Biomedical subjects
Publications and source records attributed to C A van de Kaa.
A patient suffering from severe hemophilia combined with a large pseudotumor of his left thigh is presented, and the case history discussed. The occurrence of this tumor in hemophilia is considered with respect to the clinical, radiological, and laboratory findings.
AIMS: Investigation of the histopathological changes in prostatectomy specimens of patients with prostate cancer after high intensity focused ultrasound (HIFU) and identification of immunohistochemical markers for tissue damage after HIFU treatment. METHODS: Nine patients diagnosed with adenocarcinoma of the prostate underwent unilateral HIFU treatment seven to 12 days before radical prostatectomy. The prostatectomy specimens were analysed histologically. Immunohistochemical staining and electron microscopy were performed to characterise more subtle phenotypic changes. RESULTS: All prostatectomy specimens revealed well circumscribed HIFU lesions at the dorsal side of the prostate lobe treated. Most epithelial glands in the centre of the HIFU lesions revealed signs of necrosis. Glands without apparently necrotic features were also situated in the HIFU lesions, raising the question of whether lethal destruction had occurred. This epithelium reacted with antibodies to pancytokeratin, prostate specific antigen (PSA), and Ki67, but did not express cytokeratin 8, which is indicative of severe cellular damage. Ultrastructural examination revealed disintegration of cellular membranes and cytoplasmic organelles consistent with cell necrosis. HIFU treatment was incomplete at the ventral, lateral, and dorsal sides of the prostate lobe treated. CONCLUSIONS: HIFU treatment induces a spectrum of morphological changes ranging from apparent light microscopic necrosis to more subtle ultrastructural cell damage. All HIFU lesions are marked by loss of cytokeratin 8. HIFU does not affect the whole area treated, leaving vital tissue at the ventral, lateral, and dorsal sides of the prostate.
BACKGROUND: High-intensity focused ultrasound (HIFU) consists of focused ultrasound waves emitted from a transducer that are capable of inducing tissue damage. Experimental studies have shown clear damage of malignant tissue exposed to HIFU, but knowledge of in vivo effects is limited. We studied the safety and efficacy of HIFU in patients with a T1-2 N0) M0 prostate carcinoma. METHODS: HIFU treatment was performed under general anesthesia with the Ablatherm device (Technomed Medical Systems, Lyon, France), 7-12 days prior to radical prostatectomy. Only the lobe in which carcinoma was confirmed was treated. The radical prostatectomy specimen was examined histopathologically, and the changes were compared with treatment goals. RESULTS: So far, 9 patients have been treated. On histology, a sharp delineation was noted between areas treated with HIFU and untreated areas. On the dorsal border, however, incomplete destruction of tissue was noted, and in 2 cases a small residual tumor was seen in this region. In all cases complete necrosis was seen in the treated region. CONCLUSIONS: Histology reports of radical prostatectomy specimens of patients operated 7-12 days after HIFU treatment showed marked and complete necrosis in the treated area. Due to incomplete tissue destruction at the dorsal side, however, a small focus of residual vital tumor was found in 2 of 9 patients.
To analyse the origin of multifocal prostate cancer lesions, radical prostatectomy specimens from 17 patients were examined. As a marker of genetic lineage, the allelotype based on 33 microsatellite loci was compared between the different tumours present in a given case. Some results provide evidence suggestive of a clonal origin of multiple tumours in a subset of the prostates. In five cases, for example, comparison of multifocal tumour lesions within a given case revealed at least two concordant changes in allelic imbalance (AI) sequence dosages at different loci. In addition, considerable heterogeneity of allelotype was found within and among tumour foci of a given case. In five of the six tumours analysed for intratumour heterogeneity, for example, more than five discordant AI changes were found in one tumour region but not in the other. Conclusions regarding the clonality of such heterogeneous lesions are difficult to draw. A high frequency of AI changes in four lesions exhibiting prostatic intraepithelial neoplasia (mean 6.5 changes per lesion, range 3-6) was found, compared with eight primary tumours present in the same cases (mean 5.8 changes per lesion, range 3-6). The interpretation of AI associated with clinically detected prostate cancer remains a highly complex issue. The fact that no clear evidence was obtained for either a clonal or a non-clonal origin of multiple lesions in a given prostate indicates that several different mechanisms are likely to operate in establishing the allelotype and that additional evidence from unique mutations or selective gene inactivation may be necessary to obtain definitive results.
Mutations in the tumor suppressor gene p53, analyzed in bladder washings, have positive predictive value for the progression of superficial bladder cancer to invasive disease. Bladder washings reflect the general status of the urothelium, and because sampling of bladder washings can be performed as an outpatient procedure, patients can be monitored more carefully. To determine the actual value of bladder washing specimens in assessing the p53 status of histologic specimens, we used the technique of polymerase chain reaction-single-strand conformation polymorphism to analyze bladder washings and the synchronous tumors of 15 patients for the presence of p53 mutations. A significant correlation (2-tailed Fisher's exact test) between the p53 status of bladder washings and histologic specimens was observed if the 2 were compared among the specimens of a single patient. Overall, in 2 patients the mutation present in the tumors was not detected in the bladder washings, and in 1 patient the mutation in the bladder washing was not detected in the histologic specimens. These conflicting results obtained with bladder washings and histologic specimens could be explained mainly by the architecture of the tumors. The observed specificity of 86% and sensitivity of 75% emphasizes that although the correlation between the 2 methods is good, in a number of cases they are complementary to each other. The analysis of p53 mutations in at least 2 bladder washings gives insight into the p53 status of the synchronous tumors.
PURPOSE: Sampling error is an inherent problem of prostate biopsy. Consequently the determination of whether a given carcinoma is clinically significant based on biopsy results is problematic. We assess the dimensions of sampling error and, thereby, provide insight into the potential value of prognostic markers applied to needle biopsies. MATERIALS AND METHODS: We constructed 3-dimensional computer models of 21 prostatectomy specimens, including outlines of carcinomas, regions of abnormal E-cadherin expression and individual Gleason patterns. The 6 random systematic core biopsy technique and modifications were simulated using a computer algorithm. RESULTS: In 6 of 21 cases the area of abnormal E-cadherin expression and/or high grade carcinoma was not sampled on 6 random systematic core biopsy. The areas missed were either small or inconsistently under sampled regions of the prostate. Modifying the placement of biopsy needles improved the detection of these features. In addition, percent tumor in the needle appeared to be well correlated to percent tumor in the prostate (r = 0.891, r2 = 0.642). CONCLUSIONS: To avoid underestimating the aggressiveness of prostatic carcinoma at least 6 biopsies should be taken from each patient. A more extensive sampling is probably not warranted in all patients but it may prove useful in those in whom extent of disease is unclear or whose general health makes treatment decisions difficult. A reliable estimate of tumor volume in the prostatectomy specimen can be made based on relative amount of tumor in the biopsy specimen on an individual basis.
Conventional fixation of large solid surgical specimens is a slow process. Consequently, autolytic damage to tissues may occur if the fixative does not reach the central part of the specimen in time. However, as there is also a time relationship between formalin fixation and antigen masking, fixation for too long can also be detrimental. In seeking the optimum balance for fixation, microwave irradiation might be of assistance. This study set out to evaluate methods for fixing entire prostate glands within a brief period of time, using microwave-stimulated formalin fixation. The results show that entire prostates can be optimally fixed if formalin is present throughout the tissue as the temperature is increased by microwave irradiation. This is achieved by injecting the fixative into the prostate at multiple sites immediately following prostatectomy. The technique described ensures standardization of a critical step during tissue processing, leading to uniform microscopic results with both routine and immunohistochemical stains. It is a simple, rapid method, suitable for routine diagnostic use. Using this modified approach, DNA of much larger sizes can be extracted from paraffin-embedded material, which could expand the possibilities for molecular analysis.
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Amyloid deposits within the seminal vesicles are a common finding at autopsy. The incidence increases with age. Amyloid deposits can mimic tumor extension into the seminal vesicles due to prostate or bladder cancer on T2-weighted MR images. We describe a case of seminal vesicle amyloidosis demonstrating the MR appearance and the characteristic pathologic findings. Recognizing seminal vesicle amyloidosis may prevent overstaging prostate cancer on MR images.
OBJECTIVES: To assess the value of deoxyribonucleic acid ploidy in the differential diagnosis and clinical follow-up of hydatidiform moles, the histopathologic features, deoxyribonucleic acid ploidy, and clinical follow-up were compared in 347 cases: 143 complete moles, 52 partial moles, and 152 abortions, of which 56 cases were hydropic abortions with histologic features of triploidy but lacked trophoblastic hyperplasia. STUDY DESIGN: In all cases deoxyribonucleic acid image cytometry was performed, and in 85 of these cases interphase cytogenetics was also performed. RESULTS: With use of deoxyribonucleic acid image cytometry and interphase cytogenetics, a bimodal polyploid deoxyribonucleic acid pattern was present in 97% of complete moles, 27% of partial moles, and 4% of abortions. All these cases of partial mole were reclassified to complete mole on the basis of this deoxyribonucleic acid pattern and the histopathologic features in spite of the presence of fetal blood cells, amnion, or yolk sac. Deoxyribonucleic acid triploidy was found in 95% of the remaining partial moles, in 77% of hydropic abortions with histologic features of triploidy, and in 14% of the remaining abortions. Reliable differentiation between deoxyribonucleic acid triploid partial moles and hydropic abortions with histologic features of triploidy was not possible on basis of the histopathologic features (trophoblastic hyperplasia) or 3.5c exceeding rates. Deoxyribonucleic acid diploidy was found in 1% of complete moles, 23% of hydropic abortions with features of triploidy, and 78% of the remaining abortions. Deoxyribonucleic acid tetraploidy was rarely found (1% of complete moles, 2% of partial moles, 1% of abortions). Persistent gestational trophoblastic disease developed in 33% of the bimodal deoxyribonucleic acid polyploid cases (all complete moles), in 1% of the diploid cases (concerning one of the two diploid complete moles), and in 1% of the triploid cases (partial moles). CONCLUSION: Deoxyribonucleic acid analysis is essential in the diagnosis of hydatidiform moles to decide on clinical follow-up.
PURPOSE: To assess whether a TurboFLASH (fast low-angle shot) magnetic resonance (MR) sequence can improve the accuracy of fast spin-echo (SE) endorectal coil MR imaging in the staging and localization of prostate cancer. MATERIALS AND METHODS: In 57 patients with prostate cancer, MR imaging was performed with the following sequences: T1-weighted SE, T2-weighted fast SE, single-section gadolinium-enhanced dynamic subtracted TurboFLASH (one image every 1.25 or 2.5 seconds), and late-phase gadolinium-enhanced T1-weighted SE. Retrospectively, two blinded independent readers graded onset and steepest slope of enhancement and assessed tumor involvement and capsular penetration. MR findings were correlated with histopathologic results. RESULTS: On TurboFLASH images, prostate cancer was characterized by early and rapidly accelerating enhancement compared with that of surrounding tissues. Average sensitivity, specificity, and accuracy for detection of tumor involvement for the two readers with TurboFLASH images were 73.5%, 81.0%, and 77.5%. These values with fast SE images were 57.5%, 80.5%, and 72.0%. Depiction of capsular penetration and delineation and staging of tumor were better when TurboFLASH images were included with fast SE images. Differences between the two sequences, however, were not statistically significant. CONCLUSION: Because the TurboFLASH sequence did not statistically significantly improve tumor localization and staging results, routine use is not recommended. The technique may be useful for selected patients with equivocal evidence of capsular penetration.
PURPOSE: Ever since the recognition of the inverted papilloma as a distinct lesion of the urinary tract, there has been discussion about the possible (pre)malignant potential of this rare tumor, with subsequent uncertainty about followup. Hampering the discussion are the low frequency, the unknown etiology, the difficult histopathological diagnosis and the reported association with transitional cell carcinoma. We reviewed the literature and studied our patients, resulting in the largest series reported in the literature to date. MATERIALS AND METHODS: We selected 51 patients with an inverted papilloma without a history of or a concordant transitional cell carcinoma of the urinary tract. Histology of all patients was reviewed. RESULTS: After review, as many as 14 patients appeared to be misdiagnosed (transitional cell carcinoma in 11). In 37 patients, we could confirm the diagnosis of inverted papilloma, with characteristics that were highly comparable to those described in the literature. Only 1 patient had a superficial bladder tumor after 49 months. CONCLUSIONS: Reviewing these data and our own results, we conclude that an inverted papilloma does not seem to be a risk factor for transitional cell carcinoma, although inverted papillomas and transitional cell carcinoma appear to be related to some extent. Therefore, frequent and long-term followup does not seem to be necessary provided that there is no doubt about the difficult histological diagnosis.
In order to understand the clinical and biological implications of prostate cancer multifocality and heterogeneity, we investigated their occurrence in relation to variables such as tumour volume, local invasion, and biopsy findings. In a series of 61 completely sectioned whole-mount radical prostatectomy specimens with clinical stage T2 prostate cancer, we mapped histological grade heterogeneity and tumour multifocality. We also evaluated 55 prostate biopsy cases to assess the accuracy of pre-operative grading. Among all of the prostates, only 28 per cent had a single tumour and in 16 per cent one histological grade of cancer was evident. Extracapsular invasion was not restricted to the largest tumour in each case, but also occurred in tumours of relatively small volume and low histological grade. Variability of histological grade was directly proportional to tumour volume. Both grade heterogeneity and tumour multifocality of the prostatectomy specimen showed no significant relationship to the grade accuracy of biopsies. Biopsy grading error proved greatest among small, well-differentiated, tumours. Whole-mount sectioning of prostatectomy specimens in patients with clinically localized adenocarcinoma demonstrates that grade heterogeneity is most closely related to tumour volume; that the largest (index) tumour lesion may not be representative of the pathological stage; and that grading error in prostate needle biopsies can be only partly explained by grade heterogeneity or tumour multifocality.
OBJECTIVE: To evaluate the accuracy of MR imaging of the prostate with an endorectal surface coil in determining presence, localization, volume, and local stage of prostate carcinoma. SUBJECTS AND METHODS: MR images of 34 patients with biopsy-proven cancer were correlated retrospectively with the histologic mappings of radical prostatectomy specimens. The volume and number of tumor lesions of MR images were calculated and compared with the surgical specimens used as the gold standard. Tumor stage based on MR imaging was compared with the pathologic stage according to the TNM classification. Predictive values were calculated separately for all lesions and for the lesions correctly localized with MR imaging. RESULTS: MR imaging correctly depicted the location of 67% of the tumors. Twenty percent of the lesions depicted by MR imaging appeared to be false-positive errors. The tumors that were missed were located centrally and ventrally in the prostate. Tumor volume as shown by MR imaging was within a 25% range of the actual tumor volume in 10 cases, overestimated in 16 cases, and underestimated in eight cases. Histopathology showed capsular penetration in 12 of 34 patients (35%) and in 14 of 52 lesions (27%). Sensitivity, specificity, and positive predictive values were 43%, 84%, and 55%, respectively. Histologically, capsular penetration extended less than 1 mm into the periprostatic adipose tissue in seven patients. Sensitivity for capsular penetration less than 1 mm was 14%. Sensitivity for capsular penetration more than 1 mm was 71%. Accuracy for differentiating a pT2 from a pT3 tumor was 68%. CONCLUSION: Results from this study indicate that the accuracy of the technique was not satisfactory for predicting actual tumor volume. Tumor detection and localization was more accurate in the peripheral zone than in the central zone. Accuracy was poor for detecting capsular penetration of less than 1 mm, but accuracy was much better for penetration of more than 1 mm. Because recent reports suggest that capsular penetration of less than 1 mm does not adversely affect surgical cure, MR imaging still may be practical in the selection of patients for radical prostatectomy.
DNA flow cytometry has shown a wider spectrum of DNA content in the complete hydatidiform mole (CM) than the originally reported diploidy. Conflicting results have been published about the relationship of DNA content and the occurrence of persistent gestational trophoblastic disease (PGTD). In the present study, 71 cases of CM and 4 cases of partial mole accompanied by PGTD and 100 cases of CM without PGTD were evaluated with DNA image cytometry for differences in DNA-ploidy pattern, expressed as the 2.5c and 5c exceeding rates. A pilot study of 20 cases of each group was performed using interphase cytogenetics to detect differences in the frequency of numerical chromosomal aberrations and in sex chromosome composition. For this purpose, DNA probes specific for the pericentromeric regions of chromosomes 1 and X and for the long arm of chromosome Y were incubated on 6-micron paraffin tissue sections. The results showed no differences between CMs with or without PGTD; DNA polyploidy occurred in 99% and 98% of cases, respectively; the 2.5c exceeding rate and 5c exceeding rate were 62.6 and 62.4, and 6.5 and 6.0, respectively. The frequency of numerical chromosomal aberrations as detected by interphase cytogenetics was 23.4 and 22.8%. An XY pattern was found in 3 of 20 cases of CM with PGTD and in 4 of 20 cases of CM without PGTD. The four cases of partial mole showed a DNA-ploidy pattern identical to that of a CM. For this reason, they would be better reclassified as CMs, despite the presence of nucleated red blood cells or amnion. Although nuclear atypia and corresponding increased DNA content is pronounced but variable in CMs, the occurrence of PGTD is not related to variations in quantitative DNA content nor to gross heterology or homology in sex chromosomes.
Follicular adenoma is the most frequent cause of a solitary thyroid nodule in children. We reviewed our own patient material and the literature and discuss etiology, available diagnostic methods, differential diagnosis, natural course and clinical management. In spite of the fact that the great majority of solitary thyroid nodules are benign, the treatment strategy is completely dominated by the risk for malignancy.
Retrospectively the data were examined of 69 patients with polymyalgia rheumatica (PMR) and giant-cell arteritis (GCA), of whom 62 were treated with corticosteroids. The clinical and laboratory data, and the outcome of temporal artery biopsy were compared. In addition the relation between the course of the disease and survival was investigated. PMR and GCA are closely related syndromes with a multiform clinical presentation. There even is a group of patients with merely systemic symptoms, without specific signs of PMR or GCA. Concerning the course of the disease patients can be divided into groups with a shorter and longer period of disease activity; patients with a smooth stable remission and a chronic disease. The former group shows a significantly better five-year survival. At the time of diagnosis no reliable prediction of the course of the disease is possible.
The differential diagnosis of complete (CM) and partial (PM) hydatidiform moles and hydropic abortions (HA) can be difficult when based on histology alone. Therefore, a more objective approach of chromosome ploidy analysis as detected by in situ hybridization (ISH) was performed on 6 microns paraffin sections of seven cases, originally classified as three CM, two PM, and two HA with a histologic pattern suggestive of triploidy. Probes for repetitive DNA targets in the (peri)centromeric region of chromosomes 1 and X and in the q arm of chromosome Y were used to determine chromosome ploidy and sex chromosome composition. The findings in the three CM were consistent with diploidy: two copies of chromosomes 1 and X and none of chromosome Y. In the two HA with a histologic pattern suggestive of triploidy, three copies of chromosomes 1 and X and none of chromosome Y confirmed triploidy. Two cases originally classified as PM both appeared to have two copies of chromosome 1 with an XX pattern in one case and an XY pattern in the other case, which is consistent with diploidy instead of triploidy. After reviewing, both cases most likely represented CM. We conclude that interphase cytogenetics by ISH on paraffin sections of hydatidiform moles and hydropic abortions enables chromosome ploidy analysis with preservation of histological context.(ABSTRACT TRUNCATED AT 250 WORDS)