Evaluation of HER-2/neu status by real-time quantitative PCR in malignant cartilaginous tumors.

The expression of HER-2/neu has been proposed to be a prognostic indicator in osteosarcoma. To clarify the actual frequency of HER-2/neu expression in primary malignant cartilaginous tumors, we examined 89 cases comprising 17 conventional chondrosarcomas, 33 mesenchymal chondrosarcomas, and 39 clear cell chondrosarcomas. We used real-time PCR (LightCycler) assay to quantify the HER-2/neu gene status. The crossing point of HER-2 in normal control bone was 27.77. The crossing points of HER-2 in conventional, mesenchymal, and clear cell chondrosarcomas were 28.48+/-1.79, 27.74+/-3.02, 28.57+/-1.54, respectively. In conclusion, the amplification and overexpression of the HER-2/neu oncogene is absent or at least very rare in malignant cartilaginous tumors. The level of expression of HER-2/neu was similar in all cartilaginous tumor types.

Unilateral hypertrophy of tensor fascia lata: a soft tissue tumor simulator.

OBJECTIVE: To describe the imaging findings in eight cases of unilateral tensor fascia lata (TFL) hypertrophy presenting as soft tissue masses. DESIGN: Imaging studies and medical charts of eight patients were reviewed retrospectively. The imaging studies included five radiographs, five computed tomography (CT) and six magnetic resonance imaging (MRI) examinations. RESULTS: The majority of patients (seven of eight) presented with a palpable proximal anterior thigh mass. One patient was asymptomatic and incidentally diagnosed. There were six females and two males. Ages ranged from 27 to 86 years old (mean 61). MRI and CT showed unilateral enlargement of the TFL muscle in all cases. CONCLUSION: TFL muscle hypertrophy is an uncommon clinical entity, which can simulate a soft tissue tumor. The characteristic appearance on CT or MRI allows a confident diagnosis of muscle hypertrophy to be made, avoiding unnecessary biopsy or surgical intervention.

[Neoplastic chondroneogenesis as a characteristic of mesenchymal chondrosarcomas]. / Neoplastische Chondroneogenese als Charakteristikum mesenchymaler Chondrosarkome.

Mesenchymal chondrosarcomas are rare skeletal malignancies, which are typically characterized by tumor compartmentation. One tumor area is formed by small, undifferentiated neoplastic cells, whereas the second compartment is composed of cartilaginous areas. In this study, the application of in situ detection techniques enabled us to characterize the different tumor compartments according to their cellular differentiation patterns. The use of characteristic marker genes identified all steps of chondrogenesis within the different tumor compartments. Undifferentiated tumor cells in the small-cell areas were negative for vimentin and the cytoprotein S-100, whereas other tumor cells expressed collagen type IIA and vimentin indicating a chondroprogenitor cellular phenotype in these small-cell areas. Fully differentiated chondrocytic cells expressing collagen type II were found in the chondroid areas. The focal expression of type X collagen indicated hypertrophic differentiation of the neoplastic chondrocytes. The results characterize mesenchymal chondrosarcomas as skeletal malignancies that arise from undifferentiated chondroprogenitor cells and have the potential to undergo all steps of chondrocytic differentiation.

Microscopic correlation of radiographically disparate appearing well differentiated osteosarcoma.

Well differentiated (low grade) osteosarcomas are often unrecognized and inadequately treated. We report on a patient with a well differentiated osteosarcoma of the tibia that radiographically presented with two strikingly dissimilar appearing juxtaposed lesions. Proximally, the lesion was sclerotic, and distally, osteolytic. The distal lytic half of the lesion showed focal cortical disruption on MR imaging. Microscopic correlation of the resected specimen suggested that the sclerotic component of the lesion had more fibrous dysplasia-like tissue with fewer features of well differentiated osteosarcoma, and the lytic component, features suggestive of well differentiated osteosarcoma. We believe this microscopic interpretation explains the disparate radiographic appearance as all belonging to well differentiated osteosarcoma with varying amounts of fibrous dysplasia-like tissue rather than the development of well differentiated osteosarcoma in fibrous dysplasia.

[Characterisation and differentiation of chondroblastomas and chondromyxoidfibromas - presence and expression of collagen types I and II]. / Charakterisierung und Differenzierung von Chondroblastomen und Chondromyxoidfibromen - Präsenz und Expression der Kollagentypen I und II.

AIM: Chondroblastomas and chondromyxoidfiibromas are rare benign skeletal neoplasms with reported overlapping histology. Aim of this study was to analyse the biochemical composition of the matrix of these tumour entities in order to further characterise the cellular phenotypes of these neoplasms using typical cell biological marker genes. METHODS: The matrix compositions of chondroblastomas and chondromyxoidfibromas were analyzed by HE-histology, histochemistry, and immunolocalization techniques. Cellular gene expression patterns were detected by mRNA in situ hybridization. RESULTS: Chondroblastomas are rich in collagen type I and show foci of an osteoid-like matrix, whereas collagen type II as a typical marker of chondrocytic differentiation was not detected in any of the specimens. Chondromyxoidfiibromas had foci of chondroid appearance with chondroblastic cellular differentiation characterised by collagen type II expression. CONCLUSION: These results characterise chondroblastomas and chondromyxoidfiibromas as skeletal neoplasms that have a different biology and which can be distinguished by matrix protein expression products: collagen type II, the typical marker of chondroblast differentiation, could only be detected in chondromyxoidfibromas, but not in chondroblastomas. Thus, both neoplasms are clearly different on the cell biological level.

Acral synovial chondrosarcoma.

Acral chondrosarcoma is rare. Synovial chondrosarcoma is even rarer. Synovial chondrosarcoma arising without evidence of pre-existing or concurrent synovial chondromatosis is exceedingly rare. We present a case of acral synovial chondrosarcoma involving both sides of the metacarpophalangeal joint of the thumb in a 69-year-old man. Radiographically, the lesion mimicked gout. On MR imaging, the lobulated contours of the soft tissue mass suggested synovial chondromatosis. Histological examination revealed a chondrosarcoma, which on the basis of imaging findings we present as having arisen from the synovium. The tumor invaded a portion of the cartilage of the metacarpophalangeal joint and equally destroyed the bones of the distal metacarpal and base of the proximal phalanx of the thumb, while sparing the bony joint surfaces.

Chondrosarcoma of the pelvis. A review of sixty-four cases.

BACKGROUND: Treatment of pelvic chondrosarcoma is a difficult problem for the musculoskeletal oncologist. Poor rates of survival and high rates of local recurrence after surgical treatment have been reported in previous studies. The present study was designed to review the long-term oncologic and functional outcomes of surgical management in a large series of patients with pelvic chondrosarcoma who were treated at a single institution. METHODS: The cases of sixty-four patients with localized pelvic chondrosarcoma that had been surgically treated between 1975 and 1996 were reviewed retrospectively. The study was limited to patients who had received no previous treatment for chondrosarcoma. There were forty-one male and twenty-three female patients who had a mean age of forty-seven years (range, fifteen to eighty-eight years). The patients were followed for a minimum of three years or until death. The median duration of follow-up of the living patients was 140 months (range, thirty-nine to 295 months). RESULTS: Thirty-three of the sixty-four patients were first seen with grade-1 chondrosarcoma; twenty-three, with grade-2; one, with grade-3; and seven, with grade-4 (dedifferentiated chondrosarcoma). Thirteen patients had a hemipelvectomy to achieve local tumor control, whereas fifty-one patients underwent a limb-salvage procedure. Twelve patients (19%) had local recurrence, and eleven (17%) had distant metastases. At the time of the final follow-up, forty-four patients (69%) were alive without evidence of disease, thirteen (20%) had died of the disease, six (9%) had died of unrelated causes, and one (2%) was alive with disease. Less than a wide surgical margin correlated with local recurrence (p = 0.014). High-grade tumors correlated with poor overall survival (p < 0.001). All patients who had a limb-salvage procedure were able to walk at the time of the final follow-up, and they had a mean functional score of 77%, according to the system of the Musculoskeletal Tumor Society. CONCLUSIONS: Aggressive surgical resection of pelvic chondrosarcoma results in long-term survival of the majority of patients. There is a high correlation between tumor grade and overall or disease-free survival.

Treatment of aneurysmal bone cysts of the pelvis and sacrum.

BACKGROUND: Aneurysmal bone cysts are benign, non-neoplastic, highly vascular bone lesions. The purpose of this study was to describe the prevalence, the clinical presentation, and the recurrence rate of aneurysmal bone cysts of the pelvis and sacrum and to examine the diagnostic and therapeutic options and prognosis for patients with this condition. METHODS: Forty consecutive patients with an aneurysmal bone cyst of the pelvis and/or sacrum were treated from 1921 to 1996. Their medical records and radiographic and imaging studies were reviewed, and histological sections from the cysts were examined. Seventeen lesions were iliosacral, sixteen were acetabular, and seven were ischiopubic. Seven involved the hip joint, and two involved the sacroiliac joint. All twelve sacral lesions extended to more than one sacral segment and were associated with neurological signs and symptoms. Destructive acetabular lesions were associated with pathological fracture in five patients and with medial migration of the femoral head, hip subluxation, and hip dislocation in one patient each. The mean duration of follow-up was thirteen years (range, three to fifty-three years). RESULTS: Thirty-five patients who were initially treated for a primary lesion had surgical treatment (twenty-one had excision-curettage and fourteen had intralesional excision); two patients also had adjuvant radiation therapy. Of the thirty-five patients, five (14%) had a local recurrence noted less than eighteen months after the operation. Of five patients initially treated for a recurrent lesion, one had a local recurrence. At the latest follow-up examination, all forty patients were disease-free and twenty-eight (70%) were asymptomatic. There were two deep infections. CONCLUSION: Aneurysmal bone cysts of the pelvis and sacrum are usually aggressive lesions associated with substantial bone destruction, pathological fractures, and local recurrence. Current management recommendations include preoperative selective arterial embolization, excision-curettage, and bone-grafting.

Absence of Bcl10 gene mutations in Ewing's sarcomas.

The Bcl10 gene was recently isolated from the breakpoint region of t(1;14)(p22;q32) in mucosa-associated lymphoid tissue (MALT) lymphomas. Somatic mutations of Bcl10 were found in not only t(1;14)-bearing MALT lymphomas, but also a wide range of other tumors. To clarify the actual frequency and spectrum of Bcl10 mutations in primary malignant Ewing's sarcomas, we examined 31 cases of Ewing's sarcomas. Polymerase chain reaction single-stranded conformation polymorphism (PCR-SSCP) and sequencing analyses were done. No Bcl10 mutations were found in our series of Ewing's sarcomas. While screening for mutations, we found three polymorphisms at codons 8 exon 1 of the Bcl10 gene. Our results strongly suggest that somatic mutations of Bcl10 are extremely rare in Ewing's sarcomas and do not commonly contribute to their molecular pathogenesis.

Primary mixed tumor of bone.

Mixed tumors occur most commonly in major salivary glands. They may rarely appear in other sites, such as skin, breast, and lung. There have been rare reports of similar tumors occurring in bone. We report on a patient with a primary mixed tumor of bone. No other primary site has become apparent on follow-up of 5 years. Although mixed tumors detected by bone biopsy are likely to be metastatic, they may rarely represent primary bone neoplasms.

Low incidence of genetic alterations of the p16CDKN2a in clear cell chondrosarcoma.

Mutational inactivation of the cyclin-dependent kinase inhibitors (CDKIs) (p16CDKN2a) tumor suppressor gene has been found in a variety of human tumor types. To investigate the involvement of CDKI abnormality in clear cell chondrosarcoma, alterations of CDKIs were examined in clear cell chondrosarcoma tissues using a quantitative DNA/PCR, PCR-SSCP. Two of 38 specimens (5.2%) we analyzed showed abnormally low levels of p16CDKN2a amplification, suggesting that the allelic deletion of the gene might be low frequent event in progression of this tumor. For detection of subtle sequence alterations such as point mutations, we performed SSCP analysis of the entire coding region of the p16CDKN2a gene. No altered SSCP patterns were found in 38 clear cell chondrosarcoma specimens. This study reflects the very low incidence of genetic alterations of the p16CDKN2a gene in clear cell chondrosarcoma. Therefore, we conclude that the alteration of the p16CDKN2a gene is not involved significantly in the development of clear cell chondrosarcoma.

Overexpression of p53 and absent genetic mutation in clear cell chondrosarcoma.

Clear cell chondrosarcoma is one of the extremely rare chondrosarcomas. The pathogenesis and the molecular genetic events, which contribute to the development of clear cell chondrosarcoma, are not well elucidated, due in part to the lack of sufficient tumor tissue available. To characterize the involvement of the p53 gene abnormality in this disease, we analyzed expression and sequence alteration of p53 by immunohistochemical analysis of the protein expression and quantitative DNA/PCR and PCR-SSCP assays of the gene in 28 paraffin-embedded tissue specimens. Immunohistochemical analysis demonstrated that 7 (25%) showed patchy positive nuclear staining for p53 and 5 (18%) showed diffuse positive nuclear staining patterns. Sixteen (57%) were negative for p53 immunostaining. Quantitative DNA/PCR analysis revealed that none of the cases we studied showed significantly reduced levels of p53 amplification (<0.50), strongly suggesting an allelic deletion of the p53 gene. In contrast, however, DNA/PCR-SSCP analysis failed to detect any types of mutations resulting in amino acid substitution within exons 5-9 regions of the gene. Taken together, our data suggest that genetic alteration of p53 is a relatively rare event in clear cell chondrosarcomas but a substantial fraction of this type of tumors carries abnormal overexpression of p53, which might result from an as yet unidentified mechanism(s).

Radiographic features of Ewing's sarcoma of the bones of the hands and feet.

The radiographic features of Ewing's sarcoma of the bones of the hands and feet are reviewed utilizing cases obtained from the Mayo Clinic patient files and the consultation files of Drs. D.C. Dahlin and K.K. Unni. This series consists of a total of 43 cases of pathologically proven Ewing's sarcoma involving the small bones of the hands and feet. The classic radiographic features of Ewing's sarcoma in the long bones, including lytic, permeative destruction, aggressive periosteal reaction, cortical violation, and a soft tissue mass, are also seen in the bones of the hands and feet, with similar frequency. These classic features are most commonly present in lesions affecting the short tubular bones. Lesions affecting the tarsal bones more often demonstrate atypical radiographic features. These atypical radiographic appearances may play a role in the reported delay in diagnosis of Ewing's sarcoma within the tarsal bones.

Surgical management of duodenal leiomyomas.

Duodenal leiomyomas are rare neoplasms and when present are usually asymptomatic. There are, however, isolated case reports of such leiomyomas giving rise to complications including gastrointestinal hemorrhage and obstruction. The purpose of this study was to review the surgical experience with duodenal leiomyomas at a large tertiary referral center. A retrospective review was performed of all patients with histologically proven duodenal leiomyomas encountered from 1975 to 1995. Twelve patients with surgically treated duodenal leiomyomas were identified. There were eight men and four women with a mean age of 57 years (range 20-73 years) at diagnosis. Anemia was the presenting sign in 10 patients (83%). The mean hemoglobin level at presentation was 10.8 +/- 2.67 g/dl. Other presenting signs included melena (n = 5) and epigastric tenderness (n = 4). No patient had obstructive symptoms. Upper endoscopy visualized the lesion in 9 of 10 patients, but endoscopic biopsy provided an accurate histologic diagnosis in only two of six patients biopsied. All resected specimens underwent frozen section and permanent histopathologic analysis. Local excision was performed in eight patients, as benignancy was anticipated at surgical exploration and frozen section findings. Two patients underwent segmental duodenal resection with primary end-to-end anastomosis, and two patients underwent a Whipple procedure. There was no perioperative mortality. Morbidity was minimal. There was no tumor recurrence during a median follow-up of 8.4 years. Gastrointestinal blood loss is the most common complication of duodenal leiomyomas requiring surgical intervention. Small symptomatic leiomyomas with benign features may be safely treated with local excision.

Extraskeletal osteosarcoma arising in myositis ossificans.

A 53-year-old woman had extraskeletal osteosarcoma that developed from a soft tissue bony mass present on the volar aspect of the left wrist for 4 years. Initially, the bony mass was soft and movable, but during the first year it became hard and fixed. The patient had no history of trauma. Because the lesion did not grow or cause any symptoms, the patient did not come to the hospital until 4 years after she first noticed the lesion. Radiologically, the bony mass had features characteristic of mature myositis ossificans, showing "eggshell" ossification. A nonmineralized soft tissue mass occurred between the surface of the radius and the bony shell. Histologically, a high-grade osteosarcoma was present between the surface of the radius and the well-differentiated bone tissue, which included fatty and hematopoietic marrow. All the findings indicated that our patient had an extremely rare case of malignant transformation of myositis ossificans.

P53 mutations in Ewing's sarcoma.

The p53 tumor suppressor gene is one of the most frequently altered genes in human malignancies. To explore the implication of p53 alteration in Ewing's sarcoma, we analyzed the deletion and sequence alterations of p53 and abnormal amplification of MDM2, which acts as a functional inhibitor of p53, in 35 tissue specimens. Quantitative genomic PCR analysis showed that 2 of 35 tumors have extremely low levels of the p53 gene, indicating a homozygous deletion of the gene. Mutational analysis of exons 4 to 9 of p53 by PCR-SSCP revealed that 3 of 35 tumors carry sequence alterations in exons 5 or 8, and DNA sequencing analysis identified missense point mutations at codon 132 (AAG-->ATG, lysine-->methionine) and codon 135 (TGC-->TCC, cystein-->serine) in exon 5, and codon 287 (GAG-->GTG, glutamic acid-->valine) in exon 8 from these tumors. No abnormal amplification of the MDM2 gene was recognized. Taken together, our data demonstrate that p53 is genetically altered in a small fraction of Ewing's sarcoma.

Osteochondromyxoma of bone: a congenital tumor associated with lentigines and other unusual disorders.

This article describes the clinical and pathologic features of four unusual bone tumors. Three were congenital or most likely so; the fourth, detected at age 1 year, was probably of considerable duration. The patients, three boys and one girl, each presented with a painless mass. Two had the Carney complex, a familial lentiginous and multiorgan tumorous syndrome; another probably had this disorder; the fourth did not show it, but his mother did. The tumors occurred in the nasal region (n = 2) and the diaphysis of the tibia and radius (n = 1 each). Roentgenographically, three had benign characteristics; the fourth, malignant features. Grossly, the tumors were gelatinous, cartilaginous. and bony. Microscopically, they featured benign-appearing polymorphic cells with few division figures arranged in sheets and lobules set in a myxomatous, cartilaginous, osseous, and hyaline fibrous matrix. Cellularity was low to moderate. The tumors eroded bone, one infiltrated between bony trabeculae, and three had soft tissue extension. Complete resection of one tumor was curative; incomplete excision of two tumors resulted in local recurrence (intracranial and fatal) in one and persistence in the other; the fourth tumor remains under observation after biopsy. No tumor metastasized.

Arthroplasty-associated malignant fibrous histiocytoma: two case reports.

AIMS: Sarcoma localized to the site of an arthroplasty procedure is a rare occurrence, and detailed histological depictions and descriptions are limited. We report the clinicopathological findings in two cases of arthroplasty-associated malignant fibrous histiocytoma (MFH) and review the literature. METHODS AND RESULTS: The patients were an elderly man and woman. Medical histories, radiographs and slides were reviewed. Immunohistochemistry, electron microscopy, cytogenetics, and electron dispersion spectroscopy were performed in one case. Both were destructive femoral bone tumours that appeared 2 and 8 years post-total hip arthroplasty, and pursued aggressive clinical courses. The histology was similar in both tumours, consisting of high-grade, pleomorphic sarcoma with numerous osteoclastic giant cells, prominent phagocytic activity, and entrapped particles of bone cement. Literature review disclosed 14 previous reports of arthroplasty-associated MFH, representing the most common phenotype. A number of materials and factors related to arthroplasty procedure, such as metal corrosion, wear debris, osteonecrosis, and chronic inflammation, have been implicated as causative agents. CONCLUSIONS: Arthroplasty-associated MFH is a rare and aggressive tumour. Although the aetiology remains unclear, the small number of arthroplasty-associated sarcomas compared with the large number of joint replacement operations performed over the past four decades suggests a coincidental as opposed to a causal relation.

Cartilaginous lesions of bone.

Cartilaginous lesions of the skeleton are very unusual. It is extremely important to correlate the roentgenographic features, the clinical features, and the histological features to arrive at a definite diagnosis. Most cartilaginous lesions are benign or of low-grade malignancy. However, there are some subtypes of chondrosarcoma that behave in a highly aggressive fashion.

Mutational alterations of the p16CDKN2A tumor suppressor gene have low incidence in mesenchymal chondrosarcoma.

Mutational inactivation of the cyclin-dependent kinase inhibitors (CDKIs) (p16INK4A/MTS1) tumor suppressor gene has been found in a variety of human tumor types. To investigate the involvement of CDKI abnormality in mesenchymal chondrosarcoma, alterations of CDKIs were examined in human mesenchymal chondrosarcoma tissues using a quantitative DNA/PCR, PCR-SSCP. Seven of 33 specimens (21.2%) showed abnormally low levels of p16CDKN2A amplification, suggesting that the allelic deletion of the gene might be a less frequent event in progression of this tumor. To detect subtle sequence alterations such as point mutations, SSCP analysis of the entire coding region of the p16CDKN2A gene, exons 1, 2, and 3 regions, showed no altered SSCP patterns in 33 mesenchymal chondrosarcoma specimens. A low incidence of genetic alterations of the p16CDKN2A was found in mesenchymal chondrosarcoma. Through this study, we conclude that alteration of the p16CDKN2A gene does not participate significantly in the tumorigenesis of mesenchymal chondrosarcoma.