Inflammatory infiltrates in melanocytic lesions / Infiltrados inflamatorios en lesiones melanocíticas

SUMMARY: Inflammatory infiltrates are frequently present in melanocytic lesions, with different distribution and composition. Much attention has been devoted to tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment, establishing their prognostic and predictive value in many malignancies, including melanoma. However, lymphocytes, albeit the most numerous and consistent presence, constitute only part of the immune microenvironment. Other inflammatory cells, including neutrophils, plasma cells, eosinophils and mast cells, are found in melanoma and other melanocytic lesions.Few studies offer a detailed count of these inflammatory infiltrates across the spectrum of melanocytic lesions. By using whole slide image analysis and open source software, in the present study we report the enumeration of different inflammatory infiltrates in benign melanocytic nevi, dysplastic nevi, melanoma in situ and invasive malignant melanomas. Significant higher numbers of plasma cells and neutrophils were observed in melanoma. These results indicate that composition of the inflammatory infiltrate may contribute to the diagnostic algorithm of melanocytic lesions.

RESUMEN: Los infiltrados inflamatorios están presentes con frecuencia en las lesiones melanocíticas, con diferente distribución y composición. Se ha prestado mucha atención a los linfocitos infiltrantes de tumores (TIL) en el microambiente tumoral, estableciendo su valor pronóstico y predictivo en muchas neoplasias malignas, incluido el melanoma. Sin embargo, los linfocitos de presencia más numerosa y constante, constituyen solo una parte del microambiente inmunológico. Otras células inflamatorias, incluidos neutrófilos, células plasmáticas, eosinófilos y mastocitos, se encuentran en el melanoma y otras lesiones melanocíticas. Pocos estudios ofrecen un recuento detallado de estos infiltrados inflamatorios en todo el espectro de lesiones melanocíticas. Mediante el uso de análisis de imágenes de diapositivas completas y software de código abierto, en el presente estudio informamos la enumeración de diferentes infiltrados inflamatorios en nevos melanocíticos benignos, nevos displásicos, melanoma in situ y melanomas malignos invasivos. Se observaron números significativamente más altos de células plasmáticas y neutrófilos en el melanoma. Estos resultados indican que la composición del infiltrado inflamatorio puede contribuir al algoritmo diagnóstico de las lesiones melanocíticas.

Osteonevus of Nanta: a case report in a combined melanocytic nevus

Abstract Secondary osteoma cutis is a phenomenon that may occur in several conditions. When it occurs in a melanocytic nevus it is named osteonevus of Nanta, an event considered uncommon and characterized by the presence of bone formation adjacent or interposed with melanocytic cells. There are reports of its occurrence in various melanocytic lesions, being more frequently associated with intradermal nevus. We report a case of osteonevus of Nanta in combined nevus, possibly the first description of this association.

Eruptive disseminated Spitz nevi - Case report

Abstract Spitz nevus is a benign melanocytic lesion, which presents in several ways: solitary, agminated, or disseminated. The disseminated variant is uncommon; it may have a rapid evolution (the eruptive form) and be difficult to manage. This report presents the case of a 24-year-old patient with multiple papules on his limbs, which had appeared four years previously. On physical examination, 120 pink and skin-colored papules were seen, which under dermoscopy were observed to be homogeneous, pink vascular lesions. Histopathologic study revealed epithelioid cells arranged in groups or singly in the dermis and dermo-epidermal junction. They were HMB-45 positive in the superficial dermis, and Ki-67 < 1%. Given these findings, a diagnosis of eruptive disseminated Spitz nevi was made.

Melanocitosis dérmica adquirida en la mano de un paciente pediátrico / Acquired dermal melanocytosis on the hand of a pediatric patient

Resumen Introducción: Las melanocitosis dérmicas son un grupo de enfermedades dermatológicas pigmentarias asociadas con la proliferación melanocítica. Se clasifican con base en su número y localización profunda a nivel de la dermis; pueden ser congénitas o adquiridas. Caso clínico: Paciente de sexo masculino de 11 años de edad, sin antecedentes de importancia para el padecimiento actual. Inicio con mácula oscura en la palma de la mano izquierda hace 5 años, asintomática, de crecimiento paulatino. A la exploración física, se detectó dermatosis que afectaba la palma izquierda, cara palmar de las falanges proximales del tercer y cuarto dedos, caracterizada por la presencia de mácula grisácea negruzca, bordes difusos e irregulares, no infiltrada ni indurada. En la dermatoscopia se detectó un patrón de pigmento de tono gris acero con áreas de color café, y con evidencia de puntos blanquecinos dentro de estas. En la histopatología se identificaron células fusiformes, con núcleo grande y la presencia de pigmento melánico en su interior, con distribución perivascular y entremezclados con las fibras de colágeno en la dermis superficial y media. Con base en las características clínicas e histopatológicas de la lesión, se concluyó melanocitosis dérmica adquirida de la mano como el diagnóstico definitivo. Conclusiones: Los reportes de casos de melanocitosis dérmica adquiridas atípicas son infrecuentes. La melanocitosis dérmica de la mano es una variante de estas enfermedades, de la que existen menos de 10 casos. Se presenta el primer caso reportado en Latinoamérica hasta el momento, con el objetivo de ampliar el conocimiento de sus características clínico-histológicas y dermatoscópicas.

Abstract Background: Dermal melanocytosis is a group of pigmentary dermatological diseases associated with melanocytic proliferation, which are classified based on their number and depth at the level of the dermis; they may be congenital or acquired. Case report: An 11-year-old male patient with no history of importance for the current condition started 5 years ago with a dark macula in the left hand palm, which was asymptomatic but grew gradually. On physical examination, dermatoses affecting the left palm, palmar face of proximal phalanges of the third, fourth and fifth fingers, characterized by the presence of blackish greyish macula, diffuse and irregular edges, not infiltrated or indurated were detected. The dermatoscopy identified a pattern of pigment with a greyish-brown tone with brown areas, showing whitish spots inside. In the histopathology, the presence of spindle cells was observed in the superficial and middle dermis, with a large nucleus and the presence of a melanic pigment inside, with perivascular distribution and intermingled with the collagen fibres. Based on the clinical characteristics and the histopathological findings, acquired dermal melanocytosis of the hand was concluded as the final diagnosis. Conclusions: Case reports of atypical acquired dermal melanocytosis are infrequent. Dermal melanocytosis of the hand is a rare variant of these diseases, of which less than 10 cases have been reported. At present, this case of dermal melanocytosis is the first reported in Latin America with the aim to extend the knowledge of its clinical-histological and dermatoscopic characteristics.

Melanoacanthoma: a potential pitfall of reflectance confocal microscopy

Abstract Melanoacanthoma is a rare variant of seborrheic keratosis, which is notable for dark pigmentation and fast radial growth, making it difficult to distinguish from melanoma. Histologically, it is characterized by proliferation of keratinocytes and dendritic melanocytes. The authors report a scalp lesion, fast growing, suspected by dermoscopy and confocal microscopy examination, with dendritic cells distributed throughout the lesion. Based on these findings, it was not possible to classify this lesion as clearly benign, so it was excised. Histopathologic evaluation and immunostain were consistent with melanoacanthoma.

Melanin bleaching with potassium permanganate for melanocytic lesions diagnosis in veterinary medicine / Despigmentação de melanócitos com permanganato de potássio para diagnóstico de lesões melanocíticas na medicina veterinária

The aim of this study was to microscopically re-evaluate the melanocytic lesions diagnoses established by the Animal Pathology Laboratory of the Federal University of Uberlândia, in the state of Minas Gerais, Brazil, over a period of eleven years; in addition, to perform a comparative analysis between the conventional histopathological (CH) method and the use of the melanin bleaching (MB) technique with potassium permanganate, sulfuric acid, and oxalic acid solutions. The results of the MB method presented a disagreement in 24.32% of the diagnosis previously by CH, with low agreement (61.0%) and low Kappa coefficient (0.2267). Melanoma was the most frequent lesion, more frequent in elderly and non-breed female dogs. The most frequent melanoma location was in the cutaneous tissue. The presence or absence of a pagetoid spread in cutaneous samples, distribution of melanin, pattern of cell layout, cell morphology, degree of cellular atypia, and the number of mitoses verified after MB were the most important criteria to confirm the diagnosis of malignancy or benignity of the lesions. Evaluating pathologists considered MB to be essential for the majority of diagnoses and an efficient complementary method for the diagnosis of melanocytic lesions, even in cases with a moderate degree of pigmentation.(AU)

Este estudo objetivou reavaliar microscopicamente os diagnósticos de lesões melanocíticas estabelecidos pelo setor de Patologia Animal da Universidade Federal de Uberlândia, em um período de 11 anos, e, com base nesse levantamento, realizar uma análise comparativa entre o método histopatológico convencional (HC) e o método de despigmentação de melanócitos (DM) com permanganato de potássio, ácido sulfúrico e ácido oxálico. A DM revelou discordância em 24,32% dos diagnósticos previamente estabelecidos por HC, apresentando baixa concordância (61,0%) e baixo valor de coeficiente Kappa (0,2267). A alteração mais frequente foi o melanoma, com maior ocorrência em cadelas idosas sem raça definida (SRD). A localização mais frequente dos melanomas foi cutânea. A presença ou ausência de disseminação pagetoide nos casos cutâneos, a forma de distribuição da melanina, o padrão de disposição das células, a morfologia celular, o grau de atipia celular e a quantidade de mitoses verificada após a despigmentação foram critérios de elevada importância para firmar o diagnóstico quanto à malignidade ou benignidade da lesão. A despigmentação foi considerada pelos patologistas avaliadores como essencial para o diagnóstico na maioria dos casos, o que leva a concluir que ela constitui um método complementar eficiente no diagnóstico das lesões melanocíticas, mesmo em casos com grau moderado de pigmentação.(AU)

Recurrent laryngeal neuropathy secondary to nerve compression by melanomas - case report / Neuropatia laríngea recorrente secundária à compressão por melanomas - relato de caso

Recurrent laryngeal neuropathy (RLN) etiology can be acquired, iatrogenic or idiopathic. There are no previous reports of RLN caused by recurrent laryngeal nerve compression by melanomas. This report describes a horse presenting severe dyspnea and progressive weight loss. Physical exam demonstrated tachycardia, tachypnea, inspiratory dyspnea at rest, neck extension and mydriasis. Temporary tracheotomy was performed and videoendoscopic examination diagnosed grade IV laryngeal paralysis. The animal came suddenly to death by suppurative bacterial pneumonia. At necropsy, it was possible to observe multiple melanotic epithelioid melanoma nodules compressing the recurrent laryngeal nerve, alongside with lung and parotid metastasis. This finding emphasizes the importance of establishing a differential diagnosis for tumor mass compression in the etiology of RLN, especially melanomas in gray horses, with or without cutaneous manifestations of masses.(AU)

A neuropatia laríngea recorrente (NLR) pode apresentar etiologia adquirida, iatrogênica ou idiopática. Não há relatos prévios da ocorrência da NLR causada pela compressão do nervo laríngeo recorrente por melanomas. Este relato descreve um equino apresentando dispneia grave e perda de peso progressiva. O exame físico demonstrou taquicardia, taquipneia, dispneia inspiratória em repouso, extensão do pescoço e midríase. Foi realizada traqueotomia temporária e exame videoendoscópico, mediante o qual se diagnosticou paralisia laríngea grau IV. O animal veio a óbito por pneumonia bacteriana supurativa. Na necropsia, foi possível observar múltiplos nódulos de melanoma epitelioide amelanótico comprimindo o nervo laríngeo recorrente, juntamente com metástases pulmonares e parotídeas. Este achado enfatiza a importância de estabelecer um diagnóstico diferencial nos casos de NLR, pensando-se na compressão nervosa por massas tumorais, especialmente melanomas em cavalos tordilhos, com ou sem manifestações cutâneas de massas.(AU)

Uso da técnica em "spaghetti" para tratamento cirúrgico do lentigo maligno / Use of the "spaghetti" technique for surgical treatment of lentigo maligna

O lentigo maligno (LM) é uma forma de melanoma in situ que mais comumente se apresenta como uma mácula de crescimento lentamente progressivo, pigmentada, na face de idosos com pele danificada pelo sol. Esse melanoma in situ tem um risco (30% a 50%) de progressão para lentigo maligno melanoma. A excisão cirúrgica completa da lesão requer margens de pelo menos 10mm, mesmo para lesões in situ. Porém, quando o crescimento de LM ocorre em áreas de implicações estéticas ou funcionais (face, pescoço, solas), a excisão é frequentemente reduzida para preservar estruturas anatômicas importantes e por razões cosméticas. Além disso, as margens periféricas podem ser clinicamente mal definidas e nem sempre pigmentadas, com extensão subestimada e risco de ressecção insuficiente. A "técnica de espaguete", descrita por Gaudy Marqueste, é uma cirurgia estratégica baseada na amostragem de uma faixa de tecido "spaghettilike" para determinar as margens da lesão antes da remoção do tumor. Após a confirmação anatomopatológica de margens livres de neoplasia, a lesão principal central é ressecada, permitindo a reconstrução do defeito no mesmo procedimento, sendo uma alternativa à cirurgia micrográfica de Mohs.(AU)

Lentigo maligna (LM) is a melanoma in situ that commonly presents as a macula with progressive and irregularly pigmented growth, especially in the face of elderly people with sun-damaged skin. This melanoma in situ has a risk (30-50%) of progression to lentigo maligna melanoma. Complete surgical excision of the lesion requires margins of at least 10 mm, even for lesions in situ. However, when the growth of LM occurs in areas of aesthetic or functional implications (face, neck, and soles), the excision is often reduced to preserve important anatomic structures and for cosmetic purposes. Moreover, the peripheral margins may be clinically ill-defined and not always pigmented, and thus, such cases are associated with underestimated extension and risk of insufficient resection. The "spaghetti" technique, described by Gaudy Marqueste, is a strategic surgical approach based on sampling of a range of "spaghetti-like" strips to determine the margins of the lesion prior to removal of the tumor. After the pathological confirmation of neoplasia-free margins, the main central lesion is resected, allowing reconstruction of the defect in the same procedure, as an alternative to Mohs micrographic surgery. (AU)

Histologic review of melanomas by pathologists trained in melanocytic lesions may change therapeutic approach in up to 41 9% of cases

Abstract: Melanoma Guidelines of the Brazilian Dermatology Society recommend histologic review by pathologists trained in melanocytic lesions whenever possible. Out of 145 melanoma cases identified at a private clinic in São Paulo/Brazil, 31 that had been submited to histologic review were studied to evaluate whether revision had led to change in therapeutic approach.. Differences in original/reviewed reports were found in 58.1% (n=18) of the reports, leading to changes in therapeutic approach in 41.9% (n=13). Change in diagnosis was observed in 6 out of 31 (19,3%) cases. These findings suggest that second opinion by pathologists trained in melanocytic lesions is likely to show significant differences from the original report.

Histogenetic categorization of atypical melanocytic tumor of uncertain biological malignant potential

Abstract: Several reports have demonstrated difficulties and lack of agreement in the histopathological diagnosis of particular melanocytic lesions, with problems in their management. A histogenetic approach to the study of these lesions originated the following classification: 1. superficial atypical proliferation significance; 2. melanocytic tumor of uncertain potential; 3. pigmented epithelioid melanocitoma of uncertain potential; 4. microinvasive radial growth phase of uncertain potential. The terminology remains controversial, reflecting the uncertainty of the diagnosis and the biological potential of these atypical melanocytic lesions.

Pigmented squamous cell carcinoma: case report and importance of differential diagnosis

Abstract: A few cases of pigmented squamous cell carcinoma affecting the skin and the ocular and oral mucosa of the elderly have been described in the literature. The disease manifests itself as papular and nodular erythematous or pigmented lesions. The main clinical differential diagnoses are pigmented basal cell carcinoma and melanoma. Histopathological examination is characterized by proliferation of atypical squamous cells with formation of horn pearls permeated by dendritic melanocytes. For this reason, a careful diagnosis is necessary to rule out other tumors that show melanin pigment. Surgical removal is the indicated treatment and the prognosis is similar to the classical squamous cell carcinoma. We report a case of pigmented squamous cell carcinoma with diagnosis confirmed by histological and immunohistochemical examinations.

The recurrent nevus phenomenon

Abstract: Recurrent melanocytic nevus is a proliferation of melanocytes arising from a melanocytic nevus removed partially. Asymmetry and irregular pigmentation may lead to misdiagnosis of melanoma. We report a patient presented with a lesion on the lower abdomen, which was removed by shave excision. Anatomopathological examination revealed an intradermal melanocytic nevus. Two months later, a new irregular hyperpigmented lesion appeared in the surgical scar. Histopathology of the excisional biopsy revealed a recurrent melanocytic nevus. Recurrent melanocytic nevus manifests as a scar with hyper or hypopigmented areas, linear streaking, stippled pigmented halos, and/or diffuse pigmentation patterns. Histologically, the dermoepidermal junction and the superficial dermis show melanocytic proliferation overlying the scarred area. When a pathological report of the previous lesion is not available, complete excision is the gold standard. Otherwise, regular dermoscopic monitoring is a therapeutic option. The present report emphasizes the importance of histopathological examination of the excised material - even in cases of suspected benign lesions - and warns patients about the possibility of recurrence in case of incompletely removed lesions.

Synchronous melanomas arising within nevus spilus

Abstract: Nevus spilus is a melanocytic cutaneous lesion consisting of a light brown background macule with numerous superimposed darker maculopapular speckles. Melanoma arising from a nevus spilus is rare, with less than 40 cases reported to date. The absolute risk for malignant transformation is not well defined, lacking a standardized management approach. We report a new case of melanoma arising from nevus spilus, with the additional peculiarity of multifocality. We offer our recommendations for the management of the condition.

Kissing nevus of the penis: a case report and dermatoscopic findings

Abstract Divided nevus, also known as kissing nevus, is a rare variant of congenital melanocytic nevi in which there are two adjacent nevi in areas of the body that undergo embryonic cleavage. The original description of this type of lesion was on the eyelid. The location on the penis is even rarer, with only 17 case reports in the literature so far, and only one of them described the dermoscopic findings. We report the case of a patient with divided nevus of the penis and its clinical, dermoscopic and histopathological features.

Blue nevus with satellitosis: case report and literature review

Abstract: Blue nevus is a benign melanocytic lesion, typically asymptomatic and of unknown etiology. Many histological subtypes are recognized, the most commons being: common blue nevus, cellular blue nevus, and combined blue nevus. New rare variants have been described in the literature, with emphasis on eruptive blue nevus, plaque, agminate, linear, with satellitosis, disseminated, familial and targetoid. The diagnosis of blue nevus usually presents no difficulties, however, the presence of structures such as irregular edges or satellitosis, are highly suggestive of malignancy, and the differential diagnosis with malignant blue nevus and melanoma with peripheral spread should be considered. We report a case of blue nevus with satellitosis in a 15-year-old female patient.

Chemical leukoderma induced by dimethyl sulfate

Abstract Chemical leukoderma occurs due to the toxic effect of a variety of chemical agents. Mechanisms include either destruction or inhibition of melanocytes. We report two male patients (36 and 51 years old) who presented with multiple hypopigmented macules and patches on the neck, wrist, and legs after exposure to dimethyl sulfate in a chemical industry. Physical examination revealed irregular depigmentation macules with sharp edges and clear hyperpigmentation around the lesions. History of repeated exposure to a chemical agent can help the clinical diagnosis of chemical leukoderma. This diagnosis is very important for prognosis and therapeutic management of the disease.

Agminated blue nevus - Case report

Abstract: Blue nevi are benign melanocytic lesions located in the deeper reticular dermis, consequence of failure of melanocytic migration into the dermal-epidermal junction from the neural crest. Lesions are usually asymptomatic and solitary, but may present in a multiple or agminated (grouped) pattern. The agminated subtype is formed when bluish-pigmented lesions cluster together in a well-defined area. Lesions can be flat or raised. We report the case of a patient who presented multiple bluish macules (1-3 mm in diameter) grouped on the left upper back. Dermoscopy and anatomic pathological examination were consistent with blue nevus.

Conjunctival tumors in children: histopathologic diagnosis in 165 cases / Tumores conjuntival em crianças: diagnóstico histopatológico em 165 casos

ABSTRACT Purpose: Conjunctival tissue tumors have a varied presentation, and few series studies on pediatric patients have been published. The objective of this paper is to report the histopathologic diagnoses (spanning over 1988-2013) of conjunctival tumors in children younger than 14 years. Methods: We conducted a retrospective, descriptive, and observational study by reviewing the database of all children in whom a conjunctival tumor was surgically removed at Hospital de Ojos y Oídos "Dr. Rodolfo Robles V.," Benemérito Comité Pro Ciegos y Sordos de Guatemala. The data pertaining to gender, age, and histopathologic diagnosis of all cases was collected. The same ocular pathologist made all diagnoses. Results: One hundred sixty-five cases were found, with a mean age of 7.88 years, being 91 (55.15%) male subjects. Melanocytic lesions were the most common tumors found (30.91% of cases), with only one case (0.60%) being malignant. Conclusions: Melanocytic lesions were the most common tumors found, and of all the cases, only one was malignant; this was in a patient with xeroderma pigmentosum. These findings are consistent with those reported in other studies regarding the frequencies of the histopathology of conjunctival tumors in the pediatric population.

RESUMO Objetivo: Tumores do tecido conjuntival tem uma apresentação variada. Poucas séries de pacientes pediátricos foram publicadas. O objetivo deste trabalho é apresentar os diagnósticos histopatológicos de tumores conjuntivais em crianças com menos de 14 anos de idade, obtidas durante um período de 25 anos. Métodos: Estudo retrospectivo, descritivo e observacional foi realizado. Nós revisamos o banco de dados de todas as crianças em quem um tumor conjuntival foi removido cirurgicamente no Hospital de Ojos y oidos "Dr. Rodolfo Robles V.," Benemérito Comité Pro Ciegos y Sordos de Guatemala. Sexo, idade e diagnóstico histopatológico de todos os casos foram compilados. O mesmo patologista ocular fez todos os diagnósticos. Resultados: Cento e sessenta e cinco casos foram encontrados, com média de 7,88 anos, sendo 91 (55,15%) do sexo masculino. Lesões melanocíticas foram as mais frequentes (30,91% dos casos). Apenas um caso (0,60%) era maligno. Conclusões: Lesões melanocíticas foram as mais frequentes. Do total, apenas uma lesão era maligna, o que correspondeu a um paciente com xeroderma pigmentoso. Estes resultados são consistentes com o relatado em outros estudos quanto à frequência de diagnóstico histopatológico de tumores da conjuntiva na população pediátrica.

Spitz nevi in the classic histopathological pattern - lamb in wolf`s clothing

Spitz nevus is a benign melanocytic lesion and also one of the main differential diagnosis of melanoma. A descriptive and retrospective study of surgical specimens from patients with a diagnosis of Spitz nevus was conducted at two institutions in Niterói - RJ. 32 cases were analyzed. The most frequent histological subtype was compound (60 %), with a predominance of epithelioid cells (17 cases - 53%). Pagetoid spread was observed in 21 cases (68%). Maturation of melanocytes was present in 13 cases (81%). Kamino bodies were found in eight cases (25%). Atypical melanocytes were present in 18 cases (56%). Mitoses were present in 11 cases (34%). Detailed knowledge of the classical form of Spitz nevi is essential for the differential diagnosis with melanoma. However, no single criterium is definitive in the differential diagnosis between Spitz nevus and melanoma.