<b>Uterine Leiomyosarcoma and HRT

Abstracts of Medical Journal Reference Articles</b>

compiled by doctordee

Environ Health Perspect 2000 Oct;108 Suppl 5:779-84

<b>Pathology and pathophysiology of uterine smooth-muscle tumors.</b>

Robboy SJ, Bentley RC, Butnor K, Anderson MC. Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710,USA. stanley.robboy@duke.edu

Smooth-muscle tumors of uterine origin encompass a broad family of neoplasms. <b>The leiomyoma, by far the most common of all the neoplasms, generally is hormone sensitive, with rates of growth semiquantitatively related to estrogen and progesterone receptor levels. Several forms of degenerative change can occur in the leiomyoma.</b> The most common is hyaline degeneration, which is important in that it should not be mistaken for the coagulative tumor cell necrosis seen in leiomyosarcoma. Red degeneration (necrobiosis) is a form of degeneration that occurs characteristically but not exclusively in pregnancy, and the process is often the cause of pain and fever. Several forms of treatment have been used medically in the treatment of leiomyoma. <b>Gonadotropin-releasing hormone analogs or agonists or selective arterial embolization with polyvinylformaldehyde particles may lead to substantial degeneration or infarction of the leiomyoma, respectively.</b> Several variants of leiomyoma, the cellular and symplastic leiomyomas, are important to recognize, as they can be misinterpreted as sarcoma. In addition, there are two unusual growth patterns of leiomyoma that are important to recognize. <b>Both the benign metastasizing leiomyoma and disseminated peritoneal leiomyomatosis are found outside the uterus, and neither is malignant.[the benign metastasizing leiomyoma has been postulated to be a low grade, slow growing leiomyosarcoma] Recent studies offer insights into their origin and hormonal influences. From a diagnostic and therapeutic point of view, the leiomyosarcoma, while rare, is clinically of great import. Coagulative necrosis, cytologic atypia, and mitotic counts are all important in diagnosing the condition.</b> Publication Types: Review, tutorial 
&&url PMID: 11035982

Arch Pathol Lab Med 1999 Oct;123(10):960-2

<b>Benign metastasizing leiomyoma of the uterus: histologic and immunohistochemical characterization of primary and metastatic lesions.</b>

Esteban JM, Allen WM, Schaerf RH. Department of Pathology, Providence/Saint Joseph Medical Center, Burbank, Calif 91505, USA.

<b>Benign uterine leiomyoma metastasizing to the lung is a recognized entity that has been reported infrequently in the medical literature. There is persisting controversy regarding the pathogenesis and biology of these lesions.</b> We report a well-studied and well-characterized case of benign leiomyoma metastasizing to the lung. The patient was a 72-year-old woman with an enlarged uterus that contained several leiomyomas with usual histology. Areas of fibrosis, hyalinization, edema, and focal infarction together with small foci with mildly increased cellularity and minimal nuclear pleomorphism were seen. Careful and repeated mitotic counts ranged from 0 to 2 mitoses per 10 high-power fields. In summary, based on histopathologic criteria, the neoplasm was determined to be a focally cellular benign leiomyoma. <b>Four years later, the patient underwent surgical resection of a single nodule in the lung</b>, which had been detected on routine radiographs. <b>Histopathologic evaluation showed a low-grade leiomyosarcoma with moderate nuclear pleomorphism, necrosis, and brisk mitotic activity. Immunohistochemical studies performed on both neoplasms showed them to be of mesenchymal derivation with smooth muscle differentiation. Both neoplasms expressed estrogen receptors with moderate to strong intensity. The patient received no further treatment and, to date, shows no evidence of recurrent disease.</b> The diagnosis of benign metastasizing leiomyoma can only be made with certainty after careful and extensive sampling of the primary tumor to exclude small foci of sarcoma and of the pulmonary tumor to rule out a primary neoplasm. Although it is biologically peculiar, benign metastasizing leiomyoma should continue to be recognized as a distinct entity because current morphologic criteria do not allow primary myometrial tumors to be reclassified as leiomyomas of uncertain malignant potential even if they have metastasized to the lung. 
&&url PMID: 10506455

Gynecol Oncol 1999 Oct;75(1):158-63

<b>Leiomyomatosis peritonealis disseminata: does malignant transformation occur? A literature review.</b>

Bekkers RL, Willemsen WN, Schijf CP, Massuger LF, Bulten J, Merkus JM. Department of Obstetrics and Gynaecology, University Hospital, St. Radboud, Nijmegen, 6500 HB, The Netherlands.

<b>The following is a summary of the abstract...as the abstract is under copyright.</b>

<b>Leiomyomatosis peritonealis disseminata (LPD) is a rare smooth muscle tumor of which more than 100 cases have been described. It typically presents as multiple small nodules on the peritoneal surface, mimicking a malignant process with metastases. But the pathology reports are benign. Estrogen exposure has an etiologic role, and many patients have uterine leiomyomas as well, for which estrogen exposure also has an etiologic role. The diagnosis of LPD is made by biopsy. Reducing estrogen exposure is usually causes regression of LPD. Surgical castration or gonadotrophin releasing hormone agonists seem good alternatives if LPD progresses or recurs.</b> In six patients a malignant leiomyosarcoma has been described shortly after the diagnosis of LPD was made. Five of these patients did not have uterine leiomyomas, exposure to exogenous estorgen, or increased endogenous estrogen, and the relationship with pregnancy in the sixth patient may be coincidental. Whether LPD undergoes malignant transformation is unknown. Characteristics of the LMS patients differ from those of LPD patients and may indicate a high malignant potential, needing a different approach. <b>Copyright 1999 Academic Press.</b> Review of reported cases 
&&url PMID: 10502446

Int J Gynecol Pathol 1999 Jan;18(1):20-8

<b>Expression of steroid receptors, Ki-67, and p53 in uterine leiomyosarcomas.</b>

Zhai YL, Kobayashi Y, Mori A, Orii A, Nikaido T, Konishi I, Fujii S. Department of Obstetrics and Gynecology, Shinshu Univ. School of Medicine,Matsumoto, Japan.

<b>The expression of estrogen receptor (ER), progesterone receptor (PR)</b>, tumor suppressor oncogene p53, and Ki-67 <b>was compared in uterine smooth muscle tumors, including leiomyosarcoma (LMS)</b>, tumor of uncertain malignant potential (UMP), cellular leiomyoma (CL), bizarre leiomyoma (BL), and usual leiomyoma (UL). ER and PR were expressed in all ULs. PR was expressed in UL irrespective of the phase of the menstrual cycle; this staining was also observed in CL, UMP, and BL, although BL showed variable staining for ER. <b>Compared to these tumors, the expression of both ER and PR was markedly reduced in LMS.</b> The results of ER and PR transcripts by reverse transcription-polymerase chain reaction were compatible with those of immunohistochemistry. The number of Ki-67 positive cells in LMS was significantly higher than in UMP, BL, CL, and UL. p53 immunoreactivity was seen in 10 of 14 LMSs, and missense mutation in the p53 gene was found in 4 of 10 LMSs. These results suggest that abnormal expression of ovarian steroid receptors, p53, and Ki-67 is frequently associated with LMS of the uterus. 
&&url PMID: 9891238

Mod Pathol 1999 Nov;12(11):1001-9

<b>Comparative immunohistochemical and molecular analysis of uterine and extrauterine leiomyosarcomas.</b>

Rao UN, Finkelstein SD, Jones MW. Department of Pathology, University of Pittsburgh Medical Center, Presbyterian University Hospital, Pennsylvania 15213-2582, USA.

Histologic criteria defining malignancy in smooth muscle tumors are currently site specific. <b>This study was undertaken to determine whether, in leiomyosarcomas (LMS) occurring in different anatomic locations, there were differences in patterns of expression of molecules that have been demonstrated to be associated with biologically aggressive behavior in malignant neoplasms, and also to determine their diagnostic utility. Formalin-fixed paraffin-embeddedtissue blocks were selected from 16 extrauterine leiomyosarcomas (EULMS), 14 cases of uterine leiomyosarcomas (ULMS) and from five cases each of uterine and extrauterine leiomyomas (LM).</b> Utilizing immunohistochemical (ABC) techniques with antigen retrieval, <b>we assessed serial sections of each tumor</b> for immunoreactivity with Glut1, CD44s, bcl2, cyclin D1, and <b>estrogen receptor.</b> Molecular genotyping for detecting k-ras-2 point mutation, p53 gene loss, and mdm2 gene amplification was performed on microdissected tumor samples from the same histologic sections. All of the uterine and extrauterine LM were diffusely positive for CD44s, bcl2, and cyclin D1, and uniformly negative for Glut1. In contrast, 50% of the ULMS and 25% of EULMS were Glutl positive. Moreover, Glut1 positivity closely correlated with aggressive biologic behavior reflected by distant metastatic spread. <b>Eighty-percent of LM and 70% of the ULMS were estrogen receptor positive, whereas only one retroperitoneal tumor had focal weak positivity.</b> Over 80% of the extrauterine and 50% of the uterine sarcomas showed absence of CD44s immunoreactivity. Percentage of cyclin D1 immunoreactivity was independent of tumor grade and inversely proportional to the percent of bcl2 positivity. An LMS of the male breast contained k-ras-2 exon 1 point mutation (codon 12 aspartate substitution of glycine). P53 allelic imbalance was present in 29% of ULMS and 57% EULMS. Mdm2 amplification was present in three of six EULMS but not in ULMS. In addition to clinical staging, Glut1 positivity together with patterns of immunoreactivity of CD44 and bcl2 may be helpful in identifying aggressive smooth muscle tumors of the uterus and some EULMS. <b>The presence of estrogen receptor staining may be helpful in identifying uterine versus nonuterine LMS. Although sample numbers are too small for definite conclusions, this study suggests that there are differences in glucose transport, expression of adhesion molecules, and estrogen receptors in ULMS and EULMS, which in part may be due to the estrogen dependency of the ULMS.</b> P53 mutations and mdm2 amplifications appear to be more frequent in EULMS. Publication Types: Clinical trial Randomized controlled trial 
&&url PMID: 10574596

Eur J Gynaecol Oncol 1999;20(5-6):379-82

<b>Hormone replacement therapy after uterine leiomyosarcoma treatment. Case reports.</b>
Ursic-Vrscaj M. Institute of Oncology, Ljubljana, Slovenia.
Uterine sarcomas are extremely rare uterine malignancies; with a review of the literature we could not find any data dealing with exogenous oestrogens or combined hormone replacement therapy (HRT) after leiomyosarcoma treatment. We report two cases of patients with leiomyosarcoma of the uterine corpus. Both patients were without pelvic irradiation or exogenous oestrogen treatment before the diagnosis. Leiomyoma of the uterus was found during surgery in both cases. Both patients were receiving HRT with non-conjugated oestrogens, after an intensive non-hormonal treatment had failed. No recurrence was established after surgical treatment in the patient with 12 mitoses per 10 high power fields (HPF). The patient is still on HRT (61 months). The other patient with a leiomyosarcoma with very high mitotic activity (40 mitoses per 10 HPF) received cytostatic and irradiation therapy after surgery because of locally widespread disease. Ten months after the diagnosis and 3 months after beginning HRT, recurrence was observed. The patient thereupon stopped HRT. After two additional operations, the patient is alive and without evidence of disease. We presume that the present case reports observations might suggest that HRT did not appear to have a pronounced adverse effect on the leiomyosarcoma outcome in our patients. Nevertheless, until more collected data determine that HRT is safe, caution is needed.
&&url PMID: 10609499  

Pathol Res Pract 1996 Mar;192(3):215-23

<b>Immunohistological detection of estrogen and progesterone receptors in multiple and well differentiated leiomyomatous lung tumors in women with uterine leiomyomas (so-called benign metastasizing leiomyomas). A report on 5 cases.</b>

Jautzke G, Muller-Ruchholtz E, Thalmann U. Institut fur Pathologie, Universitatsklinikum Rudolf Virchow, Berlin, Germany.
<b>Seventy-four cases of so-called "benign metastasizing uterine leiomyomata" are reported in the literature. In these cases, well differentiated, leiomyomatous lung tumors developed, usually after a period of several years. Histologically, these tumors appear to be benign. We report on five more such cases in which we investigated the contents of estrogen and progesterone receptors in the pulmonary tumors</b> by immunohistological procedures. <b>All the lung tumors exhibited a high content of progesterone receptors, and in 4 out of the 5 cases a high estrogen receptor content was also found. Modern immunohistological techniques permit the investigation of routinely fixed tissue blocks, and it is thus recommended that the contents of these hormone receptors should be determined in well differentiated, leiomyomatous lung tumors from women. This would both provide information on the pathogenesis of these tumors and establish a basis for possible later institution of hormone treatment. It is likely that the majority of these lung tumors are in fact metastases of extremely well differentiated leiomyosarcomas of the uterus.</b> The possibility that lung tumors of this type may constitute a small group that develop in situ as hormone-sensitive proliferations cannot, however, be fully excluded. Publication Types: Review of reported cases 
&&url PMID: 8739468

Cancer 1996 Feb 15;77(4):717-24

<b>Exogenous sex hormone use, correlates of endogenous hormone levels, and the incidence of histologic types of sarcoma of the uterus.</b>

Schwartz SM, Weiss NS, Daling JR, Gammon MD, Liff JM, Watt J, Lynch CF, Newcomb PA, Armstrong BK, Thompson WD. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center,Seattle,Washington, 

BACKGROUND: <b>We analyzed data from a population-based, multi-center, case-control study to determine whether the occurrence of histologic types of uterine sarcoma is related to exogenous hormone use and/or to two correlates of endogenous estrogens: excess weight and cigarette smoking.</b> METHODS: One hundred sixty-seven women with newly-diagnosed uterine sarcoma (<b>56 leiomyosarcoma</b>, 85 mixed mullerian tumors, and 26 endometrial stromal sarcomas) were interviewed by telephone regarding possible risk factors for these neoplasms, For comparison, 208 women identified at random from the general population of the study areas were interviewed as controls. RESULTS: <b>Use of oral contraceptives was positively associated with the risk of leiomyosarcoma (odds ratios [OR] = 1.7, 95% confidence interval [CI] = 0.7, 4.1), primarily among women who last used these medications 15 or more years prior to diagnosis.</b> Use of noncontraceptive estrogens was directly associated with the risk of mixed mullerian tumors, but only among recent and long-term users of these medications. <b>Women in the highest quantile of body mass index (> or = 27.5 kg/m2) one year prior to diagnosis were at increased risk of each type of uterine sarcoma (leiomyosarcoma, OR = 2.5, 95%</b> CI = 1.1, 5.7; mixed mullerian tumors, OR = 2.9, 95% CI = 1.3, 6.7; stromal sarcoma, OR = 3.5, 95% CI = 1.1, 10.9). <b>Women who had ever smoked cigarettes were at reduced risk of leiomyosarcoma (OR = 0.6, 95% CI = 0.3, 1.1) and stromal sarcoma (OR = 0.5, 95% CI = 0.2, 1.2), but the relationship was not more pronounced among heavy smokers;</b> no association with smoking was observed with mixed mullerian tumors. CONCLUSIONS: <b>Several of these findings parallel those from studies of endometrial carcinoma and may indicate a role for unopposed estrogen in the etiology of histologic types of uterine sarcoma.</b> 
&&url PMID: 8616764 

Surg Today 1996;26(2):138-41

<b>The effectiveness of medroxyprogesterone in the treatment of multiple metastasizing leiomyosarcomas: report of a case.</b>

Uchida T, Nakakawaji K, Sakamoto J, Kojima H, Murakami H, Kato J, Yasue M. Department of Surgery, Aichi Prefectural Hospital, Kakemachi, Okazaki, Japan.

A 51-year-old woman was admitted to our hospital for further investigation of chest X-ray films which showed multiple shadows that had been growing slowly over 2 years. Her only symptom was hemosputa. <b>The lesions were suspected of being metastasizing leiomyoma due to her past history of uterine leiomyoma.</b> Just 1 week before undergoing scheduled open lung biopsy, the lung lesions increased remarkably in size and number. A thoracotomy was performed and six of the numerous nodules were removed. <b>The resected specimens were pathologically diagnosed as metastasizing leimyosarcoma which was positive for the progesterone and estrogen receptors. Thus, 1 month postoperatively, a course of medroxyprogesterone (MPA), 600 mg daily, was commenced. The residual lesions in her chest started to diminish, shortly afterward. She has remained well on this MPA regimen for 45 months. The prognosis of patients with metastasizing leiomyosarcoma is poor because of its low sensitivity to chemotherapy; however, some types of leiomyosarcoma are hormone-sensitive. It is therefore important to examine the hormone receptors of excised tumors from patients suspected of having metastasizing leiomyoma or leimyosarcoma.</b> 
&&url PMID: 8919287

Gynecol Oncol 1994 Jan;52(1):74-9

<b>Uterine leiomyosarcomas coexistent with cellular and atypical leiomyomata in a young woman during the treatment with luteinizing hormone-releasing hormone agonist.</b>

Lee WY, Tzeng CC, Chou CY. Department of Pathology, National Cheng Kung University Hospital,Tainan,Taiwan,RepofChina.

We report a case of a 28-year-old woman who had received 2 months of intranasal buserelin (a luteinizing hormone- releasing hormone agonist; LH-RH agonist) therapy for presumed uterine leiomyomata. In addition to no reduction of the tumor size evaluated by sonography, heavy vaginal bleeding and abdominal pain recurred and worsened during the therapy. Pathological examination of the myomectomy and hysterectomy specimens revealed leiomyosarcomas coexistent with cellular, atypical, and classical leiomyomata. <b>We suggest that this is a case of leiomyosarcomas arising in preexisting leiomyomata</b> rather than de novo from the smooth muscle fibers of the myometrium. <b>Furthermore, the potential of LH-RH, agonist therapy to delay the surgical treatment of an unsuspected leiomyosarcoma is high-lighted.</b> Close monitoring of the treatment response by improvement of clinical symptoms and sonographic assessment of tumor size may be helpful in early diagnosis of an underlying malignant tumor. Review of reported cases 
&&url PMID: 8307505 


Nihon Kyobu Shikkan Gakkai Zasshi 1993 Jul;31(7):890-5
<b>[A case of so-called benign metastasizing leiomyoma responsive to progesterone].[Article in Japanese]</b>

Motegi M, Takayanagi N, Sando Y, Ubukata M, Imai S, Suzuki T, Nakajima T,Yoshida I. Second Department of Internal Medicine, Gunma University School of Medicine,Japan.

A 47-year-old female, who had undergone hysterectomy and unilateral oophorectomy in 1975, was admitted to our hospital in 1989 because chest X-ray films revealed an increase in size and number of pulmonary nodules for two years. On admission, a left inguinal tumor was found and histologically it consisted of smooth muscle cells with nuclear atypia arranged in interlacing fascicles. An open-lung biopsy was performed. Pulmonary tumors revealed similar histology to the inguinal tumor. <b>They were diagnosed as metastatic low-grade leiomyosarcoma, so-called benign metastasizing leiomyoma (BML), on the basis of location and history, reinforced by mild histologic atypia. The tumor contained a high progesterone receptor level (400 fmol/mg). Therefore, medroxyprogesterone acetate, 600 mg daily, was administered orally. At two years the pulmonary lesions had regressed. BML is a rare condition, considered to be pulmonary metastasis from low-grade leiomyosarcoma of the uterus. Measuring estrogen and progesteronereceptors in lung biopy material may help determine the most appropriate therapy.</b> 
&&url PMID: 8366630 

Acta Cytol 1986 Mar-Apr;30(2):93-8

<b>Comparison of cytohormonal status of postmenopausal women with cancer to age-matched controls.</b>

Cassano PA, Saigo PE, Hajdu SI.
<b>To determine whether the cytohormonal status of postmenopausal women with cancer involving the uterus and vagina differs from that of women free of cancer, 100 women 60 years of age or older with positive cervicovaginal smears were compared with an age-matched control group without malignant neoplasms.</b> Epidermoid carcinoma was identified in 64 patients (average age: 67 years) and adenocarcinoma in 34 patients (average age: 69 years). <b>One patient had leiomyosarcoma</b>, and another had bladder carcinoma. The paucity of benign squamous cells in the smears precluded hormonal evaluation in 32% of the index cases; the smears from 10% of the controls were also indeterminate. Of the evaluable cases with epidermoid carcinoma of the cervix, a high maturation was noted in 46% as compared to 11% for the matched controls. In addition, <b>high maturation was noted in 69% of those patients with endometrial adenocarcinoma as compared to 19% for the matched controls. None of the index cases were atrophic; 31% of the controls were. A history of exogenous estrogen usage was obtained in three patients with endometrial adenocarcinoma, all with high maturation, and in five controls, none with high maturation. These data appear to indicate a difference in the cytohormonal status of patients with cervical or endometrial carcinoma as compared to those without; consequently, cytologists should be especially attentive to smears showing high maturation from postmenopausal women.</b> 
&&url PMID: 3457512 

Acta Obstet Gynecol Scand 1984;63(6):505-8

<b>Estradiol and progesterone receptors in gynecologic sarcomas.</b>

Lantta M, Karkkainen J, Wahlstrom T, Widholm O.
<b>We report the concentrations of estradiol and progesterone receptors found in the tumor tissue of 5 patients with leiomyosarcoma, 4 of uterine and one of ventricular origin, and of 5 patients with uterine or ovarian carcinosarcoma. Steroid receptor positive and negative tumors were present in both groups of sarcoma. One uterine leiomyosarcoma had a high concentration of estradiol and progesterone receptors, 37 fmoles/mg protein and 156 fmoles/mg protein, respectively. We suggest that steroid receptors should be analysed in all gynecologic sarcomas.</b> 
&&url PMID: 6507052 


Arch Surg 1980 Mar;115(3):244-8

<b>Estrogen receptor proteins in diverse human tumors.</b>

Stedman KE, Moore GE, Morgan RT. 
<b>One hundred three diverse benign and malignant human tissues have been assayed for estrogen receptor proteins. Receptors were detected in many endocrine and nonendocrine tumors. Tissues with estrogen receptor activity included four of five male breast carcinomas, 11 of 14 malignant melanomas, four of eight colon carcinomas, five of seven renal carcinomas, and various sarcomas and benign and normal tissues. Some tumors also had progesterone, androgen, and/or glucocorticoid receptors. These results suggest the use of hormones and hormone antagonists for therapy of a broad range of human cancer. Clinicians of diverse expertise should be aware of, and responsive to, potential endocrinological involvement in many dissimilar disease states.</b> 
&&url PMID: 7356378

Cancer 1980 Mar 1;45(5):932-7

<b>Metastasizing leiomyoma of the uterus. S-phase fraction, estrogen receptor, and ultrastructure.</b>

Cramer SF, Meyer JS, Kraner JF, Camel M, Mazur MT, Tenenbaum MS.
A 33-year-old woman had a metastasizing leiomyoma in which mitotic figures could not be found. The tumor was composed of well differentiated smooth muscle indistinguishable from uterine leiomyoma or normal myometrium by light and electron microscopy. The S-phase fraction of the tumor, measured by in vitro tritiated thymidine labeling, was near the upper limit of the range seen in seven ordinary uterine leiomyomas and was distinctly lower than that in a uterine leiomyosarcoma. The content of estrogen receptors in the cytosol was within the range seen in uterine leiomyomas. <b>Metastasizing leiomyoma is an actively proliferating neoplasm of mature smooth muscle that appears to be hormonally responsive. The tumor in our patient showed no clear differences from ordinary leiomyomas in findings relating to the rate of cellular proliferation, morphology, or estrogen receptor content.</b> 
&&url PMID: 7260844 

Am J Surg Pathol 1979 Aug;3(4):325-42

<b>Pulmonary metastases (with admixed epithelial elements) from smooth muscle neoplasms. Report of nine cases, including three males.</b>

Wolff M, Silva F, Kaye G.
This study pertains to an entity characterized by the presence of multiple intrapulmonary nodules, which consist of an admixture of bundles of well-differentiated smooth muscle cells and epithelial-lined spaces. These lesions have been frequently interpreted as a variant of hamartomas. However, in this review of the literature, and careful analysis of nine cases of this entity, we concluded that they should be considered metastases from smooth muscle tumors which incorporate some structures of mature lung parenchyma as they slowly expand. We affirm that the designation "fibroeliomyomatous hamartoma" should be discarded. Our cases occurred in six female and three male patients. <b>In all but one female the primary source for lung metastases was uterus, while the male patients had primary lesions in the saphenous vein,diaphragm, and soft tissues. These lung lesions increase in size and number and are potentially fatal, though this may take many years. Even though the smooth muscle cells of the lung nodules appear bland on light microscopy, we were always able to demonstrate mitotic activity; electron microscopy indicated immaturity of the cells. For these reasons, we believe the tumors to represent metastatic leiomyosarcomas.</b> Publication Types: Review 
&&url PMID: 395847



