Epidemiological and histopathological profile of malignant melanoma in Malawi

The aim of this study was to assess the potential role of tumor diameter in explaining variations in tumoral invasion and in the initial prognosis for patients with malignant melanoma (MM). This was a multicenter, cross-sectional study that recruited between 2000 and 2009 patients with primary in-situ MM (Tis) and invasive cutaneous MM. Tis and MMs with a Breslow's thickness less than 1 mm (T1) were grouped (Tis-T1) and tumors with a Breslow's thickness 1 mm or more were also analyzed in combination (T2-T4). The tumor size was measured after routine formalin tissue fixation. Primary outcomes were the correlation between Breslow's thickness and tumor size, and the role of tumor size in explaining variations in Breslow's thickness, as assessed by the Pearson correlation test and logistic binary regression with calculation of the odds ratios. A total of 1610 MM patients were included and analyzed. The Pearson correlation between tumor size and Breslow's thickness was 0.42, with a determination coefficient of R2=0.18 (P>0.01). Correlations between tumor size and thickness were stronger in patients aged 30-60 years (r=0.42, R2=0.1764, P<0.001) and in tumors arising on the upper limbs (r=0.55, R2=0.3025). The odds ratio of identifying a T2-T4 stage MM in patients with tumors larger than 1 cm in size was 2.76 (95% confidence interval 2.25-3.39, P<0.001). Even though a direct, positive, and strong association between tumoral size and Breslow's thickness might be expected in melanoma cases, the strength of this association has been moderate. Tumor size explains a low burden of the variation observed in the Breslow's thickness.

BackgroundCutaneous cancer is the most common malignancy type, among which melanomas are considered the most aggressive and lethal. In Morocco, skin melanoma is the 25th most common cancer. To our knowledge, this is the first and largest Moroccan study specifically describing cutaneous melanoma. Materials and methodsWe obtained data for 100 patients diagnosed with cutaneous melanoma in the Department of Pathology of Hassan II University Hospital, Morocco. Clinical, histopathological, molecular, and follow-up data were recorded from pathology request forms and the patient’s medical records. ResultsThe mean age of our patients was 65 years old. Histologically, the most prevalent were the nodular (48%) and acro-lentiginous (38%) melanoma subtypes. A total of 66% of the patients had a Breslow thickness of >4 mm. The presence of ulceration was noted in 46% of cases. The average mitoses was 9/1 mm². A total of 44% of patients had metastatic melanoma at the time of diagnosis. The BRAF V600E mutation was found in six cases, and the C-KIT mutation in five cases. The five-year overall survival and metastasis-free survival were 85% and 15%, respectively. There was a significant correlation between Breslow thickness and Clark’s level (p<0.001), histologic subtype (p=0.012), and presence of metastasis (p=0.002). There was a significant difference between the head and neck melanomas and those of the feet, particularly in the histological subtype and the presence of ulceration. BRAF V600E mutation was found in six cases of metastatic melanomas of the head and neck, of which three cases were positive for this mutation, as compared with the 23 cases of acral melanomas, which tested negative for the same mutation. ConclusionThe results of our study showed that cutaneous melanomas were characterized by advanced age at diagnosis and late-stage diagnosis with a high Breslow index. The lower limbs were the most affected sites, especially in the plantar region. The acral lentiginous subtype was the most common. The presence of BRAF V600E mutation was associated with a better prognosis.

Pediatric melanoma: a single-institution experience of 150 patients

Classification and Staging of Melanoma in the Head and Neck.

A 52-year-old woman presented in 1999 with an atypical erythematous plaque on her left thigh containing a flesh-coloured nodule surrounded by four pink scaly papules. She had no significant past medical, drug or family history. Excision of the nodule revealed an amelanotic malignant melanoma (MM) of Breslow thickness (BT) 1 mm. Biopsies of the four surrounding lesions confirmed satellite MM in one, with no radiological evidence of metastases. She received adjuvant interferon therapy for 1 year. Repeat imaging was normal. Eighteen years later, she developed a new pigmented lesion on her left thigh confirmed as MM (0.9 mm BT), with three further erythematous plaques on the left thigh reported as (i) proximal left-thigh MM (1.08 mm BT), (ii) middle-left-thigh amelanotic MM (0.6 mm BT) and (iii) left-thigh MM (1.7 mm BT). Wide local excision (WLE) failed to obtain histological clearance of (i) and (iii), with mildly dysplastic naevus and melanoma in situ (MiS), respectively, at the peripheral margins. Reflective confocal microscopy (RCM) was used to guide further surgery, with continued incompletely excised MiS and field change at the margins. Eighteen months later she presented with another MiS and MM (0.5 mm BT) on the left thigh. Imiquimod 5% once daily for 8 weeks to the affected area was instigated to treat any residual in situ component. BRAF, CDKN2A, CDK4 and BAP1 showed no pathological variants, and xeroderma pigmentosum testing was negative. Six months later a further MM (1.2 mm BT) on the left thigh was treated with WLE and skin graft. Sentinel lymph node biopsy was deemed not possible due to previous multiple surgical excisions. Ultrasound groin scan and whole-body FDG-PET computed tomography showed no occult metastases. Several months later, another MM (0.5 mm BT) was excised at the edge of the graft site. Residual dysplastic lentiginous proliferation at the edge with no MM was reported on the 1-cm WLE. This represents a complex case with recurrent MM, often indistinguishable from primary MM histologically. Widespread dysplastic field change evidenced by involvement at the edges of the WLEs and the RCM images was also challenging. RCM can be a noninvasive adjunct in identification of superficial skin tumours. Adjuvant interferon therapy for high-risk MM has demonstrated an increase in disease-free survival (Petrella T, Verma S, Spithoff K et al. Adjuvant interferon therapy for patients at high risk for recurrent melanoma: an updated systemic review and practice guideline. Clin Oncol 2012; 24: 413–23). This may have contributed to the 18-year delay between her first and second melanomas, as well as her complex, recurrent presentations and ongoing local confinement of the MM to the left thigh with lack of disease progression.

Background: It is well known that there are site-specific differences in melanoma characteristics and prognosis. Scalp melanoma has been described to have a worse prognosis than melanoma elsewhere, though the reasons for this are poorly understood. Furthermore, the clinical and histological features of scalp melanoma are not well described. Objectives: This thesis aims to describe the features of scalp melanoma (including epidemiology, clinical presentation, histological characteristics and patient survival), to determine if there are any differences between these features and features of other head and neck melanoma, and to determine if scalp location is independently associated with survival in cutaneous head and neck melanoma. Methods: Firstly, a narrative review was conducted examining all existing literature on scalp melanoma. Secondly, a cross-sectional study was conducted of all cases of cutaneous head and neck melanoma seen at a multidisciplinary melanoma clinic in Melbourne, Australia over 20 years; clinical and histological features of all scalp melanoma cases were compared with other cutaneous head and neck melanoma cases. Finally, a retrospective cohort study was undertaken of all patients with invasive cutaneous head and neck melanoma seen at the same clinic over the same period, with follow-up mortality data obtained; survival of all scalp melanoma cases were compared to survival of other cutaneous head and neck melanoma cases, and multivariable survival analysis performed. Results: Invasive scalp melanoma was associated with male sex, increasing age, amelanosis, rapid growth rate, and being noticed by a person other than self, relative/spouse or doctor. Histologically, scalp melanoma had greater Breslow thickness than melanoma elsewhere in the head and neck, and was independently associated with satellite metastases, nodular and desmoplastic subtypes. Scalp melanoma had poorer overall and melanoma-specific survival compared to other cutaneous head and neck melanoma, but after taking into account patient age, sex and tumour histological features, scalp location was no longer associated with survival. Conclusions: Scalp melanoma appears to be clinically and histologically distinct from other head and neck melanoma. It occurs in predominantly in older men, is frequently non-pigmented, rapidly-growing, and is often overlooked by patients, their families and doctors. Not only should clinicians routinely examine the scalp for melanoma, they should also adjust their diagnostic criteria to accommodate this distinctive spectrum of clinical presentation. Due to the increased frequency of high risk histological features in scalp melanoma, careful histological assessment of scalp melanoma excision specimens is required.. Scalp melanoma patients had poorer survival than patients with other head and neck melanoma, which may be explained by tumour Breslow thickness and higher proportion of male patients.

This study investigates the mutational profile of the KIT gene in primary and metastatic melanomas, highlighting the significance of genetic heterogeneity. This research is a retrospective cohort that includes formalin-fixed and paraffin-embedded melanoma samples obtained from Hospital São Paulo, Brazil, between the years of 1996 and 2010. The research encompasses primary melanomas of the superficial spreading (SSM) and acral lentiginous (AL) subtypes and their metastases, using next-generation sequencing to explore genetic heterogeneity. Despite losing 57 samples due to quality issues, 27 samples from 20 patients were analyzed, revealing a nearly equal distribution between AL and SSM subtypes. Both histological subtypes revealed KIT gene variants, including previously undescribed variants and polymorphisms, emphasizing the role of such mutations in melanoma pathogenesis and the potential for targeted therapies. Tumor heterogeneity was also observed in both histological subtypes. The study underscores the complexity of melanoma, driven by diverse mutational landscapes within and across tumors and advocates for personalized treatment approaches based on detailed molecular profiling. Despite limitations like sample size, this research lays the groundwork for further investigation into melanoma's genetic intricacies and therapeutic vulnerabilities.

Cutaneous malignant melanoma in Eastern Taiwan: Clinicopathologic analysis of 56 cases

There is a world-wide increase in the incidence of cutaneous malignant melanoma among white people. Absence of accurate population-based data on the incidence of melanoma in South Africa prompted a study to determine the incidence, anatomical sites and pathological details of melanoma in Cape Town. In a prospective study from 1 January 1990 to 31 December 1995, all the histopathology reports of melanoma presenting in a geographically defined area of Cape Town, were actively retrieved from every pathologist practising in this area. The data evaluated included information on age, sex, ethnic group and location of residence. Details of melanoma comprised body site, Clark level of invasion, Breslow thickness in millimetres and histogenetic type. The histology slides were reviewed by a panel in those cases where the recorded information was ambiguous or incomplete. A final number of 595 reports of primary invasive cutaneous melanomas in white people was analysed. Of these 50.3% were men and 49.7% women. The overall age-standardized incidence rate was 24.4 per 100,000 per annum (27.5 for men and 22.2 for women). There was no change in the incidence rate over the study period. Most melanomas in both sexes (74% of women and 71% of men) were < 1.5 mm Breslow thickness. Results of this study indicate a high incidence rate of melanoma in white South Africans, comparable with that in Australia, which demands urgent preventive health measures.

Revised UK guidelines for the management of cutaneous melanoma 2010

Resection and adjuvant immunotherapy for melanoma metastatic to the lung and thorax

Malignant melanoma is a common skin cancer among Asians. However, some features, such as tumor type and initial stages, are not comparable with those found in Western countries. We audited a large cohort of patients at a single tertiary referral hospital in Thailand to identify factors affecting the prognosis. A retrospective study was conducted of patients diagnosed with cutaneous malignant melanoma between 2005 and 2019. Details of demographic data, clinical characteristics, pathological reports, treatments, and outcomes were collected. Statistical analyses of overall survival and factors affecting survival were investigated. The study enrolled 174 patients (79 men and 95 women) with pathologically confirmed cutaneous malignant melanoma. Their mean age was 63 years. The most common clinical presentation was a pigmented lesion (40.8%), with the plantar area being the most common site (25.9%). The mean duration of onset and hospitalization was 17.5 months. The 3 most common types of melanoma were acral lentiginous (50.7%), nodular (28.9%), and superficial spreading (9.9%). Eighty-eight cases (50.6%) had concomitant ulceration. Pathological stage III was the most common (42.1%). The 5-year overall survival was 43%, and the median survival time was 3.91 years. Multivariate analysis showed that clinically palpable lymph nodes, distant metastasis, a Breslow thickness ≥ 2 mm, and evidence of lymphovascular invasion were poor prognostic factors for overall survival. In our study, most patients with cutaneous melanoma presented with a higher pathological stage. Independent factors affecting survival are palpable lymph nodes, distant metastases, Breslow thickness, and the presence of lymphovascular invasion. The overall 5-year survival rate was 43%.

Objective: To determine malignant melanoma cause-specific and overall survival among patients with melanoma diagnosed after organ transplantation compared with a national sample with malignant melanoma. Design: Retrospective review. Setting: Mayo Clinic sites. Patients: Immunosuppressed organ transplant recipients with malignant melanoma identified from surgical and medical databases at Mayo Clinic (1978-2007), the Organ Procurement and Transplantation Network/United Network for Organ Sharing database (1999-2006), and the Israel Penn International Transplant Tumor Registry (1967-2007). Main Outcome Measures: Prognostic analyses by Breslow thickness and Clark level of overall and melanoma cause-specific survival. Expected survival rates were estimated by applying the age-, sex-, and calendar year–specific survival rates of patients with malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program to the study cohort. Results: Malignant melanoma was diagnosed in 638 patients (724 cases) after transplantation. Breslow thickness was available for 123 patients; Clark level, for 175. Three-year overall survival rates for patients stratified by Breslow thickness (≤0.75, 0.76-1.50, 1.51-3.00, and >3.00 mm) were 88.2%, 80.8%, 51.2%, and 55.3%, respectively, and 3-year cause-specific survival rates (95% confidence intervals) were 97.8% (93.7%-100%), 89.4% (76.5%-100%), 73.2% (53.2%-100%), and 73.9% (56.4%-96.6%), respectively. Three-year cause-specific survival rates (95% confidence intervals) for patients stratified by Clark level (I-IV) were 100%, 97.4% (92.4%-100%), 82.8% (65.3%-100%), and 65.8% (51.8%-83.7%), respectively. For patients with Breslow thickness of 1.51 to 3.00 mm and Clark level III or IV, the cause-specific survival rate in the study sample was significantly different from the expected estimates for patients with the same Breslow thickness or Clark level. Conclusions: Compared with the expected survival rates derived from malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program, immunosuppressed organ transplant recipients with thicker melanomas (ie, with a Clark level of III or IV or a Breslow thickness of 1.51 to 3.00 mm) had a significantly poorer malignant melanoma cause-specific survival rate. The overall survival rate was worse among patients with a prior history of transplantation, regardless of Breslow thickness or Clark level.

The aim of the study was to investigate the importance of consumption of the epidermis as an additional diagnostic criteria for malignant melanoma and to evaluate its relationship to clinicopathological findings. The age, gender, localization of the lesion and the histopathological parameters such as tumor type, Breslow thickness, ulceration, Clark's level, mitosis/mm2, lymphocytic infiltration were noted in 40 malignant melanoma cases. Consumption of the epidermis was evaluated in tumor sections. Consumption of the epidermis (COE) due to thinning of the epidermis and loss of rete ridges was noted as (+) or (-). Furthermore, COE was compared with clinical and histopathological parameters. The Shapiro Wilk and Logistic Regression tests were used for statistical analysis. The results were accepted as significant if the p value was < 0.05. COE was detected in 60% (24/40) of malignant melanoma cases. A positive correlation was present between COE and head and neck localization (p = 0,698), superficial spreading melanoma (p = 0,341), ulceration (p = 0,097) and brisk lymphocytic infiltration (p = 0,200) but the results were not statistically significant. COE was frequently detected in males but the difference was not statistically significant (p = 0.796). There was no correlation or significant statistical association between COE and age, Breslow thickness, Clark's level or the mitotic index. The detection of COE in most of the patients suggests that COE could be a histopathological criterion in the diagnosis of malignant melanoma. The frequent association between COE and the presence of ulceration could also direct attention to COE as regards prognostic importance.

The purpose of the study was to determine the frequency of expression p53 and p16INK4a proteins and bcl-2 oncoprotein in malignant skin melanoma and to determine their correlation with the proliferative index and tumor thickness. The study involved 53 patients: 27 (51%) male and 26 (49%) female. Mitotic index showed a correlation with p53 protein expression, a negative correlation with p16INK4a protein expression. Statistically significant correlations were determined between the Breslow tumor thickness, Clark invasion level and p53 protein expression, as well as Breslow tumor thickness and bcl-2 oncoprotein expression (p<0.05), whereas there was no correlation between the p16INK4a protein expression and melanoma thicknes and Clark invasion level. Overexpression p53 protein and bcl-2 oncoprotein, with the loss p16INK4a protein of expression in the nodular melanoma, confirms a frequent loss of function of these tumor suppressor gene and oncogene, and indicates a vertical tumor growth phase. The loss of tumor suppression function the p53 protein and bcl-2 oncoprotein overexpression in cutaneous melanoma correlates with larger tumor thickness, whereas the overexpression of mutated p53 protein and loss p16INK4a protein of expression indicate a higher proliferative tumour potential. Therefore, these evaluated proteins may be the aggressive biological tumour activity markers.