The clinical presentation may be completely asymptomatic, but most frequent symptoms in the setting of ULMS are vaginal bleeding, nonspecific pain in the pelvis and a palpable pelvic mass [8]. In the setting of NULMS, swelling of the affected area is frequently reported [1] but no other symptoms may be seen.

• Swelling

  If you have a swelling on the body that has not been there before, it is always advisable to visit a physician immediately – even if it is a painless swelling. [leiomyosarcoma.org]

  This report describes a case of primary leiomyosarcoma of the inferior vena cava (IVC) in a 52-year-old male who presented with complaints of abdominal pain, chest pain, and bilateral lower limb swelling for 4 months. [ncbi.nlm.nih.gov]

  Symptoms may include: • A lump or swelling; • Abdominal discomfort or bloating; • Swelling or pain in any area of the body; or • Unusual bleeding. ICD-9: 171.5; 171.6; 171.8 PROGRESSION LMS generally occur in adults, but may affect children. [secure.ssa.gov]

• Weight Loss

  loss, mass Head;20 cm Pancreatodudenectomy ; Lung & liver metastases 15 months later 14 1990 Murata et al 55/F No data available Head & tail; no metastases Caudal pancreatectomy 15 1991 Lakhoo & Mannell 68/M Abdominal pain, weight loss, mass Body;17 [casesjournal.biomedcentral.com]

  A 20-year-old female was admitted to our hospital, complaining with nausea, weight loss and progressive headache in recent 2 years. [ncbi.nlm.nih.gov]

  Case report 1 A 79-year-old male patient presented with right upper quadrant abdominal pain radiating to the back, anorexia and weight loss of one month' duration. His past medical history included chronic atrial fibrillation and diabetes mellitus. [scielo.isciii.es]

  Abdominal leiomyosarcoma tumors can measure over 4 inches (10 centimeters) across and may be accompanied by pain, weight loss, nausea or vomiting. [mayoclinic.org]

  The patient denied having nausea, vomiting, diarrhea or loss of appetite, but had noticed a weight loss of 4.6 kg over the course of the last 3 months. She was a never-smoker but had been exposed to the prolonged second-hand smoke of her husband. [archbronconeumol.org]

• Fatigue

  Vague complaints, such as malaise, fatigue, and nonfocal abdominal pain, are often described. The sign most often cited is bleeding. These tumors sometimes necrose and bleed into the bowel. [emedicine.medscape.com]

  Chemotherapy is a treatment option, but has its side effects such as: fatigue, nausea and the most well-known; hair loss. Another traditional form of treatment includes removal by surgery which is followed by radiotherapy. [knowcancer.com]

  Mild exercise, small, frequent nutritious snacks, and limiting physical and emotional stress also help to combat fatigue. [encyclopedia.com]

  Smooth muscle is specialised for a slow and prolonged contraction, and may contract in a wave-like manner (peristalsis) or may remain contracted for an extended period of time without becoming fatigued. [healthengine.com.au]

• Fever

  Hepatic leiomyosarcoma is a rare malignant tumor, and in rare instances, its combination with fever may lead to misdiagnosis of liver abscess. [ncbi.nlm.nih.gov]

  Abnormal vaginal bleeding (amount of bleeding can vary from spotting to menorrhagia (abnormal heavy bleeding during menstruation) Pelvic or abdominal pain Foul-smelling vaginal discharge Less common symptoms can include: Weight loss Weakness Lethargy Fever [baumhedlundlaw.com]

  LMS can cause these general cancer symptoms : Bloating in your abdomen Fatigue Fever Lump or swelling under your skin Nausea and vomiting Pain Weight loss LMS in your stomach or intestines can cause: Stomachache Black-colored stools Vomiting blood LMS [webmd.com]

  Preoperative diagnosis is very difficult due to nonspecific symptoms (abdominal pain, anorexia, weight loss, palpable mass, fever, jaundice, intestinal obstruction) and radiological findings (distended gallbladder with thickened wall and liver mass) [scielo.isciii.es]

• Malaise

  Vague complaints, such as malaise, fatigue, and nonfocal abdominal pain, are often described. The sign most often cited is bleeding. These tumors sometimes necrose and bleed into the bowel. [emedicine.medscape.com]

  Their diagnosis is often challenging, as patients may present with non-specific complaints such as dyspnea, malaise, weight loss, abdominal pain, or back pain, preceding the diagnosis by several years. [ijpmonline.org]

  General symptoms associated with cancer may occur including fatigue, fever, weight loss, a general feeling of ill health (malaise), and nausea and vomiting. Pain may occur in the affected area but is uncommon. [rarediseases.org]

• Abdominal Pain

  This report describes a case of primary leiomyosarcoma of the inferior vena cava (IVC) in a 52-year-old male who presented with complaints of abdominal pain, chest pain, and bilateral lower limb swelling for 4 months. [ncbi.nlm.nih.gov]

  Abdominal pain, weight loss, epigastric tenderness & abdominal mass are the most commonly presenting symptoms [ 4 ]. Pancreatic leiomyosarcoma is more common in fifth decade of life or older (mean age 44.7 years; range 14 to 80 years). [casesjournal.biomedcentral.com]

• Nausea

  A 20-year-old female was admitted to our hospital, complaining with nausea, weight loss and progressive headache in recent 2 years. [ncbi.nlm.nih.gov]

  Nausea, vomiting, anemia, lower resistance to infection, and hair loss ( alopecia ) are common side effects. Medication may be given to reduce the unpleasant side effects of chemotherapy. [encyclopedia.com]

  […] originating in the smooth muscle cells within the muscularis propria or the muscularis mucosa, most often found in the jejunum, and presenting with gastrointestinal bleeding and anemia and sometimes with other non-specific symptoms such as vomiting, nausea [orpha.net]

  LUQ Whole pancreas; wide spread metastases without lymph node involvement Autopsy case 2 1956 Berman & Levene 47/M Jaundice Head of pancreas;5.5 cm; no metastases Pancreatodudenectomy ; well 1 year later 3 1957 Feinberg et al 14/M Epigastric pain; nausea [casesjournal.biomedcentral.com]

• Vomiting

  […] malignancy, originating in the smooth muscle cells within the muscularis propria or the muscularis mucosa, most often found in the jejunum, and presenting with gastrointestinal bleeding and anemia and sometimes with other non-specific symptoms such as vomiting [orpha.net]

  LMS can cause these general cancer symptoms : Bloating in your abdomen Fatigue Fever Lump or swelling under your skin Nausea and vomiting Pain Weight loss LMS in your stomach or intestines can cause: Stomachache Black-colored stools Vomiting blood LMS [webmd.com]

  Abdominal leiomyosarcoma tumors can measure over 4 inches (10 centimeters) across and may be accompanied by pain, weight loss, nausea or vomiting. [mayoclinic.org]

• Pelvic Mass

  […] typical duration of symptoms prior to diagnosis is 6 months Physical exam pelvic masses can be difficult to appreciate on inspection exam can be tender or nontender to palpation masses will be firm Imaging Radiographs involved extremity purely osteolytic [orthobullets.com]

  LMS of the round ligament of the uterus which can represent as an inguinal or pelvic mass is extremely rare. To our knowledge, there is only one case report of LMS arising from the round ligament available in the literature. [ncbi.nlm.nih.gov]

  It should be mentioned that the symptoms including vaginal bleeding, pelvic pain/pressure and abdomino-pelvic mass do not normally last long (mean duration = 6 months) (7). [jmrh.mums.ac.ir]

  […] coding ICD-10: C55 - malignant neoplasm of uterus, part unspecified Clinical features Usually discovered incidentally during hysterectomy for fibroids (Am J Obstet Gynecol 2019;220:179.e1) Symptoms include abnormal vaginal bleeding and those related to a pelvic [pathologyoutlines.com]

• Abdominal Mass

  Physical exam and ultrasound lead to the conclusion of a large abdominal mass. A computed tomography scan showed a mass arising from the pelvis and a large amount of ascites. [ncbi.nlm.nih.gov]

  The abdominal mass shows, and then there’s bleeding; at that point, it’s metastatic. Some patients who are presumed to have fibroids will undergo a procedure called morcellation, where the uterus is broken into parts and then they are suctioned out. [onclive.com]

  Common symptoms include: Abdominal pain An abdominal mass Enlargement of the liver Jaundice Ascites Hepatic vein obstruction Renal vein obstruction Kidney dysfunction Swelling of the legs Abdominal discomfort The exact cause of the condition is unknown [disability-benefits-help.org]

  Abdominal pain, weight loss, epigastric tenderness & abdominal mass are the most commonly presenting symptoms [ 4 ]. Pancreatic leiomyosarcoma is more common in fifth decade of life or older (mean age 44.7 years; range 14 to 80 years). [casesjournal.biomedcentral.com]

• Alopecia

  The most common adverse events associated with eribulin included neutropenia (44%), pyrexia (28%), peripheral sensory neuropathy (20%) and alopecia (35%). Of these adverse events, 63% were grade 3, 26% were grade 4 and 4% were fatal. [healio.com]

  Varanasi 221 005, Uttar Pradesh India Source of Support: None, Conflict of Interest: None DOI: 10.4103/0377-4929.44977 [Figure 1A], [Figure 1B], [Figure 1C], [Figure 1D] [Table 1] This article has been cited by 1 Testicular leiomyosarcoma and marked alopecia [ijpmonline.org]

  Nausea, vomiting, anemia, lower resistance to infection, and hair loss ( alopecia ) are common side effects. Medication may be given to reduce the unpleasant side effects of chemotherapy. [encyclopedia.com]

  Grades of toxicity, grouped as: haematological (leucopenia, anaemia, thrombocytopenia, neutropenia, haemorrhage); gastrointestinal (nausea, vomiting, anorexia, diarrhoea, liver, proctitis); genitourinary; skin (stomatitis, mucositis, alopecia, allergy [cochranelibrary.com]

• Back Pain

  Leiomyosarcoma presents with non-specific symptoms, including abdominal pain or back pain. There is an increased incidence in immunosuppressed individuals. [ncbi.nlm.nih.gov]

  W had a past medical history significant for hypertension, chronic renal insufficiency and worsening lower back pain of six months duration radiating to his lower extremities. [pennmedicine.org]

  Their diagnosis is often challenging, as patients may present with non-specific complaints such as dyspnea, malaise, weight loss, abdominal pain, or back pain, preceding the diagnosis by several years. [ijpmonline.org]

• Suggestibility

  CONCLUSIONS: Although metastasis to the oral region is very rare as suggested from the literature review, when patients present with unusual symptoms after a diagnosis of LMS, physicians should be aware of the possibility of LMS metastases. [ncbi.nlm.nih.gov]

  SUGGESTED PROGRAMMATIC ASSESSMENT* Suggested MER for Evaluation: • Clinical history and examination that describes the diagnostic features of the impairment and laboratory studies are needed to confirm the diagnosis, including biopsy and imaging. [secure.ssa.gov]

  […] extensive necrosis and hemorrhage MRI: has been speculated that an irregular margin of leiomyoma could be suggestive of sarcomatous transformation but it is not specific (J Magn Reson Imaging 2019;49:e282) Radiology images Images hosted on other servers [pathologyoutlines.com]

• Irritability

  […] cancer The tumor may also adversely impact adjoining/surrounding structures, such as the nerves and joints, leading to discomfort or a loss of feeling Topical therapy for initial stage cancers can result in side effects such as severe vaginal and vulvar irritations [dovemed.com]

  A 28-year-old male presented to us with lower abdominal pain and irritative lower urinary tract symptoms. Physical examination was unremarkable. Routine blood and urine investigations were normal. [urologyannals.com]

  It is often accompanied by irritability. I see a lot of infectious mononucleosis relapses, and the main complaint is often "I can't think" or "I'm losing my mind, I snap at everyone" rather than " I'm so tired I can't think straight." [leiomyosarcoma.info]

• Vaginal Bleeding

  Although the most frequent symptoms are vaginal bleeding and abdominal pain, the symptoms are generally associated with dimensions and localization of the tumor. [ncbi.nlm.nih.gov]

  The clinical presentation may be completely asymptomatic, but most frequent symptoms in the setting of ULMS are vaginal bleeding, nonspecific pain in the pelvis and a palpable pelvic mass. [symptoma.com]

  The Symptoms of Leiomyosarcoma Swollen areas or lumps on the body Bloating and abdominal swelling Pain or unusual swelling anywhere in the body A change in menstruation (or vaginal bleeding after menopause) Trouble breathing It is important to remember [leiomyosarcoma.org]

  bleeding and those related to a pelvic mass 70 - 75% of patients present with stage I and II disease Radiology description CT: might show irregular central zones of low attenuation, suggesting extensive necrosis and hemorrhage MRI: has been speculated [pathologyoutlines.com]

  Some of the most frequent presenting symptoms include: Abnormal vaginal bleeding (amount of bleeding can vary from spotting to menorrhagia (abnormal heavy bleeding during menstruation) Pelvic or abdominal pain Foul-smelling vaginal discharge Less common [baumhedlundlaw.com]

• Pelvic Pain

  It should be mentioned that the symptoms including vaginal bleeding, pelvic pain/pressure and abdomino-pelvic mass do not normally last long (mean duration = 6 months) (7). [jmrh.mums.ac.ir]

  The main presenting symptoms of uterine LMSs are abnormal vaginal bleeding, pain in the lower abdomen and a pelvic or abdominal mass [5]. [austinpublishinggroup.com]

  Case report Case 1 In July 2010, a 62-year-old female presented pelvic pain. Pelvic echography showed a right tissular latero-uterine mass with cystic component. Pelvic MRI showed a 16 cm mass, compatible with a necrobiotic myoma. [spandidos-publications.com]

  These common symptoms include abnormal vaginal bleeding, a palpable pelvic mass and pelvic pain. Fibroids and leiomyosarcoma often co‐exist which can make diagnosis difficult. [cochranelibrary.com]

• Flank Pain

  An IVC filter was inserted, and the patient was discharged home, but 20 days later, she returned to the hospital with worsening right flank pain. [ncbi.nlm.nih.gov]

  No No 14 [ 26 ] 2011 65 Female Flank pain Right - 13 × 11 RN No 15 months No No 15 [ 27 ] 2012 74 Female Abd pain Left RCC 8 × 6 RN No 1 month No No 16 [ 28 ] 2013 70 Male Flank pain Right RCC 4 LN No 2 months No Yes Bone 17 [ 29 ] 2013 69 Female Flank [jcmtjournal.com]

  Case Report A 56-year-old man with hematuria and left flank pain presented to the Inje University Haeundae Paik Hospital. [omicsonline.org]

  Patients present with similar symptoms of an abdominal mass and lower extremity edema, but they may also have flank pain. [cancernetwork.com]

  Adrenal cortical neoplasm in a 44-year-old woman who presented with a 2-week history of epigastric abdominal pain radiating to her right flank and back with increasing shortness of breath. [pubs.rsna.org]

• Enlarged Uterus

  According to the Society of Gynecologic Oncology, morcellation was developed to reduce the size of an enlarged uterus so that it could be removed through small laparoscopic incisions or through a woman’s vaginal canal. [drugwatch.com]

Imaging studies including CT or MRI are useful to assess the status of the adjacent tissue and organs, especially in the setting of a peritoneal tumor and both abdominal and thoracic evaluation should be performed, since the lungs and the liver (but also the skin) are the most common sites of metastasis [4]. On MRI, features of LMS include a large infiltrating myometrial mass of varying intensity on T1-weighted images, whereas an intermediate-to-high signal intensity may be observed on T2 [8]. Additionally, signs of hemorrhage, focal calcifications and extensive necrosis may be present [8]. Unfortunately, a significant proportion of patients is diagnosed with LMS incidentally, either after a surgical procedure that subsequently identifies a tumor (such as hysterectomy) or during other examinations [14]. To confirm LMS, it is necessary to perform a biopsy of the tumor and subsequent histopathological and immunohistochemical examination [9], but this procedure is also important in determining the therapeutic approach.

For ULMS, total hysterectomy and bilateral salpingo-oophorectomy is recommended, while proximal lymphadenectomy is performed when a suspicion of extrauterine disease is present [1] [15]. In advanced stages and in the case of involvement of other organs or tissues, surgical excision of the tumor with wide margins, is the recommended course of therapy [15], while cytoreductive surgery is performed if such approach is not possible [1] [9]. Depending on the site of the tumor, various surgical procedures have been recommended, such as prosthetic replacement of the infrahepatic inferior vena cava [16]. Chemotherapy, in addition to surgery, is the mainstay of treatment and doxorubicin is considered as first-line therapy, but because of its significant toxicity (cardiac changes, leukopenia and thrombocytopenia), as also due to development of resistance [6], gemcitabine and docetaxel, as well as ifosfamide pose as alternative regimens [17]. Trabectedin has also been used for patients who do not respond to standard regimens (or do not tolerate their toxic effects) [10]. For still unknown reasons, a response of the tumor to chemotherapy varies with the anatomical site and uterine LMSs respond more efficiently than vascular lesions [17]. Pazopanib, an inhibitor of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), has shown some benefit in patients who do not respond to chemotherapy and is being used in advanced stages of the disease [9]. Most recent studies have evaluated experimental drugs that target the PI3K/AKT/mTOR pathway and promising results were obtained both in vitro and in vivo [6]. Although radiotherapy is used frequently in oncology, numerous reports have confirmed that adjunctive radiation therapy does not improve outcome in patients suffering from this tumor [18] [19].

The staging system for sarcomas is based on four cardinal features [7]:

• Histologic grade - Well-differentiated (G1), moderately differentiated (G2), poorly differentiated (G3) and undifferentiated (G4) tumors may be determined by histopathological examination.
• Tumor size - ≤ 5 cm (T1), ≥ 5 cm (T2), and involvement of the superficial (Ta) or deep fascia (Tb).
• Absence or presence of lymph node dissemination (N0 and N1, respectively).
• Metastatic spread (M0 or M1).

Depending on the presence of various features, the following stages have been recognized, with their established survival rates:

• Stage I - Divided into Stage IA (G1 or G2; T1a or T1b; N0; M0) and IB (G1 or G2; T2a; N0; M0), 5-year survival rates are estimated at 98.8%, showing that early recognition of the disease favors a very good prognosis.
• Stage II - Three substages are recognized - IIA (G1 or G2; T2b; N0; M0); IIB (G3 or G4; T1; N0; M0); and IIC (G3 or G4; T2a; N0; M0), with survival rates being around 82%.
• Stage III - G3 or G4; T2b; N0; M0 are typical features for this stage, which carries a somewhat poor prognosis, as 5-year survival is around 50%.
• Stage IV - G1-4, T1,2; N1; M0 or presence of distant metastases (M1) are markers of advanced disease and a very poor prognosis is expected, as 5-year survival is achieved in < 20% of patients recognized in this stage.

It can be concluded that factors such as observed mitotic rate, but also tumor size depth significantly impact the outcome and development of recurrent disease (which develops in approximately 6-9% of cases) [12] [13]. Even without tumor recurrence, reports show that 5-year survival rates across all stages are around 50% [14]. ULMS, in particular, has a poor prognosis, compared to NULMS, with studies reporting 5-year survival rates of 41.2% and 82.6%, respectively [1]. One of the reasons for such results may be the fact that the majority of ULMS patients are diagnosed when the disease has already advanced to later stages, primarily because little or no symptoms may be observed, while NULMS provokes an earlier appearance of symptoms [1].

LMS arises either from smooth muscle cells or mesenchymal stem cells that eventually differentiate into smooth muscle cells [4]. The exact cause remains unknown, but numerous mutations have been described. Defects in p53 tumor suppressor gene, retinoblastoma 1 (RB1) gene, phosphatase and tensin homolog (PTEN), FANCA, ATM, as well as increased expression of tyrosine kinase-like orphan receptor 2 (ROR2) have been documented [9], while additional genetic studies have shown that different subtypes of LMSs exist on the basis of their molecular structure [10]. In addition to genetic mutations, several pathological events have been associated with the development of sarcomas, most important being [11]:

• Viral infections - Human herpesvirus type 8 (HHV-8), the causative agent of Kaposi's sarcoma and Epstein-Barr (EBV) virus, the cause of infectious mononucleosis, have both shown carcinogenic properties, especially patients who suffer from chronic immunosuppression (HIV, transplant recipients).
• Ionizing radiation - various reports have shown a significantly increased risk of STS after exposure to high-dose radiation, but also cyclophosphamide (alkylating chemotherapeutic agent) and tamoxifen, which is frequently used for a treatment of breast cancer.
• Familial syndromes - Several hereditary syndromes, such as Li-Fraumeni syndrome, Rothmund-Thompson syndrome, neurofibromatosis, enchondromatosis, and retinoblastoma carry a much higher rate of sarcomas compared to the general population, especially in individuals with confirmed p53 mutations.

Other risk factors include a presence of diseases such as Diamond Blackfan anemia and Paget's disease, but also exposure to dioxin, chlorophenols and other organic solvents through industrial and medical occupations [11].

Epidemiology studies have shown that the incidence rate of LMS ranges between 0.5-1.8 per 100,000 individuals, depending on gender and ethnic background [3]. When it comes to ULMS, a significant predilection toward African American women was observed, with the majority of tumors appearing during childbearing age [3]. The fact that almost 80% of tumors express progesterone, estrogen and androgen receptors shows that a connection between hormonal changes during this age period and tumor growth may be present [3]. Other reports suggest that the overall incidence of NULMSs increases in older age and peaks around the seventh decade of life, like with all other soft tissue sarcomas [4]. By far, the most common site of LMS occurrence is the uterus and approximately 40% of all uterine sarcomas are LMSs [1]. Additional sites include the retroperitoneum and various parts of the abdominal cavity, whereas LMS arising in the extremities comprises approximately 10% of all STSs in adults [2]. Certain reports have estimated that LMS comprises approximately 1% of all uterine malignancies [3].

The pathogenesis model of LMS remains unclear. Several genetic mutations have been identified, however, most prominent ones being functional mutations of p53, one of the key tumor suppressor genes [6] [9]. The role of PRUNE gene in differentiation, invasiveness, and proliferation of neuroblastoma has been well-documented and its increased expression in LMS was established [5]. In fact, a correlation between high expression of PRUNE and both tumor size and overall survival has been made, suggesting that it plays an important role in tumorigenesis [5]. Additionally, the PI3K/AKT/mTOR pathway, which is activated by tyrosine kinases involved in signal transduction from the extracellular environment, was shown to be dysregulated through mutations of AKT or PTEN [6]. Once the tumor reaches an advanced stage of development, metastatic spread via hematogenous route occurs, most commonly to the lungs, the skin and the liver [4].

Current strategies for prevention do not exist, as the cause of tumorigenesis remains unknown.

Leiomyosarcoma (LMS) is a rare but very aggressive tumor that belongs to a large group of soft tissue sarcomas (STSs), comprising 24% of all tumors encompassed in this group [1] [2]. In theory, LMS can appear at any site in the body, but the most common sites are the retroperitoneum, upper and lower extremities (designated as non-uterine LMS or NULMS) and the uterus (ULMS) [1]. Large-scale reports have estimated that ULMS is responsible for approximately 1% of all uterine malignancies and a significant predilection toward women of African American ancestry was documented [3]. In fact, ULMS is the most common sarcoma of the uterus, but one of its main features is a very poor prognosis, especially if recognized in advanced stages of the disease, which is rather common [1]. This tumor is most prevalent in women of childbearing age, whereas older age is shown to be a risk factor for a development of LMS in sites other than the uterus [3] [4]. The pathogenesis remains unclear, but mutations of p53 tumor suppressor gene, prune homolog 2 (PRUNE) and the PI3K/AKT/mTOR pathway have been discovered [5] [6]. The prognosis depends on tumor staging, which is based on the degree of cellular differentiation, tumor size, depth of invasion and presence of dissemination into either lymph nodes or distant organs and survival rates range from 98% in initial stages to < 20% in advanced disease [7]. The clinical course of LMS is often insidious and little or no symptoms may be present. In ULMS, vaginal bleeding, nonspecific pain in the pelvic area and a palpable mass in the pelvis were reported as most frequent complaints [8]. On the other hand, local swelling is characteristic for NULMS [1] [8]. Unfortunately, many women are diagnosed with ULMS incidentally, during hysterectomy or myomectomy, primarily because nonspecific abdominal symptoms mask the true nature of the disease [1]. For these reasons, it is imperative to perform either computed tomography (CT) or magnetic resonance imaging (MRI) prior to surgery or during assessment for the mentioned complaints, in order to define the exact stage of the tumor (achieved only through biopsy and histopathology) and determine optimal therapy [8]. Wide excision surgery and adjunctive procedures (depending on the site of the tumor), together with chemotherapy, are main therapeutic modalities, but survival rates are still very poor, as median survival times are around 12-15 months, indicating the aggressive nature of this tumor [9]. One of the biggest concerns is that almost 90% of tumors are either moderate or high-grade [9], meaning that more needs to be done when it comes to early diagnosis so that better patient outcomes can be achieved.

Leiomyosarcoma (LMS) is an aggressive tumor that originates from smooth muscles and belongs to a large group of malignancies called soft tissue sarcomas (STSs). LMS most commonly develops in the uterus, but because of its origin, it may appear anywhere in the body. Approximately 0.5-1.8 per 100,000 individuals develop this tumor around the world and a significant predilection toward individuals of African American ancestry (especially women) has been observed. In terms of age, it is known that LMS of the uterus most commonly develops in women of childbearing age, while advanced age is a recognized risk factor for tumors that develop in other sites, most commonly the abdomen and the extremities. The cause and the mechanism of disease remain unclear, but several genetic mutations were established. LMS is characterized by an insidious onset and clinical presentation, since the majority of patients are diagnosed in advanced stages of the disease, suggesting a poor overall prognosis. Most common symptoms are vaginal bleeding, nonspecific pain in the abdomen and a palpable mass in the pelvis in the setting of LMS in the uterus, whereas local swelling of tissues surrounding the tumor may be present if this malignancy develops in other sites. The diagnosis is most often made during evaluation for other conditions or surgical procedures (such as hysterectomy), but if the physician is considering LMS in the differential diagnosis, computed tomography (CT scan) and magnetic resonance imaging (MRI) should be performed to assess the status of the organs and determine the stage of the tumor as well. Depending on the size of the tumor, a degree of invasion and findings obtained during biopsy, stages range from 1 (a minimally invasive tumor) to 4 (presence of distant metastases) may be confirmed. 5-year survival rates range from 98% in stage 1 to < 20% in stage 4, implying that early recognition of the disease is detrimental to achieving good patient outcomes. Treatment comprises surgery that aims to remove tumor tissue as much as possible and chemotherapy, mostly used for patients in advanced stages of the disease. The emphasis on early recognition should be strengthened because of the fact that only 30% of patients respond to chemotherapy and surgical management of a metastatic disease is extremely difficult.

1. Lamm W, Natter C, Schur S, et al. Distinctive outcome in patients with non-uterine and uterine leiomyosarcoma. BMC Cancer. 2014;14:981.
2. Svarvar C, Böhling T, Berlin O, et al. Clinical course of nonvisceral soft tissue leiomyosarcoma in 225 patients from the Scandinavian Sarcoma Group. Cancer. 2007;109:282-291.
3. Toro JR, Travis LB, Wu HJ, et al. Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978-2001: an analysis of 26,758 cases. Int J Cancer. 2006;119:2922-2930.
4. Duffaud F, Ray-Coquard I, Salas S, Pautier P. Recent advances in understanding and managing leiomyosarcomas. F1000Prime Rep. 2015;7:55.
5. Zhao L-R, Tian W, Wang G-W, Chen K-X, Yang J-L. The prognostic role of PRUNE2 in leiomyosarcoma. Chinese Journal of Cancer. 2013;32(12):648-652.
6. Maruzzo M, Brunello A, Diminutto A, Rastrelli M, Basso U. Long-term response to first-line trabectedin in an elderly female patient with a metastatic leiomyosarcoma unfit for anthracycline. Anticancer Drugs. 2016;27(3):264-267.
7. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
8. Santos P, Cunha TM. Uterine sarcomas: clinical presentation and MRI features. Diagn Interv Radiol. 2015;21(1):4-9.
9. Babichev Y, Kabaroff L, Datti A, et al. PI3K/AKT/mTOR inhibition in combination with doxorubicin is an effective therapy for leiomyosarcoma. J Transl Med. 2016;14:67.
10. Guo X, Jo VY, Mills AM, et al. Clinically relevant molecular subtypes in leiomyosarcoma. Clin Cancer Res. 2015;21(15):3501-3511.
11. Amankwah EK, Conley AP, Reed DR. Epidemiology and therapies for metastatic sarcoma. Clin Epidemiol. 2013;5:147-162.
12. Radkowski CA, Dodd LG, Johnson JL, et al. Leiomyosarcoma of the somatic soft tissues. J Surg Orthop Adv. 2012;21:96–101.
13. Gladdy RA, Qin L-X, Moraco N, et al. Predictors of survival and recurrence in primary leiomyosarcoma. Ann Surg Oncol. 2013;20(6):1851–1857.
14. Bonvalot S, Raut CP, Pollock RE, et al. Technical considerations in surgery for retroperitoneal sarcomas: position paper from E-Surge, a master class in sarcoma surgery, and EORTC-STBSG. Ann Surg Oncol. 2012;19:2981-2991.
15. Gockley AA, Rauh-Hain JA, del Carmen MG. Uterine leiomyosarcoma: a review article. Int J Gynecol Cancer. 2014;24(9):1538-1542.
16. Illuminati G, Calio' FG, D'Urso A, et al. Prosthetic replacement of the infrahepatic inferior vena cava for leiomyosarcoma. Arch Surg. 2006;141:919-924.
17. Scurr M. Histology-driven chemotherapy in soft tissue sarcomas. Curr Treat Options Oncol. 2011;12(1):32–45.
18. Reed NS, Mangioni C, Malmström H et al. Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an european organisation for research and treatment of cancer gynaecological cancer group study (protocol 55874). Eur J Cancer. 2008;44:808-818.
19. Wright JD, Seshan VE, Shah M, et al. The role of radiation in improving survival for early-stage carcinosarcoma and leiomyosarcoma. Am J Obstet Gynecol. 2008;199(5):536.