,,,,, PATHOLOGY QUIZ PATHOLOGY Q U I Z

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1 ,,,,, PATHOLOGY Q U I Z,,,,, PATHOLOGY QUIZ CASE HISTORY Alex Ferenczy, MD, Professor of Pathology and Obstetries and Gynaecology, The Sir Mortimer B. Davis ]ewish General HosPital, McGill University This 25-year-old woman's last routine Pap. smear was reported "ASCUS, favour low grade SIL." She had previously three negative Pap. smears obtained at ages 18, 20 and 22, respeetively. She denied treatment for HPV infeetions of t~e lower genital traet, has been taking birth eontml pills for five years, had reeently switehed to an lud and had quit smoking at age 22. QUESTION #1 In this ease, the following management options are appropriate except one: 1. Repeat Pap. smear in six monthsj 2. Perform eolposeopy at oneej 3. Take sample for HPV DNA testing in three to six monthsj 4. Repeat Pap. smear in one year. QUESTION #2 The patient's HPV DNA test (hybrid eapture II HPV DNA assay) was positive for high-risk HPV types (16,18,31,33,35,39,45,51,52,56,58,59,68). What would you do next? (ehoose one): 1. ColposeopYj 2. Repeat HPV testingj 3. Repeat Pap. smear in six monthsj 4. Repeat Pap. and HPV test in 12 months. QUESTION #3 The rationale for HPV DNA testing in a patient with an ASCUS smear includes the following, except: 1. To identify over 90 pereent ofhigh grade SILsj 2. T 0 identify persistent/progressive type low-grade SILj 3. T 0 deerease the number of unneeessary eolposcopiesj 4. To localize lesional tissue. QUESTION #4 (FIGURE 1) Colposcopic examination of eervix eontains (ehoose one): 1. Acetowhite immature transformation zone and lud stringj 2. Acetowhite epithelium with indistinct marginsj 3. Gray-white epithelium with sharp, peeling margins and coarse punctationj 4. Congenital transformation zone. Residents in obstetrics and gynaecology as weh as practising physicians are invited to prepare case reports of clinical interest. The manuscripts should be prepared according to pathology quizzes published in the Journal SOGe, and must be illustrated with two to four high-quality photographs of grass specimens, histology and, if applicable, colposcopy and ultrasonography. Pathology quizzes should be sent to Alex Ferenczy, MD, for review prior to final editorial assistance and publication. JOURNALSOGC 1325 DECEMBER 1998

2 ,,, FIGURE 1 FIGURE 2 COLPOSCOPY OF CERVIX HISTOLOGY OF ENDOCERVICAL CURETTINGS QUESTION # Recolposcope the cervix and determine the position of the squamocolumnar junction in externaios; if fully visible, LEEP in the office using local anaesthesia; 2. Perform LEEP under general anaesthesia; 3. Hysterectomy with preservation of ovaries; 4. C old knife conization under general anaesthesia. Colposcopic patterns are consistent with (choose one): Immature squamous metaplasia; Low-grade SIL; High-grade SIL; Micro-invasive cancer. QUESTION #9 QUESTION # Colposcopic examination is (choose one): Satisfactory; Unsatisfactory; Cannot be established; lud string interferes with examination. The LEEP specimen contained high-grade SIL with gland involvement and positive endocervical margins. The next step should be (choose one): 1. Repeat electroconization in six weeks; 2. Repeat cytology and colposcopic examination in three months and manage the patient according to findings; 3. Total abdominal hysterectomy; 4. Refer patient to gynaecologic-oncologist. QUESTION #7 One should take the following investigational steps except (choose one): 1. Endocervical curettage prior to exocervical biopsy; 2. Multiple punch biopsies particularly focusing on the posterior lip of the cervix; 3. Colposcopic examination of the endocervical canal using an endocervical speculum; 4. Endocervical curettage after biopsy. QUESTION #10 The patient was recolposcoped at the fourth postleep month. Because of positive margins, the likelihood of residual disease in this case is (choose one): percent; 2. ~ 50 percent; 3. :::; 14 percent; 4. :::; five percent. QUESTION #8 (FIGURE 2) The endocervical curettage was reported positive, containing two tiny strips of neoplastic epithelium (SONE), and the biopsies contained high-grade SIL (CIN 3/carcinoma in situ) with gland involvement. What would be the ideal approach to managing this patient (choose one): JOURNALSOGC QUESTION #11 (FIGURE 3) The patient's cervix at four months after LEEP is shown in this colpophotograph. Ir contains the following except: 1326 DECEMBER1998

3 ,,, FIGURE 3 COLPOSCOPY OF CERVIX 3 MONTHS POST-LEEP 1. Squamocolumnar junction at os; 2. Residual CIN; 3. Native, mature portio-type epithelium; 4. Glycogen. ANSWER TO QUESTION #1 One should not wait one year to repeat a Pap. smear because the patient may be lost to follow-up or may already have either high-grade lesion or invasive disease. A Pap. smear is a screening test, not a diagnostic test; as a result, a positive Pap. smear may only indicate the least severe form of disease. ANSWER TO QUESTION #2 Several studies have shown that a repeat Pap. smear or HPV DNA test detects up to 75 percent ofhigh-grade SIL in ASCUS patients; the combination of cytology and HPV DNA testing (Super-Pap.) identifies over 90 percent of high-grade SILs in this particular population of women. Because of the high sensitivity of the Super-Pap., its negative predictive value is equally high, in the order of 97 to 98 percent, thereby eliminating a substantial number of unnecessary colposcopies. 2 ANSWER TO QUESTION #3 The rationale for performing HPV DNA testing for high-risk HPV types in patients with an ASCUS Pap. smear is to identify better those patients who, in fact, have coexistent high-grade SIL. This is observed in less than ten percent of ASCUS patients. Also, those who have low-grade but high-risk HPV types positive SIL are likely to have persistent/progressive type low-grade lesions. In one study, 29 percent of women with HPV 16 positive LGSILs progressed to high-grade SIL within a 36-month follow-up period. 1 An HPV test cannot localize the lesion, colposcopy can. ANSWER TO QUESTION #4 There are four important colposcopic patterns to evaluate; these are colour tone, margins, vessels and iodine-staining reaction. High-grade SILs are characterized by dul1 gray-white, oyster-white epithelium with sharp, often rol1ed and peeling margins, coarse punctation and/or mosaic type vessels and mustard-yellow iodine staining. The latter is due to lack of intracytoplasmic glycogen in high-grade SILs. Correct answer is: 3. ANSWER TO QUESTION #5 Correct answer is: High-grade SIL. ANSWER TO QUESTION #6 By definition, the squamocolumnar junction of the transformation zone (either normal or abnormal) must be ful1y visualized to consider a colposcopic examination satisfactory. Correct answer is: 2. ANSWER TO QUESTION #7 Endocervical curettage (ECC) should be performed before cervical biopsy to prevent dilution of the endocervical specimen by blood originating from the biopsy sites, and possible contamination of ECC by neoplastic epithelium wh ich has been disrupted by the punch biopsies. A thorough ECC and multiple rather than one "colposcope-oriented" biopsy provide nearly as much information as a cone biopsy. One must be thorough to avoid missing hidden invasive carcinoma. This is particularly important if the patient is to be managed by such ablative methods as cryosurgery or laser vaporization. ANSWER TO QUESTION #8 An ECC must be interpreted by the pathologist. If only one or two strips of neoplastic epithelium (SONE) JOURNAL SOGC 1327 DECEMBER 1998

4 ,,, ANSWER TO QUESTION #9 FIGUREI COLPOSCOPY OF CERVIX Neither endocervical gland involvement nor positive margins (with SIL) should influence management; in either ca se the patient is examined cytologically and by colposcopy in three to four months. Endocervical gland involvement does not mean invasion but rather extension of SIL along and within the basement membrane of the endocervical glands. This membrane is in direct continuity with that lining the squamous epithelium_ Similarly, positive surgical margins do not necessarily indicate failure of treatment and residual disease. On the other hand, it is likely that the repeat six-week LEEP specimen contains only repair-type epithelium making the repeat excisional procedure unnecessary. Transabdominal hysterectomy (TAH) is definitely not indicated at this time in the management scheme, particularly if the patient desires to preserve her reproductive functions. A gynaecologic-oncologist may not do anything differently from the colposcopist. Grey-white epithelium with peeling margins (near extern al os, posterior lip) and irregular punctation, typical of high-grade squamous intra-epitheliallesion. The lud string is visible. are seen by histology, they are most likely a reflection of contamination by an SIL located elose or at the external os (Figure 2). In such cases, it is important to stop endocervical curettage above the externalos, collect the material in the canal and remove the curette's jaw carefully, avoiding the possibility of scraping SIL inadvertently near the externalos. In case of a positive ECC but visible squamocolurnnar junction (SC]) (recorded in the patient's chart), the patient should be recolposcoped to verify previous findings, and if SC] is confirmed as fu11y visible, a relatively sha110w LEEP can be performed. If the pathologist reports numerous strips of squamous neoplastic epithelium, such reports usually correspond to a high-grade lesion extending deep into the endocervical canal. In this case, electroconization or cold knife conization should be tailored according to the presumed location of a deeply-seated SC]. In a11 cases, an ECC must be correlated with the colposcopic findings. ANSWER TO QUESTION #10 In most experiences with LEEP with positive margins, finding a normal cervix is comparatively more frequent than finding residual disease.3 This is due to the destruction of the "left-over" lesion by repair-related granulation tissue. Correct ans wer is: 3. ANSWER TO QUESTION #11 eure rates after LEEP for high-grade SIL have been excellent, in the order of 90 percent after one session and 95 percent after a repeat procedure.4 Correct answer is: 2. FIGURE3 FIGURE 2 HISTOLOGY OF ENDOCERVICAL CURETIINGS COLPOSCOPY OF CERVIX 3 MONTHS POST-LEEP A single strip of squamous neoplastic epithelium (Ieft) contrasts with the adjacent pale staining strips of squamous metaplastic epithelium (right). Note cervix devoid of residual disease, the squa junction is at the externaios, and the exocervix is covered by native, portio-type mature squamous epithelium. JOURNAL SOGC 1328 DECEMBER 1998

5 T T T REFERENCES 1. Meijer CJLM, van den Brule AJC, Snijders P JF et al. Detection of human papillomavirus in cervical scrapes by the polymerase chain reaction in relation to cytology: possible implications for cervical cancer screening. In: Munoz N, Bosch FX, Shah KV et aj. (Eds). The Epidemiology of Human Papillomavirus and Cervical Cancer. IARC Scientific Publication No Oxford: Oxford University Press, 1992: Ferenczy A. Viral testing for genital human papillomavirus infections: recent progress and clinical potentials. Int J Gynecol Cancer 1995;5: Murdoch JB, Morgan PR, Lopes A, Monaghan JM. Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment. Br J Obstet GynaecoI1992;99: Ferenczy A, Choukroun D, Arseneau J. Loop electrosurgical excision procedure for squamous intraepithelial lesions of the cervix. Advantages and potential pitfalls. Obstet GynecoI1996;87: J SOC OBSTET GYNAECOL CAN 1998;20(14), SOGC 9 th WEST /CENTRAL CME PROGRAM (13ANFF, AB March 25-27, 1999 The Rimrock Resort Hotel The Preliminary Program will be distributed by early January. The Society of Obstetricians and Gynaecologists of Canada Tel.: (613) jbrown@sogc.com SOGCnet: JOURNAL SOGC 1329 DECEMBER 1998