The mitotic rate as a prognostic biomarker after preoperative radiotherapy for high-grade limb/trunk soft tissue sarcoma.

PURPOSE: Currently there is no generally accepted standardized approach for the pathological evaluation of soft tissue sarcoma (STS) histology appearance after preoperative radiotherapy (PORT). This study aimed to investigate the prognostic value of pathological appearance after PORT for patients with high-grade limb/trunk STS. METHODS: A cohort of 116 patients with high-grade STS of the limb/trunk treated with PORT followed by resection were evaluated. Patient characteristics, imaging tumor morphology (size, volume), and histopathology (mitotic and necrosis rate, viable cell, hyalinization/fibrosis cytopathic effect) were reviewed and reassessed. Disease free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and the hazard ratio was derived from Cox proportional hazard models. Two predictive nomograms were calculated based on significant predictors identified. RESULTS: The 5-year DFS and OS were 52.9% and 70.3%, respectively. Tumor size before (HR:1.07, 95%CI: 1.01-1.14) and after PORT (HR:1.08, 95%CI: 1.01-1.14), tumor volume (HR:1.06, 95%CI: 1.01-1.12), mitotic rate after PORT (HR: 1.06, 95%CI: 1.02-1.11), mitotic rate change after PORT (HR:1.04, 95%CI:1.00-1.09) were independent risk factors for DFS. Tumor size before (HR:1.08, 95%CI: 1.03-1.14) and after PORT (HR:1.09, 95%CI: 1.04-1.15), tumor volume (HR:1.05, 95%CI: 1.01-1.09), mitotic rate after PORT (HR: 1.09, 95%CI: 1.04-1.13), mitotic rate change after PORT (HR:1.05, 95%CI:1.01-1.09) were independent risk factors for OS. The C-index of pathologic predictive nomogram based on mitotic rate for DFS and OS were 0.67 and 0.73, respectively. The C-index of morphology-pathology predictive nomogram for OS was 0.79. CONCLUSION: Tumor size before and after PORT, tumor volume, mitotic rate after PORT, mitotic rate change after PORT were independent risk factors for DFS and OS in high-grade STS patients treated with PORT. The mitotic rate, independent of tumor morphology, showed its potential as a prognostic biomarker for pathologic evaluation in patients treated with PORT.

The Prognostic Value of Proliferative Activity in Cutaneous Melanoma: A Pilot Study Evaluating the Mitotic Rate and Ki67 Index to Predict Patient Outcomes.

Proliferative activity in cutaneous melanomas can be appreciated both histopathologically by counting mitotic figures and immunohistochemically through the Ki67 index, but the prognostic value of each method is still a matter of debate. In this context, we performed a retrospective study on 33 patients diagnosed with cutaneous melanomas between 2013 and 2018 in order to evaluate progression-free survival and overall survival. Multivariate Cox proportional hazards regression was performed by considering both clinical histopathological and immunohistochemical features. The mitotic rate was significantly independently associated with both outcomes, while the Ki67 index was not an independent prognostic factor. However, the Ki67 predictive accuracy could be improved by establishing both a cut-off value and a standardized protocol for evaluating its expression. Until these desiderata are met, the mitotic rate remains superior to the Ki67 index for predicting prognosis in cutaneous melanomas, as also has the advantage of being easily interpreted in a standard histopathological examination regardless of the pathologist's experience and with no further financial expenses. Importantly, this is one of very few articles that has shown perineural invasion to be an independent prognostic factor for both progression-free survival and overall survival in cutaneous melanomas. As a consequence, this parameter should become a mandatory feature in the histopathological evaluation of cutaneous melanomas as it can improve the identification of patients who are at high risk for disease progression.

Invasive Cutaneous Melanoma: Evaluating the Prognostic Significance of Some Parameters Associated with Lymph Node Metastases.

Background and Objectives: This study aimed to assess the clinical-pathological profile of patients with invasive cutaneous melanomas and to identify the parameters with a prognostic role in the lymph nodal spread of this malignant tumor. Materials and Methods: We performed a retrospective study on patients with invasive cutaneous melanomas who underwent surgery in the "Pius Brînzeu" County Clinical Emergency Hospital from Timișoara, Romania, and were evaluated for the status of loco-regional lymph nodes. We selected and analyzed some parameters searching for their relationship with lymph node metastases. Results: We identified 79 patients with invasive cutaneous melanomas (29 men and 50 women, mean age 59.36 years). A percentage of 58.3% of melanomas had Breslow tumor thickness >2 mm; 69.6% of melanomas showed a Clark level IV-V. Tumor ulceration was present in 59.5% of melanomas. A mitotic rate of ≥5 mitoses/mm2 was observed in 48.1% of melanomas. Tumor-infiltrating lymphocytes (TILs), non-brisk, were present in 59.5% of cases and 22.8% of patients had satellite/in-transit metastasis (SINTM). Tumor regression was identified in 44.3% of cases. Lymph nodes metastases were found in 43.1% of patients. Statistical analysis showed that lymph node metastases were more frequent in melanomas with Breslow thickness >2 mm (p = 0.0002), high Clark level (p = 0.0026), mitotic rate >5 mitoses/mm2 (p = 0.0044), ulceration (p = 0.0107), lymphovascular invasion (p = 0.0182), SINTM (p = 0.0302), and non-brisk TILs (p = 0.0302). Conclusions: The Breslow thickness >2 mm, high Clark level, high mitotic rate and ulceration are the most important prognostic factors for lymph nodal spread in cutaneous melanomas. However, some melanomas without these clinical-pathological features can have an unexpected, aggressive evolution, which entails the necessity of close and prolonged clinical follow-up of patients, including those with lesions considered without risk.

The Association between the Growth Pattern and Malignancy in the Formation of Ulceration in Gastric Gastrointestinal Stromal Tumor.

Objective In general, surface ulceration in gastric gastrointestinal stromal tumor (GIST) is considered a malignant feature; however, the mechanism underlying its formation has not been evaluated in detail. In this study, we analyzed the factors involved in ulceration using resected specimens of gastric GIST. Methods A total of 48 samples were retrospectively analyzed. We examined the association of surface ulceration of gastric GIST with the MIB-1 labeling index, mitotic number, tumor size, endoscopic ultrasound (EUS) findings and growth pattern on computed tomography (CT). Results The proportion of men was significantly higher in the ulceration group than in the non-ulceration group (p=0.04146), whereas age was not significantly different between the groups. Tumor was significantly larger in the ulceration group than in the non-ulceration group (p=0.0048). There was no correlation between tumor size and ulcer number. The MIB-1 index was not related to ulceration, nor were EUS findings. The number of mitotic cells tended to be higher in the ulceration group than in the non-ulceration group (p=0.05988). Intraluminal growth pattern was strongly associated with ulceration (p=0.00019). After a multivariate analysis, the growth pattern was the only factor associated with ulceration of gastric GIST. Conclusion Although formation of surface ulceration in gastric GIST was partially associated with the degree of malignancy, the growth pattern was the most important factor associated with ulceration in gastric GIST.

Regulation and functions of cell division in the intestinal tissue.

In multicellular organisms, epithelial cells are key elements of tissue organization. In developing epithelial tissues, cellular proliferation and differentiation are under the tight regulation of morphogenetic programs to ensure correct organ formation and functioning. In these processes, proliferation rates and division orientation regulate the speed, timing and direction of tissue expansion but also its proper patterning. Moreover, tissue homeostasis relies on spatio-temporal modulations of daughter cell behavior and arrangement. These aspects are particularly crucial in the intestine, which is one of the most proliferative tissues in adults, making it a very attractive adult organ system to study the role of cell division on epithelial morphogenesis and organ function. Although epithelial cell division has been the subject of intense research for many years in multiple models, it still remains in its infancy in the context of the intestinal tissue. In this review, we focus on the current knowledge on cell division and regulatory mechanisms at play in the intestinal epithelial tissue, as well as their importance in developmental biology and physiopathology.

Liver metastases 2 years after resection of a very-low-risk duodenal gastrointestinal stromal tumor: a case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors, but are the most common mesenchymal tumors of the gastrointestinal tract. The risk classification of GISTs is based on the tumor size, mitotic index, tumor site, and presence of tumor rupture. Recurrence in the very-low-risk group is extremely rare. We herein report a case of liver metastases 2 years after resection of a very-low-risk duodenal GIST. CASE PRESENTATION: A 57-year-old woman presented to the hospital for evaluation of melena. Esophagogastroduodenoscopy showed bleeding from the exposed blood vessels at the top of a submucosal tumor approximately 20 mm in size located in the second (descending) part of the duodenum, and the bleeding was controlled with electrocoagulation. A GIST was suspected, and the patient underwent wedge resection of the duodenum. The resected specimen contained a 16- × 12-mm (< 20-mm) white submucosal tumor composed of spindle cells with a mitotic count of 4 per 50 high-power fields, and a histologically negative margin was achieved. Immunochemical analysis revealed positive tumor staining for c-kit protein and alpha-smooth muscle actin and negative staining for CD34, desmin, and S-100 protein. Therefore, the tumor was diagnosed as a very-low-risk duodenal GIST based on the Fletcher classification and modified Fletcher classification (Joensuu classification). The postoperative course was uneventful, and the patient was discharged on postoperative day 11. At the follow-up visit 2 years postoperatively, contrast-enhanced computed tomography revealed liver tumors in S8 and S6 measuring 26 × 24 and 10 × 10 mm, respectively. Both lesions showed peripheral dominant hyperenhancement with hypoenhancement inside, indicating tissue degeneration within the tumors. These imaging findings closely resembled those of the duodenal GIST. Hence, the patient was diagnosed with liver metastases of GIST 2 years postoperatively. She was subsequently started on treatment with 400 mg of imatinib. At the time of this writing (2 months after diagnosis), the patient was clinically well and asymptomatic and was continuing imatinib therapy. CONCLUSIONS: Recurrence of very-low-risk GISTs is extremely rare. Even a small GIST with low mitotic activity can never be considered completely benign, and long-term follow-up is necessary.

Clinicopathologic features of scrotal leiomyosarcoma: single institutional experience of ten cases.

Scrotal leiomyosarcoma arises from the subcutaneous smooth muscle layer and is an exceptionally rare disease process, with only six patients in the largest reported case series. This rarity creates uncertainties regarding diagnosis, surgical management, and clinical outcomes. Our purpose was to retrospectively describe our institutional experience with scrotal leiomyosarcoma from 2010 to 2022. Slides were reviewed with case inclusion requiring both nuclear atypia and mitotic activity. Ten patients with scrotal leiomyosarcoma were identified. Clinical impression included scrotal cyst in nine cases. The median age at diagnosis was 52 years (range: 29-75 years). The mean tumor size was 1.6 cm (range: 0.4-3.7 cm). Margins were positive in three cases and close in one case, prompting four re-excisions. The mean mitotic rate was 2.3 per 10 high-power field (range: 1-11), with mean Ki67 of 4.6% (range: 1-15%). Nine of the tumors were grade 1, while 1 was grade 2. Four patients had disease-specific follow-up. The remaining six patients have not had disease-specific surveillance. None of the ten patients have shown evidence of recurrence (median follow-up: 75 months, range: 0-116 months). Our series demonstrates that scrotal leiomyosarcoma has a deceptive clinical presentation with a wide age range and small tumor size. With complete surgical resection, scrotal leiomyosarcoma has an excellent prognosis and rigorous follow-up or adjuvant treatment is not likely to be necessary. Cases with unusual clinical or pathologic findings, such as large tumor size or high mitotic rate, may merit more intensive disease-specific surveillance.

Diagnostic Benefit of the Detection of Mitotic Figures in Endometriotic Lesions.

Objectives Endometriosis is a chronic disease which is diagnosed by surgical intervention combined with a histological work-up. Current international and national recommendations do not require the histological determination of the proliferation rate. The diagnostic and clinical importance of the mitotic rate in endometriotic lesions still remains to be elucidated. Methods In this retrospective study, the mitotic rates and clinical data of 542 patients with histologically diagnosed endometriosis were analyzed. The mean patient age was 33.5 ± 8.0 (17 - 72) years, and the mean reproductive lifespan was 21.2 ± 7.8 (4 - 41) years. Patients were divided into two groups and patients' reproductive history and clinical endometriosis characteristics were compared between groups. The study group consisted of women with confirmed mitotic figures (n = 140, 25.83%) and the control group comprised women without proliferative activity according to their mitotic rates (n = 402, 74.27%). Results Women with endometriotic lesions and histologically confirmed mitotic figures were significantly more likely to have a higher endometriosis stage (p = 0.001), deep infiltrating endometriosis (p < 0.001), ovarian endometrioma (p = 0.012), and infertility (p = 0.049). A mitotic rate > 0 was seen significantly less often in cases with incidental findings of endometriosis (p = 0.031). The presence of symptoms and basic characteristics such as age, age at onset of menarche, reproductive lifespan and parity did not differ between the group with and the group without mitotic figures. Conclusion This study shows that a simple histological assessment of the mitotic rate offers additional diagnostic value for the detection of advanced stages of endometriosis. The possible role as a predictive marker for the recurrence of endometriosis or the development of endometriosis-associated cancer will require future study.

Predictive accuracy of elevated mitotic rate on lymph node positivity and recurrence in thin melanomas.

Background: Mitotic rate (MR) is considered an important prognostic factor for melanoma but is not currently used for staging because its nuanced effect is not yet well-delineated. We sought to determine if T category-specific MR is predictive of sentinel lymph node (SLN) positivity, recurrence, and melanoma-specific mortality (MSM). Methods: A retrospective review of patients with primary cutaneous melanoma from 1994 to 2020 at a single academic center was performed. Patient demographics and tumor characteristics were recorded. MR was considered elevated for each AJCC8-defined T category if it was ≥2 mitoses/mm2 for T1, ≥4 mitoses/mm2 for T2, ≥6 mitoses/mm2 for T3, or ≥7 mitoses/mm2 for T4. Statistical analysis was performed to assess the predictive accuracy of MR on selected outcomes while controlling for ulceration. Results: Data from 2,984 patients with complete records were analyzed. Along with Breslow thickness and ulceration, elevated MR was associated with higher risk of MSM (HR 1.816, P=0.0001). There was no difference among patients with ulcerated T1 or T2 tumors regardless of MR, but those with non-ulcerated T1 or T2 tumors and elevated MR were more likely to have positive SLNs (P<0.0001 and P=0.0043, respectively) and recurrence (P=0.0007 and P=0.0004, respectively) compared to counterparts with low MR. There were no notable differences for T3 or T4 tumors based on MR. Conclusions: Elevated MR is associated with SLN positivity and recurrence in thin melanomas, independent of ulceration. SLN biopsy should therefore be strongly considered for patients with non-ulcerated lesions <0.8 mm thick if the MR is ≥2 mitoses/mm2.

Radiopathologic predictors of recurrence in patients with a gross totally resected atypical meningioma.

BACKGROUND: Atypical meningiomas (AM) comprise a heterogeneous conglomeration of meningiomas with higher local recurrence rates than their benign counterparts. Although adjuvant therapy following subtotal resection is the standard, the use of adjuvant therapy following gross total resection (GTR) remains controversial. This study seeks to add to the literature by identifying radiopathologic predictors of recurrence in patients with a GTR AM and better identify those patients who may benefit from adjuvant therapy. METHODS: A total of 103 consecutive patients who received gross total resection for AM at our center between Apr 2010 and Apr 2019 were evaluated retrospectively. Recurrence was defined as new enhancing masses on MRI without requiring biopsy confirmation. Cumulative incidence plots were used to estimate survival, and the log-rank test was used to assess differences between groups. Cox proportional hazards models were used to evaluate the effect of radiopathologic variables on the hazard of recurrence. RESULTS: Of the 103 patients included in this study, 68 (66.0%) were female, and the mean age was 51.1 ± 11.4. The median overall survival for patients following surgery was 71 months while the median progression-free survival was 64 months. Recurrence occurred in 36 (35.0%) patients. Factors correlated with AM recurrence following GTR included peritumoral edema (p = 0.005), necrosis (p < 0.001), mitotic rate greater than 7/10 high-power field (HPF) (p < 0.001), and Ki67 > 15% (p < 0.001). However, following Cox proportional hazards regression analysis, only mitotic rate greater than 7/10HPF (p = 0.018) and Ki67 > 15% (p = 0.035) were significantly associated with AM recurrence. CONCLUSIONS: Our results showed high mitotic index (greater than 7/10 HPF) and Ki67 greater than 15% as independent predictors of recurrence in patients with a GTR AM. These findings could help stratify patients who may benefit from adjuvant therapy.Abbreviations: AM: Atypical meningiomas; GTR: gross total resection; HPF: high power field; STR: subtotal resection; RFS: recurrence-free survival.

Clinical and Histopathological Variables and Prognostic Factors of Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive tumor with a poor prognosis. The literature on prognosis from low-income or low-middle-income countries is limited and scarce. This study aimed to determine the clinical and histopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and the factors affecting ACC's prognosis. This was a retrospective study of patients that presented with ACC to the Shaukat Khanum Memorial Cancer & Research Center, Lahore, Pakistan, between January 2011 and May 2018. Information regarding demographics and clinical and histopathological variables were extracted and analyzed. Of the 25 subjects, 16 (64%) were female. The median age of the sample was 35 years (range; 21 - 72 years). Statistically significant associations were found between RFS and functional status of the tumor (p = 0.014), cortisol overproduction (p = 0.02), androgen excess (testosterone [p = 0.03] and dehydroepiandrosterone sulfate [DHEA SO4] [p = 0.004]), Ki-67 score (p = 0.03), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.01), and composite variable of disease (p = 0.004). The OS was found to have statistical associations with cortisol hypersecretion (p = 0.02), DHEA SO4 excess (p = 0.01), Modified Weis Score (p < 0.001), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.003), and composite variable of disease (p = 0.001). Linear regression (forward-type) analysis suggested that the functional status of the tumor and the disease recurrence index statistically predicted the variance in RFS and OS, respectively. Multiple clinical and histopathological variables appear to affect the prognosis of ACC. However, based on multivariable analysis, it appears that the functional status of the tumor and the composite variable of disease recurrence are predictors of RFS and OS, respectively.

Mitotic rate in node-positive stage III melanoma: it might be as important a prognostic factor as node number.

BACKGROUND: Stage III melanoma is a heterogenous disease, and the number of tumor-involved lymph nodes is the most significantly unfavorable prognostic indicator for relapse and outcome. The aim of this study is to investigate the possible effects of the various clinicopathological factors on the course of node-positive stage III disease. METHODS: A total of 389 node-positive stage III cutaneous melanomas were included in the study and analyzed retrospectively. All underwent pathological nodal staging by sentinel lymph node biopsy or elective lymph node dissection. RESULTS: The group was male-dominant (59%) and the median age was 50 years. The largest group of patients was N1 (n = 221, 56.8%) followed by N2 (n = 105, 27.0%) and N3 (n = 63, 16.2%). N1 melanomas were less frequently associated with relapses than melanomas with multiple lymph node metastases (P = 0.05). The 5-year relapse-free survival rate was 37.9%. The melanomas with multiple lymph nodes metastases (P = 0.01), higher mitotic rate (P = 0.005) and ulceration (P = 0.02) had worse RFS. In the multivariate analysis only the significances of the N2-N3 stage (P = 0.016) and higher mitosis (P = 0.012) persisted. The severe lymph node metastasis (N2-N3) was associated with a higher mortality rate in comparison with the single nodal involvement (P = 0.05). The 5-year overall survival rate was 52.1%. Presence of relapse (P = 0.0001), higher mitotic rate (P = 0.03) and N2-N3 stage (P = 0.04) were inversely correlated with the overall survival. When relapse was included in the multivariate analysis, it was the only significant prognostic factor on survival (P = 0.0001), whereas mitosis became the only significant factor on survival with the exclusion of relapse from the multivariate analysis (P = 0.031). CONCLUSION: In node-positive stage III melanoma, tumor mitotic rate might be just as significant a prognostic indicator as the metastatic lymph node number.

Reappraisal of the prognostic significance of mitotic rate supports its reincorporation into the melanoma staging system.

BACKGROUND: Mitotic rate is a strong, independent prognostic factor in patients with melanoma. However, incorporating it into the melanoma staging system has proved challenging. METHODS: The prognostic impact of mitotic rate was assessed in a melanoma cohort comprising 5050 patients from 2 geographically distinct populations. Computer-generated cut points for mitotic rate were constructed to determine its impact on melanoma-associated survival using Kaplan-Meier and multivariate regression analyses. The impact of mitotic rate also was assessed in randomly split training and validation sets. RESULTS: Mitotic rate had a nonlinear impact on survival, as evidenced by unequally spaced cut points. An index incorporating these cut points that was constructed from one population produced significantly more accurate predictions of survival in the other population than using the entire scale of mitotic rate. An index constructed from the combined cohort was found to be independently predictive of survival, with an impact comparable to that of ulceration. Optimal high-versus-low cut points for mitotic rate were generated separately for each T category (<2 mitoses/mm2 vs ≥2 mitoses/mm2 for T1 melanoma, <4 mitoses/mm2 vs ≥4 mitoses/mm2 for T2 melanoma, <6 mitoses/mm2 vs ≥6/mitoses/mm2 for T3 melanoma, and <7 mitoses/mm2 vs ≥7 mitoses/mm2 for T4 melanoma). Using Kaplan-Meier analysis, elevated mitotic rate was found to have an impact on survival comparable to that of ulceration within each T category. Application of the index for mitotic rate that was constructed from the training data set demonstrated an independent impact in the validation data set, with a significance similar to that of ulceration. CONCLUSIONS: The results of the current study demonstrated the comparable prognostic impact of mitotic rate and ulceration, providing support for its reincorporation into the T category.

High Mitotic Rate Predicts Sentinel Lymph Node Involvement in Thin Melanomas.

BACKGROUND: Indications for sentinel lymph node (SLN) biopsy in the population with thin melanoma have frequently changed over time. The objective of our study was to evaluate T1 melanoma pathologic features predictive of SLN positivity with a primary focus on identifying a specific mitotic value that is most predictive of lymph node disease. Further detailed predictive features would help physicians select patients with thin melanoma for SLN biopsy. METHODS: The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed with trunk or extremity cutaneous melanoma with ≤1 mm depth who underwent SLN biopsy between the years of 2010 and 2013. Patient demographics and tumor characteristics including depth, mitotic rate (MR), ulceration, and tumor location were evaluated. MR was dichotomized at multiple cut points to identify the ideal number of mitosis for MR as a predictor of SLN status. Multivariable logistic regression analyses were performed to identify the factors affecting nodal positivity and the impact of MR threshold. Kaplan-Meir curves were used for overall survival (OS) analysis. RESULTS: Factors significantly associated with SLN positivity in the entire cohort included MR (P < 0.001, OR 1.24, 95% CI 1.18-1.31), tumor location (P = 0.017, OR 1.48, 95% CI 1.07-2.05), and ulceration (P < 0.001, OR 2.01, 95% CI 1.39-2.93,). An MR ≥ 4 was significant for SLN positivity (P = 0.049, OR 1.08, 95% CI 1.01-1.38). Mean OS was 46.7 mo for MR < 4 compared with 43.2 mo for MR ≥ 4 (P < 0.001). CONCLUSIONS: MR ≥ 4 was significant and associated with SLN positivity in thin melanomas and asulceration. Thus, MR ≥ 4 should be considered as an indication for SLN biopsy in thin melanoma.

Cutaneous Head and Neck Melanoma: Changes in Clinical and Histologic Features From 1995 to 2015 in a Tertiary Hospital in Madrid, Spain. / Melanoma cutáneo de cabeza y cuello: evolución de las características clínico-patológicas en un hospital terciario de Madrid (1995-2015).

OBJECTIVES: Few epidemiological studies have analyzed cutaneous head and neck melanoma (CHNM) in the Spanish population. The aim of this study was to describe the clinical and histologic features of a representative sample of CHNM in Spain and to analyze changes observed over a period of 21 years. MATERIAL AND METHODS: Descriptive, retrospective, cross-sectional study of 280 patients diagnosed with CHNM at Hospital General Universitario Gregorio Marañón in Madrid, Spain, between January 1, 1995, and December 31, 2015. The main clinical and histologic features were analyzed and compared between 3 periods: 1995-2001, 2002-2008, and 2009-2015. RESULTS: Mean age at diagnosis was 71.3 years (median, 74 years; interquartile range [IQR], 65-81 years). The most common location was the face, followed by the scalp. The main histologic subtype was lentigo maligna (n=172, 64%). Mean tumor thickness was 1.6 mm (median, 0.4mm; IQR, 0-2.1mm). Median follow-up was 111 months; in this time 51 patients experienced CHNM recurrence (18.2%) and 29 died of the disease (10.4%). In the years analyzed, we observed a significant increase in the number and percentage of patients aged 75 years or older (P=.001) and in the percentage of melanomas in situ (P=.003). We also observed a significant decrease in mean tumor thickness (P=.018), the number of cases with 6 or more mitotic figures (P=.013), the percentage of patients with metastasis (P=.014), and melanoma-specific mortality (P=.005). CONCLUSIONS: CHNM affects elderly patients and is preferentially located on the face. The predominant subtype is lentigo maligna. Patients presented with thinner tumors over time and are now less likely to develop metastasis and to die of melanoma.

The prognostic value of tumor mitotic rate in children and adolescents with cutaneous melanoma: A retrospective cohort study.

BACKGROUND: Mitotic rate is a strong predictor of outcome in adult patients with primary cutaneous melanoma, but for children and adolescent patients this is unknown. OBJECTIVE: We sought to assess the prognostic value of primary tumor mitotic rate in children and adolescents with primary melanoma. METHODS: This was a cohort study of 156 patients who were <20 years of age and who had clinically localized cutaneous melanoma. Patients <12 years of age were classified as children and those 12 to 19 years of age as adolescents. Clinicopathologic and outcome data were collected. Recurrence-free and melanoma-specific survival were calculated. Univariable and multivariable analyses were performed using Cox proportional hazard models. RESULTS: Thirteen of 156 patients (8%) were children. The mitotic rate was ≥1/mm2 in 104 patients (67%) and correlated with increasing Breslow thickness. A positive sentinel node was found in 23 of 61 patients (38%) in whom a sentinel lymph node biopsy specimen was obtained. The median follow-up was 61 months. Five-year melanoma-specific and recurrence-free survival rates were 91% and 84%, respectively. Mitotic rate was a stronger predictor of outcome than tumor thickness and was the only factor independently associated with recurrence-free survival. LIMITATIONS: This research was conducted at a single institution and the sample size was small. CONCLUSION: Mitotic rate is an independent predictor of recurrence-free survival in children and adolescents with clinically localized melanoma.

Is it Necessary to Perform Sentinel Lymph Node Biopsy in Thin Melanoma? A Retrospective Single Center Analysis.

Sentinel lymph node biopsy (SLNB) is a standard procedure for regional lymph node staging and still has the most important prognostic value for the outcome of patients with thin melanoma. In addition to ulceration, SLNB had to be considered even for a single mitotic figure in thin (<1 mm) melanoma according to AJCC7th guideline, therefore, a retrospective review was conducted involving 403 pT1 melanoma patients. Among them, 152 patients suffered from pT1b ulcerated or mitotic rate ≥ 1/ mm2 melanomas according to the AJCC7th staging system. SLNB was performed in 78 cases, of which nine (11.5%) showed SLN positivity. From them, interestingly, we found a relatively high positive sentinel rate (6/78-8%) in the case of thin primary melanomas ˂0.8 mm. Moreover, the presence of regression increased the probability of sentinel positivity by 5.796 fold. After reassessing pT stage based on the new AJCC8th, 37 pT1b cases were reordered into pT1a category. There was no significant relation between other characteristics examined (age, gender, Breslow, Clark level, and mitosis index) and sentinel node positivity. Based on our data, we suggest that mitotic rate alone is not a sufficiently powerful predictor of SLN status in thin melanomas. If strict histopathological definition criteria are applied, regression might be an additional adverse feature that aids in identifying T1 patients most likely to be SLN-positive. After reassessing of pT1b cases according to AJCC8th regression proved to be independent prognostic factor on sentinel lymph node positivity. Our results propose that sentinel lymph node biopsy might also be considered at patients with regressive thin (˂0.8 mm) melanomas.