Congenital Juvenile Xanthogranuloma in the Perioral Region: A Case Image.

Juvenile xanthogranuloma (JXG) is the most common form of non-Langerhans cell histiocytosis in childhood. It often presents with cutaneous involvement and exhibits a predilection for the head and neck region. This article illustrates a case of congenital JXG in a 5-month-old boy, characterized by a solitary, well-circumscribed nodule above the left upper lip. Histopathologically, the lesion exhibited histiocytes with eosinophilic cytoplasm and Touton giant cells. Immunohistochemistry revealed histiocytes positive for CD68 and Factor XIIIa, while negative for S-100 protein. Clinicians should become familiar with the broad clinical spectrum of cutaneous JXG, particularly its congenital presentation, in order to ensure timely and accurate management.

Oral Juvenile Xanthogranuloma: A Clinicopathological, Immunohistochemical and BRAF V600E Study of Five New Cases, with Literature Review.

Juvenile xanthogranuloma (JXG) is the most common form of non-Langerhans cell histiocytosis and oral mucosal involvement is exceedingly rare. Histiocytic disorders harbor activating mutations in MAPK pathway, including the report of BRAF V600E in JXG of extracutaneous site. However, no information is available for oral JXG. Herein, the clinicopathological and immunohistochemical features of five new oral JXG were evaluated in conjunction with literature review. Also, we assessed the BRAF V600E in oral samples. Five oral JXG were retrieved from pathology archives. Morphological and immunohistochemical analyses were performed. The BRAF V600E status was determined with TaqMan allele-specific qPCR. The series comprised of three female and two male patients, most of them adults, with a median age of 39 years (range 13-68 years). Clinically, the lesions appeared as asymptomatic solitary nodules, measuring until 2.5 cm, with more incident to the buccal mucosa. Morphologically, most of the cases presented classical histological features of JXG, with histiocytic cells consistent with the non-Langerhans cell immunophenotype. BRAF V600E was not detected in the cases tested. This is the first and largest published series of oral JXG affecting adults and a Brazilian population. The molecular pathogenesis of oral JXG remains unknown. Clinicians and pathologists must recognize JXG to avoid misdiagnoses with oral benign or malignant lesions.

Erdheim-Chester disease presenting at the central nervous system.

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis (LCH) that affects different body systems. It was recently recognized as a neoplastic disorder after identifying an activating mutation of the MAPK pathway. Neurological presentations of ECD are rare. We present a case of a 35-year-old male who presented to the emergency department with neck pain, headache and vomiting for 2 months; MRI showed multiple heterogeneous intracranial masses. Neurosurgery performed a suboccipital craniotomy, partially resected the cerebellar mass, and placed a parietal to frontal shunt catheter. Biopsy results from the cerebellar mass demonstrated cerebellar tissue involved by a diffuse proliferation of foamy histiocytes and spindle cells admixed with prominent lymphoplasmacytic infiltrate and positive for CD68, CD163, Factor XIIIa and Fascin. PET scan showed hypermetabolic uptake within the medullary portions of the diffuse abnormal lesions of the distal femurs, tibias, and fibulas, and cardiac MRI was nonsignificant. The patient was started on vemurafenib and continued to show improvement in a 3-month outpatient follow-up.

Estudo clinicopatológico, imuno-histoquímico e molecular do xantogranuloma juvenil oral / Oral juvenile xanthogranuloma: a clinicopathological, immunohistochemical and BRAF V600E study of five new cases, with literature review

O xantogranuloma juvenil (JXG) é a forma mais comum de histiocitose de células não Langerhans na infância. Embora as lesões cutâneas sejam comuns, o envolvimento da mucosa oral é extremamente raro. Alguns estudos investigaram a base genética do JXG cutâneo e extracutâneo. No entanto, não há dados disponíveis para o JXG oral. Distúrbios histiocíticos têm sido associados a mutações da via proteína quinase ativada por mitogênio (MAPK) de ativação, incluindo o relato de BRAF V600E em JXG de locais extracutâneos. No presente estudo, as características clinicopatológicas e imuno-histoquímicas de cinco novos casos de JXG oral foram avaliadas em conjunto com uma revisão da literatura. Além disso, investigamos a ocorrência da mutação BRAF V600E nas amostras. Cinco JXG orais foram recuperados em dois serviços de patologia oral no Brasil. Os dados clínicos e demográficos foram coletados dos prontuários médicos. Foram realizadas análises clinicopatológicas e imuno-histoquímicas. O status do BRAF V600E foi determinado com Reação em Cadeia da Polimerase (PCR) alelo-específico com uso de uma Sonda Taqman. A série foi composta por 2 homens (40,0%) e 3 mulheres (60,0%), com média de idade de 38,8 ± 22,9 anos (variação: 13­68 anos) e proporção de mulheres para homens de 1,5: 1. A mucosa jugal (n = 3, 40,0%) foi a localização mais comum. Clinicamente, as lesões apresentavam-se como nódulos normocrômicos ou amarelados assintomáticos medindo de 1,0 a 2,5 cm (1,7 ± 0,6). Nenhum caso apresentou lesões cutâneas. Todos os casos foram excisados cirurgicamente. Morfologicamente, a maioria dos casos (n = 4, 80,0%) apresentou características histológicas clássicas de JXG com células histiocíticas positivas para CD68, CD163 e fator XIIIa. Considerando o status do BRAF, o BRAF V600E não foi detectado nos casos testados. Esta é a primeira e maior série publicada afetando adultos e uma população brasileira. A patogênese molecular do JXG oral permanece desconhecida.

Juvenile xanthogranuloma (JXG) is the most common form of non-Langerhans cell histiocytosis in childhood. Although cutaneous lesions are common, oral mucosa involvement is exceedingly rare. Some studies investigated the genetic basis of cutaneous and extracutaneous JXG, however, no data is available for oral JXG. Histiocytic disorders have been associated with activating MAPK pathway mutations, including the report of BRAF V600E in JXG extracutaneous sites. Herein the clinicopathological and immunohistochemical features of five new cases of oral JXG were evaluated in conjunction with a literature review. Also, we assessed the BRAF V600E mutation in oral samples. Five oral JXG were retrieved from two oral pathology services in Brazil. Clinical and demographic data were collected from medical records. Clinicopathological and immunohistochemical analyses were performed. The BRAF V600E status was determined with TaqMan allele-specific qPCR. The series comprised of2 men (40.0%) and 3 women (60.0%), with a mean age of 38.8 ± 22.9 years (range: 13­68 years) and a 1.5:1 female-to-male ratio. The buccal mucosa (n = 3, 40.0%) was the most common location. Clinically, lesions appeared as a normochromic or yellowish asymptomatic nodules measuring from 1.0 to 2.5 cm (1.7 ± 0.6). No cases presented cutaneous lesions. All cases were surgically excised. Morphologically, most cases (n = 4, 80.0%) presented classical histological features of JXG with histiocytic cells positive for CD68, CD163, and factor XIIIa. Considering the BRAF status, BRAF V600E was not detected in the cases tested. This is the first and largest series published affecting adults and a Brazilian population. Molecular pathogenesis of oral JXG remains unknown.

Erdheim-Chester disease presenting at the central nervous system

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis (LCH) that affects different body systems. It was recently recognized as a neoplastic disorder after identifying an activating mutation of the MAPK pathway. Neurological presentations of ECD are rare. We present a case of a 35-year-old male who presented to the emergency department with neck pain, headache and vomiting for 2 months; MRI showed multiple heterogeneous intracranial masses. Neurosurgery performed a suboccipital craniotomy, partially resected the cerebellar mass, and placed a parietal to frontal shunt catheter. Biopsy results from the cerebellar mass demonstrated cerebellar tissue involved by a diffuse proliferation of foamy histiocytes and spindle cells admixed with prominent lymphoplasmacytic infiltrate and positive for CD68, CD163, Factor XIIIa and Fascin. PET scan showed hypermetabolic uptake within the medullary portions of the diffuse abnormal lesions of the distal femurs, tibias, and fibulas, and cardiac MRI was nonsignificant. The patient was started on vemurafenib and continued to show improvement in a 3-month outpatient follow-up.

Juvenile Xanthogranuloma: An Entity With a Wide Clinical Spectrum. / Xantogranuloma juvenil: una entidad con amplio espectro clínico.

Juvenile xanthogranulomas (JXGs) are rare, benign lesions that belong to the large group of non-Langerhans cell histiocytoses. JXG presents with 1 or more erythematous or yellowish nodules that are usually located on the head or neck. Most JXG lesions are congenital or appear during the first year of life. Extracutaneous involvement is rare, but the literature traditionally suggests investigating the possibility of ocular compromise. JXG is mainly a clinical diagnosis, but a skin biopsy may sometimes be needed for confirmation. JXGs on the skin are self-limiting and usually do not require treatment. This review describes the clinical and therapeutic aspects of JXG, emphasizing available evidence and the diagnosis of extracutaneous involvement.

Oral juvenile xanthogranuloma in a child: Clinical, histological and immunohistochemical profile of a rare entity.

Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis (non-LCH) affecting normolipemic infants and children most frequently in the first year of life, often showing spontaneous regression within 3 to 6 years. Classic JXG is characterized by a yellowish asymptomatic papule or nodule, often located in the skin of the head, neck and upper trunk. Oral JXG has been reported, but is rare. Histologically, JXG is composed mainly of an infiltrate of macrophages with a variable degree of lipidization (foamy macrophages), and (most of the time) scattered Touton-type giant cells. Because of the rarity of oral lesions and possible variations in the clinical and histological presentation, the correct diagnosis can be challenging, requiring a careful clinical and histopathological evaluation with adjuvant immunohistochemical studies. Our review of the English-language literature disclosed 33 cases of oral JXG, including this case report. The purpose of this study is to present a new case of this uncommon entity as well as to review and discuss its main clinicopathologic features and immunohistochemical findings.

Doença de Rosai-Dorfman cutânea: relato de caso / Cutaneous Rosai-Dorfman disease: a case report

A doença de Rosai-Dorfman, também denominada histiocitose sinusal com linfadenopatia maciça, é histiocitose de células não Langerhans, idiopática e de curso benigno. Descrita em 1969, caracteriza-se por linfadenomegalia não dolorosa, sendo a cadeia cervical a mais envolvida, além de febre, perda de peso e sudorese. O envolvimento extranodal ocorre em 43 por cento dos casos, em que múltiplos sítios podem ser acometidos. Já foram descritos casos exclusivamente extranodais, inclusive formas limitadas à pele. Relata-se um caso de doença de Rosai-Dorfman extranodal cutânea pura, devido à raridade dessa apresentação clínica.

Rosai-Dorfman disease, otherwise known as sinus histiocytosis with massive lymphadenopathy, is a non-Langerhans cell histiocytosis with a benign course and unknown etiology. It was described in 1969 as a painless cervical lymph node enlargement in association with fever, weight loss and sweating. Extranodal disease has been reported in 43 percent of cases, with involvement of multiple organs. Purely extranodal Rosai-Dorfman disease has been already reported, including forms restricted to the skin. This paper reports a case of purely cutaneous Rosai-Dorfman disease, which is of interest in view of the rarity of this condition.