cy to pathology

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    CYTOPATHOLOGY

    Randanan BandasoBagian Patologi Anatomi FK Unhas.

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    DEFINITION

    Cytopathology refers to diagnostic techniques

    that are use to examine cells from variousbody sites to determine the cause or natureof disease

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    H I STORY 1

    IN THE MID -19 CENTURY INVESTIGATOR DETECTED ABNORMALCELLS IN BODY FLUIDS, SUCH USURINE,SPUTUM,EFFUSION AND GASTRICSECRETION1928 GEORGE PAPANICOLAOU IN THENEW YORK CITY PRESENTED PAPER:NEW CANCER DIAGNOSTICIN THE SAME YEAR AURELI BABES OFBUCHAREST INDEPENDENTLYREPORTED SIMILAR FINDING.

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    HISTORY 2

    PAPS TEST INITIALLY RECEIPTSKEPTICISM.NOWADAYS PAPS TEST HAS BEENWIDELY ACCEPTED AS THE MOST

    RELIABLE SCREENING TEST

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    CYTOL OGI CAL M ETH ODS

    EXFLOATIVE CYTOLOGY ABRASIVE CYTOLOGYFINE NEEDLE ASPIRATION CYTOLOGY

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    TO OBTAIN OPTIMAL RESULT

    In aspirating solid masses one need not to see material enteringthe syringe.Stopped aspiration as soon as blood appear in the hub of theneedle.If the lesion is cystic, the fluid aspirated into the syringe and sentto cytology laboratory for processingSometimes aspiration must be repeated several times.When aspirating large masses, it should be keep in mind thatthe center of tumor maybe necrotic the needle should beplaced in the periphery of the mass

    Europian cytopathologist prefer air dried Romanowsky stain. American favors alcohol fixed smear Papanicolaou or HE

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    ADVANTAGES OF CYTOPATH OLOGY

    Less trauma.No complication of anesthesia because does notneed general or local anesthesia.

    A large sampling surface is available.Tumor that are difficult to access by biopsy may besampled by cytological methods

    A rapid diagnosisGreater convenience

    Combining with biopsy Increased detection rate ofmalignancy

    A greater cost effectiveness

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    APL I CATI ON OF CYTOPATH OL OGY

    Screning for the early detection ofasymptomatic cancer.Diagnosis of Symptomatic Cancer.Surveillance of Patients Treated for cancer

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    SCREENI NG I N TH E EARLY DETECTI ONOF ASYM PH TOM ATI C CANCER

    The most important application of cytopathology cancerprevention is Paps Smear. Paps Smear Reduction of Cervical Cancer in the USA andother country.The rate of decline varies from one country to another Depending on the proportion of the Population Screened.Bladder, lung and endometrium cytopathology is useful in thedetection of cancer in the early stagesEconomic Consideration preclude mass screening

    Specific population in high risk:Uranium mine workers Lung cancerUlcerative colitis Ca ColonIn China Oesophageal cancer Cytological screening.

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    ADVANTAGES OF CYTOPATH OLOGY

    1. LESS TRAUMAFewer complication hemorrhage orperforation.FNA of Pleura open biopsy or largeneedle biopsy.Brushing the surface of endobronchial tumor orcolonic lesion biopsy.Hemorhage,infection or tumor spread is negligible.

    Complication of anesthesia are no concern because usually does require general or localanesthesia.

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    ADVANTAGES OF CYTOPATH OLOGY

    2. A Larger sampling surface is availableEndoscopic proceduresPeritoneal Washings

    3. Tumor that are difficult to acces by biopsy may be

    sampled by cytological methods.4. A rapid diagnosis5. Greater Convinience6. An increased detection rate of malignancy in

    endoscopic procedure is achieved bycombining cytological sampling with biopsy.

    7. A greater cost effectiviness

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    L I M I TATI ON OF CYTOPATH OL OGY

    Clasification of the typhe of tumor is more difficult.The pattern of tumor infiltration and invasion to vasculer cannot be evaluated.The small size of the specimen may preclude accurateclasification of some neoplasm with mixed elements adenosquameus carcinoma, carcinosarcoma.The extent and depth invasion cannot be assessed In situcarcinoma and invasive carcinoma.microinvasive deeply invasive cervical Paps Smear. Intraductal carcinoma Invasive Ductal Carcinoma of the

    breast in FNA.in situ carcinoma invasive transitional carcinoma incytological examination of urine.

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    ACCURACY OF CYTOLOGI CALMETHODS.

    The accuracy cytological diagnosis depends on:The experience of the collector of the specimen.The target organThe expertise of the examinerFalse positif are rarely made by experiencedcytopathology Specificity 100%.Sensitivity 80-90 % depends on specimenCerebrospinal fluid 30% of primary and 50%of metastastatic cancer.Low grade transtitional carcinoma little or no atypia

    difficult to detect High grade neoplasms diagnosedcorectly

    The existence of false negative result the abcense ofmalignancy does not completely rule out.

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    CAUSES OF ERROR I N CYTOL OGY

    INADEQUATE SAMPLINGPOOR FIXATION OF THE SMEARS ORINADEQUATE PRESERVATION OF FLUID.SUBOPTIMAL LABORATORYPREPARATION AND STAINING.

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    POOR FI XATI ON OF TH E SM EAR ORI NADEQUATE PRESERVATI ON OF A F L UI D

    Pap Smear ethanol 95% or spray fixativeimmediately. A few scond of delay can cause airdrying artefact difficulty in interpretation.Cell in body fluid undergo degeneration.

    Rate of degeneration Depends on the body fluid.Pleural effusion long.Urine and cerebrospinal fluid Rapid.

    To prevent:Fluid must be transported and processed rapidly.

    A preservative should be used.Ethanol 50% an equal volume is good.Refrigeration slow degeneration and bacterialgrowth.

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    SUBOPTI M AL L ABORATORYPREPARATI ON AND STAI NI NG

    Diffulty in the interpretation.Examples:

    Inadequate cell concentration

    Poor adhesion to glass slideThicks smearOverstaining

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    I NADEQUATE SAM PL I NG

    Paps Smear should contain endocervicalcellsSputum should contain pulmonary

    macrophage.Peritoneal washing should contain mesothelial cells

    Smear of cutaneous vesicle squameus cellGastric brushing epithelial cell

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    M ORPH OL OGI CAL PARAM ETERS USEDI N CYTOL OGI CAL EVAL UATI ON

    CELLULARITY OF THE SPECIMENCELL ARRANGEMENTCELL SIZE AND SHAPECYTOPLASMNUCLEUSMITOSIS

    EXTRACELLULAR MATERIAL ANDCELLULAR BAKGROUND

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    CELLULARITY OF THE SPECIMEN (1)

    Factor influence the cellularity:Sampling method brushing or washingDevice Spatula or cytobrushExpertise of the the physicianTyphe of tissue being sampledEpithelial cell easier than stromal cellMalignant cells lower cohesiveness than benigncells amount of conective tissue Low CTeasier than more CT Lymphoma Scirrhous carcinoma

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    CEL L ARRANGEM ENT(1)

    The tissue pattern is lostThe relation between cells is a helpfulcriterion for cytological diagnosis

    Cells may appear:SinglySmall groupsIn monolayer sheet

    Three dimensional clusterSeveral cells fuse forming largemultinuceleated cells syncytium

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    CELL ARRANGEMENT(2)

    Cells cluster may form:Papillary configuration : papillarytransitional cell carcinoma, papillary

    adenocarcinoma, malignantmesothelioma.Glandular or tubular structure : AdenocarcinomaFollicles : Follicular adenomaRosettes: NeuroblastomaPearls :Squameus cell Carcinoma

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    CELLS SIZE AND SHAPE(1)

    The size of tumor cells varies greatly depending onthe typhe of neoplasmSmall regular cells:

    Small carcinoma of lungsSome typhe of lymphomaMany typhe of childhood tumor

    Large cells:Squameus cell carcinomaGiant cell carcinomaPleiomorphic sarcomaChoriocarcinoma

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    CYTOPLASM(1)

    Evaluated in :color,texture,presence of inclusions,vacuoles, pigments and other cell

    product.Papanicolaou Methods pink to bluekeratin orange color.

    Pigments : melanin,hemosiderin,bile,lipofuscin, carbon particles helpful inidentifying cell typhe.

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    CYTOPLASM(2)

    Single or multiple vacuoles degenerativechanges, secretory activity or phagocytosisViral and chlamydial infection inclusion in

    cytoplasmSquameus cells infected by HPV Koilocyticatyphia

    Reactive or neoplasma of plasma cells eosinophylic globule Russel body

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    NUCLEUS(1)

    Important parameter:Size and shape of the nucleus

    Alterations of nuclear membrane and

    chromatin.Prominent of nucleolusNuclei of normal cells little variation in sizeand shape.

    Modest enlargement normal cell during Sphase, reactive or regenerating cells

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    NUCLEUS(2)

    Malignant cells significant nuclear enlargement increased nuclear to cytoplasmic ratio.Significant variations in nuclear size and shape anisokaryosis.Irregular contour with protrusions, identitations and groovesMolding of the nuclei against one another seen sometumors clasically in small cell carcinoma

    The nuclei of cancer cells are usually darker hyperchromatic,Chromatin coarser and unevenly distributed

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    MITOSIS

    Mitotic activity can occur in both benign andmalignant cells.Cancer cells in general have a higher rate ofmitosis.The presence of abnormal mitosis:

    abnormal distribution of chromosonesmore than two mitotic poles

    reliable criterion for the diagnosis ofmalignancy

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    EXTRACEL L UL AR M ATERI AL ANDCEL L UL AR BACKGROUND(1)

    The back ground of the smear is evaluatedfor the presence of :

    InflammationBloodVarious extracellular substances

    Cell productsnecrotic debriesmicroorganisms

    Type of inflamation(acute,chronic,granulomatous ) and somevarities of microba can be identified

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    EXTRACEL L UL AR M ATERI AL ANDCEL L UL AR BACKGROUND(2)

    Cell necrosis may occur in benign conditions infection, trauma, ischemia and irradiation.In the absence of recognizible intact cells adefinitive diagnosis cannot be madeWhen presence with malignant cells necrosis isgenerally an indication of invasive cancer.Carcinoma in situ of cervix no necrosis invasivecarcinoma necrosisThe criterion of necrosis cannot be generalized.Carcinoma in situ of the breast may contain foci ofnecrosis Comedocarcinoma.

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    REPORTING SYSTEMS

    VARIOUS METHODS HAVE BEEN USED.PAPANICOLAOU:

    Class I : Absence of abnormal cells

    Class V: Conclusive Evidence of Cancer1988: A group of Pathologist and

    Gynaecologist met in Bethesda, MarylandUSA The Bethesda System1991: Revised the original classification

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    TH E BETH ESDA SYSTEM (1)

    Each cytology report should include thefollowing elements:

    A statement regarding the adequacy of

    the specimen. A general categorization of of the

    diagnosis ( as within normal limits,

    benign cellular changes or epithelialcell abnormality

    A descriptive diagnosis

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    THE BETHESDA SYSTEM(2)

    The elements must be presents to deem a cervical smearsatisfactory for evaluation:

    1.Technical intrepretability (optimal smearing, properfixation, lack of exessive blood or inflamation)

    2.Adequate samping of the transformation zone(presence of ectocervical cells and endocervical cells)

    The Bethesda System Introduced a new clasification for cervicalprecancerous lesion:

    1.Low Grade squamous intraepithelial lesion (HPVinfection and mild dysplasia).

    2.High Grade squameous intraepithelial lesion ( Moderatedysplasia, severe dysplasia, carcinoma in situ).

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