[show abstract][hide abstract] ABSTRACT: Tumors of peripheral nerve are largely neuroectodermal in nature and derived from 2 elements of nerve, Schwann or perineurial cells. In contrast, mesenchymal tumors affecting peripheral nerve are rare and are derived mainly from epineurial connective tissue. The spectrum of the latter is broad and includes lipoma, vascular neoplasms, hematopoietic tumors, and even meningioma. Of malignant peripheral nerve neoplasms, the vast majority are primary peripheral nerve sheath tumors. Malignancies of mesenchymal type are much less common. To date, only 12 cases of synovial sarcoma of nerve have been described. Whereas in the past, parallels were drawn between synovial sarcoma and malignant glandular schwannoma, an uncommon form of malignant peripheral nerve sheath tumor, molecular genetics have since clarified the distinction. Herein, we report 10 additional examples of molecularly confirmed synovial sarcoma, all arising within minor or major nerves. Affecting 7 female and 3 male patients, 4 tumors occurred in pediatric patients. Clinically and radiologically, most lesions were initially thought to be benign nerve sheath tumors. On reinterpretation of imaging, they were considered indeterminate in nature with some features suspicious for malignancy. Synovial sarcoma of nerve, albeit rare, seems to behave in a manner similar to its more common, soft tissue counterpart. Those affecting nerve have a variable prognosis. Definitive recommendations regarding surgery and adjuvant therapies await additional reports and long-term follow-up. The literature is reviewed and a meta-analysis is performed with respect to clinicopathologic features versus outcome.
Human pathology 02/2011; 42(4):568-77. · 3.03 Impact Factor
[show abstract][hide abstract] ABSTRACT: Malignant peripheral nerve sheath tumors (MPNSTs) arising from cranial nerves or their branches are very uncommon. The literature consists mainly of isolated case reports and small series. We identified 17 such cases in 14 males and 3 females. With one exception, the tumors affected adults (age range 5 to 69 y, mean 39, median 32). Sites of involvement included vestibular nerves (n=6), vagal nerves (n=4), facial nerves (n=3) (1 centered in the geniculate ganglion), and 2 unspecified cranial nerves in the posterior fossa. In addition, 1 tumor involved the optic chiasm (n=1). Only 1 tumor arose in brain parenchyma of (frontal lobe). All but 3 lesions were intracranial. Five tumors arose in patients who satisfied clinical criteria for neurofibromatosis type 1 (NF1). One patient with a vestibular tumor and presumed NF2 had previously undergone resection of a contralateral vestibular cellular schwannoma. One posterior fossa tumor was a malignant melanotic schwannoma. Four patients had postirradiation malignant peripheral nerve sheath tumors, 2 having been treated for optic chiasm glioma, both being NF1 affected. One patient was irradiated for hypothalamic pilocytic astrocytoma and another for cervical Hodgkin disease. Identifiable precursor lesions included schwannoma (n=4), plexiform neurofibroma (n=2), and solitary intraneural neurofibroma (n=2). All tumors were histologically high grade (6 grade III and 10 grade IV). Three tumors showed heterologous elements, 2 osseous, and 1 rhabdomyoblastic. More often scattered than diffuse, S-100 protein staining was noted in 11 of 16 tumors and variable collagen IV staining in 10 of the 16. Immunoreactivity for p53 protein was diffuse and strong in 7 of 11 tumors. Twelve patients died within 17 months to 3 years of diagnosis, 1 was lost to follow-up, 2 are very recent cases, and 2 patients are currently alive, 1 after 2 recurrences, and another with spinal leptomeningeal metastases. Malignant cranial nerve sheath tumors are rare and are associated with the same poor prognosis as those of spinal nerves at other sites.
American Journal of Surgical Pathology 02/2009; 33(3):325-338. · 4.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
Histology and histopathology 07/2006; 21(7):743-52. · 2.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: We present six cases of a plexiform nerve sheath tumor of childhood that previously had been designated a form of malignant peripheral nerve sheath tumor (MPNST), and we provide evidence that such tumors are in fact benign plexiform cellular schwannomas. At presentation, the four girls and two boys ranged in age from 2 to 15 months with tumors of the leg (four), deep groin and upper thigh (one), and pelvis (one). Of the six lesions, five were congenital and none was associated with type 1 neurofibromatosis. Tumor sizes ranged from 2.0 to 9 cm, with three larger than 5 cm. Three tumors were well circumscribed, two were purely infiltrative, and one had a mixed circumscribed and infiltrative growth pattern. Peripheral nerve involvement was evident in two cases. Grossly, the tumors were multinodular or plexiform in configuration and, on sectioning, lobulated and homogeneously tan without necrosis. Characteristic histologic features included hypercellularity, composition of cells spindle in shape with elongate hyperchromatic nuclei, and indistinct cellular outlines. Their nuclei varied minimally in size and shape but were at least three times the size of typical neurofibroma nuclei. Mitoses were seen in every tumor and in the areas of greatest proliferative activity ranged from 4 to 31/10 high power fields. MIB-1 staining of at least 30% of the cells was noted in three cases. In five cases in which p53 immunoreactions were performed, no nuclear staining was evident. That the tumors are schwannomas was evident from their uniform strong staining for S-100 protein and an ultrastructure in all five cases showing only differentiated neoplastic Schwann cells. Architecturally, the tumors differed from conventional schwannoma and nonplexiform cellular schwannomas by their lack of both well-formed capsules and degenerative changes. Follow-up was available in all cases and ranged from 2 to 13.6 years. All tumors recurred locally and were treated by local resections. With the exception of one child lost to follow-up at 25 months, all the children are alive and free of disease. Our data combined with cases previously reported by Meis-Kindblom and Enzinger show a childhood peripheral nerve tumor unassociated with type 1 neurofibromatosis, occurring most commonly in infants, often presenting as a congenital tumor and, though prone to local recurrence, having no metastatic potential. The behavior is that of a benign tumor, although its often rapid growth, hypercellularity and increased mitotic activity, sometimes locally aggressive behavior, and difficulties encountered in obtaining tumor-free margins are unsettling to pathologist and clinician alike. These features may lead to a misdiagnosis of malignancy, which could result in harmful overtreatment.
American Journal of Surgical Pathology 11/2003; 27(10):1321-9. · 4.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Activating mutations of the KIT juxtamembrane region are the most common genetic events in gastrointestinal stromal tumors (GISTs) and have been noted as independent prognostic factors. The impact of KIT mutation in other regions, such as the extracellular or kinase domains, is not well-defined and fewer than 30 cases have been published to date.
One hundred twenty GISTs, confirmed by KIT immunoreactivity, were evaluated for the presence of KIT exon 9, 11, 13, and 17 mutations. The relation between the presence/type of KIT mutation and clinicopathological factors was analyzed using Fisher's exact test and log-rank test.
Forty-four % of the tumors were located in the stomach, 47% in the small bowel, 6% in the rectum, and 3% in the retroperitoneum. Overall, KIT mutations were detected in 78% of patients as follows: 67% in exon 11, 11% in exon 9, and none in exon 13 or 17. The types of KIT exon 11 mutations were heterogeneous and clustered in the classic "hot spot" at the 5' end of exon 11. Seven % of cases showed internal tandem duplications (ITD) at the 3' end of exon 11, in a region that we designate as a second hot spot for KIT mutations. Interestingly, these cases were associated with: female predominance, stomach location, occurrence in older patients, and favorable outcome. There were significant associations between exon 9 mutations and large tumor size (P < 0.001) and extragastric location (P = 0.02). Ten of these 13 patients with more than 1-year follow-up have developed recurrent disease.
Most KIT-expressing GISTs show KIT mutations that are preferentially located within the classic hot spot of exon 11. In addition, we found an association between a second hot spot at the 3'end of exon 11, characterized by ITDs, and a subgroup of clinically indolent gastric GISTs in older females. KIT exon 9 mutations seem to define a distinct subset of GISTs, located predominantly in the small bowel and associated with an unfavorable clinical course.
Clinical Cancer Research 09/2003; 9(9):3329-37. · 7.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adult soft tissue sarcomas are a heterogeneous group of tumors, including well-described subtypes by histological and genotypic criteria, and pleomorphic tumors typically characterized by non-recurrent genetic aberrations and karyotypic heterogeneity. The latter pose a diagnostic challenge, even to experienced pathologists. We proposed that gene expression profiling in soft tissue sarcoma would identify a genomic-based classification scheme that is useful in diagnosis. RNA samples from 51 pathologically confirmed cases, representing nine different histological subtypes of adult soft tissue sarcoma, were examined using the Affymetrix U95A GeneChip. Statistical tests were performed on experimental groups identified by cluster analysis, to find discriminating genes that could subsequently be applied in a support vector machine algorithm. Synovial sarcomas, round-cell/myxoid liposarcomas, clear-cell sarcomas and gastrointestinal stromal tumors displayed remarkably distinct and homogenous gene expression profiles. Pleomorphic tumors were heterogeneous. Notably, a subset of malignant fibrous histiocytomas, a controversialhistological subtype, was identified as a distinct genomic group. The support vector machine algorithm supported a genomic basis for diagnosis, with both high sensitivity and specificity. In conclusion, we showed gene expression profiling to be useful in classification and diagnosis, providing insights into pathogenesis and pointing to potential new therapeutic targets of soft tissue sarcoma.
American Journal Of Pathology 09/2003; 163(2):691-700. · 4.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Histology and histopathology 08/2003; 18(3):925-34. · 2.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
American Journal of Surgical Pathology 07/2003; 27(6):848-53. · 4.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hemangiopericytoma (HPC) is a rare vascular tumor, and pathologic distinction from synovial sarcoma and solitary fibrous tumor is a significant problem due to shared histologic features. In the current report the authors defined the clinical behavior and prognosis for patients with HPC.
Between July 1982 and February 1998, 62 patients with a diagnosis of primary, recurrent, or metastatic HPC were identified from a prospectively maintained database. The pathology of all cases for which material was available (57 cases) was re-reviewed for histologic confirmation of the HPC diagnosis. Using strict pathologic criteria, including immunohistochemistry and electron microscopy, tumors from 25 of 57 patients qualified for the diagnosis of conventional hemangiopericytoma; those tumors formed the basis of the current report. Survival was determined by the Kaplan-Meier method.
At the time of initial presentation, 19 patients had primary tumors, 3 had locally recurrent disease, and 3 had metastatic disease. The most frequent anatomic sites for HPC were the extremities, the pelvis, and the head and neck, accounting for 80% of the total cases. The median followup (n = 25) was 49 months (range, 1 to 160 months). The two and five year overall survival rates (n = 25) were 93% and 86% respectively. The disease-specific survival was 86% at last followup. Patients undergoing complete resection (n = 16) showed a 100% median survival at 60 months.
At present, complete tumor resection for patients with conventional HPC is recommended. However, considering the favorable outcome in this disease, the authors caution against performing operations that may potentially cause loss of function or are limb threatening.
Cancer 11/2002; 95(8):1746-51. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Clear cell sarcoma (CCS), also known as melanoma of soft parts, is an uncommon deep soft tissue tumor presenting typically in the lower extremities of young adults. Previous cytogenetic studies have established the specificity of the recurrent t(12;22)(q13;q12), resulting in a EWS-ATF1 fusion, for CCS. The prevalence of the EWS-ATF1 fusion in CCS remains unclear, since most genetically confirmed CCS have been reported as isolated cytogenetic or molecular diagnostic case reports. We therefore studied histologically confirmed CCS from 12 patients for the presence of EWS-ATF1 by reverse-transcriptase polymerase chain reaction (RT-PCR), using RNA extracted from either frozen (four cases) or formalin-fixed paraffin-embedded (eight cases) material. All primary tumors were located in the deep soft tissues of the extremities. Histologically, 10 cases had a typical epithelioid nested appearance. Most or all cases showed immunostaining for HMB45 (12 of 12), S-100 protein (10 of 12), and MITF (12 of 12). Ultrastructural analysis showed melanosomes in six of seven cases. The presence of an EWS-ATF1 fusion transcript was identified by RT-PCR in 11 of 12 cases (91%), all of which showed the same fusion transcript structure, namely the previously described in-frame fusion of EWS exon 8 to ATF1 codon 65. RT-PCR analysis for the melanocyte-specific splice form of the MITF transcript was positive in all cases tested (4 of 4). These data confirm that EWS-ATF1 detection can be used as a highly sensitive diagnostic test for CCS and that CCS expresses the melanocyte-specific form of the MITF transcript, further supporting its genuine melanocytic differentiation.
Journal of Molecular Diagnostics 03/2002; 4(1):44-52. · 3.95 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
[show abstract][hide abstract] ABSTRACT: Synovial sarcomas are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18;p11;q11), which usually represents either of two gene fusions, SYT-SSX1 or SYT-SSX2, encoding putative transcriptional proteins differing at 13 amino acid positions. Previous studies have suggested that patients with SYT-SSX2 tumors do better than those with SYT-SSX1 tumors, but the study groups were too limited to be conclusive. To address this issue more definitively, we collected data on SYT-SSX fusion type, pathology, and clinical course in a retrospective multi-institutional study of 243 patients (age range, 6-82) with synovial sarcoma. SYT-SSX1 and SYT-SSX2 fusions were detected in 147 tumors (61%) and 91 tumors (37%), respectively. Histologically, 61 (25%) were classified as biphasic type and 180 (74%) as monophasic type based on the presence or absence of areas of glandular epithelial differentiation, respectively. Median and 5-year overall survivals for the SYT-SSX1 and SYT-SSX2 groups were 6.1 years and 53%, and 13.7 years and 73%, respectively. Overall survival was significantly better among SYT-SSX2 cases (P = 0.03), among cases localized at diagnosis (P < 0.0001), and among patients with primary tumors < 5 cm in greatest dimension (P = 0.01). Age, sex, histological type, and axial versus peripheral primary site had no impact on overall survival. The impact of fusion type on survival remained significant when stratified for primary tumor size (P = 0.03) but was no longer significant when stratified for disease status at presentation. This may reflect the tendency for patients with SYT-SSX1 tumors to present more often with metastatic disease (P = 0.05). Cox regression identified disease status (P < 0.0001) and primary tumor size (P = 0.04) as the only factors independently predictive of overall survival in the subset of 160 patients with information on all of the factors. Within the subset of patients with localized disease at diagnosis (n = 202), the median and 5-year survival for the SYT-SSX1 and the SYT-SSX2 groups were 9.2 years and 61% versus 13.7 years and 77%, respectively. Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8). In a Cox regression analysis considering all of the factors, SYT-SSX fusion type emerged as the only independent significant factor (P = 0.04) for overall survival within the subset of 133 patients with localized disease at diagnosis who had information on all of the factors. Among other comparisons, there was a strong association of fusion type and morphology (P < 0.001), with almost all of the SYT-SSX2 tumors showing absence of glandular differentiation (monophasic histology) and almost all of the biphasic tumors containing SYT-SSX1. There was also a statistically significant association of fusion type and patient sex (P = 0.03); specifically, the male:female ratio of SYT-SSX1 cases was 1:1, whereas for SYT-SSX2 cases, it was close to 1:2. Overall, SYT-SSX fusion type appears to be the single most significant prognostic factor by multivariate analysis in patients with localized disease at diagnosis. SYT-SSX fusion type also appears to exert part of its impact on prognosis before presentation through its association with stage at diagnosis. In addition, the associations of SYT-SSX fusion type with patient sex and tumor epithelial differentiation point to interesting mechanistic biological differences.
Cancer Research 01/2002; 62(1):135-40. · 8.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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).
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.
Clinical Cancer Research 12/2001; 7(12):3977-87. · 7.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sott tissue sarcomas (STS) of the groin may present a difficult problem because or misdiagnosis as groin hernia and proximity to major neurovascular structures. We evaluated our management and survival in a large cohort of patients.
Patients treated between July 1, 1982 and July 1, 1998 with primary or recurrent STS of the groin were included. Groin sarcomas were defined as those tumors within 5 cm of the inguinal crease. Patient, tumor, clinical, and survival data were analyzed using a log rank test and Cox regression.
We treated and followed 88 patients with STS of the groin. The median age was 52 years (range 16 to 86 years) and 55 patients (63%) were male. Disease-specific survival was 72% at 5 years. Tumors tended to be larger than 5 cm (52%), deep (72%), and high-grade (60%). Unfavorable prognostic factors for disease-specific survival were high grade (p < 0.001), neurovascular invasion (p < 0.001), positive margin (p < 0.01), deep depth (p < 0.01), and selection for adjuvant therapy (p < 0.005). Multivariate analysis indicated age greater than 50 years (p < 0.05), high grade (p < 0.001), neurovascular invasion (p < 0.001), and positive microscopic margins (p < 0.001). Fourteen patients (16%) were diagnosed with STS at hernia operation then went on to a definitive operation with no impact on survival. Seventeen patients (19%) had involvement of a major vessel or nerve, and 5 of these ultimately required amputations, 3 for local recurrence.
High grade, neurovascular invasion, and positive microscopic margins are associated with poor outcomes. The biology of these tumors is similar to other extremity STS, and similar principles of management apply. Even with neurovascular involvement, most patients with primary groin STS do not require amputation.
Journal of the American College of Surgeons 08/2001; 193(2):130-6. · 4.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
American Journal of Surgical Pathology 07/2001; 25(6):699-709. · 4.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Primary perineal sarcoma in adults is a rare disease that has only been documented to occur in isolated case reports.
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).
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.
Aggressive therapy and follow-up beginning with wide excision can be associated with long-term survival in adults with primary perineal sarcoma.
Journal of Surgical Oncology 06/2001; 77(2):101-4. · 2.64 Impact Factor