Histiocytosis and adult-onset orbital xanthogranuloma in 2023: a review of the literature and mini case series.

PURPOSE: Within the large umbrella of histiocytosis are a few similar yet heterogenous entities involving the orbit and periocular tissues with or without systemic infiltration, termed adult onset xanthogranuloma or orbital xanthogranuloma. Due to rarity of these conditions, different classifications in use, diverse clinical presentations and still unknown etiology, the aim of this paper was to provide an up-to-date literature review of the actual understanding of histiocytosis and its subgroups involving the orbit and periocular area, diagnostic strategies and therapeutic modalities. METHODS: We present a review of literature and small case series comprising four patients diagnosed and treated in the period from 2001 until 2023 in our hospital. Clinical files of 4 patients with adult-onset xanthogranulomatous disease of the orbit and ocular adnexa (AOXGD) were reviewed retrospectively. Clinical, laboratory, radiological, histopathological, and immunohistochemical findings were reexamined. RESULTS: Reviewing medical records of our patients with AOXGD, we found significant overlap between histiocytosis and different immune disorders. A broad workup should be considered in these patients as they can harbour severe immune disfunctions and hematologic disorders. Preferred treatment modality depends on a histopathologic type of AOXGD, clinical presentation and systemic involvement and should be conducted multidisciplinary. CONCLUSION: The diagnosis is often delayed because of its rarity and diverse clinical findings. Development of molecular genetic tests, detection of BRAF V600E mutation and different types of kinase mutations, mutations in transcriptional regulatory genes as well as tyrosine kinase receptors have shed a new light on the etiopathogenesis and potential targeted treatment of histiocytosis.

Multisystem Langerhans Cell Histiocytosis following Treatment of Initially Presumed Atopic Dermatitis with Dupilumab: A Case Report of an Extremely Confusing Scenario.

Introduction: Atopic dermatitis (AD) is a common chronic, recurrent, and non-infectious inflammatory skin disease. Dupilumab is a human monoclonal antibody with clinical efficacy in severe AD and has a good safety profile. Case Presentation: We hereby describe a previously unreported case of multisystem Langerhans cell histiocytosis (MS-LCH) that is associated with a history of AD treatment using dupilumab. Conclusion: A single case of MS-LCH with a history of dupilumab treatment for AD was described for the first time. This case highlights that given its susceptibility to skin involvement, LCH needs to be considered as a differential diagnosis for skin lesions that are not improved by established therapies.

Multisystemic recurrent Langerhans cell histiocytosis misdiagnosed with chronic inflammation at the first diagnosis: A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by diabetes insipidus and is an uncommon occurrence. Pathological biopsies still have a certain degree of diagnostic probability. We present a case in which LCH initially affected the pituitary gland. This resulted in a misdiagnosis of chronic inflammation upon pathological examination. CASE SUMMARY: A 25-year-old female exhibited symptoms of diabetes insipidus. Magnetic resonance imaging revealed an enhanced foci in the pituitary gland. After surgical resection of the pituitary lesion, the pathological diagnosis was chronic inflammation. However, the patient later experienced bone destruction in the skull and lower limb bones. After the lower limb bone lesion was compared with the initial pituitary lesion, the final diagnosis was modified to LCH. The patient was treated with multiple chemotherapy courses. However, the patient's condition gradually worsened, and she eventually passed away at home. CONCLUSION: LCH should be considered when patients exhibit diabetes insipidus and absence of high signal intensity in the pituitary gland on sagittal T1-weighted image and abnormal enhancement in the pituitary region.

Unusual orbital, scleral and choroidal findings in Erdheim-Chester disease: a case report.

This case report highlights a unique presentation of Erdheim-Chester Disease (ECD) with bilateral scleral lesions, choroidal infiltration, and extensive sinus involvement. It is the first case report where the diagnosis was confirmed through a scleral biopsy after an initial presentation of a unilateral nodular scleritis. There was a gradual disease progression and ocular examination later revealed bilateral subconjunctival hyperemic lesions and mild exophthalmos, ophthalmoplegia, and extensive choroidal infiltration. Infiltration of the frontal and maxillary sinus was present and extended into the nasal cavity and both orbits. The diagnostic work-up is described in detail. Current treatment options are analyzed. It is emphasized that the ophthalmologist can play a crucial role in the diagnosis of ECD, given the substantial prevalence of orbital and ocular symptoms. The overall prognosis for ECD remains unfavorable, particularly in cases with orbital involvement. This case underscores the complexity and importance of a multidisciplinary approach in managing ECD.

A challenging diagnosis of Langerhans' cell histiocytosis with hypothalamic-pituitary and mandibular involvement: case report and literature review.

Background: Langerhans cell histiocytosis (LCH) is a rare bone marrow derived neoplasm that mainly affects children. It is a multiorgan disorder and hypothalamic-pituitary involvement is uncommon. LCH reveals a wide spectrum of indications; thus, the diagnosis and treatment are usually challenging. Case Report: A 22-year-old male presented with polydipsia, polyuria with nonspecific radiological findings, later on, developed a mandibular lesion and a biopsy was conducted which led to LCH diagnosis. After many improper treatments due to unclear diagnosis, the patient was finally placed on chemotherapy and is now under surveillance. Discussion: LCH is a rare disease with diverse clinical manifestations affecting various organs. Associated mutations, such as BRAF V600E, contribute to its complexity. In adults, initial symptoms include pain, weight loss, and fever, with potential pituitary involvement leading to Arginine vasopressin (AVP) deficiency. Commonly affected organs include bone, skin, and the pituitary gland. The disease can be categorized into single-system and multisystem. Pathological diagnosis involves electron microscopy or immunohistochemical staining. Treatment options vary; the presented case utilized Desmopressin acetate and prednisolone before transitioning to cyclophosphamide for multisystemic LCH. Conclusion: AVP deficiency can suggest hypothalamic-pituitary LCH, and a biopsy, if possible, is recommended to confirm the diagnosis.

Rosai-Dorfman Disease as Constrictive Pericarditis: An Unusual Childhood Presentation.

Rosai-Dorfman disease (RDD) is a rare, multisystemic, histiocytic disorder that usually presents with painless cervical lymphadenopathy. We describe a case of constrictive effusive pericarditis with congestive cardiac failure in a six-year-old child as an initial presentation of RDD. The child underwent pericardiectomy and was treated with steroids, following which the symptoms resolved entirely. While tuberculosis accounts for the majority of cases presenting with constrictive pericarditis in developing countries, the presentation of RDD can be easily missed if not kept in mind as a possibility. This case report documents the unique presentation of a rare disease.

[Smoking-related interstitial lung disease : Radiological findings, histopathological correlations, and clinical observations]. / Raucherassoziierte interstitielle Lungenerkrankungen : Radiologisches Erscheinungsbild, histopathologische Korrelation und klinische Aspekte.

CLINICAL/METHODOLOGICAL ISSUE: Identifying smoking-related interstitial lung diseases (SRILD) in smokers is challenging, as clinical manifestations can be nonspecific, and there is a variety of SRILD entities that not only interconnect but can also overlap. RADIOLOGICAL STANDARD PROCEDURES: In diagnosing SRILD, imaging techniques such as high-resolution computed tomography (HRCT) allow the identification of characteristic features, serving as crucial pieces of the puzzle for definitive differentiation. PERFORMANCE: Studies have demonstrated that HRCT exhibits a sensitivity of approximately 80-90% in identifying SRILD, with a specificity around 70-80%. The conclusive diagnosis often requires a correlation between histopathological findings and clinical observations. PRACTICAL RECOMMENDATIONS: Regular monitoring of smokers, especially when experiencing symptoms like shortness of breath and cough, coupled with a comprehensive diagnosis of SRILD, is crucial for accurate identification and individualized therapy.

Pulmonary involvement in children with Langerhans cell histiocytosis.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (pLCH) is a rare disease, mostly a component of multisystemic LCH. We aimed to investigate the clinical features and treatment results in children with pLCH. METHODS: We retrospectively reviewed the clinical, radiological, and treatment data of 37 patients with pLCH, diagnosed from 1974 to 2022. RESULTS: 10% (n=37) of 367 patients with LCH had lung involvement. The median age was 1.8 years (range: 0.4 & 17.7) with a male-to-female ratio of 2.3. At admission 29.7% (n=11) presented with respiratory symptoms. Imaging showed a spectrum from nodular opacities to multiple cysts. All but one patient had multisystem disease. Twenty-nine received vinblastine-containing therapy. Ten-year event-free (EFS) and overall survival (OS) rates were 47.8% and 63.3%, respectively. In children younger and older than two years of age, the 10-year EFS was 53.3% vs. 40.2% and the 10-year OS was 58.7% vs. 68.8%, respectively. In children with and without risk organ involvement, 10-year EFS was 51.9% vs. 46.3% and 10-year OS was 51.9% vs. 73.7%. CONCLUSIONS: Lung and multisystem involvement are significant concerns in LCH, highlighting the need for careful management to reduce morbidity and mortality.

Surgical resection of pediatric craniocervical junction Rosai-Dorfman histiocytosis-a case report and literature review.

Rosai-Dorfman disease (RDD) with craniocervical junction involvement is a rare clinical entity. We present herein a case of a pediatric patient with craniocervical junction RDD which was surgically treated. A 10-year-old female with a history of B-cell acute lymphoblastic leukemia (B-ALL) in remission and RDD presented with frontal migraine headaches. She previously had a right posterior chest wall lesion which was biopsy-proven RDD. She was found on imaging to have a dural-based right craniocervical junction lesion. Given her history of B-ALL, after a multidisciplinary discussion, the decision was made to proceed with resection with possible initiation of cobimetinib or clofarabine. The patient underwent a suboccipital craniotomy, C1 laminectomy, and resection of the dural-based lesion. Gross total resection was achieved, and histopathology confirmed the diagnosis of RDD. She was discharged home on postoperative day 4. No recurrence was seen on follow-up imaging at 3 months. We conducted a systematic literature review examining all cases of pediatric intracranial RDD and all cases of craniocervical junction RDD. This represents, to the best of our knowledge, only the second case of pediatric craniocervical junction RDD. Although RDD is often self-limiting, medical treatment is often considered for intracranial disease, but tissue confirmation is necessary. Surgical resection provides histopathologic diagnosis and can sometimes serve as definitive treatment for a particular lesion.

Case report: Uncommon manifestations of Rosai-Dorfman disease in the liver mimicking HCC.

Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis (LCH) disorder characterized by systemic extranodal lesions. Common cases include skin lesions, whereas liver lesions are rare. This study presents a case of a 66-year-old woman with a solitary extranodal liver lesion who underwent successful surgical treatment followed by glucocorticoid therapy. The patient did not experience any symptoms before surgery. The liver lesion was incidentally discovered during a routine ultrasound examination. Enhanced CT scan revealed the lesion with the characteristic of washout, similar to primary hepatic cancer (HCC). CT scans of the head, neck, chest, and abdominal pelvis revealed no lymph node or other organ lesions. After surgery, the liver lesion was diagnosed as RDD, and subsequent whole-body examinations did not reveal any skin lesions. The definitive diagnosis was solid liver RDD in adults. Although there were no typical cases of bilateral cervical lymph node lesions, ultrasound and CT examinations promptly detected liver lesions, leading to the correct diagnosis through surgical resection. The findings from this case indicate that RDD can occur in rare extrasegmental areas, and the imaging characteristics of liver lesions are not specific, indicating the importance of avoiding delayed diagnosis.

Living-donor lobar lung transplantation for pulmonary Langerhans cell histiocytosis complicated by extensive thrombi in central pulmonary arteries.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterized by the proliferation of Langerhans cells along the small airways, which causes nodular and cystic changes in the lung parenchyma. Lung transplantation can be a life-saving option for patients with severe respiratory failure or pulmonary hypertension. Herein, we present a case of successful lung transplantation in a patient with PLCH who developed unusually large thrombi in the central pulmonary artery. CASE PRESENTATION: A 47-year-old woman with 16-year history of PLCH with rapidly developing respiratory failure was admitted to our hospital for the evaluation of a lung transplant. Enhanced computed tomography revealed large thrombi in dilated central pulmonary arteries. Right heart catheterization revealed severe pulmonary hypertension, with a mean pulmonary artery pressure of 48 mmHg. The thrombi shrank markedly after 3 months of anticoagulation therapy. However, the respiratory status of the patient did not improve. We performed bilateral living-donor lobar lung transplantation with thrombectomy under extracorporeal membrane oxygenation for the remaining thrombi in the main pulmonary arteries. The dilated main pulmonary arteries of the recipient required direct plication for size mismatch. The patient survived in good condition for more than 2 years with no recurrence of thrombosis. CONCLUSION: Preoperative anticoagulation therapy for massive thrombi in the pulmonary arteries was effective and led to safe lung transplantation.

Cladribine Use in Xanthoma Disseminatum: A Rare Case Presentation and Brief Updated Literature Review.

Xanthoma disseminatum (XD) is a rare, non-Langerhans cell histiocytosis. While treatment is notoriously difficult, 2-chlorodeoxyadenosine (cladribine) has recently emerged as a potential effective therapeutic option. Here, we describe the case of a 65-year-old male with XD who experienced significant cutaneous improvement after cladribine treatment. We also provide an updated literature review on cladribine use in patients with XD in light of reported adverse effects (AEs). While the efficacy of cladribine in XD is clear, no consensus exists for treatment duration and AE management. Hence, we strongly encourage interdisciplinary discourse involving dermatology and oncology in these cases.

Potential indication of chemotherapy for hypodipsia and arginine vasopressin deficiency secondary to hypothalamic-pituitary Langerhans cell histiocytosis: a case report and literature review.

Hypothalamic-pituitary Langerhans cell histiocytosis (HP-LCH) is often associated with arginine vasopressin deficiency (AVD). Patients with AVD caused by HP-LCH rarely develop an impaired osmotic threshold for thirst (OTT). Improvement in OTT among such patients has not been reported in the literature. To our knowledge, here we report the first case of AVD due to HP-LCH in which hypodipsia resolved during chemotherapy. A nine-year-old Japanese girl presented with polydipsia, polyuria, anorexia, and hypernatremia (149.8 mEq/L) and was diagnosed with AVD secondary to HP-LCH. Visual analog scale examination showed a reduced OTT following the water deprivation test. During chemotherapy for Langerhans cell histiocytosis (LCH), serum sodium concentrations became stable between 138.9 and 142.9 mEq/L under the replacement of desmopressin. Repeated visual analog scale examinations showed that she experienced a sense of thirst at a serum sodium concentration of 142.3-144.6 mEq/L, at which she did not experience any thirst prior to the initiation of chemotherapy. These data suggest that chemotherapy directly improved the OTT in our patient. Improved mechanical compression or infiltration of the hypothalamus related to OTT may lead to the recovery of the sense of thirst. This report highlights the potential role of chemotherapy for solitary HP-LCH in patients with hypodipsia and AVD.

Rosai-Dorfman disease differentiated from a posterior mediastinal tumour: a case report.

Rosai-Dorfman disease presenting solely with intrathoracic lesions is exceptionally rare. Herein, we report the case of a 53-year-old man presenting with a posterior mediastinal tumour. Computed tomography revealed a 7-cm soft tissue shadow in the posterior mediastinum. Positron emission tomography-computed tomography demonstrated a high maximum standardized uptake value of 10.35 in the tumour, with no evidence of lymph node or other organ involvement. Serum marker levels were within the normal range. Thoracoscopic surgery was performed to obtain a biopsy for a definitive diagnosis and treatment planning. Postoperative histological findings revealed a diffuse infiltration of eosinophilic histiocytes, lymphocytes, and plasma cells. Immunohistochemical analysis indicated positivity for S-100 protein, oct-2, and cyclin D1 in these histiocytes. Consequently, the patient was diagnosed with Rosai-Dorfman disease and is currently asymptomatic, undergoing regular monitoring without treatment as an outpatient. The absence of characteristic findings, such as bilateral cervical lymphadenopathy, posed challenges in preoperative diagnosis.

Advancements in the understanding and management of histiocytic neoplasms.

Histiocytic neoplasms are rare diseases involving macrophages, dendritic cells, and monocytes. They include Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and histiocytic sarcoma. Histiocytic neoplasms are characterized by varied clinical courses and prognoses, necessitating a nuanced understanding of their classification, epidemiology, and clinical manifestations. Genetic studies have revealed somatic mutations, predominantly in the MAPK pathway, suggesting a clonal neoplastic nature. This review covers the current understanding of histiocytic neoplasms, molecular pathophysiology, with a particular focus on mutations in genes such as BRAF, MAP2K1, and the PI3K-AKT signaling pathways, and evolving treatment strategies, especially focusing on LCH, ECD, RDD, and JXG. The treatment landscape has evolved with advancements in targeted therapies. BRAF inhibitors, such as vemurafenib and dabrafenib, have shown efficacy, especially in high-risk LCH cases; however, challenges remain, including relapse post-treatment discontinuation, and adverse effects. MEK inhibitors have also demonstrated effectiveness, and cobimetinib has recently been approved for use in adults. Further research is required to determine the optimal treatment duration and strategies for managing therapy interruptions. Advancements in molecular genetics and targeted therapies have revolutionized the management of histiocytic neoplasms. However, ongoing research is crucial for optimizing patient outcomes.

Unusual presentation of histiocytosis X in the cranial vault: A rare case report.

Langerhans histiocytosis or histiocytosis X is an oligo-clonal proliferation of Langerhans cells. We report the case of an 11-month-old infant who had presented with a parieto-occipital swelling since birth, which progressively increased in volume without any other presenting signs. The radiological work-up initially suspected osteitis of the vault, which was removed in its entirety. The anatomopathological study concluded that it was histiocytosis X. The extension work-up was negative. Follow-up of this patient showed no local recurrence or appearance of other localizations. A review of the literature shows that little is known about its pathophysiology. It mainly affects children and young adults. There are several possible sites of involvement, and cranial vault involvement is a fairly frequent form among the bony sites of this pathology. The diagnosis is confirmed histologically or cytologically, and extension workup is required to confirm the diagnosis. Therapeutic management has not been standardized, and sometimes requires chemotherapy in addition to surgery. The prognosis depends on whether vital organs are affected or not.

Histiocitosis de células de Langerhans en un paciente con lesión perianal. Caso clínico / Langerhans cell histiocytosis in a patient with perianal lesion. A case report

La histiocitosis de células de Langerhans es una expresión de células dendríticas mieloides, asociada a un componente inflamatorio significativo y compromiso sistémico variado. La edad más frecuente de presentación es entre 1 y 4 años, y predomina en el sexo masculino. Se comunica el caso de un niño de 5 años de edad cuya forma de presentación fue una lesión granulomatosa con fístula perianal, afectación pulmonar y de oído externo. El abordaje interdisciplinario permitió llegar al diagnóstico, realizar las intervenciones necesarias e iniciar el tratamiento adecuado.

Langerhans cell histiocytosis is an expression of myeloid dendritic cells, associated with a significant inflammatory component and varied systemic involvement. The most common age at presentation is between 1 and 4 years, and it prevails among male subjects. Here we describe the case of a 5-year-old boy who presented with a granulomatous lesion with perianal fistula and lung and external ear involvement. An interdisciplinary approach helped to make a diagnosis, provide the necessary interventions, and start an adequate treatment.

Managing adult-onset Still's disease in pregnancy: A case report.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder characterized by fever, arthritis, skin rash, and systemic symptoms. The etiology of AOSD is unknown; however, it is thought to be related to immune dysregulation. Although a rare disease, AOSD can significantly impact reproductive health, particularly during pregnancy. This case study assesses the implications of pregnancy in a patient with AOSD, as well as the potential for heredity of the disease. Neonatal hemophagocytic lympho-histiocytosis (HLH) is a rare and life-threatening disorder characterized by hyperinflammation and uncontrolled activation of immune cells, leading to multiple organ dysfunction. This case report aimed to introduce neonatal HLH from a mother with AOSD. CASE SUMMARY: This case study presents a 29-year-old female with AOSD who became pregnant and gave birth to a premature infant who was diagnosed with neonatal HLH. AOSD can significantly impact pregnancy and childbirth, as it may become more severe during pregnancy, with an increased risk of fetal loss and preterm birth. The management of AOSD during pregnancy involves the use of nonsteroidal anti-inflammatory drugs and glucocorticoids, as well as immunosuppressive agents in severe cases. However, the use of immunosuppressive agents during pregnancy may be associated with potential risks to the fetus. The hereditary implications of AOSD are unclear; however, available evidence suggests that genetic factors may play a role in the disease development. CONCLUSION: AOSD can have significant implications for pregnancy and childbirth, including an increased risk of fetal loss and preterm birth. Neonatal HLH, a complication of AOSD in pregnancy, requires prompt diagnosis and management. Women with AOSD who are considering pregnancy should discuss their options with their healthcare provider and develop a management plan that addresses the potential risks to both mother and fetus.

Cranial Rosai-Dorfman disease: a case report and literature review.

Rosai-Dorfman Disease (RDD) is a rare, benign, idiopathic histiocytic proliferative disorder, with its occurrence in the cranial bones being particularly uncommon and prone to misdiagnosis in preoperative radiological examinations. This article reports a case of RDD in the left temporal bone. The radiological presentation of intraosseous RDD includes osteolytic bone destruction, infrequent periosteal reaction, clearly defined tumor margins, and marked uniform enhancement on contrast-enhanced scans. However, these radiological features lack specificity, highlighting the necessity of histopathological examination for a definitive diagnosis, especially for the rarer extranodal subtypes of RDD. Surgical excision of the lesion can lead to favorable therapeutic outcomes.