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Leiomyosarcoma in soft tissue: examination of p53 status and cell proliferating factors in different locations.

The biological behavior of soft tissue leiomyosarcoma varies with its location: tumors in deep soft tissue show a worse prognosis than those in superficial soft tissue. In this study, we analyzed cell proliferating factors (mitotic and Ki-67 indices) and the p53 status of both types of leiomyosarcoma (37 cases) to evaluate the possibility that these factors may serve as indicators in prognosis. Expression of both of the cell proliferating factors were higher in the superficial type, but these differences were not significant. The incidence of abnormal p53 detected by immunohistochemistry and mutation analysis was also higher in the superficial type, but, again, no significant difference was observed. Abnormal p53 and a high Ki-67 index in the deep type, and a large tumor size (>6 cm) in the superficial type may be useful as prognostic factors. Interestingly, all of the superficial cases who died of the disease showed abnormal p53. In conclusion, these two types of leiomyosarcoma are essentially the same, and their location remains a good prognostic factor. Furthermore, abnormality of the p53 gene was related to a poor prognosis regardless of the tumor's anatomic location.

Adult↗

Leiomyosarcoma in urinary bladder after cyclophosphamide therapy for retinoblastoma and review of bladder sarcomas.

We report an unusual case of a leiomyosarcoma of the urinary bladder after chemotherapy for retinoblastoma and the results of a review of the published reports of bladder sarcomas. A 22-year-old man presented with hematuria and was found to have a mass in his urinary bladder on computed tomography. Transurethral resection of the mass revealed a leiomyosarcoma. The patient underwent radical cystectomy and an ileal conduit was created. The final pathologic examination confirmed high-grade leiomyosarcoma. Prospective randomized combination trials similar to the Intergroup Rhabdomyosarcoma Study in the pediatric population are necessary to better understand and manage these potentially curable sarcomas.

Adult↗

Paratesticular leiomyosarcoma in an elderly man.

Soft tissue tumors, both benign and malignant, of the testes are relatively uncommon. Primary leiomyosarcoma of the testis is rare, and its clinical behavior is difficult to predict. We report a case of paratesticular leiomyosarcoma in a 71-year-old man. Routine histologic examination and immunohistochemical staining were performed. The tumor was composed of interlacing fascicles of smooth muscle cells with marked nuclear pleomorphism and three to four mitoses per high power field, with few atypical mitoses. On the basis of the microscopic examination and immunohistochemical studies, the tumor was identified as a paratesticular leiomyosarcoma. The published studies on this entity are reviewed.

Aged↗

Evaluation of paclitaxel in previously treated leiomyosarcoma of the uterus: a gynecologic oncology group study.

OBJECTIVE: The purpose of this phase II trial was to evaluate the efficacy of intravenous paclitaxel in patients with recurrent or advanced leiomyosarcoma of the uterus. METHODS: To be eligible, patients with recurrent or persistent leiomyosarcoma of the uterus were to have measurable disease not previously treated with paclitaxel and adequate hematologic (WBC >or=3000/microl, platelet count >or=100000/microl), renal (serum creatinine <or=2.0 mg%), and hepatic (bilirubin <or= 1.5 x institutional normal) functions. Paclitaxel was given at a dose of 175 mg/m(2) (135 mg/m(2) for patients with prior radiotherapy) intravenously over 3 h every 3 weeks. RESULTS: Fifty-three patients were entered on this study; 48 were evaluable for toxicity and response. Fifteen had prior irradiation and 39 had prior chemotherapy. A median of 2 (range: 1-12) courses was given. Grade 4 neutropenia occurred in 3 (6.3%) patients. No grade 4 thrombocytopenia was reported and no deaths were attributable to therapy. Four (8.4%) patients had a complete or partial response and 22.9% had stable disease. CONCLUSIONS: Although toxicity was minimal, this regimen demonstrated modest activity in patients with previously treated advanced or recurrent leiomyosarcoma of the uterus.

Adult↗

Atrial fibrillation and tumor emboli as manifestations of metastatic leiomyosarcoma to the heart and lung.

Leiomyosarcoma is a malignant tumor of the smooth muscle that rarely occurs in the gastrointestinal tract. High-grade leiomyosarcomas of the rectosigmoid usually metastasize to the liver and lungs. Although it is unusual, metastases to the heart have been reported. When this occurs, the metastatic tumor usually seeds in the right atrium and pulmonary artery. We report on and discuss a patient who had atrial fibrillation, peripheral emboli, and thrombocytopenia resulting from a low-grade rectosigmoid leiomyosarcoma metastatic to the pulmonary vein and left atrium. Atrial fibrillation is not a common manifestation of malignant neoplasms that have spread to the heart. Surgical removal of the tumor terminated the arrhythmia and thrombocytopenia.

Atrial Fibrillation↗

[Leiomyosarcoma and Stauffer syndrome].

INTRODUCTION: Stauffer's syndrome is a non-metastatic anicteric cholestasis and an inflammatory syndrome usually associated with renal cell carcinoma. EXEGESIS: We present a case report of an eighty-four-year-old woman who had a leiomyosarcoma revealed by Stauffer's syndrome, which disappeared after surgery. CONCLUSION: Abnormal secretion of interleukin-6 by the leiomyosarcoma could explain this syndrome. The association of Stauffer's syndrome and leiomyosarcoma has never been described.

Aged↗

Leiomyosarcoma of the vagina.

Vaginal leiomyoma is uncommon and borderline leiomyoma of the vagina is an extreme rarity. Leiomyoma of the vagina may undergo malignant change to become borderline malignancy or leiomyosarcoma. A 38-year-old woman, complaining of foul vaginal discharge and dyspareunia with 2 months duration, underwent total excision of tumor. The removed tumor was diagnosed as borderline case of leiomyoma histologically. Unfortunately, she had tumor recurrence within 4 months. Thus, it was more likely that the primary diagnosis was incorrect and that the diagnosis leiomyosarcoma has been missed. She underwent total abdominal hysterectomy, bilateral salphingo-oophorectomy and total vaginectomy. The final diagnosis was leiomyosarcoma. Three months later tumor recurred again and re-excision followed by chemotherapy was performed. However, she died of her disease on her 5th month following three courses of chemotherapy.

Adult↗

Relative quantitation of p53 and MDM2 gene expression in leiomyosarcoma; real-time semi-quantitative reverse transcription-polymerase chain reaction.

To investigate the etiology of leiomyosarcoma, we examined abnormalities of p53 and its regulation in 13 cases of leiomyosarcoma using fresh tumor specimens. We estimated p53 and MDM2 mRNA level and MDM2 gene amplification using a real-time semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) based on the TaqMan fluorescence method. We also used immunohistochemistry (IHC) for p53 and MDM2 protein overexpression, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and direct sequencing to detect p53 mutation. Eight of the 13 cases (62%) showed an overexpression of p53 protein on IHC and eight of 13 cases (62%) had p53 gene point mutations. Five of the 13 cases (38%) showed positive staining for MDM2 protein and only one case (7.7%) demonstrated MDM2 gene amplification. The relative p53 mRNA level of the tumors compared with normal tissue ranged from 1.14 to 12.19 arbitrary units (AU), and the MDM2 mRNA level ranged from 1.06 to 17.17 AU. The mRNA level in the p53-positive cases was higher than in the negative cases (positive: 7.70 AU on average; negative: 3.38 AU on average; P=0.0344). However, there was no significant correlation between the MDM2 mRNA level and other factors, such as p53 IHC, p53 mutation status, p53 mRNA level and MDM2 IHC. Our results indicate that p53 abnormalities are major events and that an increasing level of p53 mRNA is associated with an overexpression of p53 protein in leiomyosarcoma and they may play an important role in the tumorigenesis in this tumor.

Adult↗

Subsequently occurring leiomyosarcoma and desmoid tumor of the right thigh.

We present the case of a 44-year-old patient with a primary leiomyosarcoma of the right upper thigh, who developed a second mesenchymal lesion at the same thigh, diagnosed as an extra-abdominal desmoid tumor, some months after surgical treatment of his leiomyosarcoma. Clinically, histomorphologically, DNA cytometrically, immunohistochemically and radiologically the different histogenetic origin of the two lesions could be proven. The patient died 17 months after his first tumor diagnosis of lung metastases of his leiomyosarcoma.

Adult↗

[Leiomyosarcoma of the middle segment of the inferior vena cava: tactical problems raised by renal and caval revascularisation].

INTRODUCTION: Leiomyosarcoma of the inferior vena cava is mesenchymal tumor accounting for 95% of primary tumors of the vena cava. Characteristic features include late invasion of adjacent structures and metastases, and delayed diagnosis. OBSERVATION: We report a case of inferior vena cava (IVC) leiomyosarcoma (LMS) found in a 53 year-old man who complained of abdominal pain. Morphologic exams found a very large polycyclic mass in the inferior vena cava involving the middle segment of the vena cava extending from the renal veins to the hepatic veins. An "en bloc" resection of the tumor was achieved. Caval outflow was restored using a ring-reinforced PTFE tube graft, the left renal vein was ligated and not re-implanted, the right renal vein was implanted in a lumbar sub-renal vein using a short prosthesis. Pathological examination documented a grade II leiomyosarcoma of the inferior vena cava and the patient was given adjuvant chemotherapy (anthracycline). One year later, there was no local or regional relapse. COMMENT: We emphasize the importance of restoring caval outflow which provides effective results when used with a ring-reinforced polytetrafluoroethylene (PTFE) prosthesis. Furthermore, the importance of restoring right renal outflow is highlighted because ligature of the renal vein can lead to renal ischemia and nephrectomy which should only be performed in specific cases. The tactical problems of renal and caval revascularisation, including the place of prosthetic replacement, are discussed.

Blood Vessel Prosthesis↗

MR imaging of primary leiomyosarcoma of the thyroid gland.

Primary leiomyosarcoma of the thyroid gland is extremely rare and radiological information on this tumor is scant. We presented radiological findings on primary thyroid leiomyosarcoma in a 66-year-old woman in which anaplastic carcinoma was suspected based on clinical and cytological features and discussed the radiological clues to distinguish between the two diseases. Ultrasonography showed an ill-defined hypoechoic mass without halo in the left lobe and the isthmus of the thyroid gland. Computed tomography depicted a low-density mass with calcification and necrosis, which invaded the thyroid cartilage. No lymphadenopathy was seen. The tumor was demonstrated as an isointense mass on T1-weighted MR images and a mass of intermediate signal on T2-weighted images. The tumor showed a fair enhancement on gadolinium-enhanced T1-weighted images. Although the radiological picture was nonspecific, primary thyroid leiomyosarcoma appeared less invasive and far less frequent in developing nodal metastasis than anaplastic carcinoma in light of the literature.

Aged↗

A leiomyosarcoma of the oesophagus presenting incidentally without dysphagia.

Leiomyosarcoma is a rare tumour that accounts for 0.5% oesophageal sarcomas. The most common presenting symptom is dysphagia. This report presents a case of oesophageal leiomyosarcoma in a 56-year-old Caucasian man found incidentally while being investigated for refractory cough. There was no history of dysphagia in spite of tumour mass occupying most of the oesophageal lumen. The leiomyosarcoma was managed successfully with surgical resection and adjuvant radiotherapy. The patient remains disease free after 15 months after surgical intervention. The unusual case presentation is discussed and the surgical management of this rare condition reviewed.

Esophageal Neoplasms↗

Surgical treatment and outcomes of patients with primary inferior vena cava leiomyosarcoma.

BACKGROUND: The inferior vena cava (IVC) is a rare site for primary soft tissue sarcoma. There are limited data in the literature regarding surgical management of the IVC and longterm survival of these patients. STUDY DESIGN: From 1982 to 2002, a total of 25 patients with primary IVC leiomyosarcoma was treated as inpatients and followed in a prospective database at Memorial Sloan-Kettering. Presenting symptoms, tumor characteristics, operative management, postoperative morbidity, and disease-specific survival were assessed for each patient. RESULTS: The 25 patients with primary IVC leiomyosarcoma accounted for 0.5% of all adult patients with soft tissue sarcoma treated during this time. The median patient age was 56 years (range 41 to 79 years). The three most common presenting symptoms were abdominal pain (52%), distention (20%), and deep venous thrombosis (12%). Of the patients, 21 (84%) underwent complete resection of the tumor. The IVC was managed in one of three ways: ligation (n = 11), primary/patch repair (n = 8), and expanded polytetrafluoroethylene tube grafting (n = 2). Among patients undergoing IVC ligation and primary/patch repair (n = 19), 11% had severe postoperative edema and none had worsening renal function. Local recurrence occurred in 33% of patients and distant recurrence occurred in 48% of patients. Patients undergoing complete resection had 3-year and 5-year disease-specific survival rates of 76% and 33%, respectively. There were no 3-year survivors among patients with incomplete resections. CONCLUSIONS: Complete resection of primary IVC leiomyosarcomas is feasible and associated with improved survival. The IVC can be managed by primary repair or ligation with a low risk of severe postoperative edema.

Female↗

Post-radiation primary intranodal leiomyosarcoma.

An unusual case of post-radiation primary intranodal leiomyosarcoma of the cervical lymph node is presented. The patient was a 32-year-old white man who was treated in 1986 with hemiglossectomy and right neck dissection, followed by radiation therapy, for squamous cell carcinoma of the tongue. Six years later, he presented with an enlarged left cervical lymph node which on biopsy showed a high grade spindle cell malignant neoplasm. Immunohistochemistry and electron microscopic study verified the smooth muscle origin of the tumour. Extensive work-up for a second primary lesion was negative. Primary intranodal leiomyosarcoma is extremely rare. We briefly discuss the histological differential diagnosis of spindle cell lesions of lymph nodes, leiomyosarcoma of the vessel wall and radiation-associated sarcoma.

Adult↗

Leiomyosarcoma of the larynx.

Tumours of smooth muscle origin are extremely rare in the upper aerodigestive tract. Immunohistochemical studies are helpful for accurate diagnosis of leiomyosarcoma. Here, we report a case of well-differentiated laryngeal leiomyosarcoma that showed rapid local growth but no metastasis. Diagnosis and treatment of leiomyosarcoma are discussed.

Actins↗

Do DNA copy number changes differentiate uterine from non-uterine leiomyosarcomas and predict metastasis?

DNA copy number changes were investigated in 51 (19 uterine and 32 nonuterine) primary leiomyosarcomas by comparative genomic hybridization. The aim was to evaluate whether true biological differences exist between uterine and nonuterine leiomyosarcoma and whether changes revealed by comparative genomic hybridization have prognostic value. Genomic imbalances were found in 48 (94%) cases. The most frequent DNA copy number changes were losses in 10q (35%), 13q (57%), and 16q (41%), gains in 1q (41%), and gains and high-level amplifications in 17p (39%). Gains were nearly as frequent as losses in both uterine and nonuterine leiomyosarcoma. Correlation-based tree modeling revealed two clusters that segregated significantly a group of uterine (gains at 1q11-q24) and a group of nonuterine (losses at 13q14-q34, 16q11.1-q24, and 10q21-q26) cases. The nonuterine cluster was associated with subcutaneous origin and a trend toward increased metastasis-free survival. Further explorative analyses identified aberrations associated with shorter metastasis-free survival time, including losses at 2q32.1-q37 and gains at 8q24.1-q24.3, whereas the cases with losses at 6cen-p25 showed longer metastasis-free survival time.

Adult↗

Epithelioid leiomyosarcoma in a non-immunocompromised infant: additional differential diagnosis of pediatric "round cell tumors".

We report an 18-month-old Japanese girl with purely epithelioid leiomyosarcoma presenting as a huge intraabdominal mass. The patient had been well from birth and had shown no signs of immunodeficiency. She was negative for human immunodeficiency virus. Blood examination revealed elevated serum neuron specific enolase (NSE). Histologically, the tumor was comprised of solid growths of round or polygonal cells with vesicular nuclei and often vacuolated cytoplasm rich in glycogen. The tumor cells were positive for vimentin, NSE, and MIC2, and were negative for desmin and neurofilament. The age, clinical presentation, and histologic findings mostly favored Ewing's sarcoma/primitive neuroectodermal tumor. Silver stain, however, demonstrated well-developed reticulin fibers often outlining individual tumor cells. An expanded panel of immunostains showed that the tumor cells were intensely positive for smooth muscle actin, and ultrastructural study revealed abundant fine cytoplasmic filaments with focal subsarcolemmal densities, various amounts of glycogen, and irregularly arranged, thick basal lamina. The diagnosis of epithelioid leiomyosarcoma was made. Following reduction in tumor size by chemotherapy, the serum NSE level was normalized. From the surgical finding, the primary site was presumed to be the urachus or the urinary bladder dome. Although extremely rare, epithelioid leiomyosarcoma should be added in the list of differential diagnoses of pediatric "round cell tumors."

Abdominal Neoplasms↗

Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling.

In this study, we have used genome-wide expression profiling to categorise synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas (MFHs). Following hierarchical clustering analysis of the expression data, the best match between tumour clusters and conventional diagnosis was observed for synovial sarcomas. Eight of nine synovial sarcomas examined formed a cluster that was characterised by higher expression of a set of 48 genes. In contrast, sarcomas conventionally classified as leiomyosarcomas and MFHs did not match the clusters defined by hierarchical clustering analysis. One major cluster contained a mixture of both leiomyosarcomas and MFHs and was defined by the lower expression of a set of 202 genes. A cluster containing a subgroup of MFHs was also detected. These results may have implications for the classification of soft tissue sarcomas, and are consistent with the view that sarcomas conventionally defined as MFHs do not represent a separate diagnostic category.

Cluster Analysis↗