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PubMed2003

Electron microscopy and other ancillary techniques in the diagnosis of small round cell tumors.

The current study disusses a new approach to the group of small round cell tumors (SRCTs) independently of their primary anatomical location. We perform this analysis supported mainly by morphological means and particularly with the help of immunohistochemistry and electron microscopy; the last of which continues to play a decisive role in their differential diagnosis. The microscopical similarity of many of these tumors often makes the diagnosis in routine histology extremely difficult, due to the varying degree of heterogeneity present, and may have important therapeutic and prognostic implications. Thus a correct final diagnosis is mandatory for the clinic. Within the group of tumors that express a dominant or occasional small round cell pattern "SRCT" (neoplasms of the Central Nervous System excluded) are included: Ewing's sarcoma and peripheral neuroectodermal tumor (Es/pPNET) comprising its varieties, neuroblastoma, desmoplastic small round cell tumor, rhabdomyosarcoma, alveolar, solid and embryonal, small cell osteosarcoma, chondrosarcoma, myxoid and mesenchymal, round cell and myxoid liposarcoma, synovial sarcoma (monophasic undiffentiated), primitive malignant peripheral nerve sheath tumor (malignant small cell schwannoma), malignant non-Hogdkin lymphoma, Merkel cell tumor of the skin (small cell carcinoma including neuroendocrine carcinoma). This study discusses in each case not only the histology, supported by immunohistochemistry, but also the main ultrastructural characteristics. We are conscious that in some cases further cytogenetic or molecular biology support may be necessary, when considering the limits of morphology today. Thus, short references on molecular genetics, complementing the structural findings, are given.

Humans↗
PubMed2003

Primary nonphylloides breast sarcomas.

BACKGROUND: The prevalence of primary breast sarcoma is low, occurring in fewer than 1% of women with breast malignancies. The purpose of this study was to examine the presentation, treatment, and prognosis of patients presenting with these neoplasms. METHODS: This was a retrospective review of patients with a primary breast sarcoma treated at Mayo Clinic, Rochester, Minnesota, between 1975 and 2001. Follow-up information was obtained. RESULTS: Of the 55 patients, 17 had breast-conserving therapy and 38 women had mastectomy. The mean patient age at presentation was 52 years (range 22 to 82). The types of sarcoma included angiosarcoma (18), malignant fibrous histiocytoma (11), stromal sarcoma (8), liposarcoma (4), leiomyosarcoma (4), dermatofibrosarcoma protuberans (4), osteosarcoma (3), fibrosarcoma (2), and rhabdomyosarcoma (1). Follow-up information was available for 53 patients, with a mean follow-up of 81 months. Twenty-nine of 53 patients (55%) developed recurrent sarcoma, and 23 patients (43%) died of their disease. Twenty-seven patients had no evidence of recurrence, and 3 patients were alive with disease at last follow-up. Overall median survival of patients with breast sarcoma was 58 months. Patients with angiosarcoma had a poorer outcome than other sarcoma patients. Twelve of 18 patients (67%) died of angiosarcoma, compared with 11 of 32 patients (34%) of all other sarcoma patients combined. Of 34 patients who did not receive adjuvant chemotherapy or radiation, 13 died of their disease (38%), as compared with 10 of 16 patients (63%) who did receive adjuvant therapy. CONCLUSIONS: While primary nonphylloides breast sarcomas are rare tumors, their treatment and prognosis are poor. Adjuvant chemotherapy and radiation did not improve survival in this report. Surgical extirpation remains the only effective treatment.

Adult↗
PubMed2007

Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma.

BACKGROUND: Survivors of hereditary retinoblastoma have an increased risk for second malignancies, especially soft tissue sarcomas. However, the risks of individual histologic subtypes of soft tissue sarcomas have not been evaluated. METHODS: We estimated the risk for six subtypes of soft tissue sarcomas (fibrosarcoma, liposarcoma, histiocytoma, leiomyosarcoma, rhabdomyosarcoma, and others) in a cohort of 963 one-year survivors of hereditary retinoblastoma among patients diagnosed at two US institutions from 1914 through 1984. We calculated standardized incidence ratios (SIRs) for specific subtypes of soft tissue sarcomas by comparison with population data from the Connecticut Tumor Registry or from National Cancer Institute Surveillance, Epidemiology, and End Results database. We also calculated the cumulative risk for all soft tissue sarcomas combined. RESULTS: We observed 69 soft tissue sarcomas in 68 patients with hereditary retinoblastoma. Risks were elevated for soft tissue sarcomas overall (SIR = 184, 95% confidence interval [CI] = 143 to 233) and for individual subtypes. Leiomyosarcoma was the most frequent subtype (SIR = 390, 95% CI = 247 to 585), with 78% of leiomyosarcomas diagnosed 30 or more years after the retinoblastoma diagnosis (SIR = 435, 95% CI = 258 to 687). Among patients treated with radiotherapy for retinoblastoma, we found statistically significantly increased risks of soft tissue sarcomas in the field of radiation. Irradiated patients also had increased risks of soft tissue sarcomas, especially leiomyosarcomas, outside the field of radiation, and risks of soft tissue sarcomas were increased in nonirradiated patients as well, indicating a genetic predisposition to soft tissue sarcomas independent of radiation. The cumulative risk for any soft tissue sarcoma 50 years after radiotherapy for retinoblastoma was 13.1% (95% CI = 9.7% to 17.0%). CONCLUSION: Long-term follow-up of a cohort of survivors of hereditary retinoblastoma revealed a statistically significant excess of leiomyosarcoma and other soft tissue sarcomas that persists decades after the retinoblastoma diagnosis. Retinoblastoma survivors should undergo regular medical surveillance for sarcomas in their adult years.

Adult↗
PubMed1993

Cytogenetics and experimental models of sarcomas.

The sarcomas are an extremely heterogeneous group of neoplasms that continue to present substantial diagnostic and therapeutic challenges. It is notable, therefore, that great strides have been made in the genetic characterization of sarcomas over the past few years. The very consistent chromosome translocations in Ewing's sarcoma, myxoid liposarcoma, and alveolar rhabdomyosarcoma have been cloned, and the oncogenes deregulated by these translocations have been identified. These characteristic genetic aberrations can now be used as diagnostic markers.

Humans↗
PubMed1978

Intracellular collagen fibrils in human sarcomas.

Intracellular collagen was detected by electron microscopy in 14 sarcomas including six osteogenic sarcomas, three liposarcomas, three malignant fibrous histiocytomas, one pleomorphic rhabdomyosarcoma, and one childhood rhabdomyosarcoma. It was contained in not only the fibroblastic cells, but also in the osteoblastic, lipoblastic, myofibroblastic, and primitive cells of the various tumors. The banded intracellular collagen fibrils were observed in large phagocytic vesicles and in smaller membrane-bound vesicles which also appeared to fuse with lysosomes. Residual banding could be seen as well in many such phagolysosomes. Banded collagen was also noted in a primary explant in tissue culture. These findings suggest that the configurations of intracellular collagen seen, are parts of a continuum of a secondary pathway of collagen degradation in mesenchymal tissue and that pathway is one factor indicating a close interrelationship between these sarcomas.

Child↗
PubMed1997

Skeletal metastases from soft-tissue sarcomas. Incidence, patterns, and radiological features.

We reviewed 277 patients with soft-tissue sarcoma (STS) treated between 1975 and 1995 to study the incidence, distribution, time of appearance, and radiological findings of skeletal metastases. Of these, 28 (10.1%) had metastases within a mean period of 18.6 months after admission. The incidence of skeletal metastases differed among the histological subtypes of sarcoma; alveolar soft-part sarcoma, dedifferentiated liposarcoma, angiosarcoma, and rhabdomyosarcoma tended to show higher incidences. The regional bones close to the primary tumour were affected in 13 (46.4%) of the 28 patients, and the axial bones in 18 (64.3%). Radiologically, the metastatic bony lesions predominantly showed osteolytic changes, and there were pathological fractures in 21 of 44 lesions.

Adolescent↗
PubMed1988

Multivariate analysis for histologic prognostic factors in soft tissue sarcomas.

To investigate histologic prognostic factors in soft tissue sarcomas (STS), multivariate analysis was performed on 236 patients with complete clinical information. These included 141 males and 95 females with an age range from 1 to 85 years (median, 47.6 years). Histologically, malignant fibrous histiocytoma (33.5%) was the most common type followed by synovial sarcoma (11%), liposarcoma (10%), rhabdomyosarcoma (7%), and leiomyosarcoma (7%). Monofactorial analysis revealed that sex, depth, location, histologic grade, cellularity, frequency of mitosis, and necrosis were significant prognostic factors. By multivariate analysis, only frequency of mitosis and depth of tumors were proved to be of prognostic significance. The prognostic importance of the frequency of mitosis as shown in previous and the present studies indicates that further investigation of the cell proliferation in patients with STS is required.

Age Factors↗
PubMed1996

The effect of 1, 25-dihydroxyvitamin D3 on the growth of soft-tissue sarcoma cells as mediated by the vitamin D receptor.

BACKGROUND: Soft-tissue sarcomas, malignant neoplasms originating from mesenchymal tissue, are rare but highly aggressive tumors. Present modes of therapy are associated with high rates of recurrence. 1, 25-Dihydroxyvitamin D3, the active metabolite of vitamin D, serves as a potent antiproliferative agent in human cancer cells. METHODS: In this study, six soft-tissue sarcoma cell lines were analyzed for vitamin D receptor (VDR) expression, which was then correlated with the degree of growth inhibition in response to 1, 25-dihydroxyvitamin D3. These cell lines included rhabdomyosarcoma (HS729, A204), fibrosarcoma (HS913t), synovial sarcoma (SW982), liposarcoma (SW872), and leiomyosarcoma (SKLMS-1). The level of VDR messenger RNA (mRNA) expression was determined using a ribonuclease protection assay, and functional receptor content was determined by using a ligand-binding assay. Growth studies, including [3H]thymidine uptake and growth curves, were performed on two of the six cell lines that expressed the highest and lowest receptor levels. RESULTS: Ribonuclease protection and ligand-binding assays demonstrated variable levels of VDR, with HS729 showing high expression and A204 showing no expression. In HS729, [3H]thymidine uptake was significantly decreased at 10(-7) M (33%) and 10(-6) M (40%) 1, 25-dihydroxyvitamin D3. Growth curve studies showed significant growth inhibition of 55% at 10(-6) M. A204 cells showed no growth inhibition upon treatment with 1, 25-dihydroxyvitamin D3. CONCLUSION: This study demonstrates the existence of VDR in soft-tissue sarcoma cells and suggests a correlation between the level of VDR in cells and the degree of growth inhibition caused by 1, 25-dihydroxyvitamin D3 which may potentially serve as an alternative form of therapy for soft-tissue sarcomas.

Calcitriol↗
PubMed2004

Current soft-tissue sarcoma classifications.

In order to analyse the impact of modern sarcoma classification criteria, pathological material from 281 extremity soft-tissue sarcomas (STS) was reviewed. The cases were originally diagnosed between 1972 and 1994, and the most frequent diagnoses then were malignant fibrous histiocytoma (MFH) (26%), liposarcoma (21%), fibrosarcoma (11%), and leiomyosarcoma (10%). After reclassification, the proportions had changed significantly, with the largest group now being leiomyosarcomas (20%), liposarcomas (17%), synovial sarcomas (14%), and sarcomas "not otherwise specified" (NOS) (11%). The original diagnosis was changed in 57% of the cases; in particular, the number of fibrosarcomas was reduced from 32 to 6, and MFHs from 72 to 2, with 22 renamed as myxofibrosarcomas; 20 (7%) were found not to be sarcomas. The main reasons for these results are the recent advances in immunohistochemistry (IHC) together with changes in nomenclature. The findings have obvious implications, in particular for retrospective research.

Fibrosarcoma↗
PubMed1976

Myxomas of the head and neck.

Myxomas are benign mesenchymal tumors that occur rarely in the head and neck. When they do occur, they are prevalent in the jaws and occur less frequently in the subcutaneous tissues. We report ten new cases and review the clinical, structural, and behavioral characteristics of myxomas arising in various head and neck locations. All ages are affected. The most common initial complaint is the presence of a slow-growing mass. The sarcomas, especially liposarcomas and fibrosarcomas, rank high in the differential diagnosis of myxomas. These tumors are stubborn infiltrators. When a capsule is present, it is usually incomplete and insufficient to contain the tumor. Treatment is by wide surgical excision. The high recurrence rate previously reported is probably due to incomplete excision and is higher when enucleation or curettage are used. Long-term follow-up is mandatory since recurrences may develop several years after treatment.

Adolescent↗
PubMed1999

Fine-needle aspiration cytology and immunocytochemistry of soft-tissue tumors and osteo/chondrosarcomas of the head and neck.

The purpose of the study was to present the clinical and cytological findings of 28 cases of malignant or borderline mesenchymal tumors of the head and neck, of which 22 originated from soft tissue and 6 were found in bone or cartilage. The basic procedures employed involved a cytologic review and subclassification of fine-needle aspiration (FNA) smears from the tumors, which were diagnosed as: pleomorphic sarcomas (5 poorly differentiated, 1 angiosarcoma, and 1 epithelioid sarcoma), spindle-cell sarcomas (2 leiomyosarcomas, 2 malignant mesenchymal tumors, and 1 malignant schwannoma), myxoid sarcomas (2 liposarcomas and 1 high-grade tumor), round-cell tumors (1 malignant histiocytic tumor and 1 chloroma), osteosarcomas (3), chondrosarcomas (3), and borderline tumors (2 pleomorphic lipoma, 1 myxolipoma, 1 cranial fasciitis, and 1 fibromatosis). Histological correlation and problems in subtyping on both cytologic and histological material are discussed. It is concluded that FNA cytology can be used with high accuracy to diagnose musculoskeletal tumors in rare sites such as the head and neck.

Adolescent↗
PubMed1985

Haemangiosarcoma of bone.

Haemangiosarcoma of bone is a very rare primary tumour with a variable history and differing radiographic and histological appearances. In some cases the lesion has similar features to the so-called "adamantinoma of long bones" in which the histogenesis is also unknown. Such a lesion is described which occurred in the shaft of the right humerus of a 31-year-old man. Radiographically a centrally located area of osteolysis was seen without marginal sclerosis, but with erosion of the bony cortex. A biopsy was performed 16 months after the first radiographic examination and showed malignant tumour tissue which was difficult to classify histomorphologically. Several different neoplasms such as Ewing's sarcoma, myeloma, liposarcoma, malignant fibrous histiocytoma or a bone metastasis were suggested. Finally, a haemangiosarcoma or so-called "adamantinoma of long bones" was considered. The tumour was completely removed by en-bloc resection. Careful histomorphological investigation of the tumour tissue by means of light microscopy, cytology and electronmicroscopy showed a vascular pattern characteristic of a haemangiosarcoma. Using cytophotometric DNA measurements of the tumour cells, the lesion could be classified as being of low-grade malignancy. This is confirmed since there has now been a 4-year follow up with no local recurrence or metastasis. There are many similarities between a well-differentiated haemangiosarcoma and an "adamantinoma of long bones". The differential diagnosis and the histogenesis of the latter lesion is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Imaging of Soft Tissue Neoplasms in the Adult: Malignant Tumors.

This review discusses the spectrum of malignant soft tissue tumors usually found in adults. Lesions most commonly identified in the pediatric population, as well as tumorlike masses, are not covered. Rather than presenting a complete review, the focus of this discussion is on common lesions and those lesions in which the diagnosis may be suggested on the basis of imaging. Diagnoses covered include malignant fibrous histiocytoma, fibrosarcoma, dermatofibrosarcoma protuberans, liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, leiomyosarcoma, aggressive vascular tumors, extraskeletal chondrosarcoma and osteosarcoma, lymphoma, and metastatic carcinoma.

Journal Article↗
PubMed1983

Omental-mesenteric myxoid hamartomas. Infantile lesions simulating malignant tumors.

Three infants presented with multiple nodular tumors of the omentum and mesentery characterized histologically by plump mesenchymal cells in a myxoid, well-vascularized stroma. Electron microscopy of one tumor revealed reticulated inclusions in dilated cisterna of endoplasmic reticulum. Diagnoses by the original pathologist, or by consultants from referral centers in the United States included liposarcoma, primitive sarcoma, possible leiomyosarcoma, and fibromatosis, but the subsequent evolution of the patients questions the validity of such diagnoses. Two patients received what was deemed ineffective therapy, yet survived with no evidence of disease for over a decade of close follow-up. Another patient received no therapy other than the initial surgery, and has been well for more than a year. Infantile lesions may show deceptive features of immaturity and high cellularity that are apt to be confused with a true malignancy. Omentalmesenteric "myxoid" lesions are probably hamartomatous in origin.

Diagnostic Errors↗
PubMed2005

Recent developments in salvage chemotherapy for patients with metastatic soft tissue sarcoma.

The number of effective cytotoxic agents for the treatment of patients with metastatic adult soft tissue sarcoma is limited, especially when patients have failed anthracycline- and ifosfamide-based chemotherapy. For the subgroup of patients with inoperable gastrointestinal stromal tumour (GIST), progress has been made via the rapid development and approval of the targeted therapy imatinib. Small round cell tumours (SRCTs), such as Ewing's sarcoma/primitive neuroectodermal tumour, desmoplastic SRCT and rhabdomyosarcoma, are chemotherapy-sensitive and potentially curable malignancies, which are treated with multimodality, dose-intensive, neoadjuvant protocols regardless of size or overt metastatic disease. Most other high-grade (grading >I), so-called 'adult type', soft tissue sarcomas such as fibrosarcoma, liposarcoma, pleomorphic and synovial sarcomas are treated with an anthracycline-based regimen with or without ifosfamide as front-line therapy. In relapsed 'adult type' soft tissue sarcomas, trofosfamide, gemcitabine and trabectedin (ecteinascidin 743) appear to be drugs associated with some activity and an acceptable toxicity profile. A high activity has been reported for the taxanes, in particular for paclitaxel, in vascular sarcomas located in the scalp or face and in Kaposi's sarcoma. It is interesting to note that the different drugs have particular effects in distinct subtypes of soft tissue sarcoma; however, it should be taken into account that the number of patients included in the phase II trials is limited. The role of the newer agents (e.g. epothilones, brostallicin) is currently undefinable. Targeted therapy inhibiting vascular endothelial growth factor receptor, epidermal growth factor receptor, RAF kinase, c-KIT or platelet-derived growth factor receptors will continue to be tested in GIST patients refractory to imatinib and in other sarcoma histologies.

Animals↗
PubMed1998

Myxoid tumors of soft tissues: a challenging pathological diagnosis.

Myxoid tumors (Mts) of soft parts constitute an heterogeneous group of lesions characterized by a similar bland, hypocellular morphological appearance, reminiscent primitive mesenchyma. In this article the overall diagnostic approach is presented with reference to clinical characteristics and distinctive histological criteria. In particular for intramuscolar myxoma, superficial angiomyxoma, aggressive angiomyxoma low grade fibromyxoid sarcoma, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma and myxofibrosarcoma, we discuss the diagnostic clues and the differential diagnosis with regard to immunohistochemical, ultrastructural and molecular genetic characteristics.

Journal Article↗