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EClinicalMedicine Jul 2024Erdheim-Chester disease (ECD) is a rare histiocytosis that may overlap with Langerhans Cell Histiocytosis (LCH). This "mixed" entity is poorly characterized. We here...
BACKGROUND
Erdheim-Chester disease (ECD) is a rare histiocytosis that may overlap with Langerhans Cell Histiocytosis (LCH). This "mixed" entity is poorly characterized. We here investigated the clinical phenotype, outcome, and prognostic factors of a large cohort of patients with mixed ECD-LCH.
METHODS
This retrospective study was performed at two referral centers in France and Italy (Pitié-Salpêtrière Hospital, Paris; Meyer Children's Hospital, Florence). We included children and adults with ECD diagnosed in 2000-2022 who had biopsy-proven LCH, available data on clinical presentation, treatment and outcome, and a minimum follow-up of one year. Outcomes included differences in clinical presentation and survival between mixed ECD-LCH and isolated ECD; we also investigated response to treatments and predictors of survival in the mixed cohort. Survival was analyzed using the Kaplan-Maier method and differences in survival with the long-rank test. Cox regression models were used to evaluate the potential impact of age and gender on survival and to identify predictors of non-response and survival.
FINDINGS
Out of a cohort of 502 ECD patients, 69 (14%) had mixed ECD-LCH. Compared to isolated ECD, mixed ECD-LCH occurred more frequently in females (51 26%, < 0.001) and in patients with multisystem disease (≥4 sites). Mixed ECD-LCH more frequently involved long bones (91 79%, = 0.014), central nervous system (51 34%, = 0.007), facial/orbit (52 38%, = 0.031), lungs (43 28%, = 0.009), hypothalamic/pituitary axis (51 26%, < 0.001), skin (61 29%, < 0.001), and lymph nodes (15 7%, = 0.028); the mutation was also more frequent in mixed ECD-LCH (81 59%, < 0.001). Targeted treatments (BRAF and/or MEK inhibitors) induced response more frequently than conventional therapies (interferon-α, chemotherapy), either as first-line (77 29%, < 0.001) or as any line (75 24%, < 0.001). After a median follow-up of 71 months, 24 patients (35%) died. Survival probability was comparable between ECD alone and mixed ECD-LCH (log-rank = 0.948). At multivariable analysis, age at diagnosis (HR 1.052, 95% CI 1.008-1.096), associated hematologic conditions (HR 3.030, 95% CI 1.040-8.827), and treatment failure (HR 9.736, 95% CI 2.919-32.481) were associated with an increased risk of death, while lytic bone lesions with a lower risk (HR 0.116, 95% CI 0.031-0.432).
INTERPRETATION
Mixed ECD-LCH is a multisystem disease driven by the mutation and targeted treatments are effective. Age at diagnosis, bone lesion patterns, associated hematologic conditions, and treatment failure are the main predictors of death in mixed ECD-LCH.
FUNDING
None.
PubMed: 38841707
DOI: 10.1016/j.eclinm.2024.102658 -
Archives of Pathology & Laboratory... May 2024Intraoperative (frozen section) analysis of lung lesions (nodules, masses, ground-glass opacities) can occasionally be diagnostically challenging.
CONTEXT.—
Intraoperative (frozen section) analysis of lung lesions (nodules, masses, ground-glass opacities) can occasionally be diagnostically challenging.
OBJECTIVE.—
To describe selected pitfalls in thoracic frozen sections with a focus on the differential diagnosis between adenocarcinoma and its mimics, and to provide tips to prevent misinterpretation.
DATA SOURCES.—
Peer-reviewed literature and the author's experience.
CONCLUSIONS.—
A common challenge in thoracic frozen sections is the differential diagnosis between lung adenocarcinoma and its mimics. Diagnostic difficulties arise because mimics of adenocarcinoma often entrap reactive lung epithelium that can appear atypical on frozen section slides. Entities that can be misinterpreted as adenocarcinoma include ciliated muconodular papillary tumor/bronchiolar adenoma, hamartoma, inflammatory myofibroblastic tumor, and pulmonary Langerhans cell histiocytosis. Knowledge of the key clinical, radiologic, and histologic features of these entities can help prevent overdiagnosis of adenocarcinoma. Pathologic findings that facilitate the distinction between adenocarcinoma and its mimics at frozen section include the appearance and contour of the lesion at low magnification, growth patterns, cilia, stromal features, shape of the epithelial cells (cuboidal versus columnar), nuclear features of malignancy (crowding, hyperchromasia, irregular contours), and abruptness of the junction between the lesion and adjacent uninvolved lung. Knowledge of the clinical context, imaging findings, and the surgical consequence of the intraoperative diagnosis can also prevent diagnostic errors. Finally, since adenocarcinomas of the lung are often relatively bland and lack the stromal desmoplasia seen in adenocarcinomas of other organs, familiarity with the morphologic spectrum of lung adenocarcinomas at frozen section analysis is important.
PubMed: 38818706
DOI: 10.5858/arpa.2024-0023-RA -
Journal of Medicine and Life Feb 2024Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis disorder characterized by the proliferation of histiocytes within the lymph nodes. Extranodal...
Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis disorder characterized by the proliferation of histiocytes within the lymph nodes. Extranodal involvement can occur; however, only 10% of extranodal RDD involve the skin. We present a unique case of a 66-year-old woman with cutaneous RDD followed by the development of multiple myeloma (MM). To our knowledge, this is only the second reported case where RDD preceded a diagnosis of MM, with the first documented instance occurring in 2018. The patient presented to the dermatology clinic with a 5-year history of painless, solitary lesion over the right cheek. Local examination revealed a single 6 mm x 7 mm well-circumscribed pearly telangiectatic lesion resembling basal cell carcinoma over the right nasolabial fold and cheek. The lesion was excised with a 3 mm circumferential margin. Histopathology showed a mixed lymphohistiocytic cell infiltrate with emperipolesis and immunohistochemical staining patterns consistent with RDD. Two years later, the patient presented with hip pain and was diagnosed with MM. She was treated with lenalidomide, bortezomib, and dexamethasone, and was later maintained on lenalidomide. Our case adds to the limited evidence suggesting a potential association between RDD and MM. Further research in this field is required to promptly identify and manage patients with such a presentation in the future.
Topics: Humans; Histiocytosis, Sinus; Female; Aged; Multiple Myeloma; Carcinoma, Basal Cell; Diagnosis, Differential; Skin Neoplasms; Face
PubMed: 38813357
DOI: 10.25122/jml-2023-0337 -
Federal Practitioner : For the Health... May 2024Rosai Dorfman disease is a rare non-Langerhans cell histiocytosis that affects lymph nodes, soft tissues, and other organs. The etiology of Rosai Dorfman disease is...
BACKGROUND
Rosai Dorfman disease is a rare non-Langerhans cell histiocytosis that affects lymph nodes, soft tissues, and other organs. The etiology of Rosai Dorfman disease is poorly understood, though it may involve an immunologic processes or infection. Treatment varies according to the disease presentation.
CASE PRESENTATION
A male aged 56 years was evaluated for a cutaneous mass on his right medial thigh. Initially, the patient received surgical debulking with subsequent observation and no systemic therapy. However, the mass recurred, prompting another surgical removal 9 years after the initial surgery. A mass biopsy showed infiltration of plasma cells, lymphocytes, histiocytes, and occasional neutrophils with noted reactivity of S-100 protein and CD163, but not CD1a. No systemic therapy was initiated, and the patient agreed to a period of watchful waiting.
CONCLUSIONS
Rosai Dorfman disease of soft tissue occurs in older adults and is often associated with soft tissue abnormalities, and more rarely, in lipomas. Multidisciplinary management of the disease and research for mutations and microenvironment of RDD is needed to better understand its clinicopathological nature and improve novel therapies.
PubMed: 38813251
DOI: 10.12788/fp.0475 -
Internal Medicine (Tokyo, Japan) May 2024We herein report an unusual case of Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, and emphasize its unique presentation and diagnostic...
We herein report an unusual case of Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, and emphasize its unique presentation and diagnostic challenges. Our patient exhibited uncommon symptoms and significant organ involvement, particularly pancreatic enlargement that is not typically associated with ECD. Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) and EUS-fine needle aspiration (EUS-FNA) play crucial roles in the comprehensive assessment of the disease, demonstrating their superiority in identifying and characterizing elusive ECD lesions. This is the first report to document pancreatic lesions in patients with ECD evaluated using CEH-EUS. EUS-FNA is valuable for diagnosing rare diseases, including ECD, with diffuse pancreatic enlargement.
PubMed: 38811216
DOI: 10.2169/internalmedicine.3864-24 -
Asian Pacific Journal of Cancer... May 2024Disease reactivation/refractory remains a major challenge in managing Langerhans cell histiocytosis (LCH). Outcomes and late sequelae should be explored.
BACKGROUND
Disease reactivation/refractory remains a major challenge in managing Langerhans cell histiocytosis (LCH). Outcomes and late sequelae should be explored.
METHODS
A multi-institutional retrospective study was conducted to describe clinical characteristics, predictive factors, outcomes and late sequelae of pediatric reactivation/refractory LCH in Thailand.
RESULTS
In all, 47 patients were studied, 25 (53.2%) patients had disease reactivation and 22 (46.8%) patients had refractory LCH. The median reactivation and refractory time were 1.59 and 0.33 years from diagnosis, respectively (p <0.001). The most common site of reactivation/refractory was the bone (n = 26, 55%), and 20 (42.6%) patients developed late sequelae. The 5-year overall survival (OS) was 76.1%. Patients with reactivation and refractory LCH performed similarly in 5-year OS (88% vs. 63%, p = 0.055). Prognostic factors associated with mortality were liver, spleen, hematopoietic system and lung reactivation (p <0.05). Lung reactivation was the only independent risk factor associated with the survival outcome (p = 0.002).
CONCLUSIONS
The outcomes of pediatric patients between reactivation and refractory LCH in Thailand were similarly desirable and mortality was minimal although late sequelae may evolve. Pulmonary reactivation/refractory was an independent risk factor associated with survival.
Topics: Humans; Histiocytosis, Langerhans-Cell; Male; Female; Retrospective Studies; Child; Prognosis; Child, Preschool; Thailand; Survival Rate; Infant; Follow-Up Studies; Adolescent; Risk Factors
PubMed: 38809656
DOI: 10.31557/APJCP.2024.25.5.1831 -
Endocrinology, Diabetes & Metabolism... Apr 2024RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented...
SUMMARY
RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented efficacy compared to previous multi-kinase treatments. Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm usually driven by somatic BRAF mutations, resulting in dysregulated MAPK signalling. We describe a 22-year-old woman with metastatic MTC to regional lymph nodes, lung and liver. Tumour tissue harboured a somatic pathogenic RET variant p.(M918T) and selpercatinib was commenced. She experienced sustained clinical, biochemical and radiological responses. Two years later, she developed rapidly progressive apical lung nodules, prompting biopsy. Histopathology demonstrated LCH with a rare BRAF variant p.(V600_K601>D). The lung nodules improved with inhaled corticosteroids. We hypothesize that selective pressure from RET blockade may have activated a downstream somatic BRAF mutation, resulting in pulmonary LCH. We recommend continued vigilance for neoplasms driven by dysregulated downstream MAPK signalling in patients undergoing selective RET inhibition.
LEARNING POINTS
Patients with RET-altered MTC can experience rapid disease improvement and sustained disease stability with selective RET blockade (selpercatinib). LCH is a clonal neoplasm driven by MAPK activation, for which the most common mechanism is BRAF mutation. Both MTC and pulmonary LCH are driven by dysregulated MAPK signalling pathway activation. We hypothesise that the RET-specific inhibitor selpercatinib may have caused the activation of dormant LCH secondary to selective pressure and clonal proliferation.
PubMed: 38804700
DOI: 10.1530/EDM-23-0079 -
International Journal of Surgery Case... Jul 2024LCH in adults is rarely encountered, with the preference in children and axial skeleton as predilection site. Limited understanding of adult LCH causes frequent...
INTRODUCTION AND IMPORTANCE
LCH in adults is rarely encountered, with the preference in children and axial skeleton as predilection site. Limited understanding of adult LCH causes frequent misdiagnosis, as our experience in an adult case of LCH threw off our differential diagnosis.
CASE PRESENTATION
A 21-year-old male was referred to our hospital due to pain in his right shoulder. Plain radiograph and MRI showed a solitary well-marginated lytic lesion on the distal third of the clavicle. Together with a clear history and physical exam, the benign bone cyst was suspected and we performed an open biopsy simultaneously with curettage followed by internal fixation using a bone graft. Pathology and immunohistochemistry dismissed our suspicion and confirmed LCH as the main diagnosis. At six months post-surgery, no signs of recurrence were seen on the fixated site nor complained by the patient.
DISCUSSION
Diagnosing LCH involves considering imaging appearances and patient demographics as initial clues. However, confirming the diagnosis requires a biopsy with proven CD1 expression. Currently, the majority of studies recommend confirming the diagnosis before initiating therapy. This precaution is necessary due to the unclear pathophysiology of LCH, which complicates the implementation of specific therapies. Based on benign features of skeletal lesions found from imaging, invasive treatment before biopsy confirmation still gave a satisfactory outcome despite not being in line with the current recommendation.
CONCLUSION
Excisional biopsy and curettage in solitary LCH yield satisfactory outcomes. However, further studies are needed with larger sample sizes and interventional designs.
PubMed: 38796936
DOI: 10.1016/j.ijscr.2024.109801 -
International Journal of Surgery Case... Jun 2024Introduction and importance: Langerhans cell histiocytosis is a rare disorder characterized by the proliferation of Langerhans cells in various tissues. While it...
UNLABELLED
Introduction and importance: Langerhans cell histiocytosis is a rare disorder characterized by the proliferation of Langerhans cells in various tissues. While it commonly affects bones, skin, and other organs, oral manifestations are less frequent but can be diagnostically challenging.
CASE PRESENTATION
we present a clinical case of LCH with an oral manifestation in a 14-year-old adolescent. The patient presented with progressive jaw pain for approximately two months.
CLINICAL
Intraoral examination revealed vestibular swelling at the mandibular angle, with painful vestibular palpation. However, the adjacent teeth to the lesion were not mobile, and the vitality test was positive. Radiographic examination showed an inhomogeneous hypodense osteolytic lesion at the left mandibular angle. Histopathological analysis confirmed the diagnosis of LCH with diffuse infiltration of Langerhans cells in the gingival tissue. The patient was referred to Hospital in Marseille and therapeutic abstention is chosen, clinical and radiological follow-up is established every 6 months for 5 years. At 6 weeks, a significant decrease in the lesion and an osteoperiosteal reconstruction phenomenon are observed. After one year, the lesion has spontaneously resolved. Clinical discussion: The disease activity score allows defining the severity and activity of the disease and determine the treatment. The clinical presentation of Langerhans cell histiocytosis is highly variable. The severe form of the disease occurs before the age of 2 and is characterized by multi-system involvement and neurodegenerative involvement.
CONCLUSION
The lesion resolved spontaneously after the biopsy was performed. Prompt diagnosis and multidisciplinary management are crucial for successful treatment outcomes in such cases. This case highlights the importance of recognizing oral manifestations of LCH in dental practice for early diagnosis and appropriate management.
PubMed: 38776823
DOI: 10.1016/j.ijscr.2024.109605