Locoregional recurrence of retroperitoneal soft tissue sarcoma: second chance of cure for selected patients.

BACKGROUND: Locoregional recurrence of a retroperitoneal soft tissue sarcoma (RSTS) may offer a second chance of curative surgical treatment. In a population-based study the proportion of patients developing isolated locoregional recurrences (LR) was determined and the outcome of these patients was analysed. METHOD: In a retrospective nationwide study, data were collected on 142 patients treated between 1 January 1989 and 1 January 1994 for primary RSTS. In patients who had been treated radically for their primary sarcoma (77/142, 54%), the pattern of recurrence was evaluated. Factors predictive of survival for patients with LR were studied. RESULTS: After a median follow-up of 86 (range 60-101) months, 32 patients (42%) had developed LR, and distant metastasis (DM) had been diagnosed in 17 patients (22%). Median disease-free interval between the initial operation and the establishment of LR or DM was 22 and 19 months, respectively. Five-year cumulative survival of patients with established LR was 37% in comparison with 11% for patients with DM (P=0.062). Factors predictive of favourable outcome in patients with LR were the absence of multifocal recurrence (n=13 P=0.01), lipomatous histomorphology (n=20 P=0.02), and a complete resection of recurrent sarcoma (n=17 P=0.04). CONCLUSION: After a median follow-up of 7 years following radical treatment of a primary RSTS, 42% of the patients had developed isolated locoregional recurrences. A complete resection of recurrent disease, lipomatous histomorphology and the absence of multifocal growth influenced prognosis favourably.

Soft tissue carcinoma in the retroperitoneum: an often neglected diagnosis.

AIMS: Successful surgical treatment of patients with retroperitoneal soft tissue sarcoma (RSTS) is based on pre-operative planning that starts with a correct pre-operative diagnosis. In a population-based study, we determined which patients were initially treated for assumed other conditions. The effect of an erroneous diagnosis on the installed treatment was analysed. METHOD: With the help of the Dutch Network and National Database for Pathology (PALGA), data were collected on 143 patients in the Netherlands in whom a primary RSTS was found and confirmed histologically between 1 January 1989 and 1 January 1994. Satisfactory clinical information was obtained on 138 patients, 64 males and 74 females (54%). The median age was 60 (range 18-88) years. RESULTS: At the time of actual treatment 37% of the patients with RSTS were assumed to have another disorder (group 1 n=51), whereas 87 patients were diagnosed as having RSTS (group 2). In group 1, an acute presentation was more common (18 vs 2% P=0.002), and the tumour was less often palpable at physical examination (43 vs 69% P=0.004), while clinical work-up less frequently included CT-imaging (57 vs 89% P<0.001) and a biopsy (29 vs 77% P<0.001). Although tumours in group 1 were smaller (median diameter 13 vs 19 cm P<0.05), this was not reflected in a better operative result: less patients underwent complete tumour resection (51 vs 57%) and more patients underwent surgery for tumours that proved to be irresectable (14 vs 1% P=0.004). CONCLUSIONS: (1) More than one-third of patients with RSTS are misdiagnosed and inappropriately treated; and (2) biopsies and cross-sectional imaging improve diagnosis.

Vulvar sarcoma: clinical implications.

This is a review of the histories of 47 patients with vulvar sarcoma, consisting of leiomyosarcoma (25), malignant fibrous histiocytoma (5), epithelioid sarcoma (8), dermatofibrosarcoma protuberans (9), including 7 from our own institute. When compared to the biological behaviour of sarcomas from other anatomic sites of the body, no essential differences were found. The prognosis after the appearance of regional or distant recurrence was poor and prevention of local recurrence by wide excision was the best way to improve the prognosis of leiomyosarcoma and dermatofibrosarcoma protuberans. However, the poor prognosis of epitheloid sarcoma did not change. Elective treatment of regional lymph nodes was not indicated in the four tumor types discussed and dissection of metastatic inguinal nodes was rarely beneficial. However, distressing local problems were prevented in a patient with epithelioid sarcoma and lasting benefit was seen in a patient with malignant fibrous histiocytoma who developed an inguinal metastasis after a 3-year disease-free interval. The beneficial effect of resection of pulmonary metastasis needs more attention.

Limb-sparing therapy of extremity soft tissue sarcomas: treatment outcome and long-term functional results.

The purpose of this study is to assess the long-term success rate and functional results of limb-sparing therapy in a group of 156 patients with soft tissue sarcomas of the extremities in the Netherlands Cancer Institute, treated according to a standard protocol of surgery and radiotherapy, if indicated. The patients (79 females and 77 males) were treated between 1977 and 1983 by an intended wide local excision with a margin of at least 2 cm. Postoperative radiotherapy was applied in 117 patients; 26 patients had surgery only, including 13 patients who had to be treated by amputation. The total dose was 60 Gy, with 40 Gy to a large volume and a boost of 20 Gy to the tumour bed at 2 Gy per fraction, five fractions per week. Most sarcomas were located in the proximal part of the lower extremity (51%). The group comprised 50 liposarcomas, 47 malignant fibrous hystiocystoma (MFH) and 59 other histologies; 69 (44%) had high-grade tumours. Three treatment groups with limb-sparing treatment were defined: group I (n = 26) patients who had a complete excision receiving no further treatment, group II (n = 64) with narrow surgical margins and radiotherapy and group III (n = 53) with incomplete resection and radiotherapy. The 10-year actuarial overall survival and local control rate for all patients was 63 and 81%, respectively. Multivariate analysis showed that histological grade (P < 0.0001), age (P = 0.0005) and location deep to the fascia (P = 0.0008) were independent prognostic factors for survival, while local control was predicted by grade (P = 0.0014) and treatment group (p = 0.028). Patients with surgery only (group I) had 81% 5-year local control as compared to 92% with radiotherapy after narrow surgery (group II) and 74% with incomplete surgery and radiotherapy (group III). Limb preservation when attempted was achieved in 90% of the patients. After limb-sparing treatment, 7% had severe impairment of mobility, 3% had lymph oedema and 16% marked fibrosis. Fractures in the irradiated bone occurred in 6% of the patients. The combination of limited surgery followed by radiotherapy resulted in a high local control rate with good functional results. Ultimately limb sparing treatment was successful in 83% of all patients with extremity sarcomas.

Grading of soft tissue sarcomas: experience of the EORTC Soft Tissue and Bone Sarcoma Group.

A practical grading system for soft tissue sarcomas was developed, based on 282 eligible patients entered in an EORTC adjuvant clinical trial. The primary tumours in this trial had to be adequately treated. Histopathological parameters, which appeared significant in two preceding studies, were tested. These parameters were differentiation of the tumour, presence and amount of necrosis, the presence and amount of myxoid areas and the number of mitoses. In addition, the size of the tumour was also analysed. The quantitative data (mitotic count and size of the tumour) were not a priori grouped, but were divided into categories based on the results of the statistical analysis. Based on a multivariate analysis only mitotic count, the presence or absence of necrosis and the size of the tumour were significantly correlated with the duration of survival or the time to distant metastases. Of these parameters, the mitotic count was the most important.

Dermatofibrosarcoma protuberans: treatment and prognosis.

Dermatofibrosarcoma protuberans (DFSP) is a rare tumor of the skin with a strong tendency to recur locally. Nineteen cases of DFSP are presented. In eight of them a total of 20 local recurrences occurred, in five after irradical and in three after 'narrow' excisions. After wide excision (greater than 2 cm) for primary or wide re-excision for recurrent tumor, all patients remained free of tumor with a mean follow-up of 13.2 years (range 2-28 years). An extensive literature review revealed 913 cases of DFSP. The overall recurrence rate is about 50%; after adequate wide excision, 13%. Recurrent tumor is safely treated by wide re-excision and the recurrence rate is then 12%. Regional and distant recurrences are infrequent. Eleven cases (1%) were reported to have regional lymph node metastases and 37 (4%, 17 of whom were histologically confirmed) distant metastases, principally in the lung. The prognosis after appearance of regional or distant recurrence is bad. The role of radiotherapy in the management of this tumor is unclear. Primary or recurrent DFSP is best treated by surgical excision with a minimal margin of 2- preferably 3-cm of surrounding skin including the underlying fascia. Elective lymph node dissection is not advised.

Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities.

From 1975 to 1986, 26 patients with soft tissue tumors of the extremities underwent a total of 29 perfusions. The cytostatics used were doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) (19 perfusions), melphalan (two perfusions), and a combination of these agents (eight perfusions). Before perfusion most patients had been treated by surgical excision(s), radiotherapy, or systemic chemotherapy. Of 17 patients perfused because of local inoperable tumor, four showed prolonged complete remission of the tumor mass, stable disease was seen in three, and ten showed progression. The complete remissions observed in three patients with aggressive fibromatosis and in one with lymphangiosarcoma occurred after perfusion with doxorubicin combined with melphalan. Doxorubicin added to the perfusate as the sole cytostatic was not effective. Local recurrence was observed in five of nine patients treated by adjuvant perfusion, always after dubiously radical tumor excision. Toxicity was high, especially in the first few years. Tissue necrosis necessitated amputation in three cases (in two after perfusion with doxorubicin and melphalan and in one after repeated perfusion with doxorubicin only). This complication was no longer seen after adjustment of the dosage and dose distribution of doxorubicin, but the morbidity after perfusion with doxorubicin remained considerable.

Epithelioid sarcoma.

In a 9-year period we treated 11 patients with an epithelioid sarcoma. Most patients were young adults. The tumour affected mainly the distal upper extremity (hand and fingers: four patients; wrist and forearm: three patients); one patient had an epithelioid sarcoma of the knee. Trunk localizations were seen in two patients and one patient presented with a vulva localization. Treatment consisted of surgery, regional isolation perfusion with doxorubicin (Adriamycin) or melphalan, radiation therapy, systemic chemotherapy or a combination of these modalities. Radical surgery in eight patients resulted in only two local recurrences. Locoregional metastases occurred in five patients. In five patients a therapeutic lymph node dissection was performed, in all instances followed by extensive recurrent disease. Distant metastases were seen in seven patients and mainly affected the skeleton (6x) and the lungs (4x); in the majority of cases these metastases occurred within a year after excision of the primary. Remissions following regional or systemic chemotherapy were not observed. At the time of analysis seven patients had died as a result of their epithelioid sarcoma; two patients were still alive with tumour 18 and 27 months after diagnosis. Only two patients remained tumour free for 17 and 65 months respectively following radical surgery, postoperative radiation therapy and (in one case) adjuvant chemotherapy. It is concluded that epithelioid sarcoma is a rare but exceedingly aggressive tumour. Since early diagnosis can only be auspicious, familiarity with the clinical features is of great importance.

Leiomyosarcomas: three cases with desmin positive tumour cells, lacking ultrastructural features of smooth muscle cells.

A combined study of light and electron microscopy and of immunolabelling of three pleomorphic spindle cell sarcomas is presented. The light and electron microscopic features of these sarcomas were most compatible with those described for malignant fibrous histiocytoma (MFH, pleomorphic-storiform subtype). Electronmicroscopically undifferentiated and fibroblast-like cells, fibrohistiocytes and multinucleated histiocytes were observed. Characteristics belonging to smooth muscle cells were absent. By immunostaining, vimentin and desmin could be observed in tumour cells of all three cases, at least on frozen sections. Other markers such as alpha 1-antichymotrypsin, S-100 proteins, laminin, collagen IV and markers specific for skeletal muscle cells (myoglobin, actin and myosin specific for skeletal muscle) could not be demonstrated. These findings indicate that three MFH's are, in fact, poorly differentiated variants of smooth muscle tumours. It is concluded that immunophenotyping is very useful for this type of neoplasm.

Regional lymph node metastases in patients with soft tissue sarcomas of the extremities, what are the therapeutic consequences?

In the period 1977-1983, 183 adult patients with soft tissue sarcomas of the extremities were treated in the Netherlands Cancer Institute. One hundred and seventy-one patients had initially operable tumors. Fifteen patients (8.2%) developed regional lymph node metastases (RLNM) during the course of their disease. Only two patients (1.2%) developed RLNM as first site of tumor recurrence. The incidence of RLNM varied according to the histological subtypes: liposarcoma: 1/64, fibrosarcoma: 1/12, tendosynovial sarcoma: 5/24, unclassifiable sarcoma: 3/8. The outcome in patients with RLNM was invariably fatal. In all cases with RNLM distant metastases were present either at the time RLNM were found or shortly afterwards (median 4 months). Based on this experience we now consider RLNM in soft tissue sarcoma an expression of systemic tumor spread, which should be treated as such. We find no indication for elective lymph node dissection as part of the initial treatment of soft tissue sarcoma of any histological subtype. Therapeutic lymph node dissection might be indicated as part of the palliative management.

Pleomorphic rhabdomyosarcoma in adults: immunohistochemistry as a tool for its diagnosis.

Pleomorphic rhabdomyosarcoma in adults over 30 years of age was a diagnosis frequently made in the 1960s and 1970s. Since the general acceptance of malignant fibrous histiocytoma (MFH) as a tumor entity at the end of the 1970s, however, it has become a very rare tumor in adults. Therefore, 21 cases originally diagnosed on the basis of histology and clinical data as pleomorphic rhabdomyosarcoma in the 1960s and 1970s were reexamined immunohistochemically. Other types of pleomorphic sarcomas involved in the differential diagnosis were also studied. Specific antibodies against vimentin, desmin, creatine kinase subunit M, skeletal muscle actin and myosin, and myoglobin, and the avidin-biotin-peroxidase complex technique were used. The immunohistochemical findings indicate that rhabdomyosarcoma occurs only rarely in adults over 30 years of age and that the majority of the tumors have to be reclassified as MFH or leiomyosarcoma. On the other hand, several pleomorphic sarcomas were found to be diagnosed incorrectly as MFH or liposarcoma by routine histologic stains and electron microscopy. The revised diagnosis was pleomorphic rhabdomyosarcoma for one case and pleomorphic leiomyosarcoma for the other cases. Thus, this study clearly shows the usefulness of immunohistochemistry as a technique in the diagnosis of pleomorphic sarcomas in adults.

Characterization of two cell lines, derived from two malignant fibrous histiocytomas.

We have investigated the phenotype and ultrastructure of tumour cells from two cell lines each derived from a malignant fibrous histiocytoma (MFH) as a means of studying the histogenesis of this group of tumours. The first MFH (MFH-I) was of the pleomorphic subtype, with a predominantly histiocytic appearance, the second was of the pleomorphic subtype associated with myxoid and storiform areas (MFH-II). In vitro tumour cells from both neoplasms showed aberrant growth properties. Xenografts in nude mice from both neoplasms showed a similar histology to that of the original tumour. Both tumours showed hyaluronidase sensitive alcian blue staining. Phenotypic studies of the two cell lines and of the tumour tissues demonstrated that the cells differed in the presence of collagen types I and III. They did not show evidence of histiocytic, endothelial, leiomyoblastic, rhabdomyoblastic, lipoblastic of schwannian origin. Ultrastructurally, the two cell lines were found to be different. In vitro and in xenografts the cell type of MFH-I resembled a primitive mesenchymal cell. Whereas that of MFH-II resembled a fibroblast-like cell. We concluded that the group of MFH is heterogeneous and is probably derived from more than one progenitor cell.

Malignant schwannoma with a rhabdomyoblastic component, a so-called triton tumor. A clinicopathologic study.

Triton tumors, malignant schwannomas with a rhabdomyoblastic component, are rare. This article reports the clinical course, therapeutic approach, and histopathologic aspects of three cases. Immunoperoxidase staining for the Schwann's cell marker S-100 protein and for the skeletal muscle proteins desmin, myosin, and myoglobin proved to be useful for diagnosis. The clinical histories of 24 previously reported cases are analyzed, and the therapeutic possibilities are discussed.

Characterization of tumour cells in malignant fibrous histiocytomas and other soft tissue tumours in comparison with malignant histiocytes. I. Immunohistochemical study on paraffin sections.

We have studied the possible origin of histiocytic cells, present in fibrous histiocytomas (MFH) by using immunohistochemistry to demonstrate lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin and receptors for peanut and soy bean agglutinin in tumour cells of MFH compared with their presence in tumour cells of malignant histiocytosis (MH) ('true' histiocytic lymphoma, 'true' histiocytic sarcoma). We included in this study a number of other soft tissue tumours (STT). Lysozyme was detected in half of the cases of malignant histiocytosis (n = 16) but in only two out of 77 MFH. alpha 1-Antitrypsin and alpha 1-antichymotrypsin usually occurred together although the latter was seen in more cases. Both markers were present in majority of cases of MH whereas they were detected in a minority of cases of MFH. MFH cases of the storiform subtype were less frequently stained than the pleomorphic or giant cell subtypes. Receptors for peanut or soy bean agglutinin were detected in nearly all MH cases, whereas their presence was only detected in a small number of MFH. Lysozyme was not detectable in other STT. alpha 1-Antitrypsin and alpha 1-antichymotrypsin were uncommonly present in other STT, except in osteosarcoma and rhabdomyosarcoma. These markers therefore have a limited value as indicators of a possible histiocytic origin of MFH. Lectins showed weak affinity for other STT. In accordance with others, we therefore conclude that the progenitor cell of MFH has to be sought within the undifferentiated mesenchymal cells and that histiocytes themselves probably do not give rise to MFH.

Creatine kinase subunits M and B as markers in the diagnosis of poorly differentiated rhabdomyosarcomas in children.

Antibodies against the M and B subunits of creatine kinase were assessed for their usefulness in the diagnosis of poorly differentiated rhabdomyosarcoma. Routinely processed formaldehyde-fixed tissue and the avidin-biotin-peroxidase complex technique were used. The majority of the poorly differentiated and all of the moderately and well-differentiated rhabdomyosarcomas studied showed immunostaining for the M subunit. The rhabdomyoblastic component of malignant "triton" tumors was also positive. Staining, although weak compared with that of the rhabdomyosarcomas, was also observed in a few leiomyosarcomas, hemangioendotheliosarcomas, malignant fibrous histiocytomas, and ganglioneuroblastomas. On the other hand, staining for the B subunit was seen in many types of soft tissue tumors, including rhabdomyosarcoma, Ewing's sarcoma, and (ganglio)neuroblastoma. The results indicate that creatine kinase subunit M is a useful marker for distinguishing poorly differentiated rhabdomyosarcoma from other types of small round cell tumors in children, such as neuroblastoma, Ewing's sarcoma, and malignant lymphoma.

Skeletal muscle actin as tumor marker in the diagnosis of rhabdomyosarcoma in childhood.

Immunoaffinity-purified and tissue-specific antibodies against carp skeletal muscle actin have been assessed for their usefulness in diagnosing rhabdomyosarcoma. Routinely processed formaldehyde-fixed tissue and the avidin--biotinyl--peroxidase complex technique were used. Thirty-six tumors of patients varying in age from less than 1 year to 17 years were diagnosed as rhabdomyosarcoma on the basis of routine histological stains or electron microscopy, and on clinical grounds. Among them were 20 poorly differentiated tumors. All moderately and well-differentiated rhabdomyosarcomas and the majority of the poorly differentiated tumors (13 of 20) showed positive immunostaining for actin. Positive staining was observed in all three types of rhabdomyosarcoma, i.e., embryonal, alveolar, and pleomorphic. Besides rhabdomyosarcomas, the only other positive neoplasms were those that contained rhabdomyoblastic differentiation such as malignant "triton" tumors and malignant mixed müllerian tumors. Our results indicate that antibodies against skeletal muscle actin are a powerful tool for diagnosing rhabdomyosarcoma and that they can be used to distinguish the poorly differentiated forms from other types of small round cell tumors in childhood such as neuroblastoma, Ewing's sarcoma, and malignant lymphoma. The results are discussed in the light of the embryogenesis of cross-striated skeletal muscle.

Myosin and myoglobin as tumor markers in the diagnosis of rhabdomyosarcoma. A comparative study.

Antibodies against the myosin heavy chain of adult chicken pectoral muscle and heart muscle which cross-react with myosin of human fast type II fibers ( antifast myosin) and slow type I fibers ( antislow myosin), respectively, and antibodies against human myoglobin have been assessed for their usefulness in diagnosing rhabdomyosarcoma. Formaldehyde-fixed and paraffin-embedded tissue and the avidin-biotinyl-peroxidase complex technique were used. Of 23 rhabdomyosarcomas studied, 20 were positive with antifast myosin and 11 with antimyoglobin . All tumors were negative with antislow myosin. Positive staining was observed in all three types of rhabdomyosarcoma, i.e., embryonal, alveolar, and pleomorphic, regardless of the antiserum used. Staining with antimyoglobin was generally limited to the cytoplasm-rich tumor cells. Besides rhabdomyosarcomas, the only other positive neoplasms were those which contained rhabdomyoblastic differentiation such as malignant Triton tumors and malignant mixed müllerian tumors. Our results indicate that antibodies against the fast myosin heavy chain are a useful tool for diagnosing rhabdomyosarcoma and that they can be used to distinguish that tumor from other small round cell tumors in childhood. The results are discussed in the light of the embryogenesis of skeletal muscle.