Multispectral Imaging Algorithm Predicts Breslow Thickness of Melanoma

Breslow thickness is a major prognostic factor for melanoma. It is based on histopathological evaluation, and thus it is not available to aid clinical decision making at the time of the initial melanoma diagnosis. In this work, we assessed the efficacy of multispectral imaging (MSI) to predict Breslow thickness and developed a classification algorithm to determine optimal safety margins of the melanoma excision. First, we excluded nevi from the analysis with a novel quantitative parameter. Parameter s’ could differentiate nevi from melanomas with a sensitivity of 89.60% and specificity of 88.11%. Following this step, we have categorized melanomas into three different subgroups based on Breslow thickness (≤1 mm, 1–2 mm and >2 mm) with a sensitivity of 78.00% and specificity of 89.00% and a substantial agreement (κ = 0.67; 95% CI, 0.58–0.76). We compared our results to the performance of dermatologists and dermatology residents who assessed dermoscopic and clinical images of these melanomas, and reached a sensitivity of 60.38% and specificity of 80.86% with a moderate agreement (κ = 0.41; 95% CI, 0.39–0.43). Based on our findings, this novel method may help predict the appropriate safety margins for curative melanoma excision.

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.

Evaluation of Sentinel Lymph Node Status and its Association with Clinicopathological Factors in Patients with Cutaneous Melanoma: A Retrospective Study

Background: Cutaneous Melanoma (CM) is cancer with rising prevalence worldwide. The most significant predictor of CM is regional lymph node metastasis. Sentinel Lymph Node (SLN) biopsy has been used to stage CM and to identify lymphatic metastasis. This study aims to evaluate the SLN association with clinicopathological factors in the CM patients for a better surgical management. Methods: This retrospective study included 80 CM patients who had gone through lymphatic mapping and SLN biopsy at Imam Khomeini Hospital in Tehran from 2011 to 2018. The clinical and histologic factors, including sex, age, tumor location, Breslow thickness, ulceration, angiolymphatic invasion, tumor mitotic rate (TMR), and Clark level, were analyzed.Results: Fifty-six patients (70%) were found to have SLN, 19 patients (33.9%) were SLN-positive, and 37 patients (66.1%) were SLN-negative. Breslow thickness was the only variable that was significantly associated with the prediction of SLN. SLN was not correlated with other features such as ulceration, angiolymphatic invasion, and tumor mitotic rate. Complete Lymph Node Dissection (CLND) was carried out in 18 out of 19 SLN-positive patients. Moreover, 5 patients (27.8%) were found to be non-SLN-positive out of 18 SLN biopsy+CLND-positive patients. Furthermore, there was not any significant relationship between the clinicopathological features and the prediction of non-SLN. Conclusions: Breslow thickness was significantly correlated with positive SLN biopsy. Thus, it can be a strong predictor of positive SLN in CM patients.

The Role Of Sentinel Node Tumor Burden In Modeling The Prognosis Of Melanoma Patients With Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup Study (N=2,086)

Background: The management of melanoma patients with metastatic sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients. Methods: A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed. Overall survival (OS) was the outcome of interest; included independent variables were the following: age, gender, primary melanoma site, Breslow thickness, ulceration, sentinel node tumor burden (SNTB), number of positive SN, non-sentinel lymph nodes (NSN) status. Univariate and multivariate survival analyses were performed using the Cox proportional hazard regression model. Results: The 3-year, 5-year and 10-year OS rates were 79 %, 70% and 54%, respectively. At univariate analysis, all variables, except for primary melanoma body site, were found to be statistically significant prognostic factors. Multivariate Cox regression analysis indicated that older age (P< 0.0001), male gender (P= 0.04), increasing Breslow thickness (P <0.0001), presence of ulceration (P =0.004), SNTB size (P <0.0001) and metastatic NSN (P <0.0001) were independent negative predictors of OS. Conclusion: The above results were utilized to build a nomogram in order to ease the practical implementation of our prognostic model, which might improve treatment personalization.

HSP105 expression in cutaneous malignant melanoma: Correlation with clinicopathological characteristics

Background Heat shock proteins can protect against stress-associated cellular challenges, but they can also protect some tumors from human immune system monitoring. Heat shock protein 105 (HSP105/110) is a high molecular weight protein whose expression has been reported in many cancers, but few studies on its role in cutaneous malignant melanoma have been published. In this study, we analyzed the relationship between HSP105 expression and the clinicopathological characteristics of CMM. Methods This retrospective study included 91 patients with CMM. The clinicopathological characteristics of CMM patients, including age, lesion duration, location, pathological classification, Clark’s level, Breslow thickness, metastasis and recurrence, were collected. Immunohistochemical staining and Western blot analysis for HSP105 were performed. Pigmented nevi (n = 20) served as a control. The staining intensity and percentage of stained cells were expressed as a histochemical score (HSCORE). Results HSP105 was overexpressed in melanoma compared with nevi. Differences in the HSCORE between nevi (HSCORE = 1.05(0.15,1.50)) and CMM (HSCORE = 2.68(1.80,3.60)) were remarkable (P<0.001). Exposed site lesions, recurrent and metastatic lesions, nodular melanoma and lentigo maligna melanoma were closely associated with higher HSP105 expression (P = 0.011, P = 0.001 and P = 0.001, respectively). Moreover, no significant difference was observed in Clark’s level, Breslow thickness, or lesion duration (P>0.05). Conclusion HSP105 is overexpressed in CMM. Higher HSP105 expression in lesions is associated with different clinicopathological variables. HSP105 may be a potential target for the diagnosis, treatment and prognostic prediction of CMM.

Effect of changes in Breslow thickness between the initial punch biopsy results and final pathology reports in acral lentiginous melanoma patients

Acral lentiginous melanoma (ALM) is the most common subtype of cutaneous melanoma among Asians; punch biopsy is widely performed for its diagnosis. However, the pathologic parameters evaluated via punch biopsy may not be sufficient for predicting disease prognosis compared to the parameters evaluated via excisional biopsy. We investigated whether changes in Breslow thickness (BT) between initial punch biopsy results and final pathology reports can affect the prognosis of ALM. Pathologic parameters were recorded from specimens acquired through the initial punch biopsy and wide excision. Patients were classified into two groups based on a change in Breslow depth: the BT increased or decreased on comparing the samples from the initial punch biopsy and final wide excision. We compared clinical characteristics, and a Cox regression model was used to identify independent prognostic factors influencing melanoma-specific death (MSD). Changes in BT did not affect MSD (hazard ratio [HR]: 0.55, P = 0.447). In multivariate analysis, a higher BT (> 2 mm) (HR: 9.93, P = 0.046) and nodal metastasis (HR: 5.66, P = 0.041) were significantly associated with an increased MSD risk. The use of punch biopsy did not affect MSD despite the inaccuracy of BT measurement as long as ALM was accurately diagnosed.

Predictive Factors for Metastasis of Skin Melanoma of Varying Thickness According to Breslow to Sentinel Lymph Nodes

Purpose: To evaluate the prognostic factors in patients with Breslow skin melanoma of various thicknesses that affect the incidence of metastases in the signal lymph nodes (SLN).Material and methods: From November 2018 to November 2020, 324 patients with diagnosed melanoma of the skin of various localization and stages were examined and operated on. We used lymphotropic colloidal radiopharmaceutical (RPh) labeled with 99mTc. RPh with an activity of 150 MBq was administered one day before the operation intradermally around the scar of resected melanoma or peritumorally at 4 points in the case of a primary tumor. Lymphoscintigraphy was performed 1–3 hours after the RP injection on a Symbia E or Symbia E gamma camera (Siemens, Germany). Anteroposterior and lateral static polypositional scintigraphy was performed to determine the topography and mark the SLN. 324 planar studies were performed. In 259 cases, an additional study was performed SPECT (including SPECT / CT) on a Symbia T2 device (Siemens, Germany). Surgical intervention was performed the next day, taking into account the data of intraoperative radiometry using a domestic specialized hand-held gamma detector Radical (Amplituda, Russia).Results: The mean primary melanoma Breslow thickness was 2.77 ± 2.2 mm (range 0.2–13.0 mm). Localization of SLN: axillary (n = 161. 51 %), inguinal (n = 100. 31 %), cervical (n = 16. 5 %), submandibular (n = 9. 3 %), supraclavicular (n = 4. 1 %), more than one basin (n = 34. 9 %). In the group of melanomas <0.75 mm thick, no SLN metastases were found, among 0.75–1 mm melanomas, one positive lymph node with metastasis (SLN+) was found, in the largest group of melanomas of medium thickness (1–3.5 mm) — 25 (17 %). The largest percentage of metastases in SLN is determined in thick melanomas (>3.5 mm) — 17 (28 %), which is consistent with the data of foreign literature, while SLN is most often affected with a Breslow tumor thickness of more than 7 mm.In the group with negative sentinel lymph nodes (SLN–), the average tumor thickness according to Breslow was 2.6 ± 2.0 mm, in the SLN+ group — 4.0 ± 2.9 mm, the differences between the groups are statistically significant, which is confirmed by the result of one-way analysis of variance.The optimal threshold value of tumor thickness according to Breslow for the isolation of patients with a positive prognosis of metastasis in the SLN is 2.0 mm. It is characterized by the maximum levels of sensitivity (79 %) and specificity (59.1 %). An older age of patients (over 35 years old) is also associated with an increased incidence of metastases in the SLN, but this indicator is not statistically significant. Most often, SLN metastases were detected when the primary tumor was localized in the back (more often in men) and lower extremities (more often in women), while they are thicker (> 3.5 mm).Conclusion: 1. According to the ROC-analysis, the optimal threshold value of the tumor thickness according to Breslow for the isolation of patients with a positive prognosis of metastasis in the SLN is 2.0 mm. It is characterized by the maximum levels of sensitivity (79 %) and specificity (59.1 %). 2. Statistically significant prognostic factors of metastasis in SLN: localization of the primary tumor in the back (more often in men) and lower extremities (more often in women); Breslow thickness over 3.5 mm. 3. The absence of the influence of gender and age was noted, with a slight predominance of women in both groups.

Subungual Melanoma: A Single Institution Experience

Despite the changing paradigms of melanoma treatment in recent years, there remains a relative paucity of data regarding subungual melanoma in the literature. From 2002–2018, 25 patients with subungual melanoma were surgically treated at our facility. A retrospective chart review was conducted to collect relevant demographic, clinical, pathologic, and outcomes data. The median age at diagnosis was 69 years. Most patients (60%) were male, and the melanoma lesion was most often located on the foot (68%). Acral-lentiginous was the most common histologic subtype (59%), and the median Breslow thickness was 3.4 mm. Fifteen patients (63%) underwent a sentinel lymph node biopsy as part of their surgical resection, and four of these patients (27%) had metastatic disease in the lymph nodes. In total, 10 patients underwent lymph node dissection of the involved basin. The median follow up was 21 months in this patient population. Age, gender, tumor location, ulceration, and lesion histology were not significantly associated with recurrence free survival (RFS). Increasing Breslow thickness was found to be significantly associated with shorter RFS (HR: 1.07, CI: 1.03–1.55). In total, 13 patients developed a disease recurrence, and RFS rates were 66% at 1 year and 40% at 3 years. Additionally, 91 and 37% of patients were alive at one year and three years, respectively. Subungual melanomas are rare lesions that often have a more advanced stage at diagnosis, which contributes to the poor prognosis of these cutaneous malignancies.