免疫组化在鉴别皮脂腺瘤和基底细胞癌中的应用

目的:探讨免疫组化在鉴别皮脂腺瘤和基底细胞癌(BCC)中的意义。方法:对31例皮脂腺瘤和31例结节型BCC患者标本分别行常规苏木精-伊红(HE)染色和免疫组化染色,并观察其结果。结果:免疫组化示31例皮脂腺瘤患者上皮抗原(EA)均为阴性;上皮膜抗原(EMA)在导管及成熟皮脂腺细胞中均呈阳性表达;24例雄激素受体(AR)呈阳性表达,余7例均为阴性;D2-40阳性表达28例,阴性3例。而结节型BCC患者中30例EA阳性,1例阴性;EMA阳性4例,阴性27例;AR阳性表达15例,阴性16例;D2-40 5例灶状阳性,余26例均阴性。结论:免疫组化示皮脂腺瘤患者EA阳性、EMA阴性和D2-40阳性,可较好地与结节型BCC相鉴别。     

先天性皮脂腺瘤恶变

报告1例先天性皮脂腺瘤恶变。患者女，56岁。左上眼睑结节56年。皮肤科检查：左上眼睑一0.9 cm×0.9 cm黄褐色丘疹，质硬，表面结痂，边缘少许渗出，边界清楚；剥除表面痂皮后可见红色糜烂面。皮损组织病理检查：肿瘤由多个大小不等的分叶状团块组成，肿瘤团块由基底样细胞和少量皮脂腺细胞构成。免疫组化：上皮特异抗原（Ber-EP4）（-）、癌胚抗原（CEA）（-）、上皮膜抗原（EMA）（+）、雄性激素受体（AR）（+++）、p53（+++）、增殖核抗原（Ki-67）(20%+)。诊断：先天性皮脂腺瘤恶变为皮脂腺癌。予手术扩大切除肿瘤，目前术后随访中。     

皮脂腺痣并发小汗腺汗孔癌1例

患者男,39岁。左侧头皮、面部丘疹、结节、斑块39年,部分菜花样隆起1年。皮损组织病理检查:面部前额斑块病理片显示表皮角化过度,乳头瘤样增生,真皮层皮脂腺明显增生。菜花样增生物病理片示真皮可见一个或多个上皮肿瘤细胞团,呈巢索状;肿瘤细胞团内见多角形、核位于细胞中央的的鳞状细胞样瘤细胞和含丰富的糖原且细胞膜清楚的浅染瘤细胞,核分裂相多,有病理性核分裂;瘤细胞浸润真皮及皮下,可见局灶有导管分化。免疫组化提示肿瘤结节混合性CK(细胞角蛋白)阳性,肿瘤内导管结构EMA(上皮膜抗原)强阳性,PAS染色可见胞浆内糖原染色阳性。根据临床资料、组织病理及免疫组化诊断为皮脂腺痣并发小汗腺汗孔癌。     

巨大皮肤混合瘤

报告1例鼻部巨大皮肤混合瘤。患者男,72岁。鼻根部皮下结节4年,皮损组织病理检查示:肿瘤呈结节状生长,有边界,但无明显包膜、纤维黏液背景中可见分化成熟的脂肪、汗腺导管、肌上皮及角化鳞状上皮多种成分,阿辛蓝染色阳性,免疫组化:癌胚抗原(CEA)(+),上皮膜抗原(EMA)(+),细胞核增殖抗原(Ki-67)(5%+),S-100蛋白(+),诊断皮肤混合瘤手术切除肿瘤。     

烫伤后表皮内皮脂腺增生

报告1例患有多囊卵巢综合征的16岁女性患者,在背部烫伤后形成的色素减退斑基础上出现多发性淡红色丘疹,丘疹组织病理显示表皮内有较多成熟皮脂腺,在表皮中下层呈水平方向排列,其上方棘层轻度肥厚.PAS染色可见表皮内增殖的棘细胞部分呈阳性,而成熟的皮脂腺细胞呈阴性.免疫组化上皮膜抗原(EMA)染色见表皮内成熟皮脂腺强阳性而角质形成细胞阴性,细胞角蛋白(CK)染色见表皮内成熟皮脂腺及角质形成细胞广泛阳性,雄激素(AR)染色见表皮内成熟皮脂腺细胞核广泛呈阳性;而癌胚抗原(CEA)和S-100蛋白染色为阴性.根据患者病史、临床表现和组织病理特征,建议命名为"烫伤后表皮内皮脂腺增生".     

上皮样肉瘤

报告1例上皮样肉瘤.患者男,19岁.右侧臀部出现结节并渐增多伴破溃4个月来诊.皮损组织病理检查显示真皮及皮下组织内有一肿瘤浸润,瘤细胞由上皮样细胞和梭形细胞构成,部分细胞有异形性,瘤团内见小的坏死灶.免疫组化染色显示肿瘤细胞表达角蛋白(CK)和波形蛋白(VIM),而不表达CD34、平滑肌肌动蛋白(SMA)、上皮膜抗原(EMA)、S-100蛋白及CD68.患者的临床表现、组织病理改变及免疫组化染色均符合上皮样肉瘤的特点.     

上皮样肉瘤

报告1例跖部上皮样肉瘤.患者男,40岁.右足跖部结节2年,溃疡4～5个月.皮肤科检查:右足跖中央一5 cm×2 cm、深约1 cm的溃疡,周边少许肉芽样组织生长.皮损组织病理检查:真皮中下部可见栅状肉芽肿样瘤细胞团块,中央有坏死表现,周边主要由上皮样细胞和梭形细胞组成,核分裂象增多.免疫组化染色显示肿瘤细胞表达细胞角蛋白(CK)、上皮膜抗原(EMA)、波形蛋白(vimentin)和CD34,而不表达CD31和S-100蛋白.患者的临床表现、组织病理改变及免疫组化染色均符合上皮样肉瘤的特点.     

细胞角蛋白阴性的上皮样肉瘤

报告1例细胞角蛋白（CK）阴性的上皮样肉瘤。患者男，40岁。左前臂结节2年，渐增多8个月伴破溃1个月来诊。皮损组织病理检查显示真皮内有一环状肿瘤团块，团块由两种形态的细胞构成，一种细胞数量多、形态多样、胞质丰富。数量少的细胞呈梭形，分布于肿瘤边缘。免疫组化染色显示肿瘤细胞表达上皮膜抗原（EMA）、波形蛋白（vimentin）和CD34，而不表达CK，CD68和结蛋白（desmin）。患者的临床表现、组织病理改变及免疫组化染色均符合上皮样内瘤的特点。     

伴皮脂腺增生的结缔组织增生性毛发上皮瘤一例

【摘要】 患者男,67岁,因头顶部皮损1年余来院就诊。体检：头顶部一淡红色环形斑块,约1.5 cm × 1cm,中央凹陷,边缘见淡黄色丘疹样突起,表面无毛发生长。皮损组织病理检查：表皮轻度增生,表面部分区域凹陷,真皮内见多个皮脂腺融合增生;真皮浅层见较多条索状嗜碱性上皮细胞及角囊肿,周围胶原纤维明显增生。免疫组化结果：CD34阳性（毛源性间质）,上皮膜抗原、细胞角蛋白20阳性,bcl?2、P53、CD56、Ⅳ型胶原纤维均阴性,增殖指数Ki67 2% ~ 5%。病理诊断：结缔组织增生性毛发上皮瘤伴皮脂腺增生。     

栅栏状包膜神经瘤七例分析

目的 探讨栅栏状包膜神经瘤的临床和组织病理特点.方法 回顾性分析7例栅栏状包膜神经瘤的一般情况、临床表现和组织病理表现.结果 7例患者平均发病年龄32岁(22～41岁),男女比例为2∶5.皮损均为单发孤立的小丘疹,质地由软到韧,呈皮肤颜色、红色或黄白色,均无自觉症状.组织病理表现为真皮内界限清楚、有包膜的良性肿瘤,以Schwann细胞增生为主,呈束状排列,肿瘤组织间可有人工裂隙.免疫组化检查肿瘤细胞S100抗体阳性,平滑肌肌动蛋白抗体阴性;上皮细胞膜抗原抗体在肿瘤包膜阳性.结论 栅栏状包膜神经瘤主要依靠组织病理诊断.临床上需要与神经鞘瘤、神经纤维瘤及平滑肌瘤等鉴别.     

Sebaceoma and related neoplasms with sebaceous differentiation: a clinicopathologic study of 30 cases

The classification of benign sebaceous neoplasms has been challenged both by the assertion that sebaceous adenomas are really carcinomas and by difficulties in drawing the boundaries between sebaceomas and other lesions. We performed a clinicopathologic study of 30 cases of basaloid neoplasms with sebaceous differentiation, excluding cases of definite sebaceous carcinoma with severe nuclear atypia invading deep within the subcutaneous tissue and those of ocular sebaceous carcinoma. We tried to classify sebaceous neoplasms in six categories with defined histopathologic criteria. All the neoplasms were characterized by aggregations of basaloid cells admixed with sebocytes and sebaceous duct-like structures located in the dermis with or without connection to the epidermis. The categories were 1) sebaceoma (14 cases); 2) trichoblastoma with sebaceous differentiation (3 cases); 3) apocrine poroma with sebaceous differentiation (2 cases); 4) low-grade sebaceous carcinoma (6 cases); 5) sebaceous carcinoma (4 cases); and 6) basal cell carcinoma with sebaceous differentiation (1 case). The sebaceoma was further subclassified as classic type (12 cases) or verruca/seborrheic keratosis type (2 cases). Although most sebaceomas can be distinguished from other lesions, there are problematic cases. We discuss the histopathologic diagnostic problems associated with sebaceoma and also argue in favor of the concept of sebaceous adenoma.     

Sebaceous neoplasm with reticulated and cribriform features: a rare variant of sebaceoma

Troy and Ackerman defined the term sebaceoma (Am J Dermatopathol 1984: 6: 7-13) as benign neoplasm of basaloid cells with varying numbers of mature sebocytes. Steffen and Ackerman (Neoplasms with sebaceous differentiation. Philadelphia: Lee and Febiger, 1994: 401-425) illustrated many examples of sebaceoma, two of which had a reticulated and cribriform pattern. We report a case of sebaceoma from the scalp of a 52-year-old white female. Histologically, it displayed reticulated and cribriform basaloid epithelial islands. This is the third reported case of sebaceoma, to our knowledge, with these unusual features.     

Sebaceous mantleoma (mantle adenoma): reappraisal of the myth of the problematic benign neoplasm with sebaceous mantle differentiation

Few cases of a true benign neoplasm with sebaceous mantle differentiation have been reported, and little is known about this tumor. Herein, we present a rare case of the neoplasm called sebaceous mantleoma, along with a comparison of the histology and immunoprofile with those of normal sebaceous mantles. A pedunculated polyp occurred on the scalp of a 51‐year‐old woman. Histopathologically, the tumor showed lobulated epithelial‐mesenchymal units that were separated from the normal dermis by clefts. The lesion was composed of cords and columns of basaloid cells containing a few mature sebocytes, with a focal connection to infundibulocystic structures as well as dense fibrotic or fibromyxoid stroma. Immunohistochemically, androgen receptor, estrogen receptor, and CD117 were partially positive for the tumor, and CD8 (C8/144B) and epithelial membrane antigen were focally positive. Additionally, cytokeratin 20‐positive Merkel cells were individually admixed in the tumor nests as well as in normal sebaceous mantles. This case report reveals the characteristic histology and immunoprofile of this problematic benign neoplasm and helps to understand this entity.     

Spatial analysis of p63, K5 and K7 defines two groups of progenitor cells that differentially contribute to the maintenance of normal sebaceous glands,extraocular sebaceous carcinoma and benign sebaceous tumors

The histogenesis of extraocular sebaceous carcinomas is – in contrast to ocular sebaceous carcinomas – unclear, and information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce. This study attempts to elucidate the histogenesis of sebaceous tumors, using multicolor immunofluorescence stainings to analyze 21 cases of sebaceous tumors (six each of extraocular sebaceous carcinoma, sebaceous adenoma and sebaceoma, and three cases of steatocystomas) and eight cases of normal sebaceous glands for p63, several keratins, androgen receptor, adipophilin, epithelial membrane antigen (EMA) and Ki‐67. The data of this observational study provide evidence for the existence of two subpopulations of progenitors in normal sebaceous glands: (i) p63⁺ K5⁺ progenitors which generate the K10⁺ luminal cells of sebaceous ducts; and (ii) p63⁺ K5⁺ K7⁺ progenitors which finally generate K7⁺ adipophilin⁺ EMA⁺ sebocytes. Without exception, all types of sebaceous tumors contained p63⁺ K5⁺ cells. Furthermore, these tumors showed a cellular hierarchy and differentiation to adipophilin⁺ and/or EMA⁺ mature sebocytes and to K10⁺ ductal cells through intermediary cells. Notably, a considerable number of sebaceous tumors lack the K7 pathway of cell maintenance in the normal sebaceous lobule. Based on our data, we propose a cellular algorithmic model of the hierarchy of normal sebaceous glands and of sebocytic tumors in which p63⁺ K5⁺ cells play a major role.     

Progressive differentiation of human sebocytes in vitro is characterized by increasing cell size and altering antigen expression and is regulated by culture duration and retinoids

Abstract Increasing cell size, lipid accumulation, and altered antigen expression are features of sebaceous differentiation in vivo. Enhanced lipid synthesis with progressive differentiation is also present in cultured human sebocytes. This study was conducted to investigate the evolution of cell size and antigen expression of human sebocyles with progressive differentiation in vitro. Subconlluent human sebocyte cultures were examined for sebocyte differentiation evaluated on cytocentrifuge preparations by light microscopy and classified in stages according to morphological criteria described for sebocytes in vivo. Rates of 5.1 ±2. 2% undifferentiated sebocytes. 29.2 ±4.9% early differentiated, 20.7 ±4.1% advanced differentiated, 37.6±6.4% fully differentiated, and 5.9± 1.9% mature sebocytes were calculated in secondary cultures. The size of cultured sebocytes measured by computer-assisted planimetry significantly increased with progressive differentiation up to 4-5.5 times. The low rates of mature sebocytes and the only moderate increase of their size with progressive differentiation indicate an incomplete terminal differentiation in vitro. Sebocytes were subsequently stained with a series of monoclonal antibodies (mAb) to determine antigen expression using the alkaline phosphatase anti-alkaline phosphatase technique. The number of sebocytes labeled with the anti-keratin mAb CK8.12 and KLI, and the mAb 34DII (82 kD protein) increased with progressive differentiation; significant differences were found after comparing early and advanced differentiated sebocytes. Sebocytes were positively stained with the anti-keratin mAb 6BIO (K 4). RPNI162 (K 7), CK.I3 (K 13), RPNI165 (K 19). CK.8.60, and the mAb 115F5 (MAM-6c). OM-I (sebaceous gland antigen), and 24F10 (basic polypeptides) only at late-stage differentiation. The expression of keratins 4, 7, 13, and 19 was confirmed by gel electrophoresis and immunoblotting. The data obtained were used to study the effects of the duration of cultivation and of the retinoids isotretinoin and tretinoin on sebocyte differentiation in vitro. Subcultivalion of sebocytes upregulaled, and treatment with isotretinoin but not with tretinoin downregulated labeling with mAb which recognize indicating progressive and late-stage differentiation.     

Intraepidermal benign sebaceous neoplasm: apocrine poroma (hidroacanthoma simplex type) with extensive sebaceous differentiation with sebaceoma‐like features

We herein report a patient who clinically presented with a yellowish, flat plaque that histopathologically showed a benign lesion mainly composed of intraepidermal basaloid nests with sebaceous differentiation. This lesion was considered to be fundamentally apocrine poroma (hidroacanthoma simplex type) with sebaceous differentiation. Nests composed of typical poroid cells were seen, and the results of immunostaining for lumican supported this diagnosis and excluded the possibility of clonal seborrheic keratosis. The sebaceous differentiation in apocrine poromas mostly occurs in Pinkus type lesions, and is usually seen in only part of the lesions, as solitary, mature sebocytes within the poroma nests. However, our apocrine poroma case was unique not only in that sebaceous differentiation occurred in the hidroacanthoma simplex type, but also in that it was observed extensively (approximately 60% of the nests). We therefore called this lesion an ‘intraepidermal benign sebaceous neoplasm’. Although it may be hard to differentiate sebaceous germinative cells (seen in sebaceoma) from poroid cells, in this case, some poroma nests could be judged to neighbor or contain the sebaceoma‐like areas. Therefore, the presented apocrine poroma was considered to have some features of (intraepidermal and dermal) sebaceoma.     

Relationship of sebaceous cell stage to growth in culture

The maturational stage at which sebaceous epithelial cells are irreversibly committed to autolysis has not been determined in a biologic system. The purpose of these experiments was to determine the relationship of sebocyte maturation to their ability to grow in culture. Single cell suspensions from adult rat preputial glands were prepared, and sebocyte stages were classified using lipid staining as one criterion of maturation. Cells were subjected to one-step, isokinetic discontinuous density gradient centrifugation in Percoll. Cells were cultured on 3T3 feeder layers in an epithelial cell medium containing 20% fetal calf serum, growth factors, and antibiotics. Growth in culture occurred from sebocytes in all gradient fractions. The least growth was found from cells in the lightest density fraction (1.020), which contained sebocytes with the most lipid, i.e., the most mature. Over fivefold more growth occurred from cells in the most dense fraction (1.080), which contained undifferentiated and immature sebocytes. Cell growth in culture was then correlated with the type of sebocyte in each fraction plated. Although cell growth in culture correlated significantly with the number of undifferentiated cells (r2 = 0.460), epithelial colonies were found in the absence of discernible undifferentiated cells in most fractions. Growth in culture correlated much better with the number of early plus mid-differentiated sebocytes (r2 = 0.702). These data suggest that, whereas mature sebocytes are not capable of attachment/proliferation, early differentiation of sebocytes is compatible with retention of the capacity to proliferate. If this property is shared by human sebocytes, it would contribute to the intransigence and diversity of acne-form lesions.     

Assessment of Cellular Proliferation of Sebaceous Neoplasms by AgNOR Counts and Immunohistochemical Demonstrations of PCNA and Ki-67

We assessed cellular proliferation of sebaceous neoplasms by AgNOR counts and the immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) and Ki-67, using formalin-fixed and paraffin-embedded tissue specimens. We used three categories of sebaceous neoplasms: four cases of sebaceoma, three cases of basal cell carcinoma with sebaceous differentiation (BCSD), and seven cases of sebaceous carcinoma (SC). Significant differences were noted between SC and non-SC tumors (sebaceoma and BCSD) in AgNOR counts and semi-quantitative grading of PCNA and Ki-67 labelling indices (P<0.01). When a cut-off value of 6 was chosen, the AgNOR value discriminated SC from non-SC tumors with high specificity and sensitivity. When a cut-off value of 25% was chosen, PCNA and Ki-67 labelling indices also discriminated between these tumors. Significant differences were not observed between sebaceoma and BCSD with PCNA and Ki-67 labelling indices. AgNOR counts of BCSD were a little higher than those of sebaceoma, but the number of cases was too small to perform statistical assessment. We consider AgNOR counts and semi-quantitative grading of PCNA and Ki-67 labelling indices to be useful in differentiating SC from BCSD and sebaceoma.     

A case of sebaceoma with extensive apocrine differentiation

Apocrine differentiation is a rare event in sebaceoma, and only 3 cases have been reported. We report a case of sebaceoma with extensive apocrine differentiation on the scalp in a 73-year-old Japanese woman. The resected tumor was located entirely within the dermis and subcutis as a well-circumscribed, lobulated, solid, and partially cystic mass, measuring 35 mm at the largest diameter. Histopathologically, it was composed of uniform basaloid cells with clusters of sebocytes, squamous islands of ductal structures, and apocrine cells with apparent decapitation secretion. Nuclear atypia of all types of cells was inconspicuous, and mitotic figures were infrequent. We considered the lesion to be a sebaceoma with apocrine differentiation.