Eosinophilic granuloma of the calvarium: is conservative management a valid option? Illustrative case and systematic review of the literature.

INTRODUCTION: Eosinophilic granuloma (EG) is the most common form of Langerhans cell histiocytosis, presenting as a single osteolytic lesion of the calvarium. Its diagnosis is based on typical clinical and radiological features. While surgical resection has been the standard treatment for EG, growing evidence favors watchful waiting, as unifocal calvarial lesions appear to frequently undergo spontaneous remission. However, histopathological confirmations of this hypothesis are still very limited. METHODS: Methods. Here, we report a case of EG with typical clinical and radiological features which, due to intervening circumstances, was resected in a delayed fashion. Moreover, we perform a systematic review of the literature on conservative management of EG. RESULTS: In our case, histological examination showed ongoing bone regeneration with no traces of the disease. Through our literature review, we found 47 cases of calvarial EG managed with watchful waiting. No active intervention was required in 43 cases (91%). Four patients (9%) received surgery or chemotherapy due to the persistence/progression of symptoms or family request. Three reports other than ours documented spontaneous disease remission in surgically resected EG upon histopathological examination. CONCLUSION: Our report provides further evidence that watchful waiting can be a reasonable option in the management of single calvarial EG.

Acquired butterfly vertebra as a sequela of eosinophilic granuloma.

Butterfly vertebras are an abnormal embryological formation of the spinal bodies that occur because of a lack of fusion of the chondrification centers of the vertebral bodies. Langerhans cell histiocytosis is an entity that frequently involves vertebral bodies resulting in flat vertebras, and recovery of the vertebral body height is a very unusual finding. We present a case report of a pediatric patient with a thoracic acquired butterfly vertebra which occurred secondary to a Langerhans cell histiocytosis involvement. It is extremely rare to find vertebra plana that regains its complete height but is even more infrequent to evidence of a butterfly vertebra deformity that is not congenital.

Vertebra Plana in Children May Result from Etiologies Other Than Eosinophilic Granuloma.

BACKGROUND: Vertebra plana in children is a diagnostic dilemma for orthopaedic surgeons. This radiographic finding sometimes has been said to be pathognomonic for eosinophilic granuloma (Langerhans cell histiocytosis); however, vertebra plana may also be caused by a range of other conditions. We sought to determine whether vertebra plana can be associated with malignancies other than eosinophilic granuloma. QUESTIONS/PURPOSES: (1) To report the underlying diagnoses for children with vertebra plana and determine how frequently these patients were found to have eosinophilic granuloma as opposed to an underlying malignant process, (2) to evaluate the occurrence of nondiagnostic results on biopsy, and (3) to determine whether the presenting characteristics of spinal lesions were associated with the ultimate clinical diagnosis. METHODS: As part of a retrospective review, our institutional electronic medical record was searched for all patients younger than 18 years between 1976 and 2017 whose clinical record included the term vertebra plana. Patients with trauma were excluded. Twenty-seven patients met the inclusion criteria (mean [range] age 9 years [0 to 18]; 12 girls). To address our first research purpose about the underlying diagnoses of patients with vertebra plana, we reviewed the final clinical diagnosis. To address our second research purpose about the utility of biopsy, we reviewed which patients underwent a biopsy and whether it had been diagnostic. To address our third research purpose about the radiographic criteria, we classified the radiographs and compared this to the clinical diagnosis. Vertebral collapse was described as less than 50% collapse, 50% to 100% collapse, symmetrical, and asymmetrical. The location of each lesion was noted. RESULTS: Twelve of 27 patients had a diagnosis of eosinophilic granuloma. Six of 27 had other neoplastic etiologies, including acute lymphoblastic leukemia, primary germ cell tumor, giant cell tumor, rhabdomyosarcoma and teratoma. Seventeen of 27 patients underwent biopsy to confirm the diagnosis; six biopsies were consistent with eosinophilic granuloma, six for other etiologies, and five were nondiagnostic. With the limited patient numbers available, there was no difference in the frequency of less than 50% loss of height or 50% to 100%, or symmetric and asymmetric loss of height, and location of the lesion among patients with eosinophilic granuloma and those with other diagnoses. CONCLUSIONS: Eosinophilic granuloma or Langerhans cell histiocytosis is a common cause of vertebra plana, but other causes must be considered in children presenting with this radiographic finding. Six of 27 of patients presenting to our center with vertebra plana had an underlying neoplasm other than eosinophilic granuloma. With the limited patient numbers available, pain, spinal location, and the degree and symmetry of collapse were not associated with a diagnosis of eosinophilic granuloma in this series. Thus, patients presenting with vertebral plana and back pain need a comprehensive work-up and potentially tissue biopsy to determine diagnosis and appropriate treatment. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Long-term Follow-up of Eosinophilic Granulomas of the Axial and Appendicular Skeleton Managed With Biopsy Alone.

BACKGROUND: This study aimed to evaluate the long-term clinical and radiologic follow-up results of eosinophilic granulomas (EGs) of the axial and appendicular skeleton managed with biopsy alone. METHODS: Fifty-five patients with unifocal osseous EGs of the axial and appendicular skeleton were followed after biopsy. Patients were divided into 2 groups on the basis of localization of the lesions. In group 1, there were 32 (58.2%) children with extremity long bone involvement: femur, tibia, humerus, ulna, and radius. Group 2 included 23 (41.8%) patients with lesions located in other appendicular and axial skeleton bones: pelvis, scapula, clavicle, lumbar, and thoracic vertebrae. After confirming the diagnosis by a closed biopsy, no further surgical intervention was performed. Clinical recovery included regression of the localized symptoms, mainly pain resolution. Functional improvement was assessed by Musculoskeletal Tumor Society (MSTS) scoring. Radiologic healing was defined as ossification of the entire lesion with cortical thickening in long and flat bones, and restoration of vertebral body height in the spine. Complications, including local recurrence, were determined. RESULTS: The patients comprised 28 boys and 27 girls with an average age of 9.2 years (range, 3 to 16 y). The average follow-up was 76 months (range, 28 to 132 mo). The median time from biopsy to clinical recovery was 17 days [95% confidence interval (CI), 13.3-20.6] and 36 days (95% Cl, 32.8-39.1) in group 1 and group 2, respectively. MSTS scores increased progressively till the end of 12 months in both groups. The median time from biopsy to radiologic healing was 16 months (95% CI, 11.5-20.4) and 42 months (95% Cl, 39.3-44.6) in group 1 and group 2, respectively. Both clinical recovery (P=0.021) and radiologic healing (P=0.009) were significantly faster in group 1 compared with group 2. No major complication was seen after biopsy. All lesions regressed without a local recurrence. CONCLUSIONS: Unifocal osseous EGs have spontaneous healing potential and confirming the diagnosis by biopsy is enough to obtain good clinical and radiologic results without any additional surgical intervention. TYPE OF STUDY: This was a therapeutic study. LEVEL OF EVIDENCE: Level IV.

Management of eosinophilic granuloma in pediatric patients: surgical intervention and surgery combined with postoperative radiotherapy and/or chemotherapy.

BACKGROUND: Eosinophilic granuloma (EG) of spine in pediatric patients presents kinds of clinical manifestation and a difficult management scenario. The choice of treatment, issues of surgical intervention versus conservative treatment, combination therapy or single treatment, all these factors, including neurological deficits, spinal stability, long-term complications, and continued skeletal growth, must be considered. METHODS: From 2008 to the 2015, 31 pediatric patients of spinal EG were retrospectively reviewed. They were 17 males and 14 females, with a mean age 8.89 ± 2.84 years old (range, 3.5-14 years old). All the cases were divided into two groups. Twenty-three cases (Group S) accepted surgical interventions and surgery combined with local low-dose radiotherapy and/or chemotherapy. Eight patients (Group C) accepted radiotherapy and/or chemotherapy. All the patients had imaging studies of the lesion including standard radiography, three-dimensional computed tomography (CT) scan, and magnetic resonance imaging (MRI) prior to and after treatment. Cases in group S underwent surgery-related treatment, which include six patients accepted surgery only, nine patients accepted postoperative low-dose radiotherapy, four patients accepted additional chemotherapy, and four patients accepted both. Cases in group C accepted radiotherapy and/or chemotherapy, which include five patients accepted radiotherapy, one patient accepted chemotherapy, and two patients accepted both radiotherapy and chemotherapy. Clinical symptoms, neurologic status, radiologic manifestations, treatment, outcome, and/or complications were recorded and analyzed. RESULTS: All the 31 patients had pain relief (both in group S and group C) but the patients in group S obtained more prompt pain relief. All the patients in group S obtained local kyphosis correction, reconstruction of stability of spine, and recovery of neurological deficit after treatment. They have no surgery-related complications after treatment and in follow-up. Seventeen patients who received additional postoperative radiotherapy and/or chemotherapy also had good outcomes. There were no severe radiation and chemotherapy complications in procedure. The patients (group C) who accepted non-surgical treatment also have no severe complications, and a new femur lesion was found in one patient in follow-up. CONCLUSION: Surgical intervention, including anterior and/or posterior approach with bone graft or surgery combined with postoperative low-dose radiotherapy and/or chemotherapy is a safe and effective way for treatment of the spinal EG. Compared with radiotherapy and/or chemotherapy, more prompt pain relief can be achieved via surgical intervention or surgery combined radiotherapy and/or chemotherapy.

Spontaneous and complete regeneration of a vertebra plana after surgical curettage of an eosinophilic granuloma.

PURPOSE: The eosinophilic granuloma is a unifocal or multifocal Langerhans cell histiocytosis characterized by an expanding proliferation of Langerhans cells in bones. Skeletal LCH is a rare condition, and vertebral regeneration in cases of vertebral body collapse is even rarer. We report the case of a girl with spontaneous complete healing. METHODS AD RESULTS: A 3-year-old girl was referred for nighttime back pain, with no fever and no neurologic signs. Within a few days, she developed sudden painful restriction of all spine movements. X-ray and computed tomography (CT) of the spine showed reduced T7 vertebral body height (vertebra plana).The patient underwent T7 curettage and the histopathological exam was suggestive of LCH. Two additional skull lesions were found and therefore she underwent chemotherapy. After 7 years of follow-up, total vertebral reconstruction was observed. CONCLUSIONS: Despite the rarity of the condition and despite the rarity of vertebral body lesion resolution, total vertebral body reconstruction was observed over a 7-year period. Long-term follow-up is necessary for a better understanding of the final outcome of patients with EG.

Eosinophilic Granuloma of Skull with Fluid Level and Epidural Hematoma: A Case Report and Review of the Literature.

Intracranial Langerhans cell histiocytosis commonly presents as skull lesions in children. An intratumoral cyst with fluid level and epidural hematoma occurring with eosinophilic granuloma is very rare. We report a 15-year-old boy who presented with a spontaneous epidural hematoma which was the result of a temporal eosinophilic granuloma. Multiple explanations for epidural hematoma in such cases have been discussed. Intratumoral hemorrhage followed by cyst formation and rupture may explain the pathophysiology of epidural hemorrhage formation.

[Eosinophilic granuloma of the parietal bone of an adult patient with BRAF mutation]. / Éozinofil'naia granulema temennoi kosti s mutatsiei gena BRAF u vzroslogo patsienta.

The paper describes a case of eosinophilic granuloma of the parietal bone in a 32-year-old man. Histological examination revealed a large number of bean-shaped Langerhans cell histiocytes with lobed nuclei and nuclear grooves. The histiocytes alternated with the foci of obvious eosinophilic infiltration and with eosinophilic microabscesses. There were osteoclast-like multinucleated giant cells, bone resorption, and numerous bone rods covered with osteoblast chains. The histiocytes expressed CD1α, langerin, CD68, S100, and p53 (in 90.0% of the tumor cells). The Ki-67 proliferation index was 18.0%. A molecular genetic study identified BRAFV600E mutation (nucleotide substitution s.1799 T>A (p.V600E) in the heterozygous state). Clinical and morphological data and the results of molecular genetic studies led to the conclusion that there was eosinophilic granuloma of the right parietal bone (the unifocal form of Langerhans cell histiocytosis (LCH), type I, group A1, with the monoossal nature of lesion and with BRAFV600E mutation). In adults, this disease is extremely rare (2-5 cases of LCH per million people, bone loss in the fourth decade of life in 2.5% of the patients).

Pandora's box: eosinophilic granuloma at the cerebellopontine angle-should we open it?

BACKGROUND: Langerhans cell histiocytosis (LCH) is a disorder of immature LCH cells, eosinophils, macrophages, lymphocytes, and multinucleated giant cells. Eosinophilic granuloma (EG) is a focal form of LCH that presents mostly in the skull, femur, vertebrae, pelvis, mandible, and ribs. Intracranial presentation of EG is very rare in the literature. CASE DESCRIPTION: A 17-year-old boy visited our clinic with headache, dizziness, and tinnitus that were present for 2 months. Brain MRI depicted a lesion at the right cerebellopontine angle. The lesion was hypointense on T1-weighted and hyperintense on T2-weighted brain MR images. The lesion enhanced homogenously after I.V. contrast material administration. Pre-operative diagnoses were vestibular schwannoma and meningioma. Surgery was planned. Retrosigmoid approach was preferred in the surgery. The lesion was excised partially. Pathological analysis depicted cell infiltration composed of eosinophils besides histiocytes, plasma cells, and lymphocytes in different amounts. CD1a was positive yet S100 was negative. Final diagnosis was eosinophilic granuloma. Post-operative course was uneventful. The patient was referred to pediatric oncology unit, and steroid therapy was initiated. Post-operative follow-up brain MRIs showed that the lesion had regressed further than immediate post-operative images by only steroid use. In long-term follow-up, new lesions appeared on the patient's skin in multiple locations and in the sclera of his left eye. At the last follow-up (3 years post-operatively) skin and scleral lesions were noticed to have regressed spontaneously and the intracranial structures were tumor free. DISCUSSION AND CONCLUSION: To the best of our knowledge, EG at the cerebellopontine angle has not been presented in the literature. What makes our case further unique is its negativity for S-100 antigen. Eosinophilic granuloma should be kept in differential diagnosis of mass lesions presented at the cerebellopontine angle, especially in children and young adults with high eosinophils and lymphocytes in their peripheral blood. Sole steroid trials could be conveyed in suspicious cases before any further intervention. If the lesions do not regress or enlarge with time, surgery should be considered. However, long-term follow-up of these patients is necessary since natural history of the disease has not been defined, yet.

Monosystem multifocal Langerhans cell histiocytosis (multifocal eosinophilic granulomas of the bone) in a 36-year old patient: case report, therapeutic doubts and review of literature.

Our aim is to provide review of available studies on Langerhans cell histiocytosis (LCH) and discuss treatment for polyostotic monosystem form of disease based on our clinical experience. LCH is an enigmatic disease with insufficiently understood etiology, pathophysiology, and variety of clinical presentations ranging from solitary eosinophilic granuloma to severe multisystem disease. It is marked by formation of granuloma in practically any organ. We present rare case of multifocal bone disease in 36-year old patient without visceral involvement. Treatment protocols for adult LCH patients, especially for uncommon form in our case have not yet been defined. Our therapeutical trial with corticosteroids showed limited success with numerous side-effects. We conclude that LCH treatment can commence only after diagnosis and staging of the disease. Other factors like patient's age, comorbidity, general condition, severity of symptoms and contraindications for therapy modalities should also be considered. In our experience expectative approach has better clinical outcome than immunosuppressive therapy in patients suffering from polyostotic multifocal form LCH with mild symptoms.

Multiple metastasis-like bone lesions in scintigraphic imaging.

Multiple benign osteolytic lesions are very hard to differentiate from disseminated bone metastasis. Whole-body bone scintigraphy (WBBS) with technetium-99m methylene diphosphonate (Tc-99m MDP) demonstrates multiple lesions with increased uptake in any bone involved. Even combined with medical history and multiple imaging results, such as MRI and CT, the clinical diagnosis of metastasis lesion remains as a challenge. These clinical characteristics are similar to multiple malignant bone metastases and therefore affect the following treatment procedures. In this paper, we analyzed multiple benign osteolytic lesions, like eosinophilic granuloma (EG), multiple myeloma (MM), disseminated tuberculosis, fibrous dysplasia, or enchondroma, occurring in our daily clinical work and concluded that additional attention should be paid before giving the diagnosis of multiple bone metastases.

Solitary eosinophilic granuloma of the adult lumbar spine.

INTRODUCTION: Eosinophilic granuloma (EG) is a benign bone tumor that rarely occurs in adults. It is usually found occurring in flat and long bones, but spine is often affected too. EG is of unknown aetiology, and the course of the disease is unpredictable. MATERIALS AND METHODS: Two cases of EG of the adult lumbar spine are reported, representing a difficult challenge for diagnosis and treatment. CONCLUSION: CT scan guided trocar biopsy allowed to achieve a definitive diagnosis, and CT scan guided intralesional infiltrations of corticosteroids were the successful treatment.

Eosinophilic granuloma of the temporal bone in an adult: controversies in the management.

Eosinophilic granuloma is a rare, benign, lesion characterized by uncontrolled proliferation of Langerhan's cells. It is commonly found in a bone and has been described in almost every bone in the body. It usually affects children and is seldom found in adults. A case of 60-year-old adult male with an eosinophilic granuloma of the right temporal bone with infiltration of the temporal and infratemporal fossa and osteolysis of the squama of the temporal bone is presented. Diagnostic procedure and course of treatment are described. Controversies in the management and different approaches in therapy of such lesion are discussed because there is no agreed treatment protocol established.

CT-guided corticosteroid injection for solitary eosinophilic granuloma of the spine.

OBJECTIVE: To evaluate the clinical and imaging outcome of patients with symptomatic eosinophilic granuloma of the spine treated with CT-guided intralesional methylprednisolone injection after biopsy. MATERIALS AND METHODS: Patients (n =19) with symptomatic solitary eosinophilic granuloma of the spine treated by CT-guided intralesional methylprednisolone injection were retrospectively studied. There were 12 males and seven females with a mean age of 17 years (range, 3-43 years). The mean follow-up was 6 years (median, 4 years; range, 0.5-19 years). Spinal location included the cervical (two patients), thoracic (seven patients), lumbar spine (eight patients), and the sacrum (two patients). Vertebra plana was observed in two patients. All patients had biopsies before treatment. RESULTS: Complete resolution of pain and healing of the lesion was observed in 17 patients (89.5%); none of these patients had recurrence at the latest examination. Reconstitution of the T1 and L1 vertebra plana was observed in both patients. Two patients initially diagnosed and treated for a solitary eosinophilic granuloma had constant pain after the procedure; in these patients, 6 and 12 months after the procedure, respectively, imaging showed multifocal disease and systemic therapy was administered. Complications related to the procedure were not observed. General anesthesia was administered in two patients because of intolerable pain during the procedure. CONCLUSIONS: In view of the benign clinical course of eosinophilic granuloma, in patients with symptomatic lesions, CT-guided intralesional corticosteroid injection is a safe and effective outpatient treatment with a low complication rate.

Eosinophilic granuloma: resolution of lesion after biopsy.

Langerhans cell histiocytosis is a collective term used to describe a group of enigmatic proliferative disorders. Three disease variants include eosinophilic granuloma, Letterer-Siwe disease, and Hand-Schuller-Christian syndrome. Eosinophilic granuloma is reported to be the most benign type of the triad. In this report, a 7-year-old child with an eosinophilic granuloma of the left side of her mandible is presented. There was a painless, hard, tender mass arising from the left side of the molar region. Panoramic radiographs showed a radiolucent area at the molar region. The lesion was resolved 2 weeks after the biopsy. The 1.5 years of radiographic and clinical follow-up was satisfactory.

Eosinophilic granuloma of bilateral humerus with unusual diagnostic process.

A 15-year-old boy presented with a right shoulder pain and the inability to use his right upper limb after carrying a heavy object. Physical examination and local imaging revealed a benign tumor or tumor-like lesion in the upper ends of both humeri and a pathologic fracture in the right humerus. An initial biopsy was reported as fibroblastic osteosarcoma. But the CT-guided biopsy was diagnosed as eosinophilic granuloma (EG). Bone curretage and grafting confirmed diagnosis of EG. This case illustrates the importance of combining a clinical impression with imaging and pathology in bone and soft tissue tumors.

Multifocal eosinophilic granuloma of the jaws with long-term follow-up: a case report.

Eosinophilic granuloma, a rare disease, has various clinical manifestations and no specific X-rays features and is thus easily misdiagnosed. This paper reports a case of multifocal eosinophilic granuloma of jaw with long-term follow-up. The patient initially presented with periodontal tissue destruction.The diagnosis, treatment and prognosis of multifocal eosinophilic granuloma of jaw were discussed in combination with the literature to alert this disease in clinical practice.

Recurrent eosinophilic granuloma involving maxilla and mandible in an adult male: an unusual case report.

Langerhans' cell histiocytosis (LCH) is a disease spectrum characterized by the intense infiltration/accumulation of Langerhans' cells in the affected tissues. Eosinophilic granuloma is the mildest form of LCH which mainly affects the skull, mandible, ribs and femur in children and young adults but rarely occurs in the maxilla. Here, we describe an unusual case of eosinophilic granuloma affecting the tissues adjacent to tooth #25 and tooth #46 (FDI numbering system) in a 35-year-old male. Although lesions underwent clinical remission after local radiotherapy, a new lesion appeared 11 months after initial therapy in tooth #18, indicating recurrence of eosinophilic granuloma. Subsequently, the patient was treated with corticosteroid therapy, achieved remission and is disease free after 3 years of follow-up.