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JFP/Nov/Dec 1974 • Vol. 1, Nos. 3/4 fteAnra Ppnclo Smear Papanicolaou Abnormal the of New Concepts in the Evaluation Evaluation the in Concepts New ihl o, .. Dae . oned MD, hlp . iaa MD, n C Pu Mro, M.D. Morrow, Paul C. and M.D., DiSaia, J. Philip M.D., Townsend, E. Duane M.D., Roy, Michel o Agls California Angeles, Los nee, aiona 90033. California Angeles, ee Cut-nvriy f oten aiona eia Center, Medical California Southern of County-University geles is n Cnclg-eto o Gnclgc nooy Ls An Los Oncology, Gynecologic Obstet of of Department Cynecology-Section Townsend, and E. rics Duane Dr. Los to addressed Hospital, Women's Center, Medical California Southern nee, aiona Rqet fr erns hud be should reprints for Requests California. Angeles, yeooi Oclg, o Agls onyUiest of County-University Angeles Los Oncology, Gynecologic n boml evcl yooy “Pp ma”) smear” Pap (“ cytology cervical abnormal An rm h Dprmn o Oserc ad yeooyScin of Gynecology-Section and Obstetrics of Department the From oe' Hsia, om 0 L 14 Nrh iso Ra, Los Road, Mission North 1240 L, 903 Room Hospital, Women's W to used be can investigation of can forms Two cervical cer. of suspicion arouse always should absence of invasive cancer. Fortunately, the overwhelming overwhelming the Fortunately, cancer. invasive of absence h Shle’ ett ofr a anra cervical abnormal an confirm to test Schiller’s the to and abnormality of degree the determine naie acnm bt rte, n nreihla fr of form intraepithelial an rather, but, have not do carcinoma test Pap abnormal invasive an with patients of majority worse, or or presence the III) establish to is (Class obligation dysplasia important of most his suggestive smear") Pap (“ iey mlyd oiain f h cri, fol cervix, the of conization employed the widely is method first The cancer. invasive exclude oigpnhbos ftennsann areasfrom non-staining ofthe biopsy punch lowing henever a physician is confronted with a patient who who patient a with confronted is physician a henever has an abnormal Papanicolaou stained cervical smear smear cervical stained Papanicolaou abnormal an has
f oe ipy Clocp, hn available, is when Colposcopy, biopsy. cone of diagnosis, accurate an provide will examination punch colposcopically-directed and colposcopy f ptet ih n boml a smear. Pap abnormal an with patient a of Women's Hospital, Los Angeles County-University County-University Angeles Los Hospital, Women's becoming the method of choice in the evaluation the in choice of method the becoming colposcopic a cases, the of 95 Inpercent biopsy. method conservative more is second, The lesion. and will avoid hospitalization and the complicationstheand hospitalization avoid will and will be presented. It is particularly appropriate to review tothe appropriate particularly is It presented. be will is ab cytology cervical whose individual the of evaluation only but yearly, evaluated patients are 1,000 smears Pap almost Center, abnormal Medical with California Southern tion in which dysplasia and carcinoma-in-situ are surprisingare popula carcinoma-in-situ and younger a to dysplasia which in extended tion being is test Pap the cause unhurried and careful, systematic, a in low phy the This encourage conduct cancer. should to carcinoma cervical sician invasive of invasive have cidence percent five y rvln ad naie acnm i rare. is carcinoma invasive and prevalent ly timebe this at cytology cervical abnormal colposcopy the of without problem and with Evaluation test. Pap normal normal. carcinoma-in-situ.1 or dysplasia i.e., neoplasia, malignant
This article updates the approach to the patient withab patient the to approach the updates article This At
of Pathophysiology be due to regeneration following inflammation, obstetrical of the Uterine Cervix injury, or some type of therapeutic procedure on the cervix, such as freezing, electrocauterization or biopsy. However, A review of the pathophysiology of the cervical epitheli on occasion the most minimal epithelial changes on um is helpful to understand properly the origin and signifi cytology will be associated with invasive cancer. In addi cance of an abnormal Pap smear. It has been believed for tion, patients can have cellular aberrations suggestive of in overacentury that the junction between the squamous and vasive cancer, but due entirely to an intense inflammatory columnar epithelium of the normal cervix is at the external change. The best way to an accurate diagnosis and proper : os. Studies by Pixley and Coppleson,2 Stafl,3 and others, to management of a patient with an abnormal Pap test is a gether with daily experience in our colposcopy clinic, con thoughtful diagnostic evaluation scheme, methodically ap tradict this concept. In the majority of patients during the plied in every case. reproductive years, the squamocolumnar junction is found on the ectocervix. The presence of columnar epithelium on Standard Evaluation Scheme theectocervix is embryologically determined; it does not ar rive there by eversion, nor does it grow out onto the cervix. The first step in the evaluation of the patient with the ab Pixley7s exhaustive studies on female fetuses and adoles normal cervical cytology is to repeat the Pap test. This cents have shown that over 70 percent have columnar tis should not be performed sooner than four weeks after the sue laid down on the ectocervix during intrauterine life. original cervical sampling because the false-negative rate is Under hormonal influence and the acid secretions of the higher if taken sooner. The cervix is cleaned of mucus with vagina, this columnar epithelium is transformed into squa a soft cotton ball prior to sampling. This must be a gentle mous epithelium through a process referred to as meta wipe; vigorous rubbing causes bleeding which may obscure plasia. The transformation of columnar into squamous epi the presence of dysplastic cells. Once the cervix has been thelium occurs throughout an individual's life, but is most well exposed, a careful inspection should disclose the junc active during adolescence and first pregnancy. It is an or tion between the smooth, pink, squamous epithelium and a derly process occurring both as a peripheral ingrowth from redder, often granular appearing, columnar epithelium. This the original squamous epithelium towards the endocervical is the squamocolumnar junction (SCj) and it is the area of canal, as well as focal or patchy transformation within the the cervix where nearly all neoplastic lesions arise because ectocervical columnar epithelium itself. Initially, the meta of the presence of immature tissue susceptible to carcino plastic squamous epithelium is composed of very immature gens. The SCJ and one centimeter on each side should be cells, which gradually develop the features of mature firmly scraped using a spatula with two complete passes squamous epithelium. It is postulated that these immature over the entire area. An additional sample from the endo metaplastic squamous cells are particularly susceptible to cervical canal should be taken either with a saline- genetic injury by environmental carcinogens. The earliest moistened cotton tip applicator or an endocervical aspira recognizable microscopic change that occurs in the neo tor. The two samples can be mixed on a single slide but one plastic squamous epithelium is a nuclear anaplasia confined slide for each sample is also satisfactory. In order to prevent to the epithelium. This is referred to as dysplasia. It is im drying of the cervical scrape specimen, the endocervical portant to detect and eradicate these intraepithelial malig canal sample is taken first. In cases where the SCJ appears to nant lesions, since some of them will progress to invasive be at the external cervical os or within the canal, it is im cancer. 4-5 perative that the Pap test be taken from the endocervical The most reliable and economical means to detect prein- canal. Cytology specimens obtained from the vaginal pool vasive neoplasia of the cervix is by exfolliative cytology. are frequently inadequate since they have a false-negative However, the Pap test is only a screening test and not a rate as high as 50 percent for cervical neoplasia.7 diagnostic tool. It has a false-negative rate of 10-30 per- After the Pap smear is obtained, the cervix is thoroughly JFP/Nov/Dec 1974 * Vol. 1, Nos. 3/4 cent.6 One must never undertake treatment guided solely cleansed with saline or three percent acetic acid. The cervix dy the abnormal Pap test. Abnormal cervical cytology can is carefully inspected with a strong light and any grossly sus- 11 12 ferred for management to a specialist in gynecologic cancer. gynecologic in specialist a to management for ferred 12 JFP/Nov/Dec 1 974 • Vol. 1, Nos. 3/4 or ECC show invasive cancer, conization of the cervix is un is cervix the of conization cancer, invasive show ECC or eesr ad otaniae. h ptet hud e re- be should patient The contraindicated. and biopsies the If necessary ECC. the and biopsies cervical the cytology, h canal. the Figure 1. Following positive ECC, with lesion extending high in Figure 2. Following negative ECC for lesion on the ectocem the on lesion for ECC negative Following 2. Figure in high extending lesion with ECC, positive Following 1. Figure h tn to fu n egt 'lc pstost sml the sample to positions o'clock eight and four two, ten, the glycogen- brown, Normal deep does or a yellow cervix. rather is stains tissue squamous the epithelium neoplastic whereas to squamous containing (Lugol's) iodine percent two a solution applying by performed is test Schiller's oee, o hruhy ape l idn ngtv areas. negative iodine important, all is It sample neoplasia. thoroughly to cervical of however, location likely most random quadrant four If cervix. anterior the the of on lips predominantly posterior found and is neoplasia Cervical a areas, suspicious no are there If biopsied. are areas picious punch biopsies are to be performed they should be taken at taken be should they performed be to are biopsies punch discarded. be should positions o'clock nine twelve, and the at six biopsies three, punch random of concept The areas. nor epithelium columnar normal neither tissue, squamous debris is placed on a paper towel, molded into a small small a into molded towel, paper a on placed is debris re be should stain not glyco do that areas all sufficient of stains contain location not The do process) gen. also they since transformation iodine, the in with epithelium columnar neoplastic invasive and neo for preinvasive to non-specific is test addition In Schiller's plasia. The all. at stain not strument for this procedure. All blood, mucus, and tissue tissue and mucus, blood, in All recommended procedure. the is this for curette strument endocervical Kevorkian vigor aA is of curettage The presence canal. the the out in rule to epithelium (ECC) abnormal curettage canal cervical reference. future for corded replaces that tissue (the epithelium metaplastic immature on ad lcd n fixative. a in placed and mound os. external the to internal the from canal the of scrape ous endo- an have should pregnant, are who those except tient, The next step depends on the results of the repeat repeat the of results the on depends step next The Cervical biopsies are then taken from all Schiller positive positive Schiller all from taken then are biopsies Cervical ne h idn sann hs en are ot eey pa every out, carried been has staining iodine the Once acnm o te evx a be poel excluded. properly been has cervix— the of carcinoma in s are ot n he mnh. h pyiin and the physician The months. three in out carried is tion iu ies sgetd yteanra Pp et invasive test— Pap abnormal the by mostthe suggested that sedisease knowledge rious the in comfort take can patient h cnl hw o epatc pteim a eet evalua repeat a epithelium, curettage neoplastic the no and show (figure biopsies canal the cervical ectocervix the cytology, on repeat areas the negative iodine with ounr ucin nt te oo ad oorpy of topography and color the note junction, columnar cal tissue, but only the distal portion ("shallow cone") along cone") ("shallow portion distal the only but tissue, cal opsoe rvds i i psil t lct te squamo- the locate to possible is it magnification the provides, With colposcope colposcope. the through evx fgr 1. f h edcria crtig show curettings ofthe biopsy'' endocervical the "cone If so-called 1). the (figure cervix, cervix the of areas tnad vlain cee xet ht i addition in that, except scheme evaluation standard epatc ise t s o ncsay o xie l endocervi all excise to necessary not is it tissue neoplastic h bose ngtv, h ptet hud ae n excision an have should patient the abnormal is negative, but cytology biopsies repeat the the if or carcinoma-in-situ, sn te ae ee te hsca eaie te cervix the examines physician the eye, naked the using h qaiy f h cria lso rsosbe o the ab for responsible lesion cervical andassess the locate of to able is quality the physician examining the scope, ipy f h edcria cnl n te oie negative iodine the and canal endocervical the of biopsy oml a test. Pap normal valuable, extraordinarily proven has colposcope the years ing the woman with an abnormal Pap smear. With acolpo With smear. Pap evaluat in abnormal but an with cancer, woman cervical the ing for women screening in not America North in attention little received it cancer, cervical f h bose o edcria crtae hw dysplasia show curettage endocervical or biopsies the If ainny y xolaie yooy Drn te past few the During cytology. cervical detecting exfolliative of by simplicity and malignancy efficacy the of Although because 40X. to ago to detectcentury 6X half a than from more Europe ranging in developed power magnifying a opsoi Evaluation Colposcopic h clocpc vlain s ital ietcl to identical virtually is evaluation colposcopic The h clocp i seocpcveig instrument with viewing steroscopic a is colposcope The t h a t the the t a h t ) If 2).
the the the no of or to
epithelial surfaces and study the vascular architecture. Major fetal and maternal complications are reported to oc nder colposcopy, normal squamous epithelium has a cur in 30-50 percent of cases coned during pregnancy, in shiny, pink, smooth surface through which the tiny hairpin cluding abortion, premature labor, premature delivery and vessels of the stroma are apparent. Normal columnar hemorrhage. With the aid of colposcopy, conization is rare epithelium appears like a collection of small grapes. The ly necessary.11 Because the cervix is physiologically most important area to evaluate colposcopically is the trans "everted" during pregnancy, the entire lesion is almost al formation zone, which is that portion of the columnar epi ways visible and easy to evaluate by colposcopy. Only in thelium which has been transformed by metaplasia to vasive carcinoma requires therapy during pregnancy and squamous epithelium. This is the region where dysplasia, only invasive carcinoma contraindicates vaginal delivery. carcinoma-in-situ, and invasive cancer of the cervix nearly always originate. The entire transformation zone must be Treatment thoroughly inspected. Dysplasia and carcinoma-in-situ in The management of the patient with a proven carcinoma- variably appear as white patches with sharp borders and in-situ or severe dysplasia of the cervix is becoming more minor alterations of the surface contour. In some cases the and more conservative. In the United States, hysterectomy bloodvessel pattern will be particularly prominent, and pat is the most common treatment but it is seldom necessary in terns referred to as mosaic and punctation are present. This the management of carcinoma-in-situ or dysplasia. In the is in contrast to the pattern of invasive squamous cell car Scandinavian countries and Australia, clinical trials have cinoma, which has a highly irregular surface contour and demonstrated that conization which removes the entire le heavy vessels. These abnormal surface vessels are responsi sion is a satisfactory treatment. Simple excision biopsy, elec ble for the invasive lesion bleeding easily on contact. trocautery, and cryosurgery are currently under investiga Once a lesion has been located by colposcopy, it is im tion in this country. Preliminary results are very encouraging portant to determine its extent. Its border on the ectocervix and these methods will probably become a major course of is usually quite easy to delineate and the margin closest to treatment of preinvasive carcinoma of the cervix. the external os can also be readily defined in most cases. The physician should fully discuss the management with These lesions can be adequately evaluated by the patient, stressing the effect of the treatment on her colposcopically-directed punch biopsies on an outpatient childbearing capacity. If future pregnancy is desired, the basis. Occasionally, a lesion will extend into the endocervi- most conservative approach should be taken and the pa cal canal. If the lesion extends high in the canal, beyond the tient followed up by cervical cytology and colposcopy view of the colposcopist, the examination is unsatisfactory. twice a year after treatment. If the patient does not wish to It is mandatory in such cases that cervical conization be per have more children, or has other benign gynecologic dis formed because the hidden part of the lesion may be inva ease, hysterectomy is a logical approach if she is otherwise a sive cancer. Fortunately, the need for diagnostic conization suitable candidate for major surgery. because the limit of the lesion cannot be seen occurs in no more than five to ten percent of patients with an abnormal Pap test. In more than 90 percent of the cases, the source of References the abnormal Pap test is adequately assessed by a colpo 1. Fidler HK, Boyes DH, Duersperg N, et al. The cytology program scopically directed biopsy of the worst lesion. In a study of in British Columbia "An evaluation in the effectiveness of cytology 1,410 cases in Wisconsin, Stafl 8 showed that when the col- in the diagnosis of cancer and its application to the detection of car poscopic examination is satisfactory (entire lesion seen), cinoma of the cervix." Can Med Assoc / 86:779, 1962. only 0.3 percent of the cases had a more advanced lesion 2. Coppleson M, Pixley E, Reid B. Colposcopy. Springfield, on conization or hysterectomy than the colposcopically di Charles C. Thomas, 1971. rected biopsy. No invasive cancer was missed by 3. Kolstad P, Stafl A. Atlas of Colposcopy. Baltimore, University coiposcopy. Park Press, 1972. 4. Ritchart RM, Barron BA. A follow-up study of patients with cer Although colposcopy affords excellent visualization of vical dysplasia. Am I Obstet Gynecol 705:386, 1968. the cervix and can provide a direct approach to localized 5. Koss L. Significance of dysplasia. Clin Obstet Gynecol 73:873, biopsies, the procedure requires considerable experience 1970. on the part of the colposcopist and a substantial outlay for 6. Coppleson M. The value of colposcopy in the detection of pre- the necessary equipment. For these reasons, consultation clinical carcinoma of the cervix. / Obstet Gynaecol Br Commonw with a specialist skilled in this procedure will usually be 67:11, 1960. indicated when family physicians desire to utilize this diag 7. Ritchart RM, Vaillant HW. Influence of cell collection tech nostic technique to follow up abnormal Pap smears. niques upon cytological diagnosis. Cancer 78: 1474, 1965. 8. Stafl A, Mattingly RF. Colposcopic diagnosis of cervical neo plasia. Obstet Gynecol 47:168, 1973. Pregnancy 9. Oritz R, Newton H. Colposcopy in the management of ab normal cervical smears in pregnancy. Am I Obstet Gynecol 709:46, During pregnancy cervical cytology is reported to have a 1971. Positive rate of 0.7 percent to 1.6 percent.9 Because of the 10. Villasanta V, DunKan JP. Indication of complications of cold low yield of invasive cancer and the high maternal and fetal
conization of the cervix. Obstet Gynecol 27:717, 1966. JFP/Nov/Dec 974 1 • Vol. 1, Nos. 3/4 morbidity related to conization in pregnancy,10 no patient 11. Daskal JL, Pitkin RM. Cone biopsy of the cervix during preg
:hould be managed without the benefit of colposcopy. nancy. Obstet Gynecol 32:1 , 1968. J j J 13