Tumour-to-tumour metastasis is very unusual and has been defined as a tumour metastasis into another histologically different tumour. It is extremely rare in bone. We report a case of lung squamous... Show moreTumour-to-tumour metastasis is very unusual and has been defined as a tumour metastasis into another histologically different tumour. It is extremely rare in bone. We report a case of lung squamous cell carcinoma metastasized to an enchondroma in the femur of a patient with Ollier disease. A 60-year-old female had a history of a poorly differentiated squamous cell carcinoma of the lung. She underwent a video-assisted thoracoscopic lobectomy, and a follow-up MRI scan showed three lesions in the left distal femur and proximal tibia, which were initially interpreted as metastasis on radiology. Resection of the left proximal tibial lesion was performed, and the pathological findings were consistent with enchondroma with no evidence of metastasis. Subsequent curettage of lesions in the distal left femur revealed metastatic poorly differentiated carcinoma with foci of hyaline cartilage, which was most consistent with metastatic carcinoma in a pre-existing enchondroma. The MRI films were re-reviewed. Characteristic MRI features of enchondroma were found in the lesion in the left proximal tibia and one of the lesions in the left distal femur, while the features of the other lesion in the left distal femur included cortical destruction and extensive oedema in surrounding soft tissue, which were consistent with a malignant tumour. In addition, the enchondroma in the lateral condyle showed blurring and irregular inner margin and adjacent bone oedema, which likely represents a co-existing metastatic tumour and enchondroma. The difference in lineage was confirmed by immunohistochemistry. The final diagnosis was metastatic poorly differentiated carcinoma of the lung into a co-existent enchondroma. The diagnosis can be challenging and could be easily overlooked both radiologically and histologically. Thorough clinical and radiological information is critical for the diagnosis, and despite a very unusual event, awareness of the tumour-to-tumour metastasis phenomenon can avoid an inaccurate diagnosis by the pathologist, therefore preventing inappropriate clinical intervention. Show less
The main purpose of the studies described in this thesis is to find the genetic deficit in Ollier disease and Maffucci syndrome. They are very rare, non-inherited syndromes with a unilateral... Show moreThe main purpose of the studies described in this thesis is to find the genetic deficit in Ollier disease and Maffucci syndrome. They are very rare, non-inherited syndromes with a unilateral predominance of the multiple enchondromas. Enchondroma is a benign cartilage forming tumor which can undergo malignant transformation towards chondrosarcoma. We hypothesized the presence of somatic mosaicism with an early post zygotic mutation. We used genome-wide and hypothesis driven approach to identify genes causing Ollier disease and Maffucci syndrome. Ultimately, we identified mutations in two genes (IDH1 and IDH2) that were present in the majority of the tumors from patients with Ollier disease and Maffucci syndrome. A subgroup of patients did not show mutations in IDH1, IDH2 or PTH1R and therefore, other genes (except ACP5, PTPN11, PTHLH, GNAS, NDST1) might be involved. Moreover, one can not exclude the possibility of functional links or pathways shared between IDH1 or IDH2 with EXT1, EXT2, PTH1R, PTPN11, PTHLH, TET2 and ACP5. We have shown that IDH1 mutations are associated with hypermethylation and consequently downregulation of several genes. DLX5 was the most differentially methylated gene between enchondromas with, and without IDH1 mutations which was found in our study. Show less
Centrale chondrosarcomen zijn zeldzame kraakbeen-producerende tumoren die zich van oorsprong bevinden midden in het bot. Deze soort tumoren zijn op dit moment alleen te behandelen door middel van... Show moreCentrale chondrosarcomen zijn zeldzame kraakbeen-producerende tumoren die zich van oorsprong bevinden midden in het bot. Deze soort tumoren zijn op dit moment alleen te behandelen door middel van operaties. Dit kan zeer ingrijpend voor de pati_nt zijn (bijvoorbeeld bij een amputatie) en er is een kans dat de tumor weer terugkomt of dat er metastases ontstaan. In dit proefschrift is onderzoek gedaan naar de moleculaire en genetische veranderingen in deze tumoren. Hiermee hoopten we een beter inzicht te krijgen in het hoe en waarom van deze tumoren. Daarnaast hebben we gekeken of we factoren konden vinden die zouden helpen bij het voorspellen van de prognose van de betrokken pati_nten en of we mogelijk toekomstige doelwitten voor medicatie van deze tumoren kunnen vinden. Uit de resultaten behorende bij dit proefschrift zijn nieuwe invalshoeken voor verder onderzoek gekomen, bijvoorbeeld met betrekking tot het vaststellen van de diagnose en regelkringen betrokken bij de progressie naar tumoren met een slechtere prognose. Show less
