Management Of Langerhans Cell Histiocytosis Research Articles

Upfront Low-Dose Cytarabine with Prednisolone for Langerhans Cell Histiocytosis with Liver Dysfunction: A Ray of Hope

AbstractThe management of Langerhans cell histiocytosis (LCH) with accompanying liver dysfunction poses significant challenges, and this prompted the development of a modified low-dose cytarabine and prednisolone regimen. In this prospective observational study on children with LCH and liver dysfunction, four patients underwent induction and maintenance chemotherapy. The induction phase included 5 days of 100 mg/m2 cytarabine and 4 weeks of 40 mg/m2 daily prednisolone, with subsequent tapering. Maintenance included a regimen of 5 days of 100 mg/m2 cytarabine, along with oral prednisolone, repeated every 3 weeks. Complete disease resolution occurred after varying chemotherapy cycles. Three patients had liver transplants, and the chemotherapy resumed for 52 weeks after the transplant. In one child, chemotherapy was continued after reaching remission. In conclusion, a modified, less toxic low-dose cytarabine-based chemotherapy effectively managed LCH with liver dysfunction, with liver transplantation as a postremission treatment option.

From mutation to management: Advancing Langerhans cell histiocytosis treatment through combination therapies.

The treatment landscape for relapsed Langerhans cell histiocytosis (LCH) is fraught with uncertainty due to a scarcity of data. Karri etal.'s study provides promising evidence that combining MAPK pathway inhibitors with chemotherapy could improve outcomes, even for patients with multiple relapses. Although larger studies are needed, this approach suggests a shift towards more aggressive, potentially curative strategies in the management of LCH. Commentary on: Karri etal. Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis. Br J Haematol 2024;204:1882-1887.

LBSAT310 A Rare Disease Engulfing Thyroid And Masquerading As Common Thyroid Disorders

Abstract Introduction – Langerhans cell histiocytosis (LCH) is a rare clonal disorder caused by the CD207+ Langerhans cells derived from the myeloid origin. We present a case of LCH where it mimicked Hashimoto's and Riedel's thyroiditis and completely infiltrated the thyroid gland. Case description – A 54-year-old female was initially diagnosed with hypothyroidism, goiter, and bilateral parotid and submandibular glands enlargement. CT imaging revealed a diffuse goiter which imposed infraglottic airway narrowing and a suspicious left inferior thyroid nodule. Biopsy revealed atypia of undetermined significance. GSC showed a 50% suspicion of malignancy with a negative BRAF. Follow up imaging revealed increased infiltrative masses within the salivary glands, enlarging thyroid gland, and increased infiltration of the superior component of the right thyroid lobe into the submandibular space. A core needle biopsy revealed a background of acute and chronic inflammation without evidence of malignancy. Sjogren's, sarcoidosis and IgG4 diseases were ruled out. She was then referred to us after a myriad of work up. She had a diffusely enlarged goiter with a crusted area of skin over the thyroid gland and significant bilateral parotid swelling. We repeated a thyroid ultrasound which revealed diffusely enlarged and heterogeneous thyroid glands with pseudo-nodules and 3 suspicious nodules greater than 1cm on right and left lobes. She also had prominent reactive lymphadenopathy. Her submandibular glands were hypoechoic, avascular, markedly enlarged and abnormal appearing. She underwent total thyroidectomy. Pathology revealed proliferation of histiocytes, few islands of lymphoid tissue, and eosinophilic micro abscesses without any identifiable thyroid parenchyma in the entire resected specimens. Immunohistochemistry confirmed the diagnosis of Langerhans Cell Histiocytosis with atypical features. BRAF (V600E/V600K) mutation was again not detected. Flow cytometry showed no evidence of neoplastic myeloid blast population. She was referred to an oncologist for further management of LCH. Discussion – Our patient had a remarkably diffuse goiter with a sonographic appearance mimicking Hashimoto's thyroiditis or Riedel's thyroiditis. Initial thyroid FNA failed to reveal LCH. The diagnosis was reached only after total thyroidectomy. Treatment depends on single or multi-system involvement, presence or absence of risk organ involvement, and presence or absence of BRAF mutation. Conclusion In the cases of infiltrated thyroid diseases, Langerhans cell histiocytosis should be on the differential diagnosis, especially if there is concomitant infiltrative process in other organs. The sonographic finding can mimic Hashimoto's or Riedel's thyroiditis which may lead to misdiagnosis and treatment delay. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Head and Neck Langerhans Cell Histiocytosis in Children

Langerhans Cell Histiocytosis (LCH) is a sporadic myeloid neoplasm with proliferation of dendritic cells.1 In the United States, LCH has an estimated annual incidence of approximately 1 per million children.2 Controversy exists regarding management of LCH in head and neck: debridement, chemotherapy, or both. Few reports describe LCH in the OMS literature. The purpose of this study was to present experience with LCH of head and neck in children.This was a retrospective review of children with LCH at Children's Healthcare of Atlanta from 2009 to 2020. A patient was included when he or she: 1) was 18 years old or younger, 2) had LCH in the head and neck, and 3) had complete medical records. Medical records were reviewed for demographic information, lesion characteristics, and clinical presentations. Radiographic images were reviewed for specific findings characteristic of LCH (e.g., osteolytic changes, lymphadenopathy). Treatment regimen (debridement, debridement with chemotherapy, or chemotherapy only) and length of follow-up were recorded. The outcome variable was disease reactivation defined as: 1) a new LCH lesion or 2) an increase in size/recurrence of a lesion after treatment. Data were collected using a standardized collection form. Descriptive statistics were calculated.Overall, 67 patients (42 males) with a mean age of 6.5 years old met inclusion criteria. According to clinical, radiographic, and histological features, there were 3 presentations of LCH in the head and neck: 1) lesions in 1 system without CNS risk (i.e., single system without CNS risk, SS-), 2) lesions in 1 system with CNS risk (i.e., single system with CNS risk, SS+), or 3) multisystem (> 2 systems, MS) presentations. As a group, length of follow-up was on average 3 years (3 months-10.5 years).There were 24 patients (17 males) with an average age of 10 years old (19 months to 18 years) with SS- LCH. Lesions appeared as persistent local swelling (n = 18, 75%) and/or pain (n = 8, 33.3%). Lesions were predominately located in calvaria (n = 15, 62.5%) and mandible (n = 7, 29.2%). Radiographically, most patients had osteolytic changes (n = 18, 78.3%). Patients were treated via debridement (n = 16, 72.7%), chemotherapy (n = 5, 22.7%), or debridement with chemotherapy (n = 2, 9.1%). Three patients (12.5%) experienced reactivation.There were 30 patients (18 males) with an average age of 6 years old (9 month to 15 years) with SS+ LCH. Patients presented with persistent local swelling (n = 21, 70%), recurrent ear infection (n = 5, 16.7%), localized pain (n = 4, 13.3%), or systemic symptoms (n = 2, 6.5%). Radiographic findings were osteolytic changes (n = 24, 77.4%) and/or soft-tissue mass (15, 48.4%). All except 2 patients completed treatment consist of debridement (n = 1, 3.3%), chemotherapy (n = 17, 56.7%), or debridement with chemotherapy (n = 11, 36.7%). One patient (3.3%) who was treated with chemotherapy had disease reactivation.Thirteen patients (9 males) with an average age of 2 years old (1 day to 7 years) had MS LCH. LCH was found in skin (n = 9, 69.2%), lymphatic system (n = 6, 46.2%), and at least 1 bone (range 1-5). In this group, patients presented with extracranial visceral organ involvement on imaging (e.g., hepatosplenomegaly, pulmonary nodules). Patients were treated with chemotherapy (n = 12, 92.3%) or debridement with chemotherapy (n = 1, 7.7%). Six patients (40%) experienced reactivation, and 1 patient passed away during treatment.There are 3 separate categories of LCH in the head and neck. Oral and maxillofacial surgeons who provide care to children would benefit from approaching head and neck LCH based on these categories. A referral to hematology/oncology is necessary for appropriate diagnosis and management.

Langerhans cell histiocytosis in the oral and maxillofacial region: An update.

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by abnormal proliferation and infiltration of histiocytic cells. This review focused on the main aspects associated with LCH. LCH can involve single or multiple organs and systems, with bone and skin being the most commonly affected sites. Regarding skeletal manifestations, the jawbones are involved in about 20%-30% of all cases. Such lesions may present as unilocular or multilocular images mainly affecting the posterior mandible. Oral soft tissue lesions may also occur, with the gingiva and hard palate being the most frequently affected sites. The diagnosis and management of LCH are challenging, requiring a multidisciplinary approach, with dentists playing a central role since oral manifestations can be the first sign of the condition.

Contribution of a Three-Phase 99m Tc-HMDP Bone Scintigraphy Protocol Completed by SPECT-CT Scan in the Diagnosis and Management of Langerhans Cell Histiocytosis of Bones in an Adolescent

Langerhans Cell Histiocytosis (LCH) or Histiocytosis X is a rare disorder of the reticuloendothelial system due to the accumulation of Langerhans cells in the tissues, most often organized into granulomas. The bone is the most affected organ. It can be a single osteolytic lesion or a multi-systemic form with organ dysfunction. We report herein the case of a 15-yearold adolescent male with bone pain in the hip evolving for two months in whom the diagnosis of unifocal bone langerhansian Histiocytosis was confirmed by a triple phase bone scintigraphy supplemented by SPECT CT objectifying a single focus of the disease at the greater left trochanter of the femoral bone without any other pathological bone fixation clearly identifiable on the other parts of the skeleton. This clinical case allows us to clarify the key role of a triple phase bone scan supplemented by SPECT CT in the diagnosis and management of Langerhans Cell Histiocytosis of bone in our context.

Specific Guidelines Including Multidisciplinary Approach Is Critical of Management of Langerhans Cell Histiocytosis in Adults

The knowledge of Langerhans Cell Histiocytosis (LCH) is based on pediatric studies. Adults with LCH are usually treated with pediatric protocols. In 2001, guidelines for adults with LCH (GIMEMA LCH 2001) were proposed, in order to standardize the diagnostic and therapeutic approaches for this category of patients. The aims of this retrospective study are: a) to evaluate the role of a multidisciplinary assessment in adults with LCH, according to the GIMEMA LCH 2001 guidelines, and b) to analyze the results obtained with the GIMEMA LCH 2001 guidelines and those obtained with pediatric protocols. Pts aged >18 years with a diagnosis of LCH (S-100+, CD1a+, CD207+) managed at our Institution since 1985 to 2018 were considered. As diagnostic and treatment approaches, two different strategies were used over time: the GIMEMA LCH 2001 guidelines and the pediatric protocols. The GIMEMA LCH 2001 guidelines included a multidisciplinary diagnostic work-up with complete odontostomatologic, pulmonary and endocrinologic assessments; treatment strategy consisted of: wait and see or local therapy in unifocal single system (SS), indomethacin in bone multifocal SS and vinblastine combined with low-dose prednisone (PDN) in multi-system (MS), PDN in pulmonary honey-combing disease (PHCD) and cladribine in central nervous system involvement. DAL-HX 83 and 90, LCH-I and LCH II were the pediatric protocols utilized over time. Response to treatment was defined as complete (CR) or intermediate (IR). Persistence of the symptoms and/or appearance of new lesions were defined no response (NR). Progression was considered the appearance of symptoms and/or new lesions after initial response. One-hundred-thirty-one LCH pts (females 72, males 59) with a median age at diagnosis of 36 years (range 18 - 71) were considered. Median follow up was 43 months (range 12 - 330). One-hundred-seven patients were managed according to the GIMEMA LCH 2001 guidelines, 16 of them previously treated with a pediatric protocol. Pulmonary and/or oral involvements were identified in 31/107 (29%) and 12/107 (11%) patients, respectively, 5/16 (31%) and 3/16 (19%), respectively, of previously treated asymptomatic patients. Ninety-one newly diagnosed patients (median age at diagnosis: 36 years) were treated according to the GIMEMA LCH 2001 guidelines and 40 (median age at diagnosis: 33 years) were managed with pediatric protocols. All patients treated with the GIMEMA LCH 2001 were evaluable for response. In particular, all patients with SS-LCH achieved a response (100%), that was complete in 20/26 (76.9%) unifocal-SS and in 10/14 (71.4%) multifocal-SS. All but one patient with MS-LCH reached a response that was complete in 22/45 (48.9%). Of 6 pts with PHCD, 5 had a IR and one a CR. No pt presented CNS involvement at initial diagnosis. Thirty-nine of 40 pts managed with pediatric protocols were evaluable for response. All 13 pts with SS-LCH had a response that was complete in 6 (46.1%). Among 26 patients with MS-LCH, 3 of them with organ risk involvement achieved a response, that was complete in 1, while among 23 patients without organ risk, 12 (52.2%), 8 (34.8%) and 3 (13%) had a CR, IR and NR, respectively. Overall, 12 patients were lost to follow-up. Disease progression was recorded in 47/95 pts (49.5%) after a median time of 19 months (range: 6-147 months). The progression-free survival at 43 months was significantly better for patients treated according to the GIMEMA LCH 2001 guidelines compared to those managed with pediatric protocols, 67% (IC95% 53.14 - 80.86%) vs 48% (IC95% 31.37 - 64.63%), respectively (p 0.005). Overall, 7 deaths were recorded, 5 in patients treated with the pediatric protocols. The overall survival at 43 months, was similar in patients managed with the GIMEMA LCH 2001 guidelines and in those treated with pediatric protocols (97.9%, CI 95%: 93.75% - 100% and 97.3%, (IC95% 91.96% - 100%). BRAF V600E mutation was found in 13/35 (37%) evaluable cases. No differences in response and outcome between BRAFV600E-mutated patients and those not-mutated were found. Our experience in a large cohort of LCH adults shows that a multidisciplinary approach is useful in identifying organ involvement in adults, including those asymptomatic. This is critical for an adequate treatment. Moreover, guidelines specific for adults with LCH proved efficacy in improving the outcome in this category of patients. Disclosures No relevant conflicts of interest to declare.

Langerhans Cell Histiocytosis (LCH) in Egyptian Children: Does Reactivation Affect the Outcome?

To report a single centre outcome of management of Langerhans cell histiocytosis (LCH), a clonal disease with involvement of various body systems. Retrospective analysis of 80 pediatric LCH patients at Children Cancer Hospital-Egypt between July 2007 and December 2011 was performed. Patients were stratified and treated according to LCH III protocol. The median follow up period was 42mo (range: 1.18 to 71mo). At wk 6 and 12, 'better' response was obtained in 61 (76%) and 74 (93%) patients respectively. Afterwards, reactivation occurred in 25 patients (38%), of them multiple episodes occurred in 5 patients (6.25%), managed by repetition of 1st line treatment for once or more. The 5y overall survival (OS) and event free survival (EFS) was 96.3 and 55% respectively. At last follow up, better status was reached in 70 patients, 3 in each 'intermediate' and 'worse' status. Three high risk patients died and one patient was lost to follow up. In a single Egyptian pediatric LCH experience, the response to treatment is satisfactory and survival remains the rule except in high risk organs disease that still needs a new molecule for salvage. However in multiple reactivations, patients do well with repetition of the 1st line of treatment with or without methotrexate.

Langerhans cell histiocytosis of thyroid-a diagnostic dilemma.

Langerhans cell histiocytosis (LCH) is a rare disease of antigen presenting cells and involvement of thyroid is really uncommon. The thyroid if involved is usually seen in multisystem disease but isolated thyroid involvement is very rare. The diagnosis of Langerhans cell histiocytosis of the thyroid is very challenging due to its rarity and is usually misdiagnosed as benign goiters, undifferentiated carcinoma, lymphoma, etc. Management of Langerhans cell histiocytosis of the thyroid also remains controversial. Prognosis in an isolated Langerhans cell histiocytosis of the thyroid is usually good but as it may precede a multisystem involvement, prolonged follow-up is required. We present a rare case of Langerhans cell histiocytosis of the thyroid, with variable diagnoses on fine needle aspiration cytology.

Clinical Outcomes of Radiation Therapy in the Management of Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH) is a rare disease with variable clinical presentation. In the present study, we report on the effectiveness and clinical complications of radiation therapy in children with LCH. We retrospectively reviewed all patients with LCH treated with radiation therapy over a 6-decade period at a single institution. Radiotherapy data, clinical features, radiographic data, and vital status were analyzed. The mean age at diagnosis for 69 patients was 5.3 years (3 mo to 37 y) and the median duration of follow-up was 6 years (7 d to 32 y). Radiation therapy was performed for 169 sites, primarily bone lesions. The median radiotherapy dose was 10 Gy (2.5 to 45 Gy). Radiographic follow-up data were available for 139 of the sites treated and clinical follow-up was available for 156 of sites treated. The radiographic local control was 91.4%, and 13% of lesions showed complete sclerosis or reconstitution of bone. A total of 90.4% of patients reported stabilization or improvement in lesion-related symptoms, most often pain. Twelve patients had diabetes insipidus at diagnosis or during follow-up. Eight of these patients received radiation treatment to the pituitary and none experienced a reduction in desmopressin dosage posttreatment. Radiation complications were few, including femoral neck fracture in 1 patient and facial asymmetry in 3 patients. No secondary malignancies were observed. Radiotherapy for LCH has high rates of local control and symptomatic improvement. Importantly, however, there is evidence of short-term and long-term morbidity when children are treated with low-dose irradiation.

Langerhans Cell Histiocytosis of the Orbit

The management of Langerhans cell histiocytosis is controversial. This study evaluated our clinical experience and therapeutic results in orbital Langerhans cell histiocytosis. This is a retrospective, noncomparative interventional case series involving 17 consecutive patients with biopsy-proven orbital Langerhans cell histiocytosis. Response to surgery and chemotherapy and development of diabetes insipidus were the main outcome measures. Thirteen (76.5%) of the patients were male and the mean age at diagnosis was 10.7 years (range 2-39 years). The most frequent presenting sign was proptosis (8 patients) and upper eyelid edema (4 patients). Pain was present in 5 cases and periocular redness in 6. No patient reported a history of trauma. The frontal bone was involved in 16 patients followed by the zygomatic in 9 cases. Five patients also had lesions in the calvarium, femur, facial, temporal, and parietal bones. No patients had systemic disease. Ten patients were managed with vinblastine (0.2 mg/kg, 6-12 months) chemotherapy because of major residual tumor burden (5 cases) and multi-bone involvement (5 cases). Four patients were observed following macroscopically complete tumor removal. Three patients with limited anterior orbital soft tissue tumors and single bone involvement received systemic corticosteroids (40 mg/m2/d, 6-10 weeks). No patients developed diabetes insipidus after a median follow-up of 46 months. Macroscopically complete excision of the unifocal tumors may not necessitate any further treatment. Vinblastine chemotherapy following incomplete tumor removal and in patients with multifocal bone disease resulted in recurrence-free survival at 3 years in 90% of patients.

Comparison of FDG‐PET scans to conventional radiography and bone scans in management of Langerhans cell histiocytosis

We evaluated the effectiveness of FDG-PET scans in identifying sites of active disease and assessing response to therapy in patients with Langerhans cell histiocytosis (LCH). Changes in standardized uptake value (SUV) indicated increased or decreased disease activity before changes are evident by plain films or bone scans. One hundred and two PET scans for 44 patients (41 children, 3 adults) with biopsy-proven LCH were compared with 83 corollary imaging modalities and were rated for overall clinical utility: false positive or negative ("inferior"), confirming lesions identified by another imaging modality ("confirmatory"), or showing additional lesions, response to therapy or recurrence of disease activity ("superior"), in comparison to bone scans, MRI, CT or plain films. FDG-PET was rated superior in that 90/256 (35%) new, recurrent, or lesions responding to therapy were identified via change in standard uptake value (SUV) before other radiographic changes. PET scans confirmed active LCH in 146/256 (57%). FDG-PET was superior to bone scans in that 8/23 (34%) lesions, 11/53 (21%) comparisons to lesions found by MRI, 13/64 (20%) CT, and 58/116 (50%) plain films. PET scans confirmed lesions found by: 14/23 (61%) bone scans, 33/53 (62%) MRI, 45/64 (65%) CT, and 54/116 (46%) of plain films. Whole body FDG-PET scans can detect LCH activity and early response to therapy with greater accuracy than other imaging modalities in patients with LCH lesions in the bones and soft tissues. Whole-body FDG-PET scanning is an important and informative study at diagnosis and for following disease course in patients with LCH.

Successful outcome of Langerhans cell histiocytosis complicated by therapy-related myelodysplasia and acute myeloid leukemia: a case report.

BackgroundVarious therapeutic options are available for the management of Langerhans cell histiocytosis. However, treatment administered to control this disease may be complicated by acute leukemia.Case presentationA 34 years old male was diagnosed to have Langerhans cell histiocytosis in March 1999. Unfortunately, the cytotoxic chemotherapy and radiotherapy given to control the repeated relapses and exacerbations of the primary disease predisposed him to therapy-induced myelodysplastic syndrome which transformed into acute myeloid leukemia. After achieving complete remission of his leukemia, the patient received an allogeneic hematopoietic stem cell transplant. The allograft was complicated by chronic graft versus host disease that was controlled by various immunosuppressive agents and extracorporal photophoresis.ConclusionManagement of complicated cases of histiocytosis requires various therapeutic modalities and a multidisciplinary approach. Having complications of therapy eg myelodysplasia or acute leukemia make the outcome more dismal and the management options limited to aggressive forms of treatment. High dose chemotherapy followed by an allograft may be a curative option not only for therapy-related myelodysplasia/acute leukemia, but also for frequently relapsing and poorly controlled Langerhans cell histiocytosis.

An unusual case of adult disseminated cutaneous Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) represents a group of rare histiocytic syndromes characterized by tissue infiltration with dendritic cells. The management of LCH is difficult because these disorders respond inconsistently to immunosuppressive and chemotherapeutic strategies. We describe a refractory and relapsing case of skin and nail limited LCH in a 27-year-old man. He presented with a 7-year history of an erythematous papular eruption of the scalp, ears, face, trunk, axillae, groins, fingernails, feet, and toenails. Diagnosis of LCH was made based on skin histopathology and immunohistochemical staining. Histological studies of biopsy specimens revealed a dense infiltrate of histiocytic mononuclear cells beneath the epidermis; these cells reacted strongly with anti-S-100 antibodies. In addition, CD1a was positive in most of the infiltrating cells. Extensive investigations failed to detect systemic involvement. The patient's cutaneous eruption did not respond to various therapeutic interventions, including phototherapy with oral psoralen with long-wave UV radiation in the A range (PUVA) and cyclosporine. Marked but temporary clinical improvement was achieved with thalidomide, etoposide with systemic steroid, and total body electron beam radiotherapy. Now the patient is on maintenance therapy with thalidomide and is under acceptable control.

Radiation therapy in the management of langerhans cell histiocytosis

Twenty-two patients with Langerhans cell histiocytosis (LCH) were managed in the UCLA Department of Radiation Oncology from 1974 to 1987. Their median age was 17 years (range 1-42 years) and median followup 4.5 years (range 1-13 years). Fourteen patients had disease localized to a bone (13) or a soft tissue (one). Eight patients had LCH involving multiple bones (3) or soft tissues plus bones (5). Nine of 10 patients less than 19 years old had disease confined to bone(s) compared to 7 of 12 older patients. Fifty-six sites of LCH (40 bone, 16 soft tissue) were irradiated. Pediatric patients received therapy to 15 sites (14 bone, 1 soft tissue) and adults 41 sites (26 bone, 15 soft tissue). Median dose for bone lesions was 900 cGy (range 600-1,500) and for soft tissue 1,500 cGy (range 600-2,600). Local control was achieved in 46 of 56 sites (82%). Control rates for bone and soft tissue lesions were 35 of 40 (88%) and 11 of 16 (69%), respectively. Fifteen of 15 sites in pediatric patients were controlled compared to 29 of 41 (72%) in adults. Ten sites (18%) recurred 10 months to 4 years after irradiation. Recurrences were in-field and noted only in adults with involvement of multiple soft tissues plus bones. All recurrent soft tissue lesions had been treated with orthovoltage. Five patients developed new foci of LCH subsequent to irradiation. Four of these patients had disease involving soft tissues and bones. One patient with progressive LCH initially presented with a single bone lesion. The acute and chronic effects of radiation therapy were minimal. One patient suffered transient enlargement of adenopathy. An elevated serum TSH level was detected 9 years after irradiation of a cervical vertebra in another patient.