Chondromyxoid Fibroma Arising in Craniofacial Sites: A Clinicopathologic Analysis of 25 Cases.

Chondromyxoid fibroma (CMF) is a rare benign tumor, usually arising in the metaphysis of long bones in young adults. Occurrence in craniofacial bones presents a particular diagnostic challenge given its unusual location and resemblance to malignant mimics. We describe the clinicopathologic features of 25 cases of craniofacial CMF identified between 1999 and 2017. Patients were 14 men and 11 women, with median age of 44 years (range, 5 to 83 y). Sites of involvement were sphenoid (7), ethmoid (5), maxilla (3), occipital (2), nasal septum (2), palatine (2), temporal (2), orbit (1), and undisclosed skull (1). Tumor size ranged from 0.8 to 6.0 cm (median, 2.0 cm). Of the 21 tumors with available radiology, 15 arose on the bone surface with expansion into adjacent sinuses; 6 were intraosseous. Bony erosion/destruction was present in most (13/16) cases, and 7/12 showed calcification on imaging. Microscopically, most tumors showed a lobulated growth pattern with hypocellular central chondromyxoid areas and peripheral hypercellularity, though many samples were fragmented. Tumor cells had ovoid to tapered nuclei and abundant palely eosinophilic cytoplasm, frequently with stellate cell processes. Mitoses ranged from 0 to 2 per 10 high-power fields (median count, 0). None showed necrosis. Significant atypia was present in 2 cases, 1 of which was a previously radiated recurrence. Bone infiltration was present in 6 cases. Thirteen tumors had focal calcification, and 2 had foci of hyaline cartilage. All tumors were negative for keratin and GFAP (0/24), with frequent positivity for SMA (7/7) and occasional staining for EMA (5/24) and S-100 (2/24). Most patients underwent piecemeal excision or curettage (5/5 positive margins when reported). Follow-up data were available for 15 patients, and 5 suffered local recurrence. Craniofacial CMF poses diagnostic pitfalls including frequent aggressive radiologic features and lack of a specific immunophenotype. Tumors may recur, largely due to the difficulty of obtaining clear surgical margins in this anatomic region. Furthermore, propensity for local destruction and invasion can create significant morbidity.

ERG expression in chondrogenic bone and soft tissue tumours.

AIM: We studied ERG expression in a large series of chondrogenic bone and soft tissue tumours to assess the value of ERG as a possible marker of chondroid/cartilaginous differentiation. METHODS: Formalin-fixed, paraffin-embedded whole sections from 111 bone and soft tissue tumours with chondroid differentiation or a morphology that may mimic cartilaginous differentiation were retrieved. Immunohistochemistry was performed using anti-ERG monoclonal antibody directed against the N terminus. Nuclear staining was scored as negative (<5%), 1+ (5%-25%), 2+ (26%-50%), 3+ (>51%). RESULTS: Nuclear ERG expression was seen in all cases of soft tissue chondroma (8), chondromyxoid fibroma (7), chondroblastic osteosarcoma (6) and clear cell chondrosarcoma (1). 10/12 conventional chondrosarcomas were also positive for ERG. In cases of dedifferentiated chondrosarcoma, the well-differentiated component was positive in 7/9 cases, while all dedifferentiated foci were negative. In cases of mesenchymal chondrosarcoma, the hyaline cartilage component was positive in 2/4 cases, whereas the primitive component in all cases was negative. Variable positivity was identified in extraskeletal myxoid chondrosarcomas (4/9), chondroblastomas (3/8) and mixed tumours/myoepitheliomas (2/11). Only 1/12 chordoma was positive for ERG (1+). Interestingly, 15/17 enchondromas were negative for ERG. CONCLUSIONS: In this study, we further characterise the expression of ERG in mesenchymal tumours and found relatively constant nuclear ERG expression in selected chondrogenic tumours including conventional chondrosarcoma, chondromyxoid fibroma, chondroblastic osteosarcoma and clear cell chondrosarcoma. We also show that ERG may be a helpful ancillary tool in certain select diagnostic scenarios and that awareness of ERG expression in tumours with cartilaginous differentiation is important.

An unusual case of mediastinal mass and bilateral nodules.

A 23-year-old woman presented with a mediastinal paraganglioma and multiple pulmonary chondromas following antral gastric resection for gastrointestinal stromal tumor. These tumors form the Carney triad, a rare disorder of unknown genetic background. First described in 1977, approximately 120 cases have been documented in the literature. The tumors do not harbor the specific c-kit or PDGFRA gene mutations often found in sporadic gastrointestinal stromal tumor. In most cases, gastric gastrointestinal stromal tumor is the first tumor to be detected, with secondary tumors appearing years later. Even if it is rare, Carney triad should be suspected in young patients with history of gastrointestinal stromal tumor.

Analysis of angiogenic factors and cyclooxygenase-2 expression in cartilaginous tumors- clinical and histological correlation.

OBJECTIVES: To study the role of angiogenesis and cyclooxygenase-2 expression in cartilaginous tumors and correlate these factors with prognosis. INTRODUCTION: For chondrosarcoma, the histological grade is the current standard for predicting tumor outcome. However, a low-grade chondrosarcoma can follow an aggressive course-as monitored by sequential imaging techniques-even when it is histologically indistinguishable from an enchondroma. Therefore, additional tools are needed to help identify the biological potential of these tumors. The degree of angiogenesis that is induced by the tumor could assist in this task. Angiogenesis can be quantified by measuring the expression of vascular endothelial growth factor and CD34, and cyclooxygenase-2 can induce angiogenesis by stimulating the production of proangiogenic factors. METHODS: In total, 21 enchondromas and 58 conventional chondrosarcomas were studied by examining the clinical and histopathological findings in conjunction with the immunostaining markers of angiogenesis and cyclooxygenase- 2 expression. RESULTS: The significant variables that were associated with poor outcome were 1) higher-grade chondrosarcomas, 2) tumors that developed in flat bones, and 3) over-expression of CD34 (with a median count that was higher than 5.9 vessels in 5 high power fields). Moreover, CD34 expression (measured using the Chalkley method) revealed significantly higher microvessel density in flat bone chondrosarcomas. DISCUSSION: Previous studies have shown a positive correlation between Chalkley microvessel density and histological grade; however, in our sample, we found that the former is predictive of the outcome. Chondrosarcomas in flat bones have been shown to correlate with a poor prognosis. We also found that CD34 microvessel density values were significantly higher in flat-bone chondrosarcomas. This could explain-at least in part-the more aggressive biological course that is taken by these tumors. CONCLUSIONS: These results provide evidence that CD34 microvessel density in chondrosarcomas can be helpful in predicting patient outcome and may add to our understanding of chondrosarcoma pathogenesis.

Analysis of angiogenic factors and cyclooxygenase-2 expression in cartilaginous tumors: clinical and histological correlation

OBJECTIVES: To study the role of angiogenesis and cyclooxygenase-2 expression in cartilaginous tumors and correlate these factors with prognosis. INTRODUCTION: For chondrosarcoma, the histological grade is the current standard for predicting tumor outcome. However, a low-grade chondrosarcoma can follow an aggressive course-as monitored by sequential imaging techniques-even when it is histologically indistinguishable from an enchondroma. Therefore, additional tools are needed to help identify the biological potential of these tumors. The degree of angiogenesis that is induced by the tumor could assist in this task. Angiogenesis can be quantified by measuring the expression of vascular endothelial growth factor and CD34, and cyclooxygenase-2 can induce angiogenesis by stimulating the production of proangiogenic factors. METHODS: In total, 21 enchondromas and 58 conventional chondrosarcomas were studied by examining the clinical and histopathological findings in conjunction with the immunostaining markers of angiogenesis and cyclooxygenase- 2 expression. RESULTS: The significant variables that were associated with poor outcome were 1) higher-grade chondrosarcomas, 2) tumors that developed in flat bones, and 3) over-expression of CD34 (with a median count that was higher than 5.9 vessels in 5 high power fields). Moreover, CD34 expression (measured using the Chalkley method) revealed significantly higher microvessel density in flat bone chondrosarcomas. DISCUSSION: Previous studies have shown a positive correlation between Chalkley microvessel density and histological grade; however, in our sample, we found that the former is predictive of the outcome. Chondrosarcomas in flat bones have been shown to correlate with a poor prognosis. We also found that CD34 microvessel density values were significantly higher in flat-bone chondrosarcomas. This could explain-at least in part-the more aggressive biological course that is taken by these tumors. CONCLUSIONS: These results provide evidence that CD34 microvessel density in chondrosarcomas can be helpful in predicting patient outcome and may add to our understanding of chondrosarcoma pathogenesis.

Gadd45ß expression in chondrosarcoma: a pilot study for diagnostic and biological implications in histological grading.

BACKGROUND: Although the diagnosis of chondrosarcoma, especially the distinction between enchondroma and low-grade chondrosarcoma or low-grade chondrosarcoma and high-grade chondrosarcoma, is pathologically difficult, differential diagnosis is very important because the treatment strategies for these diseases are completely different. The grading system is crucial in predicting biologic behavior and prognosis, however, exact pathological grading is difficult using only routine examinations because the criteria of the grading system are not necessarily definitive. Growth arrest and DNA damage-inducible protein 45ß (GADD45ß) is an essential molecule for chondrocytes during terminal differentiation. In the present study, we investigated the immunohistochemical expression of GADD45ß in enchondroma, and chondrosarcoma of histological grades I, II, and III, to clarify the diagnostic significance of GADD45ß in pathological grading of chondrosarcoma. METHODS: Twenty samples (enchondroma = 6, chondrosarcoma grade I = 7, grade II = 6, grade III = 1) were used for immunohistochemical analysis to investigate the expression of GADD45ß. Quantitative analysis was performed to compare the number of GADD45ß positive cells and pathological grading. RESULTS: Over 70% of the cells in enchondromas expressed GADD45ß. On the other hand, the expression of GADD45ß decreased significantly according to the histological grade of chondrosarcoma (grade I: 45%; grade II: 13.8%; and grade III: 3.8%). CONCLUSIONS: The association of GADD45ß expression and pathological grading of chondrosarcoma in the present study suggests that the immunohistochemical study of GADD45ß may be a specific diagnostic parameter for chondrosarcoma cell differentiation.

Distinguishing chordoid meningiomas from their histologic mimics: an immunohistochemical evaluation.

Chordoid meningioma, World Health Organization grade II, is an uncommon variant of meningioma with a propensity for aggressive behavior and increased likelihood of recurrence. As such, recognition of this entity is important in cases that show similar morphologic overlap with other chondroid/myxoid neoplasms that can arise within or near the central nervous system. A formal comparison of the immunohistochemical features of chordoid meningioma versus tumors with significant histologic overlap has not been previously reported. In this study, immunohistochemical staining was performed with antibodies against D2-40, S100, pankeratin, epithelial membrane antigen (EMA), brachyury, and glial fibrillary acidic protein (GFAP) in 4 cases of chordoid glioma, 6 skeletal myxoid chondrosarcomas, 10 chordoid meningiomas, 16 extraskeletal myxoid chondrosarcoma, 18 chordomas, 22 low-grade chondrosarcomas, and 27 enchondromas. Staining extent and intensity were evaluated semiquantitatively and mean values for each parameter were calculated. Immunostaining with D2-40 showed positivity in 100% of skeletal myxoid chondrosarcomas, 96% of enchondromas, 95% of low-grade chondrosarcomas, 80% of chordoid meningiomas, and 75% of chordoid gliomas. Staining with S100 demonstrated diffuse, strong positivity in all (100%) chordoid gliomas, skeletal myxoid chondrosarcomas, low-grade chondrosarcomas, and enchondromas, 94% of chordomas, and 81% of extraskeletal myxoid chondrosarcomas, with focal, moderate staining in 40% of chordoid meningiomas. Pankeratin highlighted 100% of chordoid gliomas and chordomas, 38% of extraskeletal myxoid chondrosarcomas, and 20% of chordoid meningiomas. EMA staining was positive in 100% of chordoid gliomas, 94% of chordomas, 90% of chordoid meningiomas, and 25% of extraskeletal myxoid chondrosarcomas. Brachyury was positive only in the chordomas (100%), whereas GFAP was positive only in the chordoid gliomas (100%). EMA was the most effective antibody for differentiating chordoid meningioma from skeletal myxoid chondrosarcoma, low-grade chondrosarcoma, and enchondroma, whereas D2-40 was the most effective antibody for differentiating chordoid meningioma from extraskeletal myxoid chondrosarcoma and chordoma. Our findings demonstrate that in conjunction with clinical and radiographic findings, immunohistochemical evaluation with a panel of D2-40, EMA, brachyury, and GFAP is most useful in distinguishing chordoid meningioma from chordoid glioma, skeletal myxoid chondrosarcoma, extraskeletal myxoid chondrosarcoma, chordoma, low-grade chondrosarcoma, and enchondroma. A lack of strong, diffuse S100 reactivity may also be useful in excluding chordoid meningioma. Among the neoplasms evaluated, brachyury and GFAP proved to be both sensitive and specific markers for chordoma and chordoid glioma, respectively. Of note, this study is the first to characterize the D2-40 immunoprofile in extraskeletal myxoid chondrosarcoma, results that could be of utility in differential diagnostic assessment.

Chordoma of the anterior cranial fossa and ethmoids with orbital involvement.

PURPOSE: To report a case of orbital chordoma, emphasizing the clinical, operative, and histopathologic findings, and to review similar English-language reports. METHODS: This is a single case report with histopathologic correlation. Search of the English-language literature and review of referenced citations was performed. RESULTS: After treatment with resection and proton beam radiation, our patient is alive, without recurrence at 3-year follow-up. Biopsy of the recurrent tumor was consistent with chordoma. The original biopsy had S100 and pancytokeratin-positive tumor cells, with abundant clear to eosinophilic cytoplasm. Focal EMA positivity was present. Literature review identified 14 additional cases. CONCLUSION: Orbital chordoma is rare. Extraocular motility disturbances occur solely with intracranial lesions as well as those extending into the orbit, but globe displacement is the most common sign of orbital involvement. This tumor often recurs in the path of previous resection. Diagnosis is confirmed by distinctive histopathologic features and positive staining for S100, pancytokeratin, and EMA. Treatment and outcome analysis of orbital chordoma is difficult due to its rarity and lack of reported follow-up and may need to be extrapolated from reported skull base cases.

Dual CD117 expression in gastrointestinal stromal tumor (GIST) and paraganglioma of Carney triad: a case report.

Carney triad is a rare syndrome, with only 20 complete cases reported. We report a 36-year-old white woman with complete Carney triad, including metastatic gastric stromal tumor (GIST), pulmonary chondroma, and nonfunctioning extra-adrenal paraganglioma. Immunohistochemistry was positive for CD34 and CD117 (c-kit) in the GIST, and positive for chromogranin and CD117 in the paraganglioma. Ultrastructural studies demonstrated skeinoid fibers in the GIST. To our knowledge, this is the 21st complete Carney triad case reported and the first report of dual expression CD117 in both GIST and paraganglioma, a finding with intriguing pathogenetic implications related to the organization of the autonomic nervous system.

Intermuscular chondrolipoma of the thigh: the diagnostic way of a rare entity.

Cartilaginous metaplasia in lipomas (chondrolipoma) is rare and mainly encountered in large-sized, long-standing lipomas. Chondrolipomas can be found at almost any site of the body, particularly in the connecting tissue of the skeletal system, breast, pharynx, and nasopharynx. We report on an intermuscular tumor of the thigh in a patient who suffered from lipomatosis in his past medical history. We describe how the diagnosis of chondrolipoma was reached and discuss the differential diagnoses.

Expression of leukemia inhibitory factor by cartilage-forming tumors of bone: an immunohistochemical study.

Recent studies have implicated leukemia inhibitory factor in connective-tissue metabolism involving the remodeling of bone and the destruction of cartilage tissue. This cytokine, which has also been implicated in the proliferation of solid tumor, is expressed by osteotropic tumor cell lines. The present study investigated the presence of leukemia inhibitory factor in cartilage tissue harvested from cartilage-forming bone tumors. Immunohistochemical study showed that it was present in all benign enchondromas (n = 8) and malignant chondrosarcomas (n = 6) but not in control tissue (n = 3). The cytokine was localized in only cytoplasmic areas of cartilage cells. The number of stained cells ranged from less than 5% in enchondroma of the hand to more than 70% in grade-III chondrosarcoma. Moreover, high levels of leukemia inhibitory factor were found in the primary culture of tumor tissues (n = 7). These results question the significance of leukemia inhibitory factor in tumor-associated bone resorption and the potential role of this cytokine as a prognostic marker.

Immunolocalization of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas.

We have immunohistochemically examined the localization of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in human chondrosarcomas (CHS) (23 cases) and benign chondroid lesions (BCL) (16 cases of osteochondromas and 11 cases of enchondromas). In CHS, all the MMPs and TIMPs examined were positive. Among them, MMP-1 was immunolocalized in more than 90% of both CHS and BCL, but positive score of MMP-1 was significantly higher in CHS than that in BCL (p < 0.01). Compared with BCL, CHS expressed MMP-3 at a low level, and more often positive in MMP-9. It is possible that chondrosarcoma might have a tendency to lose the ability to secrete MMP-3, which is a metalloproteinase that can degrade cartilage proteoglycans and is related to normal cartilage turnover. MMP-2, TIMP-1 and TIMP-2 were immunolocalized in more than 70% of the cases of both BCL and CHS, but the positive scores of these were not statistically different between the two groups. Interestingly, in several cases of CHS, both MMP-1 and MMP-9 immunostains were observed preferentially within the cells at the marginal areas of cartilaginous lobules. These findings suggest that increased expression of MMP-1 and MMP-9 and decrease in MMP-3 expression are associated with the malignant phenotype of the cartilaginour tumors.

C-erb B-2 staining in primary synovial chondromatosis: a comparison with other cartilaginous tumours.

In this study C-erb B-2 immunostaining has been used to highlight distinct differences between the cartilage found in primary synovial chondromatosis (n = 20), normal articular cartilage (n = 10), benign enchondromas (n = 10), and chondrosarcomas (n = 10). There was no positive staining in either the normal cartilage or the chondromas, but 15 cases of synovial chondromatosis showed at least some staining, although in the majority of cases fewer than 50 per cent of cells stained positive. There was no correlation between cellularity/pleomorphism and the extent or intensity of staining. Five of the chondrosarcomas were positive, with more than 50 per cent of cells showing positive staining in three of these cases. All positive cases in this series showed a diffuse cytoplasmic staining pattern. Despite these results, there was no Ki-67 positive staining in synovial chondromatosis, which tends to suggest that the demonstrated expression of C-erb B-2 is not related to proliferative activity. The significance of this staining remains undetermined.

Cartilaginous tumors: prognostic applications of cytophotometric DNA analysis.

BACKGROUND: Traditionally, selection of cancer therapy is based on the assessment of the prognosis of the individual patient. The specific type of tumor and the stage of disease have been the most reliable indicators of prognosis. METHODS: Image cytometry to determine DNA content was used in conjunction with clinicopathologic parameters and patient survival to investigate 16 cartilaginous tumors. Histopathologic characteristics, cytometric DNA ploidy status, 2c deviation index (2cDI), DNA malignancy grade (DNA-MG), and 5c-exceeding event (5cEE) were used to learn more about the determination of tumor prognosis. Prognosis was analyzed with a maximum follow-up of 148 months. RESULTS: DNA ploidy status, 2cDI, DNA-MG, and 5cEE are indicators of prognosis. After 148 months of follow-up, patients with aneuploid tumors had a significantly lower overall survival rate compared with those with diploid tumors (P < 0.05). Patients with DNA-MG less than 0.8 or 2cDI less than 1.5 had a significantly longer overall survival rate with respect to the group of patients with a DNA-MG greater than 0.8 or 2cDI greater than 1.5 (P < 0.001). A significant difference was noted in the overall survival rates between patients with tumors with 5cEE less than 3 and 5cEE 3 or greater (P < 0.001). CONCLUSION: Image cytophotometry DNA ploidy status, 2c deviations index, DNA malignancy grade, and 5c exceeding event were investigated and were found to be of prognostic value for patients with cartilaginous tumors.

Differentiation and proliferative activity in benign and malignant cartilage tumors of bone.

To assess the histological grade in benign and malignant cartilage tumors of bone by more objective methods, we examined the differentiation and proliferative activity of tumor cells in six enchondromas, five chondroblastomas, and 13 chondrosarcomas immunohistochemically. A variable number of cells in all tumors showed S-100 protein and vimentin immunoreactivity. In fully differentiated cartilage of enchondromas and low grade chondrosarcomas, tenascin, which is an extracellular matrix glycoprotein, was present in small amounts or absent but was increased at the periphery of tumor lobules and even in the matrix throughout the high grade chondrosarcomas. Higher rate and intensity of proliferating cell nuclear antigen (PCNA) reactivity were found in chondrosarcomas, especially in spindle-shaped cells of high grade tumors, than in enchondromas. The distribution of PCNA-positive cells almost corresponded to the regions with tenascin reactivity. One tumor of high grade chondrosarcoma showed p53 protein immunoreactivity. Aberrant expression of cytokeratin was observed in four chondroblastomas. The expression of desmin was identified in relatively large proportions of enchondromas and chondrosarcomas, regardless of their benign or malignant nature and histological grade. Smooth muscle or muscle-specific actins also were present in a smaller number of tumors. Based on these findings, it is concluded that unusual staining characteristics were present, in addition to those of a chondroblastic nature, in the cartilage tumors of bone. Tenascin and PCNA positivity of various degrees in all chondroblastomas may suggest that they are chondrogenic tumors having a relatively high proliferative activity, albeit their benign clinical course. Proliferative activity of tumor cells in enchondromas and chondrosarcomas correlated well with their histological grade. Tenascin may play a role in promoting tumor cell proliferation of cartilagenous neoplasms and, on the other hand, the alterations of extracellular matrix involving tenascin synthesis seem to be a result of tumor development.

Immunohistochemical study on collagenous proteins and biophysical analysis of crystals in extraskeletal chondroma.

The immunohistological distribution of collagen types I, II, III, and VI in five cases of extraskeletal chondroma was examined and compared with that in six cases of enchondroma. In addition, the composition of crystals deposited in three cases of extraskeletal chondroma were biophysically analyzed with special attention to the relationship between the collagen types of the matrix and the crystal deposition. In extraskeletal chondroma, immunoreactivity of type II collagen in the extracellular matrix and type VI collagen in the pericellular area, which were strongly and diffusely recognized in the normal hyaline cartilage and enchondroma, was diminished. Instead, additional types of collagen, types I and III, were demonstrated in the matrix. Electron roentgenographic microanalysis and infrared light spectroscopic analysis revealed that calcium pyrophosphate dihydrate (CPPD) was included in the crystals of extraskeletal chondroma. CPPD crystals were observed in/around collagen types I and III. The possible relationship between the difference of collagen composition in the matrix and the CPPD crystal deposition is discussed.

p53 expression and DNA ploidy of cartilage lesions.

The aim of this study was to investigate the expression of a tumor suppressor gene (p53) in cartilage lesions of bone and its relationship to their histological grade and DNA ploidy. An immunohistochemical assay for p53 and Feulgen-stained DNA preparations was subjected to computerized image analysis. Enchondromas, synovial chondromatosis, and low grade (grade I and II) chondrosarcomas were diploid. High grade (grade III) chondrosarcomas and high grade sarcomatous components of dedifferentiated chondrosarcomas were aneuploid. Well differentiated cartilaginous components of dedifferentiated chondrosarcomas were diploid. Microscopic examination showed weak focal positivity for p53 in one of 10 enchondromas one of six examples of synovial chondromatosis, and three of four low grade (grade I and II) chondrosarcomas. All three high grade (grade III) chondrosarcomas were strongly positive for p53. The high grade sarcomatous component of all four dedifferentiated chondrosarcomas was strongly positive for p53, whereas only focal weak positivity was noted in the well differentiated cartilaginous areas. These results were confirmed by quantitative computer-assisted image analysis, which showed that high grade aneuploid cartilage tumors demonstrated strikingly higher levels of p53 than did diploid low grade malignant tumors or benign cartilage lesions.

Localized amyloid deposition in cartilage is glycosaminoglycans-associated.

Localized amyloid deposition is known to occur commonly in the articular cartilage of elderly patients. Its pathogenesis is uncertain and it is not known if other cartilage-containing tissues also contain amyloid deposits. Systemic amyloid deposits are known to contain highly sulphated glycosaminoglycans, a major constituent of cartilage. As the composition of articular cartilage glycosaminoglycans is known to change with age, we sought to identify whether localized amyloid deposition in cartilage was glycosaminoglycan-related. We examined specimens of articular cartilage over a wide age range and also examined a variety of cartilaginous tumours and tumour-like lesions for the presence or absence of amyloid deposits. Using mucin histochemistry (alcian blue: MgCl2 critical electrolyte concentration) and immunohistochemistry, we found that highly sulphated glycosaminoglycans (0.9 M and 1 M MgCl2), in particular keratan sulphate, localized to amyloid deposits in both articular cartilage and loose bodies derived from the articular surface. Other cartilaginous lesions (including loose bodies of primary synovial chondromatosis) were negative for amyloid and did not contain highly sulphated glycosaminoglycans. These findings suggest that changes in specific highly sulphated glycosaminoglycans may play a role in localized amyloid deposition in articular cartilage.

The identity of proliferating cells in bone tumors with cartilaginous components: evaluation by double-immunohistochemical staining using proliferating cell nuclear antigen and S-100 protein.

S-100 protein (S-100) appears to be a marker for bone tumors of cartilaginous origin. Any analyses of proliferative activity in S-100-positive tumor cells, however, has not yet been presented. This study assessed the proliferative activity of those cells by means of a double-immunohistochemical staining method using proliferating cell nuclear antigen (PCNA) and S-100. The most intense reactivity for S-100 was found in the well-differentiated chondrocytes of enchondromas, osteochondromas, and osteosarcomas. On the contrary, the more immature the tumor cells were, the more intensely positive they were for PCNA. In parosteal chondrosarcoma, exceptionally, PCNA-positive as well as S-100-positive cells were abundant, suggesting that these proliferating cells produced S-100. In periosteal osteosarcoma, however, the proliferating cells labeled by PCNA revealed little reactivity for S-100. This immunohistochemical method is potentially useful to know the identity and origin of proliferating cells and may sometimes be diagnostic for bone tumors containing cartilaginous elements.