myelofibrosis
Introduction
Introduction to myelofibrosis Myelofibrosis (MF) is referred to as myelin. It is a kind of myeloproliferative disease caused by collagen hyperplasia in bone marrow hematopoietic tissue, and its fibrous tissue seriously affects hematopoietic function. Primary medullary fiber is also called "osteomyostacle" and "unexplained myeloid metaplasia" ". The disease has different degrees of myelofibrosis, as well as extramedullary hematopoiesis mainly in the spleen, followed by liver and lymph nodes. The typical clinical manifestations are juvenile, immature erythrocyte anemia, and more teardrop-shaped red blood cells. The bone marrow puncture often shows dry pumping, the spleen is often swollen, and has different degrees of bone sclerosis. basic knowledge The proportion of illness: the incidence rate is about 0.0001%-0.0002%, more common in middle-aged and elderly people. Susceptible people: people who are born in 50-70 years old Mode of infection: non-infectious Complications: anemia
Cause
Cause of myelofibrosis
Abnormal stimulation (80%)
It has not been elucidated that some scholars believe that bone marrow fibrosis is caused by abnormal stimulation of hematopoietic stem cells, leading to fibrous tissue hyperplasia and even new bone formation, and bone marrow hematopoietic tissue involvement eventually leads to hematopoietic failure.
The main pathological changes of myelofibrosis (MF) are myelofibrosis and extramedullary hematopoiesis in the spleen and hepatic lymph nodes. The occurrence of myelofibrosis occurs from the center to the periphery, first from the spine, ribs, pelvis and femur, proximal to the tibia. The epiphysis begins and gradually spreads to the distal end of the limbs.
1) Early whole blood cell hyperplasia with mild bone marrow fibrosis in bone marrow cells with varying degrees of hyperplasia, red, granulocyte, and megakaryocyte cell lines all proliferate, with megakaryocytes being the most obvious, fat vacuoles disappearing, reticular fibers increasing, but still Does not affect the normal structure of the bone marrow, hematopoietic cells account for more than 70%, and the bone marrow matrix is mainly composed of soluble collagen.
2) Metaphase bone marrow atrophy and fibrosis stage fibrous tissue hyperplasia, accounting for 40% to 60% of bone marrow, hematopoietic cells account for 30%, megakaryocytes still proliferate, trabecular bone increases, thickening, new bones adjacent to bone marrow Formed, each scattered hematopoietic region is separated by parallel bundles or helical materials formed by reticular fibers, collagen fibers, plasma cells, and stromal cells.
3) Advanced medullary fibrosis and osteosclerosis MF end stage, mainly trabecular bone hyperplasia of bone, accounting for 30% to 40% of bone marrow, fibrous and osteosclerosis tissues are significantly proliferated, medullary cavity narrow, except The megakaryocytes are still visible, and other hematopoietic cells are significantly reduced. In this period, the bone marrow matrix component is mainly composed of polymeric proteins, mainly showing fibronectin, and the distribution of exogenous protein and TENASCIN is increased.
Prevention
Myelofibrosis prevention
First, prevention
Avoid contact with radiation and chemicals such as benzene and lead. If occupational needs are often exposed to these damaging factors, protective measures should be strictly implemented. Daily life, diet and daily life should be regular, work and rest should be combined, diet should be moderate, especially pay attention to Do not eat too much frying, smoked, over-focus, rubberized food, avoid, eliminate the effects of bad emotions, maintain an optimistic, lively state of mind, carry out appropriate sports activities, such as jogging, playing Tai Chi, etc. Blood, regulate body and mind, if suffering from chronic diseases, osteomyelitis, bone tuberculosis and other diseases, should be active, patient, long-lasting, standardized treatment, to prevent further development of the disease, especially emphasis on the application of traditional Chinese medicine syndrome differentiation to reduce the side effects of Western medicine, Adjusting the body can reduce secondary myelin.
Second, conditioning
(1) Life conditioning
Appropriately strengthen exercise, enhance physical fitness, to reduce the chance of infection, and have a regular life.
(two) diet conditioning
Strengthen nutrition, add more protein and various vitamins, can be more appropriate to kidney, nourishing food, such as walnuts, red dates, peanuts, etc., for anemia, weakness and other symptoms and chemotherapy after bone marrow suppression, Source: Medical Education Network
1. Ginseng stewed lean red ginseng or American ginseng 10 grams, a little lean pork, add water 200ml, simmer for 2 hours, add a little salt to eat, make up the vitality, suitable for qi deficiency.
2. Black chicken stew: half a dry black chicken, 10 grams of wolfberry, add water 300ml, 2 slices of ginger, simmer for 2 hours, add a little salt to eat, nourish kidney yin, suitable for kidney yin deficiency.
3. Black bean mutton soup: a small black bean, 2 slices of ginger, 50 grams of mutton, simmer for 2 hours, add a little salt to eat, warm Yang kidney, suitable for kidney yang deficiency.
4. Black bean soup: a small black bean, sauteed, 2 slices of ginger, 1 pond carp, washed, add 1000ml of water, simmer for 1 hour with a little salt of edible oil, warming kidney yang, suitable for kidney yang deficiency .
(3) Spiritual conditioning
Maintain open-minded optimism, build confidence in the fight against disease, and cultivate a strong will.
Complication
Myelofibrosis complications Complications anemia
Common complications include various symptoms caused by spleen compression, anemia, and bleeding.
Symptom
Symptoms of myelofibrosis Common symptoms Loss of fatigue, weakness, bone pain, fatigue, bone sclerosis, abnormal sweating, pale, snot, hepatomegaly
Most of the diseases are concealed and progress is slow. Many patients often diagnose the symptoms after months or years of symptoms. The most common symptoms are fatigue, weight loss and spleen compression. At first, the general condition is still good, and the spleen gradually appears. Increased, hypermetabolic, anemia aggravated symptoms, late bleeding may have symptoms, the main clinical manifestations are:
1) Spleen, hepatomegaly and splenomegaly are the most important clinical manifestations, the incidence is almost 100%. Occasionally, the patient himself found a lump in the left upper abdomen or was found during physical examination. Some people think that the degree of spleen is related to the course of the disease, and every 1 CM under the spleen rib On behalf of the course of one year, due to the splenomegaly, often feel full or heavy pressure on the abdomen, the spleen touches solid, generally no tenderness; but if the spleen grows too fast, local pain may occur due to local infarction of the spleen, and even rubbing sound can be heard.
2) Most of the patients with systemic symptoms are fatigue, weight loss, heat, sweating and other symptoms, appetite is generally reduced or decreased, especially late weight loss.
3) There is mild anemia in the early stage of anemia, which gradually increases with the decrease of hemoglobin. In the late stage, the complexion is pale, fatigue, weakness, shortness of breath after physical activity, and palpitations and other symptoms are more obvious.
4) Early bleeding platelet count increased or normal, no bleeding symptoms, late thrombocytopenia, skin often with purpura or ecchymosis, may have nasal discharge.
5) A small number of patients may have unclear bone pain, and a small number of patients develop secondary gouty arthritis due to increased blood uric acid.
Examine
Examination of myelofibrosis
1. Blood picture: Most patients have anemia of varying severity at the time of treatment. In the advanced stage, there may be severe anemia. Anemia is usually a positive cell positive pigment type. The morphology of red blood cells is obviously different in size and deformity, and reticulocytes are 2%-5%. Teardrop-like red blood cells, young red blood cells, and myelocytes or giant platelets in peripheral blood are one of the characteristics of this disease.
2. The white blood cell count varies, most of the patients increase in the early stage, generally 10-30×10^9/L. The classification is mainly mature neutrophils, and the young and late granulocytes can also be seen. A few 5% of the original granules and promyelocytes can be seen. Eosinophils and basophils may also be slightly increased, and granulocyte alkaline phosphatase activity is abnormally increased in 70% of patients.
3. Platelet count and function are abnormal, early platelets can increase, individual up to 1000 × 10 ^ 9 / L, platelets gradually decrease with the progress of the disease. Large and abnormal platelets can be seen in the peripheral blood, occasionally megakaryocyte fragments.
4. Bone marrow puncture smear and biopsy: "dry pumping phenomenon" in bone marrow puncture is a feature of this disease. Bone marrow smear can be hyperplasia in the early stage. In the middle and late stage, nucleated cells proliferate, and when converted to leukemia, the original cells Significantly increased. Bone marrow biopsy showed a large number of reticular fibrous tissue as the basis for the diagnosis of this disease. In severe cases, bone hyperplasia was observed. In a small number of patients, the bone marrow reticular fiber Giemsa staining was unclear, and silver staining was needed. According to the degree of hematopoietic tissue and fibrous tissue proliferation in the bone marrow, pathological changes of bone marrow can be divided into three phases (1) early stage: whole blood cell proliferation with fibrous tissue hyperplasia, and (2) medium stage: bone marrow atrophy and fibrosis. (3) Late stage: myelofibrosis and osteosclerosis.
5. Chromosome and molecular biology examination: No characteristic chromosomal changes have been found at present, and a few patients have trisomy chromosomal abnormalities.
6. X-ray examination: about 50% of patients with X-ray examination showed osteomal sclerosis, increased bone density heterogeneity, accompanied by spotted translucent areas, forming a so-called "glass-like" change, and also visible new bone formation and The periosteal lace-like thickening, bone changes occur in the sternum, ribs, spine, humerus, clavicle, pelvis, etc., some patients also have skull changes.
7. Radionuclide bone marrow scanning: The patient's liver, spleen and other extramedullary hematopoietic regions accumulate a large number of radionuclides, and there is a radioconcentrated area. The proximal part of the long bone with fibrous tissue hyperplasia and the red pulp of the trunk cannot show the radioconcentrated area.
8. Other examinations: Some patients showed elevated serum uric acid, lactate dehydrogenase, alkaline phosphatase, vitamin B12 and histamine.
Diagnosis
Diagnosis and differentiation of myelofibrosis
diagnosis
For patients with middle-aged or above, there are spleen with unknown causes, granulocytes and young red blood cells in peripheral blood, teardrop-shaped red blood cells, and bone marrow puncture with dry pumping. The possibility of this disease should be considered and bone marrow biopsy should be further confirmed by pathology. The obvious increase of reticular fiber collagen and collagen fibers in bone marrow cases is one of the basis for the diagnosis of this disease. The diagnostic criteria for the IMF and its new developments are listed below.
Diagnostic criteria
(1) Domestic diagnostic criteria:
1. The spleen is obviously swollen.
2, the appearance of immature granulocytes and / or nucleated red blood cells in the peripheral blood, there are a number of teardrop-shaped red blood cells, the course may have increased or decreased red blood cells, white blood cells and platelets.
3, bone marrow puncture multiple dry or proliferative reduction.
4, pathological examination of spleen and liver lymph nodes have hematopoietic foci.
5, bone marrow biopsy pathological sections showed significant proliferation of fibrous tissue.
Article 5 above is a prerequisite, plus any two of the other four, and discharge secondary fibrosis, can be diagnosed as primary myelofibrosis.
(II) Foreign diagnostic criteria: The diagnostic criteria for IMF established by PVSG are:
1, splenomegaly.
2. The peripheral blood smear has immature granules and immature red blood cells.
3. The number of red blood cells is normal and the Ph1 chromosome is negative.
4, the well-taken bone marrow biopsy section, fibrous tissue accounted for more than 1/3.
5. Excluding other systemic diseases.
(C), the latest diagnostic criteria of the IMF
According to the latest research progress of the pathogenic mechanism of BCR/ABL-negative MPD molecules, according to the 2001 WHO diagnostic criteria, IMF is divided into pre-fibrosis and fibrosis stages.
1. The pre-fibrosis period includes:
1. Clinical: no or slight hepatosplenomegaly;
2, peripheral blood: mild anemia, mild to moderate leukocytosis, light to significant platelet increase, visible or no immature granules, immature red blood cells, visible or no abnormal red blood cells, a little teardrop-like cells;
3, bone marrow: increased cell capacity, neutrophil proliferation, megakaryocyte proliferation and dysplasia (meganuclear cell stack, abnormal lobulated nucleus, naked nuclei), mild or no net hard protein.
2. The fibrosis period includes:
1. Clinical: moderate to significant hepatosplenomegaly;
2, peripheral blood: moderate, severe anemia, low, normal or elevated white blood cells, low, normal or elevated platelets, visible immature granules, immature red blood cells, abnormal red blood cells with teardrop-like cells;
3, bone marrow: retinoic acid, collagen fibrosis, cell volume reduction, sinus enlargement with intracavitary hematopoiesis, significant megakaryocyte proliferation and dysplasia, osteosclerosis.
Differential diagnosis
The disease should be differentiated from the following diseases due to hepatosplenomegaly and abnormalities of peripheral blood.
1. Chronic myeloid leukemia: Both can have splenomegaly, megakaryocyte counts increase, and peripheral blood appears middle and late immature granulocytes. The detailed differences are shown in the table:
2. Bone marrow metastasis: often accompanied by young red, young blood cells, may have anemia, the general course of disease is short, splenomegaly is lighter. Cancer cells can be found in the bone marrow. Some patients can find the primary lesion. Sometimes, bone marrow fibrosis can occur after cancer metastasis, but fibrosis is often limited.
3. Low-proliferative acute leukemia: peripheral blood may appear naive cells, which may be accompanied by a decrease in whole blood cells and a decrease in myeloproliferation. However, usually the onset is more urgent, the hepatosplenomegaly is not significant, and a large number of immature cells can be seen in bone marrow aspiration and biopsy.
4. Myelodysplastic syndrome: the course of disease can be long or short, peripheral blood examination can be seen anemia or whole blood cell reduction, there may be naive cells. However, the liver and spleen usually do not enlarge significantly. Bone marrow puncture showed pathological hematopoietic cells and a higher proportion of naive cells. Bone marrow biopsy may have Abnormal Localization of Immature Precursor (ALIP) or abnormal chromosome discovery.
5. Aplastic anemia: Complete blood cell reduction can occur in the late stage of primary myelofibrosis, which is easily confused with aplastic anemia. However, patients with aplastic anemia have no splenomegaly, no immature granules and immature red blood cells in the blood, and bone marrow biopsy is significantly different from bone fibrosis. Aplastic anemia can sometimes be proliferative, but there is no fibrous tissue and megakaryocyte proliferation.
6. Liver cirrhosis hypersplenism: a clear history of viral hepatitis and a positive virological examination. In severe cases, there may be decompensated liver function such as portal hypertension and ascites. The bone marrow examination was normal.
7. Hairy cell leukemia: with complete blood cell reduction, hairy cells appear in peripheral blood and bone marrow, immunophenotype is B cell, CD11C+CD25+CD38+, more with medullary fibrosis, spleen is massive and hard, bone marrow puncture is often dry, Alkaline phosphatase is negative, generally no lymphadenopathy.
8. B-cell lymphoma in the marginal zone of the spleen: more common in older men, splenomegaly is the main sign, may have liver and lymph node enlargement, peripheral blood whole blood or one or two lines are reduced, bone marrow hematopoiesis is normal, peripheral blood And bone marrow lymphocytes were significantly elevated, showing villous lymphocytes, immunophenotype SmIg+, CD22+, CD5-, CD23-, CD79b+, FMC7+, bone marrow without reticular fibers, often with monoclonal immunoglobulinemia.
9. Acute lymphocytic leukemia: young people are mostly, anemia, infection and bleeding symptoms are heavier, sternal tenderness is positive, superficial lymph nodes are swollen, spleen is soft, light, moderately swollen. Peripheral blood can be seen in immature lymphocytes, bone marrow hyperplasia is extremely active, primordial and naive lymphocytes are 30%, and megakaryocytes are significantly reduced.
