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.

Laterality and site-specific distribution patterns of Lentigo Maligna and Lentigo Maligna Melanoma

Background: Melanoma has been described to have preferential left-sided laterality on the human body. The distribution and invasion patterns of lentigo maligna (LM) and lentigo maligna melanoma (LMM) have not been well described. Methods: This was a cross-sectional, retrospective study at a single, academic center. LM and LMM cases from 2008-2018 in the dermatopathology registry were analyzed. Results: A total of 392 cases were included (241 LM and 151 LMM). There was no laterality preference overall. The only exception were neoplasms located on the head/neck, which showed a left-sided laterality. LM and LMM had the highest incidence on the head/neck, followed by upper extremities, trunk, then lower extremities. Men had a higher incidence on the head/neck and trunk, while women had a higher incidence on the extremities. Interestingly, the upper extremities and the right side of the female body had a higher propensity for invasive lesions. Conclusion: While melanomas demonstrate preferential left-sided laterality, LM and LMM only share this pattern in respect to the head/neck region. Our results complement previous study findings which characterize LM and LMM as a head/neck and upper extremity pathology. Finally, our study suggests that certain body sites and laterality have an increased propensity for invasion.

Diagnosis and Management of Lentigo Maligna: Clinical Presentation and Comprehensive Review

Lentigo maligna (LM), also known as Hutchinson’s melanotic freckle, is a form of in situ melanoma characterized by the proliferation of atypical melanocytes along the basal epidermis in sun-damaged skin. If left untreated, LM will progress to lentigo maligna melanoma (LMM), a form of invasive melanoma with the same prognosis as other forms of invasive melanoma. LM is more common in the elderly, with a peak occurrence between the ages of 65 and 80 years. LM, however, is rarely present on the trunk and extremities. The diagnosis of LM, confirmed by histopathological and biopsy examination, is based on clinical and dermoscopic features. It typically begins as a tan-brown macule or patch, but it can progress to a variegated pigmentation with dark black color or even amelanotic characteristics. The risk factors involved in the LM development include a history of sunburns, lighter skin types, advanced age, history of nonmelanoma skin cancers, and tendency to form solar lentigines. This article explains the clinical presentation of LM, also reviews the available information on the diagnosis and management of LM, and discusses the potential of such information in facilitating the future prospective.

Collision Cutaneous Neoplasms Consisting of Melanoma and Basal Cell Carcinoma

Collision tumors are defined as two histologically different tumor types that arise at the same anatomical location. According to the literature review performed, there are reports of 27 cases of collision tumors involving lentigo maligna melanoma (LMM) in-situ and basal cell carcinoma (BCC). In the absence of melanocytic extension beyond the lamina propria of the BCC compartment, mixed tumors are considered as melanoma in-situ colonizing the BCC, rather than invasive melanomas. We report an uncommon case of collision of BCC with LMM, two primary skin tumors that are seen in patients with significant sunlight exposure. In our case, the patient is a 91-year-old male presented with a translucent plaque with areas of brown pigmentation on his left lateral canthus. He had a history of multiple BCCs, squamous cell carcinomas and an invasive melanoma of right cheek. Given the clinical impression of BCC, the lesion was curetted. Histological examination demonstrated melanoma in-situ heavily infiltrating the dermal nodules of BCC. Deposits of melanin pigment were scattered throughout the tumor. The BCC contained about 50% atypical melanocytes. Further immunohistochemical evaluation with melanocytic and epithelial markers (melanin A, SOX-10, pan-cytokeratin and p63) confirmed the diagnosis. An unequivocal independent invasive melanoma component was not identified in this material. The collision of BCC and LMM is very rare. However, given the sun-damaged changes promote both tumors, their development at the same site, although unexpected, can be explained. Since the prognosis of the two entities is independent, wider excision to exclude invasive malignant melanoma is indicated.

Langerhans Cells as Morphologic Mimickers of Atypical Melanocytes on Reflectance Confocal Microscopy: A Case Report and Review of the Literature

Pagetoid spread of melanocytes in the epidermis is a common indicator of melanocytic atypia, both histopathologically and with reflectance confocal microscopy (RCM). Specifically on RCM, large, bright, atypical dendritic and/or roundish cells are characteristic of melanoma. However, intraepidermal Langerhans cells (ILC) create the potential for diagnostic ambiguity on RCM. We describe one case of a pigmented facial lesion that was initially diagnosed as lentigo maligna (LM) due to numerous atypical perifollicular dendritic cells on RCM. Additionally, we present the findings of a literature review for similar reported cases conducted by searching the following terms on PubMed: reflectance confocal microscopy, RCM, lentigo maligna, melanoma, Langerhans cells, dendritic cells, and atypical cells. In our case, the lesion was determined to be a solar lentigo on histopathology. Immunohistochemistry (IHC) with CD1a identified the atypical-appearing cells as ILC, as it did in 54 reported cases of benign lesions (benign melanocytic nevus, Sutton/halo nevus, labial melanotic macule, and solar lentigo) misdiagnosed as malignant on RCM (melanoma, lip melanoma, lentigo maligna, and LM melanoma). According to our case and the literature, both ILC and atypical melanocytes can present with atypical-appearing dendritic and/or roundish cells under RCM. Currently, there is no method to distinguish the two without IHC. Therefore, the presence of pagetoid cells should continue to alert the confocalist of a potential neoplastic process, prompting biopsy, histopathologic diagnosis, and IHC differentiation.

Comparing the characteristics and predicting the survival of patients with head and neck melanoma versus body melanoma: a population-based study

Background Previous studies reported cutaneous melanoma in head and neck (HNM) differed from those in other regions (body melanoma, BM). Individualized tools to predict the survival of patients with HNM or BM remain insufficient. We aimed at comparing the characteristics of HNM and BM, developing and validating nomograms for predicting the survival of patients with HNM or BM. Methods The information of patients with HNM or BM from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The HNM group and BM group were randomly divided into training and validation cohorts. We used the Kaplan-Meier method and multivariate Cox models to identify independent prognostic factors. Nomograms were developed via the rms and dynnom packages, and were measured by the concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and calibration plots. Results Of 70,605 patients acquired, 21% had HNM and 79% had BM. The HNM group contained more older patients, male sex and lentigo maligna melanoma, and more frequently had thicker tumors and metastases than the BM group. The 5-year cancer-specific survival (CSS) and overall survival (OS) rates were 88.1 ± 0.3% and 74.4 ± 0.4% in the HNM group and 92.5 ± 0.1% and 85.8 ± 0.2% in the BM group, respectively. Eight variables (age, sex, histology, thickness, ulceration, stage, metastases, and surgery) were identified to construct nomograms of CSS and OS for patients with HNM or BM. Additionally, four dynamic nomograms were available on web. The internal and external validation of each nomogram showed high C-index values (0.785–0.896) and AUC values (0.81–0.925), and the calibration plots showed great consistency. Conclusions The characteristics of HNM and BM are heterogeneous. We constructed and validated four nomograms for predicting the 3-, 5- and 10-year CSS and OS probabilities of patients with HNM or BM. These nomograms can serve as practical clinical tools for survival prediction and individual health management.

Comparing the Characteristics and Predicting the Survival of Head and Neck Melanoma versus Body Melanoma: A Population-based Study

Background: Previous studies have reported poorer survival in head and neck melanoma (HNM) than in body melanoma (BM). Individualized tools to predict the prognosis for patients with HNM or BM remain insufficient. We aim to compare the characteristics of HNM and BM, and establish and validate the nomograms for predicting the 3-, 5- and 10-year survival of patients with HNM or BM.Methods: We studied patients with HNM or BM from 2004 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. The HNM group and BM group were randomly divided into training and validation cohorts. We performed the Kaplan-Meier method for survival analysis, and used multivariate Cox proportional hazards models to identify independent prognostic factors. Nomograms for HNM patients or BM patients were developed via the rms package, and were measured by the concordance index (C-index), the area under the receiver operator characteristic (ROC) curve (AUC) and calibration plots.Results: Of 70605 patients acquired, 21% (n=15071) had HNM and 79% (n=55534) had BM. The HNM group contained more older patients, male patients, and lentigo maligna melanoma, and more frequently had thicker tumors and metastases than the BM group. The 5-year CSS and OS rates were 88.1±0.3% and 74.4±0.4% in the HNM group and 92.5±0.1% and 85.8±0.2% in the BM group, respectively. Eight independent prognostic factors (age, sex, histology, thickness, ulceration, stage, metastases, and surgery) were identified to construct nomograms for HNM patients or BM patients. The performance of the nomograms were excellent: the C-index of the CSS prediction for HNM patients and BM patients in the training cohort were 0.839 and 0.895, respectively; in the validation cohort, they were 0.848 and 0.888, respectively; the AUCs for the 3-, 5- and 10-year CSS rates of HNM were 0.871, 0.865 and 0.854 (training), and 0.881, 0.879 and 0.861 (validation), respectively; of BM, the AUCs were 0.924, 0.918 and 0.901 (training) and 0.916, 0.908 and 0.893 (validation), respectively; and the calibration plots showed great consistency.Conclusions: The characteristics of HNM and BM are heterogeneous, and we constructed and validated specific nomograms as practical prognostic tools for patients with HNM or BM.