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P C Hogendoorn

Publications and source records attributed to P C Hogendoorn.

At least 19 recordsLinked to original sources

Nora's lesion, a distinct radiological entity?

OBJECTIVE: To describe the radiological findings of "Bizarre parosteal osteochondromatous proliferation"(BPOP)-otherwise known as Nora's lesion, to describe the natural evolution of BPOP and to assess radiologically if BPOP is indeed part of a spectrum of reactive lesions including florid reactive periostitis and turret exostosis. DESIGN: Four experienced musculoskeletal radiologists studied plain radiographs and other imaging documents of histologically-proven Nora's lesions, looking for soft-tissue changes, periosteal reaction/calcification and calcified/ossified pseudotumours, and compared those findings with findings on pathology reviewed by a peer group of pathologists. PATIENTS: Twenty-four Nora's lesions originating from a series of 200 consecutive, histologically-verified bone (pseudo)tumours of the hand, seen by the "Netherlands Committee on Bone Tumours" for review and second opinion. RESULTS: Nora's lesions have a recognised presentation on radiographs without specific MR characteristics. Natural evolution could be assessed retrospectively in four cases. Recurrent lesions were seen in seven cases and are difficult to differentiate from primary lesions. CONCLUSIONS: Nora's lesion, defined as a "well-marginated mass of heterotopic mineralization arising from the periosteal aspect of an intact cortex, without medullary changes" has a distinct radiological presentation and is part of a spectrum of reactive lesions which includes florid reactive periostitis and turret exostosis. As it has a distinct radiological appearance, differential diagnosis of malignant lesions such as osteosarcoma and chondrosarcoma should be clear. It does not require immediate biopsy unless the natural evolution is unspecific.

Adolescent↗

[Imatinib, a specific tyrosine-kinase inhibitor, for the treatment of patients with a gastrointestinal stroma cell tumor].

The c-kit oncogene, encoding for a transmembrane growth-factor receptor with tyrosine-kinase activity (KIT), plays an important role in the tumourigenesis of gastrointestinal stroma-cell tumours (GISTs). GISTs are a heterogeneous group of mesenchymal tumours, mainly localised in the abdomen. Immunohistochemical staining using antibodies directed towards the c-kit protein on the cell surface, is a useful tool in the often difficult differential diagnosis of GISTs from other mesenchymal tumours. The correct diagnosis of GISTs is crucial for the new treatment option with imatinib, the tyrosine-kinase inhibitor specifically targeted against KIT. The clinical development of imatinib for patients with GISTs has been extraordinarily rapid. As a result of the short period of time between the drug's experimental introduction and actual registration, many unanswered questions about its use for the treatment of GISTs remain. These can only be answered in well-designed clinical trials. It is therefore recommended that patients with these rare tumours are referred to a centre with experience in the diagnosis and treatment of these soft-tissue sarcomas.

Antineoplastic Agents↗

Chondrosarcoma is not characterized by detectable telomerase activity.

Reactivation of telomerase, an enzyme which elongates human telomeres, is associated with cell immortilization. In approximately 90% of malignant tumours telomerase activity can be demonstrated, whereas in benign tumours it is mostly absent. Chondrosarcomas are relatively rare malignant cartilaginous neoplasms. A small number of chondrosarcomas located centrally in bone arise secondarily to an enchondroma, while the majority of chondrosarcomas developing from the surface arise within the cartilage cap of an osteochondroma. The histological distinction between a benign lesion and low-grade chondrosarcoma is generally considered difficult. To investigate whether the progression towards chondrosarcoma is characterized by reactivation of telomerase activity, this study determined telomerase activity in ten enchondromas, five osteochondromas, and 37 chondrosarcomas using the TRAP assay. In all tumour samples except one, telomerase activity was absent. By adding tumour lysates to the positive control, an increasing inhibition of telomerase activity was found with an increasing chondroid matrix, suggesting that it may contain inhibitory factors. Inhibition due to endogenous RNAse or Taq-polymerase inhibitors was excluded. The lack of detectable telomerase activity in the high-grade component of a dedifferentiated chondrosarcoma without matrix favours the possibility that telomerase is truly absent. Either its true absence or inhibitory effects disabling telomerase detection exclude the telomerase TRAP assay as a diagnostic tool in the differential diagnosis of benign and low-grade malignant cartilaginous tumours.

Biomarkers, Tumor↗

An association between cartilaginous tumours and breast cancer in the national pathology registration in The Netherlands points towards a possible genetic trait.

Breast cancer and cartilaginous tumours (enchondroma and chondrosaroma) were found to occur rather frequently in the same patient. In order to identify a possible association between occurrence of these tumour types, a population-based study was performed. This was a nation-wide case-control study, using the Dutch national pathology database. Between 1973 and 1998, the study identified 2295 cases of cartilaginous tumours in female patients and 132 636 females with breast cancer. Of these patients, 61 were diagnosed with both tumour types. To exclude a possible bias due to screening for occult bone metastases in breast cancer patients, a similar analysis was performed for lung cancer, since screening is performed similarly in lung cancer patients. Of 16 559 females diagnosed with lung cancer, only one case with a cartilaginous tumour was found. The odds ratio for a potential association of breast and cartilaginous tumours is 7.62, implicating a 7.62 increased risk for the same female patient having both breast cancer and a cartilaginous tumour. Furthermore, the mean age of onset in patients with breast cancer as the first tumour is nearly 10 years earlier than breast cancer in general, i.e. 51 years versus 60.9 years. The association of breast cancer and cartilaginous tumours and the early age of onset of breast cancer in these patients may suggest a genetic trait.

Adolescent↗

Adamantinoma-like Ewing's sarcoma and Ewing's-like adamantinoma. The t(11; 22), t(21; 22) status.

Adamantinoma of the long bones and Ewing's sarcoma are two malignant tumours between which, at first sight, there seems to be no morphological and clinical relationship. Both tumours, however, are known to express cytokeratins. Adamantinoma is a tumour of true epithelial nature, predominantly expressing cytokeratins 14 and 19. Ewing's sarcoma, believed to be from neuroectodermal origin, like other mesenchymal tumours, can aberrantly express cytokeratin 8 and 18. In the literature there are some reports of tumours showing clinical and/or morphological overlap between adamantinoma and Ewing's sarcoma, suggesting a possible relationship. These studies are mostly based on the epithelioid configuration of these lesions and their cytokeratin expression on immunohistochemistry. This raises the question of whether there is occasionally a morphological similarity between adamantinoma and Ewing's sarcoma, or whether there is a common genetic background. The Ewing's sarcoma/primitive peripheral neuroectodermal tumour (PNET) family is characterized in 90-95% of cases by a t(11; 22) and in 5-10% of cases by t(21; 22). In the few reports in the literature on cytogenetic investigations on adamantinoma, these translocations were never found using classical karyotyping. This study investigated the putative presence of t(11; 22) and t(21; 22) in 14 cases of adamantinoma by RT-PCR. These translocations were not found in any of these cases. The results support the view that these tumours are genetically and clinically distinct, but may eventually show overlapping morphological and immunohistochemical features.

Ameloblastoma↗

Synovial sarcoma: dynamic contrast-enhanced MR imaging features.

OBJECTIVE: To determine whether previously described so-called malignant dynamic contrast-enhanced magnetic resonance (MR) imaging features--early start, peripheral enhancement and early plateau or washout phase--occur consistently in synovial sarcoma. DESIGN AND PATIENTS: Dynamic contrast-enhanced MR images of 10 patients with histologically proven synovial sarcoma were reviewed. The start, pattern and progression of tumor enhancement were assessed and correlated with histopathology. RESULTS: In all patients, the time interval between arterial and early tumor enhancement was less than 7 s (mean 4.40 s, SD 2.09 s). Six synovial sarcomas showed enhancement with a subsequent rapidly progressive linear increase in signal intensity followed by a plateau in one lesion and washout in five. Four lesions showed a late sustained increase in enhancement after the initial rapid increase in enhancement. The pattern of initial enhancement was peripheral in only two lesions, diffuse in four and heterogeneous in four lesions. CONCLUSIONS: Enhancement of tumor within 7 s after arterial enhancement is, of the three parameters described previously, the only sign that occurs consistently in synovial sarcoma.

Adolescent↗

Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts).

Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) and conventional malignant melanoma may demonstrate significant morphologic overlap at the light microscopic and ultrastructural level. Consequently, the clinically relevant distinction between primary clear cell sarcoma and metastatic melanoma in the absence of a known primary cutaneous, mucosal or ocular tumour may occasionally cause diagnostic problems. A balanced translocation, t(12;22)(q13;q13), which can be detected, amongst others, using the reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization (FISH), has been identified in a high percentage (50-75%) of clear cell sarcomas and is presumed to be tumour specific. Whether this chromosomal rearrangement is present in malignant melanoma has, to date, not as yet been studied by molecular genetic or molecular cytogenetic techniques. Using RT-PCR and FISH, a series of metastases from 25 known cutaneous melanomas and 8 melanoma cell lines (5 uveal and 3 cutaneous) were screened for the t(12;22)(q13;q13) translocation. Primers for RT-PCR were chosen based upon published breakpoint sequences. The Cosmids G9 and CCS2.2, corresponding to the 5' region of EWS and 3' region of ATF-1 respectively, were used as probes. The translocation was not identified in any of the melanomas or melanoma cell lines analysed in this study; in contrast this translocation was identified in 3 out of 5 clear cell sarcomas using these techniques. This allows distinction between translocation positive cases of clear cell sarcoma and malignant melanoma at a molecular genetic level. Consequently, in diagnostically challenging cases, this represents a valuable tool for the clinicopathologic differentiation between these two entities, with an important impact on patient management and prognosis.

Chromosomes, Human, Pair 12↗

Human granzyme B mediates cartilage proteoglycan degradation and is expressed at the invasive front of the synovium in rheumatoid arthritis.

OBJECTIVE: To investigate the cartilage-degrading capacity of granzyme B and the presence of granzyme B-positive cells at sites of erosion in the rheumatoid synovium. METHODS: Granzyme B was added to [(3)H]proline/[(35)S]sulphate-labelled cartilage matrices and to cartilage explants. Proteoglycan degradation was assessed by the release of (35)S and glycosaminoglycans into the medium and collagen degradation was assessed by the release of (3)H and hydroxyproline and by measuring the fraction of denatured collagen. Granzyme B expression was studied at the invasive front of the synovium by immunohistochemistry. RESULTS: Granzyme B induced loss of both newly synthesized, radiolabelled proteoglycans in cartilage matrices and resident proteoglycans of the cartilage explants. No effect on collagen degradation was found. Granzyme B-positive cells were present throughout the synovium and at the invasive front. CONCLUSION: The presence of granzyme B-positive cells at the invasive front of the synovium together with its ability to degrade articular proteoglycans supports the view that granzyme B may contribute to joint destruction in rheumatoid arthritis.

Animals↗

Chromosome 9 alterations and trisomy 22 in central chondrosarcoma: a cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes.

Chondrosarcomas are malignant cartilaginous tumors. Most are located in the medullar cavity (central chondrosarcoma), and a minority develop in a preexisting osteochondroma (peripheral chondrosarcoma). The authors present karyotypes for 37 central, peripheral, juxtacortical, and dedifferentiated chondrosarcomas. Using loss of heterozygosity (LOH) analysis and DNA flow cytometry, the authors previously showed that central and peripheral chondrosarcomas probably evolve by different genetic mechanisms. Peripheral chondrosarcoma is characterized by genetic instability, as was previously shown by a high percentage of LOH and a broad range in DNA ploidy. The authors now show that all peripheral chondrosarcomas tested are aneuploid, combined with many nonspecific chromosomal aberrations. Two juxtacortical chondrosarcomas showed normal chromosome numbers combined with limited structural alterations, substantiating that juxtacortical and peripheral chondrosarcomas are two clinicopathologically different entities with a different genetic background. Central chondrosarcomas were previously found to be peridiploid with limited LOH, most frequent at 9p21. In the current study, chromosome 9 was involved in five of seven central chondrosarcomas compared with only one of four peripheral chondrosarcomas. Three central tumors showed involvement of the 9pl2-22 region, suggesting an important role for chromosome 9 in the oncogenesis of central chondrosarcoma. Moreover, trisomy 22 was found in four central chondrosarcomas only.

Adolescent↗

High quality RNA isolation from tumours with low cellularity and high extracellular matrix component for cDNA microarrays: application to chondrosarcoma.

AIMS: High quality RNA isolation from cartilaginous tissue is considered difficult because of relatively low cellularity and the abundance of extracellular matrix rich in glycosaminoglycans and collagens. Given the growing interest and technical possibilities to study RNA expression at a high throughput level, research on tissue with these characteristics is hampered by the lack of an efficient method for obtaining sufficient amounts of high quality RNA. METHODS: This paper presents a robust protocol combining two RNA isolation procedures, based on a combination of Trizol and RNA specific columns, which has been developed to obtain high molecular weight RNA from fresh frozen and stored tissue of normal cartilage and cartilaginous tumours. Using this method, RNA was isolated from normal cartilage, peripheral chondrosarcoma, and central chondrosarcoma. RESULTS: The yields ranged from 0.1 to 0.5 microg RNA/mg tissue. RNA isolated with this method was stable and of high molecular weight. RNA samples from normal cartilage and from two chondrosarcomas isolated using this method were applied successfully in cDNA microarray experiments. The number of genes that give interpretable results was in the range of what would be expected from microarray results obtained on chondrosarcoma cell line RNA. Signal to noise ratios were good and differential expression between tumour and normal cartilage was detectable for a large number of genes. CONCLUSION: With this newly developed isolation method, high quality RNA can be obtained from low cellular tissue with a high extracellular matrix component. These procedures can also be applied to other tumour material.

Bone Neoplasms↗

The histopathological differential diagnosis of gastrointestinal stromal tumours.

Gastrointestinal stromal tumours (GISTs), initially presumed to be of "true" smooth muscle origin, encompass a heterogeneous, and as yet incompletely understood, group of mesenchymal tumours with respect to their origin, cellular differentiation, and prognosis. Cellular morphology ranges from predominantly spindle shaped to epithelioid in character, whereas differentiation pathways, as determined primarily by immunohistochemistry and ultrastructure, can vary from indeterminate to myoid and/or neural. Recent work has indicated that the interstitial cells of Cajal, a complex cellular network postulated to act as pacemaker cells of the gastrointestinal tract, which exhibit both myoid and neural features, could be candidates for tumour histogenesis. This would provide a plausible and attractive explanation for the variable differentiation pathways identified in the GIST category to date. Nevertheless, the occasional but undisputed location of GISTs outside the gastrointestinal tract (omentum, peritoneum, and retroperitoneum) might mitigate against such an origin, and their histogenesis remains open to debate. The c-kit proto-oncogene, encoding a growth factor receptor with tyrosine kinase activity, has been postulated to play an important role in tumorigenesis because "gain of function" mutations in this gene, localised to chromosome 4q11-21, are being increasingly identified in hereditary and sporadic cases. Monoclonal and polyclonal antibodies directed at the c-kit gene product expressed on the cell surface (CD117/c-kit) appear to be increasingly helpful in resolving the histopathological differential diagnosis between GISTs and true gastrointestinal smooth muscle neoplasms, schwannomas, and other far less frequently occurring mesenchymal tumours at this site. Although tumours with a clinically benign course appear to be more common than their malignant counterparts, no specific histological criteria have as yet been identified to enable an unambiguous prediction of biological behaviour. Increasing tumour size and mitotic activity favour aggressive tumour behaviour, whereas the prognostic value of germline and somatic mutations within the c-kit proto-oncogene remains to be elucidated further. It is the aim of this synopsis to highlight the relevant fundamental and diagnostic developments with respect to this complex group of neoplasms.

Biomarkers, Tumor↗

Retain or sacrifice the posterior cruciate ligament in total knee arthroplasty? A histopathological study of the cruciate ligament in osteoarthritic and rheumatoid disease.

BACKGROUND: The decision whether to retain or resect the posterior cruciate ligament in total knee arthroplasty is at present determined clinically by preoperative radiological variables focusing upon the amount of joint destruction, and subsequent soft tissue contractures. However, these variables give only indirect information on the histological integrity and proprioceptive properties of the posterior cruciate ligament. METHODS: Twenty posterior cruciate ligaments, obtained during total knee arthroplasty, were evaluated histologically to study the relation between the degree of preoperative radiological joint destruction, structural integrity of the posterior cruciate ligament and the neurological integrity of the targeted tissue. Eleven patients had osteoarthritis and nine patients rheumatoid arthritis. Haematoxylin and eosin, Alcian blue (mucoid degeneration), elastica von Gieson, Gomori (elastic fibres and collagen), and immunohistochemical staining for neural structures were used. RESULTS: In all but one of the posterior cruciate ligaments, morphologically intact neural tissue was present in the peritendineum of the ligaments. Structural integrity of the collagen framework was present in only seven posterior cruciate ligaments. These cases all had grade three or four radiological joint destruction. In 13 of the specimens a certain degree of mucoid degeneration of collagen was present. All patients with grade five radiological knee joint destruction displayed mucoid degeneration and irregularity of the posterior cruciate ligament fibres. CONCLUSION: Because of the extensive architectural and probably functional damage of the posterior cruciate ligament in patients who have grade five radiological knee joint destruction, retention of the posterior cruciate ligament in knee prosthesis should not be advocated.

Adult↗

[Adamantinoma of the long bones: an anatomo-clinical review and its relationship with osteofibrous dysplasia].

Adamantinoma of long bones is a perplexing tumor for its histology as well as for its histogenesis. Recent progress has been made with ultrastructural and immunohistochemical works. The possible relationship with osteofibrous dysplasia is the subject of conflicting discussions and the potential link has implications for the diagnosis, prognosis, and treatment. Clinical aspects of adamantinomas are described: location, age, gender, symptoms, imaging, diagnosis, treatment, clinical course, prognosis. Histopathology is extensively covered for usual and peculiar forms. Immunohistochemical results are described and discussed. Data of electron microscopy, cytological findings, and DNA flow cytometry are also reported. The putative association with osteofibrous dysplasia is the subject of an extensive development with the report of the personal experience and works of the authors, and arguments for viewing osteofibrous dysplasia and "osteofibrous dysplasia-like" adamantinomas as precursor lesions of classic adamantinomas are favoured.

Bone Neoplasms↗

MR imaging of clear cell sarcoma (malignant melanoma of the soft parts): a multicenter correlative MRI-pathology study of 21 cases and literature review.

OBJECTIVE: To evaluate MR imaging and pathology findings in order to define the characteristic features of clear cell sarcoma of the soft tissues (malignant melanoma of the soft parts). DESIGN AND PATIENTS: MR examinations of 21 patients with histologically proven clear cell sarcoma of the musculoskeletal system were retrospectively reviewed and assessed for shape, homogeneity, delineation, signal intensities on T1- and T2-weighted images, contrast enhancement, relationship with adjacent fascia or tendon, secondary bone involvement, and intratumoral necrosis. In 19 cases the pathology findings were available for review and for a comparative MR-pathology study. RESULTS: On T1-weighted images, lesions were isointense (n=3), hypointense (n=7) or slightly hyperintense to muscle (n=11). Immunohistochemical examination was performed in 17 patients. All 17 specimens showed positivity for HMB-45 antibody. In nine of 11 lesions with slightly increased signal intensity on T1-weighted images, a correlative MR imaging-pathology study was possible. All nine were positive to HMB-45 antibody. CONCLUSIONS: Clear cell sarcoma of the musculoskeletal system often has a benign-looking appearance on MR images. In up to 52% of patients, this lesion with melanocytic differentiation has slightly increased signal intensity on T1-weighted images compared with muscle. As the presence of this relative higher signal intensity on T1-weighted images is rather specific for tumors displaying melanocytic differentiation, radiologists should familiarize themselves with this rare entity and include it in their differential diagnosis when confronted with a well-defined, homogeneous, strongly enhancing mass with slightly higher signal intensity compared with muscle on native T1-weighted images.

Adolescent↗

Bone tumors.

We present an overview of the imaging modalities in bone tumors. The imaging strategies of preoperative work-up, monitoring the effect of chemotherapy and the detection of recurrences by long-term follow-up are discussed.

Adolescent↗

Near-haploidy and subsequent polyploidization characterize the progression of peripheral chondrosarcoma.

Chondrosarcomas are malignant cartilaginous tumors arising centrally in bone (central chondrosarcoma), or secondarily within the cartilaginous cap of osteochondroma (peripheral chondrosarcoma). We previously used DNA flow cytometry to demonstrate that near-haploidy is relatively frequent in peripheral chondrosarcomas. We performed fluorescence in situ hybridization (FISH) to interphase nuclei using centromeric probes, a genome wide loss of heterozygosity (LOH) analysis, and comparative genomic hybridization on five peripheral chondrosarcomas. We demonstrated near-haploidy in two low-grade tumors with only one copy and LOH of most chromosomes. Few chromosomes are disomic, with retention of heterozygosity and overrepresentation at comparative genomic hybridization. One tumor contains both a near-haploid clone with chromosomes in monosomic and disomic state, and an exactly duplicated clone. Two high-grade tumors clearly demonstrate polyploidization because most chromosomes show LOH and two copies at FISH, whereas few chromosomes have four copies with retention of heterozygosity. Using DNA from a relative, we demonstrate that chromosome loss is random regardless of parental origin. Using FISH on paraffin slides, we exclude near-haploidy to result from meiosis-like division in binucleated cells, characteristic for chondrosarcoma. In conclusion, our results indicate that near-haploidy characterizes the progression from osteochondroma toward low-grade chondrosarcoma. Moreover, further progression toward high-grade chondrosarcoma is characterized by polyploidization.

Adult↗