Histiocitosis / Histiocytosis

Las histiocitosis son un grupo de enfermedades raras que se caracterizan por la inflamación y acúmulo de células derivadas de los monocitos y macrófagos en diferentes tejidos. La clínica es muy variable, desde formas leves con afectación de un solo órgano a formas multisistémicas graves que pueden comprometer la vida. Su diagnóstico se basa en la clínica, hallazgos radiológicos y la anatomía patológica. Se recomienda realizar una biopsia del tejido afecto en todos los casos dado que puede tener implicaciones terapéuticas. En este sentido, durante la última década se han identificado mutaciones en tejido afecto que condicionan activación de la vía de las proteínas cinasas activadas por mitógenos (MAPK/ERK) y fosfatidilinositol 3 kinasa (PI3K/AKT), en proporción variable, en función del tipo de histiocitosis. En esta revisión nos centramos fundamentalmente en la histiocitosis de células de Langerhans, la enfermedad de Erdheim-Chester y la enfermedad de Rosai-Dorfman (AU)

Histiocytosis is a group of rare diseases characterized by inflammation and accumulation of cells derived from monocytes and macrophages in different tissues. The symptoms are highly variable, from mild forms with involvement of a single organ to severe multisystem forms that can be life compromising. The diagnosis of histiocytosis is based on the clinic, radiological findings and pathological anatomy. A biopsy of the affected tissue is recommended in all cases as it may have therapeutic implications. During the last decade, some mutations have been identified in the affected tissue that condition activation of the MAPK/ERK and PI3K/AKT pathway, in a variable proportion depending on the type of histiocytosis. In this review we mainly focus on Langerhans Cell Histiocytosis, Erdheim-Chester Disease and Rosai-Dorfman Disease (AU)

Neurological Manifestations of Histiocytic Disorders.

PURPOSE OF REVIEW: Histiocytic disorders, including Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman disease (RDD), are rare neoplasms that may present with a spectrum of neurologic involvement. Diagnostic delay is common due to heterogeneity in presentation and challenging pathology. RECENT FINDINGS: Recent advances in the treatment of these diseases targeted towards mutations in the MAP kinase pathway have led to an improved prognosis in these patients with neurologic involvement. It is critical for clinicians to have a high index of suspicion to allow for early targeted treatment and optimize neurologic outcomes. A systematic approach to diagnosis is presented in this article to allow for accurate diagnosis of these rare diseases.

Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors.

Histiocytic disorders are rare diseases defined by the clonal accumulation of a macrophage or dendritic cell origin. These disorders include Langerhans cell histiocytosis, Erdheim-Chester disease, juvenile xanthogranuloma, malignant histiocytoses, and Rosai-Dorfman-Destombes disease. These histiocytic disorders are a diverse group of disorders with different presentations, management, and prognosis. This review focuses on these histiocytic disorders and the role of pathological ERK signaling due to somatic mutations in the mitogen--activated protein kinase (MAPK) pathway. Over the last decade, there has been growing awareness of the MAPK pathway being a key driver in many histiocytic disorders, which has led to successful treatment with targeted therapies, in particular, BRAF inhibitors and MEK inhibitors.

Clinical features, diagnosis, treatment and prognosis of otolaryngological extranodal sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease, RDD).

PURPOSE: To investigate the clinical features, diagnosis, treatment and prognosis of otolaryngological extranodal RDD. METHODS: A retrospective analysis was performed on 16 patients who were initially diagnosed and treated with otolaryngological extranodal RDD in our hospital from January 2013 to January 2019. RESULTS: There were 9 females and 7 males. The mean diagnostic age was 45.35. Nasal, laryngeal and otic RDD were, respectively, accounting for 56.25%, 31.25% and 12.5%. The median interval diagnostic time was individually 1, 0.5 and 0.2 year for nasal, laryngeal and otic RDD. The most common symptoms were separately progressive nasal congestion, dyspnea, otorrhea in nasal, laryngeal and otic RDD. 13 had cervical lymph node swelling on MRI. Surgery or postoperative radiotherapy were conformed. In the end, 14 patients with RDD survived. The survival rate is as high as 87.5%. One of them died of RDD in the fifth year. One case was lost to follow-up 2 years after treatment. Patients survive for at least 2 years and up to 9 years. There was no significant difference in life expectancy of extranodal RDD among different parts of ENT (P = 0.508 > 0.05). The average ages of laryngeal and nasal RDD were similar (P = 0.898 > 0.05). However, the age of both was significantly higher than ear RDD (P = 0.023 and 0.019 < 0.05). CONCLUSIONS: The average diagnostic age was more than 20 years. Nasal RDD was the most common in this area. All laryngeal RDD had infiltrated subglottis. Functional surgery and postoperative radiotherapy can be used to achieve long-term remission and survival.

Rosai-Dorfman-Destombes Disease in the Pediatric Head and Neck.

BACKGROUND: Rosai-Dorfman-Destombes disease (RDD), or sinus histiocytosis with massive lymphadenopathy, is a rare form of non-Langerhans cells histiocytosis. It has a wide-ranging variability in presentation since first described in 1969 but much of its characteristics in children remain unknown. METHODS: A retrospective chart review of children diagnosed with RDD at a tertiary care children's hospital was conducted from 2000 to 2021. RESULTS: Twelve RDD patients were identified, with an average age of 7 years (SD 4.3). Males comprised 58% of the cohort, and African American ethnicity was most common (42%). Nodal RDD was found in 7 patients (58%). Nine patients (75%) presented RDD within the head and neck, 6 of whom had nodal RDD. The most common presentation was cervical lymphadenopathy, which most often involved levels V (67%), II (56%), III (44%), and I (11%), in order of frequency. Recurrence and persistence of disease after initial treatment was common, with 5 (42%) being disease free at the time of the last follow up. Fifty-eight percent (7/12) developed recurrence or had persistent disease and 4 required adjuvant systemic treatment with corticosteroids and/or chemotherapy. One patient succumbed after developing treatment related acute myelodysplastic leukemia (t-AML) from chemotherapy used to treat recurrent RDD. CONCLUSION: Pediatric RDD presents at a young age and most commonly involving cervical lymphadenopathy. Ongoing surveillance in the setting of persistence or recurrence without clearly defined prognostic risk factors is important.

Rosai-Dorfman-Destombes disease of the nervous system: a systematic literature review.

BACKGROUND: Rosai-Dorfman-Destombes disease (RDD) is a rare histiocytic disorder with heterogeneous clinical manifestations and rare neurologic involvement. The existing clinical literature about neurologic RDD has yet to be critically examined. METHODS: We performed a four-database English-language systematic literature search for cases of RDD neurohistiocytosis, excluding secondary literature. Individual patient data for neurologic symptoms, disease sites, treatments, and responses were captured. Responses to first-line and second-line surgical interventions, post-surgical radiotherapy, and systemic therapies were analyzed. RESULTS: Among 4769 articles yielded by literature search, 154 articles were fully reviewed, containing data on 224 patients with neurologic RDD. 128 (83.1%) articles were single case reports. 149 (66.5%) patients were male, 74 (33.5%) female, with a median age of 37.6 years (range 2-79). Presenting neurologic symptoms included headache (45.1%), focal neurological deficits (32.6%), visual symptoms (32.1%), and seizures (24.6%). RDD involvement was multifocal in 32 (14.3%) cases. First-line treatment involved resection in 200 (89.6%) patients, with subsequent progression in 52 (26%), including 41 (78.8%) with unifocal disease. No difference was observed in progression-free survival comparing post-operative radiotherapy to no radiotherapy following partial resection. Chemotherapy given alone as first-line treatment led to complete or partial response in 3/7(43%) patients. Second-line treatments led to complete or partial response in 18/37(37.5%) patients. Mutational data were reported on 10 patients (4.46%). CONCLUSIONS: This review highlights the limited published data about neurologic RDD, which presents with varied symptomatology and outcome. Further study is needed about its mutational landscape, and more effective therapies are needed for recurrent and refractory disease.

Enfermedad de Rosai-Dorfman nasosinusal: actualización a propósito de un caso de obstrucción nasal progresiva / Nasosinusal Rosai-Dorfman disease: update on a case of progressive nasal obstruction

Resumen La histiocitosis sinusal con linfadenopatías masivas, conocida como enfermedad de Rosai-Dorfman (ERD), es una patología poco frecuente cuya presentación clásica consiste en el desarrollo de grandes adenopatías cervicales bilaterales indoloras. La manifestación extranodal puede involucrar compromiso cutáneo, del sistema nervioso central, hematológico, óseo, de la vía aérea, entre otros. Su diagnóstico es un desafío y requiere una evaluación completa del paciente incluyendo historia clínica, examen físico, exámenes de laboratorio, imágenes y estudio histopatológico que confirme el diagnóstico. El tratamiento debe ser individualizado para cada paciente. Las alternativas incluyen la observación, corticoides sistémicos, radioterapia, quimioterapia, inmunomoduladores y cirugía. Se presenta el caso de una paciente de 65 años con antecedente de enfermedad de Rosai-Dorfman localizada en glándulas lagrimales y linfoma no Hodgkin, que comienza con obstrucción nasal bilateral progresiva refractaria a tratamiento médico, por lo que se decide realizar cirugía, cuyo estudio histopatológico confirmó enfermedad de Rosai-Dorfman.

Abstract Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare pathology, with a classic clinical presentation of painless bilateral massive cervical lymphadenopathy. The extranodal manifestations may involve skin, central nervous system, hematological, bones, and airway compromise, among others. Its diagnosis is challenging and requires a complete evaluation of the patient including medical history, physical examination, laboratory testing, imaging and histopathological study to confirm the diagnosis. Treatment should be individualized for each patient, including follow-up, systemic corticosteroids, radiotherapy, chemotherapy, immunomodulators and surgery. We present the case of a 65-year-old patient with a history of RDD located in the lacrimal glands and lymphoma, which begins with progressive bilateral obstruction refractory to medical treatment, for which it is decided to perform surgery, whose histopathological study confirmed RDD.

Survivorship Issues in Adult Patients With Histiocytic Neoplasms.

Adult-onset histiocytoses (AOH), primarily Rosai-Dorfman disease (RDD), Erdheim-Chester Disease (ECD), and adult Langerhans cell histiocytosis (ALCH), are a group of related histiocytic neoplastic disorders featuring multisystemic manifestations. The disorders are largely incurable, and are essentially chronic neoplastic diseases with a variable prognosis. Prompt diagnosis and treatment is important to prevent debilitating and even life-threatening complications. Survivorship issues abound in AOH, due to their multisystemic manifestations and the sometimes recalcitrant chronic inflammation, which can lead to other debilitating complications such as fatigue, weakness, and pain. Because these disorders are rare, few healthcare professionals are proficient in their management; therefore the aim of these guidelines is to offer guidance on how to manage patients, and how to create survivorship care plans through the efforts of an interdisciplinary team.

[Systemic Rosai-Dorfman-Destombes disease associated with a myelodysplastic syndrome. Efficacy of hematologic treatment]. / Maladie de Rosai-Dorfman-Destombes (RDD) multifocale réfractaire associée à un syndrome myélodysplasique. Efficacité du traitement hématologique.

INTRODUCTION: We report an original observation of multifocal refractory Destombes-Rosai-Dorfman disease associated with a myelodysplastic syndrome. The treatment of myelodysplasia allowed a good and prolonged response of both pathologies. CASE REPORT: A 35-year-old patient was investigated for bilateral exophthalmia, histologically related to Destombes-Rosai-Dorfman disease. The extension workup showed sinus, kidney and lymph node involvement. It was treated unsuccessfully with corticosteroids, colchicine, methotrexate, infliximab, cladribine and tociluzimab. The secondary appearance of myelodysplasia (AREB IPSS score intermediate-2) led to induction treatment with aracytin and idarubicin, and maintenance with azacytidine for 2 years. With 5 years of follow-up, the patient is in remission both of the myelodysplastic syndrome and Destombes-Rosai-Dorfman disease. CONCLUSION: Our observation discusses the interest of the treatment of myelodysplastic syndrome for the management of associated extra-hematological manifestations.

Primary cutaneous Rosai-Dorfman disease; a case-based review of a diagnostically and therapeutically challenging rare variant.

Primary cutaneous Rosai-Dorfman disease is a rare form of Rosai-Dorfman disease limited to the skin. The diagnosis of primary cutaneous disease is based on a combination of clinical presentation, histopathology, and the detection of S100+, CD68+, and CD1a- histiocytic immunophenotyping. However, the diagnosis of primary cutaneous disease is often difficult and significantly delayed due to the non-specific nature of its histologic and clinical features. In this review, we describe four cases in order to familiarize pathologists and dermatopathologists with the clinicopathologic correlation of primary cutaneous Rosai-Dorfman disease and to help facilitate early diagnosis. In addition, we discuss the proposed pathophysiology and molecular etiology of this tumor, and its relationship with IgG4 sclerosing disease.

Clinicopathological features, treatment approaches, and outcomes in Rosai-Dorfman disease.

Rosai-Dorfman disease is a rare subtype of non-Langerhans cell histiocytosis. With the last major report published in 1990, there is a paucity of contemporary data on this disease. Our objective was to report the clinicopathological features, treatments and outcomes of patients seen at a tertiary referral center. Sixty-four patients with histopathological diagnosis of Rosai-Dorfman disease were identified from 1994 to 2017 (median age 50 years; range, 2-79). The median duration from symptom onset to diagnosis was seven months (range, 0-128), which was also reflected in the number of biopsies required to establish the diagnosis (median 2; range, 1-6). The most common presentation was subcutaneous masses (40%). Of the 64 patients, 8% had classical (nodal only) and 92% had extra-nodal disease (67% extra-nodal only). The most common organs involved were skin and subcutaneous tissue (52%), followed by lymph nodes (33%). Three patients had an overlap with Erdheim-Chester disease, which had not been described before. Two of these were found to have MAP2K1 mutations. Commonly utilized first line treatments were surgical excision (38%) and systemic corticosteroids (27%). Corticosteroids led to a response in 56% of the cases. Of those treated initially, 15 (30%) patients developed recurrent disease. The most commonly used systemic agent was cladribine (n=6), with 67% overall response rate. Our study demonstrates that Rosai-Dorfman disease has diverse clinical manifestations and outcomes. While this disease has been historically considered a benign entity, a subset of patients endures an aggressive course necessitating the use of systemic therapies.

Rosai-Dorfman disease masquerading as Uveal Melanoma: Case report and review of literature.

OBJECTIVE/BACKGROUND: Intra ocular Rosai-Dorfman disease (RDD) is an extremely rare disease. We are reporting the first case of RDD presenting as ciliary body mass mimicking ciliary body melanoma, and we are reviewing the English literature reporting on cases of RDD presented with intraocular disease. METHODS: An 18-year-old lady presented with loss of vision in the right eye, and was found to have intraocular mass lesion. She was diagnosed clinically and radiologically as a case of ciliary body melanoma associated with total retinal detachment. RESULTS: Histopathological sections and stains proved to be intraocular RDD. Review of the literature revealed three cases of intraocular RDD; two of them had choroid thickening associated with serous retinal detachment, and one presented with intraocular mass mimicking choroid melanoma. Two of the three cases were enucleated. Our case is the first case in English literature of intraocular ciliary body RDD, mimicking ciliary body melanoma. CONCLUSION: RDD can present as an intraocular mass that mimics ciliary body melanoma. This case emphasizes the importance of diagnostic biopsy before considering the final therapy in unclear cases, mainly when associated with unusual systemic features like lymphadenopathy.

When a Meningioma Isn't: Endoscopic Endonasal Orbital Decompression and Biopsy of Skull Base Rosai-Dorfman Disease Treated Previously with Empiric Radiation Therapy.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, benign histiocytosis disorder with only approximately 100 reported central nervous system cases in the literature. Even less common is skull base involvement of RDD, with about 41 reported cases. Radiographically, RDD can appear similar to a meningioma; the true diagnosis is only found with histologic analysis. Although "benign," RDD can lead to significant neurologic morbidity from the disease or unnecessary surgical and nonsurgical treatment. While rare, intracranial RDD has been treated with chemotherapy or radiotherapy, with surgery playing a limited role to relieve mass effect. Surgical approaches to the skull base are invasive and pose risk, especially for a benign and self-limiting disease like RDD. CASE DESCRIPTION: Here we present the case of a 63-year-old woman with a presumed spheno-orbital meningioma for which the patient previously underwent radiation therapy. On presentation to our facility, the patient noted pressure headaches and blurry vision, and imaging demonstrated progression of her disease. For these reasons, surgical debulking and biopsy were undertaken. CONCLUSIONS: This report demonstrates the role of EEA for tissue biopsy and decompression of the affected cranial nerves and orbit. This paradigm seems to provide a safe and effective way to manage patients with compressive symptoms, while also allowing for tissue sampling.

Management and outcomes of sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman Disease).

Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman Disease [RDD]), is a rare, benign but clinically heterogeneous histiocytic disorder. Our aims were to analyze the clinical characteristics of the disease and explore the outcomes of patients with RDD followed at our institution. Between January 2000 and February 2019, there were 15 patients with a pathologically confirmed diagnosis of RDD. Median age at diagnosis was 48 years old (range 26-78). The majority (87%, n = 13) of the patients had extranodal disease. Frontline approaches included surgical intervention/complete excision (n = 5, 33%), rituximab monotherapy (n = 5, 33%), observation (n = 3, 20%), and radiation (n = 2, 13%). Two of the five patients underwent surgical excision and were subsequently treated with rituximab. Of the 7 patients who were given rituximab, 64% remained progression free 24 months after the initial rituximab administration. Our review parallels previous reports and highlights rituximab as a favorable option for therapy if ineligible for surgery or radiation.

Nonresectable Thoracic Rosai-Dorfman Disease: A Case Report and Review of the Literature.

INTRODUCTION: Rosai-Dorfman disease (RDD) is a rare disease that can be triggered by either viral or bacterial infection. Several parts of the body can be involved, from the central nervous system to the pelvic regions had been reported. At present, there is a serious lack of guidelines as to how to treat cases of RDD involving the spine. Current trends show that surgery remains the first method of choice to cure this disease, but in refractory or recurrent RDD, repeat surgery cannot guarantee total resection. Under such circumstances, adjuvant therapy can be very useful. Here, we share our experience of treating recurrent spinal RDD. CASE DESCRIPTION: Our patient was a 32-year-old male patient with hepatitis B virus infection. He suffered from lower back pain with lower limb weakness after being hit by a metal pipe. Laminectomy of T11-12 was performed to decompress the spinal cord. The final pathological results demonstrated chronic inflammation. After surgery, the lower limbs improved and the patient recovered quite well. However, he returned 3 years later with the same complaints and was diagnosed with RDD. Durectomy was performed and repaired with an artificial dura. Thalidomide therapy was initiated. Currently, 9 years later, the patient has not experienced recurrence or any form of neurological deficit. CONCLUSIONS: RDD is a rare disease and can be misdiagnosed easily. Although it may resolve spontaneously, recurrence is possible. Hence, extensive follow-up is necessary. Surgery remained the first choice of surgery, however, when encountered recurrent or nonresectable RDD, adjuvant therapy such as corticosteroids, thalidomide, and radiotherapy could help. In this article, we shared our experience using thalidomide in treating nonresectable RDD.

The Mayo Clinic Histiocytosis Working Group Consensus Statement for the Diagnosis and Evaluation of Adult Patients With Histiocytic Neoplasms: Erdheim-Chester Disease, Langerhans Cell Histiocytosis, and Rosai-Dorfman Disease.

Histiocytic neoplasms, a rare and heterogeneous group of disorders, primarily include Erdheim-Chester disease, Langerhans cell histiocytosis, and Rosai-Dorfman disease. Due to their diverse clinical manifestations, the greatest challenge posed by these neoplasms is the establishment of a diagnosis, which often leads to a delay in institution of appropriate therapy. Recent insights into their genomic architecture demonstrating mitogen-activated protein kinase/extracellular signal-regulated kinase pathway mutations have now enabled potential treatment with targeted therapies in most patients. This consensus statement represents a joint document from a multidisciplinary group of physicians at Mayo Clinic who specialize in the management of adult histiocytic neoplasms. It consists of evidence- and consensus-based recommendations on when to suspect these neoplasms and what tests to order for the diagnosis and initial evaluation. In addition, it also describes the histopathologic and individual organ manifestations of these neoplasms to help the clinicians in identifying their key features. With uniform guidelines that aid in identifying these neoplasms, we hope to improve the awareness that may lead to their timely and correct diagnosis.

Rosai-Dorfman Disease: The MD Anderson Cancer Center Experience.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare disorder composed of a proliferation of histiocytes with varied clinical manifestations. PATIENTS AND METHODS: In this retrospective observational study, we obtained demographic, clinical, and outcome data from the medical records of 10 adult patients with RDD seen in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center between 1995 and 2015. RESULTS: Patients had a median age of 56 years (range, 20-81 years) with equal gender distribution. Five patients were initially treated with systemic therapy. Five received cladribine as initial therapy or for relapse. Other therapeutic agents included clofarabine, lenalidomide, and steroids. The overall response rate was 80% in patients receiving cladribine, with a median progression-free survival of 29 months. Surgery, radiotherapy, and observation were also treatment options for localized disease. With a median follow-up of 65 months, none of the patients have died. CONCLUSION: Currently, there is no standard of care for RDD. Treatment should be personalized for each patient depending on the clinical presentation, course of the disease, and prior treatment history. Purine analogues provide excellent responses; however, surgical resection and observation are also suitable for specific cases.

Rosai-Dorfman Disease: Cutaneous and Parotid Involvement.

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare and benign proliferative disease that affects histiocytes. Its etiology remains unclear. Rosai-Dorfman disease primarily affects lymph nodes with many extranodal manifestations present, including cutaneous, pulmonary, ophthalmic, and gastrointestinal. Diagnosis is mainly histologic with the presence of Rosai-Dorfman cells, which demonstrate emperipolesis. We report a case of a 30-year-old man who presented with a facial cutaneous mass and was diagnosed with RDD; he underwent surgical excision. The patient experienced recurrent lesions on the surgical scar and parotid gland as well as the lower back. Treatment consisted of systemic steroids and surgical excision.

Pulmonary histiocytosis: beyond Langerhans cell histiocytosis related to smoking. / Histiocitosis pulmonar: más allá de la histiocitosis de células de Langerhans relacionada con el tabaco.

OBJECTIVE: To review the imaging findings for the different types of pulmonary histiocytosis. In particular, in addition to the well-known pulmonary Langerhans cell histiocytosis related to smoking and its possible appearance in nonsmokers, we focus on non-Langerhans cell histiocytosis in Rosai-Dorfman disease and Erdheim-Chester disease. We also review the etiopathogenesis, histology, clinical presentation, and treatment of pulmonary histiocytosis. CONCLUSION: Langerhans cell histiocytosis, Rosai-Dorfman disease, and Erdheim-Chester disease are idiopathic diseases in which the proliferation and infiltration of histiocytes is the histologic finding that confirms the diagnosis. Langerhans cell histiocytosis manifests as nodules and cysts that spare the costophrenic angles; it typically appears in smokers. Although it is uncommon in nonsmokers, Langerhans cell histiocytosis should also be considered in nonsmokers treated with chemotherapy and radiotherapy in whom cavitated nodules appear and should be included in the differential diagnosis together with metastatic disease and opportunistic infections. Rosai-Dorfman disease and Erdheim-Chester disease present with less specific thoracic findings such as adenopathies, interstitial thickening, and pleural effusion. In Erdheim-Chester disease, the characteristic extrathoracic manifestations are usually key for the diagnosis.