Uterine myxoid leiomyosarcoma complicated by pulmonary embolism: a case report with a systematic literature review.

The Rare Gynecologic Sarcoma Study: Molecular and Clinicopathologic Results of A Project on 379 Uterine Sarcomas.

Uterine myxoid leiomyosarcoma with novel SULF1::PLAG1 gene fusion

Abstract Introduction/Objective Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare entity that presents significant diagnostic challenges due to its infrequency and has the potential for being misdiagnosed as a leiomyoma, endometrial stromal tumor, or myxoid leiomyosarcoma, resulting in undertreatment or overtreatment. Methods/Case Report We present a case report of a 50-year-old woman with a history of anemia due to heavy menstruation caused by fibroids, who underwent hysterectomy. The concurrent pelvic wash cytology raised suspicious for myxoid leiomyosarcoma. Results (if a Case Study enter NA) Macroscopic examination revealed both well and poorly circumscribed nodules, ranging upto 4.7 cm in maximum dimension. Cut surfaces exhibited a spectrum of appearances, including tan-pink, whorled and rubbery, as well as soft, hemorrhagic, edematous, and mucinous areas with necrosis. Microscopically, the tumor exhibited myxoid spindle cell proliferation, in the background of lymphoplasmacytic inflammatory infiltrates. She was diagnosed with IMT metastasis to left fallopian tube, ovary, and omentum. Immunohistochemical (IHC) analysis further confirmed the diagnosis, showing strong and diffuse cytoplasmic positivity for ALK (anaplastic lymphoma kinase), caldesmon, and smooth muscle actin. This case underscores the critical importance of accurate diagnosis in guiding appropriate treatment strategies. Moreover, given the morphological overlap with other uterine tumors, the identification of ALK rearrangement emerges as a pivotal diagnostic marker, distinguishing IMT from its mimics such as leiomyoma, leiomyosarcoma and smooth muscle tumor of uncertain malignant potential (STUMP). Enhancing our understanding of the histomorphological features and ALK immunostaining of uterine IMT is essential for optimizing patient management and outcomes. Conclusion IMT in the female genital tract can mimic other more common benign and malignant tumors like leiomyoma, leiomyosarcoma, and endometrial stromal sarcoma. Familiarity with clinical and histologic features and the use of ALK immunostaining can be critical for correct diagnosis.

Background: Malignant myxoid leiomyosarcoma (MMLS) is most commonly found in the uterus but can also occur in other areas, such as the extremities, vulva, chest wall, and abdominal cavity. This cancer is more prevalent in women and has a poor prognosis with a high rate of recurrence and a significant percentage of metastasis. Case Representation: Herein, we report the case of a 64-year-old female patient who presented with 3-month history of left lower abdominal mass. The patient underwent abdominal malignancy resection and was subsequently diagnosed with myxoid leiomyosarcoma. The patient experienced a recurrence and metastasis with significant ascites after the initial surgery and did not respond to treatment with oral Anrotinib in combination with Tislelizumab immunotherapy. Further genetic testing using next-generation sequencing (NGS) identified missense mutations in the PDGFRA and TP53 genes in the patient's plasma, but no mutations in the KIT gene were detected. Immunohistochemical analysis of the tumor tissue also revealed a negative expression of PD-L1. As a result, we altered her targeted therapy to Avapritinib, which resulted in significant improvement in her symptoms, including abdominal distension and pain, a decrease in ascites, and the KPS score increased from 60 points before treatment to 90 points after treatment SD (stable disease) was achieved for three months after treatment. Conclusion: In this case report, we present the instance of a patient with malignant myxoid leiomyosarcoma with a missense mutation in both the PDGFRA and TP53 genes. We found that targeted therapy with Avapritinib was effective in achieving a positive outcome in this patient. Our findings suggest that genetic detection is possible to better understand the biological behavior, genetic characteristics, and patient's response and tolerance to certain drugs, thus selecting the best treatment plan for the patient. Avapritinib may be a promising new treatment option for leiomyosarcoma patients with similar genetic mutations.

Endometrial stromal sarcomas are rare malignant uterine tumors that make up approximately 10% of all uterine sarcomas, but only around 0.2% of all uterine malignancies. The high-grade category of ESS was reintroduced in the new World Health Organization (WHO) tumor classification system based on its distinct morphologic, immunohistochemical, and molecular characteristics. ZC3H7B-BCOR is a newly described subtype of high-grade endometrial stromal sarcoma that closely mimics the appearance of myxoid leiomyosarcoma. Although its frequency is reported as low, it may, in fact, be higher, as in the past these tumors were frequently misdiagnosed as leiomyosarcoma. We hereby present a case report of a 45-year-old female who presented with disseminated peritoneal deposits of HG-ESS, which had initially posed diagnostic challenges due to its myxoid background and resemblance to leiomyosarcoma. Detailed case history and immunohistochemistry evaluation guided us to the final diagnosis.

Combined Robotic and Vaginal Surgery for Pelvic Exenteration Due to Vaginal Sarcoma Relapse in an Obese Woman

Purpose: There has been no systematic review specifically focused on spine metastasis from sarcoma. The aim of this study is to assess the clinical findings and outcomes of the treatment for spine metastasis from sarcomas from a literature review and systematic analysis. Methods: We queried PubMed for literature evaluating spine metastasis from sarcomas. Our review was constructed in accordance with preferred reporting items and meta-analyses (PRISMA) guidelines and protocol. The main outcome measure was survival time following medical and surgical management after diagnosis of metastatic sarcoma. Results: In total 451 papers were assessed. Eighteen articles in our search met inclusion and exclusion criteria. 64 patients were included in the analysis. Twenty-seven (42%) were female, and the mean age was 46. The most common location for metastasis was the thoracic spine with myxoid liposarcoma being the most common primary tumor (58%) followed by leiomyosarcoma (23%). In terms of treatment, 36 patients underwent non-surgical (chemotherapy or radiation) and surgical treatments, 13 underwent surgery only, nine underwent non-surgical treatment only, while six did not receive any treatment. The mean time from primary sarcoma diagnosis to spinal metastasis was 46.9 months. The mortality rate, based on the given follow up period of each study, was 67.7%, with a mean survival time of 48 months. We found no statistically significant difference among the groups (medical only HR 1.01, 95% CI 0.25-4.12; surgery only HR 1.19, 95% CI 0.35-3.99; medical and surgical HR 1.00 95% CI 0.34-2.92). Also, we found no statistically significant difference between patients treated with decompression and fusion versus en bloc resection (HR 1.24, 95% CI 0.58-2.64). Conclusion: Myxoid liposarcoma and leiomyosarcoma were the most common primary sarcomas that metastasize to spine and thoracic spine being the most location for them in our study. We found no significant difference in survival time after patient with spine sarcoma metastasis received medical management alone, surgical management alone, or combined medical and surgical management, and no significant difference and a trend towards decreased survival in patients who underwent wide en-bloc resection. Future studies with larger sample sizes should be conducted to explore additional outcome measures and delineate specific disease or patient specific factors that can guide our treatment algorithm for this challenging clinical presentation.

Patient: Female, 58-year-oldFinal Diagnosis: LeiomyosarcomaSymptoms: Abdominal painClinical Procedure: Hysterectomy • salpingo-oophorectomySpecialty: PathologyObjective:Rare diseaseBackground:Leiomyosarcoma is the most common uterine sarcoma. Leiomyosarcoma is classified into conventional leiomyosarcoma, epithelioid leiomyosarcoma, and myxoid leiomyosarcoma. Leiomyosarcomas with rhabdoid features have been rarely reported. Herein, we report a case of uterine leiomyosarcoma with rhabdoid features.Case Report:A 58-year-old Korean woman presented with acute abdominal pain. Computed tomography and magnetic resonance imaging of the pelvis revealed a large solid mass in the posterior wall of the uterus that extended to the uterine cervix. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy and tumor-ectomy. Microscopic and immunohistochemical examination of the tumor revealed leiomyosarcoma with rhabdoid features and high proliferation rate. Next-generation sequencing showed PI3K amplification and ERBB2 amplification. Postoperative abdominal and pelvic computed tomography performed 3 weeks after the operation showed a mass at the vaginal stump that was attached to the urinary bladder and rectum. The patient underwent pelvic exenteration of remnant vaginal stump, rectum, and urinary bladder with loop ileostomy, and was diagnosed with recurrent leiomyosarcoma. One month later, after the second operation, a 13-cm recurrent mass was noted on the computed tomography. Chemotherapy was not done and the patient died during supportive treatment 7 months after diagnosis.Conclusions:This case, which is a uterine leiomyosarcoma with rhabdoid features and high proliferation rate, recurred very fast, within 1 month, and showed an aggressive clinical course. The molecular classification and postoperative therapy are not well established in uterine leiomyosarcomas. Further studies are required to clarify the clinical and pathological characteristics of leiomyosarcomas.

Trabectedin is a therapeutic option for patients with advanced sarcoma. While a randomized trial demonstrated its prolonged progression-free survival (PFS), the reported PFS was <6 months. Some patients can achieve long-term disease control with this treatment. However, the reference information is insufficient. Herein, we retrospectively reviewed 51 sarcoma patients who received trabectedin. We analyzed the clinicopathological features, trabectedin dose, administration schedule, and clinical outcomes, including the overall response rate (ORR) and PFS. Among them, we assessed the detailed data of patients who achieved long-term disease control (PFS >1 year). The ORR in the 49 evaluable patients was 8%, and the median PFS in 51 patients was 7.5 months. Six patients (12%) achieved PFS of >1 year. Five of the six patients had metastatic lesions at trabectedin initiation. The pathological subtypes were myxoid liposarcoma (n = 2), leiomyosarcoma (n = 2), synovial sarcoma (n = 1), and Ewing sarcoma (n = 1). The final administration dose was the minimum dose (0.8 mg/m2) in two patients who continued the treatment over 20 cycles. The best radiological response was partial response (PR) in two myxoid liposarcoma patients and stable disease in four. The durations from trabectedin initiation to the first response in the two PR cases were 163 and 176 days, respectively. Our results support the validity of continuing trabectedin at a sustainable dose and interval in patients who can tolerate it. These results may be useful when considering the clinical application of trabectedin.

Introduction: Chronic Helicobacter pylori (HP) infection has been shown to be strongly associated with development of gastric malignancies, mostly gastric adenocarcinomas and lymphomas. We present a case of primary gastric leiomyosarcoma in a patient with persistent epigastric pain and HP infection. Case Description/Methods: A 59-year-old female presented to clinic with persistent, postprandial epigastric pain. Cardiopulmonary workup was negative. She had a history of esophageal leiomyoma resected endoscopically with negative margins 10 years ago. She was treated in the past for HP infection but never had repeat testing to confirm eradication. Abdominal computed tomography showed focal hepatic infiltration. She was advised to have a repeat upper endoscopy for surveillance but was lost to follow-up due to psychiatric comorbidities. She presented 6 years later with epigastric pain. Repeat CT abdomen showed a new 2.8 cm hypoattenuating lesion in the lesser curvature of the stomach. Patient did not follow up due to psychosocial issues. Two years later, she returned to clinic for epigastric pain and underwent repeat upper endoscopy and endoscopic ultrasound (EUS) with fine needle aspiration (FNA). EGD showed sub-gastric nodule attached gastric wall, about 30 mm in maximal dimension and gastric biopsy confirmed active HP infection. The EUS showed a 31.7x23.5 mm hypoechoic homogeneous gastric mass along the lesser gastric curvature. Cytology showed cellular spindle cell neoplasia with myogenic differentiation concerning for possible leiomyoma or leiomyosarcoma. Abdominal magnetic resonance imaging and chest computed tomography revealed no evidence of abdominal or thoracic metastasis. Subsequently, partial underwent sleeve gastrectomy. Pathology revealed Grade 1 myxoid leiomyosarcoma with negative margins. (Figure) Discussion: Prior studies demonstrated associations between HP infection and gastric malignancies - typically gastric adenocarcinoma or lymphomas. Few studies investigated the relationship between HP infection and gastric leiomyosarcomas.4,5 Importantly, this patient never had clearance of HP infection and may have allowed a leiomyosarcoma to develop. It is imperative that clinicians confirm eradication of HP infection given risk of leiomyosarcoma development in addition to other malignancies HP infections are known to cause.Figure 1.: Endoscopic and histologic examination of gastric leiomyosarcoma. (A) Endoscopic ultrasound visualization demonstrating tumor within lesser curvature of stomach. (B) Upper endoscopy revealing tumor approximately 4 cm from gastroesophageal junction. (C) Hematoxylin and eosin (H&E) stain of gastric tumor biopsy demonstrating spindle cell proliferation in a myxoid background with significant nuclear atypia and pleomorphism consistent with myxoid leiomyosarcoma. Magnification x400. (D) Immunohistochemical staining of gastric lesion biopsy demonstrating strong immunoreactivity to desmin. Not shown are positive stains for smooth muscle actin (SMA) as well as negative stains for Cytokeratin AE1/AE3, Myogenin, MyoD1, DOG-1, CD117, S100, SOX10, CD34, ALK-1 and ER. Positive and negative controls stained appropriately but are not included.

We describe a morphologic study of myxoid cells in myxoid tumors or with myxoid regions: myxoid fibrosarcoma, myxoma, myxoid liposarcoma, liposarcoma embryonal rhabdomyosarcoma, chondroma, chondrosarcoma, myxoid leiomyosarcoma, schwannoma, and odontoameloblastoma; and we compare with fibroblasts of umbilical cord, embryonal mesenquima and loose conective tissue in inflamatory conditions. Histologic techniques: H-E-PASS, Masson's tichroom, and Del Río Hortegas's panoptic silver staining. Histologically Del Río Ortegas's techniques reveals bipolar fibrobasts with loh processes.

We report 4 neoplasms of the kidney (2 cases) and uterus (2 cases) harboring rearrangements or amplifications of the GLI1 gene, which because of their unusual clinical presentation, morphology, and immunoprofile mimicked other neoplasms, causing significant diagnostic challenge. The neoplasms occurred in 4 female patients ages 33 to 88 years. Histologically they all demonstrated nodular growth, solid architecture, bland epithelioid to ovoid-spindle cells with pale cytoplasm set in a variably myxoid or hyalinized stroma. One uterine tumor also demonstrated a focal round cell pattern, while another demonstrated focal pleomorphism. Unlike most previously reported neoplasms with these genetic abnormalities, the neoplasms in the current series were negative for S100 protein and minimally reactive for actin. All labeled for CD10 and cyclin D1, while 2 labeled for estrogen receptor and BCOR and 1 labeled for desmin, raising consideration of endometrial stromal sarcoma, myxoid leiomyosarcoma, metastatic breast carcinoma, and glomus tumor. One renal neoplasm demonstrated a GLI1-FOXO4 gene fusion and the other harbored a GLI1 gene rearrangement (unknown partner). The 2 uterine neoplasms exhibited GLI1 gene amplifications. GLI1-altered neoplasms (particularly those with GLI1 amplification) show variable morphology and lack a consistent immunophenotype, and thus may trigger diagnostic challenges which can be resolved by molecular testing.

Although most gastrointestinal stromal tumors (GISTs) exhibit activating mutations in either KIT or PDGFRA, rare cases have shown to be driven by gene fusions involving kinases, mainly involving NTRK3, and rarely BRAF or FGFR1. BRAF gene rearrangements have been described in only two patients to date, as separate case reports. In addition, BRAF V600E mutation is an uncommon but established oncogenic pathway in GIST. In this report, we describe two new GIST cases harboring novel BRAF fusion genes, arising in two young-adult women (37 and 40 years of age) in the small bowel and distal esophagus, both with a spindle cell phenotype. The small bowel GIST measured 2.8cm and showed a high cellularity and a mitotic rate of 20/50 HPFs, while the esophageal lesion measured 7cm and 1/50 HPFs. Immunohistochemically, both tumors showed diffuse reactivity for DOG1, while KIT/CD117 was weakly positive in the small bowel GIST and completely negative in the esophageal tumor. Based on these findings, the latter case was misinterpreted as a low-grade myxoid leiomyosarcoma, as it showed a myxoid stroma, reactivity for SMA and focal positivity for desmin. Archer FusionPlex revealed a fusion between BRAF with either AGAP3 or MKRN1 gene partners. Moreover, MSK-IMPACT DNA targeted sequencing confirmed both fusions but did not identify additional mutations. In one case with available material, the BRAF gene rearrangement was also validated by FISH. The recognition of BRAF fusion-positive GISTs is critical as it may be associated with a low level of KIT expression and may result in diagnostic challenges with significant impact on therapeutic management. The clinical benefit with KIT inhibitors, such as imatinib, remains to be determined.

Frozen sections of uterine smooth muscle tumors are infrequently required, and related diagnostic difficulties are seldom discussed. We analyzed the clinicopathologic features of 112 frozen sections of uterine smooth muscle tumors and determined the accuracy, reasons for deferrals, and causes of interpretational errors. Most patients (median age, 45 y) presented with pelvic mass symptoms (53%). The main reasons for a frozen section examination were an abnormal gross appearance including loss of the usual whorled pattern of leiomyoma (36 cases, 32.1%), and intraoperative discovery of an abnormal growth pattern and extrauterine extension of a uterine tumor (28 cases, 25%). There were 9 leiomyosarcomas and 103 leiomyomas, including 18 benign histologic variants. An accurate diagnosis of malignancy was achieved in all leiomyosarcomas, with the exception of a myxoid leiomyosarcoma. In 99 cases (88%), the frozen section diagnosis concurred with the permanent section diagnosis (false positives, 0.9%; false negatives, 0%). Misinterpretation of stromal hyalinization as tumor cell necrosis in a leiomyoma with amianthoid-like fibers was a major discrepancy. Two minor discrepancies did not lead to a change in management. The diagnosis was deferred in 10 cases (8.9%) because of stromal alterations, unusual cellular morphology, uncertain type of necrosis, and abnormal growth patterns. Thus, although various stromal and cellular alterations can cause diagnostic uncertainty, leading to deferrals, frozen section diagnosis of uterine smooth muscle tumors has a high accuracy rate. While a definitive frozen section diagnosis of malignancy may be made when there is unequivocal atypia, indisputable mitotic figures, and tumor cell necrosis, it is important to remember that nonmyogenic mesenchymal tumors may also mimic uterine smooth muscle tumors. In a frozen section setting, it would be sufficient to issue a diagnosis of "malignant mesenchymal tumor." For tumors that do not meet the criteria for malignancy, issuing a frozen section diagnosis of "atypical mesenchymal tumor and defer the histologic subtyping to the permanent sections" is appropriate.

Background: Nonfunctioning pituitary adenomas (NFPAs) are most common pituitary tumors, and primary pituitary gland malignancies are extremely rare. Most malignant pituitary gland lesions metastasize from other sites. Primary malignant lesions, such as sarcomas, usually develop after radiotherapy or chemotherapy for other diseases. We report a rare case of primary sellar leiomyosarcoma (LMS) without prior therapy that arose concurrently with a pituitary adenoma. Clinical Case: A 56-year-old woman with ptosis of the right eye, headache, and progressive visual deficits visited our neurosurgery department. She had no medical history besides hypertension. Twelve months ago, she was referred to us because of decreased visual acuity and a 3.5×3.6-cm-sized pituitary mass detected on brain MRI. Normal pituitary functions with mild hyperprolactinemia suggested a nonfunctioning pituitary mass with stalk compression. After transsphenoidal surgery, histopathology revealed a pituitary adenoma; MRI immediately post-surgery revealed no grossly remnant lesion. However, during the current visit, sellar MRI revealed a re-growing mass in the pituitary fossa extending to the sphenoid sinus and compressing the optic chiasm with a suprasellar extension. Functional endoscopic sinus surgery was performed, and histopathology revealed a composite tumor, i.e., a mesenchymal tumor with a pituitary adenoma. On immunohistochemical staining, smooth muscle actin, synaptophysin, and chromagranin were positive; tumor cell mitosis was observed at 7/10 high-power fields. Finally, a composite tumor of myxoid leiomyosarcoma and pituitary adenoma was diagnosed. Hence, systemic chemotherapy with radiotherapy was planned for the remnant lesion. Hormonal replacement therapy with hydrocortisone and thyroxine was also started for subsequent hypopituitarism. Conclusion: NFPA is benign and has good prognosis if it is not grow in size or is completely resected. Conversely, primary sarcomas, such as LMS, show rapid extension and aggressive local invasion. Although their incidence is extremely rare, few primary pituitary sarcoma cases with or without pituitary adenoma have been reported. In the former case, initial diagnosis of pituitary adenoma may lead to delayed diagnosis of combined malignant lesions. Thus, clinicians should consider this possibility and high index of suspicion is required when diagnosing a pituitary mass.

Background: Uterine leiomyosarcoma is a rare gynecological disease. Myxoid leiomyosarcoma (mLMS) is an aggressive and very uncommon type of leiomyosarcoma, with few cases reported in English literature. Stromal metaplasia is rare in leiomyosarcoma. Here we present huge uterine myxoid leiomyosarcoma with stromal chondroid metaplasia. Case Report: A 48–year–old single woman with lower abdominal pain and increased abdominal circumference. The detected mass on imaging was diagnosed as uterine mLMS with stromal chondroid metaplasia in the histopathological examination after surgery. Conclusion: Myxoid leiomyosarcoma should be considered in uterine mass with extensive myxoid change, infiltrative border, low mitotic count, and mild atypia. Stromal chondroid metaplasia can be seen in the myxoid leiomyosarcoma. [GMJ.2021;10:e1817]

Background: Uterine leiomyosarcoma is a rare gynecological disease. Myxoid leiomyosarcoma (mLMS) is an aggressive and very uncommon type of leiomyosarcoma, with few cases reported in English literature. Stromal metaplasia is rare in leiomyosarcoma. Here we present huge uterine myxoid leiomyosarcoma with stromal chondroid metaplasia. Case Report: A 48–year–old single woman with lower abdominal pain and increased abdominal circumference. The detected mass on imaging was diagnosed as uterine mLMS with stromal chondroid metaplasia in the histopathological examination after surgery. Conclusion: Myxoid leiomyosarcoma should be considered in uterine mass with extensive myxoid change, infiltrative border, low mitotic count, and mild atypia. Stromal chondroid metaplasia can be seen in the myxoid leiomyosarcoma. [GMJ.2021;10:e1817]

Myxosarcomas are rare malignant tumors of soft connective tissues, classified into various subtypes, including myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma. In this study, we proposed to study the demographic, tumor characteristics, and overall survival rate and compared the treatment modalities between these cancers. Patient data collected based on locoregional metastasis presentation of the abovementioned tumors with a cutoff study of survival duration up to 10 years were obtained from the SEER database during 1975-2016. Our results indicated that elderly patients and females were more in locoregional myxoid leiomyosarcoma than myxoid liposarcoma and myxoid chondrosarcoma with locoregional metastasis. The white race represented the most patients who suffered from these cancers than other races. The heart is the primary site for the abovementioned cancers, in addition to the female genitals to the myxoid leiomyosarcoma. Myxoid liposarcoma and myxoid chondrosarcoma patients with locoregional metastasis were suffering from grade II, while locoregional myxoid leiomyosarcoma patients with blank grading were due to missed data. Surgery was the most common treatment modality in this study compared with radiotherapy and chemotherapy. Kaplan-Meier analysis showed a significant difference in survival time between the three subtypes by using histology, and myxoid leiomyosarcoma showed prolonged survival than others. Elderly, female, white, unknown grade, surgery, no radiation, and no chemotherapy variables were independent factors associated with overall survival among these cancers. Multivariate analysis also showed significant differences in overall survival between the three tumors by histology, and myxoid leiomyosarcoma was with a better prognosis than others. Multivariate analysis of locoregional myxoid leiomyosarcoma showed the statistical significance of black race, grade, and radiotherapy, indicating them as independent prognostic factors of locoregional myxoid leiomyosarcoma. We conclude that surgery was the primary treatment modality against these cancers than radiotherapy and chemotherapy. And the locoregional myxoid leiomyosarcomas showed a better prognosis and higher survival rate than locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma.

Myxoid Leiomyosarcoma of the Uterus: A Case Report With Magnetic Resonance Imaging Findings