Pediatric Non-Hodgkin Lymphoma

Introduction to Pediatric Non-Hodgkin's Lymphoma Non-Hodgkins lymphoma (NHL), also known as malignant lymphoma, originates from lymphocytes during proliferation and differentiation, and its spread is similar to that of normal lymphocytes. basic knowledge Sickness ratio: 0.05% Susceptible people: children Mode of infection: non-infectious Complications: facial paralysis pleural effusion ascites intussusception

The cause of non-Hodgkin's lymphoma in children

Causes:

The pathogenesis of most children with NHL is unknown. The patient's immune lymphoid progenitor cells proliferate uncontrolled, lose the ability to further differentiate and gradually accumulate in the host to cause NHL. There is evidence that NHL is caused by clonal hyperplasia, in patients with NHL. A clonal karyotype abnormality can be seen in malignant tumor cells. In HIV-infected patients, the incidence of lymphocytic dysplasia is high, especially in Burkitt and large B-cell lymphoma, and in patients with AIDS, NHL can be the first clinical symptom. In immunodeficient patients, EB virus is It plays an important role in lymphocyte proliferation, and B cell proliferation induced by Epstein-Barr virus provides a cell bank for the formation of subsequent malignant tumors.

Pathogenesis:

Most of the malignant tumor cells of patients with Burkitt's lymphoma have karyotypic abnormalities, and the long arm of chromosome 8 and the translocation of chromosome 14 are t(8;14)(q24;q32), for T-NHL and T-ALL studies have found that they have similar translocations, including the , , and chain translocations of TCR, which include loci associated with cell proliferation, and therefore, in all subtypes of childhood NHL, Chromosomal translocation plays a central role in the development of lymphoma, but the exact mechanism by which these chromosomal translocations lead to lymphoma is unknown.

Histopathology is the most basic and important diagnostic tool for NHL. There are multiple classification systems. According to the National Cancer Institute's Work Classification (WF) program, the main tissue types of children's NHL are lymphoblastic type, small and non-cracking type. Large cell types, almost all types are diffuse, highly malignant, a few large cell types are medium and low malignant, and the lymphoid tissue structure is destroyed in NHL. In non-lymphoid tissues, tumor cells infiltrate normal cells, collagen, Between muscle fibers.

Lymphocyte type is not identifiable in tissue cytology with acute lymphoblastic leukemia (ALL) infiltration. Children's oncologists often divide bone marrow tumor cells by more than 25% to divide ALL or NHL, but this standard is artificially divided and clinical. There will be a diagnosis of NHL, but the bone marrow will be recurred at the time of recurrence, or the diagnosis is ALL, and there is only a limited mass at the time of recurrence. It can be considered that lymphoblastic NHL and ALL, especially T-ALL, are different clinical types of the same disease. The diseased cells are slightly more mature than the latter, and the treatment of ALL can be used in the same treatment.

Small non-cracking type can be divided into Burkitt and non-Burkitt or Burkitt according to pleomorphic performance. In children, there is no clinical feature, immunophenotype, karyotype and molecular change difference, Burkitt in cell size. And morphologically uniform, rather than Burkitt pleomorphic, Burkitt lymphoma is often scattered between tumor cells in the phagocytic cells that engulf nuclear debris, resulting in star-like features, difficult to differentiate with mature B-cell ALL when bone marrow infiltration Some scholars believe that Burkitt NHL and mature B-cell ALL are the same disease with different clinical manifestations, and the same chemotherapy regimen for Burkitt NHL containing large doses of alkylating agent can be used.

Large cell type of metastatic lymphoma is characterized by infiltrating lymphatic sinus. Tumor cells are often large and deformed. They are rich in plasma and irregular nuclei. These tumors can be divided into cell variants, Hodgkin's lymphoma-like and Polymorphic T cell type (ie, peripheral T cell type) that does not express CD30, these types are sometimes accompanied by hemophagocytic proliferative responses, and some large cell lymphomas may indeed belong to tissue cell sources.

NHL tissue morphological classification can guide clinical treatment, but there are still many classification systems, and there are often contradictions between the systems. Using the same classification system, different pathologists may report different pathological types, and the repeatability is poor. It needs to be supplemented by immunophenotypes, karyotypes and molecular changes.

Pediatric non-Hodgkin's lymphoma prevention

1. Avoid contact with harmful factors: avoid contact with harmful chemicals, ionizing radiation and other factors causing leukemia. When contacting poisons or radioactive materials, strengthen various protective measures; avoid environmental pollution, especially indoor environmental pollution; pay attention to rational use of drugs, caution Use cytotoxic drugs, etc.

2. Vigorously carry out prevention and treatment of various infectious diseases, especially viral infectious diseases, and do a good job of vaccination.

3. Do a good job in eugenics, prevent certain congenital diseases, such as 21-three-body, Fanconi anemia, etc., strengthen physical exercise, pay attention to food hygiene, maintain a comfortable mood, work and rest, and enhance the body's resistance.

Pediatric non-Hodgkin's lymphoma complications Complications facial pleural effusion ascites intussusception

Hemorrhagic tendency, such as gastrointestinal bleeding; central nervous system infiltration, symptoms of craniocerebral or facial paralysis, sensory disturbance, paraplegia; liver, splenomegaly, superior vena cava compression syndrome, may be associated with unequal volume of pleural effusion, ascites; Kidney, bone marrow infiltration; inhalation dyspnea can occur; intussusception, even a small number of patients with intestinal perforation; acute abdomen.

Pediatric non-Hodgkin's lymphoma symptoms Common symptoms Lymphatic rupture acute abdomen nasal congestion nausea night sweat bleeding tendency intestinal perforation weight loss lymph node enlargement intussusception

The clinical manifestations of NHL vary greatly. Some patients have only peripheral lymphadenopathy, almost no systemic symptoms, and the pathology is clear at a glance. Therefore, the diagnosis is clear after biopsy, but other patients have complicated and critical clinical manifestations, and the pathological specimens are obtained and pathologically diagnosed. Both are very difficult, and various pathological subtypes have relatively special clinical manifestations.

Non-specific symptoms

Fever, heat type, superficial lymph nodes, night sweats, tumors can be originated in any part of the body and there are compression symptoms associated with the tumor site. If there is no effective treatment, the tumor biopsy site or mass may be cured for a long time. There are weight loss, paleness, limb pain, bleeding tendency, liver and splenomegaly, and the kidneys can also be swollen due to infiltration and can be touched.

2. Lymphocyte type

(70% T cell) 70% originated in the chest, especially in the mediastinum. Common symptoms in the mediastinum are chest pain, irritating cough, difficulty swallowing, shortness of breath, difficulty in lying down, severe cyanosis, neck Head and face and upper extremity edema, chest X-ray film visible, large anterior mediastinum mass, may be associated with unequal volume of pleural effusion, the abdominal cavity is less common in the primary site, a small number of patients have central nervous system infiltration at the time of diagnosis, The corresponding symptoms and signs appear, and it is more common in lymphoblastic NHL bone marrow infiltration. At this time, it is difficult to determine whether it is ALL or NHL bone marrow infiltration from cell morphology, immunology or cytogenetics.

3. Small crack-free type

(more than 95% are B-cell). It is more common in the abdominal cavity. It may have abdominal pain, increased abdominal circumference, nausea, vomiting, changes in bowel habits, liver, splenomegaly, ascites, and sometimes intussusception. Gastrointestinal bleeding, appendicitis-like manifestations, even a few patients with acute abdomen such as intestinal perforation, right lower abdominal mass is more common, need to be identified with inflammatory appendix mass, appendicitis, followed by the most common site of the nasopharynx , nasal congestion, snoring, bloody secretions and inspiratory difficulty breathing.

4. Large cell type

(70% T cell, 30% B cell) The disease course is relatively long, and there may be infiltration of specific sites, such as large cell B cell type NHL infiltration of mediastinum, and small non-crack B cell type infiltration of mediastinum is rare. Large intercellular variants can be found in the subcutaneous tissue of the skin, the central nervous system, the lungs, the testes, the bones, and even the muscles and gastrointestinal tract, and the corresponding symptoms appear.

5. Central infiltration

All of the above types can occur in the central nervous system infiltration of tumor cells, often accompanied by bone marrow infiltration, including meninges, cranial nerves, brain parenchyma, spinal cord and mixed infiltration, headache, vomiting and other symptoms of high blood pressure, or facial paralysis, sensory disturbance, Muscle strength changes, paraplegia, etc., if no central nervous system preventive measures are given, the central nervous system infiltration is highly likely in the course of the disease, and the optic nerve and facial nerve are more likely to be affected.

6. Clinical staging

The purpose of staging is to assess the extent of disease progression to clarify the diagnosis and guide the correct treatment. The Ann Arbor staging system has been widely used in children's HD, but not for children's NHL, because children's NHL does not present a sequence and foreseeable like HD. The clinical staging system of St.Jude Children's Research Hospital has been widely accepted (Table 2).

Bone marrow puncture, children with more than 25% of tumor cells in bone marrow cells are considered to have ALL, and one tumor in the localized site is considered to be stage IV NHL if there are 5% to 25% of tumor cells in bone marrow cells.

In most staging systems, children's NHL is divided into two categories: one is a localized localized disease (stages I and II), which accounts for 35% to 40% of children's NHL, and has a good prognosis through modern treatment; The class is a poorly located tumor and disseminated tumor (stages III and IV), most of the treatment fails, and the prognosis is poor.

Examination of non-Hodgkin's lymphoma in children

Suspected NHL can be done quickly, easily and may be diagnosed clearly, such as bone marrow smear, humoral tumor cell examination, pathological biopsy should be done in time when the diagnosis is not clear, laboratory diagnosis should include the following aspects:

1. Hematological examination: peripheral blood in the early stage of the disease is often unaffected, occasionally eosinophils increase, hemoglobin and thrombocytopenia occur in late stage of disease or bone marrow infiltration, white blood cell elevation is more common, and erythrocyte sedimentation rate can be increased. But not specific.

2. Pathological histomorphological examination: pathological histomorphological diagnosis is still the most traditional, the most important method, the morphology needs to be differentiated from other small round cell tumors, such as Ewing sarcoma, rhabdomyosarcoma and neuroblastoma, non-neoplastic Lymphoid hyperplasia, especially in children with autoimmune diseases, is difficult to differentiate with NHL by histomorphology alone when it has long-term lymphadenopathy. It needs to be combined with immunohistochemistry, cell and molecular genetics for final diagnosis, according to WF classification. The most common type of children's NHL (more than 90%) is lymphoblastic type, small non-cracking type and large cell type.

3. Immunophenotypic analysis: Adding and supplementing histomorphology, most of the immunolabels are shared with normal lymphocytes of the corresponding differentiation stage, but have clonal performance or markers of mature cells appearing in naive cells, supporting the diagnosis of tumors. According to the immunophenotype, NHL is divided into T cell type and B cell type. More than 70% of lymphoblastic NHL immunophenotype is T cell type, and more than 95% of small non-crack type is B cell type. Large cell types are more common in T cells, and a small part is B cell. Ki-1 antigen (CD30) has diagnostic significance for anaplastic large cell lymphoma.

4. Cytogenetics and molecular biology examination when conditions are available. Tumor cells have t(8;14), t(8;22), t(8;2) support for B-cell NHL diagnosis, from the level of molecular biology. If the immunoglobulin or T cell antigen receptor gene rearrangement is detected, it can be determined that the tumor is the source of the lymphatic system. The type of true tissue cell origin is very rare. At this time, the non-specific esterase is positive, and sometimes the T6 antigen is positive (Langerhans cell antigen). Or other mononuclear/tissue cell antigens appear, and phagocytic cells are seen.

5. Staged examination The diagnosis of NHL should include pathological morphology, immunophenotyping and staging. Stages can guide the intensity of clinical treatment. Staged examination should include bone marrow smear or biopsy, skull and thoracic and abdominal imaging (selective CT, MRI) , B-mode ultrasound or X-ray film), cerebrospinal fluid centrifuged sputum to find tumor cells, whole body bone scan, through these examinations to determine the extent of tumor invasion and according to the clinical stage.

6. Biochemical examination, serological examination can not provide a basis for diagnosis, VMA, HVA, -FP in NHL, carcinoembryonic antigen level is normal, LDH is non-specifically elevated, and is proportional to tumor burden, serum soluble IL-2 receptor liter High (flyers and other benign diseases can also be elevated), 2-microglobulin is elevated, monoclonal immunoglobulin bands may occur in small non-cracking forms, and liver function abnormalities may occur in liver infiltration. Can not be used as the main basis for identification of other diseases, high tumor burden can occur before treatment of spontaneous tumor cell lysis syndrome, electrolyte imbalance, such as hyperkalemia, hypocalcemia, hyperphosphatemia, hyperuricemia , high urea nitrogen and so on.

Optional chest X-ray film, abdominal B-ultrasound, chest CT, abdominal CT to determine the extent of the lesion, due to the high affinity of 67Ga for lymphoid tissue, 67Ga scan can be used as a supplementary examination to determine the extent of tumor invasion.

Diagnosis and diagnosis of non-Hodgkin's lymphoma in children

The diagnosis depends on histological biopsy (including immunohistochemistry and molecular cytogenetic examination), which can not only confirm the diagnosis, but also make a classification diagnosis, which is to understand the malignant degree of the disease, estimate the prognosis and make the correct treatment plan. It is all crucial.

Proper handling and fixation of biopsy substances is important for proper diagnosis. Proper treatment of biopsy substances can be performed in a series of complementary tests, especially immunophenotypic analysis, cellular genetic analysis, molecular examination of fusion proteins, and immunoglobulin forms and TCR gene weight. The first principle is to use the invasive procedure as much as possible for the correct diagnosis. The pleural effusion is performed by pleural cytology and immunological examination, and the diagnosis can be provided within a few hours. If the effusion is normal and there is no early effusion, the mediastinal lymph node can be selected for biopsy. If the peripheral lymph node biopsy results are negative, the parasternal mediastinal incision can be performed under local anesthesia. Acupuncture biopsy or acupuncture suction of the descending mediastinal mass.

For patients with superficial lymphadenopathy, biopsy can confirm the diagnosis. The key is to be alert to some patients with painless lymphadenopathy. Those with primary lymph nodes are easily missed. Therefore, if the cause of long-term fever is unknown, it is suspected. NHL should be surgically explored.

Patients with large abdominal lymphoma due to metabolic disorders and abnormal renal function, especially the rapid growth of Burkitt's lymphoma, also cause difficulties in diagnosis, ascites often contains a large number of malignant cells, the correct cytology combined with immunophenotype The examination provides a quick diagnosis and eliminates the additional risk of exploratory laparotomy and general anesthesia.

The diagnosis of HL should include staged differential diagnosis, and the patient can receive reasonable treatment after staging. There are several staging systems in the world. This article introduces St.Jude staging, which is derived from Ann Arbor Hodgkin's lymphoma. Staging system.

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.