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L G Kindblom

Publications and source records attributed to L G Kindblom.

At least 37 records · Page 2Linked to original sources
PubMed1999

Synovial sarcoma: identification of low and high risk groups.

BACKGROUND: Synovial sarcoma, one of the most common soft tissue sarcomas that occur in adolescents and young adults, is generally viewed and treated as a high grade sarcoma. However, the authors' own experience and some previous studies have indicated that it has a wide spectrum of biologic behavior and that low and high risk subgroups of patients with synovial sarcoma can be identified. METHODS: A total of 121 consecutive patients with synovial sarcoma (including 66 males and 55 females ages 9-74 years), treated primarily or secondarily at 2 large referral centers for musculoskeletal tumors, were included in a statistical analysis conducted to identify independent prognostic factors. RESULTS: There were local recurrences in 38 patients (31%), usually after inadequate primary surgery outside the referral centers; 64 patients (54%) developed metastasis, primarily to the lungs. The estimated 5-, 10-, and 15-year survival rates were 60%, 50%, and 45%, respectively (the mean follow-up for surviving patients was 9.8 years, with a range of 1-30 years). In multivariate analysis, independent risk factors for local recurrence included larger tumor size and primary surgical resection outside the referral center. Independent risk factors for metastasis were older patient age, tumor with poor histologic differentiation, and tumor necrosis. For tumor-related death, the independent risk factors were older patient age, tumor with poor histologic differentiation, and larger tumor size. Local recurrence was associated with a 3.66-fold increased risk of tumor-related death. A low risk group (patient age <25 years, tumor size <5 cm, and no histologic evidence of poorly differentiated tumor) with 88% overall disease free survival was identified, as was a high risk group (patient age > or = 25 years, tumor size > or = 5 cm, and poorly differentiated tumor) with 18% overall disease free survival (P < 0.001). CONCLUSIONS: The identification of low and high risk synovial sarcoma patients indicates that synovial sarcomas are not uniformly high grade tumors. It also indicates that treatment strategies should be modified for these risk groups. Adequate primary surgery is essential to both local control and outcome for synovial sarcoma patients.

Adolescent↗
PubMed1999

Amplification and overexpression of the hepatocyte growth factor receptor (HGFR/MET) in rat DMBA sarcomas.

In the present study subcutaneous fibrosarcomas were induced by the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) in rats from F1 generation cross breedings of two different inbred strains. Comparative genomic hybridization (CGH) analysis, which allows detection of DNA sequence copy changes, was applied to one of the tumors and it was found that there were increased copy numbers of sequences at chromosome 4q12-q21 in this tumor. We have previously determined that the loci for the hepatocyte growth factor (Hgf) and hepatocyte growth factor receptor (Hgfr/Met), a protooncogene, are situated in this particular chromosome region. Using probes for the two genes in FISH (fluorescence in situ hybridization) and in Southern blots we found that the Hgfr/Met gene was amplified in five of the 19 sarcomas studied, and that the Hgf gene was coamplified in two of them. Northern and Western blots and tyrosine phosphorylation analysis showed that the HGF receptor was overexpressed and functional in all five tumors, as well as in two additional tumors. In summary, both amplification and overexpression of the Hgfr/Met gene was found in about 25% of DMBA-induced experimental rat sarcomas, and HGF receptor overexpression alone was seen in two additional tumors. Possibly this reflects an involvement in paracrine or autocrine stimulation of growth and invasiveness by HGF. Our finding could provide a rodent model system to increased knowledge about causality and therapy, which may be applicable to the sizeable fraction of human musculoskeletal tumors displaying MET overexpression.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Large cell, epithelioid, telangiectatic osteoblastoma: a unique pseudosarcomatous variant of osteoblastoma.

A previously undescribed large-cell, epithelioid, and aneurysmal variant of osteoblastoma with minimal osteoid-production--simulating telangiectatic osteosarcoma, epithelioid angiosarcoma, and metastatic carcinoma is reported. The tumor occurred in the mandible of a 14-year-old girl. The light microscopic, immunohistochemical, ultrastructural, cell proliferation, and DNA-ploidy studies, as well as the 7-year disease-free follow-up period all indicate a benign osteoblastic tumor. Cytogenetically, the tumor had a pseudodiploid karyotype, distinguished by a complex t(1;5;17;22) and a terminal 1q deletion. Recognition of this unique, pseudomalignant variant of osteoblastoma is important to avoid an erroneous diagnosis of malignancy.

Adolescent↗
PubMed1999

Extraskeletal myxoid chondrosarcoma: a reappraisal of its morphologic spectrum and prognostic factors based on 117 cases.

Extraskeletal myxoid chondrosarcoma (EMC), a phenotypically and genotypically distinctive entity, has generally been viewed as a low-grade sarcoma. No studies regarding clinical and morphologic prognostic factors have been performed on a large series of cases with long-term follow-up because of the rarity and protracted clinical course of EMC. The clinical, morphologic, and immunohistochemical features of 117 previously unreported cases were studied and statistically analyzed. The male-to-female ratio was 2:1. The median patient age was 52 years (range, 6-89 years), and the median tumor size was 7 cm (range, 1.1-25 cm). All tumors occurred within the deep subcutis or deeper soft tissues, with 80% occurring in the proximal extremities or limb girdles and 20% in the trunk. Most initial tumor excisions were intralesional or marginal. Follow-up information was available in 99 cases (median, 9 years: range, 2 months-22 years). Forty-eight patients were disease-free, and 41 patients had evidence of disease (18 of these had died of disease). Ten additional patients survived, but their disease status was unknown. There were local recurrences in 40 (48%) of 83 patients, 23 (58%) of whom had multiple local recurrences. Metastases occurred in 35 (46%) of 76 patients. The estimated 5-, 10-, and 15-year survival rates were 90%, 70%, and 60%, respectively. All cases had histologic features characteristic of classical EMC, at least focally. Cellular foci devoid of myxoid matrix and reminiscent of chondroblastoma, Ewing's sarcoma, monophasic and poorly differentiated synovial sarcoma, fibrosarcoma, and rhabdoid tumor were identified in 29% cases. Older patient age, larger tumor size, and tumor location in the proximal extremity or limb girdle were adverse prognostic factors identified by multivariate analysis. Metastasis also adversely affected survival, although local recurrence did not. This study shows that EMC has a unique clinical course, including a high rate of local recurrence, prolonged survival after metastasis in some cases, and eventually a high rate of death due to tumor. These features distinguish EMC from low-grade sarcomas. This study shows that histologic grading is of no prognostic value in EMC because prognosis is dictated primarily by certain clinical features. Histologic recognition of classical EMC and cellular and solid, nonmyxoid variants is important, however, in view of EMC's distinctive biologic behavior.

Adolescent↗
PubMed1999

Expression and localization of estrogen receptor-beta in murine and human bone.

Estrogens have profound effects on bone metabolism. Cellular responses to estrogens are mediated by estrogen receptors (ERs) which belong to the nuclear receptor superfamily. Two estrogen receptors, ERalpha and ERbeta, have been cloned. Previously expression of ERalpha has been shown in osteoblasts. Here we demonstrate that the transcript for ERbeta can be detected in the human osteosarcoma cell lines (MG-63 and SaOS-2) and in cultured human osteoblast-like cells. We also show that ERbeta protein is present in nuclear extracts from these cells. Furthermore, ERbeta immunoreactivity is found in sections of murine and human bone. Murine and human osteoblast and osteocyte nuclei are immunoreactive for ERbeta. Osteoclasts are also ERbeta immunoreactive but the staining is mainly cytoplasmic. The present study demonstrates that ERbeta is present in all the cellular compartments involved in bone formation and bone resorption, both in human and in murine bone tissue.

Animals↗
PubMed1999

Synovial sarcoma--identification of favorable and unfavorable histologic types: a Scandinavian sarcoma group study of 104 cases.

Synovial sarcoma has traditionally been regarded as a high-grade sarcoma and treated as such. Recently, specific types of poorly differentiated synovial sarcoma have been defined and shown to affect prognosis adversely. We studied 104 primary synovial sarcomas of the extremities and trunk wall without metastasis at diagnosis that were retrieved from the Scandinavian Sarcoma Group Registry (SSG) and the Swedish Cancer Registry from 1986 to 1994. Follow-up was available in all patients, median 6 (3-11) years for the survivors. There were local recurrences in 15% of patients and metastases in 33%. Histologically, the tumors were divided into favorable and unfavorable types. The favorable type had no significant cytologic atypia, and in most instances, no necrosis and a mitotic count of < 10/10 hpf. The unfavorable type included so-called poorly differentiated synovial sarcomas as well as recognizable biphasic and monophasic synovial sarcomas with prominent nuclear atypia, extreme cellularity and nuclear crowding. Designation of a tumor as having favorable vs. unfavorable histology conveyed more prognostic information than any single histologic factor. Kaplan-Meier estimates of metastasis-free survival at 5 years were 83% for patients with histologically favorable tumors and 31% for patients with histologically unfavorable tumors (95% confidence intervals 72-92% and 13-51%, respectively). These findings may influence future treatment protocols for synovial sarcoma.

Adolescent↗
PubMed1998

GFAP-deficient astrocytes are capable of stellation in vitro when cocultured with neurons and exhibit a reduced amount of intermediate filaments and an increased cell saturation density.

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein predominantly expressed in cells of astroglial origin. To allow for the study of the biological functions of GFAP we have previously generated GFAP-negative mice by gene targeting [Pekny et al. (1995) EMBO J. 14, 1590-1598]. Astrocytes in culture, similar to reactive astrocytes in vivo, express three intermediate filament proteins: GFAP, vimentin, and nestin. Using primary astrocyte-enriched cultures from GFAP-negative mice, we now report on the effect of GFAP absence on (i) the synthesis of other intermediate filament proteins in astrocytes, (ii) intermediate filament formation, (iii) astrocyte process formation (stellation) in response to neurons in mixed cerebellar astrocyte/neuron cultures, and (iv) saturation cell density in vitro. GFAP-/- astrocytes were found to produce both nestin and vimentin. At the ultrastructural level, the amount of intermediate filaments as revealed by transmission electron microscopy was reduced in GFAP-/- astrocytes compared to that in GFAP+/+ astrocytes. GFAP-/- astrocytes retained the ability to form processes in response to neurons in mixed astrocyte/neuron cultures from the cerebellum. GFAP-/- astrocyte-enriched primary cultures exhibited an increased final cell saturation density. The latter leads us to speculate that the loss of GFAP expression observed focally in a proportion of human malignant gliomas may reflect tumor progression toward a more rapidly growing and malignant phenotype.

Animals↗
PubMed1998

Amplification of 12q13 and 12q15 sequences in a sclerosing epithelioid fibrosarcoma.

Sclerosing epithelioid fibrosarcoma (SEF) is a recently described entity. It is a low-grade sarcoma that occurs primarily in the deep soft tissues of the extremities of adults. It may histologically simulate benign lesions such as fibroma and myxoma or malignancies such as sclerosing carcinoma and lymphoma, extraskeletal myxoid chondrosarcoma, clear cell sarcoma of tendons and aponeuroses, and synovial sarcoma, depending on the lesion's cellularity, degree of fibrosis, and amount of myxoid matrix. There are no previously published cytogenetic studies of this tumor. We found the karyotype 40-45,XY,add(9)(p13),add(10)(p11),-12,-13,-18,add(18)(q11),add(20)(q11) in a SEF of a 14-year-old boy, by using chromosome banding. Fluorescence in situ hybridization showed that both the add(10) and the add(18) contained amplified sequences from 12q13 and 12q15, including the HMGIC gene. Chromosome 18 material was present in the add(9) and terminally in the add(10). The karyotype of this case indicates that SEF is unrelated to extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and synovial sarcoma. When compared with the findings in other soft tissue tumors such as well-differentiated liposarcoma and low-grade malignant fibrous histiocytoma, the chromosome banding and in situ hybridization data add support to the notion that SEF is a relatively low grade variant of fibrosarcoma.

Adolescent↗
PubMed1998

Angiosarcoma of soft tissue: a study of 80 cases.

The clinicopathologic, immunohistochemical, and ultrastructural features of soft tissue angiosarcomas are not well defined. Eighty cases of angiosarcoma that involved the deep subcutis, skeletal muscle, retroperitoneum, mesentery, and mediastinum are reported. The lesions occurred in 50 male and 30 female patients who were 5-97 years of age; the peak incidence was in the seventh decade of life. A variety of associated conditions were documented in 20 of these cases, including a history of other neoplasms (some irradiated), synthetic vessel grafts, heritable conditions, and prior trauma or surgery. The angiosarcomas occurred in the extremities (n = 43 cases), trunk (n = 28), and the head and neck (n = 9) regions, with the thigh and the retroperitoneum being the most common sites. They often were characterized as enlarging, painful masses of several weeks' duration and were occasionally associated with acute hemorrhage, anemia, or a coagulopathy. The tumors measured 1-15 cm in diameter (median 5 cm) and frequently were hemorrhagic and multinodular. There was a wide morphologic spectrum within and between cases, including areas similar to cavernous and capillary hemangioma, Dabska tumor, spindle cell and epithelioid hemangioendothelioma, various spindle cell sarcomas, or carcinoma. Histologically, epithelioid angiosarcoma was the most frequently observed pattern; 70% of cases had epithelioid cells that were arranged in nests, clusters, papillae, and gaping vascular channels. Hemorrhage tended to obscure the diagnosis in several cases and often was associated with papillary endothelial hyperplasia-like areas. All 42 cases studied immunohistochemically stained at least focally for Factor VIII-related antigen, and nearly all stained strongly for vimentin, which accentuated the endothelial cells and vessel lumen formation. CD34 antigen was detected in 74% of cases, BNH9 in 72%, and cytokeratins in 35%. Epithelial membrane antigen, S-100 protein, and HMB45 were not detected. Fifty-five percent of the tumors had intracytoplasmic aggregates of laminin. Immunostains for alpha-smooth muscle actin demonstrated a prominent pericytic component in several tumors (24%). Ki67 immunostains with MIB1 indicated high proliferative activity (> or =10%) in 72% of cases. p53 immunoreactivity (>20% nuclear staining) was observed in 20% of cases. Ultrastructural studies performed on poorly differentiated areas of 12 cases showed groups of cells, which were frequently epithelioid, surrounded by basal lamina, and closely associated with pericytes, along with intercellular and intracellular lumina with or without red blood cells. Whorls of abundant intermediate filaments, occasional tonofilamentlike structures, and pinocytotic vesicles also were noted. In contrast to the findings of others, Weibel-Palade bodies were not seen. Follow-up in 49 cases (61%) showed that 53% of patients were dead of disease at a median interval of 11 months, whereas 31% had no evidence of disease at a median interval of 46 months. The remaining patients were either alive with disease (14%) or alive but disease status was unknown (2%). There were local recurrences in 20% of cases and distant metastases in 49%, most frequently to the lungs, followed by the lymph nodes, soft tissues, bone, liver, and other sites. These results indicate that angiosarcoma of soft tissue is a high-grade sarcoma. Older patient age, tumor location in the retroperitoneum, and larger tumor size as well as detection of MIB1 in > or =10% of the tumor cell population were all associated with a poorer prognosis.

Actins↗
PubMed1998

Benign epithelioid schwannoma.

Benign schwannoma (neurilemoma) has various morphologic patterns that may cause problems in differential diagnosis. Although an epithelioid variant of malignant schwannoma simulating carcinoma and melanoma is well recognized, a benign counterpart has not yet been defined. In the current study, we describe five cases of benign epithelioid schwannoma that were in the subcutis (four cases) and the neck of the urinary bladder (one case). The tumors occurred in adults 28-73 years of age, were 1-4.5 cm in diameter, were well circumscribed and cellular, and were composed of epithelioid cells arranged in cords and nests. The benign nature of the lesions was evident by a constellation of features, including small size, sharp circumscription, bland morphology, low proliferative activity (four of five had < or =1% Ki67 immunostaining), and a benign clinical course after either marginal or intralesional excision. All cases had some features of classic schwannoma light microscopically and a high degree of Schwann cell differentiation both ultrastructurally and immunohistochemically. The recognition of benign epithelioid schwannoma is important because it may be misinterpreted as a malignant neuroectodermal, mesenchymal, epithelioid, or melanocytic tumor.

Adult↗
PubMed1998

Malignant granular cell tumor of soft tissue: diagnostic criteria and clinicopathologic correlation.

Seventy-three cases of malignant, atypical, and multicentric granular cell tumors of soft tissue were studied to clarify criteria for malignancy and prognostic factors. Six histologic criteria were assessed: necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (> 2 mitoses/10 high-power fields at 200x magnification), high nuclear to cytoplasmic (N:C) ratio, and pleomorphism. Neoplasms that met three or more of these criteria were classified as histologically malignant; those that met one or two criteria were classified as atypical; and those that displayed only focal pleomorphism but fulfilled none of the other criteria were classified as benign. Hence, 46 cases were classified as histologically malignant, 21 as atypical (3 were multicentric), and 6 as benign (all were multicentric). The patients with benign multicentric and atypical granular cell tumors had no metastases and there were no tumor deaths. In contrast, 11 of 28 patients (39%) with malignant granular cell tumor with follow-up information died of disease at a median interval of 3 years; 8 of 28 (29%) were alive with disease, and 9/28 (32%) were disease free (median intervals, 2 and 7 years, respectively). There were local recurrences in 9 of 28 malignant cases (32%) and metastases in 14 of 28 (50%) (median intervals, each 2 years). Forty-eight cases were studied immunohistochemically; 100% expressed vimentin, 98% S-100 protein, 98% neuron-specific enolase, 69% CD57, and 65% CD68. Alpha-smooth muscle actin, desmin, epithelial membrane antigen (EMA), cytokeratins (with CAM 5.2 and KL-1), chromogranin, and HMB45 were not detected. The proliferative index with Ki67 (MIB 1) was 10-50% in 14 of 25 malignant tumors (56%), and immunostaining for p53 was detected in 50% or more of tumor cells in 17 of 25 (68%); both of these factors were statistically significant with regard to the histologic classification as benign, atypical, or malignant. Ultrastructural examination of 13 benign, atypical, and malignant granular cell tumors showed engorgement of the cytoplasm with complex granules and lysosomes, as well as Schwannian features. By flow cytometric DNA analysis, two of six malignant tumors were aneuploid, two were hyperdiploid, and two were diploid. One atypical tumor was aneuploid and all 11 benign tumors were either diploid (9 cases) or hyperdiploid (2 cases). Statistically significant adverse prognostic factors with regard to survival included local recurrence, metastasis, larger tumor size, older patient age, histologic classification as malignant, presence of necrosis, increased mitotic activity, spindling of tumor cells, vesicular nuclei with large nucleoli, and Ki67 values greater [corrected] than 10%. This study defines clinical and morphologic criteria for malignancy in granular cell tumors and shows that malignant granular cell tumor is a high-grade sarcoma with a high rate of metastases and a short survival.

Adolescent↗
PubMed1998

Acral myxoinflammatory fibroblastic sarcoma: a low-grade tumor of the hands and feet.

Acral myxoinflammatory fibroblastic sarcoma is a unique low-grade tumor of modified fibroblasts. It characteristically occurs in the distal extremities and has a propensity to recur locally. Forty-four cases that occurred in 22 males and 22 females from 20 to 91 years of age (median, 53 years) were studied. The lesions, which were 1-6 cm (median, 3 cm), occurred in the hands (64%), the feet (20%), the ankles (11%), and the wrists (5%). The patients usually had a long history of a painless mass (median duration, 1 year). Clinically they were suspected to be ganglion cysts, tenosyonovitis, or giant cell tumors of tendon sheath. Initial histologic diagnoses, in most cases, included pigmented villonodular tenosynovitis or various reactive fibroinflammatory processes. Histologically, the lesions were multinodular, poorly delineated, and characterized by a prominent myxoid matrix containing numerous inflammatory cells, including polymorphonuclear leukocytes, eosinophils, lymphocytes, and plasma cells, as well as fibrosis. Amidst the prominent inflammation, and sometimes obscured by it, were scattered, large, bizarre tumor cells with vesicular nuclei, prominent inclusion-like nucleoli, and abundant eosinophilic cytoplasm, which was homogeneous to vacuolated and often contained intracytoplasmic inflammatory cells. Ultrastructurally, the bizarre tumor cells had features of modified fibroblasts, including an abundance of intermediate filaments and dilated rough endoplasmic reticulum. Immunohistochemically, the neoplastic cells revealed strong positivity for vimentin (25 of 25), focal positivity for CD68 antigen (17 of 25) and CD34 (7 of 25); the tumor cells did not express neuroectodermal, epithelial, or lymphoid markers. The Ki67 labeling index with MIB1 was less than 1% in 20 of 25 cases; p53 immunoreactivity (20-90%) was observed in 7 of 25 primary tumors and in 2 of 3 local recurrences. Follow-up information was available in 36 of 44 cases (median, 5 years). Most excisions were either intralesional or marginal. Ten patients underwent amputation, usually after repeated local recurrences. Radiation therapy and chemotherapy were administered in five and two cases, respectively. Twenty-four cases (67%) had at least one local recurrence. A histologically proven lymph node metastasis developed in one patient, whereas another was stated to have lung metastases, although these were not documented histologically. At last follow-up, 23 patients were alive and well, 11 were alive with disease, and 2 were dead of other causes without evidence of tumor. The prominent inflammation and fibrosis seen histologically in acral myxoinflammatory fibroblastic sarcoma simulate a reactive process. The presence of myxoid foci and scattered bizarre cells, which are occasionally multivacuolated, may cause confusion with malignant fibrous histiocytoma and liposarcoma. Based on the protracted clinical course, a high rate of local recurrence (sometimes necessitating amputation), and a low rate of metastasis, we believe these tumors are low-grade sarcomas. The intimate relationship with the synovium, the frequent association with tenosynovitis, and the prominent inflammatory infiltrate suggest that inflammation may play a role in the pathogenesis of acral myxoinflammatory fibroblastic sarcoma.

Adult↗
PubMed1998

Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.

The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor.

Adolescent↗
PubMed1998

Inflammatory fibrosarcoma: update, reappraisal, and perspective on its place in the spectrum of inflammatory myofibroblastic tumors.

Inflammatory fibrosarcoma (commonly referred to as inflammatory myofibroblastic tumor) has become increasingly recognized as part of a spectrum of inflammatory myofibroblastic proliferations. It is a potentially locally aggressive myofibroblastic tumor that occurs predominantly in the mesentery of children and young adults. No reliable morphological parameters have been identified that predict prognosis. We evaluated the ultrastructural and immunophenotypic features of 16 cases of inflammatory fibrosarcoma and studied Ki67 (MIB1), PCNA, bcl-2, and p53 in an effort to identify prognostic markers. p53 was not detected immunohistochemically in any case. None of the markers were found to correlate with local recurrences, metastases, or tumor deaths. Low proliferative activity (Ki67 < 10%) was seen in all cases. A characteristic immunophenotype was reconfirmed in which lesional myofibroblasts stained for vimentin, alpha-smooth muscle actin, cytokeratins, and rarely desmin. Ultrastructural studies of seven cases confirmed the presence of a fibroblastic-myofibroblastic spectrum. Because inflammatory myofibroblastic tumor-inflammatory fibrosarcoma is associated with systemic symptoms, polymerase chain reaction studies for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were performed in 12 cases. Evaluable results in nine cases did not show evidence of either virus. The results of this study indicate that inflammatory fibrosarcoma has a low proliferative activity, which is in keeping with the impression that this is a low-grade sarcoma; that myofibroblasts can participate in true neoplasia; and that EBV and CMV do not play a role in the pathogenesis of inflammatory fibrosarcoma. The variable phenotype of the myofibroblast and its role in reactive and neoplastic processes are discussed. A perspective on the position of inflammatory fibrosarcoma in the spectrum of inflammatory myofibroblastic tumors is also given in light of the current study and the literature.

Adolescent↗
PubMed1996

Aggressive angiomyxoma: a clinicopathologic study of 29 female patients.

BACKGROUND: Aggressive angiomyxoma is an uncommon mesenchymal tumor that preferentially involves the pelvic and perineal regions of females. Since its initial description in 1983, approximately 65 cases have been reported in the English literature. METHODS: The clinical and pathologic features of 29 cases of aggressive angiomyxoma were evaluated in a review of archival material from the Armed Forces Institute of Pathology (1960-1992). Histochemical stains for mucosubstances and immunohistochemistry (avidin-biotin complex method) were utilized to characterize the neoplasms further. RESULTS: All patients were females, between 16 and 70 years (median; 34 years). The soft tissues of the pelvis, perineum, vulva, buttock, retroperitoneum, and inguinal regions were involved. The majority of the tumors were > or = 10 centimeters in greatest dimension. Follow-up ranging from 8 to 198 months (mean, 93 months; median, 95 months) was available for 22 patients. Eight patients developed recurrent tumor, from 10 months to 7 years after the initial resection. No patient developed metastases and there were no tumor related deaths. Histologically, the neoplasms were sparsely to moderately cellular and predominantly composed of bland, relatively nondescript. stellate and spindled cells embedded in a loosely collagenized matrix with scattered vessels of varied caliber. A few cases contained some tumor cells with more abundant eosinophilic cytoplasm that raised the possibility of focal smooth muscle differentiation. The tumor matrix was no more than weakly reactive for mucosubstances; thus, while glycosaminoglycans are present to a limited extent, edema fluid appears to be a major component of the noncollagenous stroma. The neoplastic cells were at least focally immunoreactive for desmin (22/22), smooth muscle actin (19/20), muscle specific actin (16/19), vimentin (17/17), CD34/QBEND-10 (8/16), and estrogen (13/14) and progesterone (9/10) receptor. All of the examined tumors were negative for S100 protein (20/20). Ki67 (MIB1) immunoreactivity was present in <1% of the tumor nuclei in all 16 cases tested. CONCLUSIONS: Aggressive angiomyxoma is a distinctive, locally aggressive, mesenchymal tumor that appears to be relatively site specific and has a peak incidence in females in the fourth decade of life. There is a strong propensity for local recurrence but metastatic disease has not been reported. Since the first evidence of recurrence may be many years after the initial resection, long term follow-up is required. The neoplastic cells of aggressive angiomyxoma exhibit fibroblastic and myofibroblastic features and appear to be hormonally influenced. The possibility that the progenitor cell has a capacity for smooth muscle differentiation is raised.

Adolescent↗
PubMed1996

Soft tissue sarcoma after treatment for breast cancer.

In a register study all women in the West of Sweden Health Care Region with a breast cancer diagnosed between 1960 and 1980 (n = 13,490) were followed up in the Swedish Cancer Register to the end of 1988 for later occurrence of a soft tissue sarcoma (STS). Nineteen sarcomas were reported, whereas 8.7 were expected and the relative risk (RR) was 2.2 (CI 95% 1.3-3.4). The absolute risk was 1.7/10(4) person years (PY) in comparison with 0.8 expected. To obtain a more detailed analysis of the associations between arm lymphoedema, radiotherapy and STS development, and to control the quality of the register data, a case control study was also performed. Clinical records from the different hospitals in the region were collected for all the 19 cases as well as for three selected controls per case. The histopathology of the cases were reviewed, and one of the cases was reclassified as a malignant melanoma and excluded from further analysis. Thirteen of the cases were clustered around the treated breast area. To quantify the exposure to radiotherapy, the integral dose was estimated. The presence of lymphedema was included as a binary variable in the analysis. The exact conditional randomisation test indicated a significant correlation between the integral dose and the development of an STS (p = 0.008) and this association was still significant after stratification for arm oedema. A conditional logistic regression analysis with STS as the dependent variable and the integral dose as the explanatory variable gave an odds ratio (OR) of 5.2/100 J (CI 95% 1.3-21.2), and if this regression was restricted only to the STS developing in the radiation fields the OR was 3.2/100 J (CI 95% 0.8-12.9). Thus, the excess of STS in this breast cancer cohort was very low (0.9/10(4) PY). However the integral dose correlates well to the development of STS and can be useful in quantifying even small risks of secondary malignancies in the breast cancer population.

Arm↗
PubMed1996

Differential diagnosis of small round cell tumors.

The differential diagnosis of small round cell tumors includes not only the small round cell tumors of infancy and childhood, but a variety of mesenchymal, cutaneous, and lymphoreticular neoplasms that may occur in adults as well as children. Moreover, lesions considered to be the classical small round cell tumors of childhood may occasionally occur in adults, and lesions characteristically seen in adults may at times occur in children. An awareness of the diverse lesions that may present as small round cell tumors is critical to arrive at the correct diagnosis. Immunohistochemical techniques and ultrastructural studies have now become indispensable in the diagnosis of small round cell tumors. With recent developments in cytogenetic and molecular genetic techniques, the pathologist has acquired an even more powerful and precise armamentarium of diagnostic tools. Judicious use of these methods, with knowledge of their significance and limitations, is the responsibility of the pathologist and laboratory coworkers who play a pivotal role in patient care and treatment. The differential diagnosis of small round cell tumors, including adult-type sarcomas, lymphoreticular malignancies, and neuroectodermal tumors of skin and viscera that simulate classical small round cell tumors, is briefly reviewed with this perspective. Specific cytogenetic and molecular markers are covered in addition to the typical immunohistochemical and ultrastructural features of several diverse lesions.

Diagnosis, Differential↗