De novo intraepidermal epithelioid melanocytic dysplasia: a review of 263 cases

Background: De novo intraepidermal epithelioid melanocytic dysplasia (DNIEMD) is a newly characterized lesion that is associated with a personal and/or family history of malignant melanoma (MM) and/or dysplastic nevi (DN). However, the biological significance is still uncertain and the persons predisposed to this lesion have not been adequately described. Methods: Clinicopathologic data of 258 patients, from 263 biopsies diagnosed with DNIEMD, was obtained. A brief voluntary questionnaire was used to obtain demographic, risk factor and disease history. Results: There is an 82% (n=263) predominance of women with DNIEMDs. For men and women, the distributions of these lesions occur on the lower extremities (71%), the upper extremities (24%) and trunk (5%). Thirty‐one percent of the 258 patients responded to the questionnaires. 48% of the 60 respondents had green or blue eyes. 26% of 62 respondents had a history of non‐melanoma skin cancer (NMSC). Combined data revealed that 68% of 134 patients had a history of DN. As well, 24% of 89 patients had personal histories of melanoma, while 24% of 72 patients had a family history of melanoma. Conclusion: Most of these DNIEMD lesions are found on the lower extremities of women and men, and they have an increased association with MM, DN and NMSC. Jessup CJ, Cohen LM. De novo intraepidermal epithelioid melanocytic dysplasia: a review of 263 cases.     

Spitz nevus is relatively frequent in adults: a clinico-pathologic study of 247 cases related to patient's age

Spitz nevus is a clinico-pathologic entity that can cause diagnostic concern, particularly in adults. Many studies have been performed to establish reliable histologic criteria, in the attempt to differentiate this lesion from melanoma. A series of 247 Spitz nevi, 6 of which were formerly classified as melanomas, were reviewed for clinical and histopathological parameters. Patients older than 20 comprised 66% of cases, with a predominance of women. The lower extremity was more affected in females of any age, whereas the trunk was more frequently involved in men over 40. Histopathologic examination showed the following differences among Spitz nevi related to age: acanthosis, parakeratosis, pagetoid infiltration, and Kamino bodies were more frequent in young people, whereas multinucleated melanocytes were more frequent in adults. The latter also had lesions that were less pigmented, with less maturation and more desmoplasia. At a mean follow-up of 94 months (range 52-172), recurrence at the site of biopsy or metastases were absent. In our study, a greater proportion of Spitz nevi occurred in adults than in previous series. Moreover, the relative incidence of Spitz nevus compared with melanoma in our population was higher than in other studies. Histopathologic criteria elaborated to diagnose Spitz nevus, applied to our cases, appeared reliable, allowing a correct diagnosis, even in adults.     

Incidence of new and changed nevi and melanomas detected using baseline images and dermoscopy in patients at high risk for melanoma

OBJECTIVE: To determine the incidence of new, changed, and regressed nevi and melanomas in a cohort of patients at high risk for melanoma using baseline total body photography and dermatoscopy. DESIGN: Cohort study of patients at high risk for melanoma who underwent baseline cutaneous photography between January 1, 1992, and December 31, 1997, and had at least 1 follow-up visit by December 31, 1998. SETTING: Private practice rooms of 1 dermatologist in conjunction with a public hospital-based, multidisciplinary melanoma clinic in Victoria, Australia. PATIENTS: A total of 309 patients who had at least 1 of the following risk factors for melanoma: personal history, family history, 100 or more nevi, or 4 or more dysplastic nevi. MAIN OUTCOME MEASURES: Number of new, changed, and regressed nevi and melanomas detected and excised during the study interval. RESULTS: The incidence of new, changed, and regressed nevi decreased with increasing age (P<.001), whereas the incidence of melanomas increased (P = .05). The number of dysplastic nevi at baseline was positively associated with the incidence of changed nevi (P<.001) and melanomas (P = .03). The use of baseline photography and dermatoscopy was associated with low biopsy rates and early detection of melanomas. The development of melanoma in association with a preexisting nevus was not directly correlated with a change in a preexisting lesion monitored by baseline photography. CONCLUSIONS: Nevi are dynamic, and only a small percentage of all new and changed melanocytic lesions are melanomas. Patients younger than 50 years had a lower incidence of melanomas and a higher rate of new, changed, and regressed nevi when compared with patients older than 50 years. A new or changed pigmented lesion is more likely to be a melanoma in patients older than 50 years.     

Age distribution and histologic patterns of dysplastic nevi

A total of 676 dysplastic moles collected from 487 patients over a 1-year period were reviewed together with demographic data. The associated nevus in 642 cases (95%) had a superficial, or "acquired," pattern within the papillary dermis, in comparison with the nevus in the remaining 34 cases (5%), which showed a deep, or "congenital," pattern. The dysplasia was graded in severity as mild, moderate, or severe (on a scale of 1 to 3). When patients with mild to severe dysplastic melanocytic nevi were compared with those patients showing atypical intraepidermal melanocytic hyperplasia (also called in situ malignant melanoma) or early invasive malignant melanoma associated with dysplasia, a progression of ages was noted. The average ages in the five diagnostic groups were as follows: 34.8 years, mild dysplasia (group 1); 35.1 years, moderate dysplasia (group 2); 41.5 years, severe dysplasia (group 3); 44.4 years, in situ malignant melanoma (group 4), and 46.9 years, early invasive malignant melanoma (group 5). Statistical analysis revealed that the two younger groups differed significantly in age from the three older groups. Men and women had an equal proportion of acquired and congenital pattern nevi, but men were older in each category and had more severe dysplasia, a greater tendency toward truncal lesions, and more regressive changes. Biopsy of trunk lesions was done in 275 cases (80%), of extremity lesions in 60 cases (17%), and in head and neck sites in 9 cases (3%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Melanocytic nevi with features of Spitz nevi and Clark's/dysplastic nevi ("Spark's" nevi)

Background: Nevi with cytologic characteristics of Spitz nevus and architectural features of Clark's/dysplastic nevus are not well recognized in the literature.
Methods: Twenty-seven nevi with characteristics of Spitz nevus and Clark's/dysplastic nevus are reviewed.
Results: The patients' mean age was 33 years, and 17/27(63%) patients were female. Lesions were most frequent on the trunk and lower extremities. Histopathologically, these nevi were composed of large, monomorphous spindled and/or epithelioid melanocytes. Spindle cells were often oriented parallel to the epidermis, with fused rete and lamellar fibroplasias. Lateral extension of the junctional component was a feature of compound lesions. An average of 10 years of clinical follow up in 12 patients revealed no recurrence or metastasis.
Conclusions: Recognition of this type of nevus is important to avoid confusion with malignant melanoma.     

Eruptive multiple blue nevi of the penis: a clinical dermoscopic pathologic case study

Multiple blue nevi have rarely been reported, and the majority of the lesions are located on the trunk and lower extremities. The blue nevus is a rare lesion on genital mucosa and may cause confusion in differential diagnosis with other pigmented lesions such as genital melanocytic macules, lentigo simplex, and malignant melanoma. Here, we describe an unusual patient who presented with a sudden onset in adulthood of multiple blue nevi on the glans penis. The epiluminescence examination revealed a substantially homogenous bluish pigmentation, which led us to favor a diagnosis of blue nevus, whereas not entirely excluding the possibility of a regressing melanoma or a metastatic melanoma. Because of the well-known diagnostic value of the blue hue in the diagnosis of malignancy by dermoscopy, a careful examination of these lesions should be made in order to minimize any risk of misclassification with melanoma.     

On naevi and melanomas in dysplastic naevus syndrome patients

Cutaneous melanoma may occur as isolated, so-called 'sporadic’cases or in association with multiple atypical naevi and in familial clusters, in which case it is referred to as the familial dysplastic naevus syndrome (DNS). In this retrospective study (a) the number and body distribution of naevocytic naevi and (b) the body distribution of malignant melanoma (MM) in individuals with familial DNS were compared in order to study their association. In 45 patients with familial DNS aged 20–39 years naevus counts on trunk and lower extremities were compared with melanoma data and distributions from a second group of 43 patients from the same DNS families aged 12–66 years. Men had significantly more naevi of a size 2 mm or 5 mm on the back than women (P=0.02). Women showed a tendency towards a greater number of naevi on the lower extremities than men, but in women no significant difference in naevi between the lower extremities and the back was found. The total number of naevi on the trunk and lower extremities in familial DNS patients was higher than that in the general population. In conclusion, it was found that predilection sites for melanoma in familial DNS patients of both sexes correspond with the distribution of naevi; in males naevi and melanoma counts and percentage distributions were higher on the back, in females both the back and the lower extremities were affected. These findings strongly suggest an association between naevus distribution and melanoma occurrence and sire in familial DNS, analogous to earlier reports on sporadic melanoma.^1,2     

Multiple primary melanomas

BACKGROUND: Patients with clinically diagnosed dysplastic nevi or a family history of melanoma with or without histologically diagnosed dysplastic nevi seem to be at higher risk for the development of multiple melanomas. OBJECTIVE: Our purpose was to determine which factors increased the risk for the development of subsequent melanomas. METHODS: This was a retrospective study in 56 patients with 157 melanomas. RESULTS: Early age at onset (58.9%), clinically diagnosed dysplastic nevi (82.0%), a histologically diagnosed dysplastic nevus (64%), family history of clinically diagnosed dysplastic nevi (70.8%) or melanoma (64.7%) and a histologically diagnosed dysplastic nevus in combination with a family history of melanoma (48%) were found in a high percentage of patients. The mean age at diagnosis was 38.2 years. The mean interval between the first and second melanoma was 34.3 months. Of the second melanomas, 76.8% developed in a different anatomic region from the first melanomas. The mean tumor thickness (Breslow) decreased from 1.11 mm for the first melanomas to 0.90 mm for the second melanomas. CONCLUSION: The results suggest that genetic factors might be involved in a certain subset of patients in whom melanomas develop early and successively.     

黑素细胞痣1 011例的特殊组织病理学特征分析

【摘要】 目的 分析黑素细胞痣的特殊组织病理学特征及其与年龄、性别、部位和病理亚型之间的关系。方法 回顾北京医院皮肤科2005年1月至2019年1月就诊的1 011例黑素细胞痣患者的临床及病理资料。计数资料的比较采用χ2检验，计量资料的比较采用t检验。结果 1 011例黑素细胞痣患者就诊年龄为（40.90 ± 19.19）岁，男289例，女722例。皮损发生及取材部位：躯干402例（39.8%），面颈部268例（26.5%），四肢138例（13.6%），手足133例（13.2%），头皮53例（5.2%），外阴17例（1.7%）。病理亚型：皮内痣580例（57.4%），混合痣333例（32.9%），交界痣98例（9.7%）。特殊组织病理学特征：172例（17.0%）有神经化、155例（15.3%）有脂肪增生表现，女性多于男性、年长患者多于年轻患者、头皮部位多于其他部位（均P < 0.05）；313例（31.0%）有血管增生表现，头皮部位多于其他部位（P < 0.05）；502例（49.7%）可见痣细胞沿毛囊/皮脂腺分布，面颈部多于其他部位（P < 0.05）；203例（20.1%）有痣细胞松解、384例（38.0%）有裂隙表现；以上特征皮内痣多于混合痣（均P < 0.05）。20例（2.0%）有痣细胞沿血管分布的表现，四肢多于躯干、手足（P < 0.05），混合痣多于皮内痣（P < 0.05）。结论 黑素细胞痣的多种特殊组织病理学特征如神经化、脂肪增生、血管增生、痣细胞沿毛囊/皮脂腺分布等，与患者的年龄、性别、皮损发生部位和病理亚型有关。     

Expression of c-kit (CD117) in Spitz nevus and malignant melanoma

BACKGROUND: CD117, the receptor for kit-ligand, which is a growth factor for melanocyte migration and proliferation, has shown differential staining in various benign and malignant melanocytic lesions. The purpose of this study is to compare CD117 immunohistological staining in Spitz nevus versus malignant melanoma, to determine whether CD117 can aid in the diagnosis of these two lesions. METHODS: CD-117 immunohistological staining was performed in 22 clinically and pathologically diagnosed pigmented lesions including 9 cases of Spitz nevus, 10 cases of primary MM and 3 cases of metastatic melanoma. RESULTS: There was no significant difference in CD117 staining in either epidermis or dermis between Spitz nevi and primary melanomas. However staining of metastatic melanomas is less than dermal staining of primary MM and Spitz nevus. CONCLUSIONS: CD117 is unlikely a useful diagnostic tool in differentiating Spitz nevus from primary MM. On the other hand, CD 117 may be useful in differentiating metastatic melanoma from primary melanoma in patients who had a history of melanoma and who present with new dermal lesions.     

Compound blue nevus: a variant of blue nevus with an additional junctional dendritic component. A clinical, histopathologic, and immunohistochemical study of six cases

We studied six cases of heavily pigmented melanocytic lesions with features of blue nevi within the dermis, but with an additional junctional dendritic component. This compound variant of blue nevus is an uncommon lesion that has not been previously identified as a distinct histologic entity. Immunoperoxidase staining for S100 protein and counterstaining with azure B distinguished the presence of melanocytes among numerous melanophages within the dermis. The compound variant of blue nevus can be distinguished histologically from combined blue nevus, pigmented spindle cell nevus, malignant melanoma, and melanosis due to a regressed malignant melanoma. The six lesions were from three men and three women whose ages ranged from 11 to 51 years (mean, 31 years). Three lesions were located on the trunk, two on the extremities, and one on the head. After a mean follow-up period of 47 months (range, 38 to 58 months), there was no evidence of recurrence.     

Comparison of Seborrheic Keratoses, Inflamed Seborrheic Keratoses, and Inverted Follicular Keratoses Using P53, BCL‐1, and BCL‐2

Background: Recurrent nevi may histologically resemble malignant melanoma Design: Recurrent nevi with clinical history, original melanocytic neoplasm and recurrence were included. Proliferation marker Ki‐67 was used when residual and recurrent nevus was present on the same slide. Results: There were 356 biopsies from 328 patients (ages 6 to 93 years (mean = 31), female: male = 255:101, time to recurrence 1–63 months (mean = 7.85)). Sites: back (170), abdomen (46), arm (46), leg (34), head and neck (26), chest (26), and buttock (8). Initial biopsies: 208 nevi, 142 dysplastic nevi, 1 blue, 1 pigmented spindle cell, 2 Spitz nevi, and 2 melanomas in situ. 3 patterns of recurrence were observed: 1) junctional melanocytic hyperplasia with epidermal effacement and scar, 2) compound melanocytic proliferation with epidermal effacement and scar, and 3) junctional melanocytic hyperplasia with retained retiform epidermis. Recurrent and residual nevi had similar proliferation rates. Conclusion: Recurrent nevi occurred more commonly in females and on the trunk. Cytologic atypia, asymmetry, and retention of retiform epidermis were worrisome histologic features. Clinical history, effacement of the epidermis and limitation of changes to the scar, distinguished recurrence from melanoma. Low proliferation rate may be a useful adjunct to distinguish recurrent nevi from melanoma.     

Melanoma in association with acquired melanocytic nevus in Japan: a review of cases in the literature

Background Malignant melanomas clinically and/or histologically associated with melanocytic nevi have been reported worldwide. Approximately 20% of malignant melanomas in Caucasians, most of which are found on the trunk and proximal extremities, develop in association with pre‐existing melanocytic nevi. In Japan, however, over half of all melanomas are acral lentiginous melanomas (ALMs) on the hands and feet; melanomas on sun‐exposed areas are seen less frequently in Japanese people than in Caucasians. As ALMs are not usually accompanied by melanocytic nevi and there have been no reviews of the literature or statistical data regarding Japanese cases of melanomas with melanocytic nevi, dermatologists in Japan have few opportunities to see melanomas associated with pre‐existing melanocytic nevi. Methods Here we report a case of a superficial spreading melanoma that was formed on a melanocytic nevus on the trunk, and we review for the first time the case reports from the Japanese literature. Results and Conclusions With regard to the reported cases, melanomas associated with melanocytic nevi were mainly superficial spreading melanomas and nodular melanomas on the trunk or extremities; ALMs were rarely associated with nevi, indicating a trend similar to that observed in Caucasians. These findings suggest that the low frequency of associations between melanomas and melanocytic nevi in Japan reflects racial differences in the frequencies of each type of melanoma.     

Mitotic activity within dermal melanocytes of benign melanocytic nevi: a study of 100 cases with clinical follow-up

It is generally accepted that otherwise benign intradermal or compound melanocytic nevi may show mitotic activity within dermal melanocytes. However, it is not known whether there is any clinical significance to this finding. Our objective is to analyze and describe the clinicopathologic features of benign nevi with mitotic activity (NMA). To do this, we collected 100 consecutive NMA during the usual course of business in our private dermatopathology practice. These cases were seen between the years 2000 and 2008. We then collected clinical and pathologic data on these cases and compared the findings with 100 control nevi without mitotic activity (CN). We compared these nevi with regard to demographic features, clinical history provided by clinician, and clinical follow-up, as well as anatomic site and season of biopsy, type of nevus, and selected histologic features (ie, trauma). We also estimate the incidence of NMA and describe the amount and location of mitotic figures within the NMA. Our results indicate that the incidence of NMA is 0.91%. Most (80) NMA revealed only one mitotic figure, whereas some (20) NMA revealed more than one mitotic figure. Most NMA (89) showed mitotic activity in the upper portion of the nevus, whereas some (11) showed mitotic activity in the lower portion of the nevus. NMA patients were of younger age than the CN patients (P = 0.0019). Compared with CN, the NMA were more likely to be from the extremities (P = 0.0113) or head and neck (P = 0.0237) and less likely to be from the trunk (P < 0.001). The NMA were also more likely to show histologic features suggesting a congenital onset (P < 0.001) and were more likely to be Spitz nevi (P = 0.0185). Compared with the CN, the NMA were more often reexcised (P = 0.0073) and more often, there was residual nevus in the reexcision specimen (P = 0.13), although the latter finding was not statistically significant. Anecdotally, 2 of our NMA were identified adjacent to invasive melanomas; however, on clinical follow-up, we were unable to detect any increased incidence of melanoma.     

An assessment of the CDKN2A variant Ala148Thr as a nevus/melanoma susceptibility allele

Melanocytic nevi are the most potent risk factors for melanoma yet identified. Variation in the nevus phenotype within a population is predominantly genetically determined. Genes that determine nevus expression may therefore act as low penetrance melanoma susceptibility genes. Rare germline mutations in CDKN2A predispose to melanoma and appear to be nevogenic, although the correlation between nevus phenotype and mutation status is poor. It is plausible that more common CDKN2A variants may influence both melanoma susceptibility and nevus susceptibility. Ala148Thr is a G to A missense polymorphism of CDKN2A, which is found in 4%-6% of the general population. We have investigated the role of Ala148Thr as a low penetrance melanoma or nevus susceptibility allele in two separate groups of individuals. The first was a sample of 488 adults recruited from 179 families of patients with the atypical nevus phenotype and/or a family history of melanoma, and the second was a population-based sample of 599 women. Similar prevalences of Ala148Thr (4.9% and 5.2%) were found in both samples but significant variation in the prevalence of the polymorphism was seen across geographic areas within England. There was no association between Ala148Thr status and nevus number or history of melanoma, and therefore the results did not support the hypothesis that the Ala148Thr variant is a low penetrance melanoma or nevus susceptibility allele. A significant protective role of Ala148Thr on the number of atypical nevi was observed in the family sample (mean of 1 atypical nevus in those with the allele and 3.5 nevi in those without, p = 0.02). After allowing for potential confounders this was not evident in the population-based sample.     

Dysplastic nevi and the dysplastic nevus syndrome.

Patients with all the clinical features of FDNS but no family history of multiple abnormal nevi or melanoma can be compared with patients with neurofibromatosis due to a spontaneous mutation of the gene in utero. Whether or not such patients are in fact genetically identical to patients with FDNS and share their high risk of malignant melanoma remains to be determined. An isolated dysplastic nevus alone is not an adequate definition of SDNS, because current data are insufficient to show that its presence correlates with a uniquely high risk of melanoma when compared with other known risk factors. Until more specific tests for the FDNS gene become available, the diagnosis of SDNS must be made on the basis of close clinical and histopathologic resemblance to FDNS. Patients who present as adults with one or a few dysplastic nevi are best not labeled as having SDNS, because that label implies a genetic identity with FDNS that is probably not true and that deflects attention from other risk factors that are at least as important in estimating individual risks of developing melanoma.     

对色素痣恶变几个问题的探讨

收集７０例有完整记录的ＭＭ临床及病理资料，对哪些色素痣易恶变？普通后天性痣（ＡＮ）是否易恶变以及组织病理对诊断色素痣恶变的意义等进行探讨。我们认为：１．色素痣恶变的诊断有赖于对病史的正确采集和分析，仅根据病理上有痣细胞的证据，尚不足以正确判断部分ＭＭ是否源于色素痣；２．除已获一致意见的先天性巨痣、发育不良性痣易恶变外，先天性小痣（ＣＳＮ）也易恶变；３．ＡＮ恶变尚缺乏确切资料。