The impact of human immune deficiency virus and hepatitis C coinfection on white matter microstructural integrity.

The purpose of the present study is to examine the integrity of white matter microstructure among individuals coinfected with HIV and HCV using diffusion tensor imaging (DTI). Twenty-five HIV+ patients, 21 HIV+/HCV+ patients, and 25 HIV- controls were included in this study. All HIV+ individuals were stable on combination antiretroviral therapy (cART; ≥3 months). All participants completed MRI and neuropsychological measures. Clinical variables including liver function, HIV-viral load, and CD4 count were collected from the patient groups. DTI metrics including mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) from five subregions of the corpus callosum were compared across groups. The HIV+/HCV+ group and HIV+ group were similar in terms of HIV clinical variables. None of the participants met criteria for cirrhosis or fibrosis. Within the anterior corpus callosum, significant differences were observed between both HIV+ groups compared to HIV- controls on DTI measures. HIV+ and HIV+/HCV+ groups had significantly lower FA values and higher MD and RD values compared to HIV- controls; however, no differences were present between the HIV+ and HIV+/HCV+ groups. Duration of HIV infection was significantly related to DTI metrics in total corpus callosum FA only, but not other markers of HIV disease burden or neurocognitive function. Both HIV+ and HIV+/HCV+ individuals had significant alterations in white matter integrity within the corpus callosum; however, there was no evidence for an additive effect of HCV coinfection. The association between DTI metrics and duration of HIV infection suggests that HIV may continue to negatively impact white matter integrity even in well-controlled disease.

Altered patterns of RB expression define groups of soft tissue sarcoma patients with distinct biological and clinical behavior.

BACKGROUND: Function of the retinoblastoma tumor suppressor protein (pRB) may be compromised at a genetic level by gene loss or mutation or at a post-translational level by hyperphosphorylation. In this study, we examined adult soft tissue sarcomas (ASTS) to determine if alterations of pRB were associated with distinct patterns of pRB expression and clinical outcome. DESIGN: We investigated 86 ASTS patients using monoclonal antibodies that distinguish between hyperphosphorylated and underphosphorylated pRB products. We also used microsatellite analysis to investigate the genetic status of the RB locus. We correlated pRB alterations with proliferative activity, and with clinicopathological outcomes. RESULTS: Altered patterns of pRB expression are common in ASTS occurring in 84% of cases, and it is significantly associated with proliferative activity (p<0.001). Patients whose tumors either lack expression of pRB, or express hyperphosphorylated forms of pRB, have poor survivals compared to patients whose tumors exhibit a normal, underphosphorylated pattern of pRB expression (p=0.03). In addition, 63% of cases lacking expression of pRB showed loss-of-heterozygosity at the locus. CONCLUSIONS: Inactivation of pRB is common in adult STS, which may be due to either gene loss or post-translational modification, namely hyper-phosphorylation. Both mechanisms are associated with tumor cell proliferation and poor survival.

The pathobiologic spectrum of Schwannomas.

In terms of their morphology, clinical associations and behavior, peripheral nerve sheath tumors are among the most varied of human neoplasm. Not surprisingly, such tumors are subject to frequent misdiagnosis. This is particularly true of the spectrum of schwannomas which include: a) conventional schwannoma, a histologically benign tumor which, on occasion, is destructive of surrounding osseous structures, b) the relatively recently described cellular schwannoma, a tumor that histologically simulates malignant peripheral nerve sheath tumor (MPNST), c) plexiform schwannoma which, particularly in cellular form and when occurring in childhood, simulates MPNST, and d) melanotic schwannoma which is often mistaken for melanoma. The psammomatous form of the latter is often associated with Carney complex, a rare heritable disorder that: a) includes cutaneous lentigines, b) myxomas of skin, subcutaneous tissue, and heart, c) and endocrine neoplasms. The tendency to misdiagnose schwannomas and to overestimate their grade makes schwannomas worthy of note. Herein, we discuss the four major schwannoma variants, their essential clinicopathologic features, and differential diagnosis. The distinction from MPNST is given particular attention.

Schwannoma with rhabdomyoblastic differentiation: a unique variant of malignant triton tumor.

A 54-year-old woman presented with intractable perianal, bilateral buttock, and radiating thigh/calf pain. An MRI scan showed an intradural, contrast-enhancing, ovoid mass in the cauda equina region at L1-L2. At laminectomy, the ovoid mass arose from a nerve root and, intact, was gross totally resected. Histologically, the dominant pattern was that of schwannoma. One year thereafter, the symptoms recurred. An MRI scan demonstrated an irregular, heterogeneously enhancing tumor recurrence. A repeat laminectomy disclosed a large fleshy tumor involving multiple nerve roots. The lesion was subtotally resected and showed pluridirectional differentiation toward embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, and rare malignant epithelial cells. Review of the original tumor disclosed only foci of embryonal rhabdomyosarcoma and primitive neuroectodermal tumor. Based upon available data regarding divergent differentiation in peripheral nerve sheath tumors, this is a unique, previously undescribed tumor demonstrating rhabdomyosarcomatous, primitive neuroectodermal tumor and scant epithelial differentiation in a schwannoma. In essence, it is a variant of malignant Triton tumor because of its origin in a tumor consisting of well-differentiated Schwann cells. It supports the contention that the Schwann cell is the source of a variety of heterologous elements in nerve sheath tumors.

Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases.

PURPOSE: A specific TLS-CHOP fusion gene resulting from the t(12;16) is present in at least 95% of myxoid liposarcomas (MLS). Three common forms of the TLS-CHOP fusion have been described, differing by the presence or absence of TLS exons 6-8 in the fusion product. Type 5-2 (also known as type II) consists of TLS exons 1-5 fused to CHOP exon 2; type 7-2 (also known as type I) also includes TLS exons 6 and 7 in the fusion, whereas type 8-2 (also known as type III) fuses TLS exons 1-8 to CHOP exon 2. We sought to determine the impact of TLS-CHOP fusion transcript structure on clinical outcome in a group of well-characterized MLS cases. We also analyzed P53 status, because this parameter has been found to have a significant prognostic impact in other sarcomas with chromosomal translocations. METHODS: We analyzed TLS-CHOP fusion transcripts by reverse-transcription PCR using RNA extracted from frozen tissue in 82 MLS confirmed previously to harbor a CHOP rearrangement either by Southern blotting or by cytogenetic detection of the t(12;16). Parameters analyzed included age, location, size, percentage of round cell (RC) component, areas of increased cellularity, necrosis, and surgical margins. In 71 (87%) cases, adequate tumor tissue was available for immunohistochemical analysis of P53 status, using DO7 antibody. The Kaplan-Meier method, log-rank, and Cox regression tests were used for survival analyses. RESULTS: Most MLS were >10 cm (73%), arising in the thigh (70%), and localized at presentation (89%). RC component was <5% in 47 (57%) cases and > or =5% in 35 (43%). The TLS-CHOP fusion transcript was type 5-2 in 55 (67%), type 7-2 in 16 cases (20%), and type 8-2 in 8 (10%). One tumor had a unique variant fusion, between exon 6 TLS and exon 2 CHOP. Two other cases (2%) showed an EWS-CHOP fusion transcript. Overexpression of P53 (defined as > or =10% nuclear staining) was detected in 12 (17%) cases. High histological grade (defined as > or =5% RC; P < 0.01), presence of necrosis (> or =5% of tumor mass; P < 0.05), and overexpression of P53 (P < 0.001) correlated with reduced metastatic disease-free survival in localized tumors. The presence of negative surgical margins (P < 0.01) and extremity location (P = 0.02) were found to be significant in predicting local recurrence in the entire group as well as localized cases by univariate and multivariate analysis. Although there was no significant correlation between TLS-CHOP transcript type and histological grade or disease-specific survival, an association was found between the P53 status and type 5-2 fusion (P < 0.01). CONCLUSION: In contrast to some other translocation-associated sarcomas, the molecular variability of TLS-CHOP fusion transcript structure does not appear to have a significant impact on clinical outcome in MLS. Instead, high histological grade (> or =5% RC), presence of necrosis, and P53 overexpression are predictors of unfavorable outcome in localized MLS.

Sclerosing epithelioid fibrosarcoma: a study of 16 cases and confirmation of a clinicopathologically distinct tumor.

Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon tumor of deep soft tissues, originally described in 1995 by Meis-Kindblom et al. In the current study, the authors identified 16 cases of SEF in the pathology files of their institutions and studied their pathologic features and disease course. The group consisted of six male and 10 female patients (age range, 14-55 years; mean age, 40 years), and the tumors were located in a limb or limb girdle (n = 7), base of the penis (n = 1), back or chest wall (n = 3), and head and neck (n = 5). Tumor size ranged from 3.7 to 22 cm (mean, 8.9 cm). Histologically, the SEFs were composed predominantly of small to moderate-size round to ovoid, relatively uniform cells, often with clear cytoplasm, embedded in a hyalinized fibrous stroma. The only consistent immunohistochemical finding was a strong, diffuse reactivity of tumor cells for vimentin. Ultrastructural analysis performed in eight cases confirmed their fibroblastic nature. Bone invasion and tumor necrosis, features not reported before, were found in six cases each. Treatment consisted of intralesional excision (n = 2), attempted wide local excision (n = 11), and amputation (n = 3), with either adjuvant radiation therapy (n = 9) or chemotherapy (n = 3). Follow-up of at least 1 year in 14 cases revealed persistent disease or local recurrence in seven patients (50%), and distant metastasis in 12 patients (86%). Eight patients (57%) died of disease 16 to 86 months after diagnosis. Five patients were alive with disease as of last follow-up. SEF shares some pathologic features with two other fibrosing fibrosarcomas, low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes, but in the authors' experience behaves clinically as a fully malignant sarcoma.

Adult perineal sarcomas.

BACKGROUND AND OBJECTIVES: Primary perineal sarcoma in adults is a rare disease that has only been documented to occur in isolated case reports. METHODS: To better characterize and define the natural history of perineal sarcoma in adults (> or = 18 years), we reviewed our experience with treatment of perineal sarcoma between 1982 and 1999 (nine cases). RESULTS: Epithelioid sarcoma (n = 4) was the most common histologic subtype. Seven cases (78%) were histologically high grade, and lesions were most commonly < 5 cm. All patients were treated with wide local excision. External beam radiation was the most commonly used form of adjuvant therapy (n = 6). Recurrences were noted in five patients, and the recurrences were most commonly local (60%). Median time to first recurrence was 21 months. Six of nine patients are alive with a median follow-up of 54 months. Three died of recurrent/metastatic disease at 16, 51, and 54 months after initial surgery. CONCLUSIONS: Aggressive therapy and follow-up beginning with wide excision can be associated with long-term survival in adults with primary perineal sarcoma.

Characterization of molecular abnormalities in human fibroblastic neoplasms: a model for genotype-phenotype association in soft tissue tumors.

Desmoid tumors and fibrosarcomas (FS) are part of a wide spectrum of disordered fibroblastic growth that display striking clinical and phenotypic differences. This study was designed to characterize molecular abnormalities that are associated with these differences and to determine their clinical relevance. A cohort of 24 desmoid tumors and 25 low-grade (LG) and 14 high-grade (HG) FS that were clinically and pathologically well characterized was analyzed for alterations in expression of Ki-67, Bcl-2, retinoblastoma gene product (pRB), and p53 by immunohistochemistry. LG-FS and HG-FS showed abnormal expression of Ki-67 (32 versus 86%), Bcl-2 (48 versus 57%), and pRB (56 versus 93%). In contrast, desmoid tumors showed a normal phenotype with these markers. p53 overexpression was identified in 20% of LG-FS and in 29% of HG-FS cases but only in 4% of desmoid tumors. There was an increasing trend in the proportion of abnormal expression of Ki-67, Bcl-2, pRB, and p53 with the increase of tumor aggressiveness from desmoid tumors to LG-FS to HG-FS. The molecular differences between tumor entities were highly statistically significant (P < 0.01). Significant associations between abnormal expression of pRB and recurrence-free survival of LG-FS patients (P = 0.05) and between Ki-67 overexpression and recurrence-free survival for tumors of >5 cm were observed (P = 0.02). The demonstrated differences of molecular alterations in HG-FS, LG-FS, and desmoids appear to be related to biological aggressiveness of such tumors, and they might be useful to differentiate between histologically similar cases of desmoid tumors and LG-FS. pRB and Ki-67 status may be useful to predict recurrence in certain subsets of patients.

Clinicopathologic analysis of patients with adult rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma (RMS) in adults (age > or = 16 years) is rare, accounting for less than 3% of adult soft tissue sarcomas. There is little information describing the disease biology or clinicopathologic factors that influence survival in adults with RMS. The objective of this study was to define the factors in patients with adult RMS that predict outcome, disease progression, and survival. METHODS: Eighty-four adult patients with a pathologic diagnosis of RMS that was confirmed by immunohistochemistry were identified by a prospective inpatient data base during the period 1982--1999 and were analyzed for disease specific survival and metastasis free survival using the Kaplan-Meier actuarial method. Statistical significance was evaluated using the log-rank test for univariate influence and a Cox regression model for multivariate influence. RESULTS: The median disease specific survival was 22 months. Patient age, extent of disease, tumor size at the time of diagnosis, and margin status after resection were significant predictors of disease specific survival. Patients who underwent a complete resection had a significantly longer median survival (105 months) compared with any other subgroup of patients. The histologic subtype did not predict patient survival but did vary with patient age. Most notably, the proportion of the pleomorphic subtype increased with advancing age, accounting for 42% of RMS in patients over the age of 40 years. CONCLUSIONS: The most important predictors of outcome in patients with adult RMS are patient age, tumor size, extent of disease, and margin status after resection. In contrast to patients with pediatric RMS, no association was noted between survival and histologic subtype in this group of patients with adult RMS. All histologic subtypes of RMS are aggressive malignancies with poor disease specific survival despite aggressive multimodality management.

Intralesional resection of primary and metastatic sarcoma involving the spine: outcome analysis of 59 patients.

OBJECTIVE: Surgery plays an important role in achieving local tumor control and cure for primary and metastatic tumors of the spine. As has been established with regard to sarcomas at extraspinal sites, these goals may best be achieved by en bloc resection with negative histological margins. Unfortunately, sarcomas of the spine often present with tumor patterns that are amenable only to intralesional resection, if neurological preservation is a priority. This study is a retrospective analysis of the long-term outcomes of patients who had operations for sarcomas of the spine using modern surgical approaches, intralesional resections, and spinal instrumentation. METHODS: Between 1985 and 1997, 59 patients had spinal operations for sarcoma involving the extrasacral spine. Data regarding tumor histology, grade, surgical indications, patterns of spinal tumor involvement, and neurological and functional outcomes were reviewed at presentation and at tumor recurrence. RESULTS: Thirty-five patients underwent a single operation, and 24 patients required reoperation for locally recurrent tumors. At presentation, only nine patients (15%) had tumors that were amenable to marginal or wide resections. Functional outcomes after initial spinal surgery and after operations performed at first tumor recurrence showed that 95% of patients had maintained or regained ambulation. Intradural extension of tumor was seen in 5 of 12 patients who had three or more operations for locally recurrent disease. The median survival from first spine operation was 18 months, and the median event-free interval between the first and second spine operations was 13 months. CONCLUSION: Surgery for sarcoma of the spine is useful for maintaining or improving neurological and functional outcomes, but local tumor recurrences are common. Because of the anatomy of the tumor at presentation and concern for neurological preservation, few patients are candidates for marginal or wide resections.

Cytology of melanotic schwannoma in a fine needle aspirate and pleural fluid. A case report.

BACKGROUND: Melanotic schwannoma (MS) is a rare pigmented neural tumor most commonly occurring in the paraspinal region and involving spinal nerve roots and sympathetic ganglia. Few case reports describe the fine needle aspiration (FNA) cytology of MS. We report an additional case and for the first time describe the cytologic findings of MS in pleural fluid. CASE: A 44-year-old man presented with a 9.0-cm paraspinal mass associated with multiple lung nodules. FNA cytology of the paraspinal mass showed solitary and syncytially arranged spindled cells, with prominent nucleoli and variable amounts of cytoplasmic brown pigment. In pleural fluid, prominent isolated single cells were rounded and had a signet ring cell morphology. Tumor cells in both the aspirate and pleural fluid expressed S-100 protein and HMB-45. CONCLUSION: The FNA cytology findings of MS correlate well with the histologic findings. In pleural fluid, however, the cells are epithelioid, and some have a signet ring morphology, mimicking adenocarcinoma.

Adjuvant radiotherapy for margin-positive high-grade soft tissue sarcoma of the extremity.

PURPOSE: Adjuvant radiotherapy (RT) has been shown to improve local control in patients with soft tissue sarcoma of the extremities (STS). The specific impact of adjuvant radiation on patients with positive margins, however, has not been clearly defined. The purpose of this study was to determine if adjuvant RT improves local control in patients with high-grade STS who had positive margins of resection. METHODS AND MATERIALS: Between 8/82 and 2/97, 110 adult patients with primary high-grade STS of an extremity underwent limb sparing surgery and were found to have a histologically positive microscopic surgical margin. Ninety-one (83%) received RT and 19 (17%) had no RT. The two groups were balanced with regard to size, site, location, and tumor depth. Adjuvant RT was delivered with brachytherapy (BRT) alone in 34 patients, external beam radiotherapy (EBRT) alone in 33 patients, or BRT+EBRT in 24 patients. The BRT dose was 45 Gy when used alone and 15-20 Gy when used as a boost. The EBRT dose was 60-70 Gy when used alone and 45-50 Gy when given with BRT. The median follow-up time was 41 months (range, 3-186 months). RESULTS: The overall 5 year local control rate was 71%. This rate was significantly higher in the RT group compared to the no RT group (74% vs. 56%, respectively) (p = 0.01). On univariate analysis, lower extremity site and proximal location were also found to be predictors of improved local control (p = 0.03 and 0.03, respectively). However, only proximal location and the use of RT retained their significance as predictors of improved local control on multivariate analysis (p = 0.003 and 0.01, respectively). The overall 5-year distant relapse-free survival, disease-free survival, and overall survival rates were 54%, 44%, and 53%, respectively. No statistical differences were found in these survival rates between RT and no RT groups. CONCLUSION: Based on this study, adjuvant radiotherapy seems to improve local control in patients with high-grade STS of the extremity with positive margins. However, local recurrence still occurs in a substantial proportion of patients, mandating further need for improvement.

Schwannoma with angiosarcoma. Report of a case and comparison with other types of nerve tumors with angiosarcoma.

BACKGROUND: Schwannoma with angiosarcomatous change is a rare tumor, the clinical characteristics of which have not been analyzed. METHODS: A patient with schwannoma with angiosarcoma arising in the midneck and clinically mimicking a carotid body paraganglioma is described with a literature review of all previously reported cases and a comparison of their clinical features with those of schwannoma with conventional malignant transformation and cases of neurofibroma and malignant peripheral nerve sheath tumor (MPNST) with angiosarcoma. RESULTS: There are four reported cases, including the present case. Schwannoma with angiosarcoma affects older adults, mainly men. Three tumors arose from the vagus nerve in the neck. Three of the four angiosarcomas were epithelioid in type. Treatment in all cases was surgical resection followed by radiation and chemotherapy in one case and by radiation alone in another. One patient died with residual local angiosarcoma 5 months after the diagnosis. The remaining three patients were alive and disease free at 27 months, 43 months, and 90 months, with distant metastasis (after 15 months) reported only in the patient described in this case report. CONCLUSIONS: Schwannoma with angiosarcoma should be included in the differential diagnosis of presumed carotid body paragangliomas. Like angiosarcoma alone and schwannoma with conventional malignant transformation, but unlike cases of neurofibroma and MPNST with angiosarcoma, the patients are older adults, and there is a male prevalence. Schwannoma with angiosarcoma is capable of local spread with a fatal outcome and of distant metastasis, but follow-up strongly suggests that these patients have a better prognosis than patients with neurofibroma or MPNST with angiosarcoma. Recommended treatment is attempted complete surgical resection followed by radiation therapy and chemotherapy, if it can be tolerated by the patient.

Monoclonality of multifocal myxoid liposarcoma: confirmation by analysis of TLS-CHOP or EWS-CHOP rearrangements.

Multifocal presentation, defined as the presence of tumor at two or more anatomically separate sites, before the manifestation of disease in sites where sarcomas usually metastasize (e.g., lungs) occurs in about 1% of extremity soft tissue sarcomas (STSs). Debate still persists whether multifocal STSs represent an unusual pattern of metastasis or multiple separate primary tumors. Among STSs with multifocal presentation, myxoid liposarcoma is the predominant histological type. This subtype of liposarcoma contains the specific t(12;16) chromosomal translocation, which results in rearrangement of the TLS and CHOP genes that is clone specific at the DNA level. We, therefore, sought to address the question of clonality by molecular analysis in six patients who presented with either synchronous or metachronous multifocal myxoid liposarcoma. In all six cases, adequate frozen tumor was available for DNA extraction from at least two distinct anatomical sites. Southern blot analysis using CHOP, TLS, and EWS cDNA probes was performed on genomic DNA. Five cases contained a TLS-CHOP rearrangement, and one case had the variant EWS-CHOP fusion (seen in <5% of cases). The size of the rearranged CHOP fragment differed among the six patients, as expected, but was identical in all anatomically separate tumor samples from each patient. Likewise, the sizes of the rearranged bands observed with either the TLS or EWS probes supported the monoclonality of all cases. Our results confirm the monoclonal origin of multifocal myxoid liposarcoma, establishing the metastatic nature of distant soft tissue lesions in these cases. It remains unclear whether this unusual pattern of metastasis represents an intrinsic property of this subset of myxoid liposarcoma or merely a rare chance occurrence. The clinical outcomes observed in this small series suggest that the prognosis of multifocal myxoid liposarcoma is poor, regardless of its often bland or "low-grade" histological appearance.

Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2.

Hemizygosity for the NF2 gene in humans causes a syndromic susceptibility to schwannoma development. However, Nf2 hemizygous mice do not develop schwannomas but mainly osteosarcomas. In the tumors of both species, the second Nf2 allele is inactivated. We report that conditional homozygous Nf2 knockout mice with Cre-mediated excision of Nf2 exon 2 in Schwann cells showed characteristics of neurofibromatosis type 2. These included schwannomas, Schwann cell hyperplasia, cataract, and osseous metaplasia. Thus, the tumor suppressor function of Nf2, here revealed in murine Schwann cells, was concealed in hemizygous Nf2 mice because of insufficient rate of second allele inactivation in this cell compartment. The finding of this conserved function documents the relevance of the present approach to model the human disease.

Dermatofibrosarcoma protuberans: A clinicopathologic analysis of patients treated and followed at a single institution.

BACKGROUND: Despite optimal surgical therapy for patients with dermatofibrosarcoma protuberans (DFSP), some patients still continue to develop local recurrence. The authors' objective was to identify and analyze clinicopathologic factors for disease free survival in a large group of patients who were followed prospectively at a single institution. METHODS: Prospectively collected data and pathology slides were available for review from 159 patients with primary or recurrent DFSP who underwent treatment between July 1950 and July 1998. The study group was comprised of patients with either the "classic" form of DFSP or the fibrosarcomatous "high grade" variant of DFSP (FS-DFSP). Patient, tumor, pathologic, and treatment factors were analyzed using the log rank test for univariate influence and Cox regression analysis for multivariate influence. Local recurrence free survival was determined by the Kaplan-Meier actuarial method. RESULTS: Of the 159 patients who comprised the current study group, 134 (84%) had the classic form of DFSP. The FS-DFSP variant was found in the remaining 25 patients (16%). The overall 5-year local recurrence free survival rate was 75%, with a median follow-up of 4. 75 years. The 5-year recurrence free survival rate for each group was 81% and 28%, respectively. On univariate analysis, age > 50 years, very close (< 1 mm) to positive microscopic margins, FS-DFSP variant, high mitotic rate, and increased cellularity were unfavorable prognostic factors. Multivariate analysis determined very close (< 1 mm) to positive microscopic margins and FS-DFSP variant to be independent adverse prognostic factors. For the 34 patients who developed a recurrence after surgical resection (21%), the median time to local recurrence was 32 months. Of the patients in this group, two died from metastatic disease. CONCLUSIONS: The prognosis after surgical resection with negative and sometimes positive microscopic margins for patients with DFSP is very good. However, increased age, high mitotic index, and increased cellularity are predictors of poor clinical outcome. The FS-DFSP variant represents a much more aggressive tumor with metastatic potential. Patients who are treated with curative intent for FS-DFSP should undergo aggressive attempts at complete surgical resection. Patients with recurrent classic DFSP without evidence of adverse prognostic features may benefit from conservative management, especially in the setting of potentially unresectable disease.

Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity.

PURPOSE: Synovial sarcoma is a high-grade tumor that is associated with poor prognosis. Previous studies analyzing prognostic factors are limited because of inclusion of heterogeneous cohorts of patients with nonextremity and recurrent tumors. The objective of this study was to determine independent prognostic factors of primary synovial sarcoma localized to the extremity. PATIENTS AND METHODS: Between July 1, 1982, and June 30, 1996, 112 patients underwent surgical resection for cure at our institution and then were followed-up prospectively. Clinical and pathologic factors examined for prognostic value included age, sex, tumor site and location, depth, size, microscopic status of surgical margins, invasion of bone or neurovascular structures, and monophasic or biphasic histology. The end points analyzed were the time to first local recurrence that was not preceded by a distant recurrence, time to any distant recurrence, and time to disease-related mortality. These end points were modeled using the method of Kaplan and Meier and analyzed by the log-rank test and Cox regression. RESULTS: The median duration of follow-up among survivors in this cohort of 112 patients was 72 months. The 5-year local-recurrence, distant-recurrence, and mortality rates were 12%, 39%, and 25%, respectively. Tumor size > or = 5 cm (P =.001; relative risk [RR] = 2. 7; 95% confidence interval [CI], 1.5 to 5.2) and the presence of bone or neurovascular invasion (P =.04; RR = 2.3; 95% CI, 1.0 to 5. 3) were independent adverse predictors of distant recurrence. Tumor size > or= 5 cm (P =.003; RR = 2.3; 95% CI, 1.4 to 6.3) and the presence of bone or neurovascular invasion (P =.03; RR = 2.7; 95% CI, 1.0 to 6.5) were also independent adverse predictors of mortality. CONCLUSION: The natural history of primary synovial sarcoma of the extremity is related to tumor size and invasion of bone and neurovascular structures.

Surgical management of intra-abdominal desmoid tumours.

BACKGROUND: Intra-abdominal desmoids are uncommon neoplasms. The aggressive nature of these tumours and the potential for major morbidity secondary to resection can present a difficult surgical dilemma. METHODS: Patients with histologically confirmed intra-abdominal desmoid tumours undergoing laparotomy were identified from a prospective database. Clinical features and outcomes in this group were evaluated. RESULTS: The study group comprised 24 patients. Sixteen patients underwent complete resection of the tumour while eight had biopsy only, with or without intestinal bypass. Small intestinal resection was performed in 12 patients, including three who had a near-total enterectomy. Median follow-up was 62 months, with an actuarial overall survival rate of 73 per cent at 10 years. There was no difference in survival rate between completely resected and unresected patients (P = 0.73). There were seven deaths in the entire group, of which four were in those undergoing complete resection. CONCLUSION: Operation can cure patients with intra-abdominal desmoid tumours, but may result in significant morbidity, especially from loss of small intestine. No other therapy is a predictably good alternative to operation but the natural history of desmoids is often characterized by prolonged periods of stability or even regression. A period of watchful waiting, until significant symptoms develop, may be the most appropriate course in patients who risk mesenteric vascular injury or substantial enterectomy with attempts at resection.