Subtypes Of Basal Cell Carcinoma Research Articles

Angulated small nests and cords: Key diagnostic histopathologic features of infiltrative basal cell carcinoma can be identified using integrated reflectance confocal microscopy-optical coherence tomography.

Accurate basal cell carcinoma (BCC) subtyping is requisite for appropriate management, but non-representative sampling occurs in 18% to 25% of biopsies. By enabling non-invasive diagnosis and more comprehensive sampling, integrated reflectance confocal microscopy-optical coherence tomography (RCM-OCT) may improve the accuracy of BCC subtyping and subsequent management. We evaluated RCM-OCT images and histopathology slides for the presence of two key features, angulation and small nests and cords, and calculated (a) sensitivity and specificity of these features, combined and individually, for identifying an infiltrative BCC subtype and (b) agreement across modalities. Thirty-three RCM-OCT-imaged, histopathologically-proven BCCs (17 superficial and/or nodular; 16 containing an infiltrative component) were evaluated. The presence of angulation or small nests and cords was sufficient to identify infiltrative BCC on RCM-OCT with 100% sensitivity and 82% specificity, similar to histopathology (100% sensitivity, 88% specificity, kappa = 0.82). When both features were present, the sensitivity for identifying infiltrative BCC was 100% using either modality and specificity was 88% on RCM-OCT vs 94% on histopathology, indicating near-perfect agreement between non-invasive and invasive diagnostic modalities (kappa = 0.94). RCM-OCT can non-invasively identify key histopathologic features of infiltrative BCC offering a possible alternative to traditional invasive biopsy.

Clinical and dermoscopic features of Fibroepithelioma of Pinkus: case series with an emphasis on hypopigmented to pink lines intersecting at acute angles.

Fibroepithelioma of Pinkus (FEP) is a subtype of basal cell carcinoma (BCC) that can clinically resemble intradermal nevi (IDN) and fibromas. We performed a retrospective review of consecutively biopsied lesions confirmed to be FEP on histopathology diagnosed from January 1, 2008 to April 8, 2019. Clinical (n = 48), contact non-polarized dermoscopy (NPD) (n = 44), and contact polarized dermoscopy (PD) (n = 22) images from 36 patients were reviewed. Mean age was 64.5years (SD 15.1years, range 24-86years) at diagnosis of first FEP lesion. Most lesions were located on the torso (n = 28, 58.3%), followed by the lower extremity (n = 9, 18.8%). The most common differential diagnoses at the time of biopsy included BCC (n = 40) and nevus (other than IDN, n = 5). Clinically, FEP were pink (95.8%), scaly (66.7%) papules (77.1%) displaying disrupted skin markings (62.5%) and absence of hair follicles (87.5%). NPD revealed serpentine (97.7%), dotted (81.8%), or polymorphous vessels (86.4%), and hypopigmented to pink lines intersecting at acute angles (HPLA) (52.3%). PD demonstrated serpentine (95.5%), dotted (86.4%), or polymorphous vessels (81.8%), shiny white lines (50.0%), and HPLA (59.1%). Classic features of BCC such as arborizing vessels (n = 2), ulceration (n = 1), shiny white blotches and strands (n = 1), blue-gray ovoid nest (n = 1), and leaf-like areas (n = 1) were uncommon. FEP often presents as scaly, erythematous papules with disrupted skin markings and absence of hair follicles. Dermoscopy reveals polymorphous vessels with shiny white lines and HPLA.

Matrix metalloproteinases in keratinocyte carcinomas.

The incidence of cutaneous keratinocyte‐derived cancers is increasing globally. Basal cell carcinoma (BCC) is the most common malignancy worldwide, and cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. BCC can be classified into subtypes based on the histology, and these subtypes are classified further into low‐ and high‐risk tumors. There is an increasing need to identify new therapeutic strategies for the treatment of unresectable and metastatic cSCC, and for aggressive BCC variants such as infiltrating, basosquamous or morpheaform BCCs. The most important risk factor for BCC and cSCC is solar UV radiation, which causes genetic and epigenetic alterations in keratinocytes. Similar gene mutations are noted already in sun‐exposed normal skin emphasizing the role of the alterations in the tumor microenvironment in the progression of cSCC. Early events in cSCC progression are alterations in the composition of basement membrane and dermal extracellular matrix induced by influx of microbes, inflammatory cells and activated stromal fibroblasts. Activated fibroblasts promote inflammation and produce growth factors and proteolytic enzymes, including matrix metalloproteinases (MMPs). Transforming growth factor‐β produced by tumor cells and fibroblasts induces the expression of MMPs by cSCC cells and promotes their invasion. Fibroblast‐derived keratinocyte growth factor suppresses the malignant phenotype of cSCC cells by inhibiting the expression of several MMPs. These findings emphasize the importance of interplay of tumor and stromal cells in the progression of cSCC and BCC and suggest tumor microenvironment as a therapeutic target in cSCC and aggressive subtypes of BCC.

Biopsy outperforms reflectance confocal microscopy in diagnosing and subtyping basal cell carcinoma: results and experiences from a randomized controlled multicentre trial.

SummaryBackgroundReflectance confocal microscopy (RCM) is a noninvasive method for skin assessment, allowing entire lesion evaluation up to the papillary dermis. RCM is a potentially attractive alternative to punch biopsy (PB) in basal cell carcinoma (BCC).ObjectivesTo determine the diagnostic accuracy of RCM vs. PB in diagnosing and subtyping BCC, and to study patient satisfaction and preferences.MethodsPatients with a clinically suspected primary BCC were randomized between RCM and biopsy. Conventional surgical excision or follow‐up were used as reference. Sensitivity and specificity for BCC diagnosis and subtyping were calculated for both methods. BCC subtype was stratified based on clinical relevance: aggressive (infiltrative/micronodular) vs. nonaggressive (superficial/nodular) histopathological subtype and superficial vs. nonsuperficial BCC. Data on patient satisfaction and preferences were collected using a questionnaire and a contingent valuation method.ResultsSensitivity for BCC diagnosis was high and similar for both methods (RCM 99·0% vs. biopsy 99·0%; P = 1·0). Specificity for BCC diagnosis was lower for RCM (59·1% vs. 100·0%; P < 0·001). Sensitivity for aggressive BCC subtypes was lower for RCM (33·3% vs. 77·3%; P = 0·003). Sensitivity for nonsuperficial BCC was not significantly different (RCM 88·9% vs. biopsy 91·0%; P = 0·724). Patient satisfaction and preferences were good and highly comparable for both methods.ConclusionsBiopsy outperforms RCM in diagnosing and subtyping clinically suspected primary BCC. This outcome does not support routine clinical implementation of RCM, as a replacement for PBs in this patient group.

Hedgehog Pathway Alterations Downstream of Patched-1 Are Common in Infundibulocystic Basal Cell Carcinoma

The infundibulocystic variant of basal cell carcinoma (BCC) is characterized histologically by anastamosing strands of basaloid epithelium with associated small infundibular-type cysts. Since its first description in 1987, this rare entity has generated considerable controversy with some authors classifying it as a benign follicular neoplasm rather than a BCC subtype. Prior studies aiming to settle this issue using immunohistochemical analysis reached opposite conclusions. The defining feature of BCC is activation of the Hedgehog signaling pathway, and mutations in Patched-1 (PTCH1) are the most common molecular finding in both sporadic and inherited forms of BCC. Mutations in other downstream components including Smoothened (SMO) and Suppressor of Fused (SUFU) also occur, but are much less common. Here, we report a molecular genetic analysis of a small series of infundibulocystic BCC using a next-generation DNA sequencing platform. All 4 cases harbored mutations or other genetic alterations in components of the Hedgehog pathway, supporting the classification of this entity as a BCC variant. Interestingly, these tumors were enriched for genetic alterations downstream of PTCH1, involving SUFU, SMO, GLI1, and GLI2. This observation was of particular interest given that rare kindreds of the Multiple Hereditary Infundibulocystic BCC syndrome (MHIBCC), which is related, but possibly distinct from the nevoid BCC syndrome, harbored mutations in SUFU. Our results support the classification of the infundibulocystic variant as a subtype of BCC, and suggest that the level at which genetic alterations occur within the Hedgehog pathway may be an important determinant of the morphologic features in BCC.

Comparison of basal cell carcinoma subtypes observed in preoperative biopsy and Mohs micrographic surgery

BackgroundThe treatment of basal cell carcinoma depends on its histological subtype. Therefore, a biopsy should be performed before definitive treatment. However, as the biopsy is only a sample of the tumor, it does not always shows every histological subtype present in the neoplasm. Few studies have compared the histological findings of biopsies with the findings of Mohs micrographic surgery. By evaluating the totality of the peripheral margins, in addition to sampling large tumor areas, this technique provides a more representative amount of tissue than preoperative biopsy. Objectivesa) Determine the agreement between the histological subtype of basal cell carcinoma from punch biopsy and the findings of Mohs surgery; b) To assess, among the discordant cases, the prevalence of non-aggressive tumors in the preoperative biopsy that were reclassified as aggressive by Mohs surgery. MethodsRetrospective analysis of 79 cases of basal cell carcinomas submitted to punch biopsy and subsequent Mohs surgery. ResultsThe agreement between the classification of the subtypes in the biopsy and in Mohs surgery was 40.5%. Punch biopsy was able to predict the most aggressive basal cell carcinoma growth pattern in 83% of cases. Study limitationsRetrospective nature, sample size, and biopsies performed by different professionals. ConclusionsThe agreement between the histopathological subtypes of basal cell carcinoma as seen in preoperative biopsy and Mohs surgery was low. However, preoperative biopsy presented good accuracy (83%) in detecting aggressive histopathological subtypes.

Association of Multiple Aggregated Yellow-White Globules With Nonpigmented Basal Cell Carcinoma

Basal cell carcinoma (BCC) is the most common skin cancer. Dermoscopic imaging has improved diagnostic accuracy; however, diagnosis of nonpigmented BCC remains limited to arborizing vessels, ulceration, and shiny white structures. To assess multiple aggregated yellow-white (MAY) globules as a diagnostic feature for BCC. In this retrospective, single-center, case-control study, nonpigmented skin tumors, determined clinically, were identified from a database of lesions consecutively biopsied during a 7-year period (January 1, 2009, to December 31, 2015). A subset of tumors was prospectively diagnosed, and reflectance confocal microscopy, optical coherence tomography, and histopathologic correlation were performed. Data analysis was conducted from July 1 to September 31, 2019. Investigators evaluated for the presence or absence of known dermoscopic criteria. MAY globules were defined as aggregated, white-yellow structures visualized in polarized and nonpolarized light. The primary outcome was the diagnostic accuracy of MAY globules for the diagnosis of BCC. Secondary objectives included the association with BCC location and subtype. Interrater agreement was estimated. A total of 656 nonpigmented lesions from 643 patients (mean [SD] age, 63.1 [14.9] years; 381 [58.1%] male) were included. In all, 194 lesions (29.6%) were located on the head and neck. A total of 291 (44.4%) were BCCs. MAY globules were seen in 61 of 291 BCC cases (21.0%) and in 3 of 365 other diagnoses (0.8%) (P < .001). The odds ratio for diagnosis of BCC was 32.0 (96% CI, 9.9-103.2). The presence of MAY globules was associated with a diagnosis of histologic high-risk BCC (odds ratio, 6.5; 95% CI, 3.1-14.3). The structure was never seen in cases of superficial BCCs. The findings suggest that MAY globules may have utility as a new BCC dermoscopic criterion with a high specificity. MAY globules were negatively associated with superficial BCC and positively associated with deeper-seated, histologic, higher-grade tumor subtypes.

Optical Coherence Tomography for Noninvasive Diagnosis and Subtyping of Basal Cell Carcinoma: A Prospective Cohort Study

Noninvasive diagnostic strategies such as optical coherence tomography (OCT) enable detailed examination of skin tissue architecture and have potential for identification and subtyping of basal cell carcinoma (BCC). To evaluate the additional diagnostic value of OCT, a prospective cohort study was performed in 182 patients with 250 lesions suspected for non-melanoma skin premalignancies requiring a biopsy. Accuracy of BCC diagnosis and subtype on the basis of clinical examination (CE) of patients was compared with that on the basis of OCT scans in conjunction with clinical images of lesions (cOCT). Confidence levels were recorded on a 5-point scale, where score 0 indicated absence of BCC and scores 1-4 indicated increasing suspicion of BCC. Diagnostic performance parameters were compared using histopathologic diagnosis as gold standard. The patient-based area under the receiver operating characteristic curve (AUC) increased from 85.6% for CE to 91.2% for cOCT (P= 0.061) and the lesion-based AUC from 82.7% to 91.3% (P < 0.001). When confidence scores 1-4 were defined as positive, patient-based specificity increased from 47.5% (CE alone) to 76.8% (cOCT) at similar sensitivity (97.6% and 95.2%, respectively). cOCT slightly improved the ability to discriminate between superficial and nonsuperficial BCC subtypes and seemed to be a valuable addition to CE alone in the diagnosis and subtyping of BCC.

Use of Cytology in the Diagnosis of Basal Cell Carcinoma Subtypes.

Background: Basal cell carcinoma (BCC) is the most common skin cancer in the white population. Nonsurgical treatments are first-line alternatives in superficial BCC (sBCC); therefore, differentiating between sBCC and non-sBCC is of major relevance for the clinician. Scraping cytology possesses several advantages, such as an earlier diagnosis and scarring absence, in comparison to a biopsy. Nevertheless, previous studies reported difficulties in differentiating the different BCC subtypes. The objective of this study was to determine the capability and accuracy of scraping cytology to differentiate between sBCC and non-sBCC. Methods: In this retrospective study, cytological samples of histologically confirmed BCC were examined. Select cytological features were correlated to BCC subtypes (sBCC or non-sBCC). Results: A total of 84 BCC samples were included (29 sBCC; 55 non-sBCC). An inverse correlation between the diagnosis of sBCC and the presence of mucin, dehiscence, and grade of atypia in the basal cells was observed. The presence of medium and large basal cell clusters correlated directly to a sBCC diagnosis. The presence of clear cells is strongly associated with sBCC. Therefore, Conclusion: Scraping cytology is reliable in differentiating sBCC from other BCC subtypes.

Characterisation of the inflammatory response triggered by topical ingenol mebutate 0.05% gel in basal cell carcinoma.

Ingenol mebutate gel is approved for actinic keratosis field therapy, but little has been published as a treatment of basal cell carcinoma (BCC). Our objective is to characterise the histopathological changes and the infiltrating cell populations to better understand its mechanism of action. Sixteen patients with various BCC subtypes were prospectively evaluated and treated once daily for two consecutive days with ingenol mebutate gel 0.05% under occlusion. Patients were randomised to two arms: the first arm was biopsied between the third and the tenth day after treatment initiation ('early immune response'), and the second arm was biopsied at day 30 after treatment initiation ('late immune response'). The immunopathology was evaluated by immunohistochemistry: anti-CD3, anti-CD4, anti-CD8, anti-CD20, anti-CD56, anti-CD68, anti-Bcl-2, anti-CASP3, anti-FoxP3, anti-GrzB and anti-TIA-1. Ten BCCs were in complete remission after 2years of follow-up. The early immune response was characterised by a quick recruitment of T lymphocytes, macrophages and natural killer cells. At later time-points, T-regulatory cells and some pro-apoptotic markers were detected. Treatment-related adverse events were described. Ingenol mebutate gel produces a transient immuno-inflammatory response and an important necrosis reaction in BCCs. Larger studies will be required to determine the maximum effective tolerated dose of ingenol mebutate gel for BCC.

Efficacy of dermoscopy in the diagnosis of different basal cell carcinoma subtypes

Background Basal cell carcinoma (BCC) accounts for nearly 80% of all nonmelanoma skin cancers and dermoscopy is an important, noninvasive technique that aids in the diagnosis of BCC. Objectives To evaluate the role of dermoscopy as a tool for diagnosis of BCC and prediction of its histopathological types. Patients and methods Dermoscopic features of 30 clinically diagnosed BCCs were analyzed before the histopathological findings were evaluated. Results Dermoscopy was 100% accurate in the diagnosis of BCC and types of BCC predicted by dermoscopy were identical to the results of histopathological examination, both yielding 27 nodular BCCs (90%), one superficial, one morpheaform, and one lesion of the infiltrative type, each representing 3.3% of lesions, but we did not detect any specific dermoscopic findings in the aggressive micronodular subtype. Conclusions Dermoscopy is accurate in predicting the main histopathological types, but not the aggressive subtypes of BCC, thus it should be considered a routine but not a sole investigation for BCC.

Periocular basal cell carcinoma: recurrence risk factors/when to reoperate?

IntroductionThe aim of periocular basal cell carcinoma (BCC) surgery is radical excision of the tumour while maintaining eyelid functionality and facial aesthetics. Differences in management of the patients after excision of eyelid BCC with a narrow margin are described in the literature.AimThis study concerns the correlation between the recurrence rate in the periorbital area and the narrow safety margin of excision in the histopathological report with respect to various clinical and histopathological features.Material and methodsA retrospective non-randomized analysis was conducted on 158 patients with BCC of the periorbital area. These patients were operated on between January 2002 and December 2016. A database was created, comprised of patient age, sex, location of the lesion, TNM, method of reconstruction, result of the histopathological examination, date and location of the recurrence.ResultsIn 66 (41.77%) patients BCC was radically removed. In 50 (31.65%) patients BCC was removed with a narrow margin and in 42 (26.58%) cases, radical excision was not achieved. The recurrence rate was significantly higher in the aggressive BCC group compared to those with non-aggressive BCC (p = 0.004). The recurrence-free rate for non-aggressive subtypes was 98.11% in both the first and fifth years, but in aggressive subtypes it was 89.06% in the first year but fell to 80.16% in the fifth year.ConclusionsAn aggressive subtype of BCC significantly influences the risk of non-radical excision of the lesion. Aggressive BCC subtypes should have more frequent check-ups. There is no need to reoperate patients with a narrow margin of BCC excision.

Optical coherence angiography for pre-treatment assessment and treatment monitoring following photodynamic therapy: a basal cell carcinoma patient study

Microvascular networks of human basal cell carcinomas (BCC) and surrounding skin were assessed with optical coherence angiography (OCA) in conjunction with photodynamic therapy (PDT). OCA images were collected and analyzed in 31 lesions pre-treatment, and immediately/24 hours/3–12 months post-treatment. Pre-treatment OCA enabled differentiation between prevalent subtypes of BCC (nodular and superficial) and nodular-with-necrotic-core BCC subtypes with a diagnostic accuracy of 78%; this can facilitate more accurate biopsy reducing sampling error and better therapy regimen selection. Post-treatment OCA images at 24 hours were 98% predictive of eventual outcome. Additional findings highlight the importance of pre-treatment necrotic core, vascular metrics associated with hypertrophic scar formation, and early microvascular changes necessary in both tumorous and peri-tumorous regions to ensure treatment success.

Ex vivo full-field cellular-resolution optical coherence tomography of basal cell carcinomas: A pilot study of quality and feasibility of images and diagnostic accuracy in subtypes.

Studies have reported the application of conventional optical coherence tomography (OCT) in the diagnosis of basal cell carcinoma (BCC). The new OCT provides cellular details similar to those in pathology slides and may reduce user learning time. This study aimed to demonstrate the quality of ex vivo full-field cellular-resolution OCT images and compare the diagnostic accuracy between physicians with varying pathology experience. Sixty histologically confirmed BCCs were selected. Tissue samples were sectioned and scanned using OCT, and their features were compared with those of hematoxylin and eosin (H&E)-stained sections. Thirty images were selected for the test administered to dermatology residents, dermatopathology fellows, and board-certified general pathologists without any OCT experience. The pretest learning included a 3-min instruction and 10-min self-study of four BCC variants. Histopathological BCC and normal histological features were clearly recognizable on the OCT images. The pathological BCC features observed in the OCT images correlated with those found in the H&E-stained sections. Seven participants completed the test. The correct answer rates of the residents, fellows, and pathologists were 71%, 68%, and 83% for BCC and 44%, 57%, and 57% for the BCC subtypes, respectively. All the participants identified BCC in >70% cases with a learning time of only 13minutes. The results indicated that cellular-resolution OCT provided high-quality images similar to the conventional pathology slides. Pathology experience did reflect the diagnostic accuracy. However, a longer training time is still needed at all levels to recognize the BCC subtypes correctly.

Expression profile of sonic hedgehog signaling-related molecules in basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common human cancer, characterized by aberrant activation of the hedgehog (HH) signaling pathway resulting from mutations in the patched 1 (PTCH1) or smoothened (SMO) genes. In the present study, to uncover the expression profile of HH signaling-related molecules, we thoroughly examined the mRNA and protein expression levels of six molecules including GLI1, GLI2, PTCH1, PTCH2, SHH, and SMO in BCC and various other cutaneous tumors. Real-time PCR analysis demonstrated that BCC showed remarkably enhanced mRNA expression of all HH molecules, except SMO compared to other skin tumors. However, immunohistochemical analysis revealed that only GLI1 protein was specifically upregulated in BCC, while the other HH-related proteins did not show any significant differences between the tumors. Notably, other skin malignancies such as squamous cell carcinoma, sebaceous carcinoma, and malignant melanoma showed no GLI1 expression and there was no difference in GLI1 expression between the BCC subtypes. In addition, GLI1 and GLI2 expression were strongly associated with the hair follicle stem cell markers, LGR4 and LGR5, which are known target genes of the Wnt pathway. Our results suggest that GLI1 has the potential to be a diagnostically useful marker for differentiating BCC from other skin malignancies and an interaction between the HH and Wnt signaling pathways may be involved in the development of BCCs.

Dicer Sequencing, Whole Genome Methylation Profiling, mRNA and smallRNA Sequencing Analysis in Basal Cell Carcinoma.

Perturbations in the expression of microRNAs (miRNAs) and their maturing machinery components such as Dicer have been previously described for basal cell carcinoma (BCC). However, the mutational status of Dicer in BCC is unclear. Further, the sclerodermiform subtype of BCC (sBCC) has not been previously investigated regarding its methylation profile or its smallRNA expression profile via RNA sequencing. We conducted this study to investigate the mutational status of Dicer in BCC. Dicer sequencing was performed on the Illumina MiSeq System in a total of 16 BCC samples (8 nodular BCCs, 8 sBCCs) and mapped against the human reference genome (i.e., hg19). Dicer sequencing was performed in all 16 BCC samples. We performed whole genome methylation profiling with Infinium MethylationEPIC BeadChips as well as mRNA and smallRNA sequencing in 5 sBCCs with the Illumina NextSeq500 next-generation sequencing system. Compared to the wildtype Dicer sequence, we found 5 to 7 variants per sBCC sample including insertion, deletion, and multiple nucleotide variants. Global methylation profiles were highly similar between groups. mRNA sequencing revealed S100A9, KRT14, KRT10, S100A8, S100A7, COX1, KRT1, COX3, and smallRNA sequencing analysis miR-21, miR-99a, miR26-a-2, let-7f, let-7g, let-7i, miR-100, and miR-205 were the most strongly expressed in sBCCs. We identified a variety of Dicer mutations that could play a role in aberrant miRNA expression in BCC. The noted RNA sequences should be further evaluated in functional studies to explore their potential pathogenetic role in sBCC.

Single versus Multiple Level Sectioning for the Subtyping of Basal-Cell Carcinoma: A Retrospective Study

Background: The histological subtype of basal-cell carcinoma (BCC) is often based on a punch biopsy; only a small part is evaluated, possibly leading to misclassification. Consensus on the optimal approach to process punch biopsies is lacking, though accurate subtyping is important for appropriate treatment. Objective: The aim is to investigate whether evaluating 4 levels of a punch biopsy instead of 1 or 2 levels leads to more accurate subtyping of BCC. Methods: In a retrospective study we evaluated 87 punch biopsies of histologically confirmed BCCs. The primary outcome was the proportion of “more aggressive” BCCs (nonsuperficial vs. superficial, infiltrative vs. nodular subtype) that was missed by evaluation on 1 or 2 levels, using 4-level diagnosis as reference standard. Results: Eighty-five cases were available for analysis. Subtyping based on 1 level resulted in discrepancies with 4-level diagnosis in 16.5% of all cases. Underdiagnosis occurred in 14 of 58 nonsuperficial BCCs (24.1%, 95% CI: 13.9–37.2). Seven of 38 nodular BCCs (18.4%, 95% CI: 7.74–34.3) were diagnosed as superficial in 1 level, and 7 of 20 infiltrative BCCs (35%, 95% CI: 15.4–59.2) were diagnosed as superficial (n = 2) or nodular (n = 5) in 1 level. Conclusion: In order to maximize correct subtyping and plan appropriate treatment, we advise to evaluate at least 2, but preferably more, levels of a punch biopsy to determine the BCC subtype.

Spectrum of Tp53 gene mutation in basal cell carcinoma and its morphological subtypes in people of color.

Objectives: Basal cell carcinoma (BCC) is the most common cutaneous malignancy in white population. The pattern of exon specific p53 mutations in BCC and its subtypes remain undetected in our population. This study was designed to evaluate the prevalence and mutational spectrum of p53 mutations in basal cell carcinoma (BCC) and its subtypes in people of color in the population of Karachi, Pakistan. Study Design: Retrospective cross sectional study. Setting: Department of Pathology, Basic Medical Sciences Institute, Jinnah Post Graduate Medical Center Karachi, Pakistan. Period: Five-year study from January 2012 to December 2016. Material and Methods: Convenient sampling technique was used. Sample size was calculated using open EPI software. Analysis of 32 BCC cases for p53 gene mutations in exons 5-8 was detected by polymerase chain reaction technique. Sebaceous carcinoma and malignant melanoma were used as positive controls and normal skin was used as negative control. Results: Out of 32 BCC cases, 26 (81.2%) displayed p53 exon mutations. The number of cases with single exon mutation was 17 (65.3%). Exon 5 mutation was most frequently observed in 8 (30.7%) cases. This was followed by 5 (19.2%) cases with exon 6 mutation and 4 (15.3%) cases with exon 8 mutation. None of the cases revealed exon 7 mutation. A considerable number 9 (34.6%) of BCC displayed dual exon mutation. Dual mutations of exon 6 &amp; 8 were seen in 6 (23%) cases. Exon 5 &amp; 7 mutation was noted in 2 (7.6%) cases followed by a single (3.8%) case with exon 6&amp;7 mutation. The highest number 12 (46.1%) of single and dual exon mutations was recorded in nodular subtype of BCC. Conclusion: The current study confirms the expression of p53 gene mutation in BCC in colored population. Majority of the single mutations were observed in exon 5. Dual exon mutation was the most notable finding of this study. The highest number of single and dual exon mutations was recorded in nodular form of BCC.

Evaluation of Patched-1 Protein Expression Level in Low Risk and High Risk Basal Cell Carcinoma Subtypes.

Objective:Basal cell carcinoma (BCC) is the most common malignancy in humans and represents a growing public health care problem. The major etiological factors contributing to BCC development are exposure to ultraviolet radiation and genetic alterations. BCC is primarily caused by dysregulation of sonic Hedgehog (HH) signaling pathway in basal cells of the skin. BCC can be classified into low risk non-aggressive and high risk aggressive subtypes. BCC subtypes differentiation is essential for prognosis and for better disease management and treatment strategies. The aim of this study was to assess the correlation between PTCH1 protein expression level and the aggressiveness of BCC histopathology. Methods:Archival paraffin embedded blocks containing BCC were retrieved from a cohort of 101 patients. Immunohistochemistry staining was performed to assess the expression level of PTCH1 which is a key component of Hedgehog pathway.Results:101 paraffin embedded samples were evaluated and classified as high risk and low risk BCC subtypes by histopathological finding. High risk BCC subtypes were found in 40 samples (39.6%) and low risk subtypes were identified in 61 samples (60.4%). Nodular was the most frequent subtype which was found in (56/ 101), followed by infiltrative (22/101) and micronodular (14/ 101) subtypes. Positive PTCH1 expression was found highest in nodular subtypes (46.5%). Conclusion:In this study, the correlation between low risk or high risk BCC subtypes and PTCH1 expression level was not statistically significant (p>0.05), but the frequency of positive PTCH1 expression was found to be higher in low risk subtypes than high risk BCC subtypes.

STAT3, STAT5A, STAT5B and STAT6 proteins are overexpressed in human basal cell carcinoma.

The molecular pathogenesis of basal cell carcinoma (BCC) is still not precisely described and is the subject of ongoing studies. The role of signal transducers and activators of transcription (STATs) in human epithelial carcinogenesis has been poorly investigated, but in the era of studies on inhibitors targeting STAT proteins this topic seems worth exploring. Increased expression of STAT3 in human nonmelanoma skin cancer (NMSC) has been confirmed in a few studies, but to our knowledge, expression of STAT5A, STAT5B and STAT6 in BCC has not been previously evaluated. To measure expression of STAT3, STAT5A, STAT5B and STAT6 expression in different histopathological subtypes of human BCC and its correlation with selected clinical variables. Immunohistochemistry was used to assess 60 BCC tumour specimens [20 superficial (s)BCCs, 20 nodular (n)BCCs and 20 infiltrative (i)BCCs] and to compare with specimens of healthy skin. There was no significant difference in age or sex between the three groups of patients with BCC. As many tumours showed heterogeneity of staining, the H-score system was applied to calculate the intensity of immunoexpression. Expression of STAT3, STAT5A, STAT5B and STAT6 was observed in all histopathological subtypes of BCC, and was stronger than the expression within the adjacent epidermis and also stronger than the expression within the epidermis in the healthy control group. Statistical analysis revealed no significant differences in mean H-scores calculated for sBCCs, nBCCs and iBCCs. There were no statistically significant associations between STAT3, STAT5A, STAT5B and STAT6 expression and patient sex/age, and tumour size/site. Our results confirm a possible role of STATs in the pathogenesis of BCC and should encourage future investigations on the possible therapeutic implications of this finding.