Histiocytosis in the pediatric spine: a clinical and radiographic analysis of 50 patients.

STUDY DESIGN: Descriptive, retrospective. Scientific level of evidence IV. OBJECTIVES: The aim of this study was to evaluate a consecutive case series of 50 pediatric patients with LCH of the spine. Langerhans cell histiocytosis (LCH) is a rare disease characterized by abnormal proliferation of Langerhans cells in different organs. Incidence in children range from 2 to 10 cases per million. In the current literature, few series evaluate LCH in the pediatric spine. MATERIAL AND METHODS: A consecutive case series of 50 pediatric patients with LCH of the spine treated at our hospital between 1984 and 2016, with a follow-up of at least 2 years, was analyzed. Sex, age, clinical and radiographic presentation, number of lesions, treatment, complications, and outcome were assessed. RESULTS: Fifty patients, 26 boys and 24 girls, were evaluated. Mean age was 5 years and 2 months (6 months to 13 years and 3 months). 27 patients had a single spinal lesion while 23 had 2 or more lesions. A total of 100 vertebrae were involved. The thoracic spine was the most affected. The most frequent lesion location was in the vertebral body in 88% of the cases. The symptoms were pain (87%), reduced range of motion, deformity, and neurologic deficit. Biopsy was performed in 48 patients. Thirty-nine patients received medical treatment, 28 used orthoses and six required surgery. Six patients (12%) recurred at a mean of 3 years and 5 months (range 2-12 years). In all cases, neurological symptoms, torticollis, and deformities resolved after medical or surgical treatment. CONCLUSIONS: Because of the variable presentation of the disease, ranging from a solitary isolated vertebral lesion to polyostotic and multisystemic involvement, a multidisciplinary team is required to have an adequate management of these patients and to obtain good results.

Congenital Langerhans cell histiocytosis / Histiocitosis congénita de células de Langerhans

Langerhans cell histiocytosis is a rare pathology with different clinical manifestations in the neonatal period ranging from isolated bone lesions to systemic compromise. We report a case of Langerhans cell histiocytosis including a literature review focused on the clinical manifestations, diagnosis, and treatment. A one-month-old patient was brought to medical consultation with lymphadenopathy and skin lesions, which were initially managed as an infectious pathology. The disease continued its progression without improvement with the treatment until the patient died due to respiratory failure. The lymph node and skin biopsies revealed infiltration of atypical cells with positive immunohistochemistry for S100, CD1, and CD68 confirming Langerhans cell histiocytosis. This disorder represents a great challenge and, therefore, it is important to alert and sensitize medical teams about it for timely diagnosis and management.

La histiocitosis de células de Langerhans es una enfermedad poco frecuente, cuyas manifestaciones clínicas pueden aparecer en el periodo neonatal y varían desde lesiones óseas aisladas hasta un compromiso sistémico. Se describe un caso de histiocitosis de células de Langerhans y se revisa la literatura médica sobre las manifestaciones clínicas, el diagnóstico y el tratamiento. El paciente de un mes de nacido fue llevado a consulta por presentar adenopatías y lesiones en la piel que, inicialmente, fueron tratadas como reacción a una infección. La enfermedad continuó su progresión sin que hubiera mejoría con el tratamiento, hasta que el paciente falleció por falla respiratoria. La biopsia de ganglio linfático y la de piel revelaron infiltración de células atípicas, y la inmunohistoquímica resultó positiva para las proteínas S100, CD1 y CD68, con lo cual se confirmó el diagnóstico de histiocitosis de células de Langerhans. Esta alteración representa un gran desafío clínico, por lo que es importante alertar y sensibilizar al equipo médico para lograr un diagnóstico y un tratamiento más oportunos.

Histiocitosis de células de Langerhans con compromiso vertebral / Langerhans cell histiocytosis with vertebral involvement

Resumen: Introducción: La histiocitosis de células de Langerhans (HCL) es un trastorno histiocítico raro y su incidencia exacta se mantiene desconocida; se ha diagnosticado en todos los grupos de edad, pero es más común en los primeros 3 años de vida. Se caracteriza por lesiones únicas o múltiples de tipo osteolítico causadas por proliferación clonal de células histológicamente similares a las células de Langerhans; su presentación clínica es heterogénea. Caso clínico: Presentamos el caso de una paciente de sexo femenino de 7 años, con dificultad para la marcha y debilidad progresiva en los miembros inferiores de 5 días de evolución. A la exploración física presenta hallazgos concordantes con síndrome piramidal e hipoes­ tesias de miembros inferiores. Se realizó resonancia magnética (RM) de columna y tomografía computarizada de cráneo simple, que descartó patología intracraneal . En la RM de columna se detectó vertebra plana con extensión epidural y para­ vertebral, por lo que se inició manejo con esteroides y se indicó descompresión quirúrgica. Se realizó resección parcial y biopsia de la lesión. Debido a los hallazgos histológicos y la presencia de marcadores positivos para CD1a y CD207, se confirmó el diagnóstico de HCL. Conclusiones: La HCL es una enfermedad poco frecuente y de difícil diagnóstico por su presentación heterogénea. El granuloma eosinofílico y la vértebra plana como hallazgos imagenológicos pueden orientar el diagnóstico, aunque siempre se debe confirmar histológicamente.

Abstract: Background: Langerhans cell histiocytosis (LCH) is a rare disease, more common in the first three years of lite. lt is characterized by single ar multiple osteolytic lesions due to clonal proliferation of cells histologically similar to Langerhans cells; its clínical presentation is heterogeneous. Case report: 7-year-old female patient with 5 days of progressive lower extremity weakness and difficulty to walk. Physical exam findings were consistent with pyramidal syndrome and lower extremities hypoesthesia. Magnetic resonance imaging (MRI) of spine and cranial computed tomography (CT) were performed. lntracranial pathology was ruled out. The MRI findings showed vertebra plana with epidural and paravertebral involvement, so treatment with steroids and surgical decompression initiated. Partíal resection and biopsy of the lesion was performed. Due to histological findings and positive CD1a and CD207 markers, diagnosis of LCH was confirmed. Conclusions: LCH is an uncommon disease with a challenging diagnosis due to its heterogeneous clinical presentation. Eosinophilic granuloma and vertebra plana as imaging findings may guide the diagnosis. However, it should always be confirmed with histological evidence.

Oral manifestations of Langerhans cell histiocytosis: A case series.

AIM: Langerhans cell histiocytosis (LCH) is an unusual proliferative disorder of bone marrow-derived histiocytes (Langerhans cells) that can produce focal or systemic manifestations. Oral manifestations of LCH can present as single or multiple lesions and can be a challenge in clinical practice. The aim of this paper is to present the clinicopathological features of a series of nine patients with oral involvement. METHODS AND RESULTS: The patient's age ranged from 2 to 63 years being five males and four females. The most common oral site involvement was the hard-palate mucosa. Ulceration was the main clinical feature. Only two patients showed clearly jawbone involvement. In eight out of nine patients, the diagnosis of LCH was established because of the oral manifestations. CONCLUSION: The recognition of the clinical features of LCH oral manifestation is important to avoid misdiagnosis and to the establishment of the correct treatment. Thus, dentists can play a vital role in the diagnosis of LCH since oral lesions may be the earliest manifestation and sometimes the only sign of the disease. Furthermore, oral lesions may be the early signs of disease reactivation or a multisystem disease indication.

[Histiocitosis de células de Langerhans con compromiso vertebral]. / Langerhans cell histiocytosis with vertebral involvement.

Introducción: La histiocitosis de células de Langerhans (HCL) es un trastorno histiocítico raro y su incidencia exacta se mantiene desconocida; se ha diagnosticado en todos los grupos de edad, pero es más común en los primeros 3 años de vida. Se caracteriza por lesiones únicas o múltiples de tipo osteolítico causadas por proliferación clonal de células histológicamente similares a las células de Langerhans; su presentación clínica es heterogénea. Caso clínico: Presentamos el caso de una paciente de sexo femenino de 7 años, con dificultad para la marcha y debilidad progresiva en los miembros inferiores de 5 días de evolución. A la exploración física presenta hallazgos concordantes con síndrome piramidal e hipoestesias de miembros inferiores. Se realizó resonancia magnética (RM) de columna y tomografía computarizada de cráneo simple, que descartó patología intracraneal. En la RM de columna se detectó vertebra plana con extensión epidural y paravertebral, por lo que se inició manejo con esteroides y se indicó descompresión quirúrgica. Se realizó resección parcial y biopsia de la lesión. Debido a los hallazgos histológicos y la presencia de marcadores positivos para CD1a y CD207, se confirmó el diagnóstico de HCL. Conclusiones: La HCL es una enfermedad poco frecuente y de difícil diagnóstico por su presentación heterogénea. El granuloma eosinofílico y la vértebra plana como hallazgos imagenológicos pueden orientar el diagnóstico, aunque siempre se debe confirmar histológicamente. Background: Langerhans cell histiocytosis (LCH) is a rare disease, more common in the first three years of life. It is characterized by single or multiple osteolytic lesions due to clonal proliferation of cells histologically similar to Langerhans cells; its clinical presentation is heterogeneous. Case report: 7-year-old female patient with 5 days of progressive lower extremity weakness and difficulty to walk. Physical exam findings were consistent with pyramidal syndrome and lower extremities hypoesthesia. Magnetic resonance imaging (MRI) of spine and cranial computed tomography (CT) were performed. Intracranial pathology was ruled out. The MRI findings showed vertebra plana with epidural and paravertebral involvement, so treatment with steroids and surgical decompression initiated. Partial resection and biopsy of the lesion was performed. Due to histological findings and positive CD1a and CD207 markers, diagnosis of LCH was confirmed. Conclusions: LCH is an uncommon disease with a challenging diagnosis due to its heterogeneous clinical presentation. Eosinophilic granuloma and vertebra plana as imaging findings may guide the diagnosis. However, it should always be confirmed with histological evidence.

Multiple cystic lung disease.

Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt-Hogg-Dubé); other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management.

Differentiating skin-limited and multisystem Langerhans cell histiocytosis.

OBJECTIVE: To identify features associated with multisystem involvement and therapeutic failure in patients with skin Langerhans cell histiocytosis (LCH). STUDY DESIGN: We reviewed medical records of 71 consecutive patients with LCH with skin involvement evaluated at Texas Children's Hospital and analyzed clinical features, laboratory results, and the presence of circulating cells with the BRAF-V600E mutation with respect to initial staging and clinical outcomes. RESULTS: Skin disease in patients older than 18 months of age at diagnosis was associated with the presence of multisystem disease (OR, 9.65; 95% CI, 1.17-79.4). Forty percent of patients referred for presumed skin-limited LCH had underlying multisystem involvement, one-half of these with risk-organ involvement. Patients with skin-limited LCH had a 3-year progression-free survival of 89% after initial therapy, and none developed multisystem disease. Patients with skin/multisystem involvement had a 3-year progression-free survival of 44% with vinblastine/prednisone therapy, and risk-organ involvement did not correlate with failure to achieve nonactive disease. Circulating cells with BRAF-V600E were detected at higher frequency in patients with multisystem involvement (8 of 11 skin/multisystem vs 1 of 13 skin-limited; P = .002). CONCLUSION: Skin-limited LCH necessitates infrequent therapeutic intervention and has a lower risk of progression relative to skin plus multisystem LCH. The less-aggressive clinical course and lack of circulating cells with the BRAF-V600E mutation in skin-limited LCH suggest a different mechanism of disease origin compared with multisystem or risk-organ disease.

Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a poorly understood proliferative disease, with different patterns of clinical presentation. Currently it is classified according to the number and type of system involved and the degree of organ dysfunction. The aetiology of the disease remains uncertain, and in some cases the disease is polyclonal, suggesting a reactive condition. Many cytokines have been implicated in the pathogenesis of LCH. Different therapeutic approaches can be considered depending on the affected organ, including surgery, radiotherapy and chemotherapy. Long-term organ dysfunction may remain, despite disease control and/or eradication, making indefinite supportive treatment mandatory. Here we present a literature review on all of the aspects of the disease, treatment approaches and existing protocols, and finally an adult clinical case.

Histiocitosis de células de Langerhans en menores de un año / Langerhans cell histiocytosis in children under one year

Introducción. La histiocitosis de células de Langerhans se debe a la proliferación clonal de histiocitos activados que invaden diversos tejidos. Se produce en todas las edades, desde el nacimiento hasta la adultez, con un pico de mayor incidencia entre 1 a 4 años. Objetivo. Describir las características de 15 pacientes pediátricos menores de 1 año con diagnóstico de histiocitosis de células de Langerhans, las manifestacionesclínicas y evolución de la enfermedad. Métodos. Estudio descriptivo retrospectivo, realizado en el Hospital Ramos Mejía y el Hospital Alemán, entre 1999 y 2007. Resultados. Se revisaron las historias de 15 pacientes, 6 niñas y 9 niños. Las lesiones en 8 casos estaban presentes al nacer y 7 aparecieron entre los 2 y 12 meses de edad. En las congénitas se observó como única manifestación clínica inicial el compromiso cutáneo. Uno de estos pacientes presentó evolución sistémica, con compromiso pulmonar, hepático y esplénico, actualmente en tratamiento. De los pacientes con lesiones posteriores al nacimiento, sólo 3 tenían compromiso cutáneo únicamente, el resto presentó compromiso sistémico. Uno de estos pacientes falleció durante el tratamiento. En la histopatología se observaron histiocitos en la dermis papilar con marcado epidermotropismo. La inmunomarcación con CD1a y S100 fue positiva. Conclusiones. La histiocitosis de células de Langerhans es una entidad con dos variantes: la forma congénita y la de inicio posterior al nacimiento, ambas con capacidad para producir compromiso sistémico.(AU)

Introduction. Langerhans cell histiocytosis is characterized by a clonal proliferation of activated Langerhans cells that infiltrate various organs of the body. Occurs at any age, from newborn until adulthood, with an incidence peak at 1-4 years. Objective. To describe the morphologyc characteristics of skin lesions and clinical course of 15 patients with Langerhans cell histiocytosis. Methods. A retrospective review of the medical records of patients with Langerhans cell histiocytosis from Ramos Mejia Hospital and Aleman Hospital, between 1999-2007. Results. Review of medical records from 15 patients, 6 females and 9 males. Skin lesions were congenital in 8 cases and appeared between 2-12 months of age in 7 cases. The patients with congenital presentation only had a cutaneous manifestation; one patient who developed a systemic compromise (lung, liver and spleen) is currently under treatment. Three patients with presentation after birth only had cutaneous lesions, the others had a sistemic disease. One of this patients died during treatment. Histopathology showed a histiocytic infiltrate in the papilary dermis with epidermotrophism; inmunomarking with S100 and CD1a was positive. Conclusion. Both clinical manifestation (congenital and after birth) represent different ends of a spectrum of the same condition, with the potencial to develop into disseminated Langerhans cell histiocytosis.(AU)

Histiocitosis de células de Langerhans en menores de un año / Langerhans cell histiocytosis in children under one year

Introducción. La histiocitosis de células de Langerhans se debe a la proliferación clonal de histiocitos activados que invaden diversos tejidos. Se produce en todas las edades, desde el nacimiento hasta la adultez, con un pico de mayor incidencia entre 1 a 4 años. Objetivo. Describir las características de 15 pacientes pediátricos menores de 1 año con diagnóstico de histiocitosis de células de Langerhans, las manifestacionesclínicas y evolución de la enfermedad. Métodos. Estudio descriptivo retrospectivo, realizado en el Hospital Ramos Mejía y el Hospital Alemán, entre 1999 y 2007. Resultados. Se revisaron las historias de 15 pacientes, 6 niñas y 9 niños. Las lesiones en 8 casos estaban presentes al nacer y 7 aparecieron entre los 2 y 12 meses de edad. En las congénitas se observó como única manifestación clínica inicial el compromiso cutáneo. Uno de estos pacientes presentó evolución sistémica, con compromiso pulmonar, hepático y esplénico, actualmente en tratamiento. De los pacientes con lesiones posteriores al nacimiento, sólo 3 tenían compromiso cutáneo únicamente, el resto presentó compromiso sistémico. Uno de estos pacientes falleció durante el tratamiento. En la histopatología se observaron histiocitos en la dermis papilar con marcado epidermotropismo. La inmunomarcación con CD1a y S100 fue positiva. Conclusiones. La histiocitosis de células de Langerhans es una entidad con dos variantes: la forma congénita y la de inicio posterior al nacimiento, ambas con capacidad para producir compromiso sistémico.

Introduction. Langerhans cell histiocytosis is characterized by a clonal proliferation of activated Langerhans cells that infiltrate various organs of the body. Occurs at any age, from newborn until adulthood, with an incidence peak at 1-4 years. Objective. To describe the morphologyc characteristics of skin lesions and clinical course of 15 patients with Langerhans cell histiocytosis. Methods. A retrospective review of the medical records of patients with Langerhans cell histiocytosis from Ramos Mejia Hospital and Aleman Hospital, between 1999-2007. Results. Review of medical records from 15 patients, 6 females and 9 males. Skin lesions were congenital in 8 cases and appeared between 2-12 months of age in 7 cases. The patients with congenital presentation only had a cutaneous manifestation; one patient who developed a systemic compromise (lung, liver and spleen) is currently under treatment. Three patients with presentation after birth only had cutaneous lesions, the others had a sistemic disease. One of this patients died during treatment. Histopathology showed a histiocytic infiltrate in the papilary dermis with epidermotrophism; inmunomarking with S100 and CD1a was positive. Conclusion. Both clinical manifestation (congenital and after birth) represent different ends of a spectrum of the same condition, with the potencial to develop into disseminated Langerhans cell histiocytosis.

Reactivation and risk of sequelae in Langerhans cell histiocytosis.

OBJECTIVE: To evaluate disease reactivation in patients with Langerhans cell histiocytosis (LCH) and its impact on adverse sequelae. MATERIALS AND METHODS: A retrospective evaluation of 300 patients diagnosed with LCH between 1987 and 2002 with complete response to initial treatment was performed. RESULTS: Mean age at diagnosis was 5.3 years. With a mean follow-up of 4.8 years, reactivation of the disease occurred in 29.7% (89/300) of the patients, with two or more reactivations in 34.8% (31/89) of those. Reactivation occurred in 17.4, 36.8, 46.5, and 53.5% of the patients with single-system unifocal disease (Group A: 161 patients), single-system multifocal disease (Group B: 53 patients), multi-system disease without (Group C: 58 patients), and with (Group D: 28 patients) risk-organ involvement, respectively. The differences between the incidence rates of Groups A and B (P < 0.0004), A and C (P < 0.0001), and A and D (P < 0.0001) were highly significant. The most common reactivation sites involved were bone, middle ear, and skin; reactivation was rare in risk organs (9.5%). The median time between initial complete response and the first reactivation episode was 1 year for Group A, 1.3 years for Group B, and 9 months for Groups C and D. Most reactivation episodes (88%) occurred within the first 2 years of follow-up. Adverse sequelae were recognized in 242/300 patients: 71% (49/69) of patients with and 25.4% (44/173) without reactivations developed these adverse sequelae (P < 0.0001), respectively. Sites most commonly showing sequelae were bone, middle ear, and hypothalamus (Diabetes Insipidus). CONCLUSIONS: Incidence of reactivation correlates with the stage of the disease at diagnosis. Incidence of sequelae correlates with the occurrence of reactivations.

Isolated pulmonary Langerhans cell histiocytosis presenting with recurrent pneumothorax.

We describe the outcome of a 20-month-old female and a 6-year-old male, both of whom had acutely developed severe respiratory distress with tachypnea, cyanosis and, in Patient 2, thoracic pain. Chest X-ray and CT scan showed interstitial pulmonary involvement and a bullous process with bilateral pneumothoraces for both children. Pulmonary biopsy confirmed the diagnosis of Langerhans cell histiocytosis (LCH). Laboratory testing and skeletal radiography did not reveal any other involvement of LCH. The patients received chemotherapy (prednisone, vinblastine, 6-mercaptopurine). They had recurrent episodes of pneumothorax during follow-up and placement of chest tubes was the treatment chosen. They were asymptomatic, with regression of bullae and disappearance of pneumothorax at 58 and 63 months of follow-up, respectively. Pulmonary function tests done during follow-up were normal in both patients. Despite severe pulmonary involvement, conservative surgical treatment and moderate chemotherapy produced good results in these two rare cases.

Histiocitosis X: revisión de la literatura y presentación de caso clínico / Histiocytosis X: a review of the literature and clinical case presentation

La Histiocitosis X es una enfermedad rara sin causa conocida, que está caracterizada por la presencia de células histiocitáricas que deben ser tratadas para prevenir su evolución. Este artículo llega a través de una revisión de la literatura y presentación de caso clínico de un paciente del sexo femenino, que fue presentado con lesiones en la región posterior de la mandíbula, al ser tomado las radiografías se evidenció áreas alveolares de radiolucidez compatible con exodoncias recientes. El diagnóstico inicial clínico era tendencioso para la osteomielitis, sin embargo después del examen histopatológico, fue evidente que estaba con lesión rara. Su tratamiento basado en la literatura se describe más adelante con éxito.

Histiocytosis X is a rare disease with an unknown cause which characterizes by the presence of histiocytic cells which must be treated to prevent their development. This article is developed through a literature review and a clinical case presentation of a female patient who had lesions in the posterior region of her jaw and by taking X-rays; compatible radiolucency alveolar areas with recent exodontics could have been noticed. Initial clinical diagnosis was tendentious for osteomyelitis; nevertheless, after histopathological examination, it was observed that she had this rare lesion. The treatment based on the literature is described next with success.

Histiocitose de células de Langerhans perianal: relato de caso / Perianal Langerhans cell histiocytosis: case story

A histiocitose de células de Langerhans é uma doença caracterizada pela proliferação de células histiocitárias denominadas células de Langerhans, cujo acometimento perianal é raríssimo. As manifestações variam de uma lesão solitária a um envolvimento multisistêmico. O diagnóstico é confirmado por meio de estudo imunohistoquímico. O tratamento consiste em exérese da lesão perianal, podendo ser ou não complementada com quimioterapia.