Residual Adenocarcinoma In Situ Research Articles

Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience

ObjectiveHysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. MethodsA retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. Results121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. ConclusionOur study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

Margin Status Post Cervical Conization Predicts Residual Adenocarcinoma In Situ (AIS) and Occult Adenocarcinoma in a Predominantly Hispanic Population.

Background: Adenocarcinoma in situ (AIS) of the cervix, is increasing in incidence, particularly in women of reproductive age. Fertility preservation is often desired. In a predominantly Hispanic population, we sought to determine the incidence of occult cervical cancer co-existing with AIS, and evaluate how conization margin status correlates with residual disease upon hysterectomy. Methods: A retrospective study utilizing a comprehensive cancer center database was conducted. Data from patients with histologically proven AIS of the cervix were abstracted. Results: Of 47 patients that met the criteria, 23 (49%) were Hispanic, 21 (45%) were White, two (4%) were Asian, and one (2%) was Black. The median age was 37. Forty-two patients underwent cervical conizations; 13/42 (48%) had positive margins upon conization; 28/42 (67%) underwent hysterectomies. Furthermore, 6/13 (46%) patients with positive conization margins had residual disease in hysterectomy specimens, with 2/13 (15%) found to have invasive cancer. In contrast, 0/14 (0%) of patients with negative margins had residual disease (p = 0.036, Chi-squared 4.41, df = 1). In total, 2/27 (7%) patients who underwent hysterectomies had invasive cancer (7%). Conclusions: Positive margins upon cervical conization for AIS of the cervix were correlated with a relatively high rate of residual AIS and occult invasive cancer. Negative conization margins were correlated with no residual disease. Those patients may be candidates for fertility-sparing treatment.

Fertility and Pregnancy Outcomes After Conservative Management of Adenocarcinoma In Situ of the Cervix.

The aim of the study was to evaluate the pregnancy outcomes of women who underwent conservative management of adenocarcinoma in situ (AIS). We conducted a retrospective chart review of patients diagnosed with AIS at a single tertiary institution between January 1, 1991, and December 31, 2019. We collected demographic data, AIS-specific information, and fertility outcomes and performed bivariate analyses to compare demographic characteristics and AIS-specific information between patients with and without hysterectomy after diagnosis. Patients with conservative management who achieved pregnancy were described. Among 87 patients with AIS, 38 (44%) underwent a hysterectomy within 6 months of diagnosis and 49 (56%) underwent conservative management. Six of 19 patients (32%) had residual AIS despite undergoing definitive management after an excisional procedure with negative margins and negative endocervical curettage (ECC). Nine of 19 patients (47%) had residual AIS after an excisional procedure with positive margins and/or a positive ECC. Patients who opted for conservative management were younger (median = 31.6 [interquartile range = 27.4-34.9] vs 38.5 y [32.3-44.8 y], p < .001) and nulligravid. Among patients with conservative management, there were 15 pregnancies and 14 live births (29%). Seven were preterm, although 2 were for medical indications. Residual AIS in patients with negative margins and ECC leading to definitive hysterectomy (32%) and the rate of preterm birth (36%) were higher than previous reports and nationally reported rates. However, only 1 patient had a preterm birth before 34 weeks. These findings reflect important information for counseling patients who elect for conservative management of AIS.

Clinical outcomes of patients with adenocarcinoma in situ of the cervix treated by conization.

To describe the clinical outcomes of histologically confirmed adenocarcinoma in situ (AIS) of the cervix treated with cervical conization. A retrospective chart review of patients with histologically confirmed AIS from July 1998 to February 2011 included 52 patients. The rates of residual disease in subsequent excisions, the clinical recurrence rate, the average disease-free interval, and risk of progression to adenocarcinoma were described. The clinical outcomes of patients treated with cold knife cone (CKC) and loop electrosurgical excisional procedure (LEEP) were compared. Fifteen LEEPs and 37 CKC procedures were performed as initial treatment and 26 patients (50%) had positive margins. There was no significant difference in rate of positive margins between LEEP and CKC (40% vs. 54%, respectively. p = 0.55). LEEPs and CKCs resulted in similar volumes of cervical tissue resected (4.98 cm3 vs. 5.04 cm3, p = 0.40). Of patients with positive margins, ten underwent immediate hysterectomy, six underwent a second cone biopsy, seven were managed expectantly, and four were lost to follow up. Residual AIS was found in 47% (eight of 17) of repeat cone biopsy and hysterectomy specimens performed for positive cone margins. Of the 26 patients with negative cone margins, no residual or recurrent disease was found after an average follow-up of 32 months. A positive surgical margin was associated with residual disease in 47% of patients with AIS treated with conization. No patient with negative cone margins had recurrent or progressive disease. Cervical conization with negative margins appears to be a safe treatment option for patients with AIS but requires further investigation. CKC and LEEP were equally efficacious treatments in our study population.

Cervical conization of adenocarcinoma in situ: a predicting model of residual disease

To determine factors associated with the presence of residual disease in women who have undergone cervical conization for adenocarcinoma in situ (ACIS) of the cervix. We identified women who underwent a cervical conization for a diagnosis of ACIS followed by repeat conization or hysterectomy between Jan. 1, 1995, and April 30, 2010. Data were summarized using standard descriptive statistics. Seventy-eight patients met study criteria. The presence of ACIS at the internal conization margin or in the postconization endocervical curettage (ECC) correlated with residual ACIS (P < .001). A margin positive for ACIS was associated with residual glandular neoplasia in 68% of cases. An endocervical curettage positive for ACIS was associated with residual ACIS in 95% of cases. If both the margins and the endocervical curettage were positive for the presence of ACIS, 8% did not have residual disease, 77% had residual ACIS, and 15% had invasive adenocarcinoma. If both the internal conization margin and the postconization ECC were negative for the presence of ACIS, 14% of the final specimens had residual ACIS and none had invasive cancer. The addition of postconization ECC to cone biopsy for ACIS of the cervix provides valuable prognostic information regarding the risk of residual ACIS. Women with ACIS who have both a negative postconization ECC and a negative conization margin have a 14% risk for residual ACIS and can be treated conservatively if desiring fertility. A positive postconization ECC or internal margin incurs significant risk of residual disease and 12-17% will have cancer.

Long-Term Follow-Up Results From Women With Cervical Adenocarcinoma In Situ Treated by Conization

Cervical adenocarcinoma in situ (AIS) is the precursor to adenocarcinoma, and early management will often prevent the occurrence of invasive adenocarcinoma. Conservative treatment with conization has been proposed for the initial treatment for cervical AIS. To evaluate the risk of residual/recurrent disease after conization, we investigated the long-term follow-up results for patients with cervical AIS treated by conization. One hundred thirty-six patients with a biopsy diagnosis of cervical AIS followed by conization were followed up with cytologic, histologic, and human papillomavirus testing. The rate of residual AIS in the following hysterectomy was significantly increased in patients with positive margins on the conization (48.6%, 17/35) compared to patients with negative margins (0/30). No significant disease was identified in patients treated by hysterectomy as primary treatment. More importantly, only 2 patients with conization as primary management had adenocarcinoma or focal AIS, respectively, during a long-term follow-up period (mean, 45 mo). However, one of them had positive margin on the conization and did not proceed to further treatment. The other one had negative margin on the conization but only had focal AIS on the hysterectomy. Human papillomavirus-positive rate showed no significant difference between patients treated by conization and patients treated by hysterectomy during the long-term follow-up. Therefore, if a negative resection margin is achieved, conservative management with conization and careful surveillance is suitable for patients with cervical AIS and desire for future childbearing.

Risk of residual disease and invasive carcinoma in women treated for adenocarcinoma in situ of the cervix

ObjectiveCervical adenocarcinoma in situ (AIS) is increasing in incidence among reproductive-age women. Cervical conization is an alternative to hysterectomy that allows future fertility, however reports regarding the risk of residual AIS and underlying adenocarcinoma are conflicting. The purpose of this study was to determine the outcomes of a large cohort of women treated for AIS. MethodsThe medical records of 180 women with cervical AIS evaluated at the University of Texas MD Anderson Cancer Center and its outlying clinics between 1983 and 2011 were reviewed for demographic information, treatment history, pathologic findings and outcomes. ResultsThe mean age at diagnosis was 33.8years (range 17.6–76.1years). 172 of the 180 women had at least one cone biopsy performed, with 110 (64.0%) undergoing a cold knife cone (CKC), and 62 (36.0%) undergoing a loop electrosurgical excision procedure (LEEP) as their initial method of treatment. Positive margins were noted in 35.0% of patients undergoing CKC compared with 55.6% undergoing LEEP (p=0.017). 71 patients ultimately underwent hysterectomy with residual disease noted in 10 patients (14.1%), 8 patients (11.3%) with residual AIS and 2 patients (2.8%) with invasive carcinoma. Of the 101 patients who did not undergo hysterectomy, 2 patients (2.0%) developed recurrent AIS at a median of 27.5months (range 18–37months) from the last cone, and none developed invasive carcinoma. ConclusionPatients undergoing conservative management for AIS with cervical conization alone should be monitored closely and counseled regarding the potential risks of residual and recurrent disease, even when negative cone margins are obtained.

Cervical Adenocarcinoma in Situ: Update and Management

Adenocarcinoma in situ (AIS) of the uterine cervix is caused by infection with high-risk human papillomavirus and is the recognized precursor of invasive adenocarcinoma of the cervix. Because most AIS lesions are caused by HPV 16/18 infection, prophylactic HPV vaccination is an important step toward prevention of AIS, potentially reducing the incidence of invasive adenocarcinoma. Nonetheless, at the moment the incidence of AIS and invasive adenocarcinoma continues to increase, especially among young women when fertility preservation is an issue. Both diagnosis and treatment of AIS is challenging, because AIS lesions frequently extend into the endocervical canal, making detection and complete excision difficult. Hysterectomy remains the standard treatment for AIS. Selected patients, who wish to preserve fertility, with clear margins and negative ECC after initial conization are potential candidates for conservative treatment. If margins are involved after initial conization or ECC results are positive, the risk of residual or recurrent AIS and invasive adenocarcinoma of the cervix is considerably high. In these women, repeat surgery should be performed. For women, who do not undergo hysterectomy, long-term follow-up is recommended.

The safety of conization in the management of adenocarcinomain situof the uterine cervix

ObjectiveTo evaluate the occurrence of residual or recurrent disease after conization for adenocarcinoma in situ (AIS) of the uterine cervix.MethodsMedical records of 99 patients with a histologically diagnosis of AIS of the uterine cervix by conization between 1991 and 2008 were reviewed retrospectively.ResultsSeventy eight of 99 patients (78.8%) had negative and 18 (18.2%) had positive resection margins of the conization specimen, and 3 (3.0%) had unknown margin status. Of the 78 patients with negative margins, 45 underwent subsequent hysterectomy and residual AIS were present in 4.4% (2/45) of patients. Ten of the 18 patients with positive margins received subsequent hysterectomy and 3 patients (30%) had residual AIS. Twenty-eight patients had conservative treatment and during the median follow-up time of 23.5 months (range, 7 to 124 months), only one patient (3.6%) had recurrent AIS and was treated with a simple hysterectomy. Eight patients became pregnant after conization, 4 of them delivered healthy babies, one had a spontaneous abortion and 3 were ongoing pregnancies.ConclusionPatients with positive resection margins after conization for AIS of the uterine cervix are significantly more likely to have residual disease. However, negative resection margin carries a lower risk for residual AIS, therefore conservative management with careful surveillance seems to be feasible in women who wish to preserve their fertility.

The role of loop electrosurgical excisional procedure in the management of adenocarcinoma in situ of the uterine cervix

Objectives To evaluate the occurrence of residual or recurrent disease after loop electrosurgical excisional procedure (LEEP) for adenocarcinoma in situ (AIS) of the uterine cervix. Study design Records of 78 patients with a histological diagnosis of AIS of uterine cervix on LEEP who were treated and followed at our center between 1992 and 2008 were, retrospectively, reviewed. Results Of 78 patients who underwent LEEP, 47 had negative and 31 had positive resection margins. Of the 47 patients with negative margins, 30 underwent subsequent hysterectomy and residual AIS, including 1 invasive adenocarcinoma, was present in 17% (5/30) of patients. The remaining 17 had no additional procedures. Of the 31 patients with positive margins, 29 patients underwent subsequent hysterectomy and residual AIS, including 4 invasive adenocarcinomas, was present in 48% (14/29) of patients. The remaining two had no additional procedures. After a mean follow-up time of 28 months (range, 1–74 months), no recurrences were observed among the 19 patients who did not undergo hysterectomy. Conclusions The incidence of residual disease in patients with negative margins after LEEP for AIS of the uterine cervix is low but not negligible. Therefore, conservative management in these patients seems to be feasible but careful surveillance is required. However, positive resection margin carries a higher risk for residual AIS or occult invasive adenocarcinoma, warranting additional LEEP or hysterectomy in these patients.

Fertility-sparing surgery in 101 women with adenocarcinoma in situ of the cervix

Objectives Cervical adenocarcinoma in situ (AIS) is a precursor of invasive disease that is increasing in incidence primarily among reproductive-age women of low parity. Conization is an alternative to hysterectomy that allows future pregnancy, but has an inherent risk of residual AIS. The purpose of this study was to determine the outcomes of patients treated by this fertility-sparing strategy over an extended period of surveillance. Methods Women diagnosed with cervical AIS who underwent primary fertility-sparing surgery with either loop excision or cold knife conization between 1993 and 2001 were identified at three institutions. A retrospective medical record review was performed. Patients 40 years of age and older and those undergoing hysterectomy within 12 months of diagnosis were excluded. Results A total of 101 women underwent cone biopsy and expectant management. The median age was 29 years. Fifty-seven percent were nulliparous and 23% primiparous. Cold knife conization was most commonly performed (69 vs. 32 procedures) and had a higher efficacy of achieving negative margins (72% vs. 47%; P = 0.036). Thirty-five women had a total of 49 pregnancies during a mean follow-up of 51 months. Thirty-five gestations were delivered at term. There were two preterm births, eight spontaneous miscarriages, three elective terminations, and one ectopic pregnancy. Thirty-six patients had a repeat cone biopsy. Five ultimately underwent hysterectomy. No invasive cervical adenocarcinomas were observed during the study interval. Conclusion Fertility-sparing surgery enables women with cervical AIS to achieve pregnancy with minimal risk of developing invasive disease during surveillance.

An investigation of the mechanisms underlying the disparity between rate of residual endocervical adenocarcinoma in situ (AIS) in hysterectomy specimens and clinical failure rate following conservatively treated AIS.

The location, amount, and anatomic relationships of adenocarcinoma in situ (AIS) in 5 delayed second cone biopsy excision specimens and 21 definitive-therapy hysterectomy specimens were measured in relation to the neosquamocolumnar junction (nSCJ). All 5 biopsy specimens had 1 to 2 mm of AIS situated at the nSCJ. None had AIS in the proximal endocervix, despite positive or extremely close biopsy margins. Residual AIS in hysterectomy specimens was located proximal to the nSCJ in 19 (90%) of 21 cases. The mean distance between AIS and the nSCJ was 4.9 mm in 12 (86%) of 14 hysterectomy specimens. The mean maximum length of AIS was 4.6 mm in hysterectomy specimens and 1.1 mm in biopsy specimens. Some postbiopsy failures might be de novo neoplasms that begin at the nSCJ rather than recrudescence of persistent AIS. Small amounts of residual AIS following cone biopsy excision might be eradicated by the healing process. These 2 factors might underlie the disparate rates of residual AIS in hysterectomy specimens and postbiopsy excision failures and also explain the poor correlation between biopsy margin status and clinical failure. Factors that impact postbiopsy AIS eradication might be unrelated to de novo AIS beginning at the nSCJ.

Conservative Management of Adenocarcinoma in Situ of the Cervix

Objective. The purpose of this study was to determine the method of treatment and outcome of women with cervical adenocarcinoma in situ (AIS).Methods. Following institutional review board approval, all women diagnosed with cervical AIS from 1987 to 1999 were identified. Data were retrospectively collected by record review and correspondence with medical providers.Results. Of 132 women treated with cone biopsy for AIS, 95 (72%) were managed conservatively after cold knife cone or loop electrical excisional procedure alone; 37 (28%) eventually underwent hysterectomy. The median age of diagnosis was 29 years (range, 17–47) in the conservative management group and 40 years (range, 25–72) in the hysterectomy group (P < 0.0001). Seventy-four percent were nulliparous in the conservative group compared with 27% in the hysterectomy group (P < 0.0001). Of the 95 conservatively managed patients, 92 obtained negative margins; three were followed despite positive or unevaluable margins. During a median follow-up of 30 months, 9 women required evaluation for follow-up abnormalities after cone biopsy with negative margins. None had pathologic evidence of recurrent AIS. Twenty-three infants were delivered. Hysterectomy was generally performed for undesired fertility or persistently positive cone margins. One woman required hysterectomy for recurrent AIS. Thirteen (62%) of twenty-one hysterectomy specimens had residual AIS following cone biopsy with positive or unevaluable margins; 1 (6%) of 16 had residual AIS following cone biopsy with negative margins (P < 0.0001). No patient developed invasive adenocarcinoma.Conclusions. Younger women with cervical AIS may be effectively treated with cone biopsy alone if negative margins can be achieved.

Adenocarcinoma in situ of the cervix

Objective: To retrospectively review the management of adenocarcinoma in situ (AIS) of the uterine cervix.Methods: Forty-eight patients diagnosed with AIS of the cervix between March 1990 and March 1999 were identified.Results: Mean age of patients was 35.8 years (range 17–72). Cold knife conization resulted in a 28% rate of positive margins for AIS compared with 70% for large loop excision of the transformation zone (LLETZ). Fifteen of 39 conizations (37%) had AIS with negative margins of resection. Two of the 15 (13%) were treated with hysterectomy and 1 with repeat conization; none of the surgical specimens had residual AIS. Among 12 conservatively managed patients with negative conization margins, there was one recurrence (7%) of AIS. Eighteen of the 39 conizations (46%) had margins positive for AIS; 3 (8%) were positive for adenocarcinoma and 1 was positive for adenosquamous carcinoma. Twelve of the 18 (67%) were treated with hysterectomy and 6 of the 18 (33%) with repeat conization. Two of the 12 (17%) hysterectomy specimens and 1 of the repeat conization specimens contained residual AIS; 3 hysterectomy specimens (25%) contained cervical adenocarcinoma.Conclusion: This is the largest series of patients diagnosed with AIS to date. We found a significantly lower rate of positive margins with cold knife conization than with LLETZ. Among the conservatively managed patients with negative conization margins, there was one recurrence of AIS.

The status and distance of cone biopsy margins as a predictor of excision adequacy for endocervical adenocarcinoma in situ.

Cervical cone biopsy has become an important surgical procedure for endocervical adenocarcinoma in situ (AIS), especially for patients who desire to retain their fertility. Establishing the usefulness of the endocervical margin status in cone biopsy specimens as a predictor of residual AIS is paramount. We examined the status of the endocervical margin in the cone biopsy specimen, the distance between the most proximal AIS and the endocervical margin in the cone biopsy specimen, and the endocervical curettage (ECC) specimen performed at the time of cone biopsy and residual AIS in the hysterectomy specimens of 61 patients with specimens accessioned from 1968 through 1997; 43 (30%) of patients with a negative endocervical margin had residual AIS in the hysterectomy specimen. Conversely, 10 of 18 (56%) patients with a positive endocervical margin in the cone biopsy specimen had no AIS in the hysterectomy specimen. All 6 patients with AIS in the ECC specimen had residual AIS. No patient with an endocervical margin in the cone biopsy specimen greater than 10 mm had residual AIS. Patients with distances less than 10 mm had equal percentages of residual AIS. In general, more patients with a negative endocervical margin in the cone biopsy specimen had no residual AIS in the hysterectomy specimen than those with a positive endocervical margin in the cone biopsy specimen. However, the status of this margin is not useful for predicting the presence of residual AIS. Pathologists should report the distance between the endocervical cone biopsy margin and the closest AIS.

Adequacy of Conization Margins in Adenocarcinomain Situof the Cervix as a Predictor of Residual Disease

In this retrospective analysis, 18 patients with adenocarcinoma in situ (AIS) of the cervix diagnosed on cervical conization between April 1988 and June 1994 were identified. The margins of all specimens were assessed for disease involvement. If hysterectomy or repeat conization was performed, the presence of AIS in the specimen was ascertained. Eleven of 18 conizations (61%) had AIS with negative margins of resection. Two of these 11 patients (18%) were followed conservatively and have had negative Pap smears for a mean of 1.7 years. The remaining 9 patients (82%) were treated by hysterectomy, with 4 (44%) showing residual AIS in the final surgical specimen. Six of the 18 conizations (33%) had positive margins for AIS. Five of these patients (83%) were treated with hysterectomy and one patient was treated with a repeat conization. Three of the five hysterectomy specimens as well as the repeat conization specimen (67%) contained residual AIS. One conization (6%) had margins that could not be assessed. The absence of residual AIS in the final surgical specimen was not predicted by the negative margin status on the conization.

Human Papillomavirus Messenger RNA Expression in Adenocarcinoma In Situ of the Uterine Cervix

Over recent years, the association between human papillomavirus (HPV) and squamous cell carcinoma of the cervix and its precursors has been well established, largely as a result of advances in the techniques of molecular biology. A similar association between HPV and invasive adenocarcinoma of the cervix has also been recently demonstrated; however, little work has been published on the relationship between the precursor lesion, adenocarcinoma in situ (ACIS), and HPV. We have therefore undertaken an in situ hybridization study of 22 cases of known cervical ACIS using probes for HPV messenger RNA expression. Seventeen of these had residual ACIS in the blocks studied, 15 of which (88.6%) expressed HPV messenger RNA. Five cases were positive for HPV 16 and 10 cases for HPV 18. Early invasive adenocarcinoma was present with ACIS in three cases and one case had early invasion plus cervical intraepithelial neoplasia (CIN III). These invasive lesions showed a similar type and degree of HPV expression as the in situ component. One section had only residual CIN III, which was positive for HPV type 18. Four cases had only minor glandular atypias (less than ACIS) in the studied sections, and all four of these were negative for HPV expression. None of the normal endocervical epithelia in any of the sections were positive by this technique. In summary, the finding of HPV messenger RNA expression in nearly 90% of cervical ACIS supports a possible role for these viruses in the pathogenesis of glandular neoplasms of the uterine cervix.

Adenocarcinoma in situ of the uterine cervix: A clinico-pathologic study of 36 cases

Thirty-six consecutive cases of adenocarcinoma in situ (ACIS) of the uterine cervix, including 8 cases of early stromal invasion to a depth not exceeding 5 mm, were revised with specific reference to detection rate and treatment. The final histologic diagnoses were based on 31 cone biopsies, 1 hysterectomy specimen, and 4 endocervical curettings/punch biopsies. ACIS was localized in the transformation zone of all cone biopsies/hysterectomy specimen, with a mostly superficial spread in the glands. The mucosal surface was involved in 34 cases. In 29 cone biopsies, ACIS was found unifocal. ACIS was associated with lesions of the squamous epithelium, mostly severe, in 25 cases. On review, all cervical smears were positive and ACIS could be specifically diagnosed in 24 cases. Pretreatment biopsies showed ACIS in 28 cases. Detection of early invasive adenocarcinoma required cone biopsy in most cases. Colposcopy showed no characteristics of ACIS. The detection of ACIS depended on the extension of the lesion. Conization with uninvolved margins was an adequate treatment. Residual ACIS was only found in cases with coexisting early invasive adenocarcinoma. No recurrences or frankly invasive adenocarcinomas have been observed during the observation period.