More recently, there has been a trend towards conservative management of ACIS, departing from previous radical procedures like extrafascial hysterectomy and even radical hysterectomy. While cervical conisation for ACIS is the preferred procedure for women who desire to preserve their fertility, its safety is still a matter of controversy, largely due to the detection of residual disease in subsequent hysterectomy specimen in a sizeable portion of patients.

We present the findings of a review on 24 cases with histological diagnosis of ACIS of the cervix, managed at the KK Gynaecological Cancer Centre, KK Women’s & Children’s Hospital with the objective of determining: (1) the problems of diagnosis and follow-up; (2) the local practices in the management of ACIS and (3) the clinical outcome of treatment. 

The computerised Tumour Registry database at our Gynaecological Cancer Centre, KK Hospital, was searched for patients with the diagnosis of ACIS, either as the sole condition or co-existing with another condition. The case records were reviewed and the relevant information were extracted. Except for one case managed in 1989, all patients were treated between 1991- 1996.

All the diagnosis of ACIS were made largely on cone biopsies and hysterectomy specimens apart from 2 cases who had large loop excision of transformation zone (LLETZ) of the cervix. All cases were managed at our Centre.

Altogether, 24 case records of patients with the diagnosis of ACIS were analysed. There were 21 patients who had ACIS alone or in conjunction with adjoining CIN (cervical intra-epithelial neoplasia). In the remaining 3 patients, ACIS were found in the hysterectomy specimens, performed for adenocarcinoma of the cervix (2 patients) and adenocarcinoma of the fallopian tube (1 patient).

The use of standard LLETZ, laser or cold knife cone biopsies were decided individually by the surgeon in charge, as was the decision for subsequent hysterectomy. In general, laser conisation was the preferred procedure at our hospital in the last 10 years.

Of the 23 patients who had Pap smears performed prior to the diagnosis of ACIS, 21 of them were abnormal. However, only 39% (9/23) had indicated suspicion of a glandular lesion. Colposcopy were performed for 21 patients and 28% (6/21) had indicated suspicion of a glandular lesion. Of the 14 cervical biopsies taken, only 57% (8/14) confirmed the presence of ACIS. Endocervical curettage was infrequently performed (4 patients), and 3 out of these 4 specimens denoted a strong suspicion of an endocervical lesion (Table I).

For the 21 patients who had cone biopsies or LLETZ performed, the initial pre-conisation diagnoses were ACIS for 10 patients and CIN for 11 patients. ACIS was later found to be present in the histopathological specimens of the latter group of patients. Overall, a total of 14 patients (58%) had ACIS found in conjunction with CIN. Two cases of ACIS were associated histological findings of patients with adenocarcinoma of the cervix and one with adenocarcinoma of the Fallopian tube.

Of the 21 patients with a diagnosis of ACIS or in conjunction with CIN, 19 patients had cone biopsies (17 laser cone and 2 knife cone) and 2 had loop electrical excision of the cervical transformation zone. The latter 2 patients had a primary diagnosis of CIN but with a small focus of ACIS found on the histological specimen, with one of them having CIN involving the surgical margin. A repeat cone biopsy was performed for this patient and no residual disease was found (Fig 1).

The mean procedure time for the cone biopsies was 38 minutes (range :15 - 133 minutes). Five cases encountered complications with 2 secondary haemorrhages needing conservative management without transfusion, 2 mild infections and one with bladder perforation. Of the 17 laser cone biopsy specimens, 6 (35%) had surgical margin involvement, while one specimen had a dubious surgical margin. Both cold knife cone biopsies had clear surgical margins.

Following cone biopsy, 11 patients subsequently had total hysterectomy; 5 were performed for involved surgical margin in the preceding cone biopsies and one for dubious surgical margin. Three of the 6 patients had residual ACIS. Of the 8 patients who did not have hysterectomy following their cone biopsy, all but one had clear cone surgical margins. The latter patient had ACIS which involved the endocervical margin but refused further surgical treatment against medical advice and is currently undergoing close clinical surveillance.

Excluding the 3 cases of ACIS associated with adenocarcinoma, the mean follow-up duration for the group of 21 patients with ACIS alone or in conjunction with a CIN lesion was 20.5 months (range: 1 - 75 months). At the time of the study, none of these patients was known to have developed recurrent ACIS or adenocarcinoma. At follow-up, apart from symptom review and a routine examination, all patients had Pap smears done. Among the patients with conserved uterus, the use of endocervical brush was not specified and endocervical curettage was only performed in one patient.

Although the presentation leading to the diagnosis of ACIS is usually an abnormal Pap smear, only 39% of the latter (9/23) in our series suggested a glandular lesion, with the rest of them showing squamous cell lesions. A subsequent colposcopy detected a glandular lesion in only 28% (6/21 ) of the cases. This is not surprising as the latter was designed primarily to survey the ectocervix and the endocervical canal is usually obscure especially in nulliparous women. While it is evident that endocervical curettage (ECC) is not a regular practice in our Centre, 3 out of the 4 cases that had ECC proved positive for glandular abnormality. Although one could argue that a routine endocervical curettage may contribute more to the diagnosis of ACIS, this was not borne out in the study by Poynor et al(3). In this study, of the 21 patients who had a pre-conisation ECC, 7 showed ACIS and 2 showed endocervical glandular dysplasia making a total of only 9 of the 21 patients, revealing a glandular lesion in the ECC specimens. However, until a better method becomes available, ECC and cytobrush will remain the most direct method of sampling the endocervical epithelium.

Although there is no proper study comparing cold knife cone biopsy with laser cone biopsy for treating ACIS, it is conceivable that the former would possibly be superior for 2 reasons: a cold knife cone biopsy is done with our naked eyes visualising the cervix and one would tend to take a wider margin from the lesion and the cervical transformation zone (TZ). With the aid of the magnification of a colposcope, this margin tends to be closer when a laser beam is used. The latter also allows greater surgical flexibility that enables one to follow the contours of the lesion more accurately. The second possible explanation, is perhaps that the latter tends to be conical, tapering towards its apex. The glandular crypts usually dip from the surface epithelium into the cervical stromal which is unlike the squamous lesion that remains at the surface of the ectocervix. The tapering apex of a laser cone biopsy will hence cut across these glandular crypts, resulting in a positive margin being seen in the specimen. One way to circumvent this problem is to perform a more cylindrical cone biopsy using the laser beam and transecting the apex of the cone specimen with a pair of scissors to complete the procedure (Fig 2).

While there was no case of recurrence, including one patient with a positive surgical margin who refused further surgery, the follow-up period was short (mean of 20.5 months). However, the frequent employment of hysterectomy may have weeded out patients likely to develop a recurrence. Even then, the long follow-up of these patients remains relevant as the majority of them had associated squamous lesions. It was also evident that the use of ECC was not a routine procedure in their surveillance. It is the recommendation of the author that every attempt should be made in the follow-up of such patients to obtain endocervical samples (either an ECC or using an endocervical brush) to detect recurrence, in the light that diagnosis can be difficult to begin with.

In summary, we found that pre-conisation diagnosis of ACIS using Pap smear, colposcopy and cervical biopsy was difficult in our series. Concurrent CIN occurred in a sizeable portion of patients and hence should deserve appropriate attention. Laser cone biopsy was the preferred method employed at our Centre. For laser cone biopsy, there was a sizeable proportion of specimens showing surgical margin involvement although residual ACIS was found in less than half of these patients who consequently underwent total hysterectomy. The frequent employment of total hysterectomy for treating possible residual disease, may have contributed to the absence of recurrence observed, in addition to the relatively short period of follow-up.

We recommend greater vigilance of this condition, especially in patients with CIN and the need for regular endocervical sampling in the follow-up of patients treated by cone biopsy.