Can FDG PET be used to successfully direct preoperative biopsy of soft tissue tumours?

Magnetic resonance imaging (MRI) has been the most useful tool in the anatomical definition of soft tissue sarcoma, although there remains the problem of defining the lesions as benign or malignant. The management of such lesions requires biopsy prior to surgical resection. If the most malignant area could be defined more accurately, then this area could be targeted for biopsy. Fluorodeoxyglucose positron emission tomography (FDG PET) has been found to be useful in identifying malignancy and variations in grade in soft tissue masses. The aim of this study was to assess the use of FDG PET scanning with or without co-registered MRI to indicate the most appropriate biopsy site. Twenty consecutive patients presented with soft tissue masses with clinical signs of malignancy. All patients underwent MRI and FDG PET scanning and the two images were co-registered. A biopsy site that was the most likely to be malignant was defined on the PET scan. All patients underwent an initial biopsy and then complete surgical resection of the mass. The histological results from the mass were compared with those from the biopsy specimen obtained from the site suggested by the PET scan. In malignant masses the biopsy site suggested by the FDG PET scan was found to be representative of the most malignant site on the whole mass histology. Benign lesions had low or no FDG uptake. In no case did the co-registered image add significantly to the appropriate biopsy site. FDG PET can be used to appropriately direct biopsy in soft tissue sarcoma and potentially may lead to computed tomography/MRI directed outpatient biopsy prior to definitive treatment.

Proliferation of T-cell subsets that contact tumour cells in colorectal cancer.

We have investigated the proliferation rates of T-cell subsets in colorectal carcinomas using immunohistochemistry. It was found that the tumour-infiltrating T cells in contact with the tumour cells have a significantly higher frequency of proliferation than those in the stroma. In particular, the CD8+ intraepithelial lymphocytes (T-IEL) within the tumours have a significantly higher frequency of proliferation in comparison with CD8+ T cells in the stromal compartment or in any normal mucosal lymphoid tissues. It is possible that the proliferation of the CD8+ T-IEL may be driven by self-antigens expressed on the tumour cells. The proportion of CD3+ CD7- T cells is increased within carcinomas compared with the normal colon, and a population of CD57+ T cells was observed which is absent from the normal colon. It is possible that these phenotypes are acquired in situ due to repeated stimulation of the T cells by tumour antigens. Intact colorectal carcinoma explants were cultured, and the presence of tumour-infiltrating T cells analysed after 3 days of culture in isolation from the systemic compartments. CD3+ T cells were proliferating (at a low rate) within the explants after 3 days of culture, indicating that they may be sustained by factors present in the tumour microenvironment.

Gastro-oesophageal reflux and duodenogastric reflux before and after eradication in Helicobacter pylori gastritis.

OBJECTIVE: Helicobacter pylori and duodenogastric reflux (DGR) are both associated with chronic gastritis, peptic ulcer and gastric cancer. The nature of their interrelationship remains unclear. H. pylori eradication has also been reported to result in new or worsening acid gastro-oesophageal reflux (GOR). The aim of this study was to investigate the relationship between GOR, DGR and H. pylori infection. METHOD: 25 patients with H. pylori gastritis underwent ambulatory 24-hour oesophageal and gastric pHmetry and gastric bilirubin monitoring before and 12 weeks after H. pylori eradication, confirmed by 14C urea breath testing (UBT). Ten healthy subjects served as a control group. RESULTS: There were no differences between patient and control groups for gastric alkaline exposure or gastric bilirubin exposure (P> 0.25 in all categories). Oesophageal acid reflux was higher in the study group (P< 0.02). No differences were detected in oesophageal acid reflux, gastric alkaline exposure, or gastric bilirubin exposure (P = 0.35, 0.18 and 0.11, respectively) before and after eradication. CONCLUSIONS: Acid GOR is not increased by H. pylori eradication. DGR in patients with H. pylori gastritis is similar to that in healthy, non-infected subjects. H. pylori eradication produces no change in GOR or DGR. In patients with chronic gastritis, H. pylori infection and DGR appear to be independent of each other.

Fibromatoses and related tumors of the hand in children. A clinicopathologic review.

Benign and malignant tumors of the hand are rare in children. This article reviews some of the common tumors that affect the hand in children, with an emphasis on clinico-pathologic correlations. Illustrated case histories on some rare tumors are also included.

Expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma: an immunopathological study with clinical correlation.

AIMS: Changes in the histochemical characteristics of the surface epithelial mucins is the hallmark of Barrett's metaplasia. The study investigated the pattern of expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma as possible indicators of increased malignant potential. METHODS AND RESULTS: Tissue sections from 51 patients with Barrett's intestinal metaplasia, nine with dysplasia (three indefinite) and 28 resected adenocarcinomas were stained with monoclonal antibodies to MUC1 and MUC2. The majority of the patients were men (70/88, 80%) who were treated over a period of 3 years. None of the patients with dysplasia or carcinoma were under surveillance at the time of presentation. All 51 biopsies with Barrett's metaplasia expressed MUC2 and MUC1 was consistently absent. Neither MUC1 or MUC2 were expressed in the dysplastic epithelium whether in its pure form (6/6) or when associated with carcinoma (26/28) (P < 0.005). Three biopsies which were initially classified as high-grade dysplasia expressed MUC1 and these turned out to be carcinomas on further investigations. MUC1 was also expressed in 12/28 (43%) of the adenocarcinomas and majority of these were poorly differentiated stage 3 tumours (P < 0.05). MUC2 was only positive in mucin-secreting carcinomas (4/28; 14%) irrespective of the tumour stage. CONCLUSION: Despite the large number of patients with Barrett's metaplasia and carcinoma, very few patients presented with dysplasia, implying that Barrett's oesophagus is a silent disease in the community presenting late as carcinoma. The study has demonstrated aberrant expression of MUC2 (an intestinal mucin) in Barrett's metaplasia and this expression is lost when the cells become dysplastic. The lack of MUC1 in dysplastic epithelium and its expression in carcinoma could be utilized as a marker which could differentiate dysplasia from carcinoma in mucosal biopsies. Furthermore, expression of MUC1 in advanced stage oesophageal cancers (as in breast cancer) suggests an unfavourable prognosis.

3-D histo-radiographic comparison of surgical clearances of microcalcified lesions in breast localization biopsies.

There is controversy as to the value of the radiological or pathological estimation of surgical clearance of microcalcifying breast lesions. An important part of this issue has been addressed by coordinated three-dimensional radiographic and histological examination of a prospective consecutive series of 40 benign and malignant mammographically detected lesions in surgical breast biopsy specimens containing microcalcifications, including 20 cases of ductal carcinoma in situ. They were radiographed from four viewpoints by means of rotation in a radiolucent tetrahedral container. The planes of histological examination were then chosen to correspond to the radiographic view showing the minimum separation of the edge of the specimen and the outermost microcalcification. There was a close correlation (Spearman ranked) between the least tetrahedral radiographic distance and the corresponding histological distance separating the surgical margin of excision. There were, however, incompatible Wilcoxon signed ranking orders when comparing the least tetrahedral distance or the histological distance with all four single radiographic views, including the conventional specimen radiographic view. Two-dimensional specimen mammography and standardized histological examination are suboptimal and may thus have contributed to confusion as to the value of determining adequate surgical excision of ductal carcinoma in situ of the breast. Although labour-intensive, use of four-view radiography and choice of the appropriate plane of histological examination give a better correlation of the radiographic estimates of surgical clearance with histology than single-view specimen radiography and arbitrary histological sectioning.

Cytokeratin demonstration in thick breast tissue slices.

Tissue slices (500 to 1000 microns thick) of archival formalin-fixed, paraffin-embedded breast tissue were immunostained by a cytokeratin antibody (MNF116) using a streptavidin-biotin complex procedure. The technique requires prolonged exposure of tissue slices to the reagents. Use of the detergent Triton X-100 facilitated penetration of high molecular weight reagents through the tissue slices. Fifty of 58 slices 500 microns thick (86%) showed good to excellent immunostaining, and 13 of 20 slices 1000 microns thick (65%) showed similar staining. Omission of the primary antibody eliminated any immunostaining. Comparison with corresponding Haematoxylin staining of the thick slices (the conventional procedure for such breast tissue slices) showed that thick-slice cytokeratin immunostaining markedly improved visualization of the epithelial structure in normal lobules and invasive carcinomas. Although the immunohistochemical technique takes 33 days for completion, the quality of the epithelial images outweighs this disadvantage.

Factors affecting surgical margin clearance in screen-detected breast cancer and the effect of cavity biopsies on residual disease.

One hundred and fourteen localization biopsies for screen-detected breast cancers were assessed for surgical margin clearance and presence of tumour in the cavity biopsies or subsequent resections. Inadequate surgical clearance (< or = 1 mm from the margin) in 88 patients was associated with high nuclear grade ductal carcinoma in situ, or extensive in-situ change accompanying invasive carcinomas, vs pure invasive carcinomas. Smaller localization biopsies (< or =50 g), larger tumours, and absence of a definite fine-needle aspiration cytological diagnosis of malignancy were also associated with inadequate excision. The radiographic characteristics of the tumours did not correlate with inadequate excision. Sixty-five patients had cavity biopsies taken at the time of surgery and 23 (35%) biopsies were positive, 20 of which were associated with incompletely excised tumours. Further excision in 78 patients yielded residual disease in 63%, most of whom had had inadequate surgical clearance. When cavity biopsies were taken with incompletely excised tumours, 15 of 88 subsequent resection specimens harboured residual disease compared with 29 of 88 without cavity biopsies. Although cavity biopsies increase the clearance margin, a negative cavity biopsy is not always an assurance of adequate excision.

Mammary mucinous lesions: congeners, prevalence and important pathological associations.

A retrospective histopathological study was undertaken to determine the prevalence of mucin filled ducts and their associated mucinous proliferation in 962 breast cancers and 335 benign lesions. A total of 38 (3%) cases with mucin filled ducts was identified and 27 (2%) of these showed mucin extravasation into the adjacent stroma, changes characteristic of mucocoele-like lesions. This constitutes the largest series reported to date. Of the mucocoele-like lesions 12 were prototypic screen-detected cases: 11 of which were mammographically detected on account of suspicious microcalcification and eight cases (67%) exhibited mucinous atypical ductal hyperplasia without overt malignancy. A further 12 mucocoele-like lesions were incidental findings in screen-detected (11) and symptomatic (one) cancers, the majority of which were invasive ductal carcinomas of no special type. In six of these cases (50%), mucinous atypical ductal hyperplasia or ductal carcinoma in situ was present. Thirty mucinous carcinomas constituted 3% of all cancers and three cases had associated mucocoele-like lesions. Mucinous atypical ductal hyperplasia or ductal carcinoma in situ was also associated with 11 cases of mucinous carcinoma. In six mucinous carcinomas, amorphous microcalcification with a similar appearance to that of benign mucocoele-like lesions was identified in the mucin, suggesting a possible link between the two lesions. Mucin-filled ducts or mucocoele-like lesions were almost twice as frequent in screen-detected as in symptomatic lesions. The presence of mucinous atypical ductal hyperplasia in screen-detected mucocoele-like lesions, a decade earlier than the peak of mucinous carcinoma, is a possible risk factor for subsequent invasive malignancy. Mucin-filled ducts, mucocoele-like lesions, mucinous atypical ductal hyperplasia or ductal carcinoma in situ and mucinous carcinoma may represent different stages of the same disease process. Our findings suggest that patients with mucin-filled ducts of mucocoele-like lesions merit close follow-up.

Benign and malignant stellate breast lesions: structural differences in 5 microns sections and thick tissue slices.

Complex sclerosing lesions have presented a diagnostic problem since they were identified amongst benign breast lesions. Their differentiation from stellate carcinomas may cause serious difficulties for both radiologists and pathologists. In the present study the conventional and thick-slice appearances of 15 complex sclerosing lesions and 15 well differentiated and tubular carcinomas were compared, with the main emphasis on the stellate zone of the lesions. There was a marked morphological difference between the stellate extensions: the majority was formed by epithelial structures in complex sclerosing lesions as opposed to the composition of the extensions of the stellate carcinomas, where fibrovascular tissue dominates. Well differentiated carcinomas originating in complex sclerosing lesions showed an intermediate ratio of epithelial and fibrous stellate extensions. The structural differences may explain the radiomorphological differences of benign and malignant stellate breast lesions. We suggest these structural characteristics ought to be included in the pathomorphologic differential diagnostic features.

New avenues in 3-D computerised (stereopathological) imaging of breast cancer (review).

Multimodal methods of three-dimensional (3-D) imaging of breast cancer are described. These involve scanning confocal microscopy, using 50 MHz acoustic or near-infrared images, four-view (tetrahedral) radiography and x-ray projection microscopy. Computerised volume data from these techniques can be used to produce three-dimensional images of tissue ranging from 500 microns to approximately 4 mm in thickness. Preliminary findings indicate that stereoscopic images or 3-D computerised reconstructions are capable of advancing the understanding of the structure of ductal carcinoma in situ, lesions simulating microinvasive breast carcinoma, surgical clearance of high-grade calcifying ductal carcinoma in situ, and the 3-D growth patterns of invasive forms of breast carcinoma. In the future computerised image fusion techniques seem likely to be able to take advantage of multimodal imaging of breast cancers, thus correcting primary imaging artefacts, improving robustness, and combining complementary information. In addition, the use of computerised tetrahedral radiography may change the intraoperative assessment of breast cancers, which mostly depend at present upon subsequent laboratory procedures that take days to perform.

Ki-67 expression in early prostate cancer and associated pathological lesions.

AIM: To assess cell proliferation in early prostate cancer and associated pathological lesions. METHODS: Using the Ki-67 antibody, the cell proliferation index was measured in early stage prostatic carcinoma in 37 incidental tumours diagnosed at transurethral prostatectomy (TURP) and in 20 low volume cancers treated by radical prostatectomy. Proliferation indexes have also been measured in areas of normal peripheral zone, transition zone hyperplasia, atrophic appearing lobules, and high grade prostatic intraepithelial neoplasia in the radical prostatectomy cases. RESULTS: In the TURP series the proliferation index correlated with grade and stage. Logistic regression analysis, however, showed that Gleason grade was the most reliable predictor of biopsy proven residual disease and clinical progression. In the radical series transition zone carcinoma the proliferation index was half that of peripheral zone carcinoma. The atrophic lobules also showed a high proliferation index of the same order as seen in the peripheral zone carcinoma. Normal peripheral zone showed the lowest proliferation index and in hyperplastic transition zone it was also less than the other areas. CONCLUSIONS: There is only limited support for the correlation of proliferation index with grade in early stage prostatic carcinoma. The findings do not suggest that proliferation index adds to the prognostic information given by grade and stage in pT1 disease. The significant difference in proliferation index in transition zone and peripheral zone carcinomas supports the morphological distinction of these tumour types and is consistent with differences in biological behaviour. The high proliferation index in lobules considered morphologically atrophic is reminiscent of previous observations in which carcinoma was spatially associated with atrophy.