Seborrheic keratoses, solar lentigines, and lichenoid keratoses. Dermatoscopic features and correlation to histology and clinical signs

Evaluation of the three benign lesions discussed here form the basis for dermoscopic evaluation of other pigmented skin lesions. The features of seborrheic keratosis, including [figure: see text] the various forms of fissures, comedo-like openings, and milia-like cysts, often allow easy interpretation of seborrheic keratosis; however, similar structures are commonly associated with melanocytic neoplasms, notably congenital nevi. Understanding solar lentigo and its dermoscopy features allows for the appreciation of pigment networks common in lentiginous melanocytic nevi and melanoma. The lichenoid keratosis is the model for lichenoid inflammation elsewhere, notably in halo nevi, regressing melanoma, and other melanocytic neoplasms with significant host inflammatory reactions.     

Diagnostic tissue elements in melanocytic skin tumors in automated image analysis

In tissue counter analysis, digital images are divided into subregions (elements), and the digital information in each element is used for statistical analysis. In this study, we assessed the morphologic details of tissue elements that have turned out to be of diagnostic significance in the discrimination of benign common nevi and malignant melanoma. After creation of a data set based on a total of 12,000 cellular elements obtained from 100 benign common nevi and 100 malignant melanomas, classification and regression tree (CART) analysis was performed to differentiate between cellular elements of nevi and melanoma. In a second step, the slides were re-evaluated by the decision tree; cellular elements suggestive either for benign common nevi or for malignant melanoma were highlighted on zoomed images of the whole sections, and the individual elements were displayed in galleries. Eight groups of elements (so-called terminal nodes) seemed to indicate benign common nevi, whereas seven terminal nodes were suggestive for malignant melanoma. The elements of nodes suggestive for benign nevi largely contained nevus cells with amphiphilic cytoplasm intermingled with fibrillary material, whereas the elements of the nodes suggestive for malignant lesions often showed hyperchromatism, perinuclear halos, heavy pigmentation, or a lymphohistiocytic infiltrate. Tissue counter analysis automatically detects tissue elements that are in accordance with morphologic criteria used in conventional histopathology for diagnostic discrimination.     

Diagnostic imaging of melanocytic skin tumors

BACKGROUND: In tissue counter analysis, digital images are dissected into subregions (elements), and the digital information in each element is used for statistical analysis. The aim of this study was to test the applicability of tissue counter analysis and CART (Classification and Regression Tree) to the diagnostic discrimination of benign common nevi and malignant melanoma in dermatopathology. METHODS: Two hundred cases each of benign nevi and malignant melanoma were consecutively sampled. CART analyses of background versus tissue elements, cellular versus 'other' tissue elements and benign versus malignant cellular elements were performed. For diagnostic assessment, only the percentage of cellular elements suggestive for malignancy in each case was used. RESULTS: CART analysis led to a correct classification of 99% of background versus tissue elements, 96% of cellular versus 'other' tissue elements and 79.1% of benign versus malignant cellular elements. When the percentage of cellular elements suggestive for malignancy in each case was evaluated, 29.5 +/- 14% (range 4.1-62.4) 'malignant' elements were found in benign nevi (n = 200), in contrast to 75.9 +/- 13.9% (range 32.8-97.3) in melanoma (n = 200; z =-16.72, p < 0.001). It turned out that a threshold level of 52.51% provides a correct classification of 192 nevi and 186 melanoma out of 200 each (specificity 96%, sensitivity 93%, positive predictive value 95.9%). CONCLUSIONS: Tissue counter analysis combined with CART may be a useful method for diagnostic purposes in histopathology.     

Differences of expression of cytokeratin polypeptides in various epithelial skin tumors

Summary In normal skin, cytokeratin polypeptides are expressed in different cell-type-specific patterns, in the keratinocytes of the different epidermal cell strata as well as in different lateral epithelial domains. Using light microscopically controlled microdissection of defined regions from frozen sections of biopsies, we have prepared cytoskeletons of various benign and malignant keratinocyte-derived tumors of human skin and analyzed their cytokeratin polypeptide patterns by two-dimensional gel electrophoresis. Premalignant fibro-epitheliomas and basal cell epitheliomas display a relatively simple cytokeratin pattern (cytokeratins nos. 5, 14, 15, and 17). Pseudocarcinomatous hyperplasia, some squamous cell carcinomas, and a certain subtype of condylomata acuminata present a hair-follicle-like pattern (nos. 5, 6, 14, 16, 17). In addition to these components, variable, mostly low amounts of cytokeratins nos. 1 (M_r 68,000), and 11 are detected in most squamous cell carcinomas, in keratoacanthomas, verruca vulgaris, and another type of condylomata acuminata. In molluscum contagiosum, verruca plana, solar keratosis, and seborrheic keratosis, the cytokeratin expression is shifted more towards the normal epidermal pattern (polypeptides nos. 1, 2, 5, 10, 11, 14, 15 and traces of nos. 6 and 16 in the latter two tumors). No tumor-specific cytokeratins have been found. We conclude that keratinocyte-derived skin tumors contain various combinations of cytokeratins of the subset typical for normal keratinocytes of skin, but no cytokeratins typical for internal, simple epithelia. Different groups of tumors can be distinguished by their specific cytokeratin patterns. Possible applications of cytokeratin typing in clinical diagnosis are discussed.     

Dermoscopy Distinction of Eruptive Vellus Hair Cysts with Molluscum Contagiosum and Acne Lesions

Abstract: Eruptive vellus hair cysts are benign lesions that can be difficult to distinguish from other skin conditions, including molluscum contagiosum and acne vulgaris. Diagnosis can be corroborated with histopathology. We emphasize differing dermoscopy features to help distinguish eruptive vellus hair cysts from molluscum contagiosum or acne.     

GIANT CUTANEOUS HORN

A 53-year-old male presented with a giant cutaneous horn over the left leg. Cutaneous horn was excised and primary closure of the defect was done under spinal anesthesia. Histopathology showed underlying seborrheic keratosis. Cutaneous horn has been noticed on top of many clinical conditions of diverse etiology, such as actinic keratoses, wart, molluscum contagiosum, seborrheic keratoses, keratoacanthoma, basal cell and squamous cell carcinoma. We report a patient with giant cutaneous horn on the leg successfully treated by excision and wound closure.     

Melanocytes express 3G5 surface antigen

The 3G5-reactive ganglioside antigen (3G5 antigen) is expressed on the surface of various cell types including pericytes, pancreatic islet cells, thyroid follicular cells, and cells of the pituitary and the adrenal medulla. Expression on melanocytes has not yet been reported. We examined 148 5-microm cryosections of 12 normal skin samples and 45 skin tumors (21 melanocytic nevi, 8 malignant melanoma primaries, 4 metastases of malignant melanoma, 3 basal cell carcinomas, and 9 pigmented seborrheic keratoses) by triple fluorescence technique with the monoclonal antibody 3G5, DNA fluorochrome, and the anti-melanocytic antibody A103 (Anti-Melan-A). In normal skin, 3G5 reactivity was detected in epidermal melanocytes of 4 of 12 cases with 14.8 +/- 24.1% positive melanocytes; 20 of 21 nevi (72.2 +/- 29.1% positive nevus cells, mean +/- SD), 8 of 8 primary melanomas (83.9 +/- 12.3% positive melanoma cells), and 4 of 4 melanoma metastases (82.5 +/- 6.5% positive melanoma cells) expressed the 3G5 antigen. All tumor cells of investigated basal cell carcinoma or seborrheic keratosis were 3G5 negative. This is the first report of 3G5 antigen expression in melanocytes. The data demonstrate high expression of this ganglioside in the aggregated melanocytes of malignant or benign tumors but low or absent expression in singular melanocytes (normal epidermis, seborrheic keratoses) reflecting a different biologic state.     

Melanoma and seborrheic keratosis differentiation using texture features

Purpose: To explore texture features in two-dimensional images to differentiate seborrheic keratosis from melanoma.
Methods: A systematic approach to consistent classification of skin tumors is described. Texture features, based on the second-order histogram, were used to identify the features or a combination of features that could consistently differentiate a malignant skin tumor (melanoma) from a benign one (seborrheic keratosis). Two hundred and seventy-one skin tumor images were separated into training and test sets for accuracy and consistency. Automatic induction was applied to generate classification rules. Data analysis and modeling tools were used to gain further insight into the feature space.
Result and Conclusions: In all, 85–90% of seborrheic keratosis images were correctly differentiated from the malignant skin tumors. The features correlation_average, correlation_range, texture_energy_average and texture_energy_range were found to be the most important features in differentiating seborrheic keratosis from melanoma. Over-all, the seborrheic keratosis images were better identified by the texture features than the melanoma images.     

Expression of trichohyalin in dermatological disorders: a comparative study with involucrin and filaggrin by immunohistochemical staining

To investigate the function of trichohyalin during terminal differentiation of the skin, immunohistochemical studies were performed on trichohyalin and its related proteins, filaggrin and involucrin, the components of the cornified cell envelope. In skin disorders unrelated to tumours, weak trichohyalin expression was found in a few granular cells or in the horny layer of psoriasis, ichthyosis, keratosis pilaris, porokeratosis, chronic dermatitis and callus. Similar trichohyalin expression was found in epidermal tumours, such as seborrheic keratosis, actinic keratosis, Bowen's disease and well-differentiated squamous cell carcinoma. In follicular tumours, trichohyalin expression was positive in trichoepithelioma, keratotic basal cell epithelioma, proliferating trichilemmal tumour, trichilemmoma, pilomatricoma and keratoacanthoma. From comparative studies with filaggrin and involucrin, trichohyalin expression was co-localized with them in molluscum contagiosum, keratoacanthoma and pilomatricoma. From this study, trichohyalin is revealed to have close functional relationship with other markers of terminal differentiation as a precursor of the cornified cell envelope of the skin.     

Dysplastic nevus associated with seborrheic keratosis

Seborrheic keratosis is a common skin lesion which may coincidentally be associated melanocytic nevi. The authors describe a case of dysplastic nevus associated with seborrheic keratosis and discuss the clinical, dermoscopic, and histological findings of this association. They also discuss the association between seborrheic keratosis and other benign and malignant tumours.     

日光性雀斑样痣、脂溢性角化病及扁平苔藓样角化病皮肤镜特征专家共识

【摘要】 日光性雀斑样痣、脂溢性角化病及扁平苔藓样角化病是常见的良性表皮增生性疾病,其皮肤镜特征对于明确诊断、与其他皮肤肿瘤相鉴别、避免不必要的活检和手术以及动态监测皮损变化等都有一定帮助。本共识对这3种疾病的皮肤镜特征进行了总结。日光性雀斑样痣的皮肤镜特征主要为皮损边界清晰、虫蚀状边缘、模糊的色素网、指纹模式、棕色均质模式、假性网络。脂溢性角化病的皮肤镜特征主要为皮损边界清晰、粟粒样囊肿、粉刺样开口、脑回状模式、发夹样血管、摇晃试验中皮损整体移动。扁平苔藓样角化病的皮肤镜特征主要为胡椒粉样或颗粒模式以及周围可见日光性雀斑样痣、脂溢性角化病或光线性角化病的皮肤镜特征。     

Aminopeptidase M and dipeptidyl peptidase IV activity in epithelial skin tumors: a histochemical study

The activities of microsomal alanylaminopeptidase (APM EC 3.4.11.2) and of dipeptidyl dipeptidase IV (DPP IV EC 3.4.14.5) were histochemically studied in frozen sections of normal skin, seborrheic keratosis, basal cell carcinoma, solar keratosis, Bowen's disease and squamous cell carcinoma using amino acid- or peptide-4-methoxy-2-naphthylamides as specific chromogenic substrates. Compared to biochemical and immunohistochemical methods, the histochemical technique used in this study allows distinct localization of protease activity within the tumor tissue and the tumor-associated stroma. Strong APM activity was detectable only in the stroma of basal cell carcinoma, a result which reflects the particular tumor-stroma interaction of this semimalignant tumor. APM activity was not detectable in either healthy epidermis or the tumor parenchyma. Altered activity of DPP IV was found in the tumor cells as well as in the surrounding connective tissue: precancerous dermatoses and basal cell carcinomas had higher levels of DPP IV-activity than normal skin or benign seborrheic keratosis. Poorly differentiated malignant squamous cell carcinomas, however, showed no histochemically detectable DPP IV-activity at all. This result is in line with reports of decreased activity of this enzyme in cases of malignancy.     

Human monoclonal antibodies that distinguish cutaneous malignant melanomas from benign nevi in fixed tissue sections

Human monoclonal antibodies were generated by fusing a nonsecretory variant of murine myeloma cells with lymphocytes obtained from the lymph nodes of patients with metastatic cutaneous malignant melanoma. Two human IgG monoclonal antibodies, designated 2-139-1 and 6-26-3, were extensively studied for their patterns of binding to cells in 64 specimens of formalin-fixed, paraffin-embedded tissue sections. These comprised: 23 cutaneous and 2 ocular melanomas; 4 specimens of lentigo maligna; 27 benign nevi; 2 basal and 2 squamous cell neoplasms of the skin; and 4 specimens of normal skin. A direct avidin-biotin-immunoperoxidase staining method was used. Under these conditions, the antibodies reacted with variable intensity to all 18 primary cutaneous malignant melanomas, 5 metastatic cutaneous melanomas, and both ocular melanomas. Antibody 2-139-1 reacted with 1 of 4 specimens and 6-26-3 with 3 of 4 specimens of lentigo maligna. Two of 5 dysplastic nevi reacted with both antibodies, each with a smaller proportion of cells than with melanomas. There was no reactivity with the 22 other nevi representing a spectrum of histologic types or with normal melanocytes. Basal cell and squamous cell carcinomas of the skin also were not stained. These human monoclonal antibodies appear to be useful in distinguishing malignant melanomas from benign nevi, with the exception of dysplastic nevi, and from basal and squamous cancers of the skin in routinely prepared tissue sections. They may also help to identify the cytoplasmic antigens that are immunogenic in humans.     

Increased mast cell density in invasive melanoma

Mast cell participation in immune responses, tumor progression, and vascularization has been studied extensively in vitro . In situ investigation of mast cells in routinely processed tissues is hampered by difficulty in reliable detection of mast cells. We studied the tissue density of mast cells using a morphometric point-counting technique in 1 μm-thick, Giemsa-stained, tissue sections from epon-embedded samples of skin biopsies. This technique has been demonstrated to be an accurate and reproducible method for determining mast cell density.
Mast cell density in 15 cases of invasive melanoma was compared to that of 9 cases of benign melanocytic nevi and 4 cases of melanoma in situ . Mast cell density was greatest in invasive melanoma (mean density = 0.61 vol.%). The mean density of mast cells in nevi and in situ melanoma was 0.33 and 0.5 respectively. Six of 15 cases of melanoma had mast cell densities > 0.6, whereas mast cell density did not exceed 0.6 in any cases of melanoma in situ or benign melanocytic nevi (p < 0.02). Our findings confirm an increase in mast cell tissue density in some cases of invasive melanoma when compared to mast cell density in benign nevi and in situ melanoma.     

共聚焦激光扫描显微镜鉴别脂溢性角化病与鲍恩病

目的：探讨共聚焦激光扫描显微镜（CLSM）在脂溢性角化病与鲍恩病鉴别中的应用价值。方法选88例临床诊断为脂溢性角化病和18例临床诊断为鲍恩病的患者典型皮损做CLSM检查,然后取该处皮损行组织病理学检查。结果脂溢性角化病CLSM图像特征：全部有表皮脑回状结构,另有角蛋白充填的囊性包裹体,表皮突呈小梁状下延;基底层细胞排列呈条索状或放射状9例,基底层及真皮层可见折光性明亮的结构6例。鲍恩病CLSM图像特征：表皮中下层细胞灶状排列紊乱,体积较大,细胞形态不规则,有明显的异形,真皮浅层散在单个核细胞浸润。结论脂溢性角化病与鲍恩病在CLSM成像上有不同的特征性,CLSM可为二者的鉴别诊断提供帮助。     

Eccrine porocarcinoma arising in a seborrheic keratosis evaluated with dermoscopy and treated with Mohs' technique

A 78-year-old white woman returned for a routine 6-month skin cancer examination. She had a history of actinic keratosis and multiple basal cell carcinomas. She had no personal or family history of dysplastic nevi or melanoma. The patient was asymptomatic and unaware of any new or changing skin lesions. The patient had multiple lentigines, hemangiomas, and actinic and seborrheic keratoses on all sun-exposed areas. There were no less than 10 seborrheic keratoses on the right mid-back, and one was found to have a 1-cm, reddish nodule asymmetrically located within it (Figs 1 and 2). A clear papule on the left preauricular area was found on biopsy to be a basal cell carcinoma. The nodule on the back was still present 1 month later and it was felt that further evaluation was indicated. As melanoma has been reported to develop in seborrheic keratoses, we decided to examine the lesion using digital dermoscopy. With digital dermoscopy, a well-demarcated reddish nodule was asymmetrically located within a brown lesion. It blanched significantly with pressure. Within the nodule, there were dotted and irregular linear vessels (atypical vascular pattern; also known as polymorphous vascular pattern) and regular-appearing brown dots. Surrounding the reddish nodule, there were pale and pigmented, comedo-like openings, fissures, and ridges (brain-like appearance). Some of the follicular openings appeared to be within the wall of the nodule (Figs 3 and 4). Comedo-like openings, fissures, and ridges are primary dermoscopic criteria for the diagnosis of a seborrheic keratosis; however, the vascular pattern seen has not been reported in seborrheic keratosis. Due to the patient's age and the rarity of significant pathology arising in a seborrheic keratosis, a shave biopsy was performed. To our surprise, the specimen was interpreted by an experienced dermatopathologist as a well-differentiated eccrine porocarcinoma. Due to the high local recurrence rate and metastatic potential of this carcinoma, the patient was referred for Mohs' surgery. Both the basal cell carcinoma and the eccrine porocarcinoma were excised in one stage. A metastatic work-up was negative and the patient appears to be doing well.     

The influence of painful sunburns and lifetime sun exposure on the risk of actinic keratoses,seborrheic warts,melanocytic nevi,atypical nevi,and skin cancer

Painful sunburns are implicated in the pathogenesis of squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. Chronic exposure to ultraviolet radiation is known as the most important risk factor for the development of actinic keratoses and squamous cell carcinoma. The purpose of the study was to assess the effect of painful sunburns and lifetime sun exposure on the development of actinic keratoses and seborrheic warts in relation to the development of squamous cell carcinoma and basal cell carcinoma, and on the development of melanocytic nevi and atypical nevi in relation to the development of malignant melanoma. We made use of a cohort of 966 individuals who participated in a case-control study to investigate environmental and genetic risk factors for skin cancer. Exposure measurements for sunlight were collected and actinic keratoses, seborrheic warts, melanocytic nevi, and atypical nevi were counted. Relative risks were estimated using exposure odds ratios from cross-tabulation. Multivariate logistic regression was used to adjust for potential confounders. The recall of painful sunburns before the age of 20 y was associated with an increased risk of squamous cell carcinoma, nodular basal cell carcinoma, and multifocal superficial basal cell carcinoma as well as actinic keratoses. Odds ratios with 95% confidence intervals adjusted for age, sex, and skin type were 1.5 (0.97; 2.3); 1.6 (1.1; 2.2); 2.6 (1.7; 3.8); and 1.9 (1.4; 2.6) for the three types of nonmelanoma skin cancer and actinic keratoses, respectively. Painful sunburns before the age of 20 y were also associated with an increased risk of malignant melanoma and the development of its precursors, melanocytic nevi and atypical nevi. Odds ratios with 95% confidence intervals adjusted for age, sex, and skin type were 1.4 (0.86; 2.1); 1.5 (1.1; 2.0); and 1.4 (0.88; 2.3) for malignant melanoma and the two types of precursors, respectively. Lifetime sun exposure was predominantly associated with an increased risk of squamous cell carcinoma (p-value for trend=0.03) and actinic keratoses (p-value for trend <0.0001) and to a lesser degree with the two types of basal cell carcinoma. By contrast, lifetime sun exposure appeared to be associated with a lower risk of malignant melanoma, despite the fact that lifetime sun exposure did not diminish the number of melanocytic nevi or atypical nevi. Neither painful sunburns nor lifetime sun exposure were associated with an increased risk of seborrheic warts.     

Two Cases of Basal Cell Carcinoma Arising in Seborrheic Keratosis

The present study reports two cases of basal cell carcinoma arising in seborrheic keratosis. The first case is a seventy-three-year-old female who presented with a blackish nodule arising from a pigmented lesion on her chest. Histopathological analysis of the nodule and the pigmented lesion revealed a basal cell carcinoma with hair follicular differentiation and an acanthotic seborrheic keratosis, respectively. The second case is a seventy-year-old female with a blackish nodule arising from a pigmented lesion on her back. Histological analysis of the nodule revealed an atypical basaloid cell mass surrounded by a seborrheic keratosis lesion. In addition to the coexisting seborrheic keratosis with the basal cell carcinoma, a basaloid follicular hamartoma that showed muliple hamartomatous hair follicles or small cysts replaced by a branching cord or lace-like network of basaloid cells surrounded by fibrovascular stroma was identified. We concluded that both cases presented a rare combination of a seborrheic keratosis which underwent a malignant change to basal cell carcinoma. It appears that both basal cell carcinomas and seborrheic keratosis may derive from a similar source: pluripotential cells of either the epidermis or hair follicle epithelium.     

Quantitative discrimination of pigmented lesions using three-dimensional high-resolution ultrasound reflex transmission imaging

High-resolution ultrasound-reflex transmission imaging is a non-invasive method that can be performed in vivo. We have adapted and refined this technique for skin imaging. Scans can be analyzed to produce objective parameters. Previous work has highlighted sonographic differences between benign and malignant lesions. The aim of this study was to produce and test numerical parameters from ultrasound skin images that would quantify the acoustic differences between common pigmented lesions, which may aid their discrimination from melanoma. We report our findings for randomly selected patients referred from primary care with suspected melanoma. Those subsequently classified as malignant melanoma (MM), seborrheic keratosis (SK), and benign nevi by a consultant dermatologist (n=87) were imaged by high-resolution ultrasound-reflex transmission imaging. Using surrounding normal skin as a control, numerical sonographic parameters were derived for each lesion giving a relative measure of surface sound reflectance, intra-lesional sound reflection, total sound attenuation, and the relative uniformity of each parameter across the tumor. Significant quantitative differences existed between benign and malignant pigmented lesions studied. Sufficient discrimination was produced between MM (n=25), SKs (n=24) and other benign-pigmented lesions (n=38) to potentially reduce the referral of benign tumors by 65% without missing melanoma.