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Objective:To analyze clinical manifestations, pathological features and prognosis of patients with stage Ⅰ cutaneous melanoma.Methods:Clinical data were collected from 163 patients with stage Ⅰ cutaneous melanoma in Department of Dermatology, Xijing Hospital from January 2010 to January 2020, and clinical manifestations, pathological features, treatment methods and prognosis were retrospectively analyzed.Results:Among the 163 patients with stage Ⅰ cutaneous melanoma, 56 (34.36%) were males, and 107 (65.64%) were females, with a median age of 53 years at the clinic visit. Primary skin lesions were most frequently located on the extremities in 104 cases (63.80%) , of which 39 presented with lesions on the finger or toe nails and 65 with lesions on the other parts of the extremities; skin lesions were located at sun-exposed sites such as the head and face in 29 (17.79%) cases, and at non-sun-exposed sites such as the trunk and extremities except the hands and feet in 30 (18.40%) . Of the 163 patients, 56 (34.36%) were pathologically diagnosed with stage ⅠA cutaneous melanoma, and 107 (65.64%) with stage ⅠB cutaneous melanoma. According to a pathological staging system, 104 (63.80%) patients suffered from acral lentiginous melanoma, 23 (14.11%) superficial spreading melanoma, 15 (9.20%) nodular melanoma, 14 (8.59%) malignant lentigo-maligna melanoma, and 7 (4.29%) other rare or difficult-to-determine types. All the 163 patients received surgical treatment at least once, of whom 15 underwent finger or toe amputation, 94 extended resections, and 54 unextended resections; 35 received secondary surgeries, of whom 33 underwent extended resections and 2 finger amputation. Seven patients developed postoperative lymph node and/or distant organ metastases, 2 of whom died after distant organ metastases. The 5-year survival rate of the 163 patients was 98.00%.Conclusion:Stage Ⅰ cutaneous melanoma commonly has favorable prognosis, and 7 patients developed postoperative lymph node and/or distant organ metastases in this study, suggesting that long-term follow-up of patients with acral melanoma and early intervention of those with metastatic melanoma should be strengthened.
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Objective:To establish a melanoma cell line derived from a Chinese female patient of Han nationality with metastatic melanoma, and to study its basic biological characteristics.Methods:Metastatic melanoma cells were isolated from axillary lymph nodes of a 17-year-old female patient with malignant melanoma, and subjected to culture in vitro to establish a cell line. Short tandem repeat (STR) genotyping was performed to compare the information about the cell line and its derived tissue, and to detect gene mutations; cell counting kit-8 (CCK8) assay was conducted to assess the cellular proliferative activity, and soft agar cloning assay to assess the anchorage-independent proliferation; karyotype analysis was performed to determine the number and structure of chromosomes; with the highly aggressive melanoma cell line A2058 and keratinocyte line HaCaT serving as controls, Transwell assay was conducted to detect differences in cell migratory and invasive abilities, cell immunofluorescence assay and Western blot analysis were performed to determine the protein expression of melanoma-specific markers HMB45, S100 and Melan-A; the tumorigenicity was evaluated in vivo in a tumor-bearing mouse model. Results:A melanoma cell line was successfully established and named ZJMM-45, which was cultured for more than 70 passages over a 1-year period, and showed a stable shape and proliferative activity. The cells were spindle-shaped or polygonal, and could produce melanin. STR matching analysis showed that the ZJMM-45 sample was 96% matched with the cryopreserved lymph node tissue of the patient, suggesting that they were from the same source. A tumor-related gene BRAF V600E mutation (c.1799T>A) was identified in the ZJMM-45 cell line; karyotype analysis revealed that ZJMM-45 cells had triploid chromosomes and abnormal structures. ZJMM-45 cells grew exponentially in vitro and reached a plateau-phase in growth on day 5; the cells grew clonally and formed colonies in agar, showing anchorage-independent and malignant proliferative activity. Cell immunofluorescence assay and Western blot analysis showed that both ZJMM-45 and A2058 cells expressed HMB45, S100 and Melan-A; Transwell assay revealed that the numbers of invasive and migratory ZJMM-45 cells (300 ± 14, 260 ± 14, respectively) were significantly higher than those of invasive and migratory A2058 cells (150 ± 6, 160 ± 19, t = 13.25, 11.76, respectively, both P < 0.001) . The tumor-bearing mouse experiment showed that all 5 nude mice developed tumors with an inner diameter of 1.0 cm after 4 weeks, and the tumors were histopathologically characterized by proliferating hyperchromatic melanoma cell nuclei and formation of small nests, which were similar to primary solid tumors. Conclusion:The metastatic melanoma cell line ZJMM-45 derived from a Chinese patient with melanoma was successfully constructed, which carried the BRAF V600E mutation and expressed melanoma-specific markers, and was characterized by rapid proliferation, invasion and metastasis in both in vivo and in vitro culture, as well as obvious tumorigenicity in the in vivo experiment.
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Objective:To analysis clinical and histopathological features of solitary dermal melanoma (SDM) .Methods:Clinical and histopathological data were collected from 5 patients with SDM, and analyzed retrospectively.Results:The 5 patients with SDM presented with black, skin-colored or red papules or nodules without any specific anatomic predilection. These lesions pathologically manifested as localized dermal/subcutaneous solitary nodules with characteristics of malignancy but no obvious capsules, and the epidermis was not involved.Conclusion:Detailed clinical data and skin histopathological examination are the key to accurate diagnosis of SDM.
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From 1960 to 1990, some Chinese dermatologists noticed that a small number of patients presenting with granulomatous inflammation on the face eventually died of encephalitis. In 2001, Dr. Tianwen Gao summarized clinical and pathological characteristics of these patients and proposed the disease name "fatal bacterial granuloma after trauma", and Propionibacterium acnes was assumed to be the most probable pathogen at that time. In 2018, the disease was confirmed to be Balamuthia mandrillaris infection involving the skin and brain tissues. This review summarized the history of research on Balamuthia mandrillaris infection in China, as well as its clinical, pathological characteristics and treatment methods.
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Objective:To investigate clinical and histopathological features of Meyerson nevus.Methods:Clinical and histopathological data were collected from 6 patients with confirmed Meyerson nevi in Department of Dermatology, the Fourth Military Medical University from January 2015 to January 2019, and retrospectively analyzed.Results:Among the 6 patients, 3 were males and 3 were females, with a median age of 10.5 years (range, 7 months to 28 years). Skin lesions were located on the extremities of 3 cases, as well as on the trunk of 3 cases. Meyerson nevi arose from congenital pigmented nevi in 4 cases, as well as from acquired pigmented nevi in 2 cases. The duration of pigmented nevi varied from 7 months to 18 years. Four patients felt itching in the past 2 months, and 2 had no concomitant symptoms such as itching. Central pigmented nevi manifested as papules in 5 cases and a plaque in 1 case, which were brown or black in color, with regular shapes, uniform pigmentation and clear borders. Pigmented nevi were surrounded by a halo of erythema in 6 cases, and skin lesions were covered with scales or crusts in 4 cases. Histopathological examination of Meyerson nevi revealed characteristics of both pigmented nevus and eczema. Histopathologically, pigmented nevi manifested as junctional nevi or compound nevi, and eczema manifested as serous exudation, irregular epidermal hyperplasia, spongiosis and perivascular infiltration of lymphocytes in the superficial dermis.Conclusions:Meyerson nevus is rare, and mostly occurs on the trunk and extremities. When itching occurs or erythema appears around the pigmented nevus, the diagnosis of Meyerson nevus should be considered.
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Objective:To investigate dermoscopic manifestations and features of melanonychia.Methods:A retrospective analysis was carried out on dermoscopic images of 4 common types of melanonychia collected in Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from January 2016 to July 2020.Results:A total of 266 cases of melanonychia were collected, including 64 (24.1%) of subungual melanoma, 52 (19.5%) of nail matrix nevi, 89 (33.5%) of subungual hemorrhage, and 61 (22.9%) of onychomycosis. Subungual melanoma and nail matrix nevi mostly occurred in the fingernails. To be specific, subungual melanoma most frequently occurred in the thumbnails (62.8%) , while nail matrix nevi mostly involved the 2 nd - 5 th fingernails (73.9%) . Subungual hemorrhage and onychomycosis mostly occurred in the toenails, and there were 51 (57.3%) cases of subungual hemorrhage of the toenails and 46 (75.4%) cases of onychomycosis of the toenails. Subungual melanoma mostly occurred in patients aged over 40 years (49 cases, 76.8%) , while the other 3 types of melanonychia mostly affected patients aged under 40 years. Dermoscopic manifestations of subungual melanoma mainly included regular longitudinal bands (35 cases, 54.7%) or irregular bands (25 cases, 39.0%) whose width was greater than 3 mm in 87.5% cases, Hutchinson sign (36 cases, 56.3%) , and ruptures (15 cases, 23.4%) which mainly were black-brown in color; dermoscopic manifestations of nail matrix nevi mainly were a single regular pigmented band (52 cases, 100%) whose width was less than 3 mm in 36 (69.2%) cases, and Hutchinson sign (26 cases, 50%) , while no ruptures were observed in nail matrix nevus lesions; subungual hemorrhage dermoscopically manifested as diffuse macules (74 cases, 83.1%) , and globular dark red or black hemorrhagic structures were observed in 85 (95.5%) cases; fungal melanonychia was dermoscopically characterized by irregular dark brown longitudinal bands (54 cases, 88.5%) . Conclusions:Subungual melanoma was dermoscopically characterized by regular longitudinal bands with a width of greater than 3 mm, nail matrix nevi by regular longitudinal bands, subungual hemorrhage by diffuse macules, and onychomycosis by irregular longitudinal bands. Dermatoscopy can be used to identify melanonychia lesions and provide a basis for auxiliary diagnosis of subungual melanoma.
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Objective:To investigate clinical and histopathological characteristics of nevoid melanoma.Methods:A retrospective analysis was carried out on clinical and histopathological data collected from 3 patients with nevoid melanoma diagnosed in Department of Dermatology, Xijing Hospital from 2000 to 2020.Results:Among the 3 patients with nevoid melanoma, 2 were females and 1 was male. Skin lesions initially manifested as black macules and papules. After surgical resection, 2 patients developed new nodular lesions or recurrent skin lesions which enlarged into plaques. Histopathological examination showed proliferation of epithelioid melanocytes in the epidermis and dermis, with cytological atypia and some deeply stained nuclei. Immunohistochemical study revealed positive staining for Melan-A and S100 in tumor cells in the skin lesions, diffusely positive staining for HMB45 in dermal tumor cells, locally negative staining for HMB45 in the deep dermis, increased Ki67 proliferation index, and active expression of cyclin D1.Conclusion:Nevoid melanoma is easy to be misdiagnosed as pigmented nevi or seborrheic keratosis; when recurrence or metastasis occurs in patients with histologically diagnosed pigmented nevi, attention should be paid to the possibility of nevoid melanoma.
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Objective:To investigate clinical and histopathological features of congenital melanocytic nevi (CMN) complicated by proliferative nodules (PN) .Methods:Ten patients with clinically and pathologically confirmed CMN complicated by PN were collected from Department of Dermatology, the Fourth Military Medical University from 2015 to 2019, and their clinical and pathological data were analyzed retrospectively.Results:The 10 patients were aged from 2 to 45 years, with an average age of 15 years. Nine patients developed PN in infancy, and 1 in adulthood. The skin lesions were located on the extremities in 4 cases, on the head and face in 3 cases, and on the trunk in 2 cases, and the trunk and extremities were both involved in 1 case. Skin lesions clinically manifested as 1 or more nodules arising in black patches or plaques. Six patients presented with multiple PN, 4 with solitary PN, with the diameter of a single nodule being 0.2-1.5 cm, and only 1 case presented with ulcers. Histopathological examination showed mature melanocytes in the PN, with few mitotic figures, no obvious cytological atypia, and no necrosis. Immunohistochemical study showed that nevus cells diffusely expressed Melan-A, but did not express or partially expressed HMB45, and the Ki67 proliferation index was below 5%.Conclusion:CMN complicated by PN can occur on the extremities, head, face, and trunk, clinically manifesting as solitary or multiple nodules on pre-existing CMN; histopathologically, mature melanocytes can be observed in PN, immunohistochemical staining for HMB45 and Ki67 can facilitate the diagnosis, and its prognosis needs long-term follow-up.
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Objective:To explore surgical treatment strategies and prognosis of early-stage nail apparatus melanoma.Methods:A total of 115 patients with early-stage nail apparatus melanoma receiving surgical treatment were collected from Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from July 2011 to December 2019, and surgical treatment strategies and outcomes were analyzed retrospectively.Results:According to the modified ABCDEF criteria and clinical manifestations (such as deformation of the nail plate, ulcers, nodules) , 73 patients with early-stage nail apparatus melanoma received extended surgical resection based on the resection principles of melanoma in situ, 22 based on the resection principles of stage I and II melanoma, 20 based on the resection principles of stage I and II melanoma with invasion risks. During the follow-up period of 6 months to 9 years, there was no recurrence of the primary tumors in any patients; no abnormalities were observed by the ultrasound examination of lymph nodes in 101 patients; metastases occurred in 2 patients receiving finger amputation, 1 of whom died; 12 patients were lost to follow-up. Conclusion:To select extended surgical resection strategies for early-stage nail apparatus melanoma based on clinical manifestations, can ensure adequate treatment and preserve the normal function of the extremities to the greatest extent without recurrence of the primary tumors.
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Objective:To investigate clinical features and preventive measures of misdiagnosed cutaneous melanoma, as well as causes of its misdiagnosis.Methods:Clinical data were collected from patients with pathologically confirmed cutaneous melanoma which was initially clinically misdiagnosed as other diseases in Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from January 2005 to December 2019, and clinical manifestations and causes of its misdiagnosis were analyzed.Results:A total of 118 patients with clinically misdiagnosed cutaneous melanoma were collected, including 38 males and 80 females. The median age at misdiagnosis was 48 years, the median age at onset was 40.5 years, and the median disease duration was 54 months. The main skin lesions were black maculae and papules. The initial clinical diagnoses were pigmented nevi (53 cases, 44.92%) , nail matrix nevi (12 cases, 10.17%) , seborrheic keratosis (14 cases, 11.86%) , vascular tumors (10 cases, 8.47%) , squamous cell carcinoma (5 cases, 4.24%) , basal cell carcinoma (4 cases, 3.39%) and other diseases (20 cases, 16.95%) . As far as the ABCDE (asymmetry, border irregularity, color variegation, diameter > 6 mm, evolving) rule for melanoma was concerned, 78 (66.10%) , 64 (54.24%) , 57 (48.31%) , 66 (55.93%) and 39 (33.05%) cases conformed to hte A, B, C, D and E rules respectively, 14 conformed to the ABCDE rule, 13 conformed to the ABCD rule, and 13 did not conform to any of them. Among the 53 cases of melanoma in situ, 28 (52.83%) were misdiagnosed as pigmented nevi, 11 (20.75%) as nail matrix nevi; among the 66 cases of invasive melanoma, 25 (37.88%) were misdiagnosed as pigmented nevi, 9 (13.64%) as vascular tumors, and 5 (7.58%) as squamous cell carcinoma. The information of physicians of 67 misdiagnosed patients was available, and those of 42 out of the 67 patients had clincial experience of ≤ 5 years; among 27 misdiagnosed patients conforming to the ABCD or ABCDE rule, the information of physicians of 9 patients was available, and those of 7 out of the 9 patients had clinical experience of ≤ 5 years. Conclusion:Cutaneous melanoma has a variety of lesion patterns and is easily misdiagnosed, and physicians′ clinical experience and the ABCDE rule-based evaluation are important for diagnosis.
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Objective:To analyze clinicopathological characteristics of trauma-related melanoma and their relationship with the prognosis of patients.Methods:Clinical data were collected from 87 cases of trauma-related melanomas in Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from 2009 to 2020, and their clinicopathological characteristics were retrospectively analyzed. Mann-Whitney test was used to analyze the difference in Breslow thickness of tumors between patients of different ages or genders; Spearman rank correlation analysis was used to analyze the correlation between the time from trauma to the notice of melanoma and Breslow thickness, Kaplan-Meier survival analysis and Log-Rank test were employed to analyze the relationship between clinicopathological characteristics of melanoma and the prognosis of patients; Cox regression model was used to analyze risk factors for survival duration of patients with trauma-related melanoma.Results:Among the 87 patients with trauma-related melanoma, 47 (54.02%) were males and 40 (45.98%) were females. Among them, melanoma occurred in 50 (57.47%) cases after sharp injuries, and in 37 (42.53%) after blunt injuries. In addition, 31 (35.63%) cases presented with primary lesions on the hands, and 48 (55.17%) on the feet. The Breslow thickness of the primary tumors was significantly higher in the group aged > 55 years than in the group aged ≤ 55 years ( U= 623.500, P= 0.010) , but there was no significant difference between patients of different genders ( P= 0.138) . The time from trauma to the notice of melanoma was negatively correlated with the Breslow thickness of tumors ( r=-0.203, P= 0.037) . The age of patients, Breslow thickness of tumors, Ki67 proliferation index and genetic background of tumor significantly affect the survival duration of patients with trauma-related melanoma ( P= 0.011, 0.031, 0.002 and 0.031, respectively) ; the gender, type of trauma and ulceration of tumor mass did not significantly affect the survival duration of patients ( P= 0.618, 0.114 and 0.379, respectively) . Cox regression model analysis showed that the Ki67 proliferation index and Breslow thickness were independent risk factors affecting the prognosis of trauma-related melanoma (risk ratio [ RR] and 95% confidence interval [ CI] were 1.946 (1.234, 4.217) and 1.839 (1.014, 3.332) , P= 0.039 and 0.045, respectively) . Conclusion:The Breslow thickness of trauma-related melanoma is related to the age of patients and time from trauma to the notice of melanoma; the age, Breslow thickness of tumors, Ki67 proliferation index and genetic background of tumor all affect the survival duration of patients with melanoma, and Ki67 proliferation index and Breslow thickness are independent risk factors affecting prognosis.
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Objective:To analyze clinical and histopathological characteristics of infantile congenital melanocytic nevi (ICMN) .Methods:Clinical and pathological data were collected from 126 infants with confirmedly diagnosed congenital melanocytic nevi in Department of Dermatology, Xijing Hospital from January 2015 to January 2020, and were retrospectively analyzed. Chi-square test was used for comparisons of enumeration data.Results:Among the 126 patients with ICMN, 68 were males and 58 were females; 109 (86.5%) presented with skin lesions at birth; 73 (57.9%) were 2 - 3 years old at the first clinic visit. The skin lesions occurred on the head and face (76 cases, 60.3%) , trunk (24 cases, 19.1%) or extremities (26 cases, 20.6%) . There were 36 (28.6%) patients with small congenital nevi, 68 (54.0%) with M1-type medium-sized nevi, 13 (10.3%) with M2-type medium-sized nevi and 9 (7.1%) with giant nevi. Of 126 cases of ICMN, 121 (96.0%) had solitary lesions, 5 (4.0%) had multiple lesions, 44 (34.9%) had nevi with coarse hairs, 15 (11.9%) had nevi complicated by papules or hyperplastic nodules, and 6 (4.8%) had satellite lesions. Pathological subtypes included compound nevus (120 cases, 95.2%) , intradermal nevus (4 cases, 3.2%) , and junctional nevus (2 cases, 1.6%) . Under the microscope, the depth of the skin lesions was < 1 mm in 38 (30.1%) cases, 1 - 2 mm in 61 (48.4%) and > 2 mm in 25 (19.8%) , and 45 (35.7%) cases showed nevus cells infiltrating the subcutaneous fat layer or deeper tissues. Among the 126 ICMN lesions, common pathological features included nevus tissue maturation (100%, 2 cases of junctional nevi were excluded) , pigment granules in the stratum corneum (53 cases, 42.1%) , disordered/asymmetric distribution of nevus cells (80 cases, 63.5%) , scattered epidermal nevus cells (91 cases, 72.2%) , pagetoid spread of epidermal nevus cells (67 cases, 53.2%) , melanophages in the dermis (71 cases, 56.4%) , and nevus cells distributed along hair follicles/sebaceous glands (82 cases, 65.1%) . Special pathological features included nevus cells embedded in the vascular/lymphatic vessels (42 cases, 33.3%) , nevus cell lysis (45 cases, 35.7%) , fibromatous changes (25 cases, 19.8%) , involvement of the arrector pilli muscles (31 cases, 24.6%) , and mast cell infiltration (30 cases, 23.8%) . Pathological patterns of ICMN with different clinical features: the incidences of infiltration depth > 2 mm, pigment granules and columnar pigment granules in the stratum corneum were significantly higher in the giant nevi than in the small and medium-sized nevi ( χ2 = 7.93, 10.76, 5.89 respectively, all P < 0.05) ; the incidences of infiltration depth > 2 mm, epidermal spongiosis with scattered nevus cells, nevus cell nests distributed along the hair follicles/sebaceous glands, fibromatous changes and mast cell infiltration were significantly higher in the skin lesions with coarse hairs than in those without ( χ2 = 28.29, 8.11, 6.22, 7.92, 8.19 respectively, all P < 0.01) ; the incidences of pagetoid spread of epidermal nevus cells and atypical nevus cells were significantly higher in the skin lesions with papules/hyperplastic nodules than in those without papules/hyperplastic nodules ( χ2 = 4.92, 6.30 respectively, both P < 0.05) . Conclusions:The clinical and histopathological characteristics of ICMN are unique, and atypical nevus cells are common in ICMN. The diagnosis and treatment of ICMN need to be based on the combination of clinical and pathological characteristics.
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Although the incidence of melanoma is increasing rapidly, its proportion is relatively low among all the malignant tumors in China, and oncologists commonly pay little attention. The first consultation place for melanoma patients is mainly the department of dermatology. Dermatologists have unique advantages in the diagnosis and treatment of melanoma since they can comprehensively integrate clinical diagnosis, pathological diagnosis, surgical treatment and drug treatment. In recent years, Chinese scholars have made great progress in melanoma research, such as regulation of cell death, epigenetic modification, resistance to targeted drugs, tumor microenvironment and tumor immune regulation. Interferon α-1b, a unique new drug in China, not only can be used for adjuvant treatment of high-risk stage Ⅱ and Ⅲ melanoma, but also shows good efficacy in the treatment of stage Ⅳ melanoma, and adverse reactions to it are far less than those to interferon α-2b. Unlike the White population, the common subtypes of melanoma are acral and mucosal melanomas in the Asian population. The combination of interferon α-1b with programmed death receptor-ligand 1 inhibitor, targeted drugs or angiogenesis inhibitors is bringing hope for patients with stage IV melanoma.
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Objective:To analyze clinical and pathological features of 320 cases of Spitzoid tumors.Methods:Clinical and pathological data were collected from 320 patients with Spitzoid tumors in Department of Dermatology, Xijing Hospital from January 2005 to January 2020, and retrospectively analyzed.Results:The 320 patients included 141 males and 179 females, aged 0 - 65 (12.5 ± 11.7) years, and their course of disease ranged from 1 month to 30 years. Among them, there were 307 patients with Spitz nevi, 8 with atypical Spitz tumors and 5 with Spitzoid melanoma. Most skin lesions were solitary, and occurred on the head, face, trunk and limbs, with clear boundaries. Among the 307 patients with Spitz nevi, the skin lesions were mainly black (132 cases, 43.0%) and red (108 cases, 35.1%) in color, most of which were uniformly pigmented (262 cases, 85.3%) with smooth surfaces (272 cases, 88.6%) . There were several special clinical subtypes of Spitz nevi, including Spitz nevus arising in a nevus spilus (11 cases, 3.6%) , agminated Spitz nevus (11 cases, 3.6%) , disseminated Spitz nevus (6 cases, 2.0%) , nodular Spitz nevus (7 cases, 2.3%) and keloid-like Spitz nevus (1 case, 0.3%) . Characteristic histopathological manifestations of Spitz nevi included pagetoid spread of epidermal nevus cells (123 cases, 40.1%) , Kamino bodies at the dermo-epidermal junction (74 cases, 24.1%) , horizontal band-like distribution of nevus cells (177 cases, 57.8) , wedge-shaped distribution of nevus cells (118 cases, 38.4%) , fissures around nevus cell nests (177 cases, 57.8%) , physiological mitotic figures (117 cases, 38.1%) , and fine nuclear chromatin (307 cases, 100%) . According to the special histopathological manifestations, Spitz nevi were divided into pigmented epithelioid Spitz nevus (9 cases, 2.9%) , desmoplastic Spitz nevus (13 cases, 4.2%) , hemangiomatous Spitz nevus (8 cases, 2.6%) , verrucous Spitz nevus (12 cases, 3.9%) , mucoid Spitz nevus (10 cases, 3.3%) , halo-like Spitz nevus (4 cases, 1.3%) , etc. Among the 8 cases of atypical Spitz tumors, 4 skin lesions were black, 7 were uniformly pigmented, and 3 had rough surfaces; the characteristic pathological manifestations included mild to moderate atypia of cells, mitotic figures (2 - 6 cells/mm 2 in 7 cases) , and coarse nuclear chromatin (5 cases) . Among the 5 cases of Spitzoid melanoma, 3 had red skin lesions, 4 were non-uniformly pigmented, and 3 had rough surfaces; the characteristic pathological manifestations included pagetoid spread of melanocytes (3 cases) , non-polar infiltrating growth of immature tumor cells, pathological mitotic figures (3 cases, > 6 cells/mm 2) , coarse nuclear chromatin and obviously stained nuclear membrane. Conclusions:Spitzoid tumors are characterized by unique clinical and histopathological features. There are various clinical and pathological subtypes of Spitz nevi, and atypical Spitz tumors have clinical and pathological characteristics of both Spitz nevi and melanoma.
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A melanoma is a highly malignant tumor that originates from melanocytes in the skin, mucosa, or tunica pigmentosa. The incidence and mortality rate of cutaneous melanoma are increasing annually. However, the efficacy of traditional therapy is extremely limited because of its low sensitivity and high toxicity. The application of the anti-CTLA-4 antibody and the BRAF inhibitor dramatically improves the overall survival of patients with advanced melanoma. However, their limited benefit ratio and high drug resistance curtail the use of anti-CTLA-4. Since the US Food and Drug Administration approved the use of the anti-PD-1 and anti-PD-L1 antibodies for ad-vanced melanoma in 2014, a significant survival benefit has been observed in patients with advanced melanoma. This review aims to highlight the applications of the anti-PD-1 antibody (pembrolizumab, nivolumab, and pidilizumab) and the anti-PD-L1 antibody (MP-DL3280A, BMS-936559, and MEDI4736) in the clinical treatment of melanoma by succinctly summarizing the results of recent reports.
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Objective To explore the effects of NF-E2-related factor 2 (Nrf2) overexpression on mitochondrial biosynthesis and function in melanocytes.Methods An immortalized human vitiligo melanocyte cell line PIG3V was used in this study.An overexpression plasmid Nrf2-pEX-1 containing the full-length Nrf2 gene was constructed.PIG3V cells were divided into 3 groups:blank group receiving no treatment,control group transfected with the pEX-1 plasmid,overexpression group transfected with the Nrf2-pEX-1 plasmid.After transfection,real-time quantitative reverse transcription-PCR (RT-PCR) and Western blot were performed to determine the mRNA and protein levels of mitochondrial biosynthesis-related factors (including Nrf2,nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM)) respectively;RT-PCR was also conducted to measure the copy number of mitochondrial DNA (mtDNA),and flow cytometry to estimate mitochondial membrane potential (MMP);luciferase reporter system was used to estimate the intracellular adenosine triphosphate (ATP) level.Statistical analysis was carried out by using a two-sample t-test.Results After transfection,a significant increase was observed in the mRNA expression levels of Nrf2 and NRF1 at 24 hours (both P ＜ 0.001) and in those of Nrf2 and TFAM at 48 hours (both P ＜ 0.05),but no significant change was noted in the mRNA expression level of TFAM at 24 hours (P ＞ 0.05) or in that of NRF1 at 48 hours (P ＞0.05) in the overexpression group compared with the control group.In the case of Nrf2,NRF1 and TFAM protein levels,the overexpression group showed significant increases compared with the control group at 48 hours after transfection (all P ＜ 0.05),while no significant difference was noted between the two groups at 24 hours.Compared with the control group,MMP in the overexpression group increased by 2.313％ at 24 hours (t =5.546,P =0.005) and by 14.872％ at 48 hours (t =8.537,P =0.001) after transfection.Both the relative copy number of mtDNA and ATP level were similar between the overexpression group and control group at 24 hours after transfection (both P ＞ 0.05),but significantly higher in the overexpression group than in the control group at 48 hours (t =5.760,P =0.005;t =22.040,P =0.008).Conclusion Up-regulation of Nrf2 pathway can improve mitochondrial function and biosynthesis in PIG3V cells likely by promoting the expressions of mitochondrial biosynthesis-related genes and proteins.
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Objective To estimate the relationship of the functional single nucleotide polymorphism (SNP) rs1052133 in the 8-oxoguanine DNA glycosylase 1 (OGG1) gene with vitiligo in a Chinese Han population.Methods Blood samples were collected from 800 patients with vitiligo and 800 healthy human controls,and subjected to genomic DNA extraction.PCR-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to analyze the genotype of the SNP rs1052133 in the OGG1 gene.The relationship between the SNP and the risk of vitiligo was evaluated by chi-square test and unconditional logistic regression analysis.Enzyme linked immunosorbent assay (ELISA) was carried out to assess the serum level of 8-hydroxydeoxyguanosine (8-OHdG) in 83 patients with vitiligo and 83 healthy human controls,then,t test was used to compare the serum 8-OHdG level between the patients and controls.Results The frequency of CC,CG and GG genotype of the SNP rs1052133 was 16.8％,54.0％ and 29.2％ respectively in the patients,21.4％,52.8％ and 25.8％respectively in the controls (x2 =6.26,P ＜ 0.05).Increased frequency of G allele of the SNP rs1052133 was observed in the patients with vitiligo compared with the controls (56.2％ vs.52.2％,x2 =5.16,P ＜ 0.05).A statistically increased risk of vitiligo was associated with the CG (x2 =3.98,P ＜ 0.05,adjusted odds ratio 1.31,95％ confidence interval:1.01-1.70) and GG (x2 =6.01,P ＜ 0.05,adjusted odds ratio 1.45,95％ confidence interval:1.08-1.94) genotype of SNP rs1052133 compared with the CC genotype,which was more evident among the patients with the following characteristics:female,nonsegmental vitiligo,active vitiligo,long clinical course (＞ 12 months),a family history of vitiligo,and no accompanied autoimmune diseases.In addition,the patients with the CG or GG genotype of SNP rs1052133 had a higher serum 8-OHdG level than those with the CC genotype ((838.23 ± 294.11) μg/L vs.(593.84 ± 190.14) μg/L,t =3.63,P ＜ 0.01).Conclusions The SNP rs1052133 in the OGG1 gene may be responsible for the development of vitiligo in Chinese Han populations,which is likely to be associated with defects in DNA repair.
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We describe an unusual case of trichilemmal carcinoma accompanied be a large horn formation in a 79-years-old man who presented with a brown tumor mass including a 15-cm-long horn on the vertex for one and a half years. Two months after the surgical removal of the primary tumor, the tumor recurred with a dimension 10x8x8 cm. The tumor was then excised again and the wound was covered using skin from the patient's back. Microscopically, the tumor showed histology consistent with trichilemmal carcinoma. After 2 years, the patient had not shown any recurrence or metastases. We highlight the features that distinguish trichilemmal carcinoma from the other malignant tumors, such as squamous cell carcinoma, basal cell carcinoma, nodular melanoma, or keratoacanthoma.
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ObjectiveTo investigate the effects of imatinib mesylate as a tyrosine kinase inhibitor on the biological activity of and Wnt/β-catenin pathway in Hs294T melanoma cells.MethodsAfter Hs294T cells were incubated with imatinib mesylate at various concentrations(4,8,10,16,20 and 24 μmol/L) for 24 hours or imatinib mesylate at 10 μmol/L for 24,48 and 72 hours,methyl thiazolyl tetrazolium (MTT) assay was performed to estimate the proliferation of cells and to determine the effects of imatinib mesylate on the proliferation of Hs294T cells.Then,Hs294T cells were treated with imatinib mesylate at 10 μmol/L or dimethyl sulfoxide (DMSO) for different durations,followed by the detection of cell apoptosis with flow cytometry,localization of β-catenin with annexin V/propidium iodide-double staining and laser confocal microscopy,quantification of β-catenin and cyclin D1 protein with Western blot,and measurement of LEF1 and C-myc mRNA expression with real time fluorescence-based quantitative PCR.Matrigel invasion assay was performed to evaluate the invasiveness of Hs294T cells after treatment with imatinib mesylate at 5 μmol/L or DMSO for 24 hours.ResultsImatinib mesylate at 4-10 μmol/L elicited a dose-dependent decline in the proliferation of Hs294T cells (F =125.3,P ＜ 0.05),and imatinib mesylate at 10 μmol/L induced a time-dependent decrease from 24 to 72 hours(F =714.6,P ＜ 0.01 ).The percentage of early and late apoptotic cells was markedly increased,while the invasiveness was decreased by about 48％(P ＜ 0.01 ),together with a downregulation in the expression of LEF1,C-myc and Cyclin D1 in imatinib mesylate-treated Hs294T cells compared with the DMSO-treated cells.No obvious changes were observed in the protein expression of β-catenin,but a decline in the nuclear localization of β-catenin was noted in Hs294T cells after being treated with imatinib mesylate.ConclusionImatinib mesylate may suppress the proliferation and invasion of,but promote the apoptosis in,melanoma cells,by downregulating the Wnt/β-catenin pathway.
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Objective To investigate DJ-1 expression and protective effect against H2O2-induced oxidative stress in primary human melanocytes.Methods The expression and location of DJ-1 in primary melanocytes were identified by immunofluorescence.After cultured melanocytes were exposed to H2O2 for 24 hours,modified MTT assay was used to assess the proliferation of cells and to choose the suitable concentration of H2O2 for the following experiment.Western blot was used to detect D J-1 expression in melanocytes after being treated with 0.5 mmol/L H2O2 for 24 hours.Some melanocytes were divided into 3 groups to be reversely transfected with PBS(mock control group),non-targeting siRNA(negative control group)and DJ-1 targeting siRNA(DJ-1 group).Optical microscopy was utilized to observe the morphologic changes of transfected melanocytes.At 48 hours after the transfection,the melanocytes were stimulated with H2O2 for 24 hours.Subsequently,modified MTT assay,2′,7′-dichlorofluorescein diacetate(DCFH-DA)and annexin Ⅴ-fluorescein isothiocyanate/propidium iodide were used to determine cell viability,intracellular reactive oxygen species (ROS)level and apoptosis rate respectively.Results DJ-1 was expressed in both melanocyte nucleus and cytoplasm,and predominantly in the nucleus.H2O2 inhibited the cell viability in a dose dependent manner.After treatment with H2O2 of 0.5 mmol/L for 24 hours,the cell viability began to decrease in melanocytes with the expression level of DJ-1 being 2.23 times that in the untreated melanocytes(both P ＜ 0.05).Compared with the mock control group,the dendrites of melanocytes in DJ-1 group were obviously shortened with cytoplasm vacuolization.After 24-hour treatment with H2O2 of 0.5 mmol/L,the cell viability in the DJ-1 group dropped to 35％ of that in the mock control group(P ＜ 0.05),while the intracellular ROS fluorescence intensity( FI) and apoptosis rate were higher in the DJ-1 group than in the mock control group (902 ± 40 vs.529± 32,58q％ ± 6.1％ vs.30% ± 3.8％,both P ＜ 0.05).Conclusion DJ-1 can protect melanocytes against H2O2induced oxidative stress likely by decreasing intracellular ROS production and inhibiting ceU apoptosis.