Imaging features of intraosseous hemangiomas: beyond the mobile spine and calvarium.

OBJECTIVE: Describe imaging features of intraosseous hemangiomas located outside of the mobile spine and calvarium. MATERIALS AND METHODS: Imaging and medical records were retrospectively reviewed for cases of intraosseous hemangiomas located outside of the calvarium and mobile spine. Evaluation included patient demographics, histologic confirmation, and imaging characteristics. RESULTS: Thirty-six patients were included (25 F, 11 M; mean age 54 ± 17 years, range 10-84 years) with 37 total lesions (70% axial and 30% appendicular skeleton). Mixed lytic and sclerotic features were identified on 83-85% radiographs and CTs. Amorphous increased density mimicking osteoid matrix was present on 38-45% radiographs and CTs. Classic honeycomb or radial pattern was identified on 45% of CTs. Osseous expansion and cortical permeation were common features. CT identified periosteal reaction in 24% of lesions. All hemangiomas had heterogeneous MRI signal and most moderately or avidly enhanced. Intralesional fat was identified on 78% MRIs, often as a minor component and only detected on 24% of CTs. A soft tissue mass was present on 52% of MRIs. FDG PET/CT mean SUVmax of 3.2 ± 0.6 (range 1.9-5.0). Lesional FDG activity relative to background marrow was increased in 75% of lesions. Lesions with cortical permeation had higher metabolic activity versus those without (3.5 ± 0.7 versus 2.2 ± 0.3, p = 0.041). CONCLUSION: Intraosseous hemangiomas outside of the mobile spine and calvarium demonstrate more aggressive imaging features compared to vertebral hemangiomas, including cortical permeation, soft tissue mass, amorphous increased density mimicking osteoid matrix, and increased FDG activity.

Type II collagen, but not aggrecan expression, distinguishes clear cell chondrosarcoma and chondroblastoma.

AIM: Chondroblastoma and clear cell chondrosarcoma are uncommon skeletal neoplasms that have a strong tendency to involve the epiphysis of long bones. They also share some overlapping histological features. Thus, it can be difficult both radiographically and histologically to distinguish these neoplasms. So far there are no immunohistochemical markers available that have been shown to be helpful in differentiating these neoplasms. METHODS: In our study of a series of clear cell chondrosarcomas (n = 15) and chondroblastomas (n = 35), S100, vimentin, aggrecan and collagen type II were detected by immunohistochemistry. RESULTS: We detected immunohistochemical evidence of type II collagen within both the extracellular matrix-rich (chondroid) and matrix-poor areas in all 15 cases of clear cell chondrosarcoma. In contrast, immunohistochemical analysis failed to show staining of collagen type II in any of the 35 chondroblastomas. Other markers, including S100 protein, vimentin and aggrecan proteoglycan were tested in parallel and found to be focally positive in both neoplasms. CONCLUSION: Therefore, our data show that in cases when clear cell chondrosarcoma and chondroblastoma pose a diagnostic challenge, the presence of type II collagen in the extracellular tumour matrix significantly supports the diagnosis of clear cell chondrosarcoma and aids in distinguishing it from chondroblastoma.

Mesenchymal chondrosarcoma: an immunohistochemical study of 10 cases examining prognostic significance of proliferative activity and cellular differentiation.

AIMS: Mesenchymal chondrosarcoma is a rare malignant chondrogenic neoplasm that tends to affect young adults and teenagers. The prognosis is unpredictable, and the identification of prognostic markers that could aid in determining the behaviour of this tumour would be helpful. There are few studies in the literature that have attempted to address this issue. METHODS AND RESULTS: In this study, we explored the prognostic significance of three different parameters: (1) tissue morphology of small cell areas, (2) the expression of tumour differentiation marker genes, and (3) the proliferation rate. Our results did not show a correlation of prognosis with the histological features of the neoplastic small cell areas or the expression of tumour differentiation genes. However, the proliferative activity of the tumour cells appeared to have some prognostic significance as related to patient survival. CONCLUSION: Mesenchymal chondrosarcoma is a rare tumour with a wide clinical range of behaviour. Therefore, it is difficult to obtain reliable prognostic parameters. Nevertheless, our study suggests that proliferative activity may be a useful prognostic parameter for mesenchymal chondrosarcomas.

Calcific myonecrosis: a unique presentation in the upper extremity.

Calcific myonecrosis is a rare and latent condition characterized by a dystrophic calcified lesion that can present 10-64 years following initial trauma. Of the 25 cases documented in English world literature, all have occurred in the lower extremity exclusively. We report a case of a 60-year-old man with a painless enlarging left forearm mass that was subsequently diagnosed as calcific myonecrosis. Awareness of this lesion arising outside of the lower extremity is important to avoid unnecessary surgical intervention and patient reassurance.

Detection of fusion gene transcripts in fresh-frozen and formalin-fixed paraffin-embedded tissue sections of soft-tissue sarcomas after laser capture microdissection and rt-PCR.

The diagnosis of small round cell sarcomas is often very difficult, especially when only small biopsy specimens are available for examination. Recent studies have shown that some sarcomas have specific recurrent chromosomal translocations producing chimeric gene fusions, which can be detected by reverse transcription-polymerase chain reaction (RT-PCR), fluorescent in situ hybridization (FISH), or cytogenetic analysis. In this study, 12 cases of well-defined sarcomas including Ewings sarcoma/primitive neuroectodermal tumors (ES/PNET), synovial sarcoma (SS), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumors (DSRCT) were used to collect specific numbers of cells by laser capture microdissection (LCM), subsequently used for RT-PCR to detect specific chimeric gene transcripts. Tumor cells from fresh-frozen (FS) tissue sections and paraffin-embedded (PS) tissue sections from the same cases were compared directly to evaluate the sensitivity of FS and PS sections as the starting material for analysis. Samples were used for RNA extraction, RT-PCR analysis, and Southern hybridization with fluorescein-labeled internal probes followed by enhance chemiluminescence (ECL) detection. The fusion gene transcripts could be detected using 50 cells from FS materials in all cases and from 1 cell in 9 of 12 cases. For PS, a positive signal could be detected using 200 to 1000 cells in all cases, while weaker signals were detected using 50 cells in most cases. These results indicate that the fusion gene products from small round cell sarcomas can be detected by RT-PCR with 10 to 200 cells from FS and PS tissues. The sensitivity of RT-PCR with FS was 10- to 50-fold greater than with PS. These results also suggest that RT-PCR analysis for sarcoma fusion gene products can be successfully performed when only a few cells are available for analysis, although this is not recommended for routine clinical use.

[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.

Cell biology and matrix biochemistry of chondromyxoid fibroma.

We studied matrix composition and gene expression pattern in chondromyxoid fibromas on the protein and the messenger RNA levels. We could clearly identify focal chondrocytic differentiation within chondromyxoid fibroma by the expression and deposition of type II collagen, which is a marker of chondrocytic cell differentiation. We also were able to show expression of collagen types I, III, and VI in the neoplasm. The major tumor portion was, however, characterized by the presence of hydrated proteoglycans and only minor amounts of collagens, a matrix composition responsible for the myxoid matrix appearance of most parts of these neoplasms. By analyzing cytoprotein expression, we found S-100 protein restricted to cells of the chondroid areas, suggesting S-100 protein staining to be of little help as a positive diagnostic marker for chondromyxoid fibroma. Our data show a specific matrix composition of chondromyxoid fibroma, not previously found in other mesenchymal neoplasms, including chondroblastoma, osteochondroma, enchondroma, and chondrosarcoma. This justifies chondromyxoid fibroma as a specific neoplastic entity, both clinically and biologically.

Dedifferentiated clear cell chondrosarcoma.

Dedifferentiation, a change in the histologic character and clinical behavior of a tumor to a more immature and aggressive one, occurs in approximately 11% of all chondrosarcomas. The original lesion is usually a low-grade chondrosarcoma. Clear cell chondrosarcoma is a rare cartilaginous tumor of low-grade malignancy with a preference for the ends of long bones. It is usually curable by resection. Recurrence commonly follows inadequate surgery, and metastases to lung, brain, and bones can develop. However, dedifferentiation has not yet been described in association with clear cell chondrosarcoma. Three patients are described who were initially diagnosed as having clear cell chondrosarcoma of the femur. Two were treated with en bloc resection for a clear cell chondrosarcoma. One of these had an undifferentiated sarcoma in a local recurrence after 6 years. In the second, metastasis of the clear cell chondrosarcoma developed 5(1/2) years after surgery; autopsy revealed undifferentiated sarcoma in the lung, heart, and lumbar spine. The third patient had dedifferentiated clear cell chondrosarcoma at the time of resection following the biopsy diagnosis of clear cell chondrosarcoma. All three died with metastatic disease. These three patients represent three different manifestations of dedifferentiation-at initial diagnosis, at recurrence, and at metastasis. To our knowledge, this is the first description of dedifferentiation occurring in clear cell chondrosarcoma.

Primary neoplasms of the carpal bones.

Primary neoplasms of the carpal bones are rare. We found 44 primary tumors of the carpal bones of 26,800 bone neoplasms (prevalence, 0.16%). Original histologic slides and original radiographs were reviewed in 36 and 29 cases, respectively. Thirty-eight tumors (86%) were benign; 6 (14%) were malignant. The average patient age was 35 years. Benign lesions were diagnosed at a younger age (32 years) than malignant lesions (58 years). Benign tumors occurred more frequently in males (23 of 38 patients); the 6 malignant lesions were equally distributed by gender (3 males and 3 females; 95% confidence interval, 11.8-88.2). The most common tumor was osteoid osteoma (11 cases); the most common malignant neoplasm was hemangioendothelial sarcoma (3). The most common locations were the scaphoid (13 cases) and capitate (10), which together accounted for 52% of all neoplasms. Tumors were identified in every carpal bone except the trapezium. The diagnosis of tumor in a carpal bone should be considered in the undiagnosed painful wrist, especially in younger patients without imaging abnormalities.

Osseous Hodgkin disease.

BACKGROUND: Hodgkin disease rarely presents as an osseous lesion, and the majority of patients are found at staging to have concurrent disease in lymph nodes. Many cases of osseous Hodgkin disease have been misdiagnosed on initial biopsy. METHODS: All cases of Hodgkin disease diagnosed by open bone biopsy at the Mayo Clinic were identified. These included patients with primary osseous tumors, those presenting with multiple sites of involvement (with osseous lesions), and those with recurrence in bone. Recut sections were subjected to immunohistochemical stains to confirm the diagnosis. Clinical data and follow-up information were obtained from patients' charts. RESULTS: Twenty-five patients (15 males and 10 females with an average age of 37 years) with osseous Hodgkin disease were identified during the years 1927-1996. Three patients had solitary, osseous tumors and two had primary, multifocal, osseous Hodgkin disease without involvement of nonosseous sites. Twelve patients who presented with lesions in osseous sites also had nonosseous tumors detected at staging, and 8 patients had recurrent Hodgkin disease that presented in bone. The majority of patients with primary and recurrent tumors presented only with bone pain; >50% of patients with concurrent osseous and nonosseous disease also had B-type symptoms. Nearly all lesions were in the axial and proximal appendicular skeleton. Radiographic features included osteosclerotic, osteolytic, and mixed lytic/sclerotic patterns. Cortical destruction, periosteal new bone formation, and soft tissue masses were present in 50% of cases. The histologic diagnosis of osseous Hodgkin disease occasionally was problematic; osteomyelitis was the most frequent misdiagnosis. Immunohistochemical stains revealed expression of CD15 and CD30 in neoplastic cells (which were negative for CD45 and B-cell and T-cell antigens) in all but two cases. Involved lymph nodes typically exhibited nodular sclerosis Hodgkin disease. Three patients with primary solitary osseous Hodgkin disease received radiation treatment only; at last follow-up 2 patients were alive at 22 months and 10 years, respectively. Patients with concurrent osseous and nonosseous tumors exhibited a 60% overall survival rate, but at last follow-up all 4 patients diagnosed after 1986 still were alive; those with Hodgkin disease that recurred as osseous lesions had a 60% survival rate at 8 years, but only 1 of the 5 patients diagnosed since 1984 had died of disease. CONCLUSIONS: Osseous Hodgkin disease typically presents with bone pain, and the majority of patients have concurrent nonosseous lesions detected at staging. Radiographic features of osseous Hodgkin disease vary but indicate an aggressive malignant process. The histologic diagnosis may be problematic; immunohistochemical stains aid in establishing the diagnosis of Hodgkin disease in bone. Survival of patients with osseous Hodgkin disease has been found to be good for the last 10 years.

Chondroblastoma is an osteoid-forming, but not cartilage-forming neoplasm.

Chondroblastoma is defined as a 'benign tumour, characterized by highly cellular and relatively undifferentiated tissue composed of rounded or polygonal chondroblast-like cells' and the 'presence of cartilaginous intercellular matrix' (WHO). An extensive analysis of the extracellular matrix composition and gene expression pattern of a large series of chondroblastoma cases shows, however, that type II collagen, which is the main component of any cartilage matrix, is not expressed by the neoplastic cells of this tumour entity and is not deposited into the extracellular tumour matrix. Instead, osteoid and fibrous matrix is formed, with its typical biochemical composition. The multifocal expression of aggrecan proteoglycan in most chondroblastomas explains the bluish, pseudo-chondroid appearance of some of the matrix-rich areas of chondroblastomas. This study did not show chondroid matrix formation or chondroblastic cell differentiation in chondroblastomas, suggesting that chondroblastoma should be classified as a specific bone-forming, rather than cartilage-forming neoplasm.

Chondromyxoid fibroma of bone: a clinicopathologic review of 278 cases.

In a study of the clinical, radiographic, and pathological features of chondromyxoid fibroma, the tumor was slightly more common in men, usually in the second decade of life. Almost half of the tumors involved the long bones, although the ilium and the small bones were also common sites. Roentgenograms showed a sharply marginated, lobulated, lucent defect in the metaphysis. The tumor involved the medullary bone in an eccentric fashion, and the cortex was thinned and expanded. Periosteal reaction and soft tissue extension were uncommon. Mineralization was identified in 13% of the lesions. Histologically, the tumors were almost always arranged in lobules, which were prominent (macrolobular) or somewhat indistinct (microlobular). The tumor cells were spindle-shaped or stellate and arranged in a myxoid matrix. Calcification was seen in more than one third of the cases but was rarely prominent. Hyaline cartilage and chondroblastoma-like areas were not uncommon. Approximately 18% of tumors showed bizarre nuclei. Permeation of bony trabeculae was uncommon. Treatment was conservative surgical removal; approximately one fourth of the patients had recurrence.

Myxoid chondrosarcoma (chordoid sarcoma) of bone: a report of two cases and review of the literature.

BACKGROUND: Chondrosarcoma of bone is a well recognized, relatively common clinicopathologic entity. Morphologically distinct soft tissue chordoid sarcoma (CS), or extraskeletal myxoid chondrosarcoma, is a relatively rare tumor that has generally been documented in extraosseous soft tissues. METHODS: The clinical and pathologic features of two patients with biopsy-proven CS from the pathology files of the Mayo Clinic and St. Thomas's Hospital were evaluated. Routine hematoxylin and eosin-stained slides were reviewed in both cases. Sections from both were examined immunohistochemically using the avidin-biotin-peroxidase technique and employing commercially available antibodies to the following antigens: S-100 protein, cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), CD31, and factor VIII. Appropriate positive and negative controls were utilized throughout these procedures. Cytogenetic analysis was performed on fresh samples obtained from one tumor. Clinical data were obtained from the patients' medical records. RESULTS: The two cases of primary CS of bone arose from the right distal femur and right scapula, respectively, in 2 men ages 48 and 76 years, respectively. Morphologically, the tumors were lobulated, multinodular, and comprised of a uniform population of rounded to slightly spindled cells. Nuclei were hyperchromatic with inconspicuous nucleoli and surrounded by clear, vacuolated to eosinophilic cytoplasm. Neoplastic cells were arranged in anastomosing chords, strands, and, less often, nests and pseudopapillary structures embedded in an abundant, mostly hypovascular, mucinous matrix. Foci of hemorrhage and cystic degeneration were present in both tumors. No well developed hyaline cartilage or neoplastic osteoid was observed. Immunohistochemically, one neoplasm showed focal positivity for S-100 protein but was uniformly negative for cytokeratin (AE1/AE3), factor VIII, and CD31. The other tumor showed no immunopositivity with cytokeratin, EMA, or S-100 protein. Cytogenetic analysis in the latter tumor revealed a nonrandom reciprocal chromosomal translocation, t(9;22)(q22-31;q11-12). Both patients developed local recurrences and widespread distant metastases. Wide surgical excision was the primary mode of therapy. One patient died of tumor. CONCLUSIONS: Skeletal CS is an extraordinarily rare neoplasm with a distinct morphology. Although follow-up data were limited to only four examples, including two from the literature, the clinical course appears worse than that for usual chondrosarcoma of bone. Wide surgical resection appears to represent the best mode of therapy. The role of chemotherapy and radiation therapy has not been clearly defined.

Cartilaginous tumors of the larynx: clinicopathologic review of 47 cases.

We reviewed the clinical and pathologic features of 47 laryngeal cartilaginous tumors treated at the Mayo Clinic. This represents the largest reported series of these tumors. The patient group consisted of 36 men (77%) and 11 women (mean age, 63 years; range, 44 to 91 years). The tumors included 44 chondrosarcomas, all low-grade, and 3 chondromas. The overall 5-year survival was 90.1%, which did not differ significantly from the expected survival. Laryngectomy was performed as primary treatment for chondrosarcoma in 6 patients. Of the patients with chondrosarcoma, 40% had tumor recurrence or symptomatic tumor progression at an average of 4.5 years after diagnosis. Only 15 of the patients with chondrosarcoma (34%) required total laryngectomy. There were no metastases, and 4 patients died of local disease (all received treatment before 1960). At latest follow-up, 34 patients with chondrosarcoma (77%) were alive without disease or had died of other causes. We conclude that laryngeal chondrosarcoma can be treated with conservative surgery in most cases, both initially and for recurrent disease.

Classification and grading of bone sarcomas.

Bone tumors generally are classified according to the cytologic features or products of the lesional cells. In most instances, the classification corresponds to a normal cell or tissue type indigenous to bone. This article focuses on sarcomas of bone and features a classification scheme similar to what has been described at the Mayo Clinic.

Treatment of stage IE primary lymphoma of bone.

PURPOSE: A retrospective analysis was performed to assess the efficacy of various treatments of Stage IE primary non-Hodgkins lymphoma of bone. METHODS AND MATERIALS: Sixty-three patients with Stage IE primary non-Hodgkins lymphoma of bone (single osseous focus) were seen at our institution between the years 1970 and 1989. Information was obtained regarding each patients' presentation and clinical course. The histology was reviewed in all patients. Modern immunohistochemical stains were performed on each case with available paraffin-embedded tissue. RESULTS: The histologic classification of the tumors was as follows: 43 diffuse large cell, 13 diffuse mixed cell, 3 small noncleaved, and 4 unclassified. The most common presenting symptom was pain (97%) and the following bony sites were involved: 36 long bone, 9 flat bone, 13 spine, and 5 pelvis. Of the 63 cases, 50 were treated with radiation alone, 10 with chemotherapy and radiation, 2 with chemotherapy alone, and 1 with surgery alone. Univariate analysis revealed a suggestion of an improved 5-year disease-free survival for patients treated with chemotherapy and radiation vs. radiation alone (90% vs. 57% respectively, p = .08). Multivariate analysis (controlling for extent of initial evaluation, extent of pathological evaluation and other potential prognostic factors) showed that neither treatment resulted in superior outcome with respect to disease-free survival, disease specific survival, or overall survival, however, doses of radiation greater than 4000 cGy resulted in improved overall survival compared to lower doses (p = 0.01). CONCLUSION: This study supports the use of primary RT (> 4000 cGy) for Stage IE PLB, however, the addition of chemotherapy to the radiotherapeutic management may decrease the initial relapse rate of some patients. Future studies should address this question.

Prognostic significance of spontaneous tumour necrosis in osteosarcoma.

Preoperative chemotherapy is an integral part of the management of osteosarcoma, and the extent of tumour necrosis found at operation is an important prognostic variable. Knowledge about spontaneous, pretherapy necrosis is difficult to obtain but provides important quantitative information about the necrotic effect of chemotherapy. Using three different methods, we studied spontaneous tumour necrosis in 20 localized intramedullary osteosarcomas of the distal femur diagnosed between 1963 and 1972. All patients received surgical treatment only. All six patients with spontaneous necrosis involving more than 20% of tumour died. Five of 14 patients with necrosis amounting to less than 20% were long-term, disease-free survivors. The extent of necrosis was independent of tumour size. Two semiquantitative methods of evaluation were easily applied and reproducible. Spontaneous necrosis in untreated osteosarcomas occurs frequently; extensive necrosis may indicate a rapid clinical course. Tumour necrosis can be quantified reliably in clinical work.

Desmoplastic fibroma of bone.

Desmoplastic fibroma is a rare primary tumor of bone that histologically and biologically mimics the extra-abdominal desmoid tumor of soft tissue. This study reviews 27 cases of desmoplastic fibroma, consisting of 9 from the Mayo Clinic files and 18 from our consultation files. There was a male predominance, and 74% of the patients were in the first 3 decades of life. The most frequent sites of involvement were the metaphysis of long bones and the mandible. Radiographically, the tumors were lucent, expansile lesions with well-defined margins. Histologically, they contained slender spindle cells and various amounts of collagen fibers. En bloc resection is the treatment of choice because a high incidence of recurrence was noticed after lesional curettage.