Intestinal Langerhans cell histiocytosis presenting with symptoms similar to inflammatory bowel disease: a case report.

Background: Langerhans cell histiocytosis is a rare disease characterized by the abnormal proliferation of Langerhans cells within a single organ or multiple organs. This case report aims to improve the knowledge of the presentation of gastrointestinal Langerhans cell histiocytosis to facilitate the diagnosis and management of this rare disorder. Case presentation: A 19-month-old female presented with repeatedly mucinous bloody stools. The abdominal ultrasound revealed a slightly enlarged spleen. The initial colonoscopy revealed chronic enteritis with a very early onset inflammatory bowel disease. After anti-inflammatory treatment without improvement, an intestinal biopsy was performed at The Forth Affiliated Hospital of Zhejiang University. The final intestinal biopsy and histopathology examination confirmed the presence of Langerhans cell histiocytosis. After diagnosis, additional lung and head imaging examinations revealed no abnormalities. Her condition improved gradually after being treated with chemotherapy (vincristine and prednisone) and molecular-targeted drug(dalafinil) treatment. Conclusion: The clinical symptoms of Langerhans cell histiocytosis involving the gastrointestinal tract are not specific and may resemble symptoms observed in inflammatory bowel disease and other primary gastrointestinal tumors. Therefore, in cases of infants presenting with inflammatory gastrointestinal symptoms that do not resolve after treatment, a biopsy is essential to obtain a differential diagnosis.

Late Diagnosis of Langerhans Cell Histiocytosis by Skin Biopsy in a Lung Transplant Candidate Patient.

We present the case of a lung transplant candidate under veno-venous membrane oxygenation assistance (VV ECMO) whose diagnosis of emphysema of undetermined etiology was redefined as Langerhans cell histiocytosis (LCH) due to a scalp skin biopsy performed years after the beginning of his respiratory symptoms. A 20-year-old patient started three years before his admission with progressive dyspnea leading to a diagnosis of bullous emphysema of undetermined cause, which evolved into respiratory failure and evaluation for bilateral lung transplant. Three years later, he developed bilateral pneumonia requiring mechanical ventilation. When refractory hypoxemia ensued, he had to be placed on VV ECMO. Under these conditions, he was transferred to our center and listed for a bilateral pulmonary transplantation. Forty-eight hours after admission, and due to intense polyuria, central diabetes insipidus was diagnosed. In this clinical context, the presence of cutaneous lesions on the scalp was reconsidered and biopsied under the presumption of possible LCH, with pathology analysis confirming the diagnosis. He continued to be assisted with VV ECMO for 66 more days as a bridge to transplantation, developing multi-organ failure and passing away before a donor organ was available. The diagnosis of LCH should be considered in any adult patient with bullous emphysema of undetermined cause. Given the possibility of early therapeutic interventions, the search for its clinical associations (e.g., diabetes insipidus and/or skin lesions) should be a systematic part of the etiologic workup. The availability of skin specimens to reach a diagnosis makes its thorough search an important part of the diagnostic approach.

The plasma-soluble CSF1R level is a promising prognostic indicator for pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls (p < .001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients (p < .001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC = 0.782, p < .001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.

From mutation to management: Advancing Langerhans cell histiocytosis treatment through combination therapies.

The treatment landscape for relapsed Langerhans cell histiocytosis (LCH) is fraught with uncertainty due to a scarcity of data. Karri et al.'s study provides promising evidence that combining MAPK pathway inhibitors with chemotherapy could improve outcomes, even for patients with multiple relapses. Although larger studies are needed, this approach suggests a shift towards more aggressive, potentially curative strategies in the management of LCH. Commentary on: Karri et al. Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19380.

Langerhans cell histiocytosis presenting as a blueberry muffin rash.

Langerhans cells, often referred to as the "macrophages of the skin", are dendritic cells that normally reside in the epidermis and papillary dermis. Just like macrophages, they function as antigenpresenting cells that activate naive T cells. Certain mutations such as those involving the BRAF gene can cause unopposed production of Langerhans cells, which is known as Langerhans cell histiocytosis (LCH). LCH triggers an inflammatory immune response that causes systemic manifestations such as fever and fatigue, as well as other manifestations depending on the affected organs. The pathogenesis behind LCH remains poorly understood. It is still unknown whether it is a neoplastic process or a reactive cancer-mimicking illness. Diagnosis of LCH is confirmed by biopsy, and treatment is largely dependent on the extent and severity of the disease. Common treatments include corticosteroids, excision, radiation, and chemotherapy. We present a case of a 1-year-old Saudi male with LCH.

Increased AXLhigh myeloid cells as pathognomonic marker in Langerhans cell histiocytosis and Langerin expression dependence of mTOR inhibition.

Langerhans cell histiocytosis (LCH) is characterized by an expansion and accumulation of pathological histiocytes expressing langerin (CD207) and CD1a in different organs under an inflammatory milieu. The origin of pathognomonic precursors of LCH is widely debated, but monocytes and pre-dendritic cells (pre-DC) play a significant role. Remarkably, we found an expansion of AXLhigh cells in the CD11c+ subset of patients with active LCH, which also express the pathognomonic CD207 and CD1a. Moreover, we obtained a monocyte-derived LC-like (mo-LC-like) expressing high levels of AXL when treated with inflammatory cytokine, or plasma of patients with active disease. Intriguingly, inhibiting the mTOR pathway at the initial stages of monocyte differentiation to LC-like fosters the pathognomonic LCH program, highly increasing CD207 levels, together with NOTCH1 induction. We define here that AXLhigh could also be taken as a strong pathognomonic marker for LCH, and the release of Langerin and NOTCH1 expression depends on the inhibition of the mTOR pathway.

Pulmonary Langerhans Cell Histiocytosis in an African Lion: A Rare Case Report.

BACKGROUND: Feline pulmonary Langerhans cells histiocytosis (PLCH) is a rare disorder that results in progressive respiratory failure secondary to pulmonary parenchymal infiltration with Langerhans cells (LCs). A diagnosis of PLCH is proposed based on the clinical features and pathological findings and confirmed based on the infiltrating histiocytic cells. There are few documented cases of feline PLCH, and this case report of PLCH in an African Lion could present new information and aspects of this feline histiocytic disease. CASE PRESENTATION: An African lion at Hohhot Zoo showing severe hyporexia and dyspnea with subsequent mental depression and emaciation died of exhaustion after a 35-day course of illness. Empirical treatment did not have a significant effect. An autopsy revealed that the lungs were enlarged and hardened due to infiltrative lesions, with many yellowish-white foci in all the lobes and sections. Furthermore, the kidneys were atrophied and had scattered grayish-white lesions on the surface. At the same time, congestion was widely distributed in various locations, including the liver, subcutaneous loose connective tissues, serosal surface and other tissues and organs. Histologically, proliferative histiocytic cells (PHCs) were scattered in the alveolar cavities, bronchioles and submucosa of bronchioles, with evident cellular and nuclear pleomorphism, and thus the alveolar septa were obliterated. The histopathological changes in other organs included chronic sclerosing glomerulonephritis, proliferated Kupffer cells in the liver, adrenal edema and interstitial connective tissue hyperplasia, as well as atrophy of the small intestines and spleen. Furthermore, immunohistochemical analysis results were strongly positive for CD1a, vimentin, S100 and E-cadherin in the membrane or cytoplasm of PHCs, supporting an LC phenotype. CONCLUSIONS: Here, we present a rare pulmonary Langerhans cell histiocytosis case in an African lion.

Complete remission after a single bisphosphonate infusion in isolated bone Langerhans cell histiocytosis lesion: a case report and a narrative review of the literature.

Langerhans cell histiocytosis (LCH) is a rare disease with limited treatment options. We present a case involving a 57-year-old woman afflicted with an isolated LCH bone osteolytic lesion. A single bisphosphonate infusion significantly alleviated pain, and follow-up scans via CT, PET-CT, and MRI revealed a substantial recalcification of the lesion. Conducting an extensive literature review, we identified 46 cases documenting the efficacy of bisphosphonates in the context of LCH. These findings have raised interest in bisphosphonate infusion as a simple therapeutic alternative in similar situations, with benefits in terms of bone recalcification and pain control for individuals with LCH.

Langerhans Cell Histiocytosis With Unusual Hexagonal Crystals in Addition to Usual Charcot-Leyden Crystals. Report of a Patient With Possible Process of Crystal Formation and Clinical Significance of a "Necrotic" Change.

Langerhans cell histiocytosis is a rare neoplastic disorder characterized by the proliferation of Langerhans cells and often accompanied by eosinophil infiltration. Charcot-Leyden crystals, composed of galectin 10, are occasionally observed in Langerhans cell histiocytosis; however, histological images are rarely reported. We herein present a patient with Langerhans cell histiocytosis with Charcot-Leyden crystals and hexagonal crystals by describing the histologic and immunohistochemical features of a lymph node. A unique distribution of Charcot-Leyden crystals and hexagonal crystals was observed in this patient, shedding light on their possible formation process of the latter. We discuss the biological significance of eosinophilic abscesses in Langerhans cell histiocytosis and propose that these crystals may be linked to extracellular trap-cell death (ETosis). This example challenges the conventional characterization of "necrosis" in Langerhans cell histiocytosis and underscores the importance of recognizing ETosis as a potential mechanism involved in the pathogenesis of Langerhans cell histiocytosis. Further studies are underway to validate significance of these findings in a larger cohort of Langerhans cell histiocytosis patients.

Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis.

Optimal therapeutic approaches for advanced Langerhans cell histiocytosis (LCH) are not known. We assessed the safety and efficacy of combined chemotherapy with MAPK pathway inhibition in 10 patients with refractory systemic disease and/or LCH-associated neurodegeneration. Overall response rate was 9/10 (90%) for the entire cohort: 5/5 (100%) for patients with systemic disease and 6/7 (86%) for patients with central nervous system disease. BRAFV600E+ peripheral blood fraction decreased in 5/6 (83%). Toxicities included fever, skin rash, myalgias, neuropathy, cytopenias and hypocalcaemia. Prospective trials are required to optimize combination strategies, determine potential to achieve cure and compare outcomes to chemotherapy or MAPK inhibitor monotherapy.

Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis.

Over 50% of patients with systemic LCH are not cured with front-line therapies, and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with clofarabine. Clofarabine monotherapy was active against LCH in this cohort, including heavily pretreated patients with a systemic objective response rate of 92.6%, higher in children (93.8%) than adults (83.3%). BRAFV600E+ variant allele frequency in peripheral blood is correlated with clinical responses. Prospective multicentre trials are warranted to determine optimal dosing, long-term efficacy, late toxicities, relative cost and patient-reported outcomes of clofarabine compared to alternative LCH salvage therapy strategies.

Penile skin lesions and urinary tract obstruction: A rare presentation of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) can manifest in any organ or system, but the occurrence of cutaneous lesions on the penis, causing urethral stenosis, is particularly uncommon. The diagnosis primarily relies on typical clinical manifestations and pathological examination. Treatment involves the excision of local lesions combined with chemotherapy, with a generally favorable prognosis. A 3-year-old male patient experienced voiding difficulties after circumcision, revealing penile skin lesions upon examination. Postoperative pathological analysis and immunohistochemistry confirmed the diagnosis of LCH. Langerhans cell histiocytosis can present as cutaneous lesions on the penis, leading to symptoms of urinary tract obstruction.

[Xanthogranulomatous adrenalitis : A rare and difficult differential diagnosis of adrenal gland tumors]. / Xanthogranulomatöse Adrenalitis : Seltene und schwierige Differentialdiagnose von Nebennierentumoren.

A radiologically diagnosed tumor in a 29-year-old woman with a fever of around 39 °C was operated on under the suspicion of cholecystitis or a liver abscess. A solid tumor was found in the adrenal gland and resected. The frozen section findings did not reveal a clear diagnosis of entity and assignment. Histologically, the tumor was found to consist of densely clustered large histiocyte-like cells with expression of vimentin, CD68, and CD163 as well as negativity for keratin, langerin, and SMA. We diagnosed xanthogranulomatous adrenalitis and discussed the differential diagnoses (Langerhans cell histiocytosis, Rosai-Dorfman disease, malakoplakia, Erdheim-Chester disease).

A Diagnostic Dilemma and Classification Conundrum: Atypical Histiocytic Neoplasm Presenting as a Calvarial Mass.

Histiocytic disorders are a wide range of disorders arising from abnormal proliferation and infiltration of dendritic cells. The Histiocyte Society has arranged the disorders into five main groups: L, C, M, R, and H. We present a case in which an elderly woman presented with a solitary osseous lesion in her skull in the right anterior calvarium. Biopsy and histological studies were strongly positive for cyclin D1; positive for CD68, S100, and ZBTB46; weakly positive for OCT2; and equivocal for ALK1 and CD163. Genomic studies also identified KRAS and GPS2 mutations. KRAS-positive genomic analysis favors a diagnosis of histiocytoma, while the solitary calvarium and spontaneous resolution with remission favor a diagnosis of Langerhans cell histiocytosis (LHC). Despite the strong clinical evidence favoring LCH, our patient's clinical and histologic features did not fit any of the five histiocytic categories and were classified as an atypical histiocytic disorder.

Langerhans cell histiocytosis in children with refractory diarrhoea and hypoalbuminaemia as the initial presentation: two case reports and a literature review.

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.

From terminal ileum to terminal diagnosis: The critical role of terminal ileum intubation in diagnosing langerhans cell histiocytosis in a patient with TAR syndrome.

The co-occurrence of Thrombocytopenia with Absent Radius (TAR) syndrome and Langerhans Cell Histiocytosis (LCH) is exceedingly rare, with scant documentation in existing medical literature. This case report aims to shed light on this unique intersection of conditions, emphasizing the diagnostic and therapeutic challenges it presents. A 27-year-old female with a history of TAR syndrome presented with microcytic anemia, hip pain, and gastrointestinal symptoms. Terminal ileum intubation during colonoscopy revealed superficial ulcerations, leading to a biopsy that confirmed LCH. Subsequent radiologic investigations, including CT and MRI, showed multiple osseous lesions in the pelvis, sacrum, and skull. A treatment plan involving IV Cytarabine was initiated due to concerns of CNS involvement, as indicated by mastoid air cell involvement and symptoms of dizziness and ear fullness. The case highlights the diagnostic value of terminal ileum intubation during colonoscopy, which was pivotal in diagnosing LCH in this patient. It also discusses the use of IV cytarabine, a chemotherapy drug that inhibits DNA synthesis, as a suitable treatment option given the suspected CNS involvement. The case adds to the limited literature on the natural history and management of adult patients with LCH, particularly in the context of TAR syndrome. This case report serves as a compelling addition to medical literature, highlighting the diagnostic complexities and treatment considerations in a patient with both TAR syndrome and LCH. It emphasizes the importance of comprehensive diagnostic approaches, including terminal ileum intubation during colonoscopy, and introduces IV cytarabine as a viable treatment option for cases with suspected CNS involvement.

Rosai-Dorfmann Disease: A Rare Disease Presenting as a Unilateral Neck Swelling.

Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder of unknown etiology. Usually it presents with massive painless cervical lymph node enlargement. Histologically, it shows proliferation of distinctive histiocytic cells that demonstrate emperipolesis in the background of a mixed inflammatory infiltrates. Immunohistochemically, the cells are positive for markers such as CD68 and S100. A 14-year-old boy presented with painless right sided cervical lymphadenopathy without any systemic and other ear, nose, and throat manifestations. The biopsy report of the lymph node showed infiltration of sheets of histiocytes showing emperipolesis with areas of fibrosis and hyalinisation. The sinus histiocytes were strongly positive for S-100 protein. RDD must be considered in the differential diagnosis of massive or multiple lymphadenopathies.

Erdheim-Chester disease with tendon and muscle involvement: Reports of a rare presentation.

Erdheim-Chester disease (ECD) is a rare histiocytic disease that affects multiple systems in the body. While it typically targets long bones, cardiovascular structures, the retroperitoneum, and the central nervous system, reports of tendon and skeletal muscle involvement are scarce. This review presents 2 cases: a case of ECD involving the left Achilles tendon and left abductor hallucis, as well as an unusual manifestation of ECD in the thigh musculature. In Case 1, studies involved a 39-year-old man who initially presented with bone and pituitary involvement. An order for 18F-FDG PET/CT imaging was placed by marked swelling in the patient's left ankle and observed soft tissue fullness on foot radiographs, which revealed a soft tissue mass involving the left Achilles tendon, which arose along the tendon-muscle junction and involved the left abductor hallucis muscle. In Case 2, studies involved a 41-year-old man who initially presented with involvement of the cardiovascular system and retroperitoneum. 18F-FDG PET/CT scan showed an infiltrative right atrial mass and hypermetabolic lesion in the left external obturator muscle, extending to the left pectineus and right quadratus femoris muscle. Involvement of the Achilles tendon and skeletal muscle involvement, including left abductor hallucis muscle and medial thigh muscles, is one of the rare manifestations of ECD. Diagnostic delays were frequent due to the condition's rarity and nonspecific multisystemic symptoms. This should be considered in patients who present with myositis, tendinopathy, and bone pain and have other unexplained multisystemic problems.