Sclerofibroma is a locally aggressive tumor that originates from fibroblasts and may lead to severe functional loss due to its local aggressiveness, with more serious consequences when the tumor involves vital organs. Its clinical manifestations and biological behavior vary widely, and no studies have yet found a reason for the differences in biological behavior between different hard fibromas. There is no universally accepted optimal treatment for this disease, and the treatment plan for each patient depends on a variety of factors, requiring “individualized” treatment and a multidisciplinary process. The main therapeutic goal of the disease is local control. Because it is not a highly malignant tumor, the trade-off between quality of life and tumor control becomes important and the two most important aspects of individualized treatment planning. The following is a systematic introduction to hard fibroids, which we hope will enable patients to better understand what kind of disease hard fibroids are and be able to better cooperate with their doctors in treatment. The incidence of hard fibroids is a rare tumor with an annual incidence of 2-4 cases per million people, with an average age of about 40 years old and a slightly higher incidence in women. The exact cause of the tumor is not known, but hormonal, genetic and physical factors all play a role in the development of the tumor to some degree and are associated with its occurrence and growth. Although the majority of sclerofibromas are idiopathic, clinical observations to relevant basic research have found the disease to be associated with estrogen, pregnancy, and trauma. Some patients have a combination of familial adenomatous polyps (FAP). About 7.5% of patients with sclerofibrosarcoma are cases of familial adenomatous polyps (FAP). The literature reports that 12C15% of patients with FAP develop sclerofibroma. Sclerofibromas most often involve sites other than the abdominal wall in general patients, whereas in patients with FAP, there is primarily involvement of the abdominal wall. Mesenteric sclerofibroma is the second leading cause of death in patients with FAP. A general family history of APC, APC codon mutations, history of abdominal surgery and gender as female are the risk factors for the disease. The disease usually presents as a slow growing mass without pain or discomfort. Depending on where the tumor grows it may cause symptoms such as abnormal nerve function, limited joint movement or abdominal discomfort. Whereas a few cases of sclerofibrosarcoma have self-remission; in most cases, the tumor progresses slowly and requires treatment. Many of them keep progressing and need to be treated. Some studies have found that at different ages, hard fibroids grow at different rates and have a period of relative stability. 2.Pathological manifestations By and large, the tumor is tough and there is a pseudo-envelope around the tumor. Microscopically, spindle-shaped cells and collagen fibers can be seen. Immunohistochemistry is generally positive for Vimentin, SMA, and negative for S-100 and keratin. x-chromosome inactivation indicates that sclerofibroma is a monoclonal proliferation of cells rather than a reactive disease. 98% of patients with disseminated sclerofibroma have β-cantenin mutation (CTNNB1). And CTNNB1 mutation is a high factor for recurrence and CTNNB1 is associated with excessive proliferation of wound healing scars. Sclerofibromas with familial adenomatous polyps (FAP) have been shown to be associated with mutations in the colorectal polyp (APC) gene. ctNNB1 and APC are components of the Wnt signaling pathway in which β-catenin protein leads to stable or mutated genes for T-cell activation leading to TCF/LEF. recent studies have shown that proliferatively active tumors can be treated with a combination of tyrosine kinase inhibitors, PDGFR-A/B inhibitors and/or COX-2 inhibitors. Therefore, new therapeutic approaches now include tyrosine kinase inhibitors in combination with COX-2 inhibitors. 3. Treatment Sclerofibrosarcoma pathologically presents as a benign tumor that does not metastasize. However, the tumor is extremely aggressive locally, so the main goal of treatment for hard fibroids is local control. Extra-abdominal sclerofibrosarcoma is rarely a lethal disease, but usually results in functional loss or decreased quality of life due to tumor progression or complications from treatment. Randomized controlled trials comparing the relative effectiveness of various treatment modalities with an evidence-based medical grade I are lacking. Treatment options available include observation, surgery, chemotherapy, radiotherapy, and drug therapy. The appropriate treatment is selected according to the different conditions of each patient to achieve local control of the tumor with an acceptable incidence of complications. 4.Non-surgical treatment The biological behavior of sclerosing tumor is still not very clear. Some reports found that the lesions of a small percentage of patients with sclerofibroma remained stable for a long period of time and even regressed on their own afterwards. The complications of surgery and the high recurrence rate after surgery make doctors prefer a conservative treatment approach. Some cases should be treated as “wait and see”. Genetic testing may help to determine the patient’s risk of recurrence and to select appropriate drugs for high-risk patients based on some molecular type characteristics. 4.1. Observed treatment The strong local infiltration and high recurrence rate make surgery challenging. Complications or loss of function associated with aggressive surgical resection of the tumor are even more serious than the consequences of tumor progression or the tumor itself. Treatment must be individualized for each patient or case and requires a multidisciplinary, multi-modality approach. Acceptable postoperative functional and cosmetic requirements will vary from person to person, and the patient’s occupation, lifestyle, and existing functional status need to be considered during the development of the treatment plan. In order to avoid complications associated with surgery or radiation therapy, a period of observation and close follow-up in some patients may be the most appropriate treatment option. The current treatment trend is to take an observational approach for asymptomatic patients with sclerofibrosarcoma and to intervene with aggressive treatment for tumors that may endanger vital structures or continue to grow. 4.2. Systemic therapy (pharmacotherapy) Pharmacotherapy may be considered for cases that are unresectable or recurrent. Available pharmacological treatments include hormonal therapy, non-steroidal anti-inflammatory drugs (NSAIDs), interferon and chemotherapy. Treatment with hormonal therapy is based on the association of the tumor with pregnancy or contraceptive pill use, in addition to reports of tumors disappearing on their own after menopause or tumors sinking in on themselves after oophorectomy. The effectiveness of hormonal therapy in combination with other drugs (NSAIDs, vitamin C, warfarin) is in the range of 50%. The most commonly used treatment regimen is 120 mg/day of tamoxifen combined with sulforaphane. The response rate of this regimen has been reported in the literature to be over 50%. For patients who cannot tolerate it, low-dose or standard-dose antisarcoma chemotherapy treatment can be considered. Low-dose methotrexate, permethrin has been shown to be a chemotherapy regimen that can control tumor progression. More potent chemotherapy regimens include adriamycin and isocyclophosphamide based chemotherapy. Although there is no optimal treatment regimen, patients have had a rapid therapeutic response to standard antisarcoma chemotherapy, especially with adriamycin-containing regimens. The use of chemotherapy must be weighed against the potential side effects. Imatinib has some antitumor effects. Some reports have found some control of sclerofibrosarcoma with doxorafenib. The estrogen inhibitor tamoxifen is currently used in patients with estrogen receptor-positive breast hard fibroids. Recent studies suggest that mTOR plays an important role in tumor biology, especially when the APC / beta-catenin pathway is abnormal. It is currently in clinical trials. 4.3. Radiation therapy Retrospective studies have shown that radiation therapy can improve local control of hard fibers and can be used as a primary treatment or as an adjunct to other treatments. By synthesizing the literature, we can conclude that the local control rate of radiotherapy alone or surgery combined with radiotherapy is significantly better than that of surgery alone (regardless of the surgical border). Especially for cases with positive surgical margins, the advantages of radiotherapy alone or radiotherapy combined with surgical treatment are more obvious. The most significant implication is that additional radiotherapy is recommended for cases with positive incisional margins, and radiotherapy alone is recommended to be considered for unresectable cases. However, radiotherapy can also bring complications, with a 17% complication rate for short- or long-term radiotherapy at doses higher than 56Gy. The best outcome is with high-dose radiotherapy, which can control tumor progression-free up to 2 years. At radiation doses less than 50 Gy, the recurrence rate of radiation therapy alone is significantly increased. However, for combination therapy, the difference between radiotherapy alone and combination therapy is not as significant. The most common complications of radiotherapy are fibrosis, skin sensory abnormalities, edema, fracture, and local skin burns. 5.Surgical treatment Surgical resection is the main treatment modality for hard fibroids, especially when the functional and cosmetic losses brought by surgical resection are acceptable, and the local control rate of surgical resection is 75C80%. However, when the tumor is adjacent to important structures, such as blood vessels and nerves and internal organs, the complication rate of surgery will increase dramatically. Despite the high local control rate of surgical resection, the local recurrence rate reported in the literature ranges from 24% to 77%. While for soft tissue sarcoma resection, the cutting edge affects the recurrence rate, the relationship is not as clear for hard fibroids. Some studies have shown that the cutting edge does not determine recurrence rates. For recurrent tumors, surgical resection is still recommended if the boundaries of the initial surgical resection can be reached. Treatment to preserve functional control of the tumor should be considered for tumors that cannot be completely resected. In patients who have failed systemic therapy and/or radiation therapy, sometimes the only option is amputation, in which case close follow-up is recommended, and temporary observation is recommended in the absence of pain, loss of function, infection, etc. To summarize: For asymptomatic, non-progressive cases, far from important structures: close follow-up For symptomatic, progressive, adjacent to important structures in primary or recurrent cases: 1. When surgical resection brings little loss of function and acceptable appearance: surgical resection; 2. Positive surgical resection margins, surgery + radiotherapy; 3. Severe loss of function or appearance: radiotherapy 4. Unresectable: radiotherapy, chemotherapy, etc.; 5. resection and accompanied by pain, loss of function, infection, etc.: amputation.