Inflammatory Neoplasia Research Articles

Persistent purple erythematous rash: Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is an uncommon yet serious inflammatory neoplasia that frequently affects children. Skin and bone manifestations are frequent and may be isolated or associated with visceral or systemic disorders. Diagnosis is clinicopathologic, established upon typical clinical findings and immunohistochemical and histological analyses of a biopsy taken from the lesions. Prognosis depends on onset age and the quantity of affected organs. Treatment is often necessary for LCH if systemic involvement exists. Herein, we report a rare case of multifocal LCH of late onset. Key words: Histiocytosis, Langerhans cell histiocytosis, Inflammation, Systemic manifestations

The baseline metabolism parameters of 18F‑FDG PET/CT as promising prognostic biomarkers in pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare myeloid precursor cell inflammatory neoplasia, which agonizes, maims, and even kills patients. Although clinical outcomes have steadily improved over the past decades, the progression/relapse rate of LCH remains high. The purpose of this study was to evaluate the prognostic value of the pre-treatment metabolism parameters of baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F‑FDG PET/CT) in children with LCH. This cross-sectional study retrospectively and consecutively included 37 children (24 males and 13 females; median age, 5.1 years; range, 2.4-7.8 years) with pre-treatment 18F-FDG PET/CT from September 2020 to September 2022 in Nuclear Medicine Department, Beijing friendship hospital, Capital Medical University, Beijing, China. These patients were then all admitted to the hospital and diagnosed with LCH by biopsy, in Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China. Five metabolism parameters of 18F-FDG PET/CT were analyzed, including maximum standardized uptake, tumor-to-normal liver standard uptake value ratio, tumor-to-normal bone marrow standard uptake value ratio, sum of metabolic tumor volume (sMTV), and sum of total lesion glycolysis (sTLG) of all lesions. Patients were followed up for at least 1 year or until disease progression/relapse. Univariate and multivariate analyses of progression-free survival was performed. During follow-up, 11 (29.7%) patients had disease progression/relapse. Univariate analysis revealed that the risk organ involvement, the treatment response at the 5th or 11th week, pre-treatment sMTV, and sTLG were significantly associated with progression-free survival (P=0.024, 0.018, 0.006, 0.006, and 0.042, respectively). Multivariate COX analysis revealed that non-response at the 11th week, pre-treatment sMTV >32.55 g/cm3, and sTLG >98.86 g (P=0.002, 0.020, 0.026, respectively) were risk factors for progression-free survival. The baseline metabolism parameters of 18F-FDG PET/CT could be promising imaging biomarkers for predicting prognosis in children with LCH.

Langerhans cell histiocytosis: a rare cause of exudative enteropathy in a young child

Exudative enteropathy is a clinical syndrome characterized by excessive loss of proteins through the gastrointestinal tract and is a rare complication of various gastrointestinal diseases. One of the rarest causes of protein malabsorption is Langerhans cell histiocytosis, which occurs as a result of inflammatory neoplasia of myeloid precursor cells caused by mutations in the mitogenactivated protein kinase pathway. Abnormal proliferation and accumulation of Langerhans cells in the intestinal wall leads to a violation of the outflow of lymph, and causes clinical manifestations characteristic of enteropathy. Given that the lesion of the gastrointestinal tract with histiocytosis from Langerhans cells occurs in 2–3% of cases, and the clinical signs are not highly specific, timely diagnosis is difficult. Delayed verification of the diagnosis and late initiation of adequate treatment are risk factors for multisystem lesions and lead to an unfavorable outcome. The literature describes a few observations of the onset or manifestation of the disease with symptoms of protein malabsorption. We present a rare clinical case of diagnosing histiocytosis from Langerhans cells in a young child with severe manifestations of exudative enteropathy at the onset. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.Refractory gastrointestinal symptoms require mandatory endoscopic and histological examination to identify rare causes of malabsorption. Timely initiation of targeted therapy with vemurafenib in combination with subsequent chemotherapy provided the child with a favorable prognosis and stable remission of the disease.

Extensive cranial langerhans cell histiocytosis revealed by acute mastoiditis

Langerhans cell histiocytosis is a group of diseases characterized by an inflammatory neoplasia of myeloid precursor cells driven by mutations in the mitogen-activated protein kinase pathway leading to the proliferation and accumulation of Langerhans cells [1,2]. Clinical manifestations range from isolated disease to multifocal lesions and systemic involvement with a worse prognosis [2,3]. The otologic features are rare and may include otorrhea, otalgia, subjective hearing loss and vertigo misleading the diagnosis to an inflammatory process [3]. The CT scan shows destruction of the skull with characteristic “punched out” lytic lesions that can be multiple and multifocal. Tissue biopsy confirms the diagnosis [3].

Adult Langerhans Cell Histiocytosis and the Skeleton.

Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia in which somatic mutations in components of the MAPK/ERK pathway have been identified. Osseous involvement is evident in approximately 80% of all patients and may present as a single osteolytic lesion, as a multi-ostotic single system disease or as part of multisystem disease. Both exogenous, such as treatment with glucocorticoids, and endogenous parameters, such as anterior pituitary hormone deficiencies and inflammatory cytokines, may severely affect bone metabolism in LCH. Computed tomography (CT) or magnetic resonance imaging (MRI) are usually required to precisely assess the degree of bone involvement; 18F-fluorodeoxyglucose (FDG) positron emission tomography—CT can both detect otherwise undetectable LCH lesions and differentiate metabolically active from inactive or resolved disease, while concomitantly being useful in the assessment of treatment response. Treatment of skeletal involvement may vary depending on location, extent, size, and symptoms of the disease from close observation and follow-up in unifocal single-system disease to chemotherapy and gene-targeted treatment in cases with multisystem involvement. In any case of osseous involvement, bisphosphonates might be considered as a treatment option especially if pain relief is urgently needed. Finally, a patient-specific approach is suggested to avoid unnecessary extensive surgical interventions and/or medical overtreatment.

Mitogen-activating protein kinase pathway alterations in Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the infiltration of involved tissues by specialized dendritic cells. The demonstration of the constant activation of the mitogen-activated protein kinase (MAPK) pathway in LCH lesions has been a breakthrough in the understanding of the pathogenesis of this rare disease. We will summarize the current knowledge on MAPK alterations in LCH and the new therapeutic options indicated by these findings. Since the description of the B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E mutation in LCH lesions, several other molecular alterations affecting the MAPK pathway have been identified in most cases. Based on these driver alterations, LCH cells were shown to be derived from hematopoietic precursors, which yielded the current concept of LCH as a myeloid inflammatory neoplasia. MAPK pathway inhibitors have emerged as an innovative therapy in severe forms of LCH, resulting in virtually no acquired resistance. However, although they are highly effective, their effect is only temporary, as the disease relapses upon discontinuation of the treatment. LCH is an inflammatory myeloid neoplastic disorder, driven by mutations activating the MAPK pathway. MAPK-targeted treatments represent an important stepforward in the management of patients with severe progressive LCH.

Langerhans cell histiocytosis: A great imitator

Langerhans cell histiocytosis (LCH) is an uncommon but serious inflammatory neoplasia that affects many organs, including the skin. Though uncommon, it should remain high on a clinician’s differential diagnosis in treatment-resistant cases of conditions, such as seborrheic dermatitis, diaper dermatitis, arthropod bites, and many more. A thorough history nd physical examination for each patient can aid in the diagnosis; however, if clinically suspicious for LCH, a punch biopsy should be performed. Histologic evaluation of LCH is often enough to differentiate it from the many clinical mimickers. Characteristic findings include a histiocytic infiltrate with “coffee bean”–cleaved nuclei, rounded shape, and eosinophilic cytoplasm. Immunohistochemical stains, including CD1a, S100, and CD207 (langerin) are often needed for a definitive diagnosis. Electron microscopy also demonstrates the ultrastructural presence of Birbeck granules, but this is no longer needed due to immunohistochemical staining. Treatment is often necessary for LCH, if systemic involvement exists.

Head and neck Langerhans cell histiocytosis: two case reports and review of the literature

Langerhans cell histiocytosis (LCH) is an inflammatory neoplasia of myeloid precursor cells driven by mutations in the mitogen-activated protein kinase (MAPK) pathway. It can present as single or multisystem LCH. It occurs in 0.5–5.4 per million people. While it can occur at any age, it is more common in children, predominantly males, under the age of 4 years. The unifocal single system variety is the most prevalent and least aggressive presentation, making up to 70% of cases. It can affect bone (80%), lymph nodes (5–10%) or lungs (15%). The mandible and sphenoid are the least common locations; therefore, when present, it could be easily mistaken for a variety of pathologies. Depending on the clinical features, treatment can range from simple observation to chemotherapy and/or radiation. We present 2 cases of unifocal single system LCH located at the mandible and skull base, and describe the diagnostic work up and treatment.

Follicular dendritic cell tumor of the gastrointestinal tract: Report of a rare neoplasm and literature review

Follicular dendritic cell (FDC) tumor is a rare neoplasm of the accessory immune system showing FDC differentiation. Histologically, a conventional type and an inflammatory pseudotumor (IPT-like) type are recognized. The etiology of FDC tumor is unknown. While rare FDC tumors were associated with hyaline-vascular Castleman's disease (HVCD), hepatosplenic IPT-like FDC tumors consistently harbor EBV infection. FDC tumors of the gastrointestinal (GI) tract and mesentery/omentum are exceedingly rare, with only 17 cases reported so far. We report an additional case of an IPT-like FDC tumor of the ileum and mesentery in a 52-year-old schizophrenic man. The tumor consisted of highly atypical multinucleated giant cells in a background of intense lymphoid infiltrate with prominent eosinophilia reminiscent of Hodgkin's lymphoma. Tumor cells were immunoreactive for vimentin, CD21, CD35, fascin, smooth muscle actin and CD68, but were negative for all lineage-specific lymphoreticular, myeloid, mesenchymal and epithelial markers. Immunostaining for HHV-8 and in situ hybridization for EBV-encoded RNA (EBER) were negative. Some mesenteric lymph nodes showed HVCD-like changes. The differential diagnostic considerations of this unusual and rare neoplasm, mainly lymphocyte-rich GI stromal tumor (GIST), malignant lymphoma and inflammatory neoplasia of diverse histogenetic types, will be discussed together with a literature review on gastrointestinal FDC tumors.