Oral-Onset Langerhans Cell Histiocytosis in a Noncompliant Adult: A Cautionary Case of Multisystem Progression.

Multisystemic Langerhans cell histiocytosis in an adult

Spectrum of Second Primary Malignancies in Pediatric and Adult Langerhans Cell Histiocytosis Cases

Treatment Outcome and Prognostic Factors for Adult Langerhans Cell Histiocytosis

7018 Background: Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm driven by MAPK-ERK mutations in majority of patients. Contemporary data on treatments and outcomes in adult LCH are lacking. Hence, we undertook this study to analyze a large cohort of adult LCH patients. Methods: This was a retrospective study of adult (≥18 years) LCH patients seen at our institution between 1998 and 2018. Results: We included 186 patients with adult LCH (median age 43; 19-88), and 54% were females. 70% of patients were diagnosed after 2007. Common presenting symptoms were cough/dyspnea (30%), rash (17%), pain/swelling in head (17%), and diabetes insipidus (10%). 70 (38%) patients had multisystem LCH, 62 (33%) had isolated pulmonary LCH, and 35 (19%) had unifocal LCH. Common sites of involvement included lung (59%), bone (37%), skin (21%), and nervous system (16%). 121 (65%) were smokers; 48% of these had lung disease, while 52% had multisystem disease. 18 of 31 tested (58%) patients had BRAF-V600E mutation. Most common first-line treatment was smoking cessation in 24 patients, and led to an overall response rate (ORR) of 83% in pulmonary lesions. Radiation therapy was used in 11 patients, and led to an ORR 82%. Surgical resection of lesion was done in 23 patients, with relapses in 24%. Systemic therapies were used in 78 (42%) patients (Table). Most common first-line systemic therapy was cladribine with ORR of 78%. Vemurafenib was used in 3 patients with BRAF-V600E, leading to an ORR of 67% . After a median follow-up of 23 months (0-261), 21 patients had died. Of these, 10 died of progressive LCH. Median OS was not reached, and mean OS was 196 months. Conclusions: This is the largest contemporary series of adult LCH. It shows that diverse clinical spectrum, ranging from benign course to a progressive multisystem disease. Although smoking cessation was an effective treatment for pulmonary LCH, a large subset required systemic chemotherapy. [Table: see text]

ObjectivesTo explore the evidence of periodontal manifestations and treatment modalities in patients with Langerhans cell histiocytosis (LCH).Material and methodsA systematic literature search was performed and the criteria for PRISMA and risk of bias assessment were applied. Human clinical studies (≥10 patients) presenting patients with LCH and periodontal findings were considered for inclusion.ResultsFrom 298 titles identified, six case series with a total of 1278 patients suffering from LCH were included. In these studies, oral symptoms were reported in a frequency ranging from 10 to 100%. Overall, in 216 patients (17%), oral symptoms were observed. Out of these patients, 49–100% demonstrated periodontal symptoms. The most common oral findings were pain, swelling, tooth loss/mobility, and bone lesions. Specific periodontal findings comprised varying frequencies of gingival ulcerations, increased pocket depths, and gingival bleeding. Treatment measures constituted of surgical curettage of bone lesions, soft tissue excision and/or tooth extractions, radiotherapy, systemic chemotherapy, or a combination of these approaches. Healing without recurrence of oral lesions was reported in most of the cases.ConclusionsThe available evidence on periodontal manifestations in LCH patients is heterogeneous. Several oral and periodontal findings were reported and may occur as initial symptoms and/or at later stages of the disease.Clinical relevanceThe dentist should be aware of possible oral involvement of systemic diseases such as LCH, and these manifestations may mimic periodontal disease.

Treatment of adult-onset Langerhans cell histiocytosis—is it different from the pediatric approach?

7049 Background: Langerhans cell histiocytosis (LCH) can manifest as single system (SS) disease, multisystem (MS) disease, or pulmonary LCH (smoking-related). There is a paucity of data on prognostic factors including risk organ (RO) involvement (liver, spleen, and bone marrow) in adult LCH, which we sought to address in this study. Methods: Single-center retrospective study of patients ≥18y diagnosed with LCH from 1998 to 2020. Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were conducted using age, sex, organ involvement, LCH subtype, year of diagnosis, BRAF V600E status, and treatments. Results: We included 219 patients with LCH; median age 43y (range 19-88), females 51%, SS unifocal (23%), SS multifocal (6%), pulmonary (31%) and MS (40%). Commonly involved organs included lung (53%), bone (42%), skin (24%), pituitary (16%), and CNS (12%). BRAF V600E was positive in 40/88 (46%). Median follow-up duration was 6.1y (95% CI, 5.1- 7.1). On univariate analysis, factors associated with worse PFS were bone LCH, RO involvement, multifocal/MS LCH, and radiation therapy alone; those with worse OS included RO involvement, MS disease, BRAF V600E+, and age ≥45y at diagnosis. In multivariate analysis, BRAF V600E and age ≥45y at diagnosis were associated with worse mortality (Table). Median PFS was not reached (NR-NR) for SS unifocal LCH, 5mo (0-12.7) for SS multifocal LCH, 110mo (84.7-135.3) for pulmonary LCH, and 27mo (17.2-36.8) for MS LCH. 5-year OS was 97.4% for SS unifocal LCH, 100% for SS multifocal LCH, 96.1% for pulmonary LCH, and 79.9% for MS LCH. 41 (18.7%) developed a second primary malignancy (SPM), of which 11 were hematologic neoplasms. There was a trend towards a higher prevalence of SPMs in patients with BRAF V600E (28% vs. 17%; p = 0.22). Conclusions: In our large single-center study, PFS for multifocal and MS LCH was worse than SS unifocal or pulmonary LCH. RO involvement was not associated with outcomes in multivariate analysis. Overall prognosis was excellent for all subtypes except MS LCH. BRAF V600E and older age were associated with worse OS. The prevalence of SPMs was very high and needs to be explored further.[Table: see text]

Langerhans cell histiocytosis (LCH) is characterized by the proliferation of pathologic Langerhans cells. The disease can develop in any age and can affect almost any organ. Cutaneous involvement is frequent in LCH. The recent demonstration of the activating, oncogenic BRAFV600E gene mutation in LCH samples strongly supports the neoplastic origin of the disease. Our aim was to analyse the clinical data of the patients and whether BRAFV600E mutation is present in skin lesions of patients with adult onset LCH, and to investigate whether the BRAFV600E mutation status has any effect on the clinical presentation and the outcome of the disease. We diagnosed and treated 15 adult LCH patients in the period of 1987-2012 and collected their clinical data. Three of our patients suffered from skin involvement and 12 patients had multiorgan disease (five patients out of the multisystem group died). Eleven formalin-fixed paraffin-embedded skin samples from 10 patients were available for BRAFV600E mutation analysis. Among the 11 examined samples, 6 contained the BRAFV600E mutation (54.5%). Our results indicate that in the adult group of LCH patients the presence of BRAFV600E mutation is similar to what was previously suggested in case of the childhood forms, at least as far as skin lesions are concerned. The BRAF mutation status of our patients does not seem to correlate with the extent and/or the outcome of the disease. Our results support the neoplastic origin of LCH and suggest that skin lesions of LCH are sufficient for the diagnosis of the disease and for assessing its BRAF status. In addition, analysis of BRAF status of patients with LCH can lead to the administration of new targeted therapies which may provide better disease control and prognosis.

Chronic Myelomonocytic Leukemia Associated Adult Langerhans Cell Histiocytosis: A Descriptive and Comparative Study

Clinical Features and Outcomes of Unifocal Adult Langerhans Cell Histiocytosis

Methotrexate and Cytarabine for Adult Patients with Newly Diagnosed Langerhans Cell Histiocytosis: A Single Arm, Single Center, Prospective Phase 2 Study

Dear Editor: Langerhans cell histiocytosis (LCH) is a rare disease and generally affects infants and children. Adult-onset form and generalized cutaneous lesions at presentation without extracutaneous involvement are uncommon. We report an unusual case of generalized adult cutaneous LCH without extracutaneous involvement. The patient was an 81-year-old man who complained of rapidly growing eruptions on the perianal area, groins, axillae, face, and ankles. He stated that the lesions had been present for about 3 months—they first appeared on the perianal area, and then extended rapidly to the groins, axillae, face, and ankles. Physical examination revealed disseminated violaceous papules and plaques on the perianal area, groins, axillae, face, and ankles; the lesions on the perianal area and groins were confluent and ulcerated (Fig. 1). He had no weight loss and no palpable lymphadenopathy or organomegaly. The laboratory results, including complete blood count with differential, liver, and renal function tests, were within the normal range. Bone marrow biopsy examination revealed no evidence of tumor involvement. In addition, a whole body positron emission tomography/computed tomography study showed no involvement of any organ. Histopathologic findings of the lesions showed diffused infiltration of large tumor cells in the dermis, and epidermotropism was appreciated. The tumor cells had a moderate amount of eosinophilic cytoplasm and grooved nuclei consistent with Langerhans cells. These cells were mixed with small lymphocytes, neutrophils, and eosinophils (Fig. 1). The immunohistochemistry staining showed that the tumor cells were diffusely positive for S-100, CD1a, langerin, leukocyte common antigen (LCA), CD4, and CD68, but negative for CD3, CD5, CD20, CD34, CD79a, human melanoma black (HMB)-45, and melan-A (Fig. 2). The Ki-67 proliferating index was approximately 60%. Taken together, these morphological and immunological data were consistent with a cutaneous LCH according to the World Health Organization diagnostic criteria. Fig. 1 (A~C) Multiple, erythematous, rust-colored papules and plaques with erosions distributed on the perianal area, groins, and axillae; (D~F) multiple, erythematous macules and papules on the face and ankle. Fig. 2 (A) Under low-power microscopic examination, the lesion shows diffused infiltration of tumor cells in the dermis (H&E, ×25). (B) The lesion shows infiltration of large tumor cells in the dermis, and epidermotropism was appreciated (H&E, ... After diagnosis of LCH, the patient was referred to an oncologist and received chemotherapy. However, the patient died of myocardial infarction 10 days after being diagnosed with the disease. LCH is a clonal proliferative disorder of Langerhans cells, typically seen in infants and children. Occurrences of LCH in the adult population are rare, but even rarer with the disease limited to the skin1. Compared with LCH in infants and children, adult LCH occurs predominantly in bone and presents mainly as single system disease, with a more chronic clinical course and a better prognosis. The clinical presentation of cutaneous LCH in adults is variable. It can present as papules, plaques, or nodules localized to a single anatomic site or in a generalized distribution. Pruritic papules or nodules of cutaneous LCH may appear similar to prurigo nodularis, and other (non-LCH) papules or ulcers of the external genitalia1,2. Sites most frequently involved include the scalp, trunk, flexural and intertriginous areas, glabrous skin, and external genitalia1. Treatment of cutaneous LCH is controversial. Several therapeutic approaches have been reported in the literature, according to the extent of disease: topical and systemic corticosteroids, topical imiquimod, psoralen plus ultraviolet A (PUVA), thalidomide, interferon-α, vinblastine, and surgery have been used for treating this disease3,4,5.

CAN WE STOP THE POP?

Plasma Biomarker Profiling In Langerhans Cell Histiocytosis: Risk-Stratifying The Inflammatory Storm

444 Cutaneous langerhans cell histiocytosis in adults: Clinical features, disease course, and management among patients treated at the Dana-Farber Cancer Institute between 2003-2017