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ABSTRACT: The prognosis of patients with pancreatic cancer remains poor, even after potentially curative R0 resection. This discrepancy may be due to the histopathological misclassification of R1 cases as curative resections (R0) in the past.
To test this hypothesis, color coding of all resection margins and organ surfaces as part of a standardized histopathological workup was implemented and prospectively tested on 100 pancreatic head specimens.
Thirty-five patients were excluded from the analysis owing to the pathohistological diagnosis; only pancreatic ductal adenocarcinoma, distal bile duct adenocarcinoma, and periampullary adenocarcinoma were included. Applying the International Union Against Cancer criteria, 32 cancer resections were classified R0 (49.2%), while 33 cases turned out to be R1 resections (50.8%). The mesopancreas was infiltrated in 22 of the 33 R1 resection specimens (66.6%). It proved to be the only site of tumor infiltration in 17 specimens (51.5%). Applying the Royal College of Pathologists' criteria, 46 resections were classified R1 (70.8%). As expected, the mesopancreas again was the most frequent site of noncurative resection (n = 27; 58.7%).
Using the intensified histopathological workup for pancreatic head cancer specimens resulted in an increased rate of R1 resections and the mesopancreas represents the primary site for positive resection margins. Such results are of relevance for patients' stratification in clinical trials.
Langenbeck s Archives of Surgery 06/2009; 395(4):451-8. · 1.81 Impact Factor
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F Haller,
C Löbke,
M Ruschhaupt,
H-J Schulten,
S Schwager, B Gunawan,
T Armbrust,
C Langer,
G Ramadori,
H Sültmann,
A Poustka,
U Korf,
L Füzesi
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ABSTRACT: Gastrointestinal stromal tumours (GISTs) with deletions in KIT exon 11 are characterized by higher proliferation rates and shorter disease-free survival times, compared to GISTs with KIT exon 11 point mutations. Up-regulation of cyclin D is a crucial event for entry into the G1 phase of the cell cycle, and links mitogenic signalling to cell proliferation. Signalling from activated KIT to cyclin D is directed through the RAS/RAF/ERK, PI3K/AKT/mTOR/EIF4E, and JAK/STATs cascades. ERK and STATs initiate mRNA transcription of cyclin D, whereas EIF4E activation leads to increased translation efficiency and reduced degradation of cyclin D protein. The aim of the current study was to analyse the mRNA and protein expression as well as protein phosphorylation of central hubs of these signalling cascades in primary GISTs, to evaluate whether tumours with KIT exon 11 deletions and point mutations differently utilize these pathways. GISTs with KIT exon 11 deletions had significantly higher mitotic counts, higher proliferation rates, and shorter disease-free survival times. In line with this, they had significantly higher expression of cyclin D on the mRNA and protein level. Furthermore, there was a significantly higher amount of phosphorylated ERK1/2, and a higher protein amount of STAT3, mTOR, and EIF4E. PI3K and phosphorylated AKT were also up-regulated, but this was not significant. Ultimately, GISTs with KIT exon 11 deletions had significantly higher phosphorylation of the central negative cell-cycle regulator RB. Phosphorylation of RB is accomplished by activated cyclin D/CDK4/6 complex, and marks a central event in the release of the cell cycle. Altogether, these observations suggest increased KIT signalling with up-regulation of cyclin D as the basis for the unfavourable clinical course in GISTs with KIT exon 11 deletions.
The Journal of Pathology 10/2008; 216(2):225-35. · 6.32 Impact Factor
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F Haller,
C Löbke,
M Ruschhaupt,
S Cameron,
H-J Schulten,
S Schwager,
A von Heydebreck, B Gunawan,
C Langer,
G Ramadori,
H Sültmann,
A Poustka,
U Korf,
L Füzesi
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ABSTRACT: Loss of chromosome 9p is a reliable predictor of malignant behaviour in gastrointestinal stromal tumours (GISTs). p16INK4A located at 9p21 inhibits the CDK4/6/cyclin D complex from phosphorylating RB. Phosphorylation of RB through CDK4/6/cyclin D in early G(1) phase frees the transcription factor E2F1 from RB and enables mRNA transcription of genes essential for G(1)/S phase transition. This study aims to determine the impact of 9p loss on mRNA and protein expression of p16INK4A and further key cell cycle regulators in the different phases of the cell cycle. Sixty primary GISTs previously characterized for 9p loss by comparative genomic hybridization were analysed for mRNA expression of p16INK4A, p15INK4B, CDK4, CDK6, cyclin D, p21CIP1p27KIP1, CDK2, cyclin E, cyclin B, RB and E2F1, using quantitative RT-PCR. The protein expression of CDK6, CDK2, p21CIP1, p27KIP1 and phosphorylated RB (S807/S811) was evaluated using protein arrays as a novel and highly sensitive platform for profiling of protein abundance and protein phosphorylation. In parallel, the nuclear percentages of immunohistochemical staining for p16INK4A, cyclin D, E2F1 and RB were quantified on a tissue microarray. GISTs with 9p loss had significantly higher proliferation rates, higher metastatic behaviour and shorter disease-free survival. On the molecular level, GISTs with 9p loss had a significantly reduced mRNA as well as nuclear protein expression of p16INK4A. RB was significantly more phosphorylated in these tumours, together with increased mRNA expression and nuclear staining for E2F1. Furthermore, GISTs with 9p loss had up-regulation of the late G1/S phase promoters CDK2 and cyclin E. We conclude that loss of 9p accompanied by early G1 phase inhibitor p16(INK4A) down-regulation in GISTs facilitates phosphorylation of RB, enabling E2F1-dependent transcription of genes essential for late G1/S phase transition. This study provides a possible basis for the accelerated proliferation and particularly malignant behaviour in GISTs with 9p loss.
The Journal of Pathology 07/2008; 215(3):253-62. · 6.32 Impact Factor
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B Gunawan
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ABSTRACT: In recent years, gastrointestinal stromal tumour (GIST) has emerged from a poorly understood group of mesenchymal tumours to a distinct pathological entity that has become a leading model for new therapies targeting kinases. GIST pathogenesis is driven by receptor tyrosine kinase-activating mutations most often in KIT or PDGFRA that may be sporadic or result in familial GIST syndromes. In a recent issue of The Journal of Pathology (J Pathol 2008;214:302-311), Nakai and colleagues report that mutation of the previously un-modelled tyrosine kinase II domain of KIT generates a spectrum of features very similar to that in two human GIST families. Knock-in mouse models of GIST may prove extremely useful in pre-clinical evaluation of kinase-targeted compounds and of the mechanism of drug resistance, but intriguingly it now seems clearer that the distribution of GIST in mouse models and humans is different.
The Journal of Pathology 04/2008; 214(4):407-9. · 6.32 Impact Factor
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B Gunawan,
A von Heydebreck,
B Sander,
H-J Schulten,
F Haller,
C Langer,
T Armbrust,
M Bollmann,
S Gasparov,
D Kovac,
L Füzesi
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ABSTRACT: To model the cytogenetic evolution in gastrointestinal stromal tumour (GIST), an oncogenetic tree model was reconstructed using comparative genomic hybridization data from 203 primary GISTs (116 gastric and 87 intestinal GISTs, including 151 newly analysed cases), with follow-up available in 173 cases (mean 40 months; maximum 133 months). The oncogenetic tree model identified three major cytogenetic pathways: one initiated by -14q, one by -1p, and another by -22q. The -14q pathway mainly characterized gastric tumours with predominantly stable karyotypes and more favourable clinical course. On the other hand, the -1p pathway was more characteristic of intestinal GISTs, with an increased capacity for cytogenetic complexity and more aggressive clinical course. Loss of 22q, more closely associated with -1p than -14q, appeared to initiate the critical transition to an unfavourable cytogenetic subpathway. This -22q pathway included accumulation of +8q, -9p, and -9q, which could all predict disease-free survival in addition to tumour site. Thus, insights into the cytogenetic evolution obtained from oncogenetic tree models may eventually help to gain a better understanding of the heterogeneous site-dependent biological behaviour of GISTs.
The Journal of Pathology 04/2007; 211(4):463-70. · 6.32 Impact Factor
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ABSTRACT: Activation of T cells by dendritic cells (DC) is thought to play a pivotal role in induction and maintenance of Crohn's disease. Detailed analyses however concerning the phenotype and maturation of DC as well as the mechanisms underlying their recruitment are still lacking for Crohn's disease.
Different myeloid and plasmacytoid DC subsets were characterised by immunohistochemistry. Expression of the so-called "lymphoid" chemokines CCL19, CCL20, and CCL21 was determined by real time reverse transcription-polymerase chain reaction in Crohn's disease and normal controls. Furthermore, expression of CCL19, CCL20, and CCL21 as well as their receptors CCR6 (for CCL20) and CCR7 (for CCL19 and CCL21) was characterised by immunohistochemistry and, in addition, their cellular localisation was determined by double immunofluorescence investigations.
Colonic tissue affected by Crohn's disease was characterised by an increased number of mature myeloid DC forming clusters with proliferating T cells. In keeping with their advanced maturation, DC possess the chemokine receptor CCR7. Increased expression of the CCR7 ligands CCL19 by DC themselves as well as CCL21 by reticular cells and lymphatic vessels was observed in Crohn's disease, thereby causing the matured DC to be trapped at the site of inflammation.
Our results demonstrate that autocrine and paracrine actions of lymphoid chemokines in Crohn's disease may lead to increased numbers of mature DC away from their usual migration to lymphoid organs and result in the development of a tertiary lymphatic tissue within the bowel wall maintaining the autoimmune inflammation in Crohn's disease.
Gut 03/2006; 55(2):220-7. · 10.11 Impact Factor
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ABSTRACT: The tyrosine kinase inhibitor imatinib has been introduced into the treatment of gastrointestinal stromal tumors (GIST). Here we report our results of prolonged treatment in comparison to a similar group of GIST patients who had died before imatinib became available.
Fourteen patients with recurrent or metastatic GIST were treated with imatinib. Clinical data and tumor samples of ten patients from the pre-imatinib era were available for comparison. Comparative genomic hybridisation (CGH) was performed on tumors to identify changes that may predict response to treatment.
Fourteen patients were treated, mean treatment time 22.3 months (1 non-response, 2 progression after initial response, 2 stable diseases, 8 partial responses, 1 complete response). Adverse side effects were mild in general. Survival was higher in the treated group (41.1 months vs. 34.8 months in the historical group). Eleven treated patients are alive. CGH analysis showed comparable numbers of chromosomal aberations in both groups.
Prolonged treatment with imatinib is safe and effective in patients with recurrent or metastatic GIST.
Zeitschrift für Gastroenterologie 04/2005; 43(3):267-73. · 0.90 Impact Factor
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ABSTRACT: Basal cell tumours of the prostatic gland are rare, and the classification is difficult. In the present case report, a large, tumour-like proliferation of atypical basaloid cells was found incidentally in a prostatectomy specimen that otherwise contained a conventional acinar adenocarcinoma. The basaloid cells displayed a solid or adenoid-cystic growth pattern and strongly expressed high-molecular-weight cytokeratins and bcl-2. A high Ki-67 index was recorded within the atypical basaloid cells, by far exceeding the one counted in the conventional adenocarcinoma. However, there were no definite criteria for a malignant behaviour of the basal cell tumour. Comparative genomic hybridisation from microdissected tumour cells yielded losses at the short arms of chromosomes 8 and 12 in the conventional adenocarcinoma and a normal karyotype in the basal cell tumour. The pathological findings favoured the diagnosis of an atypical basal cell hyperplasia.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 04/2005; 446(3):338-41. · 2.49 Impact Factor
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C Hallermann,
K M Kaune,
S Gesk,
J I Martin-Subero, B Gunawan,
F Griesinger,
M H Vermeer,
M Santucci,
N Pimpinelli,
R Willemze,
R Siebert,
C Neumann
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ABSTRACT: Chromosomal translocations affecting the IGH locus and various oncogene loci are recurrent in many types of systemic B-cell lymphomas. Hardly any data exist, however, on such translocations in primary cutaneous B-cell lymphomas (PCBCL). Here, a series of 29 PCBCL was investigated by interphase fluorescence in situ hybridization with probes for the IGH, MYC, BCL6, and MLT1 loci. None of the six follicle center cell lymphomas and nine marginal zone lymphomas showed evidence for any translocation affecting these loci. In contrast, 11 of 14 large B-cell lymphomas of the leg harbored breakpoints in at least one of the loci. Translocations involving the MYC locus were detected in six cases, five of them derived from a MYC/IGH juxtaposition and one from a translocation involving a non-IG gene partner. Rearrangements of the BCL6 locus were detected in five B-cell lymphomas of the leg, and involved IGH (two cases), IGL (one case), and non-IG genes (two cases). This study shows that large B-cell lymphomas of the leg display a pattern of chromosomal translocations similar to their systemic counterparts whereas primary cutaneous follicle center cell lymphomas and marginal zone lymphomas lack these typical chromosomal translocations.
Journal of Investigative Dermatology 08/2004; 123(1):213-9. · 6.31 Impact Factor
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ABSTRACT: The principal objective of this study was to document morphological changes in valves with acute endocarditis in order to gain further knowledge of the pathogenesis of these diseases.
Scanning and transmission electron microscopic investigations were carried out on explanted human heart valves to reveal ultrastructural changes due to bacterial endocarditis.
Bacterial inflammation endocarditis initially induced metaplasia of the endothelial cells which then lose contact with each other. In the 2nd phase of the disease, the collagen fibres are systematically removed whereby large cavities appear. In the 3rd phase, localised hyperplasia of collagen fibres was observed often resulting in the development of vegetation. The ultrastructural changes are uniform and independent of the bacterial species.
Bacterial endocarditis is therefore a set of complex interactions between endothelial cells and bacteria which should be taken into consideration for the development of new therapeutic approaches.
The Journal of cardiovascular surgery 01/2004; 44(6):685-9. · 1.56 Impact Factor
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ABSTRACT: The purpose of this study was to review surgical experience with gastrointestinal stromal tumours (GISTs) at a single tertiary university hospital, and to identify morphological and genetic prognostic markers of tumour progression.
Forty-eight GISTs from 39 patients were reviewed retrospectively. The prognostic significance of DNA copy number changes, measured by comparative genomic hybridization (CGH), and morphological markers in low-risk and high-risk tumours were investigated.
Significantly more patients died from disease after incomplete tumour resection than after complete primary resection (P = 0.020). Tumour size of 5 cm or greater, mitotic count of 2 or more, and proliferative activity greater than 10 per cent were significantly associated with a shorter recurrence-free survival (P = 0.020, P = 0.001 and P = 0.002 respectively). Patients with low-risk tumours had a significantly better outcome than those with high-risk GISTs, both in terms of overall and recurrence-free survival (P < or = 0.001). CGH performed on 16 tumours revealed fewer DNA sequence copy number changes in low-risk than in high-risk GISTs. Non-progressive GISTs contained significantly fewer genetic alterations than recurrent or metastatic tumours (P < 0.001). Only tumours with more than five changes showed disease progression.
Complete surgical resection is the most important means of cure for GISTs. DNA copy number changes are related to the behaviour of these tumours and may serve as additional prognostic markers.
British Journal of Surgery 03/2003; 90(3):332-9. · 4.61 Impact Factor
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ABSTRACT: We present a new approach for modeling the occurrence of genetic changes in human tumors over time. In solid tumors, data on genetic alterations are usually only available at a single point in time, allowing no direct insight into the sequential order of genetic events. In our approach, genetic tumor development and progression is assumed to follow a probabilistic tree model. We use maximum likelihood estimation to reconstruct a tree model for the genetic evolution of a given tumor type. The use of the proposed method is illustrated by an application to cytogenetic data from 173 cases of clear cell renal cell carcinoma, which results in a model for the karyotypic evolution of this tumor.
Verhandlungen der Deutschen Gesellschaft für Pathologie 02/2003; 87:188-92.
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Histopathology 06/2002; 40(5):485-7. · 3.08 Impact Factor
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ABSTRACT: Our aim was to prepare a comprehensive catalogue of the changes in gene expression accompanying the development and progression of renal cell carcinoma, and to correlate these with histo-pathological, cytogenetic and clinical findings.
mRNA samples from paired neoplastic and non-cancerous human kidney tissue were labeled and hybridized in duplicate against high-density cDNA arrays. Two array technologies were used: 31,500-element transcriptome-wide nylon arrays for hybridization with 37 radioactively labelled sample pairs, and 4200-element kidney- and cancer-specific glass microarrays for hybridization with 19 fluorescently labelled sample pairs.
We identified more than 1700 cDNA clones that show differential transcription levels in kidney tumor tissue compared to normal kidney tissue. The functional classification of 389 annotated genes provided views of the changes in the activities of specific biological processes in renal cancer. Among the biological processes with a large proportion of up-regulated genes we found cell adhesion, signal transduction, and nucleotide metabolism. Down-regulated processes included small molecule transport, ion homeostasis, and oxygen and radical metabolism. Furthermore, we explored the feasibility of molecular diagnosis for renal cell tumors using cDNA microarrays on glass slides, investigating the association of transcription levels with tumor type, progression, and a putative prognostic variable. The experimental data is available from the GEO gene expression database (http://www.ncbi.nlm.nih.gov/geo; accession no. GSE3), and a comprehensive presentation of the results is available in the web supplement (http://www.dkfz-heidelberg.de/abt0840/whuber/rcc).
Transcription profiling using high-density cDNA arrays is a powerful method with the potential to improve cancer diagnosis and prognosis. The identification and classification of differentially transcribed genes, as described in our study, is the beginning of a more complete understanding of kidney cancer.
Verhandlungen der Deutschen Gesellschaft für Pathologie 02/2002; 86:153-64.
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ABSTRACT: To evaluate the prognostic significance of cytogenetic findings in clear cell renal cell carcinoma (RCC), cytogenetic results of 118 primary RCCs were evaluated in relation to classical indicators of prognosis and overall survival. Losses in 3p (98.3%) were most prevalent and included 32 (27.6%) monosomies of chromosome 3 and 84 (72.4%) structural aberrations involving 3p, of which 36 were unbalanced translocations, der(3)t(3;5)(p11-p22;q13-q31), resulting in duplication of 5q sequences. Patients with gain of 5q31-qter resulting from either polysomies or structural rearrangements of 5q, the most frequent of which was der(3)t(3;5), had a significantly better outcome than those without this aberration (P = 0.001). There was no association between gain of 5q or der(3)t(3;5) and any of the well-known variables for prognosis, including low versus high clinical stage and grade of malignancy. Among additional chromosomal aberrations, loss of chromosome 9/9p was associated with distant metastasis at diagnosis (P = 0.006). The data indicate that gain of 5q identifies a clinically favorable cytogenetic variant of clear cell RCC and demonstrate the impact of specific chromosome aberrations as additional prognostic indicators in clear cell RCC.
Cancer Research 12/2001; 61(21):7731-8. · 7.86 Impact Factor
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J M Boer,
W K Huber,
H Sültmann,
F Wilmer,
A von Heydebreck,
S Haas,
B Korn, B Gunawan,
A Vente,
L Füzesi,
M Vingron,
A Poustka
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ABSTRACT: We investigated the changes in gene expression accompanying the development and progression of kidney cancer by use of 31,500-element complementary DNA arrays. We measured expression profiles for paired neoplastic and noncancerous renal epithelium samples from 37 individuals. Using an experimental design optimized for factoring out technological and biological noise, and an adapted statistical test, we found 1738 differentially expressed cDNAs with an expected number of six false positives. Functional annotation of these genes provided views of the changes in the activities of specific biological pathways in renal cancer. Cell adhesion, signal transduction, and nucleotide metabolism were among the biological processes with a large proportion of genes overexpressed in renal cell carcinoma. Down-regulated pathways in the kidney tumor cells included small molecule transport, ion homeostasis, and oxygen and radical metabolism. Our expression profiling data uncovered gene expression changes shared with other epithelial tumors, as well as a unique signature for renal cell carcinoma. [Expression data for the differentially expressed cDNAs are available as a Web supplement at http://www.dkfz-heidelberg.de/abt0840/whuber/rcc.]
Genome Research 12/2001; 11(11):1861-70. · 13.61 Impact Factor
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ABSTRACT: Recruitment of lymphocytes is a prominent feature of the inflammatory process in Crohn's disease (CD). The present study was undertaken to investigate the expression of the novel lymphocyte-specific chemoattractant lymphotactin (Lptn) as a potential regulatory factor for the recruitment of T cells in CD. The expression of Lptn mRNA was quantified in resection specimens of patients with CD in comparison to normal controls without signs of inflammation by real-time quantitative reverse transcriptase-polymerase chain reaction and localized by nonradioactive in situ hybridization. Furthermore, the phenotype of cells expressing Lptn mRNA was characterized. In contrast to normal controls Lptn mRNA was significantly increased in tissue samples affected by CD. Cells expressing Lptn were identified as T cells, mast cells, and unexpectedly dendritic cells. Lptn mRNA was found to be up-regulated on stimulation with phorbol-12-myristate-13-acetate and concanavalin A in T cells isolated from peripheral blood, which could be prevented by dexamethasone, cyclosporine A, and FK506. A similar regulation mechanism could be identified for the Lptn receptor GPR-5 in peripheral T cells. In addition, Lptn mRNA expression could be induced in mature monocyte-derived dendritic cells. The results indicate that local expression of Lptn by activated T cells and to a lesser extent by mast cells and dendritic cells represents a key regulator for lymphocyte trafficking and maintenance of the inflammatory process observed in CD, which might be partly mediated through an autocrine/paracrine pathway of activated T cells.
American Journal Of Pathology 12/2001; 159(5):1751-61. · 4.89 Impact Factor
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ABSTRACT: Altered expression of matrix metalloproteases (MMPs) and their inhibitors, the tissue inhibitors of matrix metalloproteases (TIMPs), has been demonstrated in various tumour tissues. mRNA expression patterns of MMP-1, MMP-2, MMP-3, MMP-9, MMP-11, MMP-12, MMP-14 and TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were evaluated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in 30 renal cell carcinomas (RCC), as well as in the surrounding tissues. Expression of the MMPs was significantly stronger in the carcinomas than in non-malignant tissues. High levels were demonstrated particularly in clear cell RCCs (CC-RCC). Except for MMP-1, MMP expression in the papillary RCCs (P-RCC) was, for most MMPs, significantly lower. Expression of the TIMPs in malignant cells of both subtypes was weak, with the exception of TIMP-4 which was strongly expressed in the P-RCCs and downregulated in the CC-RCCs. The latter was correlated with chromosomal loss of 3p, harbouring the TIMP-4 gene locus. In conclusion, deregulated expression of the MMPs and TIMPs in RCCs differs according to histology, grade, size and cytogenetic characteristics, suggesting that MMP and TIMP expression patterns play an important role for the typical histomorphological features of RCC subtypes and their respective biological behaviour.
European Journal of Cancer 11/2001; 37(15):1839-46. · 5.54 Impact Factor
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ABSTRACT: To fully characterize the numerous chromosomal aberrations in two human squamous cell carcinomas (SCCs) of the lung, molecular cytogenetic characterization was carried out utilizing conventional banding analysis and multicolor fluorescence in situ hybridization (mFISH), providing simultaneous color discrimination of all 24 human chromosomes. Both tumors displayed complex aneuploid karyotypes with a host of numerical and structural chromosome abnormalities. Structural aberrations common to both SCCs included rearrangements of chromosomes 1, 3p, 7q, and 8q, contributing to net loss of chromosomal sequences on 1p, 3p, and 8p, and a net gain of 8q. The recently introduced mFISH technique enabled the disclosure of cryptic translocations and the chromosomal composition of previously unrecognized marker chromosomes. Furthermore, mFISH greatly enhanced the ability to delineate chromosomal breakpoints when integrating banding information from conventional banding analysis. Eventually, the application of mFISH as a powerful approach to refine complex tumor karyotypes is expected to result in a more detailed and complete picture of cytogenetic events associated with the development and progression of solid tumors.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2001; 439(1):85-9. · 2.49 Impact Factor
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ABSTRACT: Clear-cell odontogenic carcinoma (CCOC) is a rare neoplasm with malignant potential and unknown cytogenetic alterations. We describe the case of a 43-year-old woman who presented with an unusual odontogenic epithelial tumor. Histologically, the tumor was composed of clear-cell areas and exhibited a squamous pattern with little nuclear pleomorphism similar to benign squamous odontogenic tumor. Multiple small pulmonary nodules occurring 3 years after primary surgical treatment histologically closely resembled benign minute pulmonary meningothelial-like nodules (MPMN) with clear-cell features. Comparative genomic hybridization (CGH) and immunohistochemistry, performed as diagnostic adjuncts, revealed in the odontogenic tumor and the pulmonary lesions a very similar pattern of chromosomal aberrations (loss of 9, gains of 14q, 19 and 20 in both, and additional loss of 6 in the odontogenic tumor) and the same pattern of expression (positive for cytokeratin 5, 6, 8, 19 and negative for cytokeratin 18, epithelial membrane antigen, and vimentin), differing from that of MPMN. These findings confirmed the final diagnosis of metastasizing CCOC with partial squamous differentiation, substantiated the unfavorable prognosis of the clear-cell component, and highlighted the diagnostic impact of CGH and immunohistochemistry for classification of these morphologically peculiar pulmonary CCOC metastases.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 05/2001; 438(4):412-7. · 2.49 Impact Factor
