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.

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.

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.

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.

A Case of Erdheim-Chester Disease with Laryngeal Involvement / 대한이비인후과학회지

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis with multi-organ involvement. Bones, cardiovascular system, central nervous system, kidney, skin and many different organs can be involved but laryngeal involvement has not been reported in literatures. The diagnosis of ECD was based on clinical manifestations and immunohistochemical findings including CD68(+), CD1a(-) and S100(-). Currently, Interferon-a is the most extensively studied agent in the treatment of ECD and serves as the 1st line of treatment. Surgical resection of involved lesions can be tried but it leads to temporary improvement. A 60-year-old man visited with respiratory symptoms because of ECD with laryngeal involvement. We resected the obstructive lesion to relieve the symptoms. Tissue biopsy gave a diagnosis of ECD. As it is rare to encounter ECD involving the larynx, we report this case with a review of literatures.

A Unique Case of Erdheim-Chester Disease with Axial Skeleton, Lymph Node, and Bone Marrow Involvement / Journal of the Korean Cancer Association, 대한암학회지

Erdheim-Chester disease is a rare non-Langerhans-cell histiocytosis with bone and organ involvement. A 76-year-old man presented with low back pain and a history of visits for exertional dyspnea. We diagnosed him with anemia of chronic disease, cytopenia related to chronic illness, chronic renal failure due to hypertension, and hypothyroidism. However, we could not determine a definite cause or explanation for the cytopenia. Multiple osteosclerotic axial skeleton lesions and axillary lymph node enlargement were detected by computed tomography. Bone marrow biopsy revealed histiocytic infiltration, which was CD68-positive and CD1a-negative. This report describes an unusual presentation of Erdheim-Chester disease involving the bone marrow, axial skeleton, and lymph nodes.

A Case of Erdheim-Chester Disease with Asymptomatic Renal Involvement / Journal of the Korean Cancer Association, 대한암학회지

Erdheim-Chester disease is a rare non-Langerhans-cell histiocytosis involving bones and multiple organs. Its clinical course can vary, from an asymptomatic state to a fatal disease, with renal involvement being a common cause of death. A 41-year-old man presented with a 10-month history of bilateral lower limb pain. Left perirenal soft-tissue infiltration had been found incidentally two years earlier. No progression of the lesion or deterioration of renal function was observed for a period of two years. At admission, plain radiography and magnetic resonance imaging of the patient's lower limbs showed patchy osteosclerosis. Biopsy of the tibia revealed histiocytic infiltration, which was found to be positive for CD68 and negative for CD1a. This report describes an unusual case of Erdheim-Chester disease involving a stationary course of disease with no specific treatment for a long period of time.

Paraneoplastic multicentric reticulohistiocytosis: A clinicopathologic challenge.

Multicentric Reticulohistiocytosis (MRH) is a rare, systemic non-Langerhans cell histiocytosis (non-LCH) with prominent joint and skin manifestations. It is mostly self limiting. However, 15-30% of the cases are associated with malignancy and carry a poor prognosis. We report the case of a 42-year-old man who presented with multiple reddish-brown papules that on biopsy showed aggregates of oncocytic histiocytes with several multinucleate giant cells. Immunostains were positive for CD 68, CD 45 and were negative for S-100, CD1a. An impression of multicentric reticulohistiocytosis (MRH) was made, with the recommendation to screen for malignancy. Electron microscopy of the skin lesions showed features consistent with non-Langerhans cell histiocytosis. The patient was later diagnosed with acute myeloid leukemia at a follow-up visit several months later. Thus, it appears prudent to screen and follow-up adults with MRH, to identify an underlying malignant condition.

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.

A Case of Xanthoma Disseminatum Presenting as Pedunculating Nodules and Plaques / 대한피부과학회지

Xanthoma disseminatum is a rare mucocutaneous xanthomatosis classified as a benign form of non-Langerhans cell histiocytosis. We describe an illustrative case with extensive mucocutaneous involvement which was unresponsive to treatment. The patient presented with numerous variable-sized, yellow-brown papules and confluent plaques on the perorbital, perioral, neck, axilla, upper chest, groin, perianal, antecubital fossae and popliteal fossae including the upper respiratory tract. She was treated with oral cyclophosphamide but showed no clinical improvement. She then developed dyspnea, dysphagia and experience defecation difficulties, so was treated with palliative surgery to help relieve the symptoms.