non-Langerhans Cell Histiocytosis Research Articles

Juvenile xanthogranuloma as a differential diagnosis for sellar and suprasellar lesions in child: Case report and review of literature

Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. Its systemic form affects 4% of patients. Lesions in the Central Nervous System (CNS) occur in 2% of systemic cases. Sellar JXG should be one of the differential diagnoses for sellar lesions in young. This is a 15-year-old patient with non-specific headache, progressive visual loss and magnetic resonance imaging showing sellar lesion with suprasellar extension. The patient underwent microsurgery by pterional craniotomy with partial resection of the tumor. Pathology evidenced JXG. It progressively evolved with impairment of neuroendocrine functions, new lesions in different CNS locations and death two years after diagnosis. Sellar JXG without cutaneous manifestations is rare. There are no specific findings of the disease. Diagnosis requires additional tests, being defined by pathological analysis. Total resection presents a greater potential control comparing to partial resection. Even so, some patients may have progressive disease with poor clinical outcome.

CPC10 An unusual case of bilateral periorbital lesions

Abstract A 45-year-old man was referred to the dermatology department for a 5–10-year history of enlarging periorbital xanthelasma-like lesions with a non-significant lipid profile. The periorbital lesions episodically and spontaneously became swollen and were associated with a throbbing sensation. After exercise and minimal motion, haemorrhage into the lesions occurred. Clinical examination revealed multiple coalescing, symmetrical, thick, yellow plaques and nodules with red–brown areas of discoloration associated with eyelid telangiectasia. His past medical history included hiatus hernia, lipoma and Osgood-Schlatter disease of the knee. The differential diagnosis included adult-onset xanthelasma, necrobiotic xanthogranuloma and amyloidosis. Punch biopsy of the lesions showed histological features consistent with a xanthogranuloma. Owing to the association of this entity with underlying haematological malignancy, computed tomography was performed, which revealed a subtle 33 × 70 mm low-attenuating mass within the posterolateral aspect of the right iliacus muscle. On further radiological investigation, including magnetic resonance imaging (MRI) and positron emission tomography, an avid, nonaggressive right iliac bone lesion and nonavid bilateral, symmetrical metaphyseal and diaphyseal sclerosis involving both distal femur and proximal tibia were seen. Previous MRI of his knee, performed 3 years earlier following a fall, was reviewed and found to show an incidental signal abnormality in his distal femur. Tissue from the periocular xanthogranuloma was positive for the BRAF V600E mutation and tissue from biopsy of the right iliac crest was consistent with focal osteosclerosis. Owing to the histopathological, clinical and radiological features, a diagnosis of Erdheim–Chester disease (ECD) was established. As a result, the haematology team initiated the patient on a reducing dose of oral prednisolone with long-term methotrexate (15 mg weekly). This led to an improvement in appearance of the periorbital lesions. The differential diagnosis for periocular xanthogranuloma includes adult-onset xanthogranulomas and adult-onset asthma with periocular xanthogranuloma, necrobiotic xanthogranuloma and ECD. ECD is a rare form of non-Langerhans cell histiocytosis that is highly associated with BRAF V600E and other mitogen-activated protein kinase pathway mutations (Diamond EL, Durham BH, Haroche J et al. Diverse and targetable kinase alterations drive histiocytic neoplasms. Cancer Discov 2016; 6:154–65). The clinical course of ECD is generally aggressive, but it can vary from indolent disease to fatal multiorgan failure. Although ECD can have multiorgan involvement, approximately 25% of these patients have cutaneous manifestations (Kobic A, Shah KK, Schmitt AR et al. Erdheim-Chester disease: expanding the spectrum of cutaneous manifestations. Br J Dermatol 2020; 182:405–9). This case highlights the importance of considering ECD when faced with atypical periorbital lesions as these lesions can mimic common benign xanthelasma.

Longitudinal assessment of cardiac involvement in Erdheim-Chester disease using cardiac magnetic resonance imaging.

7067 Background: Erdheim-Chester disease (ECD) is a rare multi-systemic non-Langerhans cell histiocytosis that affects the heart in nearly half of patients. Atrial infiltration and pericardial effusion are the hallmarks of cardiac involvement and can lead to clinical complications (conduction disorders, coronary artery stenosis, tamponade, constrictive pericarditis). Evolution under treatment is poorly studied. We aimed to investigate the evolution of cardiac involvement in ECD using cardiac magnetic resonance (CMR) imaging. Methods: All ECD patients with a CMR imaging disclosing a cardiac involvement and who underwent at least one follow-up CMR imaging between 2005 and 2020 at a French tertiary center were retrospectively included. First and last CMR imaging were compared. Multivariable analysis was performed to search for independent predictors of cardiac involvement resolution. Variables were included in the model if their P-value was < 0.1 on univariable analysis. Results: Overall, 46 patients were included. Median age at first imaging was 63 years [53-69]. Median delay between the first and the last imaging was 4 years [2-7]. BRAFV600E mutation was present in 43 patients (94%). Patients received a median of 2 [1-3] treatments. All patients (100%) had cardiac involvement at baseline. Right atrio-ventricular sulcus (RAVS) was infiltrated in 38 patients (83%) and was the main cardiac feature.Overall, complete regression was observed in 6 patients (13%), partial regression in 26 patients (56%), stable imaging in 12 patients (26%), and worsening in 2 patients (5%). In patients with RAVS infiltration, complete regression was observed in 5 patients (16%) and partial regression was seen 22 patients (58%) regression. On univariable analysis, patients with regression of their infiltration had a lower rate of death (16% versus 64%, P= 0.002), a higher rate of atrial infiltration late gadolinium enhancement (LGE) (97% versus 71%, P= 0.01), a higher rate of hydronephrosis (50% versus 14%, P= 0.03) and a lower rate of interferon prescription (69% versus 100%, P= 0.02). A similar rate of vemurafenib use was observed in both groups (69% versus 54%, P= 0.3). On multivariable analysis, death remained significantly associated with follow-up imaging status (ß = -2.3 P= 0.01), while atrial infiltration LGE (ß = 2.7, P= 0.06), hydronephrosis (ß = 1.6, P= 0.1) and treatment with interferon (ß = -16, P= 1) were no longer significantly associated with imaging status. Conclusions: Partial or complete resolution of cardiac involvement was observed in 69% of patients with ECD and was significantly associated with a lower rate of death on multivariable analysis.

Tazemetostat for tumors harboring SMARCB1/SMARCA4 or EZH2 alterations: results from NCI-COG pediatric MATCH APEC1621C.

National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice assigns patients aged 1-21 years with refractory solid tumors, brain tumors, lymphomas, and histiocytic disorders to phase II trials of molecularly targeted therapies based on detection of predefined genetic alterations. Patients whose tumors harbored EZH2 mutations or loss of SMARCB1 or SMARCA4 by immunohistochemistry were treated with EZH2 inhibitor tazemetostat. Patients received tazemetostat for 28-day cycles until disease progression or intolerable toxicity (max 26 cycles). The primary endpoint was objective response rate; secondary endpoints included progression-free survival and tolerability of tazemetostat. Twenty patients (median age = 5 years) enrolled, all evaluable for response and toxicities. The most frequent diagnoses were atypical teratoid rhabdoid tumor (n = 8) and malignant rhabdoid tumor (n = 4). Actionable alterations consisted of SMARCB1 loss (n = 16), EZH2 mutation (n = 3), and SMARCA4 loss (n = 1). One objective response was observed in a patient with non-Langerhans cell histiocytosis with SMARCA4 loss (26 cycles, 1200 mg/m2/dose twice daily). Four patients with SMARCB1 loss had a best response of stable disease: epithelioid sarcoma (n = 2), atypical teratoid rhabdoid tumor (n = 1), and renal medullary carcinoma (n = 1). Six-month progression-free survival was 35% (95% confidence interval [CI] = 15.7% to 55.2%) and 6-month overall survival was 45% (95% CI = 23.1% to 64.7%). Treatment-related adverse events were consistent with prior tazemetostat reports. Although tazemetostat did not meet its primary efficacy endpoint in this population of refractory pediatric tumors (objective response rate = 5%, 90% CI = 1% to 20%), 25% of patients with multiple histologic diagnoses experienced prolonged stable disease of 6 months and over (range = 9-26 cycles), suggesting a potential effect of tazemetostat on disease stabilization.

Radiological findings in Erdheim Chester disease: A very rare multisistemic disease

Erdheim-Chester disease is an uncommon non-Langerhans cell histiocytosis affecting multiple systems. There is limited knowledge on the imaging capabilities of this disease. We present an extremely rare case of Erdheim-Chester illness in a 67-year-old man with multisystem involvement, including the cardiovascular system, skeleton, retroperitoneum (renal and adrenal infiltration) and the neurologic system. The involvement of the various organs was thoroughly assessed using multimodal imaging modalities such as computed tomography, magnetic resonance imaging, positron emission tomography and bone scintigraphy. Erdheim-Chester illness was revealed by a bone biopsy. Especially when there is cardiac and cerebral involvement, Erdheim-Chester illness is a rare condition with a poor prognosis. Knowing the imaging characteristics of Erdheim-Chester disease may be helpful in understanding the radiological results of many organs affected by the disease as described and discussed in the current case report.

Molecular and clinicopathologic characterization of pediatric histiocytoses.

The spectrum of somatic mutations in pediatric histiocytoses and their clinical implications are not fully characterized, especially for non-Langerhans cell histiocytosis (-LCH) subtypes. A cohort of 415 children with histiocytosis from the French histiocytosis registry was reviewed and analyzed for BRAFV600E . Most BRAFWT samples were analyzed by next-generation sequencing (NGS) with a custom panel of genes for histiocytosis and myeloid neoplasia. Of 415 case samples, there were 366 LCH, 1 Erdheim-Chester disease, 21 Rosai-Dorfman disease (RDD), 21 juvenile xanthogranuloma (JXG, mostly with severe presentation), and 6 malignant histiocytosis (MH). BRAFV600E was the most common mutation found in LCH (50.3%, n = 184). Among 105 non-BRAFV600E -mutated LCH case samples, NGS revealed mutations as follows: MAP2K1 (n = 44), BRAF exon 12 deletions (n = 26), and duplications (n = 8), other BRAF V600 codon mutation (n = 4), and non-MAP-kinase pathway genes (n = 5). Wild-type sequences were identified in 17.1% of samples. BRAFV600E was the only variant significantly correlated with critical presentations: organ-risk involvement and neurodegeneration. MAP-kinase pathway mutations were identified in seven RDD (mostly MAP2K1) and three JXG samples, but most samples were wild-type on NGS. Finally, two MH samples had KRAS mutations, and one had a novel BRAFG469R mutation. Rarely, we identified mutations unrelated to MAP-kinase pathway genes. In conclusion, we characterized the mutational spectrum of childhood LCH and clinical correlations of variants and subtypes. Variants responsible for JXG and RDD were not elucidated in more than half of the cases, calling for other sequencing approaches.

E029 Erdheim-Chester disease: a rare multisystem disorder

Abstract Background/Aims Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis with multiorgan involvement. Otherwise known as polyostotic sclerosing histiocytosis it is characterised by proliferation and infiltration of lipid laden macrophages into bone marrow. Extraskeletal involvement is commonly seen involving heart, CNS, skin, lung, kidney, and retroperitoneum resulting in a variety of presenting features. Methods Case: 75-year-old male referred to rheumatology connective tissue disease clinic by respiratory team with dyspnoea and unintentional weight loss of 20kg in one year. CT had shown pleural effusions and interstitial markings in mid zones felt to be due to cardiac failure. PMH - IHD, CABG. Mildly elevated dsDNA of 10. He denied cough, sputum or haemoptysis. No mouth ulceration, alopecia, sicca symptoms, Raynaud's, rashes, fevers, myalgia, or joint swelling. No family history of rheumatic disease. On examination reduced air entry to lung bases, no synovitis, no nail bed changes, no lymphadenopathy. Results Further investigations showed persistent mildly elevated dsDNA, crithidia negative, negative ANA on HEp2, Hb 136, WCC 13.8, PLT 329, complement levels normal, Igs normal, IgG4 normal, NTproBNP raised 3196, ESR 27, CRP 28. Further CT CAP - bilateral pleural effusions, thickened enhancement of pleura bilaterally without focal mass, increased interstitial markings lung mid zones, significant thick pericardial enhancement and pericardial effusion, thickening around distal oesophagus and a rind of inflammatory thickening around distal thoracic aorta. Transthoracic echocardiogram - small pericardial effusion without haemodynamic compromise, normal left and right ventricular function. NM whole body - marked increased uptake in diametaphyseal regions of tibial bones and distal aspect of femora. MRI femurs - significant symmetrical abnormality in distal femoral shaft and metaphyseal region of both femora, endosteitis with extensive linear and patchy reduction T1 signal intensity and increase in STIR intensity within medullary cavity of distal femur. CT guided biopsy of distal femur identified foamy histiocytic infiltration with fibrosis. BRAF mutation testing of plasma showed strong positive result confirming molecular diagnosis of Erdheim-Chester disease. Cardiac MRI had been requested and MRI of brain was normal. He was treated initially with 40mg prednisolone, weaned to 15mg, and weekly PEG interferon with improvement in dyspnoea and weight loss. However, he deteriorated slowly over the next year and died of cardiac failure. Conclusion Histiocytic disorders such as Erdheim-Chester disease do rarely present to rheumatology given multisystem involvement and diagnostic uncertainty. This patient had skeletal, cardiac, lung, and gastrointestinal involvement resulting in his dyspnoea and weight loss. Initial treatment involves corticosteroid and interferon. Approximately 50% of patients have BRAF mutation and may respond to vemurafenib therapy. Our patient unfortunately deteriorated prior to being considered for this treatment. Prognosis is poor with a 3-year survival of 50%. Disclosure G. Starritt: None. D. McCormick: None.

Erdheim-Chester Disease.

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis. The disease is widely variable in its severity, ranging from incidental findings in asymptomatic patients to a fatal multisystem illness. CNS involvement occurs in up to one-half of patients, most often leading to diabetes insipidus and cerebellar dysfunction. Imaging findings in neurologic Erdheim-Chester disease are often nonspecific, and the disease is commonly mistaken for close mimickers. Nevertheless, there are many imaging manifestations of Erdheim-Chester disease that are highly suggestive of the disease, which an astute radiologist could use to accurately indicate this diagnosis. This article discusses the imaging appearance, histologic features, clinical manifestations, and management of Erdheim-Chester disease.

Primary diffuse Rosai-Dorfman disease in central airway: a case report and literature review

BackgroundRosai-Dorfman disease (RDD) is a rare benign non-langerhans cell histiocytosis, mainly involving lymph nodes and skin. It is even rarer occurring only in central airway of lung and in diffuse form. Central airway RDD is similar to malignant tumor in imaging by radiological method and in bronchoscopy features. It is difficult to differentiate it from primary airway malignant tumor and to diagnose correctively in time.Case presentationHere we present a rare case of 18-year-old male diagnosed with primary diffuse RDD in central airway. Although the features examined by enhanced chest computed tomography, positron emission tomography/computed tomography, diffusion-weighted imaging of enhanced chest MRI and bronchoscopy indicate to be malignant tumor, the patient was definitely confirmed by multiple transbronchial biopsies and immunohistochemistry. After two transbronchial resections, the patient's symptoms of paroxysmal cough, whistle sound and shortness of breath were significantly reduced, as well as the airway stenosis was significantly improved. After 5 months of follow-up, the patient had no symptoms and the central airway were unobstructed.ConclusionsPrimary diffuse RDD in central airway is characterized by intratracheal neoplasm, which is usually suspected as malignant tumor according to radiological image and bronchoscopy. Pathology and immunohistochemistry are necessary for definite diagnosis. Transbronchial resection is effective and safe for patients with primary diffuse RDD in central airway.

Successful treatment of non-Langerhans cell histiocytosis with the MEK inhibitor trametinib: a multicenter analysis

AbstractErdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD) are rare non-Langerhans cell histiocytoses (non-LCHs), for which therapeutic options are limited. MAPK pathway activation through BRAFV600E mutation or other genomic alterations is a histiocytosis hallmark and correlates with a favorable response to BRAF inhibitors and the MEK inhibitor cobimetinib. However, there has been no systematic evaluation of alternative MEK inhibitors. To assess the efficacy and safety of the MEK inhibitor trametinib, we retrospectively analyzed the outcomes of 26 adult patients (17 with ECD, 5 with ECD/RDD, 3 with RDD, and 1 with ECD/LCH) treated with orally administered trametinib at 4 major US care centers. The most common treatment-related toxicity was rash (27% of patients). In most patients, the disease was effectively managed at low doses (0.5-1.0 mg trametinib daily). The response rate of the 17 evaluable patients was 71% (73% [8/11] without a detectable BRAFV600E achieving response). At a median follow-up of 23 months, treatment effects were durable, with a median time-to-treatment failure of 37 months, whereas the median progression-free and overall survival were not reached (at 3 years, 90.1% of patients were alive). Most patients harbored mutations in BRAF (either classic BRAFV600E or other BRAF alterations) or alterations in other genes involved in the MAPK pathway, eg, MAP2K, NF1, GNAS, or RAS. Most patients required lower than standard doses of trametinib but were responsive to lower doses. Our data suggest that the MEK inhibitor trametinib is an effective treatment for ECD and RDD, including those without the BRAFV600E mutation.

Erdheim-Chester Disease Involving the Left Uterine Adnexa: Mimicking an Ovarian Carcinoma Clinically.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis (LCH) that results in multiorgan disease involving the skin, bones, lungs, and kidneys. Female reproductive system manifestation of ECD was rare. Herein, we report a case of ECD involving the left ovary and fallopian tube. A 69-year-old woman presented with abdominal pain for 20 days. Magnetic resonance imaging revealed a solid and cystic mass on the left pelvic cavity. Histological examination revealed ovarian and fallopian tube infiltration by abundant histiocytes, with single small nuclei and foamy cytoplasm, reactive small lymphocytes, and plasma cells. Based on histopathological and immunohistochemical findings of positivity for CD68, CD163, and BRAF V600E and negativity for CD1α and S100, the molecular finding of BRAF V600E mutation, the patient was diagnosed with ECD. Positron emission tomography examination did not reveal any other lesions. The patient recovered well 12 months after surgery without any treatment. ECD involving the left fallopian tube and ovary was rare and needed to be differentiated from LCH, Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), IgG4+-related disease (IgG4+RD), and metastatic signet ring cell carcinoma.

Recurrent central nervous system Rosai-Dorfman disease with KRAS mutation: a case report

BackgroundRosai-Dorfman disease (RDD) is a rare, non-Langerhans cell histiocytosis of unknown etiology. we report a very rare case of recurrent central nervous system RDD with KRAS gene mutation and review the literature to improve our understanding of this disease.Case presentationA 19-year-old male patient was admitted to our hospital for headache. Cranial magnetic resonance imaging revealed a mass of abnormal signal shadows in the prepontine cistern. The mass was surgically removed and the patient was consequently diagnosed with intracranial Rosai-Dorfman disease. Seven months later, pathological examination confirmed that the RDD had recurred. Next-generation sequencing found KRAS mutation in exon 4 (C.351A > C. P. K117n).ConclusionRDD of the CNS has no distinct clinical manifestations and imaging characteristics, and the final diagnosis should be based on the results of the pathological examination. Although RDD is not currently classified as a neoplastic disorder, some evidence of clonality has changed our understanding of it. Follow up examinations over a long period are necessary to determine the efficacy of treatment.

Orbital impairment in the debut of oncohematological diseases in children

Tumor lesion of the orbit is found in the clinic of various oncohematological diseases in children. Untimely referral of such patients to an oncologist delays the timing of the necessary treatment, thereby worsening the prognosis of the disease. The literature review presents the features of clinical manifestations of orbital pathology in children at the onset of acute myeloid leukemia, myeloid sarcoma, lymphoma, Langerhans cell and non-Langerhans cell histiocytosis. The article presents our own observations and identifies factors that negatively affect the timely diagnosis of oncohematological diseases in this category of patients.

Patient with Rosai-Dorfman-Destombes disease: 18F-FDG-PET/CT scan as a diagnostic tool

Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis, with sinus involvement and massive lymphadenopathy. RDD is usually self-limited; it can appear alone or related to other diseases. We present a 9-year-old male with biopsy of that lesion was taken, giving as result a benign histiocytosis, compatible with RDD. The patient was scanned with full body 18F-FDG PET/CT, the results of the study showed hypermetabolic focal lesions in the sphenoid sinus, ethmoid sinus, and bilateral nasal involvement with hypermetabolic focal injury in the middle third of the left tibia, findings in relation to high-grade expansive injury. The study of 18F-FDG PET/CT demonstrated avid FDG lesions at nodal and extranodal sites, and it also can be used in monitoring and/or evaluating response to treatment.

Cutaneous Emperipolesis: Rosai–Dorfman Disease – An Uncommon Entity

Rosai–Dorfman disease (RDD) is a rare, benign idiopathic, non-Langerhans cell histiocytosis. The most common presentation is massive bilateral painless lymphadenopathy with fever and weight loss. Approximately 40% of patients with RDD have extranodal involvement. The cutaneous involvement is the most common extranodal manifestation comprising 11% of RDD, but only 3% presents as pure cutaneous disease (CRDD). A 55-year-old male presented with a painless swelling over the neck in the midline of 2 months duration. On examination, a firm nodular lesion measuring 1 cm × 1 cm was located on the midline of the neck. Excision biopsy was done with a differential diagnosis of calcified cyst. Histopathological examination showed emperipolesis, and immunohistochemistry was positive for S 100 and cluster of differentiation (CD) 68 and negative for CD1a confirming a diagnosis of RDD. All systemic, biochemical, and radiological examinations were unremarkable. There was no further local recurrence after 1 year of follow-up.

A meta-analysis of cases of Rosai Dorfman disease reported on the African continent and a description of two cases from a tertiary academic hospital in Johannesburg, South Africa.

Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by the accumulation of activated histiocytes within affected tissues. The original haematopathological description of RDD has links to the late South African born haematopathologist, Ronald Dorfman, with a descriptive account of two cases of the disease treated at Chris Hani Baragwanath Academic Hospital are described herein. Alongside the two case descriptions is a meta-analysis of 149 published cases from the African continent. Sequential literature searches were performed on Google Scholar and PubMed with the search terms "sinus histiocytosis with massive lymphadenopathy", "Rosai-Dorfman disease", "Rosai-Dorfman Destombes" and "lymphadenopathy" together with the name of each individual country on the African continent, from Algeria to Zimbabwe. All possible cases of RDD reported in published literature from Africa were captured on a Microsoft Excel spreadsheet recording details, where available, of demographics, nodal (nodal groups) or extra-nodal disease as well as treatment. Of the 54 African countries on the continent, published data was available from half of these countries (n=27). Nigeria (35), Tunisia (25) and South Africa (23) contributed the majority of cases for data collection with a clear paucity of reportable information available from Central Africa. Of the 149 cases from the African continent, the majority were from patients aged ten years and younger with a decrease in reported cases in patients with increasing age. The mean age at diagnosis was 25.66 years [95% CI: 21.81-29.51] with a median age of diagnosis of 24.5 years. The youngest patient in the series was 3 months old and the oldest patient aged 72 (range 71.75 years, IQR 31). The cases reported were fairly split between males and females with a male-to-female ratio of 1.07: 1. HIV seropositivity was reported in seven patients (4.8%) and no HIV results were available in 104 patients (71.2%). Disease presentation was split between nodal disease in 43% of patients (n=64), Extra nodal (EN) disease in 32.9% (n=32), mixed (nodal/EN) disease in 11.4% (n=17) and unknown in 12.8% (n=19). Fever was present in 18.1% (n=27) of cases. Hepatic enlargement was noted in nine patients (6%) and splenic enlargement in four patients (2.7%). Commonly ascribed sites of EN disease, in descending order, were skin and soft tissue, ocular, ear/nose/throat (ENT), abdominal organ(s), bone, lung/pleura, brain parenchyma (including dura), endocrine glands, spine, breast, pericardium, pseudotumour formation (unspecified site), joint(s), peripheral nerves and genitourinary tract disease. The upfront administration of glucocorticosteroids was seen in the majority of cases. Rosai-Dorfman-Destombes, although a rare disorder, should be considered as a differential diagnosis in patients with massive bilateral cervical lymphadenopathy and is confirmed with accompanying pathological changes on microscopic and immunohistochemical examination of biopsy specimens. The role of infection, particularly HIV infection, is considered to be a possible contributor to the pathogenesis of RDD and HIV testing in patients from areas of high HIV endemicity with co-existing RDD should be undertaken. Consideration for mycobacterium tuberculosis infection in patients with generalized significant lymphadenopathy still remains an important differential for massive lymphadenopathy and requires confirmation by appropriate microbiological investigations. The treatment landscape in RDD is limited in many resource-poor settings, with the upfront use of glucocorticosteroids employed routinely in the majority of cases.

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

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. A retrospective chart review of children diagnosed with RDD at a tertiary care children's hospital was conducted from 2000 to 2021. 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. 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.

Multicentric Reticulohistiocytosis Associated with an Early Form of Systemic Lupus Erythematosus: A Case Report of a Rare Disease, with Mini Review of the Literature.

Multicentric reticulohistiocytosis (MRH) is the most frequently described form of reticulohistiocytosis (RH), and it is classified as a class IIb non-Langerhans cell histiocytosis. It has been designated as multicentric, being characterized by multisystemic involvement. In fact, although mainly involving the skin, along with the joints, it is a systemic inflammatory condition potentially involving every internal organ. As MRH-related skin findings can mimic rheumatoid nodules or Gottron papules, the histopathology of the cutaneous lesions is often necessary for the correct diagnosis. Approximately one-third of MRH patients have confirmed concomitant autoimmune disorders. A wide variety of autoimmune disorders associated with the disease have been reported in the literature, suggesting immune dysfunction as a factor in the pathophysiology of MRH. A case of MRH associated with autoimmune manifestation is reported in the context of a mini review of the literature, with a focus on clinical presentation, treatments, and treatment outcomes. Moreover, eight cases of MRH associated with autoimmune diseases are briefly discussed.

PMON110 Panhypopituitarism as a Rare Presentation of Erdheim – Chester disease (ECD) in an Adolescent Patient

Abstract Background Erdheim-Chester disease (ECD) is a rare multisystemic histiocytic disorder. Only a dozen pediatric cases are reported. Here, we present a case of ECD in a pediatric patient who presented with short stature and delayed puberty. Clinical Case A 14-year-old male with history of autism and ADHD presented with short stature and pubertal delay. He grew along the 40th percentile until age 7 years when growth velocity declined. On exam, his height was 145.6 cm (0.98%ile, z-score -2.34), weight was 55.6 kg (63.19%ile, z-score 0.34), and testicular size was 5-6 mL. He had increased thirst and episodes of bedwetting since age 7. Bone age was delayed at 11 years 6 months. Further workup was recommended, but family was lost to follow up. At 16, he returned with continued poor growth, polydipsia, and nocturia. Height was 153 cm (0.26%ile, z-score -2.80), weight 61.1 kg (40%ile, z-score -0.25). Labs revealed IGF-BP3 2.8mcg/mL(3.1-8.9), IGF-1 35ng/mL(245-522), LH 1.2mIU/mL(0.29-4.77), and total testosterone <7.0 ng/dL(250-1100). Prolactin, cortisol, thyroid, and karyotype were normal. Growth hormone (GH) stimulation test confirmed GH deficiency. He was referred to oncology clinic when a brain MRI revealed a nodular enhancing suprasellar mass extending from the third ventricular floor to the dorsum sella along the pituitary stalk and rounded sclerotic lesion in the frontal bone. Biopsy of the suprasellar lesion was remarkable for foamy histiocytes positive for CD68, negative for S100 and CD1a, an eosinophilic cell background highlighted by S100 and synaptophysin, SALL4 negative. A diagnosis of xanthomatous hypophysitis was made. Additionally, lab studies confirmed diabetes insipidus (DI), treated with DDAVP. Growth hormone was trialed for 2 weeks, but he developed acute pancreatitis, so it was discontinued. He subsequently developed recurrent pancreatitis of unclear etiology requiring frequent hospitalization with development of insulin-dependent diabetes mellitus due to pancreatic damage. He was lost to follow up for 12 months after leaving home at age 18. He returned to our institution after incidental findings of 7th right rib expansile lytic bony lesions on abdominal CT during a pancreatitis admission. Biopsy of the rib lesion was positive for a BRAF-V600E mutation. Skeletal survey revealed new multiple small lytic skull lesions. Repeat brain MRI demonstrated new calvarial lesions, increased suprasellar mass. Chest CT scan showed a micronodular pattern with mediastinal lymph node enlargement. PET confirmed widespread multifocal FDG hypermetabolic lesions. Final diagnosis of ECD was made; he was started on targeted therapy with Vemurafenib, a BRAF inhibitor. Conclusion Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis, which rarely affects pediatric patients who present with bone pain and DI; however, here we present a case of ECD in an adolescent with short stature and multiple pituitary deficiencies to highlight the varied presentation of the disorder. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Clinical phenotypes and long-term outcome of kidney involvement in Erdheim-Chester histiocytosis

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that frequently infiltrates the peri-kidney space ("hairy kidney" appearance), kidney pelvis and proximal ureters, leading to obstructive uropathy. Here, we analyzed the clinical characteristics, imaging findings and long-term kidney outcome of a large multicenter cohort comprising 195 consecutive patients with ECD. Retroperitoneal peri-kidney or peri-ureteral involvement was detected at diagnosis in 147 patients. Of them, 70 had hydronephrosis (bilateral in 47), and 16 with kidney atrophy (unilateral in 14). Kidney vascular peduncle infiltration was found in 60 patients, and kidney artery stenosis in 31. The estimated glomerular filtration rate (eGFR) at diagnosis was significantly lower in patients with than in those without peri-kidney involvement (median 74 vs. 98 mL/min/1.73 m2). Ureteral stenting often failed to achieve kidney function recovery. A total of 181 patients received medical therapies: first-line treatments included interferon-α (61%), BRAF-inhibitors (17%), mTOR-inhibitors (7%), or other drugs (15%). These therapies were efficacious for ECD but rarely induced kidney function improvement (one-year eGFR increase over 25% in under 10% of patients). After a median of 43 months, 19% of patients died and 5% developed kidney failure. Among patients with peri-kidney involvement, 44% developed chronic kidney disease (CKD) 3-5 at five years vs. 5% of those without. Unadjusted predictors of advanced CKD and kidney failure/death were age over 50 years, hypertension, BRAFV600E mutation, and baseline eGFR. At multivariable analysis, cardiovascular comorbidities were associated with advanced CKD, and age over 50 years with kidney failure/death. Thus, kidney involvement is common in ECD and can lead to CKD or kidney failure despite effective medical therapies or urological procedures.