC displayed both numerical and structural aberrations, and the remaining 7 BCC showed only structural aberrations. Extensive intratumoral heterogeneity, in the form of cytogenetically unrelated clones, was found in 21 tumors, whereas related subclones were present in 10 tumors. In order to obtain an overall karyotypic picture in BCC, the findings of our previously published 25 BCC have been reviewed. Our combined data indicate that BCC are characterized by nonrandom karyotypic patterns. A large subset of BCC is characterized by nonrandom numerical changes, notably, +18, +X, +7, and +9. Structural rearrangements often affect chromosomes 1, 4, 2, 3, 9, 7, 16, and 17. A number of chromosomal bands are frequently involved, including 9q22, 1p32, 1p22, 1q11, 1q21, 2q11, 4q21, 4q31, 1p36, 2q37, 3q13, 7q11, 11p15, 16p13, 16q24, 17q21, and 20q13. When the genomic imbalance is assessed, it has been shown that several chromosome segments are repeatedly involved in losses, namely loss of the distal part of 6q, 13q, 4q, 1q, 8q, and 9p. A correlation analysis between the karyotypic patterns and the clinico-histopathologic parameters has been undertaken in the 44 BCC of the present series. The cytogenetic patterns show a significant correlation with tumor status (P=.025), that is, that cytogenetically more complex tumors are also those clinically the most aggressive. Also, the frequency of cytogenetically unrelated clones is significantly higher in recurrent BCC than that in primary lesions (P=.05). No clear-cut association has been found between the karyotypic patterns and histologic subtypes or tumor sites.     

Changes in mean telomere length in basal cell carcinomas of the skin

Human telomeres consist of arrays of the sequence TTAGGG up to 15–20 kb in length, which are essential for the maintenance of normal chromosomal stability. It has been suggested that genomic instability observed in tumours may be due to loss of telomere sequences. Somatic cells that are dividing continuously appear to progressively lose telomere sequences, and it would therefore be anticipated that cell type specific differences in mean telomere length may exist within an individual. Previous reports have suggested that mean telomere length may be different in human neoplasia when compared to control. Basal cell carcinomas are epidermal derived tumours and in order therefore to make valid cell type specific comparisons we have measured mean telomere length in 20 basal cell carcinomas as well as in both adjacent epidermis and dermis. Mean telomere length was significantly reduced in epidermis in comparison with dermis, from clinically normal skin immediately adjacent to the tumours (mean difference 2.5 kb). This result is not related to the presence of the tumour as similar results were obtained from skin samples of healthy volunteers. Basal cell carcinomas showed increased mean telomere length in 13/20 samples in comparison with matched epidermis (mean difference 3.1 kb), whereas in 7/20 mean telomere length was reduced (mean difference 2.2 kb). These results showing that mean telomere length varies from cell type to cell type underpin the importance of performing cell type specific controls when assessing changes in tumour telomeres.     

Oncogene interaction in basal cell carcinomas of human skin.

The expression of the p53 protein (p53) was compared with those of several oncogenes including c-fos (Fos), c-jun (Jun), and epidermal growth factor receptor (EGFR1) using immunohistochemistry in frozen and paraffin-embedded sections of 25 basal cell carcinomas (BCCs) to find out any correlation between p53 and oncogenes in the pathogenesis of human BCC. In normal skin, positive reactions were obtained for EGFR1 and Fos, while p53 and Jun were negative in all cases. In the lesions, EGFR1 was observed in all cases and p53 was positive in 9 of 25 (36%). Fos was expressed in 21 of 25 (84%) and four negative cases were all p53-positive; this negative correlation between p53 and Fos staining was statistically significant (P < 0.01). Jun was detected in 14 of 20 (70%) and no significant relationship was observed between the expression of Jun and Fos or p53. These data suggest the possibility of down regulation of Fos expression by high levels of p53 protein. Further work is necessary to determine the mechanism of this interaction.     

Risk factors in Central Poland for the development of superficial and nodular basal cell carcinomas

Introduction

In the last decades the number of skin carcinomas has dramatically increased, which is mainly connected with changes in lifestyle, especially with common use of artificial light sources such as sunbeds. Basal cell carcinoma (BCC) is the most common form of skin cancer in white populations. Basal cell carcinomas are divided into subtypes, depending on their clinical picture and histology. The main groups are nodular (nBCC) and superficial (sBCC) ones. The major recognized risk factors for basal cell carcinoma (BCC) are exposure to chronic and intermittent burning doses of sunlight. Other risk factors leading to the development of the nBCC and sBCC subtypes of BCC are not well established.

Material and methods

An analysis of 123 patients with either nBCC or sBCC, living in Lodz, Poland, regarding various intrinsic and environmental parameters was undertaken following the histological diagnosis of BCC.

Results

No statistical differences were observed between the BCC subtype and sex, age, hair colour, eye colour, smoking, family history of skin cancer, occupation, or past episodes of sunburn. While sBCCs tended to occur on unexposed body sites in phototype I/II subjects who mainly avoided direct sunlight, nBCCs tended to occur on sun-exposed body sites in phototype III subjects who were frequently in direct sunlight.

Conclusions

Thus the development of particular BCC subtypes is partially dependent on phototype and personal sun behaviour.     

Mutations of microsatellite instability target genes in sporadic basal cell carcinomas

Microsatellite instability (MSI) caused by a defective DNA mismatch repair (MMR) system is one of the phenotypes of genomic instability, accounting for the tumorigenesis of certain types of cancers conveying clinical and prognostic significance. Genes such as TGF-βRII, IGFIIR, hMSH3, and hMSH6 include coding mononucleotide repeats that are known targets for mutations in MSI-high tumors. The aim of our study was to investigate the prevalence of mutations in the above 4 MSI target genes in correlation with the MSI status of 75 basal cell carcinomas (BCCs), including aggressive-growth BCCs and cases with perineural invasion. TGF-βRII or hMSH3 frameshift mutations were identified in 5% of the BCCs, including two cases of aggressive-growth subtype, whereas there were no microsatellite alterations in the IGFIIR and hMSH6 genes. Mutations at the mononucleotide repeats within the hMSH3 and TGF-βRII genes occurred in certain BCCs, not always in association with MSI. It seems likely that microsatellite alterations may be important in the development of individual cases of BCCs despite the low frequency of MSI in our cohort.     

Immunohistochemical expression of ezrin in cutaneous basal and squamous cell carcinomas

Ezrin is a member of the ezrin-radixin-moesin family of proteins, which link the actin-containing cytoskeleton to the plasma membrane. Overexpression of ezrin protein is correlated with the metastatic potential in several cancers. Little is known about the distribution of ezrin in normal epidermis and nonmelanoma skin cancer; therefore, in the current study, we examined the immunohistochemical expression of ezrin in normal skin (10 biopsies) and epithelial skin tumors (25 basal cell carcinoma [BCC] and 20 squamous cell carcinoma [SCC]). Ezrin was expressed in epidermis of all normal controls with a prominent membranous pattern compared with 93.3% positivity in malignant cases with a significant higher intensity (assessed by H score) in favor of the latter (P = .002). Cytoplasmic expression of ezrin either alone or associated with membranous expression was both seen in BCC and SCC. The median value of H score in SCC (160) cases was higher than that in BCC (60). H score values of ezrin expression in BCC was significantly higher in tumors arising in sites other than the head and neck (P = .04). In SCC, the intensity of ezrin expression tended to be associated with advanced stage (P = .08). Our study demonstrated the probable tumorigenic role of ezrin in epithelial skin tumor formation. It may enhance local invasion or metastasis of epithelial skin tumors, which necessitates further larger study to clarify. The intensity rather than the pattern of ezrin expression had a more probable impact on the tumor behavior.