A comparative study of fluorescence in malignant melanoma and nevocellular nevus using a fluorescence microscope and formalin-fixed specimens

Fluorescence in malignant melanoma cells was investigated. The specimens from 18 cases of malignant melanoma and 26 cases of nevocellular nevus, which were fixed with formalin and embedded in paraffin wax, were studied by the fluorescence microscopic method. On the fluorescence microscope, the malignant melanoma cells emitted intense fluorescence from the cytoplasm. The nevus cells with large amounts of melanin granules showed moderate fluorescence. The tumor cells of melanoma in situ and nevus cells with few melanin granules emitted little fluorescence. Not only malignant melanoma cells but also nevus cells in the formalin fixed specimens had various degrees of fluorescence. Many cases of malignant melanoma emitted intense fluorescence, but this was rarely found in nevocellular nevus. This method is also useful in differentiating melanoma from nevocellular nevus.     

TRANSEPITHELIAL ELIMINATION OF NEVUS CELL NESTS

Three hundred and three biopsy specimens of nevocellular nevus were histologically examined from the point of view of the elimination phenomenon. Transepidermal elimination of nevus cell nests was observed in 6 cases. The incidence ratio of the elimination phenomenon was 5.4% in 111 nevi with junctional activity. There was a correlation between histological type of nevocellular nevus and patient age. With aging, the number of cases of both compound and junctional types tended to decrease, whereas the proportion of the intradermal type tended to increase. The elimination phenomenon may play an important role in the histological transition of nevocellular nevus with aging.     

THE INVOLVEMENT OF THE SEBACEOUS GLAND BY NEVUS CELLS

Two cases of nevocytic nevi with nevus cells in the sebaceous gland were described. In the first case, the nevus seems to have been acquired but in the second case it is apparently congenital. As the sebaceous glands were presumably embryonic when the nevus cells settled into the corium, the immigration of nevus cells into the sebaceous glands might occur at the same time. The possibility of elimination of sebaceous cells by nevus cells is also pointed out.     

Histopathologic spectrum of clinically atypical melanocytic nevi. II. Studies of nonfamilial melanoma

We studied the clinically most atypical pigmented lesion removed from each of 142 patients with newly diagnosed sporadic melanoma. The specimens were categorized as to the type of nevus, ie, junctional or compound, presence of congenital features, and degree of nuclear atypicality--presence of nuclear enlargement, nuclear pleomorphism, hyperchromatism, and prominent nucleoli--of intraepidermal nevomelanocytes. The frequency of nuclear abnormality was graded as 1 (rare cells), 2 (10% to 50% of cells), or 3 (greater than 50% of cells) for each nuclear parameter. Among all lesions, 42 (29.6%) were junctional nevi, 74 (52.1%) were compound nevi, and 14 (9.9%) were dermal nevi. Eighteen percent of the total were either dysplastic nevi (23 cases) or malignant melanoma in situ (three cases). Fourteen nevi (9.9%) had congenital features. There were 12 junctional and 39 compound nevi and one dermal nevus that exhibited nuclear abnormality, but only four junctional nevi compared with 19 compound nevi had sufficient atypia for a designation of dysplastic nevus. Only two nevi with congenital features demonstrated any nuclear abnormality, and these were clearly nondysplastic. Thus, among nevi surgically removed as the clinically most atypical lesion in this study, compound nevi were much more likely to demonstrate nuclear atypia (and dysplasia) than were other nevi, ie, junctional or dermal nevi, or nevi with congenital features.     

Malignant melanoma in children--case presentation and statistical analysis

Malignant melanoma is a well documented but rare occurrence in children. We reported a case of a 10-month-old girl with malignant melanoma arising in a giant congenital nevocellular nevus. A giant mole on the lumbar and gluteal legion had been present since birth. Six month later, a nodular legion within the giant nevus started to growth slightly. The skin nodule were widely excised and grafted. Histological examination showed a malignant melanoma. The tumor located only in dermis. An enlarged lymph node of her left inguinal was removed. The histology revealed metastases from the melanoma. She died of metastases eight months after removal of the primary tumor. To our knowledge, only 37 documented cases of malignant melanoma in children under fifteen years of age have been previously reported, to which we add our case. In Japan, two-thirds of childhood melanomas arise de novo, which are clinically and biologically analogous to adult melanomas. The other third arises in large congenital nevocellular nevus which likely lead to death within two to three years of diagnosis. A majority of at least half of malignant melanoma in large congenital nevocellular nervus arise in children under 10 years of age. ALM types of malignant melanoma which are common in adult are rare in childhood melanomas.     

Dysplastic melanocytic nevi in histologic association with 234 primary cutaneous melanomas

Dysplastic melanocytic nevi (DMN) are irregularly pigmented lesions characterized by (1) atypical melanocytic hyperplasia in a lentiginous epidermal pattern (AMHL), (2) one or more dermal mesenchymal changes, and (3) frequently a dermal nevocellular nevus. In order to determine an association between DMN and cutaneous melanoma, the dominant histologic feature of DMN (namely, AMHL) was sought in histologic contiguity with 234 primary melanomas. Of these 234 cases, 9 were lentigo maligna melanomas. Of the remaining 225 cases, 49 (21.8%) were associated with AMHL in the same histologic section as (but beyond the most lateral margin of) intraepidermal and invasive melanoma. AMHL was directly associated with the presence of dermal nevocellular nevi in histologic contiguity with melanoma, and a greater number of histologic slides with melanoma available for review. AMHL was inversely associated with nodular melanoma. Most of the AMHL cases were not associated with familial melanoma, but the total number of familial cases was low. The histologic association between AMHL and melanoma in one fifth of cases in this series supports the hypothesis that at least some cutaneous melanomas may have an origin in DMN.     

皮脂腺痣皮肤镜及反射式共聚焦显微镜特征分析

【摘要】 目的 探讨不同年龄患者皮脂腺痣的皮肤镜及反射式共聚焦显微镜特征。方法 2016年1 - 12月将武汉市第一医院皮肤科门诊经组织病理学确诊的83例皮脂腺痣患者,按年龄分成4组,采集、分析其皮肤镜及反射式共聚焦显微镜图像特征。结果 < 10岁组21 例,皮损在皮肤镜下表现为橘色背景下独立分布、较为一致的黄红色、球块状结构,似鹅卵石样排列,伴血管增生、扩张;反射式共聚焦显微镜下可见皮脂腺发育不全, 仅见幼稚毛囊。10 ~ 20岁组28例,皮肤镜下可见聚集分布、与毛囊无关、大小不同的黄色圆形、卵圆形结构,伴毛细血管扩张;反射式共聚焦显微镜下可见,真表皮交界处及真皮浅层葡萄串样皮脂腺结构,中央为管状/柄样结构,外周为簇集分布、鱼籽/蛙卵样增生的皮脂腺小叶,其上方表皮往往呈疣状/乳头瘤样增生。21 ~ 59岁组30例,影像学表现同10 ~ 20岁组。≥ 60岁组4例,影像学特征主要为乳头瘤样增生。结论 皮脂腺痣是一种动态发展的疾病,不同年龄阶段影像学表现不尽相同;在皮肤镜及反射式共聚焦显微镜下均具有特征性结构,可作为有效的无创性诊断方法。     

恶性黑素瘤Survivin和C-erbB-2的检测及其意义

目的检测恶性黑素瘤的Survivin和CerbB2及其与临床病理特征的关系。方法应用免疫组化SP法检测72例恶性黑素瘤、61例瘤旁组织、22例黑色素细胞痣和20例正常皮肤组织中Survivin和CerbB2蛋白。结果恶性黑素瘤Survivin蛋白阳性率为59.7%,明显高于瘤旁组织3.3%,黑色素细胞痣4.5%和正常皮肤组织0%(P均<0.01)。Survivin阳性与转移状况和组织学分级有显著相关性。恶性黑素瘤无转移组和Ⅰ级分别明显低于转移组和Ⅱ,Ⅲ,Ⅳ级(P均<0.05)。恶性黑素瘤CerbB2蛋白阳性率为68.1%,明显高于瘤旁组织8.3%,黑色素细胞痣5.6%和正常皮肤组织2.8%(P均<0.01),CerbB2阳性与临床病理特征无明显相关性。Survivin在CerbB2阳性和阴性患者中阳性率分别为69.4%和39.1%,两者间有显著性差异(P<0.05)。结论Survivin和CerbB2蛋白在恶性黑素瘤组织中水平上调,提示两者对恶性黑素瘤发生发展起重要作用。恶性黑素瘤中Survivin蛋白水平与肿瘤转移和组织学分级有关,Survivin可能为临床判断恶性黑素瘤转移和评估预后的有用指标。     

皮脂腺肿瘤凝集素亲合组化研究

本研究采用１７种生物素化的凝集素，应用ＡＢＣ法研究了２３例正常皮肤和２２例皮脂腺良、恶性肿瘤的肿瘤细胞凝集素受体的定位及分布，发现ＬＣＡ在皮脂腺癌的阳性率较高；正常皮脂腺、皮脂腺痣、皮脂腺增生、皮脂腺腺瘤可见胞膜及胞浆的海绵、网状着染；皮脂腺癌中胞浆失去这种规则着染，着染形状及分布极不规则，说明在皮脂腺恶性转化过程中，细胞表面复合糖糖基及细胞的正常结构发生了明显的变化。     

Multiple Hamartomas Associated with Intracranial Malformation

We examined a newborn infant with multiple hamartomas, including an epidermal nevus syndrome and a giant pigmented congenital nevocellular nevus, associated with other structural developmental abnormalities such as nevus flammeus, vascular malformation, cutis aplasia congenita of the scalp, cartilage hamartoma, and a lipodermoid of the conjunctiva. This child had a significant brain malformation, diagnosed by sonography and computerized tomography, consisting of a significant enlargement of the left hemisphere not associated with asymmetry of the skull or facial bones. We suggest a careful investigation of the intracranial structures by computerized tomography and/or ultrasonography in case of either extensive linear nevus sebaceous sequence and/or giant pigmented nevocellular nevus.     

Differing lectin-binding patterns of malignant melanoma and nevocellular and Spitz nevi

Summary The lectin-binding patterns of primary malignant melanoma, nevocellular nevus, and Spitz nevus were studied on formalin-fixed, paraffin-embedded sections using a series of biotinylated lectins —concanavalin A (ConA), Ricinus communis agglutinin-1 (RCA1), dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), maclura pomifera agglutinin (MPA), peanut agglutinin (PNA), wheat germ agglutinin (WGA), and Ulex europeus agglutinin-1 (UEA1)- and employing the avidin-biotin-peroxidase complex method. In nevocellular and Spitz nevi, all of the nevus cells were positively stained with ConA and RCA1. No positive staining was observed, however, with the other lectins and no change in binding patterns occurred following neuraminidase pretreatment. In malignant melanoma, all of the melanoma cells were positively stained with ConA and RCA1, and some were also stained with MPA, PNA, and WGA. Inaddition, DBA, SBA, MPA, PNA, and WGA labeled all of the melanoma cells after neuraminidase pretreatment. No positive staining was observed with UEA1 despite neuraminidase pretreatment. The present results showed that malignant melanoma and nevocellular and Spitz nevi have different lectin-binding patterns and different responses to neuraminidase pretreatment. We, therefore, belive that the lectin staining on paraffinembedded sections can be a useful probe for the differentiation of these diseases.     

Melanoma associated with a dysplastic nevus: report of two cases with unusual sebocyte-like melanocytes in the nevus part of the lesion

We present two cases of melanoma arising in a dysplastic nevus that contained intradermal sebocyte-like melanocytes characterized by a scalloped dark-staining nucleus surrounded by the pale multivacuolated cytoplasm imitating sebaceous differentiation. Both patients were women, aged 49 and 55 years. Location included the back and temporal area. Microscopically, both cases had the following features in common: the melanoma in situ, which was of the superficially spreading type, was associated with a dysplastic compound nevus, in which the sebocyte-like cells were identified in the intradermal nevus part of the lesion. The sebocyte-like cells comprised a minor component but were immediately recognizable and appeared as cells with multivacuolated neoplasm and scalloped nuclei arranged in nests. Some contained melanin in the cytoplasm. They stained positively for S-100 protein and melan A but were EMA and HMB-45 negative. The conventional part of the nevi demonstrated the same phenotype, with the exception of the melanocytic nests located at the dermoepidermal junction that were HMB-45 positive. The cases are discussed in the context of the pertinent literature.     

Coordinate expression of membrane type-matrix metalloproteinases-2 and 3 (MT2-MMP and MT3-MMP) and matrix metalloproteinase-2 (MMP-2) in primary and metastatic melanoma cells

Expression of MMP-2 in melanoma cells has been demonstrated to be involved in the degradation of extracellular matrix during melanoma growth and to correlate with later melanoma metastasis. MMP-2 is considered to be activated by membrane-associated matrix metalloproteinases (MT-MMPs). To know whether MT-MMPs are involved in the activation of MMP-2 in melanoma cells, immunohistochemical studies were performed in primary and metastatic melanoma by use of the antibodies for MT1-MMP, MT2-MMP and MT3-MMP. Expression of MT1-MMP, MT2-MMP, MT3-MMP and MMP-2 in nevocellular nevus (n = 5), dysplastic nevus (n = 2) and juvenile melanoma (n = 3) was undetectable or detected in only a few cells. Superficial spreading melanoma (SSM) (n = 3) and acral lentiginous melanoma (ALM) (n = 3) showed a moderate expression of MT1 approximately 3-MMP. In nodular melanoma (NM) (n = 2) and metastatic melanoma (n = 3), MT1 approximately 3-MMP was more intensely expressed. Double immunofluorescence demonstrated a consistent colocalization of MT2-MMP/MMP-2 and MT3-MMP/MMP-2 in the NM and metastatic melanoma cells. The colocalization of MT2,3-MMP and MMP-2 in nodular and metastatic melanoma cells suggests that MT-MMPs and MMP-2 co-operate in the invasive and metastatic process of melanoma cells.     

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。     

Melanoma within naevus spilus: 5 cases

BACKGROUND: Nevus spilus is defined as café-au-lait macules with dark maculopapular speckles. Histologically, it has the aspect of lentigo associated with nevocellular nevus. There are 3 types of nevus spilus: small or medium-sized (<20 cm), giant and zosteriform. Malignant transformation of nevus spilus is rare. PATIENTS AND METHODS: We analyzed the cases of 5 patients presenting melanoma within nevus spilus as well as 20 published cases. The evaluation criteria were: for nevus spilus: size, type, topography, age of onset and presence of dysplastic nevi within the nevus spilus; for melanoma: clinical aspect, histological type, thickness, level and age at diagnosis. The presence of other risk factors for melanoma was noted. RESULTS: The 14 women and 11 men had a mean age of 49 years at melanoma diagnosis. Type of nevus spilus was: small or medium-sized (15 cases), zosteriform (6 cases) and giant (4 cases). Only 3 nevi spili were<4 cm in diameter. Nevus spilus was present since birth (11 cases), childhood (7 cases), after the age of 20 years (3 cases) and was unspecified in 4 cases. Three of our five patients had other risk factors for melanoma. Two patients were presenting 2 melanomas within nevus spilus. The histological type of melanoma was not specified in 8 cases but SSM was the most common type (13 cases). Median Breslow thickness was 1.25 mm (0.27 to 8 mm) for the 19 cases in which it was specified. CONCLUSION: The following criteria appeared to be associated with risk of developing melanoma in nevus spilus patients: nevus spilus present since birth, nevus spilus over 4 cm in diameter, and giant or zosteriform nevus spilus. Development of melanoma within nevus spilus is a rare event. Consequently, guidelines for follow-up of nevus spilus cannot be defined. However, follow-up is recommended, and in particular, self-examination.     

Ten cases of sebaceous carcinoma arising in nevus sebaceus

Although nevus sebaceus is known to develop various types of secondary neoplasms, it rarely causes carcinoma and only 14 cases of secondary sebaceous carcinoma have been reported. In this study, 10 cases of sebaceous carcinoma arising in nevus sebaceus were collected. The clinicopathological features and results of immunohistochemical examinations with adipophilin, perilipin and p53 were summarized. Sebaceous carcinoma arising in nevus sebaceous predominantly occurred on the scalp (8/10) of elderly women (mean age, 67.7 years). No case was associated with Muir–Torre syndrome. We found several pathological features of sebaceous carcinoma; that is, made up mainly of germinative cells, moderate nuclear atypia without pleomorphism and many mitoses (4–28/10 high‐power field). Adipophilin and perilipin antibodies highlighted lipid drops in the cytoplasm of the malignant cells in all cases. Overexpression of p53 was seen in all cases. In two cases there were coexisting benign‐looking sebaceous lesions at the periphery of the main cancer nodule, and in these lesions p53 showed low positivity compared with the clearly malignant area. There was co‐occurrence of another neoplasm in three cases with trichoblastoma, sebaceoma and syringocystadenoma papilliferum, respectively. All cases were treated by excision of the malignant lesion, with or without inclusion of the nevus sebaceus. In a follow‐up period of 1–7 years, there was no case of recurrence, lymph node metastases or distant metastases. With these specific pathological and immunohistochemical findings using adipophilin, perilipin and p53, we have to consider the possibility that there is a tendency to underdiagnose secondary sebaceous carcinomas in nevus sebaceus. These clinicopathological features of sebaceous carcinomas developing in the nevus sebaceus seem to indicate different biological entities from de novo sebaceous carcinoma.     

The sebaceous nevus as part of the Schimmelpenning-Feuerstein-Mims Syndrome--an obvious phacomatosis first documented in 1927

The sebaceous nevus is a common nevus and can be easily diagnosed because of its typical rough fatty surface due to its amount of sebaceous glands. In some rare cases, the sebaceous nevus is part of a genetic disorder, the Schimmelpenning-Feuerstein-Mims (SFM) syndrome. If the SFM syndrome is suspected, further investigation is necessary, because multiple organ involvement is highly likely. We suggest that diagnosis of the SFM syndrome is simple, considering the special linear arrangement of sebaceous nevi in cases of SFM syndrome.     

Behavior of pigment cells on lesions of the pigmented venus with vitiligo.

When vitiligo occurred on lesions of the pigmented nevus, the behavior of pigment cells in this nevus was investigated. Three cases of giant hairy nevi, seven cases of moles, three cases of Mongolian spots and eleven specimens in nine cases of halo nevi were used. Giant hairy nevi combining with vitiligo showed intensive decreases in nevus cells, particularly superficial A and B-type nevus cells. The epidermal dopa-positive melanocytes and melanin granules in the epidermis decreased, but still remained. On the other hand, moles in vitiligo showed an almost complete disappearance of epidermal dopa-positive melanocytes and melanin granules in the epidermis; nevus cells in the dermis decreased only slightly. Mongolian spots with vitiligo showed an epidermis similar to vitiligo, but the dermal melanocytes were hardly changed. Halo nevi exhibited an intensive decrease and degeneration of nevus cells and marked lymphocytic infiltration. Some of them showed disappearance of epidermal dopa-positive melanocytes and melanin granules in the epidermis. The characteristic findings of vitiliginous skin are mostly restricted to epidermis. In contrast, however, it is interesting to note that, on the lesions of nevocellular nevi with vitiligo, the dermis also exhibited some decrease and degeneration of nevus cells and lymphocytic infiltration.     

Sebaceous carcinoma arising in nevus sebaceus of Jadassohn: a clinicopathological study of five cases

The authors report a small series of sebaceous carcinoma developing in nevus sebaceus of Jadassohn (also known as organoid nevus) and analyze similar cases reported in the literature. All of our patients were females (age range 57-71 years; median 60 years) who had the organoid nevus on the scalp, face, or nuchal area, the rest of which was recognized clinically and/or histologically. All sebaceous carcinomas manifested unquestionable architectural (asymmetry, invasive growth) and cytological features of a carcinoma (cellular and nuclear pleomorphism, plentiful atypical mitoses, necroses en masse), demonstrated unambiguous sebaceous differentiation in the form of mature sebocytes, and lacked other differentiations. The sebaceous carcinoma was always accompanied by other benign or malignant adnexal lesions such as sebaceoma, syringocystadenoma papilliferum, syringocystadenocarcinoma papilliferum, trichoblastoma, tricholemmoma, desmoplastic tricholemmoma, or syringoma. In three cases, prominent mucinous metaplasia of sweat ducts and glands was seen. In two of these cases, sweat ducts exhibited hyperplastic changes. The analysis of the previously published material and our cases indicates that sebaceous carcinoma arising in organoid nevus has a female predilection and tends to occur in elderly patients. It may involve any site where nevus sebaceus typically occurs. Clinically, the tumor presents as a solitary nodule, ulcerated tumor, or mass, often with a recent history of rapid growth. It may arise alone, but it occurs more frequently as part of multiple benign and malignant adnexal tumors. The lesion does not seem to be associated with Muir-Torre syndrome. The rest of organoid nevus is usually recognized both clinically and microscopically, although large tumors may overgrow and mask the nevus. The tumor seems to be a low-grade carcinoma in terms of clinical behavior.