Langerhans Cell Histiocytosis Presenting Research Articles

A rare case of langerhans cell histiocytosis of the gastrointestinal tract

Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the proliferation of specialized, bone marrow-derived langerhans cells and mature eosinophils. The clinical spectrum ranges from an acute, fulminant, disseminated disease called Letterer-Siwe disease to solitary or few, indolent and chronic lesions of the bone or other organs called eosinophilic granuloma. Involvement of the gastrointestinal tract is very rare in LCH. We present the case of a 53-year-old woman referred by her primary care physician for a screening colonoscopy. A single sessile polyp, measuring 4 mm in size, was found in the rectum. Histopathological examination revealed that the lesion was relatively well circumscribed and comprised mainly a mixture of polygonal cells with moderate-to-abundant pink slightly granular cytoplasm. The nuclei within these cells had frequent grooves and were occasionally folded. Immunohistochemical staining was positive for CD-1a which confirmed the diagnosis of LCH. On further workup, there was no evidence of involvement of any other organ. On follow up colonoscopy one year later, there was no evidence of disease recurrence. Review of the published literature revealed that LCH presenting as solitary colonic polyp is rare. However, with the increasing rates of screening colonoscopy, more colonic polyps may be identified as LCH on histopathology. This underscores the importance of recognizing this rare condition and ensuring proper follow-up to rule out systemic disease.

Pulmonary Langerhans Cell Histiocytosis Presenting as Rapidly Progressive Pulmonary Nodules

Pulmonary Langerhans Cell Histiocytosis Presenting as Rapidly Progressive Pulmonary Nodules

Femoral Involvement by Langerhans Cell Histiocytosis Following Total Hip Arthroplasty

Langerhans cell histiocytosis (LCH), formerly called “eosinophilic granuloma,” is a benign bone neoplasm that is rare in adults. It is a cellular lesion with histiocytes, plasma cells, small lymphocytes, neutrophils, giant cells, foam cells, and eosinophilic leukocytes1. The disease typically presents during childhood, with >90% of cases occurring between the ages of five and fifteen years. LCH typically presents as a lytic medullary lesion with sharply defined margins, most commonly in the skull and in the diaphyses of long bones. The pelvis is affected in 5% to 17% of reported cases2,3. We report an unusual case of LCH presenting in the femur of a healthy young adult man following primary total hip arthroplasty for presumed idiopathic osteonecrosis. Inspection of the joint at the time of the initial surgery demonstrated no findings that were thought to warrant formal histological investigation of bone at the arthroplasty site. One year later, repeat radiographs demonstrated changes mimicking a periprosthetic infection. The prosthesis was removed, and histological examination of tissue curetted from the lytic lesions adjacent to the prosthetic femoral stem demonstrated findings consistent with a diagnosis of LCH. Cultures of curetted tissue from the same site revealed no bacterial, mycobacterial, or fungal growth. The patient, treated initially as if he had an infection at the site of the arthroplasty, underwent placement of an antibiotic cement spacer followed by revision total hip arthroplasty. At the most recent follow-up evaluation, there had been no recurrence of the LCH and the hip prosthesis was functioning well. In retrospect, LCH, which was present at revision, could have been present at the primary operation and could have been diagnosed if tissue specimens had been submitted for histological examination. This experience underscores the importance of maintaining a high index of suspicion for unexpected diagnoses …

Presence of Erdheim-Chester Disease and Langerhans Cell Histiocytosis in the Same Patient: A Report of 2 Cases

The histiocytic disorders Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD), can both present with multisystem involvement, with the central nervous system and the bone, skin, neuroendocrine, cardiac, respiratory, and gastrointestinal systems potentially affected. The 2 entities occasionally can be difficult to distinguish. Both rarely affect the orbit and the central nervous system, and although there are rare reports of patients with coexistent LCH and ECD, there are no reported cases of the 2 diseases that involve both the orbital and neuroendocrine systems. We report 2 such cases, and review the literature of cases of LCH and ECD occurring in the same patient. The presentation of LCH and ECD in certain patients suggests a possible abnormality in the common CD34 progenitor cell. The coexistence of the 2 disease states should be suspected in patients with atypical presentations of either disorder.

Central Diabetes Insipidus as the Inaugural Manifestation of Langerhans Cell Histiocytosis: Natural History and Medical Evaluation of 26 Children and Adolescents

Isolated central diabetes insipidus (CDI) can be the first manifestation of Langerhans cell histiocytosis (LCH), creating diagnostic dilemmas such as dysgerminoma and other inflammatory lesions. In 2010, the French national LCH registry had enrolled 1236 LCH patients under 18 yr of age. Isolated CDI was the initial presentation of LCH in 26 patients. We reviewed their clinical and magnetic resonance imaging (MRI) features. Median age at the diagnosis of CDI was 9.6 yr (1.8-16.3), and median follow-up after CDI diagnosis was 9.9 yr (3.5-26.6). In addition to CDI, two patients had visual field defects, four had secondary amenorrhea, and 11 had anterior pituitary deficiency. Cerebral imaging (including computed tomography in two cases), performed in 22 patients within 3 months of CDI diagnosis, showed pituitary stalk thickening in 14 patients, which was moderate (3.0-7 mm) in nine cases and marked (>7 mm) in five cases. In eight cases, the lesion extended to the floor of the third ventricle. One child with LCH presented with a mild enlarged sellar content. During follow-up, 22 patients developed extrapituitary involvement, mainly of bone (n = 15), lung (n = 9), and skin (n = 9). Pituitary biopsy was performed in eight cases and was conclusive in six cases. Pituitary stalk thickening can be observed in LCH as well as lesions extending to the floor of the third ventricle. In all cases but one, the intrasellar content was not enlarged. Long-term follow-up with close attention to bone, skin, and lung disorders may lead to the diagnosis of LCH.

A rare case of "switch on and off" multi-system Langerhans cell histiocytosis in an adult patient

IntroductionWe report the case of a 24-year-old Greek woman with histologically proven osseous and pulmonary Langerhans cell histiocytosis whose lesions had progressively regressed with a "switch on and off" mode. This is the first report in the literature of this mode of presentation of Langerhans cell histiocytosis.Case presentationThe patient had first presented at the age of 20 years with a solitary lesion of the humerus which spontaneously regressed. At that time, no therapy or smoking cessation was indicated. Four years later she presented with bilateral pneumothorax and pulmonary lesions of Langerhans cell histiocytosis. She had pleurodesis for this disease-related complication, and no further systemic treatment was applied, except with regard to smoking cessation. During the follow-up period, her pulmonary lesions regressed without recurrence six years after the initial lung involvement.ConclusionThis uncommon case of remission of multi-system Langerhans cell histiocytosis indicates the unpredictable evolution of the disease, raising the question of conservative management in such a patient.

Multisystemic Langerhans Cell Histiocytosis Presenting As Chronic Scalp Eczema: Clinical Management and Current Concepts

Multisystemic Langerhans Cell Histiocytosis Presenting As Chronic Scalp Eczema: Clinical Management and Current Concepts

Congenital self-healing reticulohistiocytosis - an important diagnostic challenge

To present current and new knowledge on congenital self-healing reticulohistiocytosis, a benign variant of cutaneous Langerhans cell histiocytosis presenting with skin lesions in the neonatal period. We describe and photo document two cases of this rare disease and review the literature. Only few newborns have acute access to a neonatal dermatologist, and we demonstrate how the spontaneous cutaneous involution may happen even prior to the first dermatological assessment. As no sole criterion can reliably distinguish the self-healing form from disseminated disease, multidisciplinary assessment and follow-up are essential. Our data document how easily the diagnosis congenital self-healing reticulocytosis may be missed and emphasize the importance and value of instant clinical photographing at the neonatal unit and the use of teledermatology whenever congenital self-healing reticulohistiocytosis is suspected.

14. Langerhans cell histiocytosis of the hip mimicking pigmented villonodular synovitis: an unusual presentation and potential frozen section pitfall

The case we present was of a 27-year-old male who presented with a 5 month history of left hip pain and with no associated trauma. Imaging of his left hip revealed a circumscribed lesion of the left metaphysis with cortical destruction. A similar, smaller lesion was noted in the right iliac wing. At surgery for the left hip lesion, a frozen section was requested. At this time the clinical impression, based on radiology and the gross appearance of the lesion, was that of pigmented villonodular synovitis. At frozen section the lesion was misdiagnosed as pigmented villonodular synovitis based on the presence of synovial-lined nodules of epithelioid cells and multinucleated cells, many containing haemosiderin pigment. Subsequent paraffin embedded sections showed the above features as well as highlighting the cleaved morphology of many of the epithelioid cells and the abundance of eosinophils, the latter which had not stained with eosin on frozen section. The epithelioid cells as well as giant cells expressed CD1a and S100, in keeping with Langerhans cell histiocytosis. Electron microscopy confirmed the diagnosis with presence of cytoplasmic Birbeck granules. This case highlights an unusual presentation of Langerhans cell histiocytosis as well as a potential diagnostic pitfall at frozen section.

Isolated Langerhans Cell Histiocytosis of the Thyroid in an Adult Female: One-Year Followup

Thyroid gland involvement as the unique presentation of Langerhans cell histiocytosis is a rare phenomenon that can result in misdiagnosis. We report a case of Langerhans cell histiocytosis (LCH) presenting as a thyroid mass. It is a 52-year-old woman who presented an enlarged, diffusely firm, nontender, nonmobile, and not particularly nodular thyroid gland with mild compressive symptoms. Ultrasound and fine-needle aspiration showed a unique right node with benign signs. Patient was referred to our Ambulatory Surgery Department, where a hemithyroidectomy was performed. Histologic evaluation of the right thyroid gland revealed an involvement by LCH, confirmed by immunohistochemical analysis showing Langerhans cells that were positive for CD1a. LCH was a completely incidental occult finding apparent only after surgical resection and examination of the gland. Patient was evaluated, and no evidence of systemic affectation was found. LCH can rarely involve the thyroid gland in adults. Few cases have been reported in the literature. Most patients had evidence of LCH involving other anatomic sites.

New clinical score for disease activity at diagnosis in Langerhans cell histiocytosis

BackgroundThe clinical presentation and course of Langerhans cell histiocytosis (LCH) are variable, ranging from an isolated, spontaneously remitting bone lesion to multisystem disease with risk organ involvement. Treatment of LCH ranges from a wait-and-see attitude to intensive multidrug therapy and, in some cases, bone marrow transplantation. It is necessary to develop an objective score for assessing disease activity in patients with LCH. We propose a new clinical scoring system to evaluate disease activity at diagnosis that can predict the clinical outcomes of LCH and correlate it with clinical courses.MethodsClinical data, obtained from children diagnosed with LCH at Asan Medical Center and Hanyang University Hospital between March 1998 and February 2009, were studied retrospectively. The scoring system was developed according to the basic biological data, radiological findings, and physical findings and applied to a database containing information on 133 patients.ResultsThe median age of the 133 patients (74 male, 59 female) was 52 months (range, 0.6-178 months), and LCH was diagnosed based on CD1a positivity. At diagnosis, the score distributions were highly asymmetrical: the score was between 1 and 2 in 75.9% of cases, 3-6 in 15.8%, and greater than 6 in 8.3%. Initial scores above 6 were highly predictive of reactivation and late complications.ConclusionThis new LCH disease activity score provides an objective tool for assessing disease severity, both at diagnosis and during follow-up.

Vulvar ulcer as a presentation of systemic langerhans cell histiocytosis

We report a 38-year-old housewife with systemic Langerhans cell histiocytosis (LCH) presenting as a chronic vulvar and peri-anal ulcer. She had systemic involvement in the form of diabetes insipidus and bone "hot-spots". She responded favorably to etoposide, 6-mercaptopurine, and systemic steroids, and has been in remission since 10 years. Chronic vulvar ulcers not responding to routine therapy should not be neglected and need to be biopsied repeatedly to come to a specific diagnosis. The vulvar ulcer in our case provided a vital clue to a systemic LCH, with a successful outcome.

Histiocytosis X: Characteristics, behavior, and treatments as illustrated in a case series

Background:Langerhans cell histiocytosis (LCH) is a proliferative disorder predominantly found in children. It often presents with pain in calvarium or spine and may cause neuroendocrine symptoms. The gold standard for diagnosing LCH is the detection of Birbeck Granules by EM. Here, we describe two unique presentations of LCH and we review current treatment guidelines.Case Description:The first patient was a 23-year-old man who presented with progressive swelling and redness of the left eye. MRI revealed a left retrobulbar lesion extending into the middle cranial fossa with no signal abnormality in the brain parenchyma. The lesion was resected and pathological analysis revealed LCH. Bone scans were negative and the patient was discharged soon after. He later underwent fractionated radiotherapy (cumulative dose 26 Gy). Follow-up MRIs show no disease at 24 months post-op. The second patient was a 56-year-old man with left frontal skull pain for 5 months. Imaging showed a solitary osteolytic lesion extending into both dura and scalp with no signal abnormality of the parenchyma. Excisional biopsy revealed LCH. Surgery was well tolerated and follow-up imaging shows no recurrence at 24 months post-op.Conclusion:We demonstrate that LCH, though uncommon, must remain on the differential when osteolytic lesions present in the adult. Although LCH often has the clinical and radiographical presentation of an abscess, pathology analysis can successfully diagnose LCH based on markers and morphological characteristics. LCH has an excellent prognosis when treated aggressively with surgical resection and radiotherapy as both of our patients were and are now disease free at 2 year follow-up.

Langerhans cell histiocytosis: old disease new treatment

Langerhans cell histiocytosis (LCH) has been previously thought of as a rare illness, but is now increasingly diagnosed as a result of the more intensive investigations of patients with cystic pulmonary disease. In recent years, treatments developed from our new understanding of the molecular biology of malignant disease have been applied to patients with LCH, and responses seen. In this review, we describe the origins, presentation and modern treatment of LCH, showing that there is new hope for patients with this condition.

Langerhans cell histiocytosis in a 5-month-old presenting with biparietal masses

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder that occurs most commonly in the pediatric population as a result of pathological clonal proliferation of Langerhans cells with subsequent damage and destruction to surrounding tissue. Clinically, LCH presents in a variety of ways, which often results in prolonged time to diagnosis and subsequently poorer outcomes. In this case report, the authors describe an unusually early presentation of multisystem LCH in a patient at birth, which resulted in a 5-month delay to diagnosis and treatment. This patient presented both atypically young and with an uncommon initial manifestation of multisystem disease with multiple soft-tissue swellings rather than early skin involvement. Additionally, this patient had an unusual radiographic appearance with biparietal skull destruction on initial skull radiographs and biparietal soft-tissue lesions on CT resembling cephalohematoma at 3 months of age. The clinical and radiological evaluation, pathology, and treatment strategies are discussed, with particular attention paid to the importance of further workup of atypical nonresolving cephalohematomas to prevent disease progression and poorer outcomes.

Langerhans cell histiocytosis with multiple spinal involvement

To stress the clinical and radiologic presentation and treatment outcome of Langerhans cell histiocytosis (LCH) with multiple spinal involvements. A total of 42 cases with spinal LCH were reviewed in our hospital and 5 had multifocal spinal lesions. Multiple spinal LCH has been reported in 50 cases in the literature. All cases including ours were analyzed concerning age, sex, clinical and radiologic presentation, therapy and outcome. Of our five cases, three had neurological symptom, four soft tissue involvement and three had posterior arch extension. Compiling data from the eight largest case series of the spinal LCH reveals that 27.2% multiple vertebrae lesions. In these 55 cases, there were 26 female and 29 male with the mean age of 7.4years (range 0.2-37). A total of 182 vertebrae were involved including 28.0% in the cervical spine, 47.8% in thoracic and 24.2% in the lumbar spine. Extraspinal LCH lesion was documented in 54.2% cases, visceral involvement in 31.1% and vertebra plana in 50% cases. Paravertebral and epidural extension were not documented in most cases. Pathological diagnosis was achieved in 47 cases including 8 open spine biopsy. The treatment strategy varied depending on different hospitals. One patient died, two had recurrence and the others had no evidence of the disease with an average of 7.2 years (range 1-21) of follow-up. Asymptomatic spinal lesions could be simply observed with or without bracing and chemotherapy is justified for multiple lesions. Surgical decompression should be reserved for the uncommon cases in which neurologic compromise does not respond to radiotherapy or progresses too rapidly for radiotherapy.

Langerhans Cell Histiocytosis Presenting as Hypopigmented Papules

A 1(1/2)-year-old boy with Langerhans cell histiocytosis presented with a frontal bone mass showing features of eosinophilic granuloma. He subsequently developed multiple asymptomatic discrete hypopigmented papules on the face, trunk and extremities, which, on histology, were confirmed as Langerhans cell histiocytosis, a presentation hitherto unreported in literature. He responded well to surgery and chemotherapy.

Langerhans cell histiocytosis presenting in a 79-year-old man

Langerhans cell histiocytosis presenting in a 79-year-old man

Case Report: Langerhans Cell Histiocytosis Presenting as Massive Cervical Adenopathy and Retropharyngeal Thickening

To demonstrate the importance of chest radiography and special anesthetic management in children with massive cervical adenopathy. Case report of an 8-month-old infant who presented to the emergency department with fever, drooling, and massive cervical and mediastinal adenopathy. Safe anesthetic management allowed for cervical lymph node biopsy, which showed Langerhans cell histiocytosis. Chest imaging and special anesthetic techniques (intravenous anesthesia and positioning in the lateral decubitus position) should be considered for children with massive cervical and mediastinal adenopathy. Interdisciplinary airway, radiographic, and anesthetic management is recommended for children who present with massive and cervical and mediastinal adenopathy.

Langerhans cell histiocytosis: A complex recurrent disease

A six-year-old boy was referred to a paediatric hematologist/oncologist with recurrent, painful skull masses. Skeletal survey and computed tomography revealed lytic lesions in his calvarium (Figure 1) and a silent lesion in his right humerus. Positron emission tomography-computed tomography scan confirmed involvement of these sites. A biopsy of the skull mass showed infiltrates of pathogenic Langerhans cells, staining positive for CD1a, Langerin and S100, and containing Birbeck granules on electron microscopy. Of note, 14 months earlier, the boy had a soft tissue mass removed by surgical curettage from the lateral wall of his left orbit but no adjuvant therapy. The pathology of both lesions was consistent with Langerhans cell histiocytosis (LCH). Figure 1) Lytic skull lesions. Reproduced with permission from Dr Bruce Crooks The boy’s treatment at this time included vinblastine and prednisone for a year, with regression of all lesions. Three years later, another skull mass appeared and surgical curettage again showed pathogenic Langerhans cells. Meanwhile, he had developed excessive thirst and polyuria. A water deprivation test confirmed diabetes insipidus. A brain magnetic resonance imaging scan showed enhancement and thickening of his infundibular pituitary stalk, suggestive of LCH involvement. In view of this new development, a paediatric endocrinologist became involved in managing the diabetes insipidus and is closely observing any further pituitary complications. Because LCH has the potential to recur despite successful therapies, sometimes with significant sequelae, close supervision by a multidisciplinary care team is essential (1). LEARNING POINTS LCH is a rare disease of unknown causes, characterized by the proliferation of pathogenic Langerhans cells and cytokine overproduction, and causes inflammation, infiltration and destruction of many tissues in the body. Due to the recognition of the pathogenic Langerhans cell as a common cause, LCH now includes previously described conditions ranging from the acute fulminant disseminated Letterer-Siwe disease, through the intermediate Hand-Schuller-Christian disease and histiocytosis X, to the more chronic and often solitary eosinophilic granuloma. Although the Langerhans cells are not generally believed to be cancerous, the clinical manifestations of organ infiltration and the potential for fatal disease, along with a clonal population, argue in favour of a malignant process. Presentations of LCH include the following: ○ skin rashes (resembling seborrheic dermatitis [Figure 2] in infants) resistant to usual therapies; Figure 2) Seborrheic dermatitis. Reproduced from ○ unifocal or multifocal bony lumps, frequently affecting skull and facial bones; ○ central nervous system disease, often involving the pituitary/infundibulum and causing diabetes insipidus; or ○ fulminant multiorgan disease of infancy, which may be fatal. The most common treatments range from observation alone, surgical curettage with or without intralesional steroids, nonsteroidal anti-inflammatory agents (eg, indomethacin) or cytotoxic agents (eg, vinblastine, prednisone or cladribine). Fulminant multiorgan disease or recurrent/resistant disease may be treated with biological modifiers (eg, cytokine inhibitors) or may require hemopoietic stem cell transplantation. Due to its rarity and diverse presentations, the true incidence and burden of LCH are poorly understood, with estimates ranging from 2.24 to 8.9 per million children. Most data are European and are limited by being taken from institutional series or regional/national registries only. LCH can also occur in adults, although even less is known regarding incidence and outcome in this group. The recent British Paediatric Surveillance Unit (2) and French national studies (3) were more comprehensive, seeking cases from multiple sources, and reported incidences of 4.12 per million children (aged zero to 14 years) and 4.6 per million children, respectively. The British study identified 17% of cases from outside the British Paediatric Surveillance Unit program, implying that many cases are not seen by paediatricians. In North America, delays to diagnosis may be due to low awareness and understanding of LCH, and patients can first present to different specialties such as paediatrics, orthopedics, neurosurgery, ophthalmology, ear, nose and throat, and dermatology. Most cases in children are eventually managed by paediatric hematology/oncology specialties. The current national study of LCH aims to collect national data over two years, primarily via the Canadian Paediatric Surveillance Program but also by parallel survey of other allied specialty physicians and surgeons to collect additional cases and to help identify pathways of referral. Results are important for the development of a national registry to optimize care and research for LCH patients.