Group Of Nevi Research Articles

Angiographic Features of Iris Melanocytic Tumors: Nevus versus Melanoma

Introduction: Determining the nature of iris melanocytic tumors based on clinical exam alone remains challenging. Tumor-associated vasculature of iris melanocytic lesions may facilitate the ability to discern between iris nevus and melanoma. Methods: In a single-institution, retrospective, observational study of 45 patients with pathologically confirmed iris melanoma and 15 patients with iris nevi that were either clinically stable or pathologically confirmed were included. Tumor characteristics and associated vasculature were identified on clinical exam and slit-lamp photographs. Fluorescein angiographic parameters including feeder vessels, intrinsic vessels, leakage, masking, and angiographic silence were assessed. Results: Feeder vessels were present in 17 (43%) melanomas and were absent in the nevus group (p = 0.002). Thirty-three (83%) iris melanomas and 5 (33%) iris nevi were observed to have intrinsic vessels, and a statistically significant association of intrinsic vessels with malignancy (p = 0.001) was noted. Fluorescein leakage was also observed more frequently in iris melanoma 39 (98%) than in nevi 9 (60) with a significant difference (p = 0.001). Angiographic silence occurred in 3 nevi (20%) and was not observed in any melanoma (p = 0.017). Overall, the presence of intrinsic vessels +/− feeder vessels had high sensitivity (0.85) and high positive predictive value (0.87) for diagnosis of iris melanoma. Conclusions: Anterior segment fluorescein angiography allows for the assessment of tumor-associated vascular patterns and demonstrates utility in differentiating iris nevi from melanoma. Feeder vessels were only observed in iris melanoma and were absent in iris nevi. The intrinsic vessels were present more frequently in melanomas and are thus associated with malignancy. Angiographic silence is indicative of iris nevi.

Retinal Vascular Patterns and Capillary Plexus Reflectivity of Intraocular Tumors; an Optical Coherence Tomography Angiography Study

Purpose To define the vascular characteristics of malignant and benign intraocular tumors by optical coherence tomography angiography (OCTA) and consequently to determine the advantages and disadvantages of the imaging technique in clinical practice. Methods This prospective, descriptive study consisted of choroidal hemangioma, choroidal nevus, choroidal melanoma, ocular melanocytoma, congenital hypertrophy of retinal pigment epithelium (CHRPE), and choroidal osteoma. Retinal angiography images were taken by OCTA in a 6 × 6 mm HD scan protocol. OCTA characteristics were defined by considering different tumor types separately. Results This study included 93 eyes of 90 patients diagnosed with benign or malignant intraocular tumors. The mean age of the patients was 48.9 ± 16.9 years in the hemangioma group, 55.3 ± 12.9 years in the nevus group, 48.2 ± 13.4 years in the melanoma group, 48 ± 18.9 years in the melanocytoma group, 45 ± 22.9 years in the CHRPE group, and 27.8 ± 7.8 years in the osteoma group. We showed four vascular patterns at the level of the choriocapillaris layer in circumscribed choroidal hemangiomas – the appearance of a “bag of worms,” club-like appearance, giant choroidal vessels and normal choriocapillaris. The rates of these vascular patterns were 40%, 30%, 10%, and 20% in treatment-naïve hemangiomas and were 46.1%, 30.8%, 7.7%, and 15.4% in photodynamic therapy-treated hemangiomas, respectively. There was no different vascular structure in the tumor associated with the lesion in the nevus group. There were three different patterns at the choriocapillaris level in the melanomas – a vascular network (10%), avascular areas (30%) and vascular loops (60%). There were some atypical and nonspecific vascular changes demonstrated in the CHRPE and osteoma groups and a fine vascular network was observed in the melanocytoma group. Conclusion The different types of intraocular tumors had specific vascular characteristics which were easily demonstrated by the OCTA machine. This imaging technique can be a useful tool to differentiate these intraocular tumors non-invasively.

Application of immunohistochemical staining of PRAME in differential diagnosis between melanoma and melanocytic nevus

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) in differential diagnosis of benign and malignant cutaneous melanocytic lesions. Methods: Fifty-nine cases of melanoma (50 cases of skin primary melanoma, and 9 cases of metastatic melanoma) and 48 cases of melanocytic nevus (40 cases of common nevus and 8 cases of dysplastic nevus) were subject to PRAME immunohistochemistry staining.The difference of PRAME expression between melanoma and melanocytic nevus was analyzed. Results: Among the 50 patients with primary cutaneous melanoma, there were 23 males and 27 females ranging in age from 33 to 87 years (average age 62.4 years, median age 64.5 years). Among the 9 metastatic melanoma there were 7 males and 2 females ranging in age from 40 to 82 years (average age 64 years, median age 65 years). Twenty-six cases (26/50, 52.0%) of cutaneous primary melanoma and 4 cases (4/9) of metastatic melanoma showed diffuse positive PRAME staining. 40 cases (40/40, 100%) of common nevus and 8 (8/8) cases of dysplastic nevus were PRAME negative. Compared with melanocytic nevus group, the melanoma group included more cases with diffuse positive PRAME staining (P<0.05). The sensitivity and specificity of using PRAME to differentiate primary cutaneous melanoma from melanocytic nevus in the cohort is 52.0% and 100%. Conclusions: There is a significant difference in the expression of PRAME between melanoma and melanocytic nevus.Thus, PRAME can be used as an auxiliary diagnostic tool for differentiating benign from malignant cutaneous lesions.

Efficacy of a Deep Learning Convolutional Neural Network System for Melanoma Diagnosis in a Hospital Population.

(1) Background: The purpose of this study was to evaluate the efficacy in terms of sensitivity, specificity, and accuracy of the quantusSKIN system, a new clinical tool based on deep learning, to distinguish between benign skin lesions and melanoma in a hospital population. (2) Methods: A retrospective study was performed using 232 dermoscopic images from the clinical database of the Ramón y Cajal University Hospital (Madrid, Spain). The skin lesions images, previously diagnosed as nevus (n = 177) or melanoma (n = 55), were analyzed by the quantusSKIN system, which offers a probabilistic percentage (diagnostic threshold) for melanoma diagnosis. The optimum diagnostic threshold, sensitivity, specificity, and accuracy of the quantusSKIN system to diagnose melanoma were quantified. (3) Results: The mean diagnostic threshold was statistically lower (p < 0.001) in the nevus group (27.12 ± 35.44%) compared with the melanoma group (72.50 ± 34.03%). The area under the ROC curve was 0.813. For a diagnostic threshold of 67.33%, a sensitivity of 0.691, a specificity of 0.802, and an accuracy of 0.776 were obtained. (4) Conclusions: The quantusSKIN system is proposed as a useful screening tool for melanoma detection to be incorporated in primary health care systems.

Attempting to Solve the Pigmented Epithelioid Melanocytoma (PEM) Conundrum: PRKAR1A Inactivation Can Occur in Different Genetic Backgrounds (Common, Blue, and Spitz Subgroups) With Variation in Their Clinicopathologic Characteristics.

Pigmented epithelioid melanocytoma is a rare cutaneous melanocytic proliferation considered high-grade melanocytoma in the 2018 WHO Classification of Skin Tumors. Little has been reported about the associated genetic drivers in addition to BRAF and MAP2K1 mutations or PRKCA gene fusions. Here, we present a series of 21 cases of PRKAR1A -inactivated melanocytic tumors in which we could assess the associated genetic background. We identified 9 different driver genes related to the common, Spitz, blue nevi, and PRKC -fused groups. Nine cases were associated with a canonical BRAF p.V600E mutation, a hallmark of the common nevus group. They occurred mainly in young adults. All were combined (biphenotypic) cases with a variable proportion of compound nevus. The pigmented epithelioid melanocytoma component was made of thin fascicules or isolated epithelioid cells covered by a dense hyperpigmented melanophage background and was predominantly located in the upper dermis. One such case was malignant. Six cases were associated with Spitz-related genetic anomalies ranging from HRAS or MAP2K1 mutations to gene fusions involving MAP3K8 , MAP3K3 , and RET . They occurred mainly in children and young adults. Morphologically, they showed large confluent junctional nests in a hyperplastic epidermis and a fascicular dermal component of spindled and epithelioid melanocytes with a frequent wedged silhouette. Intravascular invasion was observed in 4/6 cases. Five cases were associated with canonical mutations of the blue nevus group with 4 CYSLTR2 p.L129Q and 1 GNAQ p.Q209L mutations. They were removed mainly in adults and showed a frequent junctional component with epidermal hyperplasia. The dermal component showed dense fascicules of spindled and epithelioid melanocytes predominating over melanophages. One case occurred in a PRKCA -fused tumor in an adolescent with classic morphologic features. These results could potentially shift the concept of PRKAR1A -inactivated melanocytoma, changing from a rather unified model to a more complex one, including genetic subgroup variations with clinical and morphologic specificities. The genetic background of PRKAR1A -inactivated melanocytic tumors should be systematically explored to better understand the extent and clinical behavior of these complex lesions.

Endometrial Cancer Incidence in Endometriosis and Adenomyosis.

Simple SummaryPrevious research shows that women with endometriosis and adenomyosis have an increased ovarian cancer risk. However, it is unclear whether these women have an increased risk of developing uterine cancer. This information is of key importance to women with endometriosis or adenomyosis. Therefore, this study aims to assess the uterine cancer risk in women with endometriosis or adenomyosis in a large population.Women with histologically proven endometriosis/adenomyosis have an increased risk of ovarian cancer. Small studies show conflicting results on the endometrial cancer risk in women with endometriosis/adenomyosis. Therefore, we assessed the incidence of endometrial cancer in women with histologically proven endometriosis or adenomyosis. We performed a population-based retrospective cohort study of 129,862 women with histologically proven endometriosis/adenomyosis, matched with 132,700 women with a nevus selected from the Dutch pathology registry between 1990 and 2015. Histology results for endometrial cancer were retrieved. Crude and age-adjusted odds ratios for endometrial cancer were estimated. In the endometriosis/adenomyosis group, 1827 (1.4%) women had a histological report on endometrial cancer, and in the nevus group, 771 (0.6%) women. The age-adjusted OR for endometrial cancer was 2.58 (95%CI 2.37–2.81). After excluding the first year of follow-up, the age-adjusted OR was 0.76 (95%CI 0.63–0.92), indicating that endometrial cancer is most often found at time of histological diagnosis of endometriosis/adenomyosis. In around 20% of the endometrial cancer cases, the endometrial cancer was not recognized until after hysterectomy. Of these women, 35% had no prior (micro)curettage or biopsy. This study shows an increased incidence of endometrial cancer in women with histologically proven endometriosis and adenomyosis.

26452 Impact of COVID-19 on patient willingness to seek in-person dermatologic care

The coronavirus-19 (COVID) pandemic has hindered health care provider operations, and its impact on patient willingness to seek in-person dermatologic care lacks extensive study. Understanding how a pandemic may influence patient motivation to consult a dermatologist may facilitate efficient allocation of health care provider resources both during and after COVID. Participants (n = 416) were recruited through Amazon Mechanical Turk, a web-based survey platform. Subjects were randomized to one of fourteen groups, each entailing a pre-COVID or during-COVID hypothetical scenario of a socially stigmatized skin condition: scalp psoriasis, herpes labialis, acne vulgaris, rosacea, tinea faciei, melanoma, or a benign nevus. Subjects rated their willingness to schedule an in-person dermatology appointment on a 5-point Likert scale (ie, willingness score). Sociodemographic data were collected. Herpes labialis, tinea faciei, and melanoma prompted higher willingness scores during COVID (3.94; 4.03; 3.54) compared with pre-COVID (3.81; 4.0; 3.32); scalp psoriasis, acne vulgaris, rosacea, and benign nevi prompted lower willingness scores during COVID (3.33; 2.88; 3.67; 3.07) compared with pre-COVID (3.93; 3.19; 4.21; 3.7). The benign nevus group displayed the largest decrease in willingness scores from pre-COVID (3.7) to during COVID (3.07). Patients reported higher willingness to seek in-person evaluation for conditions associated with stronger social stigmas, such as scalp psoriasis and herpes labialis, during COVID. We did not control for subject familiarity with each skin condition, and perceived degree of disfigurement was not measured. Patient willingness to seek treatment during COVID may be changing rapidly and, at this time, does not appear to be largely affected by the pandemic.

Kindlin-3 and RASSF6 are probable biomarkers for predicting metastasis in cutaneous melanoma.

It is well known that metastasis is the most crucial factor in determining the fate of the patient. The prognosis of melanoma is very poor at the stage of metastasis. Recently, several genes and proteins, including kindlin3, dioxin receptor (AhR), RASSF6, and claudin-11, which were shown as possible prognostic biomarkers for human tumours, were described. In this study, we focused on these proteins in melanoma within a clinical setting. Forty-three primary melanomas (PMs), 17 metastatic melanomas (MMs), 15 melanocytic nevi (MN), and two melanoma cell lines were included in this retrospective study. All proteins were investigated using immunohistochemistry, and analysis was performed using a semi-quantitative immunoreactive score (IRS). The nevus group showed lower RASSF6 and AhR IRS levels than PMs. RASSF6 and kindlin-3 levels in the PMs with metastasis (MwM) and also in PMs showing lymphovascular invasion were significantly lower. The logistic regression model also proved that kindlin-3 expression was a significant independent predictor of metastasis. The current study supports the role of kindlin-3 and RASSF6 as prognostic biomarkers in melanoma. Besides the prognostic roles of these proteins, they are probably potential candidates for target-oriented therapies for melanoma metastasis blocking.

Изучение дерматоскопической картины невусов в детском возрасте

Childhood and adolescence are dynamic periods regarding nevogenesis. The mechanisms of nevogenesis are not completely understood. In this regard, the use of dermoscopy to study the features of nevogenesis remains relevant. Goal – to evaluate the prevalence of dermoscopic patterns of nevi in childhood and adolescence. Three groups were formed out of 78 children aged 7-17 years by random sampling. 28 children (13 boys, 15 girls) aged 7-9 years, the average age – 7,9 ±0,7 years; 25 children (11 boys, 14 girls) aged 10-12 years, the average age – 10,9±0,4 years; 25 children (13 boys, 15 girls) aged 16-17 years, the average age – 16,1±0,3 years were in 1, 2 and 3 groups respectively. The study included nevi with a size of 3 mm and more (n=398). Nevi were separated according to the dermoscopy classification of acquired melanocytic nevi into globular, homogeneous, reticular and mixed. Nevi with the peripheral globular pattern were assigned to the group of nevi with the globular pattern. Reticular-homogeneous and globular-homogeneous patterns were evaluated as reticular and globular respectively. Reticular pattern was observed in 4 (14,3 %); 5 (20,0 %); 11 (44,0 %) children; globular pattern was revealed in 16 (57,1 %); 23 (92,0 %); 23 (92,0 %) children, peripheral globular pattern was seen in 0; 1 (4,0 %), 4 (16 %) children; homogeneous pattern was detected in 2 (7,1 %); 3 (12,0 %); 9 (36,0 %) children from 1, 2, 3 groups respectively. Mixed pattern was detected in 3 (12,0 %); 7 (28,0 %) children from 2, 3 groups respectively. Among 398 nevi in all children globular pattern was found in 303 (76,1 %) nevi, reticular pattern – 40 (10,1 %), homogeneous – 42 (10,5 %), mixed – 13 (3,3 %).

Conjunctival pigmented lesion: Clinicopathological analysis of 85 cases in Korean population

To evaluate histopathological characteristics of conjunctival pigmented lesions and analyze clinical features related to histologic classification in Asian population, we analyzed medical records, anterior segment photographs, and histological specimen of 85 eyes who had undergone biopsy for pigmented conjunctival lesions at Seoul National University Hospital between 1999 and 2018. Compound nevus was the most common type of conjunctival pigmented lesions (67.1%), followed by conjunctival melanocytic intraepithelial neoplasia (primary acquired melanosis)(11.8%), subepithelial nevus (8.2%), and malignant melanoma (MM)(7.1%). Patients with compound nevus were younger than those with non-compound nevus (22.1 ± 17.0 vs 39.9 ± 18.8 years, p < 0.001), while patients with MM were older than those without melanoma (55.7 ± 18.2 vs 25.8 ± 18.0 years, p = 0.001). The lesion in compound nevus tended to be more frequently located on the temporal conjunctiva than that in the non-compound nevus group (54.4% vs 32.1%, p = 0.053), and feeder vessels were associated with most of compound nevus (98.2% vs 78.6% of non-compound nevus, p = 0.005). The lesion in MM was larger, involved multiple quadrants, and had extrabulbar location than lesions without melanoma (p < 0.001, p < 0.001, and p = 0.002, respectively). Together, the results would help clinicians to distinguish benign conjunctival pigmentations from malignant counterparts in clinical practice without biopsy.

Expression of Notch pathway receptors and ligands in cutaneous malignant melanoma

Objective To determine the expression of Notch pathway receptors (Notch1 and Notch4) and ligands (Jagged1 and Dll4) in cutaneous malignant melanoma (CMM) tissues, and to preliminarily explore the role of the Notch signaling pathway in the pathogenesis of CMM. Methods Immunohistochemical study was performed to determine the expression pattern and intensity of Notch1, Notch4, Jagged1 and Dll4 in 40 paraffin-embedded CMM specimens and 15 paraffin-embedded pigmented nevus specimens. Statistical analysis was carried out by chi-square test and Spearman rank correlation analysis with the SPSS 21.0 software. Results Notch1 was detected in 31 (77.5%) of 40 CMM specimens, as well as in 3 of 15 pigmented nevus specimens, and the positive rates significantly differed between the two groups (χ2= 15.281, P < 0.001) . However, no significant difference in the expression intensity of Notch1 was observed between 18 in situ melanoma tissues and 22 invasive melanoma tissues (χ2= 0.631, P= 0.427) . In addition, the positive rates of Notch4, Jagged1 and Dll4 were also significantly higher in the CMM group than those in the pigmented nevus group (all P < 0.05) , and the expression intensity of Notch4, Jagged1 and Dll4 significantly differed between in situ and invasive melanoma tissues (all P < 0.05) . In CMM tissues, the expression of Notch1 was positively correlated with that of Jagged1 (rs= 0.350, P= 0.027) and Dll4 (rs= 0.562, P < 0.001) , while the expression of Jagged1 was negatively correlated with that of Dll4 (rs=-0.734, P < 0.001) . Conclusion Abnormality of the Notch signaling pathway may be involved in the pathogenesis of melanoma, but further researches are still needed to elucidate the detailed mechanism. Key words: Nevi and melanomas; Receptors, Notch; Immunohistochemistry; Jagged1; Dll4

Expression of CC chemokine ligand 18 in cutaneous malignant melanoma tissues and its relationship with vascular endothelial growth factor and Ki67 antigen expressions

Objective To measure the expression of CC chemokine ligand 18 (CCL18) in cutaneous malignant melanoma (CMM) tissues, and to explore its clinical significance, as well as relationship with vascular endothelial growth factor (VEGF) and Ki67 antigen expressions. Methods Immunohistochemistry was performed to measure CCL18, VEGF and Ki67 expressions in 58 paraffin-embedded CMM tissue specimens, as well as CCL18 expression in 20 paraffin-embedded pigmented nevus specimens, and immunofluorescence assay to confirm the expression of CCL18 in fresh CMM tissue specimens. Correlations of CCL18 expression with CMM clinicopathologic features, VEGF and Ki67 expressions were analyzed. Results CCL18 was detected in 49 (84.48%) of 58 paraffin-embedded CMM specimens, but in none of the 20 paraffin-embedded pigmented nevus specimens, with a significant difference in the positive rate of CCL18 between the CMM group and pigmented nevus group (χ2 = 45.46, P 0.05). In addition, the expression of CCL18 in CMM tissues was positively correlated with that of VEGF (rs = 0.727, P 0.05). Immunofluorescence assay showed CCL18 expression in the cytoplasm of tumor cells in CMM tissues. Conclusion CCL18 is highly expressed in CMM tissues, and may be involved in tumor invasion and metastasis. Key words: Nevi and melanomas; Chemokine CCL18; Pathologic processes; Vascular endothelial growth factors; Ki-67 antigen

Melanocytic nevi with special features: clinical‐dermoscopic and reflectance confocal microscopic‐findings

Histopathology is considered the 'gold' standard for the diagnosis and classification of melanocytic nevi, but the widespread use of in vivo diagnostic technologies such as dermoscopy and reflectance confocal microscopy (RCM), has enriched profoundly the knowledge regarding the morphological variability in nevi. This is because most morphological observations made via these in vivo tools are closely correlated with features seen in histopathology. Dermoscopy has allowed for a more detailed classification of nevi. As such, dermoscopy identifies four main morphologic groups (i.e. globular, reticular, starburst and structureless blue nevi), one group of nevi located at special body sites (i.e. face, acral, nail) and one group of nevi with special features. This latter category consists of nevi of the former categories, which are typified by peculiar clinical-histopathological findings. They can be subdivided into 'melanoma simulators' including combined nevi, recurrent nevi and sclerosing nevus with pseudomelanomatous features, 'targetoid' nevi (i.e. halo, cockade, irritated targetoid haemosiderotic and eczematous nevus) and uncommon histopathological variants such as desmoplastic, white dysplastic or ballon cell nevus. While the dermoscopic and RCM patterns of the former categories have been studied in detail, little is currently known about the clinical morphology of the heterogeneous group of 'special' nevi. In this article, we describe the clinical, dermoscopic and RCM features of 'special' nevi and review the current literature on this group of melanocytic proliferations.

Active and inactive forms of matrix metalloproteinases 2 and 9 in cutaneous melanoma

Cutaneous melanoma is the most aggressive type of skin cancer, with high implications on the morbidity and mortality of patients. Matrix metalloproteinases (MMP) 2 and 9 have been involved in melanoma progression because they degrade important components of the basement membrane. We studied the relationship between the levels of active and inactive MMP 2, MMP 9, and clinicopathological parameters. Expression of both active and latent forms of MMP 2 and MMP 9 was evaluated by zymography in 21 melanoma tissue samples and 19 benign melanocytic nevi samples. In the melanoma group, inactive MMP 2 was detected in 100% of samples and active MMP 2 in 95%. Inactive MMP 9 was detected in 85% of samples and active MMP 9 in 38%. In the nevi group, 78.9% of samples expressed inactive MMP 2, 5.26% active MMP 2, 21% inactive MMP 9, and 0% active MMP 9. Both forms of MMP 2 and MMP 9 were found to be correlated with skin tumor malignancy. Expression of active and latent MMP 9 was higher in tumors >2 mm thick (P = 0.03, P = 0.014). A correlation was also found between positive lymph node metastasis, inactive MMP 9, and active MMP 9 expression (r = 0.59 P < 0.01, r = 0.668, P < 0.01). The amount of active and latent form of MMP 2 did not have an impact on lymph node metastasis. Our study demonstrates that active and latent MMP 2 and MMP 9 correlate with melanoma, and both forms of MMP 9 correlate with positive lymph node metastasis.

Expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of MMP (TIMP)-1 in conjunctival melanomas and clinical implications

To investigate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in conjunctival melanomas and their correlations with clinicopathologic parameters and prognosis. Fourteen conjunctival melanoma tissue samples and nine conjunctival nevus tissue samples were stained immunohistochemically for MMP-2, MMP-9, and TIMP-1. Association of MMP-2, MMP-9, and TIMP-1 expression in melanoma tissues with clinical progression in terms of metastasis, recurrence, mitotic index, thickness, base diameter, and invasion depth was analyzed. In the melanoma group, 78.6% of samples showed a positive reaction for MMP-2, 85.7% for MMP-9, and 100% for TIMP-1. In the nevus group, 11.1% showed a positive reaction for MMP-2, 66.7% for MMP-9, and 100% for TIMP-1. MMP-2 expression was significantly more induced in conjunctival melanoma than in benign nevi (P = 0.002). In conjunctival melanoma, MMP-9 expression was higher in tumors >1.5 mm thick (P = 0.026) and TIMP-1 expression was higher in recurrent cases (P = 0.03). There was no significant correlation between the expression and metastasis during the follow-up period (mean, 5 years). MMP-2, MMP-9, and TIMP-1 were expressed in the majority of conjunctival melanomas, and MMP-2 might play a role in the development and clinical behavior of conjunctival melanoma.

The relationship between Fas/FasL and proliferating cell nuclear antigen expression and malignant degree in human melanoma

To study the expression of Fas, Fas-ligand (Fas/FasL), and proliferating cell nuclear antigen (PCNA) in malignant melanoma (MM), melanocytic nevus, and normal skin, and the relationship of Fas, Fas/FasL, and PCNA expressions to malignant degrees of MM. Immunohistochemistry SP methods was used to detect the expressions of Fas, Fas-ligand (Fas/FasL), and PCNA in 35 samples of MM, 21 samples of melanocytic nevus, and 28 normal skin samples obtained by operation. The positive Fas rate of the MM group was 92.86% (26/28), significantly higher than those of the melanocytic nevus group (76.19%, 16/21) and normal skin group (45.71%, 16/35) (chi2 = 16.84, v =2, P < 0.01). The positive FasL rate of the MM group was 3.57% (1/28), significantly lower than those of the melanocytic nevus group (19.05%, 4/21) and normal skin group (62.86%, 22/35) (chi2 = 27.27, v = 2, P < 0. 01). The PCNA positive rate of the MM group was 100% (35/35), significantly higher than those of the melanocytic nevus group (33.33%, 7/21) and normal skin group (10.71%, 3/28) (chi2 = 54.4, v = 2, P < 0.01). The positive index (PI) of PCNA of the MM group was 55.0% +/- 14.8%, significantly higher than those of the melanocytic nevus group (6.2% +/- 3.0%, t = 19. 89, P < 0.01) and normal skin group (4.0% +/- 2.0%, t = 22.63, P < 0.01), however, there was no significant difference in the PCNA PI between the melanocytic nevus and normal skin groups (P > 0.05). The greater the infiltration depth of MM, the higher the PCNA PI. However, there was no direct dose-effect relationship between PI and pathological types. The expressions of Fas/FasL and PCNA reflect the malignant degree of human melanoma, and the more expression of PCNA, the more malignant degree of melanoma. The expressions of Fas/FasL and PCNA are closely associated with the development of MM.

The Diagnostic Yield of Histologic Examination of Seborrheic Keratoses

To examine the diagnostic yield in submitting clinically diagnosed seborrheic keratoses for routine microscopic examination. Retrospective examination of preoperative and postoperative diagnoses based on information provided by the clinician on the laboratory worksheet and the subsequent histopathologic diagnosis. A regional nonhospital-based dermatopathology laboratory with specimens submitted by physicians (dermatologists and nondermatologists) practicing in a 4-state midwestern region of the United States. A total of 5592 cutaneous pathology reports were reviewed. Specimens submitted with a preoperative clinical diagnosis of seborrheic keratosis, with or without a modifier, were examined. A comparison group with the clinical diagnosis of melanocytic nevus was reviewed. Preoperative clinical diagnoses were compared with the microscopic diagnoses. Of 577 specimens clinically diagnosed and submitted as seborrheic keratoses, 37 (6.4%) were histologically diagnosed as malignant tumors. The rate of malignant tumors increased when clinical information suggested findings beyond the classic clinical presentation, such as irritation, or when a malignant tumor was considered in the differential diagnosis. Two lesions that histologically proved to be melanomas were in this group. Comparison of the seborrheic keratosis group with the nevus group showed that seborrheic keratoses were more likely to be malignant tumors than were melanocytic nevi. Clinically diagnosed seborrheic keratoses submitted by dermatologists were more likely than clinically diagnosed melanocytic nevi to be melanomas. Our data suggest that there were differences in the rate of malignant tumors between dermatologists and nondermatologists and that clinically diagnosed, surgically removed seborrheic keratoses are more likely than clinically diagnosed, surgically removed melanocytic nevi to be malignant tumors.