Doctors' Newsletter - Douglass Hanly Moir Pathology

Doctors’ NewsletterSummerPage 2EditorialOur Commitmentto Women's HealthDr Colin GoldschmidtPages 3-4Liquid Based Cytologyin Australia - Why not?Dr Annabelle FarnsworthPages 5-6EndometriosisDr Debra JensenPage 7Biochemical Assessmentof Feto-Maternal Wellbeingin Early PregnancyDr Michael J SinosichPage 8Latest NewsHuman Papilloma Virus TestingHIV Antibody/Antigen Testing

EditorialOur Commitmentto Women's HealthDr Colin GoldschmidtChief Executive OfficerWelcome to the Summer edition of the Doctors’ Newsletter.Our theme for this last issue of 2005 is women’s health.Cervical screening in Australia is one of the great publichealth success stories. Since the introduction of thenational screening program in 1991, cervical cancer hasshown a gratifying fall in incidence and mortality. Effortsare now focusing on ways to lower this further, and ourfirst article, by Dr Annabelle Farnsworth, concerns currentand future developments in this area. As she will explain,Douglass Hanly Moir Pathology, in conjunction with theUniversity of Sydney School of Public Health, is embarkingon an exciting and major study of new technology and itsrelevance to Australian women.Dr Annabelle Farnsworth is well known throughout Australiaand internationally for her contribution to gynaecologicalcytology. In the field of cervical cytology, it is widelyrecognised that laboratory quality is critical to ensuringoptimal outcomes, and Annabelle’s contribution in this areahas been outstanding. Indeed, as you may recall, in thelast issue of this Newsletter I spoke to you on the subjectof Quality Control, an activity which is at the heart of ourpractice. Quality assurance in cervical cytology is one ofAnnabelle’s major interests, as well as the broader areasof population screening programs and women’s health.She has published numerous research papers and is coauthorof a respected textbook on ovarian pathology. Weare therefore very fortunate to have her as our Director ofCytology. In addition, Annabelle was appointed in January2000 as Medical Director of Douglass Hanly Moir Pathology.As we have always been a practice that is managed bydoctors, for doctors, this is an extremely important role.Dr Debra Jensen’s article on endometriosis, also inthis issue, is an overview of a common gynaecologicalcondition accounting for considerable morbidity in thefemale population. Debra herself also has wide expertiseand international experience in the area of gynaecologicalpathology, and is a past Director of Pathology at the RoyalHospital for Women in Paddington.Many of our histopathologists have had extensiveexperience in women’s health, and a substantial number areFellows of the International Academy of Cytology. We haveevery reason to pride ourselves on our expertise and ourcontinuing contribution to this important area, and warmlyinvite you to make use of this body of knowledge at anytime, as our pathologists are always happy to receive yourqueries or comments.Finally, it remains for me to wish you and your families asafe and peaceful festive season. The staff of DouglassHanly Moir Pathology and Barratt and Smith Pathology joinme in these wishes, and in thanking you for your ongoingsupport.With my best wishes,Dr Colin GoldschmidtM.B.B.Ch., F.R.C.P.A., F.A.I.C.D.Chief Executive OfficerDouglass Hanly Moir PathologyBarratt & Smith Pathology2

Liquid Based Cytology in Australia? Why not?Dr Annabelle FarnsworthMedical Director/Director of CytologyDouglass Hanly Moir Pathology has offered the ThinPrepPap test, which employs liquid based cytology (LBC),for over eight years. In Australia, ThinPrep testing is stillperformed as a supplementary test to the conventionalPap smear, and there is as yet no Medicare reimbursementfor the test. Australia remains the only country where LBCis offered as a non-government funded adjunct to theconventional Pap smear. In the USA and the UK, LBC isnow the standard method for cervical screening using thedirect-to-vial method.The commonly asked question is: “Why doesn’t Australiaalso adopt this as the screening test for cervical cancer?”The improvements in detection of abnormalities using LBCshown in overseas studies (1,3) have been assessed asinsufficient in the Australian setting to justify the increasedcost of the method (2). It must be remembered thatAustralia has a very effective, well-organised CervicalScreening Program with a significant reduction in incidenceand mortality from cervical cancer possibly due to theimprovements in quality of screening and management ofscreen-detected abnormalities by the program (4).The clear monolayer of cells prepared using LBC is notonly easier for the human eye to read, but is also easier forcomputerised assessment. The company that supplies theThinPrep technology has recently introduced an advancedsystem which performs computerised imaging analysis ofthe slide. Because a conventional Pap smear contains, onaverage, more than 100,000 cells, and abnormal cells maybe present in very low numbers, the potential for screeningerror is ever-present. The advent of the ThinPrep ImagingSystem may provide a solution to this problem.Douglass Hanly Moir Pathology was the first pathologypractice in Australia to install this exciting new technology,and we have now reported ThinPrep samples, using theimaging system, for more than 12 months. We decided touse this opportunity to set up a formal trial to assess thistechnology, and to design the trial in such a way that wewould avoid many of the criticisms of other assessments.In conjunction with the University of Sydney School ofPublic Health, we have developed a formal protocol toassess samples from more than 50,000 patients. This willbe an important study and will be the largest in the world todate. Such a large number is vital for appropriate statisticalassessment. As an initial step, however, we have examineda pilot sample of 4,400 patients to ensure the efficacy ofthis new technology in the Australian setting. We report thedetails of this initial study below.Image Analyzer Initial AssessmentThe results from reading the conventional smear werecompared to the reading of the ThinPrep sample usingconventional light microscopy (TPM) and comparedto the ThinPrep sample read using the image analysissystem (TPI). From each patient the samples were readentirely independently, using each of these three differenttechniques. The most severe abnormality was reportedto the referring practitioner but the information on alltechniques was recorded for analysis. Histology resultswere obtained from the NSW Pap test register (PTR).The relative true positive rate i.e. the probability of detectinga true (histological) positive by one type of cytologycompared with another, using the cytology threshold ofpossible HSIL, was calculated. The relative true negativei.e. the probability of detecting a true (histological) negativeby one type of cytology compared with another, using thethreshold of possible HSIL, was calculated.Interpretation of the results must be circumspect as thenumbers are small, however, they are in line with otherwork in this area. The relative True Positive Rate for TPIcompared to TPM was the same i.e. the results from theimager read sample (TPI) were equivalent to manual readThinPrep sample (TPM) in detection of true High gradelesions but TPI was slightly better at finding true negativesi.e. there were less false positives.3

Liquid Based Cytology in Australia? Why not?This is very pleasing, in that we were able to continuewith confidence to use the Image Analyzer rather than themanual method to read ThinPrep samples, for ourlarge study.The 55,000 cases have been collected now and we areawaiting the histology results from the PTR. Detailedanalysis will be undertaken of all abnormalities, Lowand High Grade, and we are hoping the results will beavailable in 2006. Our results may mean that direct-to-vialThinPrep with Image analysis may be considered to replaceconventional cytology.It also has the advantage that it can be used for adjunctivetesting Chlamydia and HPV. The data from our large studyshould be available in the middle of next year and we will letyou know the results.1. Hutchinson ML, Zahniser DJ et al; Utility of Liquid Based Cytologyfor Cervical Carcinoma Screening; Results of a population-based studyconducted in a region of Costa Rica; Cancer 87:48-552. MSAC Medical Services Advisory Committee; Evaluation of NewTechnologies in Cervical Screening; http.www.msac.com.au3. Scottish Cervical Screening Program; Steering Group Report on thefeasibility of Introducing Liquid Based Cytology;Jan2002;http//www.show.scot.nhs4. Farnsworth A & Mitchell HS; Prevention of Cervical Cancer;MJA 2003:653-654The Thin Prep Image AnalyzerThe sample is pre-screened by the Image Analyzer, and 22 fields of cells of interest are recorded in the data base. Thisinformation is then used to drive an automatic microscope where these fields are presented to a cytologist. If the scientistconsiders each of these normal, the sample is called negative. If they are abnormal the whole sample is manually re-screenedand assessed by a more senior scientist and/or Pathologist.If you have any enquiries, please do not hesitate to contact Dr Annabelle Farnsworth on (02) 98 555 1804

EndometriosisDr Debra JensenHistopathologistEndometriosis can be defined as the presence of ectopicendometrial tissue, including glands and stroma, whichtends to be hormonally responsive.Clinical findingsEndometriosis is found almost exclusively in women ofreproductive age. The incidence is difficult to quantify butis about 5-10% of women in the reproductive years and isfound in 25-30% of women who are infertile.The metaplasia hypothesis suggests that peritoneum ispluripotential and metaplases into functioning endometriumwith glands and stroma, possibly under hormonalstimulation. There is little evidence to support thishypothesis. Haematogenous or lymphatic spread have beenproposed to account for the rare occurrences of pulmonaryendometriosis and lymph node endometriosis.Clinical presentation varies greatly, the commonest beingpelvic pain that occurs premenstrually and decreases oncethe menses begin. Dyspareunia, pelvic pain and infertilityare common, and rarer presentation includes constipation,diarrhoea, haematuria and pelvic pressure.Only a few patients have all four of the major symptomsdescribed above. Correlation with severity of the symptomsand extent and severity of the disease at laparoscopy ispoor and many women are asymptomatic.PathogenesisThe pathogenesis is probably multifactorial and hypothesesinclude implantation, embryonic nests (Mullerianosis), andmetaplasia of pelvic and peritoneal serosa.Implantation accounts for most of the endometriosis.It is thought that retrograde menstruation occurs withsubsequent implantation in ovaries, fallopian tubes andthe pouch of Douglas. Implantation also accounts forendometriosis found in scars, such as caesarean sectionscars and in the cervix following cone biopsies.Embryonic rests may account for endometriotic foci aswell as endosalpingiosis (ectopic tubal type epithelium) andendocervicosis (ectopic endocervical epithelium).Section through ovary demonstating several irregularareas of endometriosis.Sites of endometriosisThe common sites include ovary, fallopian tube, broadligament, pouch of Douglas and pelvic peritoneum. Lesscommon sites include abdominal wall scars followingcaesarian sections and other operations, and the cervixfollowing cone biopsies and LLETZ procedures.Aetiology of endometriosisGenetic influences are seen in the development ofendometriosis. Seven per cent of endometriosis patients’first degree relatives have endometriosis, while the controlrate is one per cent. In addition, the women with firstdegree relatives suffering from endometriosis tend to havemore severe and widespread disease. Research is findingsubtle differences in the immune systems of endometrioticpatients, suggesting a role in pathogenesis. High levels ofunopposed oestrogen predispose to endometriosis.5

EndometriosisMacroscopic featuresAppearances of endometriotic lesions vary with size, ageand depth of deposits. The earliest lesions are red and aremicroscopic. With time, the lesions turn black or brown dueto old haemorrhage and accumulation of haemosiderin,while scarring makes some deposits appear white. Ovariandeposits vary in size from microscopic to large thick walledcystic masses with associated adhesions. These cystsmay present as ovarian masses and may be mistaken formalignant tumours, both radiologically and at the timeof surgery.MicroscopyThe findings are usually easily recognised with endometrialglands and stroma admixed. But, particularly in largerlesions, old haemorrhage may obliterate part of the cystlining and identifying endometrial glands and stroma is moredifficult. A common finding is prominent smooth musclehypertrophy in association with endometriosis.The mechanism by which endometriosis causes pain ispoorly understood. Although the pain is thought to becaused by oestrogen and progesterone stimulation duringthe menstrual cycle, endometriosis does not typically cyclein parallel with the endometrium.Intermittent bleeding occurs in deposits, stimulating fibrosiswith expansion of the implants. Pain is thought to beproduced by pressure, inflammation and adhesions andby proximity to nerves and larger structures. Despite this,there is a poor correlation between clinical symptoms andseverity of disease pathologically.Endometriosis and malignancyThere is a low risk of malignant change in endometriosisand this risk is approximately the same as with endometrialtumours occurring in the endometrial cavity. If tumours dooccur they are of endometrioid or clear cell type.Section of bowel showing endometriotic tissue.Section of cervix and endometriotic tissue.If you have any enquiries, please do not hesitate to contact Dr Debra Jensen on (02) 98 555 1576

Biochemical Assessment of Feto-MaternalWellbeing in Early PregnancyDr Michael J SinosichScientific Director - Prenatal TestingSonic Clinical InstitutePrenatal screening is applied to assess the chance thata fetus may be affected with aneuploidy, such as Down’ssyndrome, or morphological defect, such as open NeuralTube Defect. Screening is a combination of biochemicaland ultrasonographic investigations undertaken in the firsttrimester (10 weeks to 13 weeks 6 days) and/or secondtrimester (15 weeks to 17 weeks 6 days). Risk assessmentis based upon the difference observed in serum markerlevels between affected and unaffected pregnancies at thesame gestational age. The markers used are: Pregnancy-Associated Plasma Protein-A (PAPP-A), Free Beta subunitof human Chorionic Gonadotrophin (Fß-hCG), unconjugatedEstriol (uE3), and Alpha Fetoprotein (AFP), as shown inthe table.TableMaternal serum and sonographic screening strategiesand suggested gestational ages for testing.SCREEN MARKERS GESTATIONFirst TrimesterBiochemistry PAPP-A, FßhCG, uE3, AFP 10w 0d to 13w 6dIn addition to detection of autosomal fetal aneuploidy,prenatal screening may identify many other early pregnancyabnormalities including failed pregnancies, pregnanciesdestined to fail, pregnancies with multiple gestations andmolar pregnancies. Other abnormalities which may bedetected are related to placental physiology, which mayaffect fetal development later in gestation.Quantitation of placenta-derived proteins (PAPP-A, FßhCG)also may be applied to monitoring of compromisedearly pregnancies, particularly in cases with a history ofrecurrent spontaneous failure. In this situation, serial testingis recommended to assess marker kinetics. Negativedeviations from regression curves, established for singletonpregnancies with normal outcome, are indicative ofpoor pregnancy prognosis. Clearly, prenatal testing withbiochemical markers is not simply limited to screeningfor fetal abnormality. Optimised screening strategies(see table) provide a ready means of assessing fetomaternalwellbeing, potentially for the entire obstetricpopulation.Ultrasonography Nuchal translucency 11w 0d to 13w 6dSecond TrimesterBiochemistry FßhCG, uE3, AFP 15w 0d to 17w 6dUltrasonography Fetal anomaly scan 18w 0d to 19w 6dIntegrated TestFirst Trimester PAPP-A, Nuchal translucency 11w 0d to 13w 6dSecond Trimester FßhCG, uE3, AFP 15w 0d to 17w 6dFurther information on prenatal testing has appeared inpast Newsletters and in our publication on Prenatal Testing,available from the Marketing Department.Dr Michael J Sinosich (Scientific Director) would be pleasedto answer any queries you may have on this subject.If you have any enquiries at any time, please contact Dr Michael J Sinosich on (02) 98 555 3747

Latest NewsHuman Papilloma Virus TestingAs from Tuesday 1st November 2005, testing for HighRisk Human Papilloma Virus will be included in theMedicare Benefits Schedule. The benefit is restrictedhowever, to the particular clinical situation of a test of curefollowing treatment of High grade disease of the cervix– CIN 2, CIN 3 Invasive SCC, adenocarcinoma in-situ oradenocarcinoma.The test may be performed twice in a two year period andaccompanies the other follow-up modalities Pap smear andcolposcopy. If the woman has two such negative HPV testsand the other tests are also negative, rather than havingannual Pap smears (the current recommendation), she canreturn to the routine screening interval for her futurePap smears.The HPV test can be performed on the sample taken for aThinPrep pap test or using a special collection brush andvial which we can supply. To order the test, the normalDouglass Hanly Moir/Barratt & Smith Pathology requestform can be used, however, the appropriate clinical historyshould be included for our records.If you have any enquiries, please do not hesitateto contact Dr Annabelle Farnsworthon (02) 98 555 180HIV Antibody/Antigen TestingInclusion in Medicare Benefits ScheduleFrom November 1, 2005, a Medicare Item Number isapplicable to HIV Antibody/Antigen testing. As a result, andfor the first time, reimbursement for HIV testing is possiblethrough Medicare or by private billing. In order to claimMedicare Benefits for this test, full patient details MUST besupplied on the request form, as is the case for any otherpathology request.Coded patient details are no longer a legal requirement forHIV testing, as long as the patient consents.Douglass Hanly Moir/Barratt & Smith Pathology has aconfidentiality and privacy policy, which is strictly adheredto by all members of staff. This policy ensures that yourpatients' pathology details remain confidential.If for any reason HIV testing must be carried out usingcoded patient details, the coded request will attract a feeof $20.00.If you have any enquiries, please do not hesitateto contact Dr Ian Chambers or Dr Miriam Paulon (02) 98 555 312Season's GreetingsThe Management and Staff ofDouglass Hanly Moir and Barratt & Smith Pathologyappreciate your support during the year.We wish you and your loved ones a safe and enjoyable Festive Season,with peace and happiness in the New Year.DOUGLASS HANLY MOIR PATHOLOGY • ABN 80 003 332 858A subsidiary of SONIC HEALTHCARE LIMITEDBARRATT & SMITH PATHOLOGYA trading name of DOUGLASS HANLY MOIR PATHOLOGY PTY LTD • ABN 80 003 332 858A subsidiary of SONIC HEALTHCARE LIMITEDwww.dhm.com.au95 EPPING ROAD • MACQUARIE PARK • NSW 2113 • AUSTRALIATEL 98 555 222 • FAX 9878 5077MAIL ADDRESS • LOCKED BAG 145 • NORTH RYDE • NSW 1670 • AUSTRALIA31 LAWSON STREET • PENRITH • NSW 2750 • AUSTRALIATEL 4734 6500 • FAX 4732 2503MAIL ADDRESS • PO BOX 443 • PENRITH • NSW 2751 • AUSTRALIAwww.bsp.com.au