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Leukemia & Lymphoma Jan 2021Histiocytoses are one of the ultimate diagnostic challenges that every physician face at least once in his/her life. Giving their protean manifestation and...
Histiocytoses are one of the ultimate diagnostic challenges that every physician face at least once in his/her life. Giving their protean manifestation and differentiated therapeutic needs, histiocytosis requires extensive characterization and multidisciplinary management. Mixed histiocytosis is an emerging group of syndromes defined by the overlap of Langerhans cell histiocytosis and another histiocytic disorder of different type. Despite rare, it may account for up to a fifth of systemic histiocytosis patients in some series. In this work, we comprehensively review for the first time the clinical, radiological, histopathological and molecular features of mixed histiocytosis in children and adults. Moreover, we propose a clinical classification in three groups that differentiate patients with systemic involvement and worse overall survival to other groups with more localized manifestations and indolent behavior, wanting to ease their recognition and treatment. Interestingly we also found that mixed histiocytosis harbor BRAFV600E mutations with a higher frequency comparing to all other histiocytoses, and may therefore benefit of specific inhibitory drugs.
Topics: Adult; Child; Female; Histiocytes; Histiocytosis; Histiocytosis, Langerhans-Cell; Humans; Male; Syndrome
PubMed: 32969291
DOI: 10.1080/10428194.2020.1824070 -
Neurology International Sep 2022Erdheim-Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis that can have various presentations and higher mortality in patients presenting with... (Review)
Review
Erdheim-Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis that can have various presentations and higher mortality in patients presenting with neurological symptoms. We performed a systematic review to investigate and chronicle the frequency of neurological manifestations, imaging findings, treatments, and outcomes in published ECD patients presenting with neurological symptoms. A PubMed literature search was conducted for articles (published between January 1980 and June 2021) on ECD cases presenting with neurological manifestations. We analyzed the data of 40 patients, including our patient. Cranial neuropathies and ataxia were the most frequent clinical manifestations. A total of 50% of the symptomatic ECD CNS lesions were intraparenchymal and nearly 33% of patients died due to the disease itself or complications. CNS involvement may be the only manifestation of ECD and sometimes may require a repeat biopsy with IHC testing for excellent treatment outcomes.
PubMed: 36135995
DOI: 10.3390/neurolint14030060 -
Presse Medicale (Paris, France : 1983) Dec 2021Hypophysitis is defined as inflammation of the pituitary gland. It is a heterogeneous condition as it can originate from different parts of the pituitary gland, can be...
Hypophysitis is defined as inflammation of the pituitary gland. It is a heterogeneous condition as it can originate from different parts of the pituitary gland, can be caused by different pathophysiological processes, and can be isolated or the manifestation of a underlying systemic disease. Hypophysitis usually presents with endocrine deficiencies, including diabetes insipidus, with varying patterns. A subset of patients presents with mass effects. The last decades major progress has been made in the understanding of this disease. New forms are now recognized, new diagnostics are being developed, and specific treatments are proposed. This review provides an overview of the current knowledge on hypophysitis using an aetiology-based approach and provides the clinician with a stepwise approach to the patient with (suspected) hypophysitis.
Topics: Autoimmune Hypophysitis; Diabetes Insipidus; Endocrine System Diseases; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Humans; Hypophysitis; Immune Checkpoint Inhibitors; Immunoglobulin G; Immunoglobulin G4-Related Disease; Pituitary Gland; Symptom Assessment; Xanthomatosis
PubMed: 34687912
DOI: 10.1016/j.lpm.2021.104076 -
Clinical Neurology and Neurosurgery Apr 2024Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis involving the central nervous system in 5% of cases. Spinal location occurs in less than 1% of... (Review)
Review
INTRODUCTION
Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis involving the central nervous system in 5% of cases. Spinal location occurs in less than 1% of extranodal RDD and can be responsible for neurological manifestations. We present a systematic review of cases of isolated spinal RDD. We also report a new case of isolated spinal RDD revealed by spinal cord compression.
MATERIALS AND METHODS
The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the MEDLINE and SCOPUS databases and included case reports and case series describing isolated RDD of the spine.
RESULTS
There were 53 patients with isolated spinal RDD (including our case). The mean age was 35.85±16.48 years. Neurological deficit was the most frequent clinical presentation (89%). RDD lesions were mainly located in the thoracic spine (51%), then the cervical spine (32%). The lesion was reported to be extradural (57%), intradural extramedullary (26%), intramedullary (7%), and in the vertebral body (10%). Histological examination showed emperipolesis in 73%. Histocytes were positive for S-100 protein in 83%. Treatment was based on surgery 96%), radiotherapy, chemotherapy, and adjunctive steroid therapy were indicated in four, one, and eight cases. After a mean follow-up period of 14.84±13.00 months, recurrence of RDD was noted in 15%.
CONCLUSION
Spinal RDD is a rare condition, requiring meticulous histological examination for accurate diagnosis. Complete surgical resection is the treatment of choice. Adjuvant chemotherapy and radiotherapy can also be indicated in patients demonstrating partial improvement following surgery.
Topics: Humans; Young Adult; Adult; Middle Aged; Histiocytosis, Sinus; Spinal Cord Compression; Cervical Vertebrae; Central Nervous System
PubMed: 38461672
DOI: 10.1016/j.clineuro.2024.108206 -
British Journal of Haematology Jun 2020Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete...
Long-term efficacy and safety of 2CdA (cladribine) in extra-pulmonary adult-onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review.
Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose <50 mg/m . Disease progression rates were 20% and 30% at two and five years, respectively. Partial response (PR) to 2CdA was predictive of disease progression. Among eight re-treated patients, five went into CR, two in PR, and one died. Single-agent 2CdA is effective in reactivated a-LCH, including at intermediate doses. Toxicity, significant but acceptable, warrants infectious prophylaxis. Complete responders may enter prolonged remission. Further studies are needed to determine 2CdA sequencing with other agents (vinblastine, cytarabine).
Topics: Adult; Age of Onset; Aged, 80 and over; Antimetabolites; Cladribine; Dose-Response Relationship, Drug; Female; France; Histiocytosis, Langerhans-Cell; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Proportional Hazards Models; Remission Induction; Retrospective Studies; Sepsis; Virus Diseases
PubMed: 32191819
DOI: 10.1111/bjh.16449 -
JAMA Dermatology Mar 2020Necrobiotic xanthogranuloma (NXG) is a non-Langerhans cell histiocytosis classically associated with paraproteinemia attributable to plasma-cell dyscrasias or...
IMPORTANCE
Necrobiotic xanthogranuloma (NXG) is a non-Langerhans cell histiocytosis classically associated with paraproteinemia attributable to plasma-cell dyscrasias or lymphoproliferative disorders. Despite the morbidity of NXG, the literature is limited to case reports and small studies, and diagnostic criteria are lacking.
OBJECTIVE
To evaluate the characteristics of NXG and propose diagnostic criteria.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter cross-sectional study was conducted at tertiary academic referral centers and followed by a systematic review and a consensus exercise. The multicenter cohort included patients with NXG diagnosed at the Brigham and Women's and Massachusetts General Hospitals (2000-2018), the University of Iowa Hospitals and Clinics (2000-2018), and the University of Pennsylvania Health System (2008-2018). The systematic review was conducted in 2018 and included patients with NXG identified in the Cochrane, Ovid EMBASE, PubMed, and Web of Science databases. The consensus exercise was conducted by 8 board-certified dermatologists to identify diagnostic criteria.
MAIN OUTCOMES AND MEASURES
Demographic factors, comorbidities, clinical features, and treatment response.
RESULTS
Of 235 included patients with NXG (34 from the multicenter cohort and 201 from the systematic review results), the mean (SD) age at presentation was 61.6 (14.2) years; 147 (62.6%) were female. Paraproteinemia was detected in 193 patients (82.1%), most often IgG-κ (117 patients [50.0%]). A malignant condition was detected in 59 patients (25.1%), most often multiple myeloma (33 patients [14.0%]). The overall rate of paraproteinemia and/or a malignant condition was 83.8% (197 patients). In the multicenter cohort, evolution of paraproteinemia into multiple myeloma was observed up to 5.7 years (median [range], 2.4 [0.1-5.7] years) after NXG presentation. Cutaneous lesions consisted of papules, plaques, and/or nodules, typically yellow or orange in color (113 of 187 [60.4%]) with a periorbital distribution (130 of 219 [59.3%]). The eye was the leading site of extracutaneous involvement (34 of 235 [14.5%]). In the multicenter cohort, intravenous immunoglobulin had the best treatment response rate (9 of 9 patients [100%]), followed by antimalarial drugs (4 of 5 patients [80%]), intralesional triamcinolone (6 of 8 patients [75%]), surgery (3 of 4 patients [75%]), chemotherapy (8 of 12 patients [67%]), and lenalidomide or thalidomide (5 of 8 patients [63%]). The consensus exercise yielded 2 major criteria, which were (1) clinical and (2) histopathological features consistent with NXG, and 2 minor criteria, consisting of (1) paraproteinemia, plasma-cell dyscrasia, and/or other associated lymphoproliferative disorder and (2) periorbital distribution of cutaneous lesions. In the absence of foreign body, infection, or another identifiable cause, fulfillment of both major and at least 1 minor criterion were proposed to establish the diagnosis of NXG.
CONCLUSIONS AND RELEVANCE
Necrobiotic xanthogranuloma is a multisystem disorder associated with paraproteinemia and malignant conditions. The proposed diagnostic criteria may advance clinical research and should be validated.
Topics: Aged; Cohort Studies; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Multiple Myeloma; Necrobiotic Xanthogranuloma; Paraproteinemias; Retrospective Studies
PubMed: 31940000
DOI: 10.1001/jamadermatol.2019.4221 -
Otology & Neurotology : Official... Apr 2024To determine if cochlear implant (CI) is safe and effective in patients with radiation therapy (XRT)-induced sensorineural hearing loss and to discuss considerations in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine if cochlear implant (CI) is safe and effective in patients with radiation therapy (XRT)-induced sensorineural hearing loss and to discuss considerations in this population through a retrospective cohort review, systematic review, and meta-analysis.
DATABASES REVIEWED
PubMed, Cochrane Library, and Embase.
METHODS
We retrospectively reviewed all CI cases after head and neck (HN) XRT at our institution, noting intraoperative findings, postoperative complications, and hearing outcomes. Change in speech discrimination scores (SDSs) was the primary outcome measure. Systematic review was performed to identify all cases of CI after HNXRT. A meta-analysis was performed to assess SDS change.
RESULTS
The retrospective cohort review identified 12 patients who underwent CI after HNXRT. One patient with HN cancer (HNC) and one with central nervous system pathology (CNSP) received bilateral implants. Six had HNC, three had CNSP, and one had Langerhans cell histiocytosis. Eleven had abnormal findings during CI. There were no postoperative complications. Twenty articles with an additional 97 patients were suitable for systematic review inclusion. Of the 109 patients, 67 (61.5%) had HNC and 18 (16.5%) had CNSP. Abnormal intraoperative findings were common (30.3%), most frequently in the mastoid (66.7%). Postoperative complications, including wound dehiscence and infection with some requiring explantation, occurred in 10.1% of patients. Sixty-six patients were included in the meta-analysis. All demonstrated SDS improvement (mean increase, 56.2%).
CONCLUSION
Patients with prior HNXRT benefit from CI. Paying careful attention to surgical planning and technique, postoperative care, and patient expectations is imperative, as complications are not uncommon.
Topics: Humans; Cochlear Implantation; Retrospective Studies; Hearing Loss, Sensorineural; Cochlear Implants; Postoperative Complications; Speech Perception
PubMed: 38361317
DOI: 10.1097/MAO.0000000000004127 -
The Journal of Clinical Endocrinology... Jan 2022Pituitary stalk thickening (PST) is often identified on magnetic resonance imaging (MRI), either incidentally or during diagnostic workup of hypopituitarism. However,... (Meta-Analysis)
Meta-Analysis
CONTEXT
Pituitary stalk thickening (PST) is often identified on magnetic resonance imaging (MRI), either incidentally or during diagnostic workup of hypopituitarism. However, the neoplastic etiology and natural course of PST are not fully understood, although this knowledge is required to establish diagnostic and surveillance strategies.
OBJECTIVE
This work aimed to investigate the neoplastic etiology and natural course of PST.
METHODS
MEDLINE/PubMed and EMBASE databases were searched up to February 2021 to identify original research investigating the etiologies of PST. The proportion of neoplastic etiology in patients with PST was meta-analytically pooled. Supplementary analysis exploring factors suggesting neoplasm was also performed. For initially indeterminate cases without confirmed diagnosis, the proportion of patients showing progression of PST during follow-up was evaluated.
RESULTS
Eighteen studies covering 1368 patients with PST were included. The pooled proportion of neoplasm was 45.2% (95% CI, 33.3%-57.8%), with substantial heterogeneity across studies (I2 = 93%). The most common neoplasm was germ cell tumor (14.0% of study population), followed by Langerhans cell histiocytosis (10.2%) and metastasis (4.7%). The studies on pediatric populations and those with more than 50% of patients having at least one pituitary hormone deficiency tended to show a higher proportion of neoplasm. The pituitary stalk was thicker in neoplasms, but the difference was not significant (pooled mean difference, 2.08 mm; P = .08). In initially indeterminate cases, 18.5% (95% CI, 7.6%-38.3%) showed progression of PST during follow-up.
CONCLUSION
PST was commonly confirmed to be neoplastic, especially in pediatric populations. As isolated PST frequently progresses, follow-up imaging is essential in initially indeterminate cases.
Topics: Diagnosis, Differential; Disease Progression; Follow-Up Studies; Humans; Hypopituitarism; Incidental Findings; Magnetic Resonance Imaging; Organ Size; Pituitary Gland; Pituitary Neoplasms
PubMed: 34614160
DOI: 10.1210/clinem/dgab732 -
Ophthalmic Plastic and Reconstructive...Langerhans cell histiocytosis (LCH) is a disorder of dendritic cell proliferation that typically involves bone. It can be diagnostically challenging when LCH presents...
PURPOSE
Langerhans cell histiocytosis (LCH) is a disorder of dendritic cell proliferation that typically involves bone. It can be diagnostically challenging when LCH presents without bony involvement, leading to delays in diagnosis and treatment. In this study, the periocular manifestations of LCH in cases where the underlying orbital bones are not involved are described through a systematic review.
METHODS
A systematic review of the literature was performed to capture all cases of LCH that involved the periocular region but not the underlying orbital bones. These included LCH cases that involved the periocular skin, the ocular surface, and the orbital tissue. The authors also highlight an additional case where LCH presented with periocular edema and multifocal, nodular conjunctival lesions.
RESULT
This review illustrates that LCH rarely presents with periocular infiltration without orbital bone involvement. In these atypical cases, LCH can present as an eyelid mass, a chalazion-like lesion, generalized periocular swelling, ocular surface lesions, or infiltration of any orbital structure. Ocular surface LCH has a higher rate of recurrence than other periocular LCH. Orbital LCH can involve any tissue including extraocular muscles, the lacrimal gland, or indistinct areas within the orbit.
CONCLUSIONS
LCH is a clinicopathologic diagnosis. Although most cases involve the bone, any soft tissue can be involved. Biopsy is required to confirm the diagnosis of this heterogeneous disease.
Topics: Biopsy; Histiocytosis, Langerhans-Cell; Humans; Lacrimal Apparatus; Neoplasm Recurrence, Local; Orbit
PubMed: 33315841
DOI: 10.1097/IOP.0000000000001906 -
World Neurosurgery Jun 2021A histiocytosis is a group of immunoproliferative disorders of clonal cells. The management protocols are still evolving, with chemotherapy as the mainstay of treatment.
BACKGROUND
A histiocytosis is a group of immunoproliferative disorders of clonal cells. The management protocols are still evolving, with chemotherapy as the mainstay of treatment.
OBJECTIVE
This study aims to evaluate the feasibility, safety, efficacy, and complication profile of stereotactic radiosurgery for intracranial histiocytosis.
METHODOLOGY
The authors reviewed PubMed, Scopus, Web of Science, and Embase for "radiosurgery" and "histiocytosis" in the English/Japanese language following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The patient profile, radiosurgical parameters (dose and isodose), target volume, and mode of radiosurgery (Gamma knife, LINAC radiosurgery, etc.) were collected. Its use as primary or adjuvant therapy, clinical and radiological outcome was also evaluated.
RESULTS
We identified 7 studies (9 patients); mean age: 41.9 years (24-57 years). Six patients received Gamma-knife radiosurgery, whereas 3 received CyberKnife radiosurgery. The Langerhans cell histiocytosis variants were eosinophilic granuloma in 3, whereas 4 were not defined. Two cases had Rosai-Dorfman disease, and 2 different yet pathogenetically related histiocytic disorders. Four patients harbored lesions in the pituitary stalk and posterior pituitary, 2 patients in the petrous region, 1 patient had a pontine lesion, and 2 patients had multiple lesions. The dose delivered ranged from 8 to 28 Gy. A total of 18 lesions (9 patients) were followed for 81.67 patient-years: 7 (39%) disappeared, 8 (44.4%) showed radiological reduction, and 2 (11%) remained stable. One lesion (5%) showed an increase in size needed surgical excision. There were no adverse effects.
CONCLUSION
The role of stereotactic radiosurgery needs to be further evaluated as the current cohort with only 9 cases (2 are Rosai-Dorfman disease) is insufficient to make conclusions. It may be a viable alternative in localized disease, along with chemotherapy and targeted surgery.
Topics: Adult; Female; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Male; Middle Aged; Radiosurgery; Treatment Outcome; Young Adult
PubMed: 33744421
DOI: 10.1016/j.wneu.2021.03.047