Mycosis fungoides
Introduction
Introduction to mycosis fungoides Mycosisfungoides (MF) is a malignant tumor of T cell origin, also known as granulomafungoides, which is an epithelial cutaneous lymphoma. It is characterized by helper T cell proliferation, and Langerhasns cells and interdigitated reticulocytes are also involved in the pathology. The course of the disease is chronic and progressive, with multiple forms of erythema and invasive lesions in the early stage, which later develop into tumors, and may involve lymphatic viscera in the late stage. basic knowledge The proportion of illness: 0.003% Susceptible people: no special people Mode of infection: non-infectious Complications: sepsis
Cause
Cause of mycosis fungoides
(1) Causes of the disease
Most cases are memory-assisted T-cell tumors, and the cause is still unknown. It has been widely believed that MF is a malignant tumor from the beginning, but in recent years, more and more people think that this disease is an immune disease at the beginning, and later developed into The fact that lymphoma, from vascular immunoblastic lymphadenopathy often progresses to immunoblastic lymphoma, demonstrates the possibility of such development, and the following observations also support the immunological origin of MF:
1 normal human lymphocytes and high terrestrial mitogen or phytohemagglutinin culture caused 5% ~ 11% of the appearance of cells and light microscopic and electron microscopic MF cells or seary cells can not be distinguished, indicating that the latter is subject to The product of stimulated lymphocytes.
Epidermotropism and Pautrier microabscessation in 2MF also represent an immune phenomenon. Langerhans cells present antigen to T lymphocytes, like contact dermatitis, resulting in lymphoid and Langerhans cell collocation, T lymphocytes and The interaction of Langerhans cells to form a Pautrier microabscess, a process that is slower than contact dermatitis suggests that it is defective in antigen handling, persists an unconfirmed antigen, and stimulates lymphocytes in a chronic process There is a malignant change.
3 In view of the malignant marker of cell infiltration, the T cell receptor gene cloning rearrangement Southern blotting analysis indicates that the monoclonality of T cells is not obvious in the early plaque stage, but When the indurated plaque progresses to the tumor stage, it can be found, and viral infection is also involved. It is reported that among 315 MF patients, 36 (11.4%) have anti-human T cell lymphoblastic virus type 1 (HTLV). -1) Special antibodies.
(two) pathogenesis
The pathogenesis is still not very clear, but the following hypothesis is proposed for the pathogenesis of this disease. The skin infiltration of this disease has gone through three stages:
1. Atypical skin infiltration stage: Although there is still debate about the initial histopathological changes of the disease, it is believed that the initial infiltration of interacting T lymphocytes and monocytes may later subside, local persistence or different. The impact develops into the next stage.
2. Skin expansion stage: The above-mentioned atypical infiltrating cells can affect the recirculating T cells. When the latter enters other parts of the skin, the same atypical interaction or the factors that trigger the initial infiltration directly affect the skin of other parts, causing atypical Polymorphic infiltration, with the development of lesions, the formation of plaques or tumors, the infiltration becomes more single, mainly T cell tumor cells, even in this period has a very slight systemic immune abnormalities.
3. Systemic disease stage: When the lesion develops or affects the blood and other internal organs, the single-shaped T-cell tumor cells infiltrate prominently, and the patient's cellular immunity is abnormal. The abnormal immune response can occur in all aspects, due to migration and further Abnormal patterns of circulation, unclear transmission of skin stimuli (sustained antigens, allergens in the environment), abnormal T lymphocyte responses or abnormal regulation of helper or inhibitory components, lymphocytes and macrophages in the tissues Cell aggregation, MF occurrence and environmental factors (such as exposure to petroleum industrial products, industrial waste, waste gas, radioactive pollutants, pesticides, pesticides and other allergens such as light or viruses), susceptibility to the body, abnormal lymphocytes - Mononuclear cells or lymphocytes - Langerhans cell interactions, or persistent antigenic stimulation are all related. According to the above assumptions and reasoning, he believes that the disease is "reactive" at an early stage and then develops into a malignant neoplasm. .
Prevention
Mycosis fungal disease prevention
Mainly based on prevention, timely detection of treatment.
Complication
Sputum fungal disease complications Complications sepsis
1. Ulcerative lesions are easy to concurrent infection and secondary sepsis is the most common cause of acute death in MF.
2. About 8% of the MF course is converted to large cell lymphoma from the diagnosis of MF to the median time of transformation 21.5 months, the disease is accelerated after transformation, the prognosis is poor, 15% to 20% of the MF process occurs skin viscera Invasion, including lymph nodes and internal organs, invasion of skin and external organs rarely occurs in localized plaques and patches, while the incidence of extensive plaques is about 8%, but occurs during tumor stage and systemic erythroderma. The rate is as high as 30% to 42%. The superficial lymph node enlargement in the early stage of skin lesions is often dermatologically reactive, and tumor invasion occurs. It usually involves the superficial lymph nodes within the lesion drainage area, such as the mediastinum and abdominal aorta. Parasitic lymph nodes are generally invaded late, and internal organ invasion often occurs after lymph node invasion, most often involving the lungs, spleen, liver, central nervous system and gastrointestinal tract. In the early localized skin lesions, bone marrow invasion is rare, but when When there are Sezary cells in the peripheral blood, the incidence of bone marrow invasion is significantly increased. The autopsy data indicates that the advanced tumor can invade any organ.
Symptom
Symptoms of mycosis fungoides Common symptoms Folds when face is affected... Lymph node enlargement Itching palmar keratosis excessive hair thinning A malnutrition Skin involvement pigmentation and hypopigmentation nodule erythema scales
MF originates in the skin, but eventually the lymph nodes and internal organs are often affected.
1. Clinical manifestations and histopathological staging typical cases can be divided into three stages in clinical and histopathological, namely, erythema stage, plaque stage and tumor stage, and the three stages can overlap each other, so the third stage damage can occur simultaneously.
(1) erythema stage: the rash is patchy, usually the flat surface does not shrink, but some patients show atrophy, flat non-atrophic patches often have scaly adhesion, similar to psoriasis or eczema, the latter is round, eggs Round, can also be ring-shaped, multi-ring or bow-shaped, atrophic patch surface bright, easy to shrink, normal sulcus disappears, telangiectasia, hypopigmentation or pigmentation, clinically, vascular atrophic skin Heterochromia, large plaque-type parapsoriasis or mottled parapsoriasis, flat non-atrophic patches usually secondary to infiltration after several months, and visceral damage can also occur, while flat atrophic patches are only 12 % of patients evolved into invasive MF, and the remaining patients remained unchanged.
(2) plaque stage: plaques that progress from the erythema stage, or occur on normal skin, are irregular, and have a slightly higher limit. The color is yellowish red, dark red to purple, and can be resolved by itself. It can also be merged into large plaques with rounded edges, bows or lizards. When the face is affected, the folds deepen to form a "lion face". The plaques can be merged into a wide range, but there are scattered normal skin and damage. Further development can produce painful superficial ulcers. In this period, lymph nodes are often enlarged, no tenderness, and the nature is solid and can be freely promoted.
(3) Tumor stage: can occur on the original plaque or normal skin, the skin lesions are of different sizes, the shape of the brownish red high nodules, tends to early ulceration, forming deep oval ulcer The base is covered with necrotizing pale grayish white material. The edge of the ulcer is curled and occurs in the trunk. It can also occur in any part, even in the oral cavity and upper respiratory tract. Once the tumor occurs, the patient usually dies within a few years. In addition, MF can be seen in erythroderma. Subtypes, systemic exfoliation and skin flushing, hair scarcity, nail dystrophy, palmar keratosis, sometimes systemic pigmentation, occasionally see follicular mucinosis, hypopigmentation damage and MF associated.
MF is a malignant lymphoma. In addition to the skin, lymph node involvement is most common. Others are spleen, lung, liver, bone marrow, kidney, tongue or epiglottis. The heart and thyroid gland, visceral involvement patients survive for about 1 year.
2.MF staging standard
(1) T refers to skin involvement:
T1 skin involvement is less than 10%.
T2 skin involvement is higher than 10%.
T3 tumor.
T4 erythroderma.
(2) N refers to lymph node involvement:
N0 lymph nodes were clinically and pathologically involved.
N1 lymph nodes are enlarged, but pathologically non-MF.
N2 lymph nodes are not enlarged, but pathologically MF.
N3 lymph nodes are enlarged, pathologically MF.
M0 viscera is not affected.
M1 visceral involvement.
(3) The MF staging is as follows:
IA is T1, N0, M0.
IB is T2, N0, M0.
IIA is T1~2, N1, M0.
IIB is T3, N0~1, M0.
IIIA is T4, N0, M0.
IIIB is T4, N1, M0.
IVA is T1 to 4, N2 to 3, M0.
IVB is T1~4, N0~3, M1.
Examine
Examination of mycosis fungoides
1. Blood: early hemoglobin is normal, there may be mild anemia in the late stage, occasionally hemolytic anemia, in some cases, white blood cells increase, eosinophils and monocytes increase, lymphocytes decrease, which is in generalized plaques and tumors Patients in the period are particularly common, suggesting a poor prognosis. Most of our cases are stage I to II, 27.5% have eosinophils, 47.5% have mononuclear cells, 76% have lymphopenia, and the literature reports about 20%. In the case (70.8% of our cases), abnormal lymphocytes can be found in the blood, accounting for 6% to 35% of the number of nuclear cells, mostly below 20%.
2. Bone marrow: normal, occasionally increased plasma cells, we examined 9 cases, 6 cases of eosinophils and plasma cells increased, 2 cases of macrophage hyperplasia, 6 cases of abnormal lymphocytes, accounting for 2% of the number of nuclear cells ~3%.
3. Peripheral blood: The electrolyte is normal. We measured 20 cases of normal blood calcium, increased uric acid, decreased serum albumin, increased 1 globulin and 2 globulin, decreased circulating helper T cells, and decreased reactivity to PHA stimulation. Ineffective cells increased, monocyte tropism decreased, monocyte inhibitory factor decreased, serum IgG and IgE increased.
4. Erythrocyte sedimentation rate: 70 cases were determined, of which 60 cases (80.5%) increased in different degrees (15 ~ 30 mm / h).
5. Immunoassay:
1 Cellular immune response (including tuberculin test, DNCB test, chain reaction and lymphocyte conversion rate) was negative or below normal, 40 cases of DNCB test, of which 22 cases (53.84%) were negative; 50 cases of OT test Among them, 32 cases (64.28%) were negative; 20 cases of LTT, 15 cases (78.58%) were lower than normal,
2 Fluorescence examination showed deposition of IgG, IgA, IgM and IgD in the vessel wall.
6. Others: If the liver is tired, the serum alkaline phosphatase value increases, and other liver function tests are abnormal. When the lung is involved, the X-ray film shows tumor-like shadow, but it is not characteristic.
7. Histopathology:
(1) erythema stage: early diagnosis is difficult, often only in the upper part of the dermis see non-specific inflammatory infiltration, but even in the early stage, epidemotropism is often seen, that is, scattered in the epidermis, single mononuclear cells, and peripheral keratin There is a transparent space between the formed cells or they are separated. Even a few mononuclear cells are gathered together, and there is a halo interval around it, suggesting a small Pautrier microabscess. This pro-epidermal phenomenon is often prompted by early MF, and Often the extracellular exocytosis common in various dermatitis differs in that sputum granulomas usually have little or no sponge edema.
(2) Plaque stage: In most cases, the current histology has diagnostic value, and banded pleomorphic cell infiltration occurs in the upper part of the dermis, including lymphocytes, histiocytes, eosinophils, plasma cells and a considerable proportion. MF cells (nuclear deep-stained, irregularly shaped T lymphocytes), patchy infiltration can also be seen in the lower part of the dermis, pro- epidermal phenomenon in the epidermis and pautrier microabscess is a diagnostic value of the disease, and erythema The difference lies in the monocytes in the epidermis of the plaque stage, some are MF cells, and not only in the epidermis, but also in the epithelium of the appendage, especially the hair follicles are also scattered in the mononuclear cells.
(3) Tumor stage: two histological manifestations can be seen. Some patients have plaque-like polymorphic infiltration, but in most cases, the infiltration spreads to the subcutaneous fat layer, and the epidermis can be typically epidermal or invasive. Even in the upper layer of the dermis, there is no infiltration zone. In other patients, the infiltration is monomorphic and consists almost entirely of tumor cells. The epidermis is no longer characteristic. In the same patient, the transition from pro-epidermal to non-pro-skin can be seen. Sexual two histological manifestations.
8. Tips for the main histological features of MF diagnosis: basal cell layer with single or small group of lymphocytes; lymphocyte pro-epidermal and epidermal sponge formation is slightly disproportionate; MF epidermal lymphocytes than normal inflammatory skin disease More in the epidermis; lymphocytes in the epidermis are larger than those in the dermis; lymphocytes in the stratum corneum and granular layer; fibrosis of the dermal papilla, collagen bundles arranged in parallel; lymphocytes are obviously folliculotropism, especially in the hair follicle Mucin deposition (follicular mucinosis).
9. The main histological features of the diagnosis of inflammatory dermatosis are: upper dermis and dermal papillary edema; epidermal sponge formation is obvious; inflammatory cells in the epidermis are clustered in a narrow bottle neck, and the top end is open to the stratum corneum.
10. Immunohistochemistry: The value of MF for diagnosis is limited. MF cells are characterized by CD4 but loss of CD7 antigen, ie MF is CD4 CD7-. This phenotype is rare for non-malignant T cells, so the evaluation week Blood lymphocytes are valuable, and immunohistochemistry is difficult to apply to early damage with only a few tumor cells, because in most inflammatory infiltrates, inflammatory infiltrates are also composed of helper T cells, while early MF has normal helper T cells. Therefore, immunohistochemical examination does not identify the two. In addition, DNA hybridization or Southern blotting tests are often performed in undetermined cases to detect clonal rearrangements of T cell receptors (TCRs), but The data must be interpreted carefully; cloning does not confirm the diagnosis of malignant tumors. Benign diseases can also contain cloned TCR rearrangements. The number of early MF infiltrating cells may be insufficient for the detection of clones, so negative results cannot rule out MF diagnosis. Similar techniques can be used. Application to check lymph nodes in patients with MF, lymph node involvement can also be detected by these molecular methods, and routine histological examination may be normal, more chronic disease Cloning is likely to exist in their lymph nodes, and indicates the presence of cloning is shorter patient survival time.
11. Other characteristic immunophenotypes are CD-, CD2, CD3, CD5, CD45Ro, CD8-, CD3-, rare cases have also been reported to express CD3, CD4-, CD8 mature T cell phenotype, in addition to tumor stage loss of T Cellular antigen.
Diagnosis
Diagnosis and differentiation of mycosis fungoides
diagnosis
Mainly based on clinical features and histological indications, early diagnosis generally needs to be confirmed by biopsy. Therefore, when the disease is suspected in the clinic, biopsy should be performed in time, and continuous slices are often needed to find specific lesions. Farber It has been proposed to use the "shaving method" to continuously observe the epidermal lesions. We suggest that the early superficial lesions can only use the sharp blade to cut the epidermis of the lesion, and the serial section to find the Pautrier microabscess, and at the same time, the cell smear examination is simple. Less damage to the patient, no need for suturing, is conducive to repeated material extraction, but even so, sometimes it is not easy to diagnose, so the early diagnosis method remains to be further studied, so the diagnosis of this disease should be cautious, should be clinical and pathological and immune group The results are closely combined, and if necessary, close follow-up, multiple materials, must not be subjective, and rashly engaged, at present, the following diagnostic indications are available for reference:
Clinical aspect
(1) The rash is polymorphous and exists at the same time, so that it is often like a disease and another disease in the clinic; or it does not completely conform to a certain disease, nor does it completely conform to another disease. In other words, these rashes are very good. It is difficult to explain or generalize with a skin disease. For example, some lesions in a patient are similar to heterochromia, while others are like ichthyosis. If it is erythema damage, it is often dark red or brownish red. With atrophy, and often pigment abnormalities, pigmentation and hypopigmentation coexist, the edge of the rash is irregular, the shape is also inconsistent, the distribution is irregular, these are the characteristics of this disease.
(2) Although itching is not a necessary symptom at the beginning or course of the disease, many cases have itching, especially the rash is widespread and it is intractable and itchy. It is difficult to control with general drugs. The possibility of illness.
(3) Although some rashes can naturally subside in this disease, in general, the rash is increasing and the infiltration is gradually increasing. Therefore, it is a chronic progressive process, and the course of the disease is often long, which is also one of its characteristics.
2. Pathological aspects
(1) pro- epidermal phenomenon: intradermal infiltrating cells often invade the epidermis or even the hair follicle epithelium, the so-called pro- epidermal phenomenon, mononuclear cells invading the epidermis, surrounded by halos, and a tendency to aggregate to form a Pautrier microabscess, this phenomenon is One of the important evidences for the diagnosis of the disease, this pro-epidermal phenomenon is different from the extracellular migration seen in general eczema and dermatitis. The latter is often accompanied by sponge edema, the cells are mostly neutrophils, and the lymphocytes are mixed together, while MF There is no obvious edema, all of which are mononuclear cells.
(2) MF cells: A considerable proportion of MF cells can appear in the dermis at the beginning of the plaque stage. The nuclei are deeply stained, irregular in shape, and even in different sizes. There is a transparent halo around the cells, which is valuable for diagnosis.
(3) Infiltration morphology: T cell mode, early infiltration is mostly limited to the upper part of the dermis, mostly banded, accompanied by basal cell liquefaction, similar to the appearance of skin heterochromia, often have to consider this disease.
Differential diagnosis
In the differential diagnosis, because this disease can be similar to many skin diseases, it can not be described one by one, can be excluded according to the clinical and pathological findings, if necessary, the course of disease needs to be observed, and multiple times can be identified in different periods.
The morphology of MF cells was observed by electron microscopy. It was found that the cytoplasm of this cell was very small, but there was a relatively large nucleus. The nuclear membrane had many wrinkles. As a result, the nucleus formed a finger-like protrusion. From the perspective of the three-dimensional, the nucleus was cerebral-like. The chromatin particles are densely aggregated on the nuclear membrane and aggregated into a mass, which is scattered throughout the nucleus. MF cells and Sézary cells (even infiltrating cells in the large patch type patchy parapsoriasis) have very good electron microscope performance. There is no similar diagnostic significance for the purpose of diagnosis. For the purpose of diagnosis, the nuclear shape of lymphocytes in skin biopsy has been tested by electron microscopy. There are reports of the average nuclear shape index (NCI) of early MF and benign inflammatory skin diseases. Significant differences, MF cell NCI is often greater than 7.1 ~ 7.5, so that more than 95% of cases can be distinguished.
Li Jie et al have measured 13 cases of MF cells, the single indicators are: lymphoid cell average nuclear profile index (mNCI) 5.66; average nuclear morphology index (mNSI) 0.44; NCI> 6.0 cell number 30%, maximum NCI (NCImax)>9.0, and the percentage of lymphoid cells with NSI of 0<19%, the maximum NCI value combined with the percentage of cells with NSI of 0 is the best judgment index by electronic computer analysis, which is helpful for early diagnosis of MF.
