Basal cell carcinoma trends in Thailand: a 10-year retrospective study of demographic, clinical and histopathological features

Background: Basal cell carcinoma (BCC) is the most common skin cancer with globally increasing incidence. To date, the information regarding BCC in Thailand is limited.Objective: To evaluate the demographic, clinical, histopathological trends of BCC and other contributing factors.Methods: We retrospectively reviewed the demographic, clinical and histological data of all BCC outpatients from January 2009 to December 2018.Results: From 278 BCC patients recruited to this study, most of them (71.6%) were older than 60 years old. The most common histological subtype was nodular BCC (63.3%). A statistically significant association was observed between histological variant and location of the tumor; H and M area were associated with nodular BCC, L area was related to superficial subtype (p-value < 0.001). Misdiagnosis of BCC was observed in 53 cases, mostly as melanocytic nevus (30.2%), and about quarter (26.4%) was made by board-certified dermatologists.Conclusions: Nodular BCC is significantly associated with H and M area, while superficial subtype is related to L location. Quarter of the patients already have large tumors at their first presentation. Misdiagnosis of BCC is not uncommon.

Transcriptome Analysis of Large to Giant Congenital Melanocytic Nevus Reveals Cell Cycle Arrest and Immune Evasion: Identifying Potential Targets for Treatment

Large to giant congenital melanocytic nevus (lgCMN) is a benign cutaneous tumor that develops during embryogenesis. A large number of lgCMN patients are ineligible for surgical treatment; hence, there is an urgent need to develop pharmacological treatments. Clinically, tumorigenesis and progression essentially halt after birth, resulting in the homeostasis of growth arrest and survival. Numerous studies have employed whole-genome or whole-exome sequencing to clarify the etiology of lgCMN; however, transcriptome sequencing of lgCMN is still lacking. Through comprehensive transcriptome analysis, this study elucidated the ongoing regulation and homeostasis of lgCMN and identified potential targets for treatment. Transcriptome sequencing, identification of differentially expressed genes and hub genes, protein–protein network construction, functional enrichment, pathway analysis, and gene annotations were performed in this study. Immunohistochemistry, real-time quantitative PCR, immunocytofluorescence, and cell cycle assays were employed for further validation. The results revealed several intriguing phenomena in lgCMN, including P16-induced cell cycle arrest, antiapoptotic activity, and immune evasion caused by malfunction of tumor antigen processing. The arrested cell cycle in lgCMN is consistent with its phenotype and rare malignant transformation. Antiapoptotic activity and immune evasion might explain how such heterogeneous cells have avoided elimination. Major histocompatibility complex (MHC) class I-mediated tumor antigen processing was the hub pathway that was significantly downregulated in lgCMN, and ITCH, FBXW7, HECW2, and WWP1 were identified as candidate hub genes. In conclusion, our research provides new perspectives for immunotherapy and targeted therapy.

Mimical reconstruction and aesthetic repair of the nail after resection of subungual melanocytic nevus

Background This study aimed to report the outcomes of mimical reconstruction and aesthetic repair of the nail. Methods When the pigmented bands were more than 1/2 the width of the whole nail, mimical reconstruction of the nail was performed, with a lateral toe pulp island flap covering the wound via the subcutaneous channel. If the pigmented bands were 1/4 to 2/5 the width of the entire nail, aesthetic repair of the nail was carried out by split-thickness excision under a microscope. Results The average age of patients at the time of surgery was 14.5 years. Five patients had lesions on their toes, while three had lesions on their fingers. There were no post-operative complications. All toenails of the five patients who had undergone mimical reconstruction exhibited a well-settled flap. The nails of the three patients who underwent aesthetic repair displayed no nail malnutrition or deformity, and all nails had an aesthetic appearance. Conclusions Both mimical reconstruction and aesthetic repair of the nail following resection of subungual melanocytic nevus are reliable and feasible. The “like tissue” repairs of complex nail defects appear to be satisfactory. All patients had excellent aesthetic outcomes. Level of evidence V

Proportion of Thick versus Thin Melanomas as a Benchmarking Tool

Background: The ratio of benign moles excised for each malignant melanoma diagnosed (number-needed-to-excise (NNE)) is a metric used to express the efficiency of diagnostic accuracy of melanoma. The literature suggests a progressive effort to reduce the NNE, thus raising concerns about missing early melanoma because the NNE does not capture the most significant outcome for melanoma prognosis, which is linked to the Breslow thickness. A lower NNE could reduce health costs related to melanoma diagnosis only if doing so does not increase the proportion of thicker melanomas. Objectives: The diagnostic performance by two tertiary referral centres using the NNE and proportion of thick (Breslow thickness > 1 mm) versus thin (Breslow thickness ≤ 1 mm) excised melanoma (thick/thin ratio: TTR) was compared to determine if a lower NNE is associated with a greater proportion of thicker melanoma. Combining TTR with NNE allows a better estimate of the effectiveness in melanoma diagnosis, assessing both the overall cost for a given pool of excised melanomas and costs due to unnecessary nevi excision at a particular dermatology centre. Methods: Demographic data and Breslow thickness of excised melanoma were extracted from patient histologic records at two referral centres for melanoma (Parma Dermatology Unit and Ravenna and Meldola Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori. IRCCS (IRST)) on all skin tumours excised between 2002 and 2011 and diagnosed as melanoma or melanocytic nevus. NNE and TTR were calculated and compared among the considered variables. Logistic regression was used to assess the contribution of each variable in predicting a higher TTR. Results: Data from 16,738 excised lesions were analysed. The IRST Unit reported a mean NNE of 4.6, whereas the Parma Unit excised 10.6 nevi for each melanoma. No statistically significant differences existed in the mean (IRST Unit, 0.56 ± 0.89 mm; Parma Unit, 1.07 ± 2.2 mm) and median (range) Breslow thickness (IRST Unit, 0.4 (9) mm; Parma Unit 0.4 (30) mm). The TTR between centres was significantly different (Parma Unit, 24%; IRST Unit, 12%; p < 0.001). Based on logistic regression, the diagnosing centre was the most powerful factor in determining a thickness of >1 mm among diagnosed melanomas (OR = 1.8; 95% CI, 1.2–2.7; p < 0.01), with all other factors being equal. The NNE decreased at both centres from younger-to-older patients, whereas the TTR increased simultaneously; however, the increase in TTR was non-significantly related to NNE reduction after adjusting for confounders (age, gender, and localization). Conclusions: A better diagnostic performance is capable of reducing the NNE and TTR, i.e., unnecessary excisions of melanocytic nevi can be reduced without increasing the risk of overlooking melanomas. The TTR, in addition to the NNE, allows stakeholders to better estimate the effectiveness in melanoma diagnosis because both overall costs for a given pool of excised melanomas and costs due for unnecessary nevi excision at a particular dermatology centre can be compared.

BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB

Benign melanocytic nevi frequently emerge when an acquired BRAFV600E mutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence in melanocytic nevus formation, necessitating investigations into alternative mechanisms for the establishment and maintenance of proliferation arrest in nevi. We compared the transcriptomes of melanocytes from healthy human skin, nevi, and melanomas arising from nevi and identified a set of microRNAs as highly expressed nevus-enriched transcripts. Two of these microRNAs—MIR211-5p and MIR328-3p—induced mitotic failure, genome duplication, and proliferation arrest in human melanocytes through convergent targeting of AURKB. We demonstrate that BRAFV600E induces a similar proliferation arrest in primary human melanocytes that is both reversible and conditional. Specifically, BRAFV600E expression stimulates either arrest or proliferation depending on the differentiation state of the melanocyte. We report genome duplication in human melanocytic nevi, reciprocal expression of AURKB and microRNAs in nevi and melanomas, and rescue of arrested human nevus cells with AURKB expression. Taken together, our data describe an alternative molecular mechanism for melanocytic nevus formation that is congruent with both experimental and clinical observations.

Mimical Reconstruction And Aesthetic Repair of The Nail After Resection of Subungual Melanocytic Nevus

Background: The purpose of this study is to report the outcomes of mimical reconstruction and aesthetic repair of the nail.Methods: When the width of the pigmented bands was more than 1/2 of the whole nail width, the mimical reconstruction of the nail, the lateral toe pulp island flap covered the wound via the subcutaneous channel, was performed. If the width of the pigmented bands ranged from 1/4 to 2/5 of the entire nail, the aesthetic repair of the nail, the split-thickness excision under microscope, would be carried out.Results: The average age at the time of surgery was 14.5 years. The lesions were located at the toes in 5 patients and fingers in 3 patients. No complications occurred postoperatively. In 5 patients with the mimical reconstruction of the nail, all of toenail showed well-settled flap. In three patients with the aesthetic repair of the nail, there was no nail malnutrition or deformity, and all nails have an aesthetic appearance.Conclusions: Mimical reconstruction and aesthetic repair of the nail following resection of subungual melanocytic nevus is reliable and feasible. It seems to be satisfactory that “like tissue” repairs the complex nail defects. All patients obtain an excellent aesthetic outcome.Level of Evidence: V