Vulvar rhabdomyosarcoma

Introduction to vulvar rhabdomyosarcoma Rhabdomyosarcoma is a highly malignant tumor, the most common soft tissue sarcoma that occurs in children, and 20% occurs in the pelvic and reproductive tract. Foreign studies have found that female genital rhabdomyosarcoma accounts for about 3.5%, of which vulvar rhabdomyosarcoma (13%). Prone to occur around the labia majora, clitoris and urethra, the tumor grows fast and metastasizes early. basic knowledge The proportion of illness: 0.0003% Susceptible people: no special people Mode of infection: non-infectious Complications: acute lymphadenitis

Causes of vulvar rhabdomyosarcoma

(1) Causes of the disease

Vulvar rhabdomyosarcoma is a tumor that originates from primitive mesenchyme and is significantly prone to myogenic differentiation.

(two) pathogenesis

In acinar RMS, there are common t(2,13) (q35, q14) and t(1,13) (p36, q14) structural chromosomal aberrations, which form PAX3 on chromosome 13. /AX7-FKHR fusion gene, PAX3-FKHR can affect cell growth, cell differentiation and apoptosis, and down-regulation of wild-type PAX3 or PAX3-FKHR by antisense oligonucleotide pathway can induce RMS cell apoptosis. The death pathway is not p53-dependent, but is achieved by regulating the transcriptional activity of the anti-apoptotic protein BCL-XL (Margue 2000), but Zhao et al. (2001) believe that the occurrence of RMS is not the function of the PAX3-FKHR fusion gene. It is due to the loss of FKHR differentiation function.

In the embryonic RMS of 70% to 100%, 11 pl5.5 allele loss, ie loss of heterozygosity, was observed. By tandem repeat PCR analysis, Barr et al. (1997) found that the microsatellite instability was caused. Allele loss, 11p15.5 allele loss can disturb the imprinted gene at this locus. These imprinted genes refer to genes that are not expressed or rarely expressed by one of the two alleles of the parent. When the gene is re-expressed and the biallelic expression is called imprinting deletion, the current study is more on H19 (a non-readable frame RNA) and IGF2 (type II insulin-like growth factor). Gene, Barr (1997) et al. believe that the occurrence of embryonic RMS is due to the loss of function of a recognized maternal-expressing tumor suppressor gene such as H19 on 11p15.5, and the increase in the expression of growth-promoting genes such as IGF2 expressed by the paternal line. In vivo, IGF2 and PAX3-FKHR inhibit each other's myogenic differentiation and lead to undifferentiation. Undifferentiated myoblasts have the migratory ability conferred by IGF2, which is also enhanced by PAX3-FKHR. of Sub-event leading to the occurrence of alveolar RMS, embryonal RMS can also be further development of alveolar RMS in the case of over-expression of IGF2 and PAX3-FKHR.

Pathology

(1) General: According to the content of tumor cells, collagen, mucus-like matrix, it has different macroscopic morphology, and often accompanied by secondary changes such as hemorrhage, necrosis, cystic changes and ulcer formation.

(2) Microscopic examination: typical rhabdomyoblasts with different numbers in embryonic type, small tumor cells, poor differentiation, mostly round, elliptical, a few cells are fusiform, banded or scorpion-like, cells are obviously shaped and Nuclear deep staining, cytoplasm rich, eosinophilic, tumor cells tend to surround the blood vessels, the cells are loosely arranged, there are a lot of mucin-like matrix and the amount of collagen is small, the grape cluster is an embryonic type, mostly occurs in the mucosa In the lower layer, the convex surface forms a polypoid or grape-like mucinous mass, usually in the subepithelial region with dense round or short fusiform cell regions, called the "cambium layer", and the acinar type is poorly differentiated. Round or oval tumor cells are irregularly aggregated, surrounded by dense, transparent fibers separated by septum, intermediate cells lose adhesion to form irregular acinar-like cavities, often with dilated vessels in the interval, multinucleated giant cells Common, also manifested as solid adenoma, difficult to identify with the embryonic type, need to rely on cytogenetic examination, electron microscopically seen in the cytoplasm with parallel phase arrangement of thick, thin muscle, sarcomere and Z-band material Wait.

(3) Special staining and immunohistochemistry: typical RMS can confirm the presence of horizontal stripes according to light microscopic phosphotungstic acid-hematoxylin staining. There are many kinds of immunohistochemical markers, and their specificity and sensitivity are different. Commonly used markers of muscle proteins include intermediate filament proteins such as vimentin, desmin and nestin; cytoplasmic proteins such as myoglobin, creatine kinase isoenzyme (CK-MM, CK) -BB); contractile proteins such as myosin, which constitutes thick myofilaments, actin, which constitutes thin filaments; regulatory proteins such as tropomyosin, troponin T, and myelin (titin) And the nuclear proteins MyoDl and myogenin, among which skeletal muscle-specific indicators are myoglobin, myosin, fast-type skeletal muscle myosin, MyoDl and myogenin, although myoglobin is a unique oxygen-binding protein of skeletal muscle. However, it is only expressed in highly differentiated rhabdomyoblasts, and the positive rate is low. The positive expression rate of myosin in RMS varies with the degree of differentiation, ranging from 10.0% to 95.0% in spindle cell type RMS. Middle muscle elastin is strongly positive because most RMS points Poor, so many of the markers of muscle protein that aid in the diagnosis of RMS, MyoDl and myogenin are high in specificity and sensitivity, and have received increasing attention in recent years, especially for long-term neutral formalin-fixed specimens. MyoDl is more sensitive than vimentin and desmin, but because antigenic heat repair increases the non-specific cytoplasmic staining of MyoD1 and myogenin, the positive staining criteria for MyoDl and myogenin must be strictly localized to the nucleus, Chen et al. (1998). It was found that MyoDl and myogenin were strongly diffusely expressed in acinar RMS, while non-uniform expression in the embryonic type was extremely low. With MyoDl and myogenin, two types of RMS could be distinguished quickly, simply and accurately.

2. Pathology type

There are mainly the following:

(1) Traditional classification: proposed by Horn and Enterline in 1985, divided into four types according to general and cell morphology: embryonic, grape cluster, acinar and polymorphic. This method was adopted by IRS and WHO, but Undifferentiated small cell sarcomas are not classified, and the type cannot be determined when there is little tissue.

(2) Cell histological classification: also known as Palmer classification, divided into mixed type according to the morphology of the nucleus instead of cytoplasmic differentiation, single round cell type and degenerative development type.

(3) International Pediatric Oncology Society (SIOP) classification: divided into embryonic type, acinar type, polymorphic RMS and embryonic sarcoma by cytological differentiation and cell-rich density, in which embryonic RMS is differentiated. The presence or absence of grape clusters and the density or looseness are divided into five subtypes.

(4) National Cancer Institute (NCI) classification: It is also divided into embryonic type, acinar type and polymorphic type, but a solid acinar type is proposed, and the embryo type is divided into leiomyomas, grape clusters and polymorphs. Sex.

(5) International Classification of Rhabdomyosarcoma (ICR): A new pathological classification method that was proposed in 1995 and has a high degree of coincidence and can reflect prognosis. It has been used until now, and it is divided into a better prognosis including grape cluster type and spindle cell. Type, moderate prognosis, embryonic type, and poor prognosis include acinar RMS and undifferentiated sarcoma, and RMS that currently cannot be estimated for prognostic features including transverse pattern.

Vulvar rhabdomyosarcoma prevention

Early detection, timely treatment, and good follow-up.

Vulvar rhabdomyosarcoma complications Complications acute lymphadenitis

Often accompanied by inguinal lymphadenopathy, infection, bleeding.

Vulvar rhabdomyosarcoma symptoms Common symptoms Ulcer appearance is cauliflower appetite loss weight loss shame area mass vulva swelling vaginal bleeding

Often manifested as swelling or progressive enlargement of the vulva, the local pain part of the polypoid or cauliflower-like appearance, the initial mass is small, located under the skin, without any symptoms, the mass gradually increases, invading the skin to form ulcers There are irregular vaginal bleeding and drainage. There may be pain when combined with infection. At the same time, there may be systemic symptoms such as loss of appetite and weight loss. Patients often see a diagnosis due to lumps, bleeding and pain. In some cases, the lumps may not change within a few years. Then it increases rapidly.

Clinical stage:

1. The IRS surgical pathology group is commonly used by the grouping system developed by the International Rhabdomyosarcoma Association (IRS).

Stage I: The tumor is limited, the tumor is completely removed, and the regional lymph nodes are not invaded.

Stage Ia: The tumor is confined to the primary muscles and organs.

Stage Ib: The tumor infiltrates beyond the primary muscles and organs, such as through the fascia.

Stage II: The tumor is limited and completely removed under the naked eye.

Stage IIa: The primary tumor was completely resected under the naked eye, but there were residual lesions at the edge of the resection of the lens and no regional lymph node metastasis.

Stage IIb: tumor limitation, complete resection, regional lymph node metastasis.

Phase IIc: The primary tumor was completely resected under the naked eye, but there were residual lesions at the edge of the resection of the lens, and there was regional lymph node metastasis.

Stage III: Incomplete resection or biopsy, residual under the naked eye.

Stage IV: There is a distant metastasis at the time of diagnosis.

2. IRS preoperative TNM staging system due to surgery, chemotherapy and radiotherapy in the treatment of rhabdomyosarcoma gradually changed, and preoperative treatment will lead to changes in surgical pathology group, therefore, in 1997 IRS proposed preoperative TNM staging The system is determined by the location, size, local lymph node status and distant metastasis of the primary mass. In this preoperative staging system, the genital rhabdomyosarcoma is a favorable site, regardless of the size of the mass and the state of the local lymph nodes. When there is no distant metastasis, it is stage I, and when there is distant metastasis, it is stage IV. Because the TNM staging system does not reflect the prognosis well, it needs further improvement.

3. SIOP's TNM staging system was developed by the International Pediatric Oncology Society SIOP.

(1) Preoperative TNM staging:

Stage I: The tumor is confined to the primary tissue or organ without regional lymph node metastasis.

Stage II: The tumor invades one or more tissues or organs around it, and there is no regional lymph node metastasis.

Phase III: distant transfer.

(2) Postoperative staging:

pT1: The tumor is confined to the primary organ, completely resected, and the margin is negative.

pT2: The tumor invaded the surrounding tissue or organ, completely resected, and the margin was negative.

pT3: The tumor is not completely removed.

pT3a: There are residual lesions under the microscope.

pT3b: There is a general residue or only a biopsy.

Examination of vulvar rhabdomyosarcoma

1. Tissue cytopathology.

2. Cytogenetics and molecular biology indicators

RMS tumor cell markers include nicotinic acetylcholine receptor (AchR) gamma subunit, sialylated neuronal cell adhesion molecule (PSA-NCAM), insulin-like growth factor type II (IGF2), etc., when PCR is used to diagnose RMS, AchR mRNA is more sensitive and specific than MyoDl and myogenin, especially when /AchR<1 is used as the diagnostic criterion for RMS (Gattenloehner 1999). Recently, Fine et al. (2002) proposed that eaveolin-3 can be used as a tumor marker for RMS.

In acinar RMS, common t(2;13)(q35;q14) and t(1;13)(p36;q14) chromosomal translocations can be detected by cytogenetic methods, but the sensitivity is poor. Fluorescence in situ hybridization (FISH) combined with RT-PCR was used to detect the specific PAX3/PAX7-FKHR fusion gene formed on chromosome 13 due to chromosomal translocation, which is visible in 54% to 87% of acinar RMS. PAX3-FKHR, while 8% to 15% of the acinar RMS can be seen in PAX7-FKtHR, the PAX3/PAX7-FKHR fusion gene can not only assist in the diagnosis of acinar RMS, but Athale et al (2001) reported the detection of bone marrow by RT-PCR or PAX3/PAX7-FKHR in other body fluids can detect metastatic lesions with a sensitivity of 100%, which is significantly better than traditional morphological methods. In addition, the heterozygosity of 11p15.5 was found by PCR combined with restriction enzyme fragment length polymorphism analysis. Deletions can contribute to the diagnosis and differential diagnosis of embryonic RMS.

X-ray film, vaginal B-ultrasound, abdominal B-ultrasound, CT and magnetic resonance imaging, hysteroscopy.

Diagnosis and differentiation of vulvar rhabdomyosarcoma

Vulvar RMS has no specific clinical manifestations. Where the vulvar subcutaneous mass gradually increases, especially in the short term, it should be suspected as a soft tissue malignant tumor. The diagnosis must be combined with acupuncture biopsy or surgical resection of the specimen for histological cytology. Need to see striate muscle cells, but even in the highly differentiated RMS often no obvious horizontal stripes, and histological diagnosis RMS subjective, the rate of misdiagnosis is as high as 40%, so the diagnosis needs to be combined with immunohistochemistry and cells, molecular genetics At the same time, X-ray film, vaginal B-ultrasound, abdominal B-ultrasound, CT and magnetic resonance imaging (MRI) were needed to understand the involvement of the lesion. Daldrup et al. (2001) compared the scintigraphy of skeletal muscle, whole body MRI. And 18F deoxyglucose positron emission tomography (FDG-PET) to find RMS bone marrow metastasis lesions, found that (FDG-PET) sensitivity is 90%, significantly higher than systemic MRI and skeletal muscle scintigraphy, However, FDG-PET imaging also has false positives. In addition, hysteroscopy, colposcopy and other monitoring techniques can help to understand the local infiltration of vulvar RMS.

Vulvar soft tissue benign tumors: generally slow development, malignant tumors develop faster, genital lumps, especially under the skin, the texture is more realistic, usually have to do a medical examination to make a final diagnosis.

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