Implication of Amyloid Precursor-like Protein 2 Expression in Cutaneous Squamous Cell Carcinoma Pathogenesis.

BACKGROUND/AIM: Regulatory functions of amyloid precursor-like protein 2 (APLP2) expression in intracellular trafficking of major histocompatibility complex class I (MHC-I) and biological behavior of tumor cells have been reported in various types of malignancies but not in cutaneous squamous cell carcinoma (CSCC). This study aimed to investigate the role of APLP2 expression in the pathogenesis of CSCC. PATIENTS AND METHODS: The expression of APLP2 and a key modulator of cancer immune escape, MHC-I, were determined in CSCC tissue samples obtained from 141 patients using immunohistochemistry. The regulatory effects of APLP2 expression on the biological behavior and surface expression of MHC-I in CSCC cells were investigated by trypan blue assay, Matrigel invasion assay, and in vivo xenograft analysis. RESULTS: APLP2 immunoreactivity was high in 73 (51.8%) tissue samples from patients with CSCC and was significantly related to subcutaneous fat invasion and poor prognosis in our cohort. Moreover, proliferation of and invasion by CSCC cells were significantly reduced after APLP2 knockdown in CSCC cells both in vitro and in vivo. A significant association was found between APLP2 and membrane MHC-I expression in patients with CSCC. In vivo xenograft analysis showed that APLP2 knockdown increased membrane MHC-I expression in CSCC cells. CONCLUSION: APLP2 not only acts as an oncogene in CSCC progression but also as a possible modulator of cancer immune escape by influencing MHC-I expression on the cell surface. APLP2 may serve as a novel molecular biomarker and therapeutic target for patients with CSCC.

Various Applications of Purse-String Suture and Its Cosmetic Outcome in Cutaneous Surgical Defects.

BACKGROUND: Purse-string suture is a simple technique to reduce wound size and to achieve complete or partial closure of skin defects. OBJECTIVE: To classify situations in which purse-string sutures can be utilized and to assess the long-term size reduction and cosmetic outcome of the final scar. METHODS: Patients (93 from Severance hospital and 12 from Gangnam Severance hospital) in whom purse-string sutures were used between January 2015 and December 2019 were retrospectively reviewed. Wound site, final reconstruction method, repair duration, final wound size, and Vancouver scar scale were assessed. RESULTS: A total of 105 patients were reviewed. Lesions were located on the trunk (48 [45.7%]), limbs (32 [30.5%]), and face (25 [23.8%]). Mean ratio of wound length/primary defect length was 0.79±0.30. Multilayered purse-string suture showed the shortest duration from excision to final repair (p<0.001) and most effectively minimized the scar size (scar to defect size ratio 0.67±0.23, p=0.002). The average Vancouver scar scale measured at the latest follow-up visit at least 6 months postoperatively was 1.62, and the risk of hypertrophic scarring was 8.6%. There was no significant difference in the Vancouver scar scale and the risk of hypertrophic scarring between the different surgical method groups. CONCLUSION: Purse-string sutures can be utilized in many stages of reconstruction to effectively reduce scar size without compromising the final cosmetic outcome.

A nomogram combining clinical factors and biomarkers for predicting the recurrence of high-risk cutaneous squamous cell carcinoma.

BACKGROUND: Although determining the recurrence of cutaneous squamous cell carcinoma (cSCC) is important, currently suggested systems and single biomarkers have limited power for predicting recurrence. OBJECTIVE: In this study, combinations of clinical factors and biomarkers were adapted into a nomogram to construct a powerful risk prediction model. METHODS: The study included 145 cSCC patients treated with Mohs micrographic surgery. Clinical factors were reviewed, and immunohistochemistry was performed using tumor tissue samples. A nomogram was constructed by combining meaningful clinical factors and protein markers. RESULTS: Among the various factors, four clinical factors (tumor size, organ transplantation history, poor differentiation, and invasion into subcutaneous fat) and two biomarkers (Axin2 and p53) were selected and combined into a nomogram. The concordance index (C-index) of the nomogram for predicting recurrence was 0.809, which was higher than that for the American Joint Committee on Cancer (AJCC) 7th, AJCC 8th, Brigham and Women's Hospital, and Breuninger staging systems in the patient data set. CONCLUSION: A nomogram model that included both clinical factors and biomarkers was much more powerful than previous systems for predicting cSCC recurrence.

Implication of COPB2 Expression on Cutaneous Squamous Cell Carcinoma Pathogenesis.

The underlying molecular mechanisms of cutaneous squamous cell carcinoma (cSCC) pathogenesis are largely unknown. In the present study, we aimed to evaluate the effect of coatomer protein complex subunit beta 2 (COPB2) expression on cSCC pathogenesis. Clinicopathological significance of COPB2 in cSCC was investigated by analyzing the Gene Expression Omnibus (GEO) database and through a retrospective cohort study of 95 cSCC patients. The effect of COPB2 expression on the biological behavior of cSCC cells was investigated both in vitro and in vivo. We found that COPB2 expression was significantly higher in cSCC samples than in normal skin samples. In our cohort, a considerable association was found between COPB2 expression and indicators of tumor immune microenvironment (TIME), such as histocompatibility complex class (MHC) I, and MHC II, CD4+/ CD8+ tumor-infiltrating lymphocytes. Additionally, COPB2 expression had an independent impact on worsened recurrence-free survival in our cohort. Furthermore, decreased proliferation, invasion, tumorigenic activities, and increased apoptosis were observed after COPB2 knockdown in cSCC cells. COPB2 may act as a potential oncogene and candidate modulator of the TIME in cSCC. Therefore, it can serve as a novel predictive prognostic biomarker and candidate immunotherapeutic target in cSCC patients.

Digital Dermatopathology and Its Application to Mohs Micrographic Surgery.

Digital pathology is being gradually adopted in hospitals due to technological advances. We propose that digital pathology can be used in Mohs micrographic surgery (Mohs surgery) to precisely check residual tumor cells in frozen tumor margin tissues. This would aid surgeons and pathologists in accurately recording tumor margins and give patients the benefit of shorter operation time.

Initial topical monotherapy may increase the risk of recurrence in patients with extramammary Paget's disease.

Although topical therapies are used to treat extramammary Paget's disease (EMPD), reliable treatment outcomes and the effects of these therapies on subsequent surgical treatments are unclear. To assess the clinical outcomes of topical treatment of EMPD and establish the treatment guidelines the medical records of 166 patients diagnosed with EMPD were retrospectively reviewed. The recurrence rate was evaluated according to the previous use of topical agents. Thirty-four patients (34/166, 20.5%) were initially treated with topical agents such as imiquimod, 5-fluorouracil, and ingenol mebutate. Three patients (3/34, 8.8%) showed clinical response, while 31 patients required subsequent therapy owing to treatment failure. Analysis of the prognostic factors of recurrence in 166 patients revealed that initial topical treatment increased the hazard ratio (HR) in both univariate and multiple Cox proportional hazards models (HR = 3.770, 95% confidence interval [CI] = 1.768-8.037, P = 0.001, and adjusted HR = 3.628, 95% CI = 1.558-8.450, P = 0.003). Patients treated with topical agents showed significantly poorer 3-year recurrence-free survival than the nontreated group (66.3% vs 88.6%, P < 0.001). Topical treatment may be deleterious for some EMPD patients, thus increasing the recurrence risk.

Hypopigmentation in Extramammary Paget Disease Is an Important Prognostic Factor for High Recurrence Rate and Poor Surgical Outcome.

BACKGROUND: Several studies have reported the presence of hypopigmentation in extramammary Paget disease (EMPD). However, an in-depth analysis regarding its clinical implication is lacking. OBJECTIVE: To evaluate the clinical characteristics of EMPD in the Korean population and to determine the implication of hypopigmentation on clinical outcomes. METHODS: We retrospectively reviewed 124 cases of EMPD who underwent surgical treatment from a single tertiary hospital from December 2005 to March 2019. Baseline characteristics of the patients and hypopigmentation patterns were analyzed. Moreover, the number of stages of Mohs micrographic surgery (MMS) and recurrence rate were evaluated in relation to the hypopigmentation. RESULTS: A total of 67.7% (n = 84) of the patients showed hypopigmentation. The adjusted odds ratio for recurrence in the hypopigmented group was 5.980, which was statistically significant (95% confidence interval = 1.347-26.553, p-value = 0.019). Furthermore, the average number of MMS stages was 2.92 in the hypopigmentation group, compared with 1.82 in the nonhypopigmentation group (p-value = .0016). CONCLUSION: Hypopigmented lesions may disguise the tumor margin, thus raising the recurrence rate after surgery and the number of stages of MMS. The hypopigmentation status must be considered when deciding the surgical margin.

Slow Mohs Micrographic Surgery for Acral Melanoma Treatment in Korean Patients.

BACKGROUND: Obtaining conventional wide surgical margins is challenging in melanomas occurring at anatomically complex sites (e.g., hands and feet). OBJECTIVE: We investigated the potential benefits of slow Mohs micrographic surgery (MMS) for acral melanomas. MATERIALS AND METHODS: This single-center retrospective study investigated 210 patients who underwent slow MMS (n = 66) or wide local excision (WLE, n = 144) for melanomas during 2005 to 2015. Slow MMS was used for melanomas in anatomically complex locations and for high-risk lesions. RESULTS: Acral melanoma (166/210) was the most common lesion observed in patients, in addition to head and neck (21/210) and trunk (23/210) melanomas. Slow MMS was more commonly performed for acral, and head and neck melanomas (32.5% and 52.4%, respectively) than for trunk melanomas (4.3%, p = .002). Local recurrence of acral melanomas occurred in 3.7% of patients after slow MMS and in 10.7% of patients after WLE. Multivariate analysis showed comparable prognostic outcomes between slow MMS and WLE used for acral melanomas. Compared with WLE, slow MMS resulted in a smaller postoperative defect after acral lesion excision (p < .001). CONCLUSION: Slow MMS is an effective alternative to WLE for acral melanomas in anatomically complex sites, as evidenced by superior outcomes and maximum tissue conservation.

Application of secondary intention for the restoration of the apical triangle after Mohs micrographic surgery.

BACKGROUND: Restoring the apical triangle (AT) to maintain the symmetry of the face after Mohs micrographic surgery can be challenging. We have applied secondary intention (SI) after partial closure in cases with large defects. OBJECTIVE: To compare the cosmetic results between immediate closure (IC) and SI. METHODS & MATERIALS: We retrospectively reviewed 24 patients (IC group: n = 15, SI group: n = 9). To evaluate the symmetry, the comparative ratio (CR; area of the AT of the involved side/area of the normal contralateral side) was calculated. RESULTS: The defects were significantly larger in the SI group than in the IC group (588.89 ± 346.53 mm2 vs. 252.87 ± 196.52 mm2, p < .01). While there was no statistically significant difference in average CR, the standard deviation was higher in the SI group (0.95 ± 0.08 vs. 0.93 ± 0.31, p = .3359), indicating the difficulty in predicting the results of SI healing. The average visual analog scale score evaluated by two dermatologists was higher in the IC group, albeit without a significant difference (8.23 ± 0.96 vs. 7.78 ± 1.52, p = .5267). CONCLUSION: SI after partial closure can be an option for large defects in the AT area.

Checkmark rotation flap for nasal tip reconstruction in Asian patients.

Background: Nasal tip reconstruction (NTR) of the Mohs defect is challenging, especially in Asians who have a relatively low nasal bridge and thin cartilages.Objective: To evaluate the usefulness of a new flap design, the checkmark rotation flap (CRF), for NTR in AsiansMethods and materials: We retrospectively reviewed 31 cases of NTR. Among these, 15 cases underwent CRF, which uses skin from the columellar or infra-tip area with a checkmark v-shaped incision (CRF group). The remaining 16 cases underwent reconstruction with other flaps such as the bilobed or island pedicle flap (Others group).Results: The average defect area was larger in the CRF than in the Others group (1.85 ± 1.01 cm2 vs. 1.10 ± 0.72 cm2, p = .0499), but the visual analog scale score was significantly higher in the CRF group (7.97 ± 1.36 vs. 6.25 ± 1.62, p = .0059). For complications, a depressed scar was observed in four cases (26.7%) in the CRF group; nine cases (56.3%) in the Others group presented with a depressed scar, hypertrophic scar, or scarring similar to a trap door deformity.Conclusion: CRF may be a favorable option for the reconstruction of intermediate-sized nasal tip defects, providing good cosmetic outcomes.

AXIN2 and SNAIL expression predict the risk of recurrence in cutaneous squamous cell carcinoma after Mohs micrographic surgery.

Recurrence is a common complication observed during cutaneous squamous cell carcinoma (cSCC) treatment; however, biomarkers for predicting recurrence in cSCC remain unknown. The present study aimed to investigate the predictive value of axis inhibition protein 2 (AXIN2) and SNAIL expression in cSCC recurrence. AXIN2 and SNAIL expression was evaluated using immunohistochemistry in 111 cSCC tissue samples obtained from 18 patients who presented recurrence (recurrence interval, 1-91 months) and 93 patients who did not experience recurrence following Mohs micrographic surgery (MMS) during the follow-up period (156 months). Nomogram construction was performed using patients' clinicopathological characteristics and AXIN2 and SNAIL protein expression. The results demonstrated that high AXIN2 (histoscore >100) and SNAIL (histoscore >100) expression was detected in 35 and 44 cSCC tissues, respectively. Furthermore, the expression levels of AXIN2 and SNAIL were significantly associated in patients with cSCC (P=0.001). AXIN2 and SNAIL expression levels were significantly associated with tumor size (P=0.021 and P=0.044, respectively) and recurrence of cSCC (P=0.017 and P=0.042, respectively). In addition, the results of the Kaplan-Meier curve analysis revealed that recurrence-free survival was significantly associated with tumor size (P=0.025), differentiation status (P<0.001), AXIN2 expression (P=0.001) and SNAIL expression (P=0.001). Furthermore, the results of the multivariate analysis demonstrated that age (P=0.043), AXIN2 expression (P=0.001) and SNAIL expression (P=0.045) were independent risk factors for cSCC recurrence in the present cohort. A nomogram for predicting the 1-, 2-, 3-, and 5-year recurrence-free survival was developed for patients with cSCC by including independent risk factors with a concordance index of 0.75. The results suggested that high AXIN2 and SNAIL expression may be considered as potential risk factors for cSCC recurrence. This nomogram may therefore be useful to assess the probability of recurrence in patients with cSCC following MMS.

Male sex and Breslow thickness are important risk factors for recurrence of localized melanoma in Korean populations.

BACKGROUND: Predicting the recurrence of localized melanoma is important; however, studies investigating risk factors for recurrence of localized melanoma are lacking in Asian populations. OBJECTIVE: To identify risk factors for recurrence of localized melanoma in Korean patients. METHODS: We retrospectively reviewed patients with cutaneous melanoma without evidence of metastasis from 2000 to 2017. Logistic and Cox regression analyses were conducted for recurrence. The average follow-up time was 46.2 months. RESULTS: We reviewed the data of 340 patients diagnosed with cutaneous melanoma and staged as melanoma in situ, stages I and II. Acral melanoma (70.3%, 239/340) was the predominant subtype. Ninety-two patients (27.1%) had a recurrence after primary melanoma removal (29 local recurrences, 49 regional metastases, and 28 distant metastases). Some patients had multiple types of recurrence at the same time. Male sex (P = .030) and Breslow thickness greater than 1 mm (P = .008) correlated with an increased risk of recurrence. Breslow thickness greater than 2.5 mm in males and greater than 4 mm in females showed a higher predictive value for recurrence than traditional stages IIB and IIC (hazard ratio 3.743 vs 2.972). LIMITATIONS: This was a single-center retrospective study. CONCLUSION: In patients with localized cutaneous melanoma, male sex and Breslow thickness are the most important prognostic factors for recurrence in Korean populations. Different cutoff values of Breslow thickness may better predict recurrence according to sex.

Risk factors for recurrence in cutaneous squamous cell carcinoma after Mohs micrographic surgery: A retrospective review of 237 Asian patients.

Even after complete removal with Mohs micrographic surgery (MMS), cutaneous squamous cell carcinoma (cSCC) may recur; however, information about risk factors for recurrence in Asian patients is limited. This retrospective study reviewed cSCC patients treated with MMS at a single tertiary referral center from 2000 to 2017. Two hundred and thirty-seven patients were included and 36 showed recurrence (20 with local recurrence, 16 with distant metastasis). History of organ transplantation, diabetes, other malignancies and poorly differentiated histology correlated with cSCC recurrence. History of organ transplantation and cryotherapy at the cSCC site were related to higher local recurrence rates, and poor differentiation related to higher distant metastasis in Asian cSCC patients treated with MMS.

Long-term outcomes of laser treatment for congenital melanocytic nevi.

BACKGROUND: Although various laser treatments have been tried for congenital melanocytic nevi (CMNs), only small retrospective studies with short-term follow-up had been done to assess outcomes. OBJECTIVE: We analyzed the long-term outcomes of laser treatment for CMN and compared these outcomes with those of a combination treatment including partial excision and lasers. METHODS: Patients with CMN treated with lasers were retrospectively reviewed, and patients with >3 years of follow-up were grouped as the long-term follow-up group. RESULTS: A total of 67 cases of CMN were reviewed. Among 20 patients (20/52, 38.5%) with near total clearance during laser-only treatment, 11 patients were in the long-term follow-up group, and 5 of 11 showed repigmentation. In total, 15 patients showed repigmentation regardless of clearance, and the mean period until repigmentation was 3.93 years from the initial treatment. Patients with partial excision and laser combination treatment showed higher Investigator's Global Assessment scores, fewer laser treatments, and shorter treatment periods compared with patients with laser-only treatment. LIMITATIONS: This is a retrospective study, and various laser devices were used. CONCLUSION: More than 4 years of follow-up is required to evaluate the efficacy of lasers in CMN, and partial excision and laser combination treatment might be an effective treatment option.

Comparison of treatment options for small to medium congenital melanocytic nevi: A retrospective review of 119 cases.

OBJECTIVES: For small to medium sized congenital melanocytic nevi (CMN), the treatment of choice is staged surgical excision. Ablative lasers or pigment-specific lasers have also been recommended for lesions difficult for surgical removal or to avoid surgery. In this study, we retrospectively analyzed the results of several treatment options for CMN to find out the optimal treatment method. METHODS: Patients with small to medium sized CMN were retrospectively reviewed. Treatment options were categorized into four groups: (i) Excision only; (ii) Excision followed by scar laser; (iii) Excision followed by pigment-specific laser; and (iv) Laser only. Treatment response was assessed by investigator's global assessment (IGA) score on a seven-point scale. RESULTS: A total of 119 cases were included. Lesions were most commonly located on the face (59/119, 49.6%), measured 2 ∼ 10 cm in size (72/119, 60.5%), and treated with excision only (50/119, 42.0%). Among treatment options, excision followed by scar laser showed the highest IGA score of 6.38. Options including surgical methods showed higher IGA scores compared to laser-only treatment (P < 0.01). Staged excisions and single excisions showed no difference in IGA scores. Patient satisfaction scores increased after scar laser treatment of the staged excision scar. CONCLUSIONS: For the treatment of small to medium sized CMN, treatment strategies including surgical methods are cosmetically superior to laser-only treatment. Also, the combination of surgical excision with scar laser has the potential for better clinical outcomes and patient satisfaction. Lasers Surg. Med. 51:62-67, 2019. © 2018 Wiley Periodicals, Inc.