The classification of malignant tumours is influenced by both immunohistochemical and molecular genetic findings. This is highlighted in the latest World Health Organization classification of renal neoplasia, which has a tumour category of 'tumours that are molecularly defined'. This implies that the defining molecular features are integral to tumourigenesis, which may not necessarily be the case. Renal oncocytoma is recognised as a benign tumour with variable morphology and immunoexpression. A variant of these tumours is hybrid oncocytic chromophobe tumour, which has features of both oncocytoma and chromophobe renal cell carcinoma and may, on rare occasions, show malignant behaviour. Recent reports have proposed two further entities with eosinophilic cytoplasm and varying nuclear pleomorphism, designated low grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT), formally known as high grade oncocytic tumour (HOT). The diagnosis of these apparently benign tumours was made on the basis of morphological and immunohistochemical features. More recently it has been claimed that the mutations in the mTOR pathway are also a diagnostic feature and it is further suggested that these mutations are key to the pathogenesis of these tumours. As is seen in oncocytoma, immunohistochemical expression of tumours included in series of LOT and EVT is variable. The mutations in the mTOR pathway, where detected, were not constant, with any combination of mTOR, TSC1 and/or TSC2 being involved. A major issue is that in many of the studies full comparative genomic hybridisation results are not presented. In addition it is well recognised that mTOR mutations are seen in a variety of renal tumours. In view of these conflicting results, the rarity of these tumours and their apparent benign nature, raises questions as to why these tumours should be considered specific entities.

Purpose To determine the site of relapse when biochemical failure (BF) occurs after iodine-125 seed implantation for prostate cancer. Materials and methods From 2001–2009, 500 men underwent implantation in Wellington, New Zealand. Men who sustained BF were placed on relapse guidelines that delayed restaging and intervention until the prostate-specific antigen (PSA) was ⩾20 ng/mL. Results Most implants (86%) had a prostate D90 of ⩾90%, and multivariate analysis showed that this parameter was not a variable that affected the risk of BF. Of 21 BFs that occurred, the site of failure was discovered to be local in one case and distant in nine cases. Restaging failed to identify the site of relapse in two cases. In nine cases the trigger for restaging had not been reached. Conclusions If post-implant dosimetry is generally within the optimal range, distant rather than local failure appears to be the main cause of BF. Hormone treatment is therefore the most commonly indicated secondary treatment intervention (STI). Delaying the start of STI prevents the unnecessary treatment of men who undergo PSA ‘bounce’ and have PSA dynamics initially mimicking those of BF.

AIM To compare the burden and outcomes of cancer in New Zealand with those in Australia. METHODS For the years 1996-1997 and 2006-2007, the incidence and mortality of cancer in New Zealand and Australia was compared to determine if differences between the two countries had changed over the decade under study. Summarised cancer data from New Zealand and Australia, age standardised to the 2002 World Health Organisation's standard population, were used to make the comparisons. RESULTS For the 11 year timeframe of this study, total rates of cancer incidence reduced in New Zealand and increased in Australia. The incidence of cancer in New Zealand, relative to Australia, changed from an excess of +10.3 to a deficit of -27.5 per 100,000 people. When considering the excess in terms of gender, the annual excess of cancer registrations for New Zealand females fell from +19.9 to +0.9 per 100,000, and male cancer registration fell from an excess of +3.7 to a deficit of -58.0 per 100,000, due almost entirely to a surge in prostate cancer registration in Australia. Over the same 11-year timeframe, cancer-specific mortality rates decreased in both countries, but there was no change in the difference between New Zealand and Australian rates, which remained 10% higher in New Zealand. Similar to findings on 1996/7 data, the main cancer sites responsible for the overall excess mortality in 2006/7 were colorectal cancer in both sexes, and lung and breast cancer in females. CONCLUSION The persisting different cancer mortality rates between the two countries is likely to have been partly due to lifestyle and ethnic differences in the populations, and partly due to New Zealanders presenting with more advanced cancers and having less easy access to some treatments. Until we know the relative contributions of these factors, it will be difficult for New Zealand to plan interventions in the future which have a good chance of lifting our cancer survival rates to those of our closest neighbour. The collection of clinical stage on all new cancer registrations would provide the base information required.

No AccessJournal of UrologyLetter to the Editor/Errata1 Jan 2011Re: Fuhrman Grade Provides Higher Prognostic Accuracy Than Nucleolar Grade for Papillary Renal Cell CarcinomaT. Klatte, C. Anterasian, J. W. Said, M. de Martino, F. F. Kabbinavar, A. S. Belldegrun and A. J. Pantuck J Urol 2010; 183: 2143–2147 Brett Delahunt, Peter B. Bethwaite, Rose J. Miller, Dianne Sika-Paotonu, and John R. Srigley Brett DelahuntBrett Delahunt More articles by this author , Peter B. BethwaitePeter B. Bethwaite More articles by this author , Rose J. MillerRose J. Miller More articles by this author , Dianne Sika-PaotonuDianne Sika-Paotonu More articles by this author , and John R. SrigleyJohn R. Srigley More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.08.045AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail References 1 : Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. Am J Surg Pathol2006; 30: 1091. Google Scholar 2 : Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol1982; 6: 655. Crossref, Medline, Google Scholar 3 : Percentage of high-grade carcinoma as a prognostic indicator in patients with renal cell carcinoma. Cancer2008; 113: 477. Google Scholar 4 : Advances and controversies in grading and staging of renal cell carcinomas. Mod Pathol2009; 22: S24. Google Scholar 5 : Kidney tumors in adults. In: Tumors of the Kidney, Bladder and Related Urinary Structures—AFIP Atlas of Tumor Pathology. Edited by . Washington, D. C: Armed Forces Institute of Pathology2004: 164. Google Scholar 6 : Recommendations for the reporting of surgically resected specimens of renal cell carcinoma: the Association of Directors of Anatomic and Surgical Pathology. Hum Pathol2009; 40: 456. Google Scholar 7 : Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med1996; 15: 361. Crossref, Medline, Google Scholar 8 : Original and reviewed nuclear grading according to the Fuhrman system: a multivariate analysis of 388 patients with conventional renal cell carcinoma. Cancer2005; 103: 68. Google Scholar © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 1January 2011Page: 356-358 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brett Delahunt More articles by this author Peter B. Bethwaite More articles by this author Rose J. Miller More articles by this author Dianne Sika-Paotonu More articles by this author John R. Srigley More articles by this author Expand All Advertisement PDF downloadLoading ...

Fuhrman grading of renal cell carcinoma focuses on features of nuclear size, nuclear shape, and nucleolar prominence. Despite the reported widespread usage of Fuhrman grading in clinical studies, there is debate as to the prognostic significance and reproducibility of its criteria. It has been noted that many pathologists rely on assessment of nucleolar prominence alone when grading renal cell carcinoma; however, the validity of this remains unconfirmed. This study was undertaken to determine the relationship of the 3 morphologic components of the Fuhrman grading system with one another and to determine which, if any of these, can be correlated with outcome for clear cell renal cell carcinoma. One hundred twenty-one organ-confined clear cell renal cell carcinomas were examined in this study. Parameters of nuclear size (area, major axis, perimeter) and nuclear shape (shape factor, nuclear compactness) were assessed by image analysis, whereas nucleolar prominence was assigned (grades 1 to 3) using the criteria of Fuhrman. On the basis of the predominant grade present, there were 17 nucleolar grade 1, 90 nucleolar grade 2, and 14 nucleolar grade 3 tumors. When the high-power field in each tumor with the worst nucleolar grade was assessed, there was 1 nucleolar grade 1, 68 nucleolar grade 2, and 52 nucleolar grade 3 tumors. Predominant and worst nucleolar grade correlated with all measures of nuclear size, but not nuclear shape. Worst nucleolar grade and all parameters of nuclear size were significantly associated with outcome. On multivariate analysis, worst nucleolar grade retained a significant association with survival when modeled with nuclear area. Neither worst nucleolar grade nor major nuclear axis/nuclear perimeter was significantly associated with survival when modeled together. In this study, we have shown that worst nucleolar grade and nuclear size are of prognostic significance for clear cell renal cell carcinoma. We have further shown the association of worst nucleolar grade with outcome to be independent of nuclear area, whereas it is a dependent variable when tested against other parameters of nuclear size. These findings indicate that worst nucleolar grading alone is a valid grading parameter for clear cell renal cell carcinoma.

The prognostic significance of perineural invasion by prostate cancer is debated. We have evaluated the association between biochemical failure and measurements of perineural invasion in radical prostatectomy specimens. Perineural invasion was identified in sections using S-100 protein immunostaining. For nerves showing invasion, the involved nerve closest to the edge of the prostate and to the surgical excision margin, as well as the diameter of these nerves, the largest nerve showing perineural invasion and its proximity to the excision margin, and the percentage of nerves showing perineural invasion up to 1.75 mm from the excision margin was determined and tested against time to prostate-specific antigen failure, along with preoperative prostate-specific antigen levels, highest Gleason primary grade, Gleason score and TNM T category. Perineural invasion was present in 90% of cases, with extraprostatic perineural invasion in 25% of tumors. Diameter of nerves showing perineural invasion ranged from 11 to 680 μm and the shortest distance to the surgical excision margin ranged from 33 to 2.57 mm. Perineural invasion density ranged from 6 to 96%. Gleason scores were six in 58 cases, seven in 43 cases, eight in three cases and nine in one case. Clinical T categories were T1c in 75 cases, T2a in 22 cases, T2b in five cases, T2c in two cases, T3 in one case. During a follow-up period of 11 to 55 months (median 26 months), 27 patients showed prostate-specific antigen failure. On univariate analysis only presence of extraprostatic perineural invasion, among parameters of perineural invasion, showed a weak correlation with outcome, while on multivariate analysis this lost significance and preoperative prostate-specific antigen levels, Gleason score and excision margin status were independently associated with biochemical failure. We conclude that the investigated parameters of perineural invasion do not predict prostate-specific antigen recurrence in radical prostatectomy specimens.

A wide variety of parameters have been investigated for their prognostic significance in mixed series of renal cell carcinoma (RCC). The classification of RCC into separate types with differing morphology, genotype and probable clinical outcome has led to a re-evaluation of many prognostic parameters with studies confined to a single RCC morphotype. Tumour stage remains the most important predictor of RCC outcome and recent investigations have focused upon tumour diameter and the prognostic significance of stromal, vascular and lymphatic invasion within the renal sinus. In large tumour series, morphotype has been correlated with patient survival, with clear cell RCC being associated with a less favourable outcome than chromophobe RCC and to a lesser extent papillary RCC, for organ confined tumours. The prognostic significance of nuclear grading remains controversial. Fuhrman grading has been shown to have prognostic utility for clear cell RCC in some series. Recent studies have shown that for papillary RCC, grading should be based upon nucleolar size and that Fuhrman grading is inappropriate for chromophobe RCC. Proliferative indices based upon a variety of markers have been correlated with outcome for clear cell RCC (Ki-67, AgNORs, p21(waf1/cip1) and p27(Kip1)) and papillary RCC (Ki-67, AgNORs), although in some series prognostic significance was lost on multivariate analysis. The presence of tumour necrosis has been shown to predict survival for clear cell and chromophobe RCC, and in clear cell RCC quantification of tumour vascular density has been correlated with outcome. Several molecular markers have been investigated for prognostic significance, mostly in clear cell RCC. Although some of these markers have been shown to be significantly associated with survival, these findings remain to be confirmed in large scale follow-up studies.

The development of a sarcomatoid morphotype is recognized as an extreme form of dedifferentiation in renal cell carcinoma and is associated with a poor prognosis. Although sarcomatoid renal cell carcinoma shows pronounced spindle cell morphology, clear cell renal cell carcinoma may show early spindle cell change with cellular elongation, and the prognostic significance of this is debated. To determine the relationship between sarcomatoid renal cell carcinoma and clear cell renal cell carcinoma showing early spindle cell change, we have investigated collagen expression using immunohistochemistry in these 2 tumor types. Both sarcomatoid renal cell carcinoma and early spindle cell change tumors showed pericellular interstitial expression of collagen types I and III, whereas sarcomatoid renal cell carcinoma also showed cytoplasmic expression of these collagen types. Expression of these collagen types in typical clear cell renal cell carcinoma was, in occasional cases, limited to faint and patchy staining in a pericellular interstitial distribution. Tumor cells did not stain for collagen type IV in sarcomatoid renal cell carcinoma, early spindle cell change, or typical clear cell renal cell carcinoma. In sarcomatoid renal cell carcinoma, there was diffuse pericellular expression of collagen type V and patchy pericellular expression of collagen type VI, whereas early spindle cell change tumors showed patchy pericellular staining with antibodies to collagen type V. Collagen type VI expression in early spindle cell change was largely confined to the vascular adventitia and areas of scarring, although very occasional foci of faint interstitial staining were also seen. In typical clear cell renal cell carcinoma, staining of collagen types V and VI was limited to the vascular adventitia and foci of desmoplasia, whereas no staining of tumor cell cytoplasm were seen. This study has shown that collagen expression of sarcomatoid renal cell carcinoma differs from that of early spindle cell change and provides validating evidence that these 2 morphotypes should not be considered together for classification purposes.

This study was undertaken to assess the prognostic effectiveness of Fuhrman nuclear grading and the individual components of this grading system, in a series of chromophobe renal cell carcinomas. Eighty-seven cases of chromophobe renal cell carcinoma were investigated. There were 47 males and 40 females, 28 to 78 years of age. The carcinomas ranged from 25 to 180 mm in size and on TNM staging there were 38 stage I, 25 stage II, 22 stage III, and 2 stage IV tumors. Whole tumor Fuhrman grading was grade 1, 6 cases; grade 2, 72 cases; grade 3, 8 cases; and grade 4, 1 case, whereas focal (single high power field) grading was grade 1, 1 case; grade 2, 62 cases; grade 3, 21 cases; and grade 4, 3 cases. On assignment of nucleolar grading using Fuhrman criteria there were 37 grade 1, 44 grade 2, and 4 grade 3 tumors on whole tumor assessment and 3 grade 1, 63 grade 2, and 21 grade 3 tumors on assessment of the high power field showing the greatest degree of nuclear pleomorphism. Measurements of nuclear size showed nuclear area to range from 26.14 to 100.74 microm2, nuclear perimeter from 19.73 to 39.28 microm, and nuclear major axis from 6.49 to 13.21 microm, whereas the ranges of measures of nuclear shape were; shape factor 0.798 to 0.890, compactness 14.260 to 15.843, and feret diameter 5.694 to 11.242. Follow-up ranged from 1 to 150 months and 8 patients died of tumor-related causes 5 to 53 months from diagnosis. On log rank testing against survival, only patient age (P=0.016) and tumor maximum diameter (P=0.0055) were significant, whereas patient sex and TNM stage were not significant. Whole tumor and focal Fuhrman grading, as well as all measures of nucleolar prominence, nuclear size, and nuclear shape showed no significant association with outcome. It is concluded that neither Fuhrman grading, nor any of the components of the Fuhrman grading system, is useful as prognostic indicators for this tumor type.

This study was undertaken to determine the validity of Fuhrman grading in a series of papillary renal cell carcinomas (PRCCs), to examine the interrelationship and prognostic significance of the individual components of the grading system, and further to determine whether any observed predictive value was independent of other prognostic indicators. Ninety cases of PRCC were studied. Fifty-nine tumors were of type 1 and 31 were of type 2. There were 33 TNM stage 1, 26 stage 2, 18 stage 3, and 12 stage 4 tumors, whereas division of cases according to pT category showed 14 pT1a, 20 pT1b, 25 pT2, 15 pT3a, 4 pT3b, and 11 pT4 tumors. Ten tumors were grade 1, 58 grade 2, and 22 grade 3 when predominant Fuhrman grade was assigned, whereas grading according to the high-power field containing the highest grade (focal grade) showed 40 grade 2, 49 grade 3, and 1 grade 4 tumors. Measurements of nuclear size (area, major axis, perimeter) and shape (shape factor, compactness) were undertaken using image analysis. Nuclear area ranged from 27.63 to 116.39 microM, major axis length 6.70 to 14.06 microM, and nuclear perimeter 20.05 to 41.77 microM. Shape factor ranged from 0.805 to 0.878 and compactness from 14.33 to 15.66. Predominant nucleolar grade using the criteria of the Fuhrman classification was nucleolar grade 1 for 13 tumors, nucleolar grade 2 for 56 tumors, and nucleolar grade 3 for 21 tumors. Focal nucleolar grade based on the high-power field showing the greatest degree of nuclear pleomorphism, was grade 2 for 38 tumors and grade 3 for 52 tumors. pT category, TNM stage, focal Fuhrman grade, and PRCC type were significantly associated with survival. Of the various measures of the components of the Fuhrman classification, only focal nucleolar grade was associated with survival, on univariate analysis. On multivariate analysis, focal nucleolar grade and tumor diameter were independently associated with survival, whereas TNM stage retained significance independent of other parameters. It is concluded that assessment of nucleolar prominence rather than Fuhrman grade is applicable for stratification of tumors within TNM stage or pT category for PRCC and that this should be based upon the high-power field showing the greatest degree of nuclear pleomorphism.

Whereas papillary renal cell carcinoma is now established as a subtype of renal cell neoplasia, division of these tumors into 2 distinctive morphotypes has been proposed. Type 1 tumors have cells with scanty pale cytoplasm arranged in a single layer on the basement membrane of papillary cores. In these tumors, psammoma bodies and foamy macrophages are frequently seen, and the tumors frequently express cytokeratin 7. Type 2 tumor cells have pseudostratified nuclei and usually have voluminous eosinophilic cytoplasm. Recent studies have supported this subclassification of papillary renal cell carcinoma by demonstrating differing genotypes for type 1 and 2 tumors. To further study the subclassification of papillary renal carcinoma, we compared clinical features, nuclear grade, stage, tumor growth kinetics, and survival in a series of 50 type 1 and 16 type 2 papillary renal cell carcinomas. Comparison of patient age at presentation, sex, and primary tumor size shows no significant difference between the 2 tumor types. Type 1 tumors were of significantly lower Fuhrman grade (P =.0001) and higher Robson stage (P =.009) than type 2 tumors. There was no significant difference when tumors were staged according to the TNM classification. Assessment of tumor growth kinetics showed significantly different mean silver-staining nucleolar organizer region (AgNOR) scores and Ki-67 indices (AgNOR type 1, 3.83, type 2, 7.24, P =.0001; Ki-67 type 1, 3.17%, type 2, 6.01%, P =.0002). Multivariate analysis showed tumor type (P =.03), presence of metastases (P =.04), AgNOR score (P =.001), and Ki-67 index (P =.03) to be independently associated with survival. These results provide evidence of the clinical utility of dividing papillary renal cell carcinomas into 2 types according to histologic characteristics.

AimsTo investigate the histogenesis of paratesticular adenomatoid tumour by use of immunohistochemical markers for a variety of carcinomas and mesothelioma.Methods and resultsImmunohistochemical staining of sections from 12 cases of paratesticular adenomatoid tumour was undertaken using primary antibodies to antigens expressed by benign epithelial cells and carcinoma (cytokeratin AE1/AE3, cytokeratin 34ßE12, epithelial membrane antigen, MOC‐31, Ber‐EP4, CEA, B72.3, LEA.135, Leu M1), stromal and vascular markers (vimentin, CD34, factor VIII), and mesothelioma‐associated antigens (thrombomodulin, HBME‐1, OC 125) and p53 protein. There was absence of immunohistochemical expression of epithelial/carcinoma markers MOC‐31, Ber‐EP4, CEA, B72.3, LEA.135, Leu M1 and to factor VIII and CD34. All tumours expressed cytokeratin AE1/AE3, epithelial membrane antigen and vimentin, with weak expression of cytokeratin 34ßE12 in 25% of tumours. Each tumour showed expression of thrombomodulin, HBME‐1 and OC 125 in a membranous distribution. p53 protein expression was not detected.ConclusionsThe immunohistochemical profile of paratesticular adenomatoid tumour is strongly supportive of a mesothelial cell origin.

Luminal epithelial antigen (LEA.135) expression has been shown to have prognostic significance in breast carcinoma, however its relationship to tumor progression in other forms of malignancy is unknown. This study evaluates LEA.135 expression in bladder transitional cell carcinoma (TCC) and compares the findings with tumor stage and grade, and polyclonal Ki-67 derived cell cycle activity. LEA.135 expression was evaluated by immunohistochemical staining using the streptavidin-biotin method. Staining distribution was graded 0 to 4 and the results were compared with World Health Organisation tumor grade, UICC TNM stage and fraction of actively cycling cells showing positive pKi-67 immunohistochemical staining. In normal bladder epithelium, LEA.135 staining was confined to the luminal surface of superficial epithelium. In lower grade, superficial TCC LEA.135 overexpression was noted and there was a progressive loss of expression in tumors of higher grade (p = 0.0001) and advanced stage (p = 0.0001). No LEA.135 staining was seen in carcinoma-in-situ. Loss of LEA.135 expression correlates with tumor progression for bladder TCC.

The proliferation kinetics of 101 cases of transitional cell carcinoma (TCC) and seven cases of transitional cell carcinoma-in-situ of the bladder were assessed following staining with polyclonal Ki-67 antibody (pKi-67).Labeling indices ranged from 49% to 60.2% with a mean value of 22.2% for all cases. A significant association between pKi-67 indices, tumor grade and tumor stage was observed, with significant differences between pKi-67 indices of Grade 1 and 3 tumors and Grade 2 and 3 tumors. Significant differences in labeling indices were also found between superficial (Ta) tumors and both musculoinvasive (T2/T3a) tumors and those infiltrating the perivesical fat (T3b). pKi-67 indices for carcinoma-in-situ were similar to those noted for Grade 1 TCC, No difference in pKi-67 index was found when tumors were classified according to the morphology of the tumor invasion front.It is concluded that pKi-67 index is a useful marker for tumor progression for vesical TCC and that this immunohistochemical stain may assist clinical assessment of the potential behaviour of tumors in individual cases.

OBJECTIVE:To investigate the association between tumour vascularity and patient survival in a series of clear-cell renal cell carcinoma (RCC), which often metastasizes via the vascular route and frequently has a prominent vascular network. MATERIALS AND METHODS:Vessels were labelled in sections from 150 cases of clear cell RCC by factor VIII immunohistochemistry. The mean microvessel density (MMD), expressed as the number of vessels per 10 high-power fields (HPFs, x400, aggregate field area 1.452 mm2) and tumour microvessel area (TMA), expressed as the percentage of the total tumour area within 10 HPFs, were measured for each case. The relationship between MMD and TMA, tumour stage and grade, and patient survival over a 5-year follow-up was determined. RESULTS:Tumour MMD ranged from 1 to 238 vessels per HPF, while the TMA was 1.2-60.8%. There was a weak but significant difference for MMD between tumour grades (P < 0.01) and stages (P < 0.05). There was no significant association between TMA and either tumour stage or grade. Division of cases according to MMD < or = 40 and > 40 per HPF showed a significant difference in survival curves between both groups, with a higher MMD being associated with longer patient survival. The significant association between MMD and survival was retained for stage 3 tumours only when cases were stratified according to Robson's stage at presentation. TMA did not correlate with survival. CONCLUSIONS:The assessment of tumour vascularity is of prognostic significance for clear cell RCC. The significant inverse relationship between MMD and patient survival suggests that for tumours with a poor prognosis, decreased MMD is associated with tumour fibrosis and the development of large diameter vascular channels.

"AgNORs, and Tumor Stage and Grade as Prognostic Markers for Renal Cell Carcinoma." Journal of Histotechnology, 20(1), p. 81

In various tumor types dentritic cell, infiltration and the presence of tumor-infiltrating lymphocytes have been associated with an improved clinical outcome. In the uterine cervix these immunocompetent cells have been associated with improved prognosis in high stage disease. The current study examines the significance of stromal and tumor T-lymphocyte infiltration together with S-100 positive dendritic cell infiltration in a series of 73 women with low stage (FIGO Ib) invasive squamous and adenosquamous cervical carcinoma. Thirty four percent of cases contained S-100 positive dendritic cells. These were under-represented in cases showing pelvic recurrence or distant disease (1 of 11 compared to 24 of 62 free of recurrence, P = 0.05) and over-represented in cases showing lymphatic/capillary space involvement (12 of 23 compared to 13 of 46 without vascular space invasion, P = 0.05). The women were followed up for an average of 5.2 years and the five-year survival for women whose tumors contained S-100 positive dendritic cells was 92% compared to 73% for negative cases (P= 0.04). There was a significant association between a low density of tumor infiltrating T-cells and risk of pelvic lymph node spread and subsequent local or distant disease control failure (P = 0.008). A five year survival advantage was seen with five or more CD 3 positive tumor infiltrating T-lymphocytes per high power field (90%) compared to a lower count (68%) (P = 0.04). A similar advantage could not be demonstrated for a high stromat infiltrate of T-cells. As yet neither the specific mechanisms that induce these cells to infiltrate some cervical carcinomas nor the nature of the immunological injury that the cells co-ordinate in tumor tissue are well understood.

HistopathologyVolume 29, Issue 3 p. 282-284 Diffuse malignant mesothelioma arising in a paracolostomy hernial sac P.B. BETHWAITE, Corresponding Author P.B. BETHWAITE Medical Laboratory (Wellington), New ZealandAddress for correspondence: Dr P.B. Bethwaite, Medical Laboratory (Wellington), 89 Courtenay Place, Wellington. New Zealand.Search for more papers by this authorR. EVANS, R. EVANS Medical Laboratory (Wellington), New Zealand Department of Surgery, Wellington Hospital, Wellington, New ZealandSearch for more papers by this authorD.K. NAIK, D.K. NAIK Medical Laboratory (Wellington), New Zealand Department of Surgery, Wellington Hospital, Wellington, New ZealandSearch for more papers by this authorB. DELAHUNT, B. DELAHUNT Medical Laboratory (Wellington), New Zealand Department of Pathology, Wellington School of Medicine, Wellington, New ZealandSearch for more papers by this authorC.A. TEAGUE, C.A. TEAGUE Medical Laboratory (Wellington), New ZealandSearch for more papers by this author P.B. BETHWAITE, Corresponding Author P.B. BETHWAITE Medical Laboratory (Wellington), New ZealandAddress for correspondence: Dr P.B. Bethwaite, Medical Laboratory (Wellington), 89 Courtenay Place, Wellington. New Zealand.Search for more papers by this authorR. EVANS, R. EVANS Medical Laboratory (Wellington), New Zealand Department of Surgery, Wellington Hospital, Wellington, New ZealandSearch for more papers by this authorD.K. NAIK, D.K. NAIK Medical Laboratory (Wellington), New Zealand Department of Surgery, Wellington Hospital, Wellington, New ZealandSearch for more papers by this authorB. DELAHUNT, B. DELAHUNT Medical Laboratory (Wellington), New Zealand Department of Pathology, Wellington School of Medicine, Wellington, New ZealandSearch for more papers by this authorC.A. TEAGUE, C.A. TEAGUE Medical Laboratory (Wellington), New ZealandSearch for more papers by this author First published: September 1996 https://doi.org/10.1111/j.1365-2559.1996.tb01405.xCitations: 7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Rosai J. Dehner LP. Nodular mesothelial hyperplasia in herniasacs: a benign reactive condition simulating a neoplastic process. Cancer 1975; 35; 165– 175. 2 Tang CK, Gray GF, Keuhnelian JG. Malignant peritoneal mesothelioma in an inguinal hernia sac. Cancer 1976; 37; 1887– 1890. 3 McCaughey WTE, Al-Jabi M. Differentiation of serosal hyperplasia and neoplasia in biopsies. Pathol. Annu. 1986; 21; 271– 292. 4 Bethwaite PB, Delahunt B, Holloway LJ, Thornton A. Comparison of silver-staining nucleolar organizer region (AgNOR) counts and proliferating cell nuclear antigen (PCNA) expression in reactive mesothelial hyperplasia and malignant mesothelioma. Pathology 1995; 27; 1– 4. 5 Brenner J, Sordillo PR, Magill GB. An unusual presentation of malignant mesothelioma: the incidental finding of tumour in the hernia sac during herniorrhaphy. J. Surg. Oncol. 1981; 18; 159– 161. 6 Whitaker D, Henderson DW, Shilkin KB. The concept of mesothelioma in situ: implications for diagnosis and histogenesis. Sem. Diag. Pathol. 1992; 9; 151– 161. Citing Literature Volume29, Issue3September 1996Pages 282-284 ReferencesRelatedInformation

Allelotypic detection of loss of heterozygosity (LOH) has been used to identify putative tumour-suppressor genes. Loci on human chromosome 11q23 are frequently altered in malignant disease, and LOH has been reported at an anonymous D11S29 locus at 11q23 in a proportion of breast and ovarian cancers and malignant melanomas. Previous studies have reported a high frequency of LOH in cervical carcinoma mapping to 11q23. Using polymerase chain reaction techniques employing probes for a recently described polymorphic dinucleotide microsatellite within this locus, we have searched for LOH in 69 cases of invasive cervical carcinoma. Genomic material was microdissected from sections cut from archival paraffin-embedded material, using the patients' constitutional genotype as a control Sixty-two (90%) of the cases were informative, and LOH occurred in 25/62 (40%) of tumours. Loss of an arm or single chromosome 11 is a well-recognised event in cervical carcinoma, and by employing other microsatellite polymorphisms mapping to 11q13 and 11p11-p12 we excluded those cases with widespread allelic loss. By doing so, LOH at D11S29 was found in 16/53 (30%) of tumours. The findings suggest a putative tumour-suppressor gene on 11q involved in cervical carcinogenesis.

Previous workers have used counts of colloidal silver-stained nucleolar organizer regions (AgNORs) to help distinguish reactive from malignant mesothelial processes. We sought to compare the demanding technique of AgNOR counting with the identification of proliferating cell nuclear antigen (PCNA) in 10 pleural malignant mesotheliomas and 11 reactive mesothelial proliferations. The mean AgNOR count was significantly higher in malignant compared to reactive lesions (5.10 [95% confidence interval, CI 4.35-5.84] vs 3.68 [95% CI 3.17-4.19], p = 0.004), as was the PCNA index (26.9 [95% CI 17.37-36.49] vs 9.67 [95% CI 4.94-14.39], p = 0.004). Less overlap was seen with PCNA indices and no reactive mesothelial proliferations had a PCNA index greater than 20%, suggesting that scores over this level may be a specific indicator of malignancy in this setting. There was only a weak correlation between the 2 proliferation indices suggesting that PCNA and AgNORs are present at somewhat different times of the cell cycle and/or persist in the post-S phase cell for variable lengths of time.