A historical review of Langerhans cell histiocytosis
Langerhanscell histiocytosis (LCH) is a disease in which abnormal proliferation of Langerhans cells results in multi-organ involvement. LCH, formerly known as histiocytosis X, is the first of a group of histocytic proliferative disorders (histocytic proliferative) characterized by the proliferation of Langerhans cells causing damage to multiple tissues and organs, and is distinct from the second class (class II) of infectious phagocytosis syndrome (IAHS), familial phagocytic lymphoid hyperplasia ( FEL) sinus histiocytosis with massive lymphadenopathy, histiocytic necrotizing lymphadenitis, and class III (malignant histiocytic hyperplasia, acute monocytic leukemia, and true cell lymphoma).
LCH is commonly seen in children. It is a group of syndromes with an unknown etiology and a wide variation in the onset, clinical symptoms and extent of lesions. It was initially thought to be three separate diseases, namely Letterer-Siwe disease (LS), Hand-Schuller-Christian disease (H-S-C), and eosinophilic granuloma of bone ( eosinophilicgranuloma of bone (EGB). Because of the commonality or overlap in clinical manifestations, affected parts, and pathology of these diseases, especially the phenomenon of histiocytosis, in 1953 Lichtenstein referred to these three diseases collectively as histiocytosis X (HX). in 1973, Nezelof reported the course of HX as a pathologic Nezelof reported in 1973 that the process of HX was the result of abnormal proliferation and dissemination of histiocytes a Langerhans cells locally or systemically, and that Birbeck granules, which are only found in Langerhans cells, were found in these cells by electron microscopy. Histochemical staining and antigen expression studies also demonstrated that the HX proliferating histiocytes were in fact Langerhans cells. Therefore, in 1985, the International Histiocyte Society recommended LCH instead of HX, as proposed by the Minnesota Research Group.
LCH can develop at any age and is more common in children, with the peak age of diagnosis being 1-3 years. In recent years, advances in chemotherapy have led to significant improvements in the prognosis of this disorder. The prognosis is directly related to the site of involvement, the number of LCH cells and the presence of organ dysfunction. Traditionally, it is classified into 3 types according to the site of involvement.
①HSC: Commonly seen in children aged 2-6 years, involving multiple sites in one system, most often bone, with head swelling with proptosis, enuresis, and fever as the main manifestations, also accompanied by rash, hepatosplenomegaly, and anemia.
②LS: Commonly seen in boys aged 3 months-3 years, involving multiple systems, with fulminant, multifocal, multi-organ lesions. The most common symptoms are rash and fever, followed by cough, pallor, malnutrition, diarrhea and hepatosplenomegaly.
(iii) EGB: Commonly seen in children 2-5 years of age and adults, it is a single lesion with restrictive changes, usually osteolytic damage to bone (especially the skull, femur, pelvis and ribs), and in rare cases involving the lymph nodes, skin or lungs, which can be secondary to neurological symptoms.
The medical understanding of the complex disease is constantly evolving, and different researchers have reported separately on certain manifestations of LCH and have named the disease by their respective names. The pathological process of LCH has gradually become clearer as later generations of scholars continue to generalize and summarize.
Historical review of LCH.
In 1865, Thomas Smith admitted a 4.5-year-old child with impetigo with three defects in the skullcap, who was soon cured of impetigo but died of whooping cough 2 months later. Based on the manuscript drawn, this case is now considered to be the earliest recorded patient with LCH.
The disease was first reported in detail in 1892 by Alfred Hand (1868-1949), who, while a resident at the Children’s Hospital of Philadelphia, encountered a case of a 3-year-old boy who presented with irritable thirst and polyuria, and on physical examination was found to have proptosis and hepatomegaly and splenomegaly, and who died after ineffective treatment. Autopsy revealed macular deposits of focal osteochondrosis visible near the right parietal bone and medial to the parietal bone. In 1915, Arhur Schuller (1874-1957), who worked in the laboratory of the Radiology Center of the Vienna General Hospital, reported two similar cases and described geographic skull signs seen radiologically, one of which had a One of them had a tendency to self-limit, and x-ray examination a few months later revealed a reduction in the cranial defect. In 1919, Herlry Asbury Christian (1876-1951), an internist who was a major in the U.S. Army Medical Reserve, reported another case of a 5-year-old girl with a triad of cranial defects, proptosis, and enuresis, and attributed the polyuria to functional involvement of the pituitary gland, which was controlled by subcutaneous injection of pituitary extract. Since 1921, Hand has referred to any person with the triad of osteodystrophy, proptosis and enuresis as HSCD. 3 cases were reported in China in 1957 by Pan Suying.
In 1924, Erich Letterer, a research assistant, reported a case of severe systemic disease in a 6-month-old infant with hepatomegaly, splenomegaly, anemia and purpura-like rash, who died 4 days after hospitalization. Sture Siwe, a pediatrician working as a research assistant, reported a case of a 16-month-old infant with enlarged liver, spleen, and lymph nodes with bone swelling, hemorrhagic tendency, and secondary anemia, with non-lipid storage like macrophage proliferation seen in all organs, and he also reviewed 2 other cases in the literature, which led him to conclude that the disease was a clinical manifestation of systemic reticuloendothelial hyperplasia. 1936 This type of disease was first described as LSD and was reported in China by Hu Yonglin et al. in 1952.
In 1935, Fraser described in detail the histological changes of several limited lesions, and in 1940, Lichtenstein et al. referred to this isolated lesion as “eosinophilic granuloma of bone”. It was first reported by Gao Tianyu et al. in 1958.
In 1941, Sidney Farber reported that a group of patients with these characteristics had rapid healing after surgery or radiotherapy, thus suggesting that HSCD, LSD, and the osteosarcoma reported by Lichtenstein and Jaffe a year earlier were different subtypes of the same disease.
In view of the similarity of the underlying pathological changes, in 1953 Louis Lichtenstein clearly proposed that the above-mentioned clinicopathological features were in fact manifestations of different types or stages of development of the same disease, and in his classic treatise he referred to these types collectively as “histiocytic proliferative disorder X”. X refers to a disease whose The etiology of the disease is unknown and the pathogenesis is not fully understood.
In 1868, Langerhans stained skin sections with gold chloride and found a type of dendritic cell in the epidermis, later called Langerhans cell, but the nature of this cell was unknown for a long time. In 1973, Christian Nezelof and colleagues further suggested that the cells responsible for the pathological process of histiocytosis X were the dendritic cells described by Langerhans 100 years earlier and examined them with electron microscopy to find the dendritic cells in Birbeek granules were found in these cells. In this way, the disease was named after Langerhans, even though it was never reported by Langjun.
In 1987 the International Histiocyte Society Writing Group recommended that all histiocytic syndromes be divided into three categories and renamed histiocytosis X as Langerhans cell histiocytosis.
Langerhans profile.
Paul Wilhelm Heinrich Langerhans (also known as Langerhans and Langerhans) was born in Berlin on July 15, 1847, to a physician. When Langerhans was 6 years old, his mother died of tuberculosis. He came to Jena (Jena) after graduating from high school at the age of 17 and began his medical education under Ernst Haeckel, then continued his studies under Cohnheim and Virchow at the University of Berlin. While still a medical student, he described the dendritic cells in the epidermis in a report published in 1868. In 1867, he was awarded a scholarship to the medical school of the University of Berlin for his work on the fine structure of the rabbit pancreas under the supervision of the famous pathologist Virchow. He discovered that among the pancreatic enzyme-secreting cells there were additional cells with unique morphological characteristics, but it was not possible to determine the function of these cells. After his death, the French histopathologist Edouard Laguesse discovered a similar group of cells in humans and named them islets of Langerhanss (islets of the pancreas).
Langerhanss also studied the clinical features of leprosy during his expedition to the Middle East in 1870. He served in the army during the Franco-Prussian War, and after the war he continued his creative academic career as assistant professor of pathology at the University of Freiburg. But shortly after his appointment as professor in 1874, he contracted tuberculosis. Despite being forced to leave his work for a long time due to illness, he remained active in academic work and kept studying the anatomy of marine animals. He later spent the rest of his life on the island of Canary Island and practiced medicine there, during the same period he also conducted research on various aspects of tuberculosis. Langerhans died on July 20, 1888, at the age of 40. During his short life, Langerhans discovered two types of cells, with which his name is associated. His extraordinary contributions played a key role in the subsequent understanding of animal physiology and pathology.
Langerhans’ cell (Langerhan’S cell) cells.
Langerhans cells are primitive monocytes that originate from the bone marrow, migrate and settle in the epidermal spiny cell layer of the human epidermis, and then move via the lymphatic vessels to the paracortical area of the lymph nodes to become dendritic cells of histiocytes with antigen-presenting function, belonging to the monocyte-phagocyte system, distributed in the skin, oral cavity, esophagus and vaginal mucosa, scattered among epithelial cells, also present in the lymph nodes, thymus and spleen, etc., with a diameter of about The nuclei are irregularly shaped, depressed, folded, twisted or lobulated, with thin nuclear membranes, one to three nucleoli, eosinophilic lightly stained cytoplasm, and fine, dense chromatin. Langerhans cells do not contain lysozyme and have weak phagocytic ability. Compared with monocytes and macrophages, they have significant differences in enzyme chemistry, immunohistochemistry and immunophenotype. Their specific immune markers include CD1a, HLA-DR and S-100 protein. The cytoplasm of Langerhan’s cells is characterized by a special organelle called Langerhan’s vesicles or Birbeck granules, which are rod-shaped tubular structures with a central longitudinal stripe and parallel horizontal periodic stripes, resembling a small zipper, sometimes with a vesicular expansion at one end resembling a tennis racket. Birbeck granules are ultrastructural features unique to Langerhan’s cells and are diagnostic for Langerhan’s cell histiocytosis.