Role of surgery in treating epstein-barr virus-associated smooth muscle tumor (EBV-SMT) with central nervous system invasion: A systemic review from 1997 to 2019.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor occurred almost exclusively in immunocompromised hosts. This article provides a systematic review of literature under PRISMA guideline on clinical features, treatment modalities, roles of surgical intervention, and outcomes of all 65 reported EBV-SMTs with central nervous system (CNS) invasion. Over 95% of reported cases were immunocompromised, while human immunodeficiency virus infection and post-organ transplantation were the most commonly associated underlying causes (near 90%). Despite a heterogeneous follow-up period, a 1-year survival rate of 76.0% and 5-year survival rate of 59.6% may support the indolent and non-deadly nature of EBV-SMT even with CNS invasion. Immune survey and reconstruction should be conducted for every patient with CNS EBV-SMT. Surgical resection is mostly adopted as primary treatment to obtain diagnosis and relieve compressive effect. A total resection of tumor may be beneficial if tumor was symptomatic and had intracranial invasion.

Smooth Muscle Tumors of the Visceral Adnexal and Uterine Ligaments and Adnexal Connective Tissue: A Clinicopathologic Study of 67 Cases.

The endopelvic fascia is a biomechanical network of supportive tissue that suspends and secures the female reproductive organs to the pelvic sidewall. Several visceral adnexal and uterine ligaments are part of this framework, and we have observed that smooth muscle tumors (SMTs) arising from these structures morphologically resemble gynecologic smooth muscle neoplasms. To determine whether gynecologic smooth muscle tumor criteria for malignancy are valid in these tumors, we evaluated the morphologic features of 67 tumors from 67 patients and correlated our findings with patient outcome. Using current uterine SMT WHO definitions, 57 tumors (85%) were classified as leiomyoma, 2 (3%) as smooth muscle tumor of uncertain malignant potential (STUMP), and 8 (12%) as leiomyosarcoma. Clinical follow-up was available for 88% of patients (range: 1-296 mo, mean: 174 mo, median: 79 mo). Only 1 case of leiomyosarcoma had metastasis at time of presentation, but 6 of 8 (75%) patients eventually died of disease. The other 2 cases of leiomyosarcoma that have not recurred are 11 and 16 mo from initial diagnosis. No cases of STUMP or leiomyoma recurred. On the basis of morphologic features and patient outcome, we believe these tumors distribute into similar categories of leiomyoma, STUMP and leiomyosarcoma, paralleling the biologic potential of uterine SMTs as well as SMTs of other gynecologic sites. We propose use of uterine WHO SMT criteria to classify spindled SMTs that arise in the visceral adnexal and uterine ligaments and adnexal connective tissue.

The mitosis-specific marker phosphohistone-H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome-based study.

AIMS: Accurate mitosis counting, which is important in the diagnosis of uterine smooth muscle tumours (USMTs), is often difficult and subjective. The mitosis-specific immunohistochemical marker phosphohistone-H3 (PHH3) has been shown to be diagnostically useful, but its expression, in relation to outcome, has not been thoroughly investigated. The aim of this study is to evaluate PHH3 as a diagnostic and prognostic marker in USMTs. METHODS AND RESULTS: PHH3 expression was evaluated in 55 leiomyosarcomas (LMSs), 26 smooth muscle tumours of uncertain malignant potential (STUMPs), 18 leiomyomas with bizarre nuclei (LBN), and 12 leiomyomas (LMs). Scores were expressed as counts per 10 high-power fields (HPFs). Median follow-up durations of patients with LMS, STUMP, LBN and LM were, respectively, 39, 78, 65.5 and 49.5 months. Twenty-eight patients with LMSs (50.9%) died, and two (7.7%) patients with STUMPs experienced recurrence. The median PHH3 scores for LMSs were significantly higher than those for other categories of tumour. A score of ≥29/10 HPFs was also independently associated with a poor outcome. To test whether the PHH3 score could distinguish between benign USMTs with atypical histology and those that were clinically malignant, two biological groups were further delineated. Patients in group 1 (18 LBNs and 24 STUMPs) all had an uneventful outcome, whereas patients in group 2 (two recurrent STUMPs and 32 LMSs) all had a recurrence or tumour-related death. Median PHH3 scores for the two groups were, respectively, 2/10 HPFs and 27/10 HPFs. A PHH3 score of ≥7/10 HPFs was highly associated with malignancy. CONCLUSION: PHH3 is useful in evaluation of the biological behaviour of USMTs, and may serve as a prognostic indicator for LMSs.

Epstein-Barr virus-associated smooth muscle tumors in AIDS patients: a largest case (series).

This study aimed to determine the outcomes of Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMTs) in AIDS patients at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, treated from 2001-2011. Of the 17 patients, there were five men with a median CD4 count of 26 cells/µL. Eight and nine patients had single and multiple sites, respectively. The most common site was the cranial epidura (58.8%). All patients had EBV within the tumor. Seven patients underwent surgery. The median follow-up was one year. The mortality rate was 41.2%. All patients with undetectable HIV viremia survived. This is the largest case series regarding EBV-associated SMTs in AIDS patients with a long follow-up period.

Epstein-Barr virus-associated smooth muscle tumors after kidney transplantation: treatment and outcomes in a single center.

BACKGROUND: Epstein-Barr virus-associated smooth muscle tumors (EBV SMT) in adult kidney transplant recipients (KTR) are rare. The aims of this study are to document the clinical features, types of treatment given, and outcomes of KTR with EBV SMT in our institution. METHODS: Sixteen patients were identified from our institution's databases. Patients' survival, tumor outcome, and graft survival were compared between patients who remained on cyclosporine-based immunosuppressant and those who converted to sirolimus-based therapy. RESULTS: The median time of diagnosis was 9.4 yr after kidney transplantation, and majority of the patients had multifocal disease at the time of diagnosis. Overall, the patient survival rate was 75% over a mean follow-up period of five yr. Two patients with non-functioning allograft at the time of diagnosis of EBV SMT were excluded from the treatment outcome analysis. Comparing the sirolimus (n = 7) vs. cyclosporine groups (n = 7), patient survival rate was 100% vs. 42.9% (p = 0.08), graft survival 71.4% vs. 28.7% (p = 0.53), and disease-free status 42.9% vs. 14.3% (p = 0.73), respectively. CONCLUSION: Surgical resection in combination with decreasing immunosuppression or conversion to sirolimus appears to be effective in the treatment of EBV SMT in KTR.

Patterns of bone morphogenetic protein-2 expression in smooth muscle tumors of the uterine corpus and other uterine tissues.

Bone morphogenetic proteins (BMPs) are extracellular, multifunctional growth factors that constitute the largest subset of the transforming growth factor ß superfamily. BMP2 is involved in cardiovascular embryogenesis, in addition to a variety of other postnatal functions, such as neovascularization, osteoinduction, tumor signaling, and in the uterus, stromal decidualization at the implantation site. Estrogen receptor signaling is common in smooth muscle tumors of the uterus, and preclinical models suggest significant interactions between BMP2 and estrogen receptor-mediated signaling. The purpose of this study is to define the patterns of BMP2 expression, as assessed by immunohistochemistry, in smooth muscle tumors and other tissues of the uterine corpus, and to establish whether BMP2 expression has any prognostic significance in uterine leiomyosarcomas. BMP2 was positive (cytoplasmic pattern, typically focal) in 24% of leiomyosarcomas and 20.7% of leiomyomata, but was either infrequently expressed or not expressed in all other tissues evaluated, including normal myometrium and endometrium, endometrial stromal tumors, typical adenomyoma, adenomyosis, and serosal endometriosis. The endothelial cells of small, thin-walled vessels were frequently, but not invariably immunoreactive for BMP2. There was no significant difference between BMP2⁺ and BMP⁻ leiomyosarcomas regarding average tumor size, average patient age, microvessel density, and proportions with high tumor grade, advanced stage and frequency of death from disease on follow-up. Two (29%) of 7 BMP2⁺ leiomyosarcomas were estrogen receptor+, compared with 5 (50%) of 10 BMP2⁻ leiomyosarcomas, a statistically insignificant difference (P=0.62). It is concluded that BMP2 is only expressed in a minority of smooth muscle tumors of the uterine corpus, and lacks prognostic significance in leiomyosarcomas. BMP2 is rarely expressed in the other nonendothelial tissues of the human uterine corpus that were evaluated. The significance of frequent BMP2 expression in small vessels of the uterus requires further investigation.

Colorectal mesenchymal tumors - from smooth muscle tumors to stromal tumors.

Colorectal mesenchymal tumors are rare. Therefore, distinguishing between gastrointestinal stromal (GIST) and smooth muscle tumors is important. This study aimed to delineate the immunophenotype and prognostic factors of 75 colorectal mesenchymal tumors. Fifty-three GIST and 22 smooth muscle tumor specimens were included from 1986 to 2007. Forty of 53 GIST were initially diagnosed as smooth muscle tumors and re-diagnosed as CD117 (+) GIST. Immunohistochemical studies were performed with antibodies of CD117, CD34, smooth muscle actin (SMA), desmin, S-100, Ki-67 and PCNA for clinicopathologic and prognostic correlation. In comparison, colorectal GIST exhibited a larger tumor size (P<0.001), higher mitotic count (P<0.001), higher cellularity (P<0.001), less spindle cell type (P=0.004), higher nuclear pleomorphism (P=0.004), and a higher NIH risk (P<0.001) than that of smooth muscle tumors. Positive immunoreactivities of GIST to a panel of antibodies were 88.6% to CD34, 28.3% to SMA, 1.8% to S-100 and 15.1% to desmin. For 75 mesenchymal tumors, survival analyses revealed that older patients (P=0.006), with a large tumor size (P<0.001), high mitotic count (P<0.001), increased NIH risk (P<0.001), non-spindle cell type (P<0.001), high cellularity (P=0.015), high cell pleomorphism (P<0.001), positive Ki-67 (P<0.001), high PCNA (P<0.001) and GIST (P=0.001) had a shorter disease-free survival than that of comparative groups. When the analyses concentrated on 53 GIST, the cell type and cellularity were no longer viable prognostic factors. The tumor mitotic count was the only independent prognostic factor for either mesenchymal tumors or GIST. In conclusion, GIST exhibited heterogeneous characteristics and was significantly larger, more mitotic and a poorer prognostic factor than smooth muscle tumor. The mitotic count is still the most valuable prognostic factor for colorectal mesenchymal tumors after KIT.

Diagnostic criteria for uterine smooth muscle tumors: leiomyoma variants associated with malignant behavior.

OBJECTIVE: To determine the prognostic accuracy of current diagnostic criteria for uterine smooth muscle tumors. STUDY DESIGN: Cases of uterine leiomyosarcoma (LMS) treated from 1976 to 1999 were analyzed retrospectively. Uterine LMS specimens were reevaluated using current criteria by a pathologist specializing in gynecologic diseases. Kaplan-Meier survival curves were evaluated. RESULTS: Specimens were available from 67 patients diagnosed with uterine LMS. On rereview, only 47 specimens were thought to represent uterine LMS. The 20 other patients were deemed to have leiomyomas or leiomyoma variants, including 13 cellular leiomyomas, 5 atypical leiomyomas and 2 leiomyomas. Median survival for patients with uterine LMS was 2.1 years. (Ninety-seven percent of disease-specific deaths occurred within 6 years after the diagnosis.) With leiomyoma variants, median survival was > 25 years. Among these 18 women were 3 disease-specific deaths (all > 6 years after diagnosis). CONCLUSION: Diagnostic criteria for uterine smooth muscle tumors require continued refinement. A small but significant number of patients diagnosed with leiomyoma variants will die of the disease. In contrast to the aggressive behavior of uterine LMS, disease-specific deaths attributed to leiomyoma variants occurred later. With this potential for delayed recurrence, these patients warrant close clinical surveillance.

[Border-line smooth-muscle tumor of the uterus: analysis of 131 patients].

OBJECTIVE: To investigate whether the border-line uterine smooth-muscle tumor is different from leiomyoma or leiomyosarcoma in history and clinical manifestations. METHODS: The medical records of 131 surgically treated patients suffering from the so-called cellular leiomyoma or mitotically active leiomyoma of the uterus treated from 1984 to 2002 were retrospectively reviewed. All pathological sections of these patients were reviewed by a senior pathologist. Chi-square test and Kaplan-Meier life table were used for statistical analysis. RESULTS: The overall 5-year survival rate of patients with the border-line uterine smooth-muscle tumors was 100%, however, 19.1% (24/131) of whom developed a late recurrence and 8 patients had repeated recurrences with a more shortened course and aggressive potential changes of mitosis and cellular atypia. The overall 5-year survival rate the patients with recurrence was 91.7%, but only 75.0% for those with repeated recurrences. CONCLUSION: Patients with border-line uterine smooth-muscle tumor do possess some difference in nature from the leiomyoma or leimyosarcoma. Long-term follow-up is very important for these patients after surgery.

Smooth muscle tumors of the ovary: a clinicopathologic study of 54 cases emphasizing prognostic criteria, histologic variants, and differential diagnosis.

We studied 54 ovarian smooth muscle tumors with an emphasis on histologic criteria for malignancy. Twenty-two leiomyomas were identified, including 7 typical, 11 cellular, 2 mitotically active, 1 with bizarre nuclei, and 1 myxoid. Follow-up ranging from 12 to 240 months (mean, 77.6 months) was available for 14 patients; all were alive with no evidence of disease. Of 26 leiomyosarcomas, including 2 myxoid leiomyosarcomas, most were readily diagnosed by the presence of at least two of the following: moderate or severe cytologic atypia, mitotic rate > or =10 mitotic figures per 10 high power fields, and tumor cell necrosis. Some cytologically atypical tumors demonstrated lesser mitotic activity of 5 to 9 mitotic figures per 10 high power fields, in the absence of tumor cell necrosis. Sixty percent of these were clinically malignant, supporting a diagnosis of leiomyosarcoma in such tumors. Follow-up was available for 21 patients. Seventy-one percent developed recurrent disease at a mean of 19 months, and 62% died of their disease at a mean of 24 months. Four tumors were deemed of uncertain malignant potential, and two that were stage II both recurred in the pelvis. One case of ovarian intravenous leiomyomatosis had a benign outcome at 42 months, as did one case of ovarian leiomyoma with leiomyomatosis peritonealis disseminata at 180 months. Overall, ovarian smooth muscle tumors encompass the same varied histologic spectrum as their uterine counterparts. The main tumors in the differential diagnosis are those in the fibroma/thecoma category, spindle cell carcinomas, and metastatic gastrointestinal stromal tumors.

Estrogen and progesterone receptors expression in uterine malignant smooth muscle tumors: correlation with clinical outcome.

Uterine leiomyosarcomas are associated with a poor prognosis, although a considerable diversity in behavior may be found, and prolonged survival may occur. The aim of this study was to analyze the expression of estrogen (ER) and progesterone (PR) receptors in tumor specimens from uterine leiomyosarcomas, and to test their correlation with disease-free interval and cause-specific survival. This additional information may help the clinician differentiate between patients who have minimal risk of recurrence and those at greater risk of developing progressive disease. We examined specimens from 31 uterine leiomyosarcoma patients with clinical history and known follow-up. Disease-free interval and cause-specific survival rates were calculated according to the Kaplan-Meier method. According to univariate analysis, with Cox proportional hazards models, the ER expression (P=0.006 and P=0.016, respectively), PR expression (P=0.005 and P=0.016, respectively), and FIGO stage disease (P=0.011 and P=0.007, respectively) were independent predictors of the risk of recurrence and death from disease.

[Immunohistochemical and ultrastructural heterogeneity of gastrointestinal stromal tumors]. / Hétérogénéité immunohistochimique et ultrastructurale des tumeurs stromales digestives.

AIMS AND METHODS: Digestive stromal tumors are the most frequent undifferentiated mesenchymal tumors. The prognosis of these tumors is difficult to predict and the histogenesis is still subject to controversy. However, the frequent and specific expression of CD117 (c-kit) by these tumors could suggest an origin from interstitial cells of Cajal. The aim of this study was to analyse the histological and immunohistochemical characteristics of 46 digestive stromal tumors surgically resected, with comparaison of CD34 and CD117 expression in these tumors. Sixteen tumors were analyzed on electron microscopy. RESULTS: Sixty three and 74% of the stromal tumors were positive for CD117 and CD34 respectively. While CD117 expression was similar in all locations, on the contrary, there was a decreasing gradient of CD34 expression between gastric (87%) and jejunal (33%) tumors. All tumors with skeinoid fibers expressed CD117. Focal expression of smooth muscle actin was noted in 43% of the cases. The ultrastructural study showed no correlation with the immunohistochemical results. CONCLUSION: Digestive stromal tumors show an immunophenotypic and ultrastructural heterogeneity. CD117 expression is frequent, but not constant.

Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site.

Although the significance of various prognostic factors, such as tumor size and mitotic index (MI), has been well established for smooth-muscle tumors of the stomach, the significance of these factors in other sites is less well defined. We studied 1004 patients with gastrointestinal smooth-muscle tumors for whom vital status could be determined. The average MI and tumor size varied significantly among the five major sites examined: esophagus (53 cases), stomach (524 cases), small bowel 252 cases), colon/rectum (108 cases), and omentum/mesentery/peritoneum (67 cases). There was a significant difference in site-specific survival (p = 0.001), with 10-year survival varying between 50% and 70%. Multivariate analysis demonstrated tumor location (p = 0.0320), size (p = 0.0003), MI (p < 0.0001), and patient age (p < 0.0001) to each carry independent prognostic value. The significance of MI was highly site dependent. Separation of survival curves for the stomach, using a threshold for analysis of either 5 or 10 mitotic figures/50 high-power fields, was very good. In contrast, small-bowel tumors showed little separation between survival curves, regardless of whether a threshold of 1, 5, or 10 mitotic figures MF/50 high-power fields was used to distinguish groups. In no site were tumor size and MI alone sufficient to provide an accurate long-term prediction of prognosis. Although tumor location, size, MI, and age have independent value in predicting the prognosis of patients with gastrointestinal smooth-muscle tumors, better methods are still required to accurately predict clinical course.

KIT mutation portends poor prognosis in gastrointestinal stromal/smooth muscle tumors.

Gastrointestinal stromal/smooth muscle tumors (GISTs) are uncommon neoplasms for which current criteria for the diagnosis of malignancy (location, size, and mitotic index) do not always reliably predict patient outcome. Recently, mutation of KIT oncogene exon 11 has been observed in some of these tumors, but the relationship between mutation and clinical outcome has not yet been determined. DNA was obtained from the formalin-fixed, paraffin-embedded tissue of 35 gastric GISTs. A segment of exon 11 was amplified by PCR and sequenced on an ABI 377 sequencer. The relationship between the presence or absence of mutation, tumor size, and mitotic index was investigated using correlation analysis, and the relationship between mutation and outcome was investigated using Kaplan-Meier plots, the Cox-Mantel statistic, and the Cox regression model. Exon 11 deletion mutations were identified in 10 cases, and point mutations were identified in an additional 3 cases; 22 cases demonstrated no KIT mutations. KIT mutation was associated with decreased survival (p = 0.001), with fewer than 30% of patients surviving more than 3 years, compared with over 65% survival for patients whose tumors did not bear the mutation. KIT mutation did not correlate with either the mitotic index or the tumor size. In conclusion, KIT mutation is associated with poor prognosis in patients with gastrointestinal stromal tumors. Whether the KIT mutation will prove to be an independent prognostic factor awaits the completion of larger studies.

[Smooth-muscle-cell tumors of the gastroenteric tract. A review of cases]. / I tumori a cellule muscolari lisce del tratto gastroenterico. Revisione casistica.

Smooth muscle tumors of the gastrointestinal tract are difficult to evaluate and to stage. Twenty-four patients surgically treated during the last ten years have been evaluated using a TGM staging to identify the more rational criteria for the therapeutic choice. Six gastric leiomyomas, 1 ileal leiomyoma, 4 gastric leiomyosarcomas, 1 esophageal leiomyosarcoma, 4 ileal leiomyosarcomas, 2 rectal leiomyosarcomas and 6 gastric leiomyoblastomas were included. 62.5% of cases presented acute clinical features. Preoperative histological diagnosis was adequate in 29% of cases. We performed 7 excisions, 6 gastric subtotal resections, 3 total gastrectomies, 1 esophageal resection, 5 ileal resections, 2 rectal low anterior resection. Fourteen patients were staged I/II, 8 staged III and 2 staged IV. The overall median survival time was 27.5 months (56, 20 and 5 months concerning stage I/II, III and IV respectively; p < 0.01). In relation to T and G factors overall survival was statistically significant. TGM staging was highly significant to predict long-term survival. Radical surgical procedure was highly effective to guarantee long-term survival. Extended follow up is requested because recurrences after many years seem to be possible also with low histologic grade at first presentation.

Gastric smooth muscle tumors: diagnostic dilemmas and factors affecting outcome.

We reviewed the 46 gastric stromal tumors that were treated at our institution between 1958 and 1992. The most common presenting symptoms were gastrointestinal bleeding, pain, and fatigue or malaise. The tumors ranged from 4 to 150 mm, with surgery most often being a wedge excision or partial gastrectomy. Abdominal computed tomography was the most specific diagnostic test obtained preoperatively. Factors associated with decreased survival included size >/= 8 cm (p = 0.02), more than 0-3 mitoses per 10 HPF (p < 0. 001), positive margins or unresectability (p = 0.008), and tumor pathologic grade II or more (p = 0.004). These tumors have an unpredictable behavior. Surgical resection with negative margins remains the best therapy, but resection for palliation is sometimes indicated as it can be associated with prolonged survival.

Malignant smooth muscle tumors presenting as mediastinal soft tissue masses. A clinicopathologic study of 10 cases.

BACKGROUND: Smooth muscle tumors presenting as mediastinal soft tissue masses are extremely rare and often are mistaken for other neoplastic conditions. METHODS: Ten cases of patients with malignant smooth muscle tumors presenting as mediastinal soft tissue masses were studied and correlated with their clinical behavior. Tissues were examined histologically and with immunohistochemical stains in all cases, and by electron microscopy in two cases. RESULTS: The patients' ages ranged from 26 to 71 years (mean, 56 years); three were women, and seven were men. Three cases were located in the anterior mediastinum and seven in the posterior mediastinum. The patients with anterosuperior mediastinal tumors all presented with signs and symptoms referable to their lesions; the patients with posterior mediastinal masses (with the exception of one) were all asymptomatic. Grossly, the lesions were well circumscribed and unencapsulated, ranging from 6 to 18 cm in greatest dimension and showed a homogeneous, rubbery cut surface with prominent cystic and myxoid areas. The tumors in all patients appeared to arise from the soft tissues within the mediastinum and were unrelated to adjacent structures. In three patients, the tumors compressed and displaced the esophagus without infiltrating its wall, and in one patient, the tumor was found in close proximity, although unattached, to a large vessel. Histologically, the lesions exhibited a spectrum of morphologic appearances that ranged from low grade leiomyosarcoma with mild-to-moderate nuclear atypia and low mitotic activity (< 3/10 high power fields [HPFs]), to high grade tumors with marked nuclear pleomorphism, extensive areas of necrosis, and high mitotic activity (> 10 mitoses/10 HPFs). One case was characterized by a striking epithelioid morphology with large, round cells arranged in small clusters; another was associated with an incidental microscopic focus of thymic seminoma in the adjacent thymus. Immunohistochemical stains in all cases showed positive labeling of the tumor cells with smooth muscle actin, desmin, and vimentin antibodies. Electron microscopy in two cases showed features of smooth muscle differentiation, i.e., spindle cells surrounded by basal lamina material, immature cell junctions, and abundant intracytoplasmic filaments with focal condensations. All patients were treated with surgical excision. On follow-up, three patients with Stage IIIb and IVa tumors died 2-7 years after surgery, and two patients with Stage Ib and IIb were alive and well 4 and 6 years after surgery, respectively. CONCLUSION: Leiomyosarcomas may arise as primary tumors originating from mediastinal soft tissues in both anterior and posterior compartments. Because of their large size and frequent areas of cystic and myxoid degeneration, they may be confused histologically with neural or other neoplasms. As with their counterparts in other soft tissue locations, histologic grade and clinical stage are the most useful parameters for assessing prognosis.

Uterine smooth-muscle tumors of uncertain malignant potential.

OBJECTIVE: To determine whether tumors meeting the criteria of Hendrickson and Kempson for uterine smooth-muscle tumors of uncertain malignant potential have a natural history different from those of leiomyomas and leiomyosarcomas. METHODS: Tumors with five to ten mitoses per ten high-power fields and with mild or moderate cellular atypia were classified as tumors of uncertain malignant potential. Tumors with two to four mitoses per ten high-power fields and severe cellular atypia would also be classified as tumors of uncertain malignant potential, but we had no tumors that fell into this latter group. Forty-seven women with leiomyosarcoma or smooth-muscle tumors of uncertain malignant potential were identified. Paraffin-embedded blocks were recut, and hematoxylin and eosin-stained sections were studied for mitotic counts and cellular atypia. Statistical analysis used chi 2, Fisher exact test, Student t test, and Kaplan-Meier life table analysis. RESULTS: Fifteen tumors were classified as uncertain malignant potential and 32 as leiomyosarcomas. The patients with leiomyosarcoma were significantly older and more likely to present with extrauterine disease. Those with tumors of uncertain malignant potential had a 5-year disease-free survival of 66% and overall survival of 92%, compared to 28 and 40%, respectively, for leiomyosarcomas; these differences were statistically significant. Patients with tumors of uncertain malignant potential tended to have a protracted clinical course after development of recurrence, and several survived longer than 5 years with metastatic disease. CONCLUSIONS: Patients with five to ten mitoses per ten high-power fields and mild to moderate cellular atypia had a prognosis significantly better than that of patients with leiomyosarcomas. In this group, only 27% developed a recurrence, and after recurrence they tended to have a protracted course. Some of these tumors do have a very aggressive course, and the term "uncertain malignant potential" is appropriate.