An Infant with Petechial Rash in Seborrheic Dermatitis Pattern: A Rare Case of Langerhans Cell Histiocytosis

High prevalence of peripheral lymphopenia in Langerhans cell histiocytosis.

Primary Langerhans cell histiocytosis of the lacrimal gland in an adult

Hemorrhagic vesicles in a newborn present a challenging differential diagnosis including both infectious and neoplastic disorders. Patients should be evaluated in an efficient manner to arrive at the correct diagnosis as quickly as possible. We present here an interesting case that outlines the methodical workup that ultimately revealed the diagnosis of congenital Langerhans cell histiocytosis. After a diagnosis of Langerhans cell histiocytosis is made, it is important to evaluate the patient thoroughly for systemic involvement. Historically, the diagnosis of congenital self-healing Langerhans cell histiocytosis was used to delineate a benign self-limited disorder limited to the skin with spontaneous resolution during the first several months of life; this disorder may also be referred to as "self-regressive Langerhans cell histiocytosis." However, some newborns with initial skin-only Langerhans cell histiocytosis progress to have multisystem disease after spontaneous resolution has occurred. For this reason, the nomenclature is changing. We suggest using the term "skin-only Langerhans cell histiocytosis." Periodic long-term follow-up is recommended to monitor for relapse or progression to systemic disease.

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

Extinguishing the TORCH Differential: Evaluation of a Neonate with Blueberry Muffin Rash.

Multisystemic Langerhans cell histiocytosis in an adult

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 Work-shop adopted the term "Langerhans' cell histiocytosis" (LCH) to differentiate it from reactive and neoplastic causes of histiocytosis. 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. 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. 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.

The sonographic (US) findings of unifocal Langerhans cell histiocytosis of the occiput are described. The patient was a 3 year-old girl who presented with a painful soft tissue mass on the scalp. US demonstrated a large soft tissue mass with destruction of the underlying bone. The mass extended through the bony defect and consisted of a solid intracranial component and a predominantly cystic extracranial component. US is not usually associated with the diagnosis of Langerhans cell histiocytosis but in this case it provided valuable information that led to the primary differential diagnosis of Langerhans cell histiocytosis, which was confirmed by bone biopsy at surgery.

Introduction: Langerhans cell histiocytosis (LCH) is a rare disorder of histiocyte proliferation occurring predominantly in children. Previous retrospective and small case studies have suggested higher rates of both hematologic and solid malignancies among LCH patients, possibly due to treatment with tumorigenic agents such as etoposide. Here, we report on our 25-year institutional experience of adult LCH patients with additional malignancies, in an era prior to the widespread use of etoposide. Methods: We identified 170 consecutive patients over 18 years of age who presented with histologically confirmed LCH (S100+, CD1a+) at our center between 1990 and 2015. Demographics and detailed oncologic history was recorded to identify patients with additional malignancies, excluding non-melanoma skin cancers. The Kaplan-Meier method was used to estimate overall survival. Results: Of 170 consecutive adult LCH patients, 62 (36.5%) patients had an additional malignancy. There were a total of 81 malignancies among the 62 patients, with 47 (58%) occurring before LCH diagnosis, 18 concurrent (≤3 months; 22%) with LCH diagnosis, and 16 (20%) after. Fifteen patients presented with 2 malignancies in addition to their LCH diagnosis, and 2 patients presented with ≥3 malignancies. Median age was 65 years (range 28–90) with a median follow-up of 3.5 years (0–22). Median overall survival (OS) was 11.2 years, with 45 (72.5%) alive at last follow-up. The following distribution among lymphomas, other hematologic malignancies, and solid tumors were observed: 10 (12%), 7 (9%), and 64 (79%). The most commonly observed lymphomas included follicular lymphoma (30%), classical Hodgkin's lymphoma (20%), and B-cell lymphoma (20%). Most common hematologic malignancies included acute myeloid leukemia and multiple myeloma (29% each). The most common solid tumor histologies were lung (24%), breast (15%), and colorectal cancer (11%). Conclusions: Our cohort of adult LCH patients demonstrates an exceptionally high number of malignancies. Although our retrospective study is open to referral bias, our findings are consistent with numerous published small retrospective studies and case reports. Other large retrospective studies were performed when etoposide was widely used, and etoposide was suggested as a possible cause for an observed increase in hematologic malignancies after LCH treatment. Yet our study shows an increased prevalence of other malignancies before or concurrent with LCH diagnosis and thus suggests a cause of malignancy independent of LCH treatment. Further exploration of the biology of this rare disease may elucidate the mechanism of increased second malignancies. Keywords: etoposide; histiocytes.

About 100 cases of Langerhans cell histiocytosis (LCH) occur annually in Japan. It predominantly occurs in infants, presenting as multisystem disease or multifocal bone involvement. However, LCH can also occur in adults aged 20 to 40. Single-system skin involvement is rare, with most cases presenting with multisystem disease, including bone lesions, which respond to chemotherapy. In adults, lung lesions that improve with smoking cessation are well-known, although multisystem disease is more common and requires aggressive therapeutic intervention similar to that in children. In some infant cases, progression of liver, spleen, and bone marrow lesions can be difficult to control and can become severe. However, targeted molecular therapies are now available as a lifesaving option. More than 30% of cases of multisystem LCH recur at least once, often leading to long-term complications. In particular, the emergence of central diabetes insipidus, anterior pituitary dysfunction, and central nervous system neurodegenerative disorders several years after the diagnosis of LCH is a unique feature not observed in other diseases. New therapeutic strategies are needed to counter these problems.

Langerhans cell histiocytosis (LCH) (cells identified in 1868, disease named in 1985), has a wide range of clinical presentations, including the rare event of infiltration of the thyroid gland. However, an association seems to exist between LCH and papillary thyroid carcinoma (PTC), as eight cases of LCH co-existing with PTC have been described in the english literature [1]. We extend this association with a metachronous case of PTC, occurring 4 years from the diagnosis of LCH, while the LCH was in remission (Table ​(TableII). TABLE I Time of Presentation of Papillary Thyroid Carcinoma (PTC) in Relation to the Diagnosis of LCH In our case PTC was metachronous and not therapy related. This is verified by the fact that the patient did not receive etoposide or high doses of methotrexate, or local radiotherapy [2,3]. The radiation exposure was minimal; only two X-rays were performed at diagnosis, while imaging of the head was performed with MRI and no CT-scans. Therefore, a causative relationship is highly unlikely. More specifically, a 9-year-old boy, with low risk [RO-]LCH, V600E BRAF mutation positive, received vinblastine/prednisolone according to the LCH III protocol, and achieved remission. Four years following diagnosis of LCH, in the routine follow-up, an 8 mm lesion was revealed in the thyroid gland by ultrasound. Total resection of the thyroid gland revealed a V600E BRAF mutation-negative papillary carcinoma, while it was negative for LCH [SD100−, CD1a−, Langerin−]. No information exists on the V600E BRAF mutation status from the LCH cases co-existing with PTC [1]. In our case, the LCH sample was positive for the V600EBRAF mutation, while the PTC was negative for the mutation. It is possible that LCH and PTC share a common determinant, despite the different BRAF mutation status, as approximately half of the reported cases of LCH are negative for the mutation and only around half of the reported PTCs are positive for the mutation [4]. The role of the V600E BRAF mutation is currently unknown. One could speculate that, since the LCH has been shown to increase the expression of T-helper type 2 cytokines [5], the presence of the V600E BRAF mutation could exacerbate this defect in LCH cytokine regulation. Thus, the particular oncogene might be eliciting an inflammatory pro-tumorigenic microenvironment, possibly linking the LCH-induced deregulated immunologic cascade to neoplastic transformation. It would be of great interest to have more information on the BRAF mutation status from cases of LCH co-existing with PTC, as it would help to elucidate the role of V600E BRAF mutation in PTC development. In summary, the thyroid gland is a potential target organ for LCH, both through direct involvement of the disease and through its association with the development of thyroid carcinoma. Thus, routine evaluation of the thyroid gland at diagnosis and during follow-up should be considered. Further research is needed to understand the association of LCH with PTC, as well as the molecular and immunological basis for this tropism to the thyroid gland.

Langerhans cell histiocytosis (LCH) is a rare disease, and the diagnosis of LCH is mainly based on clinical manifestation, imaging and pathological examinations. But during pregnancy, imaging examinations especially play an important role in the diagnosis and prognostic assessment of fetal LCH. Up to now, there has been no report about magnetic resonance imaging (MRI) features of fetal LCH. We reported a 32-year-old woman at 36 weeks' gestation took fetal MRI because of fetal anomalies diagnosed by ultrasonography. On the fetus's MR images, the thymus was slightly enlarged with smooth or lobulated contour in supra anterior mediastinum, displayed heterogeneous signals and contained multiple small cysts on T2WI. Innumerable irregular nodules and patchy shadows were present throughout both lungs. Pulmonary lesions were bilateral and diffuse with relative sparing of the costophrenic angles. The margins of these lesions were fluffy and indistinct. These lesions showed heterogeneous signals on T2WI. MRI showed no lesions in skin region. After birth, lots of round or oval skin lesions distributed all over the baby's body presenting as ulcerated or blister-like rashes. The chest computer tomography (CT) showed punctate calcification and heterogeneous enhancement in the thymus and bilateral diffuse reticular or reticulonodular opacities in both lungs with fluffy and indistinct margins. Pathological finding was consistent with LCH. Through reporting MRI features of LCH in one fetus, this study aims to improve awareness of fetal LCH in radiologists and clinicians, to improve the prenatal diagnostic rate of this disorder.

Bronchoscopic diagnosis of Langerhans cell histiocytosis and lymphangioleiomyomatosis

Background Limited number of studies have been reported regarding the utilization of F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission tomography/computed tomography (F-18-FDG PET/CT) in Langerhans cell histiocytosis (LCH). The aim of this study was to assess the role of F-18-FDG PET/CT in the diagnosis and treatment of LCH. Methods Eight newly diagnosed and seven recurrent patients with LCH received F-18-FDG PET/CT scans. The diagnosis of LCH was established by pathology, multi-modality imaging, and clinical follow-up. Results F-18-FDG PET/CT was positive in 14 patients with 13 true positives and one false positive. All 45 LCH lesions were F-18-FDG avid including six small bone lesions <1.0 cm in diameter. The mean maximal standardized uptake value (SUVmax) was 7.13±4.91. F-18-FDG uptake showed no significant difference between newly diagnosed lesions vs recurrent lesions (SUVmax: 6.50±2.97 vs. 7.93±6.60, t=-0.901, P=0.376). Among 45 LCH lesions, 68.9% (31/45) were found in bones and 31.1% (14/45) in soft tissue. The most commonly involved bones were the pelvis and vertebrae. There was no significant difference in F-18-FDG uptake between bone lesions vs. non-bone lesions (SUVmax: 6.30±2.87 vs. 8.97±7.58, t=1.277, P=0.221). In two patients, changes in F-18-FDG uptake on serial PET/CT scans reflected response of lesions to treatment. Conclusions The present study suggests that F-18-FDG PET/CT may be useful for diagnosis and assessing the treatment response of LCH. Because of the small sample size, further research is warranted to confirm our findings.

Major response to vemurafenib in patient with severe cutaneous Langerhans cell histiocytosis harboring BRAF V600E mutation