Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis with unknown aetiology. It is recently recognised to be neoplastic with genetic mutations affecting the mitogen-activating protein kinase pathway. We report a 49-year-old female patient who initially presented in 2012 to a tertiary care centre in Muscat, Oman, with bilateral facial masses. These were removed but later recurred over a period of 10 years. She then presented with xanthelasmas, bone lesions, secondary infertility due to hypothalamic hypogonadism, diabetes insipidus and Hashimoto\'s hypothyroidism. The facial masses were biopsied and they showed classic morphological features in the form of diffuse infiltration by foamy histiocytes with scattered Touton type of giant cells, patchy lymphocytic infiltrates and dense fibrosis. The patient is stable and is being followed-up. The presented ECD case is particularly interesting due to the recurrent bilateral facial masses. To the best of the authors\' knowledge, this is the first documented case in Oman.

An uncommon benign histiocytic illness, Rosai-Dorfman disease (RDD) mostly affects lymph nodes but can also manifest as extranodal involvement. We describe a case of a female patient, sixty years of age, who had joint discomfort, sleeplessness, weight loss, and headache and eye problems. A heterogeneously hypodense perirectal mass was seen on imaging. Other histiocytic diseases, metastatic cancer, and lymphoma were among the differential diagnosis. Through biopsy and immunohistochemistry staining, which revealed S-100 and CD68 positivity with CD1a negative, a definitive diagnosis of RDD was made. Over a 2-year period following surgical excision, the patient\'s symptoms significantly improved and there was no sign of recurrence. This example emphasizes the significance of taking RDD into account when making a differential diagnosis for perirectal tumors and the function of imaging in conjunction with histological testing in guiding management.

Langerhans cell histiocytosis (LCH) is a neoplastic disease characterized by aberrant proliferation of the mononuclear phagocyte system, predominantly affecting children under the age of 3 years. Although LCH can affect almost all organs, sinus involvement is rare. This case report documents a 9-year-old boy presented with vision impairment and intermittent headache on the right side. The CT scan and MRI examination revealed the presence of a soft mass in the right atrium of sphenoid sinus, which impacted the right optic canal. Biopsy results confirmed the presence of LCH. Considering the involvement of optic canal and vision impairment, meticulous debridement was performed followed by a 12-month standard chemotherapy. After 2 years of follow-up, the patient showed significant improvement, despite the presence of an encapsulated cyst in the right sphenoid sinus. This case highlights the importance of considering LCH when encountering an isolated soft mass accompanied by decreased vision in the sphenoid sinus. A thorough physical examination, laboratory tests, and imaging methods should be performed, with a biopsy being necessary to confirm the type of lesion and guide the appropriate treatment.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a clonal myeloid neoplasm with inflammatory component. Refractory disease is a challenge, but vemurafenib has emerged as a therapeutic option. We will delineate the cases of two Brazilian children suffering from refractory LCH with a positive response to vemurafenib.
METHODS: Both cases had a diagnosis of multisystem disease with involvement of organs at risk and had not responded to standard and second-line treatment. After refractoriness to classic treatment regimens, the BRAF mutation was investigated and found to be positive in both patients, and target therapy with vemurafenib was sought. The first case has been using vemurafenib for about 2 years and the second case has been using it for about 3 years, having had an attempt to suspend the medication after concomitant use with maintenance therapy. However, the disease returned 4 months after stopping the medication. Fortunately, the disease returned to remission status after the medication was reintroduced.
CONCLUSIONS: These cases represent the first reported instances of off-label vemurafenib use in Brazil for the treatment of LCH and both patients have demonstrated excellent responses to the medication. However, the long-term side effects are unknown in children, and prospective studies are needed. In addition, there is a lack of epidemiological data on histiocytosis in Brazil and studies evaluating the budgetary impact of incorporating BRAF mutation research and the use of vemurafenib into the public health system. These reports could be a starting point.

We aimed to examine the association between relative monocytosis and the recurrence of pulmonary Langerhans Cell Histiocytosis. Clinical, laboratory, radiographic and treatment data for 86 patients with a histopathological diagnosis of Langerhans Cell Histiocytosis over a 20-year duration. Parameters such as biological sex, age at diagnosis, time to diagnosis, molecular diagnostic data and imaging were collected. Treatment responses were assessed predominantly through radiography, with RECIST 1.1 criteria applied to MRI or CT scans and PERCIST utilized for serial PET imaging. Investigators also assessed peripheral blood absolute monocyte count at various time points, including initial diagnosis and the most recently available value. While peripheral blood absolute monocyte count between the earliest assessed timepoint and latest value did not differ, the mean value on progression (0.94 K/µL), however, was significantly higher than that following re-institution of therapy (0.31, p = 0.000794. Our observation of relative monocytosis on LCH disease progression may be related to an increase in circulating LCH on disease progression or from increased monocyte production for later differentiation into mature dendritic cells that participate in MHC Class 1 upregulation. This trend is especially evident in pulmonary LCH which is incited by tissue trauma and irritation by environmental factors. The phenomena observed in our study parallel other non-LCH cohorts, specifically in published findings from our own group in patients with Rosai Dorfman and Erdheim Chester Disease. To further elucidate the molecular underpinnings of LCH and explore the etiology of this monocyte trend, expanded integrated genomic-transcriptomic sequencing analyses to evaluate the molecular character of LCH and ultimately clarify the origin of this monocyte trend are in progress. These studies are poised to offer invaluable insight to the molecular mechanisms underlying LCH, specifically as they pertain to monocyte signaling and differentiation.

BACKGROUND: A 28-year-old male suffers for two weeks from new-onset very severe headache located on his left temple radiating to his jaw. He also complains about left sided retroorbital pain and chewing aggravated symptoms. In addition, nausea and emesis in the mornings during the past six months were reported. Clinical examination revealed tender swelling over the left temple, but laboratory results showed no signs of inflammation, normal electrolytes, kidney and liver values. A CT-scan revealed a circumscriptive osteolytic lesion in the left os temporale.
UNASSIGNED: 28-jähriger Patient mit in den Kiefer ausstrahlenden ­Kopfschmerzen temporal links.
UNASSIGNED: Ein 28-jähriger Mann klagt seit zwei Wochen über neu aufgetretene akute, pochende Kopfschmerzen temporal links. Die Schmerzstärke beträgt VAS 8/10 mit Ausstrahlung in den Kiefer. Schmerzauslöser sind Kauen und Druck auf die Schläfe. Zusätzlich gibt der Patient drückende Schmerzen retroorbital links an. Als Begleitsymptom besteht seit sechs Monaten Nüchternerbrechen. Die klinische Untersuchung ist bis auf eine druckdolente Schwellung der linken Schläfe bland. Die Labordiagnostik ist unauffällig. In der CT des Neurokraniums ist der Nachweis einer osteolytischen Läsion im Os temporal links sichtbar. Schlüsselwörter: Langerhans-Zell-Histiozytose, Kopfschmerzen, LZH, ZNS, Tumor.

Langerhans cell histiocytosis (LCH) is a rare disorder involving an abnormal clonal proliferation of precursor cells of the mononuclear phagocytic system. The hypothalamic-pituitary axis is commonly affected by central nervous system (CNS) involvement, with central diabetes insipidus being the most common endocrine abnormality observed. We report the case of a 55-year-old female presenting with vision changes and found to have a hypothalamic mass that was responsive to high-dose steroids. After an initial diagnostic dilemma, the surgical pathology eventually confirmed the diagnosis of LCH. She is being treated with hormone supplementation for panhypopituitarism and intensity-modulated radiation therapy (IMRT) for the LCH. Our case highlights that LCH can present as isolated hypothalamic-pituitary involvement. Early diagnosis is critical to prevent extensive progression of the disease, ultimately leading to permanent physical and endocrine abnormalities. More studies are required to develop specific guidelines and approaches for patients with isolated hypothalamic-pituitary involvement due to LCH.

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OBJECTIVE: Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement.
METHODS: We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022.
RESULTS: Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%).
RESULTS: After a median 40 months\' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, P = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P = .010) correlated with superior PFS versus chemotherapy.
CONCLUSIONS: In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease characterized by the accumulation of Langerhans cells within the lung tissue. The diagnosis of PLCH traditionally involves clinical, radiological, and lung biopsy histopathological evaluations.
METHODS: We present 2 cases where the diagnosis of PLCH was confirmed through the analysis of bronchoalveolar lavage (BAL) fluid cytology using immunoperoxidase technique, highlighting the significance of this minimally invasive technique in the diagnostic process. Clinical and radiological examination suggested advanced interstitial lung disease characterized by a fibrocystic pattern in both cases. The cytologic analysis of the BAL fluid revealed typical histiocytes with longitudinal grooves and eosinophils, which was better seen on liquid-based cytology (LBC) smears. ICC with CD1a, Langerin, and S-100 confirmed the diagnosis of PLCH.
CONCLUSIONS: Detecting PLCH through the examination of BAL cytology poses challenges, yet it is achievable, particularly with the assistance of LBC and ICC.