Immunohistochemical Markers in the Differential Diagnosis of Melanoma and Nevus in Humans

SUMMARY: Immunohistochemistry allows in situ detection of cell and extracellular components through specific antibodies. The objective was to compare the immunohistochemical expression patterns of the S-100, HMB-45 and MART-1 proteins for differential diagnosis of malignant melanoma and melanocytic nevus in human skin biopsies. Thirty-nine biopsies of human tissue were used. They were divided into two groups: 19 in malignant melanoma and 20 in melanocytic nevi. Next, the samples were fixed with paraformaldehyde and processed following the protocol for inclusion. Then, immunohistochemical staining was performed. Finally, the histological and qualitative analysis of the samples was carried out. S-100, HMB-45, and MART-1 markers showed positive immunoreaction in melanoma biopsies. HMB-45 marker was generally present with weaker expression than S-100 and MART-1 in melanocytic nevus biopsies. No expression pattern was observed which specifically associates one or more markers with some types of histopathological diagnosis. Immunohistochemistry is fundamental in differential diagnosis of melanomas and melanocytic nevi. However, there is no antibody or set of antibodies which allows unequivocal diagnosis between melanoma and nevus. It is therefore necessary to analyze with care the expression pattern and location of the lesion using standard morphological characteristics.

RESUMEN: La inmunohistoquímica permite la detección in situ de componentes celulares y extracelulares a través de anticuerpos específicos. El objetivo de nuestro estudio fue comparar los patrones de expresión inmunohistoquímica de las proteínas S-100, HMB-45 y MART-1 para el diagnóstico diferencial de melanoma maligno y nevo melanocítico en biopsias de piel humana. Se utilizaron treinta y nueve biopsias de tejido humano, las que fueron divididas en dos grupos: 19 en melanoma maligno y 20 en nevos melanocíticos. A continuación, las muestras se fijaron con paraformaldehído y se procesaron siguiendo el protocolo convencional para su inclusión. Luego, se realizó la tinción inmunohistoquímica. Finalmente, se realizó el análisis histológico y cualitativo de las muestras. Los marcadores S-100, HMB- 45 y MART-1 mostraron inmunorreacción positiva en biopsias de melanoma. El marcador HMB-45 estuvo generalmente presente con una expresión más débil que S-100 y MART-1 en biopsias de nevo melanocítico. No se observó ningún patrón de expresión que asocie específicamente uno o más marcadores con algunos tipos de diagnóstico histopatológico. La inmunohistoquímica es fundamental en el diagnóstico diferencial de melanomas y nevos melanocíticos. Sin embargo, no existe ningún anticuerpo o panel de anticuerpos que permita un diagnóstico inequívoco entre el melanoma y el nevo. Por tanto, es necesario analizar con cuidado el patrón de expresión y la localización de la lesión utilizando características morfológicas estándar.

Melanocytic lesions ≤ 6mm: Prospective series of 481 melanocytic trunk and limb lesions in Brazil.

Early diagnosis when melanoma is still small and thin is essential for improving mortality and morbidity. However, the diagnosis of small size melanoma might be particularly difficult, not only clinically but also dermoscopically. This study aimed to define clinical and dermatoscopic parameters in the diagnosis of suspicious pigmented cutaneous lesions with a diameter of ≤ 6mm and determine the sensitivity, specificity, positive and negative predictive values as well as the accuracy of each clinical and dermatoscopic criterion. This is a transversal, descriptive and analytical study of dermatoscopic analysis with the gold standard being the pathologic examination obtained from the excisional biopsy of suspicious melanocytic lesions with a diameter of ≤ 6mm. Trunk and limb lesion data from a public health service and a private clinic were prospectively collected from 2011 to 2017 by a unique observer. In total, 481 melanocytic lesions were included, with 73.8% being ≤ 4mm in diameter. Overall, 123 were diagnosed as melanoma, 56.0% in situ and 22.0% as thin melanomas (Breslow index 0.1 to 1.0mm). Melanoma presented symmetry in 53.7% of cases, regular borders in 54.5% and a single color in 60.2%. Regarding evolution, 13.8% of melanomas versus 10.9% of benign lesions (p = 0.116) were new by comparing photos from baseline with photos from the follow-up. The majority of melanomas (65%) were found on the limbs compared to 37.2% of the benign lesions at this location (p<0.001). A multiple logistic regression model adjusted for age, gender and location was created. The independent variables associated with the diagnosis of melanoma ≤ 6mm, adjusted for age, gender and location, were: streaks (adjusted Odds Ratio [aOR] 2.5; 95% CI 1.3-4.7; p = 0.006), and the presence of a structureless area (aOR 2.2, 95% CI 1.2-4.0, p = 0.011). Conversely, a symmetric typical pigment network was a protection variable (aOR 0.4, 95% 0.7-0.9, p = 0.040). In conclusion, dermatoscopic criteria have been identified which help to diagnose cases of small size melanoma. These include streaks and structureless areas that can be taken, particularly in consideration for the diagnosis of this subset of small difficult melanomas.

Survey of 138 Conjunctival Tumors in the Dominican Republic.

PURPOSE: To report the frequency of conjunctival tumors in the Dominican Republic. METHODS: Retrospective noninterventional case series. One hundred thirty-eight consecutive patients with a conjunctival mass evaluated at two tertiary referral centers from 2010 to 2018. Main outcome measures were frequency of tumors by diagnosis and distribution of tumors relative to patients' age and gender. RESULTS: The mean age at presentation was 41.2 years (median, 42 years; range 10 days - 91 years). There were 83 male patients (60%) and 55 female patients (40%). The three most common specific diagnoses were junctional, compound, and subepithelial naevi (47 [34%]), squamous cell carcinoma (SCC) (26 [19%]) and conjunctival squamous intraepithelial neoplasia (CIN) (17 [12%]). The mean age at detection was 36.5 years for non-malignant tumors and 56.3 years for malignant tumors (p < .001), with a mean difference of 19.8 years at time of diagnosis (95% CI, 10.7-28.8). Benign tumors were more common in children and young adults; malignant and premalignant tumors were more common in mid and older adults (p = .009). Malignant tumors were more common in males (73%) than in females (27%) (p = .04). CONCLUSION: In the Dominican Republic, conjunctival tumors are benign (63%), premalignant (13%) and malignant (24%). Malignant tumors are more common in older adults and men.

Dermoscopy of naevi in patients with oculocutaneous albinism.

Oculocutaneous albinism (OCA) increases predisposition to skin malignancies. Nevertheless, the differential diagnosis between melanoma and naevi in patients with OCA is still challenging, because pigmentary lesions have rarely been described in this population. We aimed to describe the dermoscopic patterns of naevi in patients with OCA. We prospectively evaluated 83 naevi from 37 patients with OCA in a single centre in Brazil. Lesions were analysed by eye and by dermoscopy and were grouped by dermoscopic pattern. Eight main patterns were identified: homogeneous structureless pattern (n = 28; 33.7%), globular pattern (n = 27; 32.5%), reticular pattern (n = 8; 9.6%), peripheral reticular pattern with central hypopigmentation (n = 8; 9.6%), peripheral globules (n = 8; 9.6%), irregular brown globules with pink background (n = 2; 2.4%), reticular globular disorganized pattern (n = 1; 1.2%) and peripheral reticular globular with central hypopigmentation (n = 1; 1.2%). We found previously undescribed dermoscopic patterns in patients with OCA, in addition to confirming previously described patterns. These descriptions may help the understanding of pigmented naevi in patients with OCA.

Fibroadnexal hamartoma in the dog: retrospective epidemiological and histopathological study of 102 cases / Hamartoma fibroanexial em cão: estudo retrospectivo epidemiológico e histopatológico de 102 casos

Fibroadnexal hamartoma (FH), also called focal adnexal dysplasia, is the most common hamartomatous lesion in dogs. There are few retrospective studies about FH in dogs, which did not describe histopathological findings in detail. The main objective was to conduct a retrospective study and to describe the epidemiological and histopathological characteristics of a series of 102 FH cases in dogs. Descriptive statistics and Odds Ratio were used to analyze the data. The lesions were exophytic and measured on average 2.5 cm in diameter. The anatomic sites most affected were the limbs and digital region. The animals were on average 7 years of age and both sexes were equally affected. Doberman (OR: 4.15; P=0.0069) and Schnauzer (OR: 2.50; P=0.049) showed a higher risk for FH. Recurrence was not observed in any case. Four histopathological FH subtypes were identified: follicle-sebaceous (73.53%), sebaceous (16.66%), follicular (8.82%) and sebaceous-apocrine (0.98%). Diffuse and perianexial fibroplasia and inflammation were frequently seen. Chronic inflammation and mature adipocytes were seen in 71.6% and 7.8% of the cases, respectively.(AU)

Hamartoma fibroanexial (HF), também denominado displasia focal anexial, é a lesão hamartomatosa mais comum em cães. Existem poucos estudos retrospectivos sobre HF em cães, os quais não descrevem detalhadamente os achados histopatológicos. O objetivo principal foi realizar um estudo retrospectivo e descrever as características epidemiológicas e histopatológicas de uma série de 102 casos de HF em cães. A estatística descritiva e Odds Ratio foram utilizadas para a análise dos dados. As lesões foram exofíticas e mediram em média 2,5 cm de diâmetro. Os locais anatômicos mais acometidos foram os membros e dígitos. Os animais tinham em média 7 anos de idade e ambos os sexos foram igualmente acometidos. Doberman (OR: 4.15; P=0,0069) e Schnauzer (OR: 2,50; P=0,049) mostraram-se com maior risco para o HF. Não foi relatada recorrência para nenhum caso. Quatro subtipos histopatológicos de HF foram identificados: folículo-sebáceo (73,53%), sebáceo (16,66%), folicular (8,82%) e sebáceo-apócrino (0,98%). Fibroplasia difusa e perianexial e inflamação foram frequentemente observadas. Inflamação crônica e adipócitos maduros foram vistos em 71,6% e 7,8% dos casos, respectivamente.(AU)

Porokeratotic eccrine and hair follicle nevus: a report of two cases and review of the literature.

Porokeratotic eccrine and hair follicle nevus is a very rare non-hereditary disorder of keratinization with eccrine and hair follicle involvement with only 9 cases described in the literature. In 2009 the term porokeratotic anexial ostial nevus was proposed to comprehend porokeratotic eccrine and hair follicle nevus and a related and more common process without follicular involvement: porokeratotic eccrine ostial and dermal duct nevus Recent findings suggest that both entities may be produced by a mutation in GJB2 gene, which is associated to KID syndrome. Herein we report 2 cases of porokeratotic eccrine and hair follicle nevus and review the existing cases in the Spanish and English literature.

Wooly hair nevus.

Woolly hair nevus is a rare condition characterized by a structural anomaly of the hair, restricted to certain areas of the scalp. The hair becomes coiled and slightly hypopigmented. The term woolly hair refers to changes that affect all the scalp and has a hereditary character. We present a case of woolly hair nevus, that developed at the age of 2 years, associated with dental diastema and verrucous epidermal nevus.

Histopathological diagnosis of small melanocytic lesions suspicious for malignant melanoma.

The concern about malignant skin neoplasms leads to the excision of smaller lesions. This study on small melanocytic lesions aims to evaluate the range of possible histopathological diagnoses, describe histopathological aspects, and assess the usefulness of serial histological sections. We performed a cross-sectional descriptive histopathological study examining 76 pigmented skin lesions up to 6 mm in diameter. Histopathological diagnoses included atypical melanocytic nevi (n=38), common melanocytic nevi (n=18), atypical lentiginous melanocytic hyperplasia with architectural features of atypical melanocytic nevi (n=7), lentigo simplex (n=2), and malignant melanoma (n=1). Ten cases were non-diagnostic. Cytological atypia was not an exclusive finding of atypical lesions. Examination of serial sections did not change histopathological impression. Early detection of malignant melanoma is important, but clinical and dermoscopy exams may be leading to the resection of a great number of benign lesions. Strict attention to histopathological criteria results in a large number of non-diagnostic cases.

Nevus lipomatosus cutaneous superficialis.

Nevus lipomatosus cutaneous superficialis is a rare benign hamartomatous skin tumor characterized by dermal deposition of mature adipose tissue. Two clinical forms have been described (classical and solitary types). We describe a case of nevus lipomatosus cutaneous superficialis with a 13-year history of growth in a young woman who had a solitary skin-colored tumoral mass on the right buttock. Histopathological findings were typical and confirmed the diagnosis. In this case, the lesion was a skin-colored isolated mass, as described in the solitary type, but its localization and age of appearance were compatible with the classical type. The combination of simultaneous clinical findings of both types had not been published before.

Nevus lipomatosus cutaneous superficialis

Abstract: Nevus lipomatosus cutaneous superficialis is a rare benign hamartomatous skin tumor characterized by dermal deposition of mature adipose tissue. Two clinical forms have been described (classical and solitary types). We describe a case of nevus lipomatosus cutaneous superficialis with a 13-year history of growth in a young woman who had a solitary skin-colored tumoral mass on the right buttock. Histopathological findings were typical and confirmed the diagnosis. In this case, the lesion was a skin-colored isolated mass, as described in the solitary type, but its localization and age of appearance were compatible with the classical type. The combination of simultaneous clinical findings of both types had not been published before.

Multiple vulvar dilated pores in a postmenopausal woman.

Winer's dilated pore is an infrequent appendageal tumor characterized by a giant comedone on the face, neck, and upper trunk in adults. We report a 57-year-old woman who developed multiple asymptomatic black papules on both labia majora. Histopathology showed grouped dilated follicles lined by keratinizing squamous epithelium in the superficial dermis. The superficial lining epithelium and interfollicular epidermis were atrophic, while the deep epithelium showed mild proliferation and melanin pigmentation with a few short projections extending into the surrounding dermis. We diagnosed multiple Winer's dilated pores based on late-onset lesions and pathological features. This patient may represent the first case of multiple vulvar Winer's dilated pores. We suggest that electrocautery may be effective for treating this type of superficial entity.

Multiple vulvar dilated pores in a postmenopausal woman

Abstract: Winer's dilated pore is an infrequent appendageal tumor characterized by a giant comedone on the face, neck, and upper trunk in adults. We report a 57-year-old woman who developed multiple asymptomatic black papules on both labia majora. Histopathology showed grouped dilated follicles lined by keratinizing squamous epithelium in the superficial dermis. The superficial lining epithelium and interfollicular epidermis were atrophic, while the deep epithelium showed mild proliferation and melanin pigmentation with a few short projections extending into the surrounding dermis. We diagnosed multiple Winer's dilated pores based on late-onset lesions and pathological features. This patient may represent the first case of multiple vulvar Winer's dilated pores. We suggest that electrocautery may be effective for treating this type of superficial entity.

Histopathological diagnosis of small melanocytic lesions suspicious for malignant melanoma

Abstract The concern about malignant skin neoplasms leads to the excision of smaller lesions. This study on small melanocytic lesions aims to evaluate the range of possible histopathological diagnoses, describe histopathological aspects, and assess the usefulness of serial histological sections. We performed a cross-sectional descriptive histopathological study examining 76 pigmented skin lesions up to 6 mm in diameter. Histopathological diagnoses included atypical melanocytic nevi (n=38), common melanocytic nevi (n=18), atypical lentiginous melanocytic hyperplasia with architectural features of atypical melanocytic nevi (n=7), lentigo simplex (n=2), and malignant melanoma (n=1). Ten cases were non-diagnostic. Cytological atypia was not an exclusive finding of atypical lesions. Examination of serial sections did not change histopathological impression. Early detection of malignant melanoma is important, but clinical and dermoscopy exams may be leading to the resection of a great number of benign lesions. Strict attention to histopathological criteria results in a large number of non-diagnostic cases.