Radiculopathy as a manifestation of Langerhans' cell histiocytosis

Langerhans' cell histiocytosis (LCH) is a rare condition of children and young adults in which Langerhans' cells proliferate. The clinical spectrum ranges from solitary or few focal lesions to multisystem involvement mimicking vasculitis or hematological malignancy. Focal bone lesions, known as eosinophilic granulomas, are the most common manifestations. Eosinophilic granuloma usually presents with a variable combination of pain, swelling, fracture, and fever. Facial bone involvement may manifest as an ear discharge, hearing loss, or exophthalmos. Nerve root pain is rarely reported, even in patients with lesions in the axial skeleton. We report four cases of nerve root pain caused by LCH. Two male patients aged 25 and 34 years, respectively, presented with truncated femoral neuralgia related to acetabular granulomas. A 25-year-old woman with involvement of the L5 vertebral body and a 41-year-old man with a sacral lesion presented with sciatica.     

Ear involvement in childhood Langerhans' cell histiocytosis

BACKGROUND: Ear involvement (EI) in Langerhans' cell histiocytosis (LCH) occurs quite often. We reviewed the Italian pediatric population of 251 children with LCH diagnosed between 1982 and 1995, focusing on EI, to highlight the prevalence, the clinical presentation, the outcome during follow-up, and the prognostic impact of otologic LCH. METHODS: EI was defined by chronic otorrhea and/or mastoid infiltration, external auditory meatus lesions, and middle/internal EI. The age at diagnosis, sex, system involved, organ dysfunction, treatment, disease control, and outcome were recorded. RESULTS: EI was noted at presentation in 34 children (13. 5%). They had a younger age at diagnosis (p=.0013) and near totality of multisystem disease (93.8% of patients with EI). Among patients with multisystem disease, children with EI seemed to have a higher risk of poor response and a higher percentage of second line treatment (p=.003). CONCLUSIONS: EI seems to identify patients with a particular disease behavior, which requires a more accurate evaluation at diagnosis, staging and treatment, and a strict follow-up, considering the possibility of an unfavorable outcome.     

Pulmonary Langerhans' cell histiocytosis presented with recurrent pneumothorax

Pulmonary Langerhans' cell histiocytosis is a relatively unusual, interstitial lung disease. Several organ systems may be involved, including the lung, bone, liver, lymph nodes and brain. It is known to occur preferentially in heavy smokers, and the cases such as ours presenting pneumothorax as the major clinical manifestation are rare.     

Langerhans' cell histiocytosis in patients older than 21 years

In this retrospective review of 541 patients with Langerhans' cell histiocytosis, 211 (39%) patients were older than 21 years of age, whereas 330 (61%) were younger than 21 years of age. The adult patients had a mean age of 32 years (range, 21-69 years) with 159 (75%) men and 52 (25%) women, whereas the pediatric patients consisted of 176 (55%) boys and 144 (45%) girls. This male predominance in adults was statistically significant. Three adults had the Hand-Schuller-Christian variant, whereas the remaining adults (208) had eosinophilic granuloma. The rib accounted for 25% of the adult lesions and only 8% of the pediatric lesions. Spine involvement was less common in the adult group (3% versus 10%) and was predominantly thoracic. The adult patients had 40 (77%) diaphyseal lesions, 12 (23%) metaphyseal lesions, and no epiphyseal lesions. The pediatric patients had 75 (54%) diaphyseal, 59 (42%) metaphyseal, and five (4%) epiphyseal lesions. Radiographic evaluation revealed similar margin and matrix patterns in both groups, with a geographic lesion without sclerotic borders being the most common pattern. Langerhans' cell histiocytosis is considered a pediatric disease. However, this study showed a significant number (39%) of patients older than 21 years of age with this condition.     

Langerhans' cell histiocytosis of the temporal lobe and pons

Intracerebral Langerhans' cell histiocytosis (LCH) is rare and tends to involve the hypothalamus. The authors report a rare case of LCH in the temporal lobe that subsequently was followed by a brainstem lesion. This appears to be the first case of temporal lobe and brainstem LCH that has been treated successfully and published. A 24-year-old man complained of cacosmia and nausea with a slight headache. He had a left temporal LCH, which was removed completely, but developed a brainstem lesion a year later. The pontine LCH was treated with radiosurgery. The follow-up period was 4 years without any neurological or radiological symptoms or signs. The 12 cases of solitary intracranial non-hypothalamic LCH reported previously are reviewed. Gamma knife radiosurgery effectively controlled the local growth of the pontine LCH without adverse effect.     

Pulmonary Langerhans' cell histiocytosis: molecular analysis of clonality

Pulmonary Langerhans' cell histiocytosis (LCH) is a form of Langerhans' cell disease that primarily affects smokers in the third to fifth decade. Extrapulmonary manifestations are rare. Its clinical course is typically characterized by stabilization or regression of bilateral micronodular infiltrates seen on chest radiographs; progression to honeycomb fibrosis is rare. Because the clinical course of pulmonary LCH is distinct from systemic multiorgan LCH, currently thought to be a clonal proliferative disorder, we examined the X-linked polymorphic human androgen receptor assay (HUMARA) locus to assess clonality in female patients with one or more discrete LCH cell nodules in open lung biopsies. Langerhans' cells (LCH cells) were excised from formalin-fixed, paraffin-embedded tissue by microdissection to assure a relatively pure cellular population, and studies for differential methylation patterns at the HUMARA locus were performed. Twenty-four nodules in 13 patients were evaluated. Seven (29%) were clonal and 17 (71%) were nonclonal. Of six cases with multiple discrete nodules, three (50%) showed a nonclonal LCH cell population. In one biopsy with five nodules, two nodules were clonal with one allele inactivated, one nodule was clonal with the other allele inactivated, and two nodules were nonclonal. In contrast to systemic LCH, pulmonary LCH appears to be primarily a reactive process in which nonlethal, nonmalignant clonal evolution of LCH cells may arise in the setting of nonclonal LCH cell hyperplasia. Cigarette smoking may be the stimulus for pulmonary LCH in contrast to other forms of LCH.     

Recurrence of recipient Langerhans' cell histiocytosis following bilateral lung transplantation

Langerhans' cell histiocytosis may cause irreversiblerespiratory failure due to progressive destruction of lung parenchyma and widespread cystic change. Transplantation offers a therapeutic option. A case is described of recurrence of Langerhans' cell histiocytosis which was associated with deterioration in lung functionfour years following bilateral lung transplantation. Patientstransplanted for Langerhans' cell histiocytosis should be followed upwith this complication in mind.

     

Langerhans' cell histiocytosis: Head and neck manifestations in children

Background. Langerhans' cell histiocytosis (LCH) is an uncommon, poorly understood granulomatous disease, characterized by the idiopathic proliferation of Langerhan's cells or their marrow precursors. In 1985, the Philadelphia Workshop adopted the term “Langerhans' cell histiocytosis” (LCH) to differentiate it from reactive and neoplastic causes of histiocytosis. Methods. This study includes 73 pediatric patients diagnosed with this condition in Dublin, Ireland, and Nottingham, England, during a 34-year period (1959 to 1993). These patients are reviewed with respect to clinical presentation, difficulty with making a histological diagnosis, their management, and outcome. Results. A total of 49 patients (67%) had head and neck involvement. Bony involvement was the most frequent sign, most frequently located in the skull. There were 11 deaths (15%) in this series, all associated with multisystem disease, and nine of these deaths were in children younger than 2 years of age. Conclusions. The role of otolaryngologists is important in the early and accurate evaluation, staging, and diagnosis of LCH. It may mimic more common diseases, such as otitis externa, acute mastoiditis, skin rash, gingivitis, or cervical lymphadenopathy. Patients with multisystem disease may be so ill at presentation that the head and neck lesions may be overlooked. The current management of LCH has become increasingly conservative, and in the 1990s, fewer cases are given chemotherapy or radiotherapy. The prognosis is very good for single-system disease and poor for multisystem disseminated disease with early onset. © 1995 Jons Wiley & Sons, Inc.     

Intralesional infiltration of corticosteroids in localized Langerhans' cell histiocytosis.

The approaches to treatment of Langerhans' cell histiocytosis (LCH) have been as varied as the clinical presentation of the disease. The clinical course of localized LCH of bone is generally benign, and it tends to heal spontaneously in a period of months to years. If treatment is required, the disease can be controlled by local measures such as surgical curettement, low-dose irradiation, or intralesional infiltration with corticosteroids. We reviewed 15 children treated with intralesional infiltration of corticosteroids, either primarily for disease of bone (8 patients) or as adjunctive therapy for disseminated LCH (7 patients). Two patients developed complications as a result of this treatment method.     

Chemotherapy for children with aggressive fibromatosis and Langerhans' cell histiocytosis

Two disorders involving histologically benign proliferations of fibrous tissue or of histiocytes occur preferentially in children and often require combined management by an orthopedic surgeon and a pediatric oncologist. Treatment of young people with aggressive fibromatosis usually begins with wide local excision of the lesion. However, some tumors cannot be completely removed either because of their location or because of the risk of subsequent serious dysfunction. Not infrequently, local recurrence supervenes despite previous wide local excision, and sometimes multiple tumors are present. In these situations a trial of multiple-agent chemotherapy incorporating vincristine, actinomycin D, and cyclophosphamide may be indicated in an attempt to control the disease. Radiation therapy may also be useful, but the relatively high dose (5000 cGy or more) needed in a growing child is at times a less attractive alternative. Biopsy of a lytic bone lesion in young patients with Langerhans' cell histiocytosis, formerly known as histiocytosis X, is also indicated for initial diagnosis. Biopsy and curettage are usually curative in the patient with an isolated lesion. Patients with multiple simultaneous or recurrent lesions need chemotherapy if dysfunction of the liver, spleen, or lungs is present. Drug therapy may also be beneficial for children with systemic symptoms. This article outlines suggestions for chemotherapeutic treatment in both diseases.     

Langerhans' cell granulomatosis (histiocytosis X) associated with malignant lymphomas

We present six patients in whom Langerhans' cell granulomatosis (histiocytosis X) was found in lymph nodes also harboring malignant lymphomas: Hodgkin's disease in five and non-Hodgkin's lymphoma in one. This brings to 12 the total number of such reported cases. Whether this represents a chance association of the two processes or a peculiar reaction of Langerhans' cells to the lymphoma is unknown. The focal intimate intermingling of the two processes and the inability to identify LCG as an incidential finding in other cancers suggests that this phenomenon may represent a peculiar reaction to the lymphoma.     

Spinal Langerhans' cell histiocytosis in a young adult: case report and therapeutic considerations

We report an unusual case of spinal Langerhans' cell histiocytosis of the cervicothoracic junction in a young adult man. A 17-year-old male was referred to our institution with a 3-week history of cervicothoracic pain associated to a weakness of his right upper limb. Computed tomography and magnetic resonance imaging showed a collapsed T1 vertebral body with epidural soft tissue showing mass effect on spinal cord. The patient underwent a classic anterior cervicotomy. Complete removal of the lesion could be achieved, but the soft consistency of C7 and T2 body precluded a solid anterior fixation and an extended resection of C7 and T2 body had to be performed. Then a C6 - T3 stabilisation using an anterior plate fixation and cyanomethylacrylate graft was performed. Postoperative course was uneventful. At 2 years follow-up, the patient was asymptomatic and radiological workup showed a perfect stability of anterior fixation system. Aggressive surgical management of eosinophilic granuloma should be considered in some selected cases particularly when spinal instability or neurological deficit occurs. In this young patient a modified anterior cervicotomy allowed a comfortable approach to the anterior aspect of T3 vertebra for spinal fixation.     

Langerhans' cell histiocytosis after living donor liver transplantation: report of a case.

We report a case of Langerhans' cell histiocytosis (LCH) occurring after a living donor liver transplantation (LDLT) for fulminant hepatitis. A 9-month-old girl underwent an LDLT for fulminant hepatitis of an unknown cause. The histology of the native liver did not show any findings of LCH. On postoperative day 42, her Epstein-Barr virus (EBV)-DNA and cytomegalovirus antigenemia were both found to be positive. As a result, she was treated with antiviral agents and a reduction of the immunosuppression dosage. On postoperative day 98, acute rejection occurred, and she was treated with FK506, methylprednisolone, and finally, anti-CD3 murine monoclonal antibody was added. Subsequently, the EBV was re-activated. Thereafter, skin eruptions, swelling of the systemic lymph nodes, and pancytopenia appeared on postoperative day 127. LCH was diagnosed based on the typical histological findings as LCH, CD1a, and S-100-positive cells in her skin and a lymph nodes biopsy. She was treated by chemotherapy. The symptoms disappeared a few weeks after the start of the chemotherapy, and a clinical remission of LCH was obtained. We could not detect any evidence of EBV infection in the tumor cells. In spite of the fact that her LCH lesions thereafter remained in remission, she died of hepatic failure at 22 months after undergoing the liver transplantation. In conclusion, we discuss the factors influencing the occurrence of LCH in our patient after LDLT, while also evaluating the relationship between LCH and the immunosuppressive therapy administered to this patient.     

Langerhans' cell histiocytosis of the spine. Analysis of twenty-three cases.

STUDY DESIGN: Retrospective review of clinical and radiologic data in four major tertiary referral centers. OBJECTIVES: To report clinical and roentgenographic findings, to evaluate the results of various treatment methods, and to propose a protocol for management. SUMMARY OF BACKGROUND DATA: Langerhans' cell histiocytosis of the spine is a rare condition, and therefore, appropriate management is still controversial. METHODS: Clinical and roentgenographic findings of 38 vertebral lesions of 23 children, with average follow-up of 5.4 years, were investigated. This is the most extensive report apparent in the literature to date. The results of treatment were assessed clinically and radiologically. Anterior vertebral body height was measured sequentially to evaluate reconstitution of the vertebral body. RESULTS: The last follow-up examination demonstrated no clinical evidence of disease in all patients, regardless of treatment method. Neurologic deficits developed in four patients, but they completely disappeared. Satisfactory restoration of height was demonstrated in all except five vertebrae: one that had collapsed maximally when the patient was more than 15 years of age and four that had been fused anteriorly or posteriorly. Unsatisfactory results were also seen in a patient with progressive scoliosis and in one with an irregular endplate with disc space narrowing. Both of these complications developed after curettage. CONCLUSIONS: For treatment of single or dual spinal lesions, observation with or without bracing seems to be sufficient. In patients with multifocal lesions, chemotherapy produces good results. For treatment of neurologic deficit, low-dose radiotherapy is favored. Patients who underwent surgery--especially curettage and anterior fusion--had the worst outcome.     

Nephrotic syndrome after stem cell transplantation

Nephrotic syndrome occurs rarely after bone marrow transplantation. We describe three patients with myeloid malignancy who developed nephrotic syndrome from 5, 22 and 25 months after allogeneic stem cell transplantation (SCT), confirmed by electron microscopy as membranous glomerulonephritis in two and minimal change glomerulonephritis in one. Proteinuria was initially severe in all and clinically distinct from prior graft-vs.-host disease in two patients. While all responded initially to prednisolone and cyclosporine therapy, two recipients with high-risk leukemia developed late solid organ and bone marrow relapse of their disease, which ultimately proved fatal. The third patient remains alive and disease-free with minimal proteinuria off immunosuppressive therapy. Hence, the onset of de novo high-grade proteinuria after allogeneic SCT should prompt renal histological confirmation, and a trial of immunosuppressive therapy after other causes of nephritic syndrome have been excluded.