Erdheim-Chester disease with chorioretinal and orbital involvement: a case report / Doença de Erdheim-Chester com envolvimento coriorretiniano e orbitário: relato de caso

ABSTRACT A 42-year-old woman presented with bilateral proptosis, chemosis, leg pain, and vision loss. Orbital, chorioretinal, and multi-organ involvement of Erdheim-Chester disease, a rare non-Langerhans histiocytosis, with a negative BRAF mutation was diagnosed based on clinical, radiological, and pathological findings. Interferon-alpha-2a (IFNα-2a) was started, and her clinical condition improved. However, 4 months later, she had vision loss with a history of IFNα-2a cessation. The same therapy was administered, and her clinical condition improved. The Erdheim-Chester disease is a rare chronic histiocytic proliferative disease that requires a multidisciplinary approach and can be fatal if left untreated because of multisystemic involvements.

RESUMO Uma mulher de 42 anos apresentou proptose bi-lateral, quemose, dor nas pernas e perda de visão. Com base em achados clínicos, radiológicos e patológicos, foi diag-nosticada doença de Erdheim-Chester com acometimento orbitário, coriorretiniano e multiorgânico. Trata-se de uma rara histiocitose não Langerhans negativa para a mutação BRAF. Foi iniciado tratamento com interferon alfa-2a (IFNα-2a) e o quadro clínico melhorou. No entanto, quatro meses depois, a paciente apresentou perda visual após a cessação do IFNα-2a. A mesma terapia foi administrada novamente e sua condição clínica melhorou novamente. A doença de Erdheim-Chester é uma doença proliferativa histiocítica crônica rara que necessita de uma abordagem multidisciplinar e pode ser fatal se não tratada, devido a envolvimentos multissistêmicos.

Progress in the diagnosis and treatment of ocular histiocytosis / 国际眼科杂志(Guoji Yanke Zazhi)

Ocular histiocytosis is a rare and heterogeneous group of disorders which can occur in children and adults. There is a great challenge in the diagnosis and treatment because of the atypical clinical and imaging manifestations. With insights into molecular mechanism of histiocytosis, the discovery of BRAFV600E mutations has changed the understanding of this disease and enabled targeted therapies in most patients. The gold standard of diagnosis has developed into histopathological biopsy combined with the testing for mutations. Surgery is not the only treatment for ocular histiocytosis and targeted therapy has become an effective treatment for patients with mutations in MAPK-ERK signal-regulated kinase pathway. However, the greatest challenge for ocular histiocytosis is establishing the early and correct diagnosis due to the diverse types and clinical manifestations. Therefore, this article reviews recent progress in diagnosing and treating ocular histiocytosis, summarizes their clinical and pathological features, and aims to improve the level of diagnosis and treatment among clinicians.

Histiocitosis de células mixtas: Reporte de un caso

Introducción: Las histiocitosis son enfermedades raras, caracterizadas por la infiltración tisular de histiocitos anormales. Se dividen en cinco grupos. Son frecuentes en la población pediátrica. La combinación de la histiocitosis de células de Langerhans e histiocitosis de células no-Langerhans es fortuita. Reporte de caso: Se reporta el caso de una paciente de 66 años que debutó con un cuadro de compromiso sistémico, del que llamó la atención la presencia de masas tumorales en la cara anterior de las piernas, dolor óseo generalizado y alteraciones endocrinológicas. Se planteó el diagnóstico de histiocitosis mixta. Se sugirió tratamiento con: anticuerpos monoclonales anti BRAF V600E, interferón alfa y/o quimioterapia. Conclusión: Es posible realizar el diagnóstico de histiocitosis a partir de los antecedentes personales patológicos del paciente y los hallazgos clínicos manifiestos con el apoyo de estudios radiológicos, histológicos e inmunohistoquímicos. Finalmente, este es el primer caso de histiocitosis mixta publicado en Ecuador.

Introduction: Histiocytoses are rare diseases characterized by tissue infiltration by abnormal histiocytes. They are divided into five groups. They are frequent in the pediatric population. The combination of Langerhans cell histiocytosis and non-Langerhans cell histiocytosis is fortuitous. Case report: We report the case of a 66-year-old female patient who debuted with a history of systemic involvement, in which the presence of tumor masses on the anterior aspect of the legs, generalized bone pain and endocrinological alterations attracted our attention. The diagnosis of mixed histiocytosis was suggested. Treatment with anti BRAF V600E monoclonal antibodies, interferon alpha and/or chemotherapy was recommended. Conclusion: It is possible to make the diagnosis of histiocytosis based on the patient's personal pathological history and the clinical findings with the support of radiological, histological and immunohistochemical studies. Finally, this is the first case of mixed histiocytosis published in Ecuador.

Tratamiento exitoso de enfermedad de Rosai-Dorfman con inmunomoduladores y quimioterapia metronómica / Successful treatment of Rosai-Dorfman disease with immunomodulators and metronomic chemotherap

RESUMEN Introducción: La enfermedad de Rosai-Dorfman es una histiocitosis linfática masiva caracterizada por emperipolesis con inmunohistoquímica positiva para S100 y CD68. Es una entidad clínica rara y de curso benigno más comúnmente presentada en varones. Objetivo: El propósito de este caso clínico es demostrar el tratamiento exitoso de la enfermedad de Rosai-Dorfman con inmunomoduladores y quimioterapia metronómica. Presentación del caso: Paciente masculino de 57 años que acude por linfadenopatía cervical bilateral, a quien se le realiza tomografía y biopsia ganglionar con resultados positivos para S100 y CD68 con marcado fenómeno de emperipolesis. Recibió esquema inmunomodulador y quimioterapia metronómica exitosa con remisión de enfermedad. Conclusiones: Los pacientes diagnosticados con Rosai-Dorfman son muy pocos debido a lo inusual de esta entidad clínica. Es importante mencionar que esta enfermedad es una histiocitosis de células tipo No Langerhans con características de benignidad y buena respuesta al manejo con corticoides y quimioterapia metronómica, terapia instaurada en nuestro paciente con buena evolución.

ABSTRACT Introduction: Rosai-Dorfman disease is a massive lymphocytic histiocytosis characterized by emperipolesis with positive immunohistochemistry for S100 and CD68. It is a rare clinical entity of benign course most commonly presenting in males. Objective: The purpose of this clinical case is to demonstrate successful treatment of Rosai-Dorfman disease with immunomodulators and metronomic chemotherapy. Case presentation: A 57-year-old male patient presenting with bilateral cervical lymphadenopathy underwent CT scan and lymph node biopsy with positive results for S100 and CD68 with marked emperipolesis phenomenon. He received immunomodulatory scheme and successful metronomic chemotherapy with disease remission. Conclusions: Patients diagnosed with Rosai-Dorfman are very few due to the unusual nature of this clinical entity. It is important to mention that this disease is a non-Langerhans cell histiocytosis with benign characteristics and good response to management with corticosteroids and metronomic chemotherapy, therapy established in our patient with good evolution.

Xantoma del hueso temporal. A propósito de n caso

Se presenta el caso de una mujer de 53 años de edad, quien presentó por un año tinnitus de frecuencia mixta en el oído izquierdo y abruptamente desarrollo cuadro de sordera súbita ipsilateral. Recibió tratamiento con corticoides por vía oral, además de infiltraciones intratimpánicas. En las evaluaciones por imágenes de tomografía y resonancia magnética con contraste, se detecta tumoración sólida de bordes bien definidos a nivel de la unión entre la porción petrosa y escamosa del hueso temporal izquierdo. Para definir el diagnóstico se realizó exéresis de la lesión por mastoidectomía a demanda; el estudio anátomo-patológico reveló xantoma de hueso temporal. Debido a que el lugar de presentación es inusual se reporta el caso y se realiza una revisión del tema.

SUMMARY We present the case of a 53-year-old female patient who presented with one-year history of mixed frequency tinnitus of the left ear and sudden development of unilateral deafness. She received treatment with oral steroids plus intratympanic infiltrations. Imaging studies using CT-Scan and MRI disclosed a solid tumor of well-defined borders in the union of the petrosal and squamous portions of the left temporal bone. A mastoidectomy was performed, the anatomopathological studies revealed a xanthoma of the temporal bone. A literature review was performed.

Enfermedad de Rosai-Dorfman primaria ósea

La enfermedad de Rosai-Dorfman es una patología poco común que suele presentarse con adenopatías cervicales indoloras. El compromiso óseo como presentación extraganglionar es aún menos frecuente. Se presenta el caso de una mujer de 38 años con 3 meses de dolor y limitación funcional en miembro inferior derecho. La radiografía simple y tomografía computarizada mostraron la presencia de una lesión ósea lítica en la metáfisis y epífisis distal del fémur derecho. Finalmente, el estudio histopatológico e inmunohistoquímico de la lesión determinó que se trataba de un caso de enfermedad de Rosai-Dorfman primaria ósea.

Rosai-Dorfman disease is a rare pathology that usually presents as painless cervical adenopathies. Bone compromise as an extra nodal presentation is even more uncommon. We present the case of a 38 years old woman with a 3 months history of pain and functional limitation of her right lower limb. X-ray and CT images showed a lytic bone lession at the distal metaphysis and epiphysis on her right femur. Histological and immunohistochemical study of the lession determined that it was a case of Rosai-Dorfman disease with bone involvement.

Cutaneous Rosai-Dorfman disease in a 40-year-old female: A case report

Introduction@#Rosai-Dorfman disease is a rare disease that manifests with painless cervical lymphadenopathy, fever, anemia, an elevated erythrocyte sedimentation rate (ESR), and hypergammaglobulinemia. Extranodal lesions occur in 1/3 of patients, and the skin is involved in more than 10% of cases. Purely cutaneous disease is uncommon and only about more than 100 cases have been reported. Cutaneous Rosai-Dorfman Disease (CRDD) appears to be a distinct entity with different age and race predilection from cases with lymph node involvement.@*Case report@#This is a case of a 40-year-old Filipino female who presented with multiple erythematous papules and plaques with pustules on the cheeks. Skin punch biopsy showed a dense dermal infiltrate of polygonal histiocytes with abundant cytoplasm and vesicular nuclei. Emperipolesis was also present. The histiocytes were highlighted by the immunohistochemical stains S-100 and CD68 and was CD1a negative. Complete blood count and ESR were normal. Cervical lymphadenopathy was absent. Findings were consistent with Cutaneous Rosai-Dorfman disease. The patient was started on methotrexate at 15mg/week with folic acid supplementation. Mild soap, benzoyl peroxide 5% gel and tretinoin 0.05% cream once daily were maintained during the treatment course. There was significant decrease in erythema and size of existing lesions after 2 months. The patient was referred to a hematologist for monitoring of possible future systemic involvement.@*Conclusion@#Because of its rarity, clinicopathological correlation is always mandatory to establish a diagnosis of CRDD. Immu- nohistochemical stains are required to differentiate this entity form other forms of Langerhans cell histiocytosis. Multidisci- plinary referral is required to rule out concomitant systemic involvement.

Traversing the spectrum of non-Langerhans Cell Histiocytosis: A case of Rosai-Dorfman Disease with features of Necrobiotic Xanthogranuloma

Introduction@#Non-Langerhans cell histiocytoses (non-LCH) are a group of rare diseases with varied clinical manifestations and overlapping features seen among the subtypes. Here, we present a case of Rosai-Dorfman disease with features of necrobiotic xanthogranuloma. @*Case@#A 45-year-old female presented with a 10-year history of an enlarging neck mass with normal overlying skin accompanied by dysphagia and multiple asymptomatic pink to yellowish-brown papules, nodules, and plaques on the face, trunk and extremities. Biopsies of a skin nodule and plaque revealed granulomatous dermal infiltrates (lymphocytes, foamy histiocytes, and Touton giant cells), emperipolesis and areas of necrosis. CD1A and Fite-Faraco staining showed negative results while CD68 and S100 positively stained the tissues of interest. Histopathology of the neck mass paralleled these findings in addition to being negative for lymphoid markers. Patient had monoclonal gammopathy and thyromegaly with enlarged cervical lymph nodes on further tests and imaging. Intralesional and systemic steroids were given which led to flattening of skin lesions and improvement in dysphagia, respectively. @*Conclusion@#Diagnosis and classification of a particular type of non-LCH may be difficult due to similarities across its subtypes. Hence, it is our belief that these diseases may occur on a spectrum. Treatment involves a multidisciplinary approach for the best possible care.

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.

Xantogranuloma múltiplo do adulto: relato de caso de tratamento exitoso com laser CO2 / Multiple adult xanthogranuloma: case report of successful treatment with CO2 Laser

O xantogranuloma múltiplo do adulto é uma apresentação mais rara e tardia do xantogranuloma juvenil, uma histiocitose de células não Langerhans. No adulto, normalmente, é uma lesão única, sendo a manifestação por múltiplas lesões infrequente e pouco descrita na literatura. Relatamos um caso de xantogranuloma múltiplo do adulto, com falha terapêutica à isotretinoína e ótima resposta ao tratamento com laser CO2 no modo cirúrgico

Multiple adult xanthogranuloma is a rare and late variant of Juvenile xanthogranuloma, a non-Langerhans cell histiocytosis. It usually corresponds to a single lesion in adults, and the manifestation of multiples lesions is uncommon. We report a case of multiple adult xanthogranuloma, with Isotretinoin therapy failure and optimal response to CO2 Laser treatment in the surgical mode.

Erdheim-Chester disease with multisystemic involvement: a diagnostic challenge

Erdheim–Chester disease (ECD) is a rare, non-inherited, non- Langerhans form of histiocytosis of unknown origin, first described in 1930. This entity is defined by a mononuclear infiltrate consisting of lipid laden, foamy histiocytes that stain positively for CD68. Individuals affected by this disease are typically adults between their 4th and 6th decades of life. The multi systemic form of ECD is associated with significant morbidity, which may arise due to histiocytic infiltration of critical organ systems. Among the more common sites of involvement are the skeleton, central nervous system, cardiovascular system, lungs, kidneys (retroperitoneum) and skin. The most common presenting symptom of ECD is bone pain. Bilateral symmetric increased tracer uptake on 99mTc bone scintigraphy affecting the periarticular regions of the long bones is highly suggestive of ECD. However, definite diagnosis of ECD is established only once CD68(+), CD1a(−) histiocytes are identified within a biopsy specimen with aid of clinical and radiological data. Here we present a rare case of Erdheim-Chester disease in a 46 year male patient based on clinical data, radiological data, histopathological and immunohistochemistry findings.

Necrobiotic xanthogranuloma associated with smoldering multiple myeloma: satisfactory response to cyclophosphamide, dexamethasone, and thalidomide

Abstract: Necrobiotic xanthogranuloma is a rare chronic condition, belonging to the group C non-Langerhans cell histiocytoses, which is relevant due to the possibility of extracutaneous involvement and association with systemic diseases, particularly hematologic malignancies. The case reported here was only diagnosed after nine years of evolution and was associated with plasma cell dyscrasia. After treatment with cyclophosphamide, dexamethasone, and thalidomide, there was a reduction of cutaneous lesions and serum levels of monoclonal protein.

Juvenile xanthogranuloma: a case report / Xantogranuloma juvenil: um caso clínico

ABSTRACT Objective: To report a rate case of Juvenile xanthogranuloma in a newborn infant. Case description: We present the case of a 31-week preterm newborn with multiple skin lesions whose clinical, histological and immunohistochemical findings allowed the diagnosis of juvenile xanthogranuloma. Currently, the patient has nine months-old, and there is no aggravation of the skin lesions or evidence of extra-cutaneous involvement, particularly ophthalmic. Comments: Juvenile xanthogranuloma is a rare and benign condition, included in the vast group of non-Langerhans histiocytosis. It typically occurs in the pediatric age and may have a neonatal presentation. It affects predominantly the skin, in the form of papules or yellow and/or erythematous nodules and could be asymptomatic, multiple or solitary. Extra-cutaneous involvement, is more common in toddlers and when multiple lesions are present. The eye is the most affected site. We highlight this clinical case by its presentation in the neonatal period and in the form of multiple lesions, which bestows an increased risk of extra-cutaneous involvement, although this has not yet been verified.

RESUMO Objetivo: Descrever um caso raro de xantogranuloma juvenil em recém-nascido. Descrição do caso: Apresentamos o caso de um recém-nascido pré-termo de 31 semanas com múltiplas lesões cutâneas cuja clínica, histologia e imuno-histoquímica permitiram o diagnóstico de xantogranuloma juvenil. Atualmente, com nove meses de idade, não apresenta agravamento das lesões nem evidência de envolvimento extracutâneo, nomeadamente oftálmico. Comentários: O xantogranuloma juvenil é uma patologia rara e benigna, pertencente ao vasto grupo das histiocitoses não Langerhans. Surge tipicamente em idade pediátrica, podendo ter apresentação neonatal. O envolvimento é predominantemente cutâneo sob a forma de pápulas ou nódulos de coloração amarela e/ou eritematosos, assintomáticos, solitários ou múltiplos. O envolvimento extracutâneo é mais frequente em crianças com menos de dois anos e com múltiplas lesões, sendo o olho o local mais afetado. Destacamos este caso clínico pela apresentação no período neonatal e sob a forma de múltiplas lesões, o que lhe confere risco acrescido de envolvimento extracutâneo, sem que, no entanto, tal se tenha verificado.

Case for diagnosis. Solitary violaceous nodule on the toe

Abstract: Reticulohistiocytomas represent a group of benign histiocytic dermal proliferations, which occur either sporadically as solitary cutaneous nodules or, when multiple, in association with systemic disease. Due to its nonspecific clinical presentation, reticulohistiocytoma may mimic other benign or malignant skin neoplasms; therefore, in most cases, a biopsy is needed in order to establish the correct diagnosis. The histology is typically characterized by the presence of large histiocytes with abundant eosinophilic cytoplasm with immunohistochemical profile positive for CD68, CD163, and vimentin. The authors report the case of a patient with solitary reticulohistiocytoma with illustrative clinical, dermoscopic, and histologic features.

Dermoscopy in the diagnosis of juvenile xanthogranuloma

Abstract: Juvenile xanthogranuloma is the most common form of non-Langerhans cell histiocytosis. It manifests clinically as a red-yellow papule, usually showing spontaneous remission. The diagnosis is based on clinical and histological findings. We report the use of dermoscopy ("setting sun" pattern) as an adjuvant tool in the diagnosis of juvenile xanthogranuloma in a female patient presenting with a 2-month history of a pre-auricular papule.

Erdheim-Chester Disease Presenting as an Anterior Mediastinal Tumor without Skeletal Involvement

Erdheim-Chester disease (ECD) is a form of non–Langerhans cell histiocytosis that most commonly involves the skeletal system. We report an unusual case of ECD presenting as an anterior mediastinal tumor without skeletal involvement. A 60-year-old man with no remarkable medical history was referred for evaluation of a mediastinal mass. The patient underwent surgical excision of the tumor via video-assisted thoracoscopic surgery. Histologic examination revealed marked proliferation of atypical histiocytes with sclerosis, and the results of immunohistochemical staining were suggestive of ECD.

Xantoma disseminado: relato de caso e revisão da literatura / Disseminated xanthoma: a case report and literature review

Xantoma disseminado é uma histiocitose não Langerhans, rara, não familiar, benigna, normolipídica, caracterizada pela deposição lipídica na pele e órgãos internos secundária à proliferação histiocitária. É caracterizado por lesões xantomatosas que geralmente afetam as regiões flexurais e, frequentemente, acomete mucosas. Tem curso em geral benigno, com resolução das lesões cutâneas em alguns anos, porém lesões em certas localizações podem resultar em morbidade e até óbito, sendo, nestes casos, o achado cutâneo uma importante pista diagnóstica. Devido à sua raridade, não há um consenso terapêutico, e as respostas às terapias têm sido insatisfatórias. Relatamos o caso de uma paciente com essa patologia, na qual não foi detectada patologia sistêmica (AU)

Disseminated xanthoma is a rare non-familial, benign, and normolipid form of non-Langerhans histiocytosis, characterized by lipid deposition in the skin and internal organs secondary to histiocytic proliferation. It is characterized by xanthomatous lesions that generally affect the flexural regions and often affects mucous membranes. Although it has a generally benign course, with resolution of cutaneous lesions in a few years, lesions in certain locations can result in morbidity and even death. In these cases, the cutaneous finding is an important diagnostic clue. Because of its rarity, there is no therapeutic consensus and responses to therapies have been unsatisfactory. Here we report the case of a patient with this disorder, in whom no systemic disease was detected (AU)

Xantogranuloma juvenil solitario congénito: Caso clínico / Solitary and congenital juvenile xanthogranuloma: Case report

El xantogranulomajuvenil es una patología benigna y representa la forma más común de histiocitosis de células no Langerhans. Está caracterizado por la presencia de pápulas o nodulos firmes de coloración rosada o amarillo amarronada, que comprometen, principalmente, la piel y, de forma excepcional, otros órganos. Es una entidad autolimitada con una involución espontánea en los primeros 5 años de vida. Presentamos a una paciente de 1 mes de vida con una lesión congénita en el abdomen, cuya histopatología mostró la presencia de células gigantes multinucleadas de Touton, características de esta patología. Destacamos la presentación infrecuente de este tipo de lesión y la importancia de los múltiples diagnósticos diferenciales que se deben tener en cuenta debido a la edad de la paciente y a sus características.

Juvenile xanthogranuloma is a bening pathology and it represents the most common form of non-Langerhans cell histiocytosis. It is characterized by the presence of papules or firm nodules of a pinkish or yellow-brownish nature, which mainly compromise the skin and, exceptionally, other organs. It is a self-limited entity having a spontaneous regression during the first five years of life. We report the case of a one-month-old patient who presented a congenital tumor in the abdomen, whose histopathology showed the presence of multinucleated giant Touton cells, which are typical of this pathology. We emphasize the rare occurrence of this type of lesion and the importance of the multiple differential diagnosis to be taken into account due to the age of the patient and the characteristics of the lesion.

Successful Treatment of Erdheim-Chester Disease with Multisystemic Involvement in a 4-year-old Child by Interferon-α and Corticosteroid / 임상소아혈액종양

Erdheim-Chester disease (ECD) is a rare form of proliferative non-Langerhans cell histiocytosis that involves multiple organs and is associated with a high mortality. The prognosis of ECD is variable, and it mainly depends on the involved anatomic sites. The treatment modalities have not been standardized, but interferon-α (IFN-α) has been reported to be effective in the management of ECD. ECD usually affects middle aged individuals with a slight male predominance but is extremely rare in children. We present an uncommon case of a 4-year-boy diagnosed with ECD who was treated with IFN-α and corticosteroid. He remained disease-free for 3 years after the completion of treatment.

Successful Treatment of Erdheim-Chester Disease with Multisystemic Involvement in a 4-year-old Child by Interferon-α and Corticosteroid / 임상소아혈액종양

Erdheim-Chester disease (ECD) is a rare form of proliferative non-Langerhans cell histiocytosis that involves multiple organs and is associated with a high mortality. The prognosis of ECD is variable, and it mainly depends on the involved anatomic sites. The treatment modalities have not been standardized, but interferon-α (IFN-α) has been reported to be effective in the management of ECD. ECD usually affects middle aged individuals with a slight male predominance but is extremely rare in children. We present an uncommon case of a 4-year-boy diagnosed with ECD who was treated with IFN-α and corticosteroid. He remained disease-free for 3 years after the completion of treatment.