Langerhans cell histiocytosis (LCH) is a heterogeneous neoplastic disorder that is rarely seen in patients aged 60 years and older. It is reported that elderly patients with LCH have a higher chance of having malignancies. In the oral cavity, patients with LCH can present with mucosal ulcers and extensive osteolysis, making it difficult for clinicians to make a proper diagnosis.
We reported an 82-year-old Chinese woman with oral symptoms as the first presentation of LCH, and eventually developed acute myeloid leukemia (AML). She suffered diffuse ulcers involving the entire gingival mucosa and the left half hard palate, and had lost several teeth. Genomic DNA sequencing of the cells from LCH revealed multiple mutations in TET2, BRAF, SRSF2, NRAS, MAP2K4 and so on. The patient declined the BRAFV600E inhibitor (Vemurafenib). Although a dramatic improvement of the oral ulcers was achieved after symptomatic treatment, the patient developed acute myeloid leukemia (AML) and died.
This report presented the diagnostic difficulties of LCH with oral manifestations and highlighted the importance of radiological assessments and laboratory tests. Moreover, many of the mutations detected in our LCH patient are frequently seen in AML, suggesting that AML and LCH cells in this patient share the same origin.

OBJECTIVE: To present a rare disease, and to point out that clinical manifestations treated for a long period of time without an adequate response to therapy may be a manifestation of a rare disease.
METHODS: We present the case of a 3-year-old girl who had been drinking a large amount of water for the previous ten days with frequent urination, and who experienced the worsening of symptoms of scalp dermatitis that had been treated for a year without success. Physical examination revealed a maculopapular rash on the scalp, neck and both ear shells, and exophthalmos of the right eye with periorbital edema. Magnetic resonance imaging of the orbits showed extensive lesions of the skull bones. Further diagnostic evaluation revealed similar lesions in other bone structures. Biopsy of the affected region, microscopic and immunohistochemical analysis led to diagnosis of Langerhans cell histiocytosis.
CONCLUSIONS: Langerhans cell histiocytosis mostly occurs in the first three years of life. The incidence is 4-5 patients per million children under 15 years of life. The clinical presentation is highly variable, and can range from isolated, self-healing skin and bone lesions to life-threatening multisystem diseases. Due to the diverse clinical picture, that is often unrecognized, these patients are often referred to other specialists, resulting in the treatment of individual symptoms rather than the underlying disease.

Histiocytosis comprises a heterogeneous group of inflammatory diseases whose main cellular components are dendritic cells and macrophages. The inflammatory infiltrate can affect the skin and other organs and the clinical outcome varies from mild to fatal depending on the involved cell subset and multisystemic compromise. Delay in diagnosis may occur due to its non-specific presentation and to a low suspicion on the part of the clinician. We report the case of an infant who despite multiple consultations with nonspecific but characteristic symptoms of the disease was only finally diagnosed thanks to histopathological findings.
La histiocitosis de células de Langerhans comprende un grupo heterogéneo de enfermedades inflamatorias cuyos principales componentes celulares son las células dendríticas y los macrófagos. El infiltrado inflamatorio puede afectar la piel y otros órganos, y el resultado clínico varía de leve a letal, dependiendo del subconjunto de células involucradas y el compromiso multisistémico. La demora en el diagnóstico puede ocurrir debido a su presentación inespecífica y a que los médicos tratantes no suelen sospecharla. Se reporta el caso de una lactante mayor a la cual, a pesar de múltiples consultas con síntomas inespecíficos pero característicos de la enfermedad, solamente se le pudo hacer el diagnóstico gracias a los hallazgos histopatológicos.

Eosinophilic granuloma is an unusual benign disease that usually affects the pediatric population and young adults. It is the most benign of the diseases traditionally known as histiocytosis X that are now called Langerhans cell histiocytosis.
Pediatric patient with a painful lump in the temporal region. The imaging tests carried out reveal the existence of an osteolytic lesion with an aggressive pattern compatible with eosinophilic granuloma. The patient underwent surgery with a conclusive definitive histological diagnosis of eosinophilic granuloma.
Eosinophilic granuloma can affect one or multiple bones, of which the most frequent are the cranial bones, epiphyses of long bones and ribs, requiring individualized diagnosis and treatment strategies for optimal management and results, with surgical treatment of First choice.
Eosinophilic granuloma is an infrequent benign condition that requires a correct anamnesis and clinical examination of the patient, as well as the demonstration of the characteristic radiological images, allowing a generally accurate presumptive diagnosis to be reached that in most cases can be considered definitive.
El granuloma eosinófilo es una enfermedad benigna poco usual que suele afectar a la población pediátrica y adultos jóvenes. Es la afección más benigna de las enfermedades tradicionalmente conocidas como histiocitosis X que en la actualidad reciben la denominación de histiocitosis de células de Langerhans.
Paciente pediátrico con bultoma doloroso en región temporal. Las pruebas de imagen realizadas ponen de manifiesto la existencia de una lesión osteolítica con patrón de agresividad compatible con granuloma eosinófilo. El paciente es intervenido mediante cirugía con diagnóstico histológico definitivo concluyente de granuloma eosinófilo.
El granuloma eosinófilo puede afectar a uno o múltiples huesos, de los cuáles los más frecuentes son los huesos craneales, epífisis de huesos largos y costillas, precisando estrategias de diagnóstico y tratamiento individualizadas para un manejo y resultado óptimo, siendo el tratamiento quirúrgico de primera elección.
El granuloma eosinófilo es un cuadro benigno infrecuente que requiere de una correcta anamnesis y exploración clínica del paciente, así como la demostración de las imágenes radiológicas características, permitiendo llegar a un diagnóstico de presunción generalmente certero que en la mayoría de ocasiones se puede considerar definitivo.

Smoking-associated interstitial lung disease manifests as several heterogeneous disorders involving the airways, pleura, and lung parenchyma with various radiological patterns. The clinical history, radiologic, and pathologic findings are important to distinguish these more uncommon diseases. A multidisciplinary approach is recommended for diagnosis and to manage these conditions appropriately.
This review provides an overview of the epidemiology, risk factors, pathogenesis, clinical features, diagnosis, and treatment of acute eosinophilic pneumonia, e-cigarettes, or vaping associated lung injury, respiratory bronchiolitis interstitial lung disease, desquamative interstitial pneumonitis, pulmonary Langerhans cell histiocytosis, idiopathic pulmonary fibrosis, and combined pulmonary fibrosis emphysema.
Cigarette smoking is associated with a variety of pathologic conditions that affect the airways and lungs. E-cigarette use and vaping present new challenges to the clinician. Consensus between the clinical, radiographic, and pathologic findings is important in identifying and differentiating between the various entities to properly diagnose smoking-related interstitial lung diseases discussed in this review.

Bone necrosis of the jaw is a serious condition with a broad differential diagnosis of pathologies such as cutaneous histiocytosis, bone metastases or malignant tumours. In addition to the most common cause, medication related osteonecrosis of the jaw (MRONJ), one must consider a number of other causes, such as histiocytosis. Langerhans cell histiocytosis (LCH) is a histiocytic disorder with a large spectrum of clinical manifestations and with possible involvement of a variety of organs. This case shows the importance of an early detection of this rare disease in order to prevent further spreading. Even if an initial diagnosis in the oral cavity is rare, dentists should be aware of this disease.
The presented case describes a patient who was referred for evaluation and treatment due to exposed bone and extensive osteolysis in the region of the upper and lower jaw. After biopsy and diagnosis of LCH, the patient was treated with systemic therapy, achieved remission and is disease free after a 2 year of follow up.
This case report illustrates that when dealing with unclear osteolytic changes of the jawbone, Langerhans cell histiocytosis must be taken into consideration in the differential diagnosis and biopsy must be performed in case of suspicion.

UNASSIGNED: Langerhans cell histiocytosis (LCH) is a rare histiocytic proliferative disorder of unknown etiology and mainly affects young children. The histological feature is granuloma-like proliferation of langerhans-type dendritic cells. Although the possible role of viruses such as Epstein-Barr virus (EBV, Human Herpes virus -4), Human Herpes virus-6 (HHV-6), Herpes Simplex virus (HSV) types 1 and 2 and Cytomegalovirus (CMV, Human Herpes virus-5) is suggested in the pathogenesis of LCH by some investigators, its exact pathophysiology has not been cleared yet. In this study, we investigated the presence of HSV types 1 and 2 in Iranian children with LCH.
UNASSIGNED: In this retrospective study, we investigated the prevalence of presence of HSV types 1 and 2 (in 30 patients with LCH), using paraffin-embedded tissue samples and 30 age and tissue-matched controls (operated for reasons other than infectious diseases) from the Department of Pediatric Pathology, Tehran, Iran, by nested Polymerase Chain reaction method. No ethical issues arose in the study, because only the pathology reports were reviewed and patients were anonymous.
UNASSIGNED: We failed to find HSV types 1 and 2 DNA in any of the 30 patients with LCH or the control group.
UNASSIGNED: According to our findings, HSV types 1 and 2 do not appear to have any etiologic role in the pathogenesis of LCH in Iranian children. These results are in accordance with previous investigations with negative findings.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare histiocytic proliferation of unknown etiology. It is characterized by granuloma-like proliferation of Langerhans-type dendritic cells and mainly affects young children. Although multiple investigators have suggested the possible role of viruses, such as Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), Herpes simplex virus (HSV) types 1 and 2, and Cytomegalovirus (CMV) in the pathogenesis of LCH, it remains, however, debated.
OBJECTIVE: The EBV infection is reported to be associated with LCH. Nevertheless, no report could be found about involved Iranian children in English medical literature. In this study, we investigated the presence of EBV in Iranian children with LCH.
METHODS: In this retrospective study, in which we investigated the prevalence of presence of EBV DNA in LCH, using paraffin-embedded tissue samples of 30 patients with LCH and 30 age and tissue-matched controls, who were operated for reasons other than infectious diseases (between the years 2002 and 2012), by real-time polymerase chain reaction (RT-PCR) method, in the department of pediatric pathology. No ethical issues arose in the study, because only the pathology reports were reviewed, retrospectively, and the patients were anonymous.
RESULTS: There was a significant difference in prevalence of EBV presence between patients and controls. The EBV was found by RT-PCR in 19 (63.33%) out of 30 patients and only in eight (26.7%) of 30 control samples. The P = 0.004, was calculated using chi-square test (OR: 4.75; 95% CI: 1.58 ‒ 14.25).
CONCLUSIONS: Our study is the first investigation performed on patients with LCH and its possible association with EBV in Iran. Considering the P = 0.004, which is statistically significant, the findings do support the hypothesis of a possible role for EBV in the pathogenesis of LCH. These results are in accordance with several previous investigations, with positive findings.

OBJECTIVE: To improve the level of \'definitive\' diagnosis of Langerhans cell histiocytosis by immunohistochemical investigation of the CD1a surface antigen and to compare outcomes in respect to age, gender, stage of the disease, treatment response and level of diagnostic accuracy.
METHODS: A retrospective study was carried out of 37 children and adolescents with possible Langerhans cell histiocytosis between 1988 and 2008. The diagnoses were revisited using immunohistochemical investigations for CD1a, S-100 and CD68 in an attempt to reach definitive diagnoses for all cases.
RESULTS: Before the study, only 13 of 37 patients (35.1%) had a \'definitive\' diagnosis; by the end of the study, this number rose to 25 patients (67.6%). All reviewed cases were positive for the CD1a antigen. Overall survival was 88.5%. Multisystem disease (Stage 2; n=19) and absence of response at the 6th week of therapy (n=5) were associated to significantly lower overall survival (p-value = 0.04 and 0.0001, respectively). All deaths occurred in patients with multisystem disease and organ dysfunction at diagnosis. Other potential prognostic factors were not significant. Reactivation episodes occurred in 75% of the patients with multisystem disease. Diabetes insipidus was the most common sequel (21.6%).
CONCLUSIONS: The level of diagnostic accuracy was increased through immunohistochemistry. The overall survival rate was similar to international multicentric studies. Multisystem disease and absence of response at six weeks of treatment were the most important unfavorable prognostic factors. The frequency of reactivation for patients with multisystem disease was higher than described in the literature, probably because maintenance chemotherapy was used only in two cases.