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ORIGINAL ARTICLE  
Year : 2012  |  Volume : 29  |  Issue : 2  |  Page : 121-124
Cytohistological correlation of endocervical gland involvement with high-grade squamous intraepithelial lesions


1 Department of Pathology, Umraniye Education and Research Hospital, Istanbul, Turkey
2 Department of Obstetrics and Gynecology, Umraniye Education and Research Hospital, Istanbul, Turkey

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Date of Web Publication12-Jun-2012
 

   Abstract 

Background: Diagnosis of endocervical glandular involvement by high-grade squamous intraepithelial lesion (HSIL-EGI) on Papanicolaou (Pap) smears can affect the clinical management of patients.
Aim: The cytological criteria for the diagnosis of HSIL-EGI are described and the accuracy of this diagnosis was investigated.
Materials and Methods: Seventeen patients diagnosed with HSIL-EGI and 40 patients with diagnosis of HSIL on Pap smears with follow-up cone or loop electrocautery excision procedure (LEEP) biopsies were included in the study. The following criteria were evaluated for the cytological diagnosis of HSIL-EGI: atypical cells with definite features of HSIL, three-dimensional atypical squamous cell clusters (TDCs) with attached benign endocervical epithelium, finger-like TDCs covered with intact epithelium on most sides, which represent the finger-like invaginations of the endocervical glandular area involved by HSIL, and the absence of cytological findings of in situ adenocarcinoma of the cervix.
Results: On subsequent histopathological evaluation, 16 of 17 (94.1%) patients with a cytological diagnosis of HSIL-EGI and 17 of 40 (42.5%) patients with HSIL exhibited endocervical glandular involvement (P < 0.001, sensitivity: 48.5%, specificity: 95.8%, positive predictive value: 94.1%, negative predictive value: 57.5% and accuracy: 68.4%).
Conclusion: Diagnosis of HSIL-EGI may be possible on Pap smears with a high positive predictive value and specificity but low sensitivity, possibly due to cytological sampling limitations. To clarify the results of the present study, more extensive studies with a particular emphasis on the sampling of the endocervical glandular area for cytological evaluation of the cervix are needed.

Keywords: Adenocarcinoma in situ; endocervical glands; high-grade squamous intraepithelial lesion; Pap test

How to cite this article:
Kir G, Karabulut M H, Yilmaz M S, Topal C S, Gocmen A. Cytohistological correlation of endocervical gland involvement with high-grade squamous intraepithelial lesions. J Cytol 2012;29:121-4

How to cite this URL:
Kir G, Karabulut M H, Yilmaz M S, Topal C S, Gocmen A. Cytohistological correlation of endocervical gland involvement with high-grade squamous intraepithelial lesions. J Cytol [serial online] 2012 [cited 2019 Nov 19];29:121-4. Available from: http://www.jcytol.org/text.asp?2012/29/2/121/97152



   Introduction Top


Very few reports have investigated the accuracy of the cytological diagnosis of endocervical glandular involvement by high-grade squamous intraepithelial lesion (HSIL-EGI) on Papanicolaou (Pap) smears. The Bethesda system does not include the diagnosis of HSIL-EGI on  Pap smear More Detailss. However, it is obvious that the cytological diagnosis of HSIL-EGI is very important in terms of clinical management of the patients. It has been demonstrated that there is an association between EGI and recurrent dysplasia, even independent of the margin status in loop electrocautery excision procedure (LEEP) cones. [1],[2],[3] Several authors reported an increased failure rate using cryotherapy when the endocervical glands were involved in cervical intraepithelial neoplasia (CIN). [3] The information concerning EGI on Pap smears may influence the decision to perform deeper conization, LEEP biopsy or cryotherapy to ensure negative margins. [1],[2],[3],[4],[5],[6],[7],[8]

A few authors described the criteria for the cytological diagnosis of HSIL-EGI in conventional Pap smear and liquid-based cervical cytology samples, and they revealed the effectiveness of their criteria. [9],[10],[11],[12] However, the results of two authors differed from those of the others; they did not demonstrate the increased frequency of EGI on subsequent cone biopsies of patients with cytological HSIL-EGI diagnosis. [13],[14] In our study, we describe simple criteria for the cytological diagnosis of HSIL-EGI and investigated the accuracy of this diagnosis on conventional Pap smears compared with that of subsequent LEEP/cone biopsies (SCBs).


   Materials and Methods Top


Seventeen patients with cytological diagnoses of HSIL-EGI and 40 patients with cytological diagnoses of HSIL and satisfactory follow-up LEEP or cone biopsies (within 3 months of cytological diagnosis) were included in the study groups. All patients were identified from Umraniye Research and Education Hospital pathology computer data files over a period of 4 years (January 2007-December 2010). All cervical samples were obtained with a cytobrush, smeared on to one glass slide for each case, alcohol-fixed, and stained according to the Pap method.

All cases were new patients without a prior history of disease. For the cytological diagnosis of HSIL-EGI, the following criteria were evaluated: atypical squamous cells with definite features of HSIL, [15] three-dimensional atypical squamous cell clusters (TDCs) with attached benign endocervical epithelium [Figure 1], finger-like TDCs covered with intact epithelium on most sides, which represent the finger-like invaginations of the endocervical glandular area involved by HSIL [Figure 2], and the absence of cytological features of in situ adenocarcinoma of the cervix [15] (AIS). The 40 cases with cytological diagnosis of HSIL were reviewed retrospectively and they did not include either of the two types of TDCs.
Figure 1: Three-dimensional atypical squamous cell cluster with attached benign endocervical epithelium (Pap, ×100)

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Figure 2: Finger-like three-dimensional atypical squamous cell cluster that belongs to the invagination of the endocervical glandular area (Pap, ×100)

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The majority of biopsy specimens were oriented by a single suture designating the 12 o'clock position. All specimens were fixed in formaldehyde and processed in a standardized fashion. Surgical margins of the whole specimens were inked and then divided into four quadrants starting from the 12 o'clock position. All quadrants were radially sectioned, submitted clockwise, embedded in paraffin, and stained with hematoxylin and eosin. All specimens were examined by one surgical pathologist. Only the specimens that represented both ectocervical squamous and endocervical glandular tissue were included in the study. The highest degree of cervical dysplasia and EGI were recorded.

Statistical analysis

The McNemar test was used to assess the homogeneity between paired categorical variables. P values (two-sided test) less than 0.05 were considered significant. All statistical analyses were performed using Number Cruncher Statistical System 2007, Power Analysis and Sample Size 2008 statistical software (Kaysville, Utah, USA).


   Results Top


[Table 1] lists the cytological criteria of HSIL-EGI. Of these criteria mentioned above, features required for the diagnosis of HSIL-EGI were as follows: atypical squamous cells with definite features of HSIL, the absence of cytological features of AIS, at least one TDC with attached benign endocervical epithelium, and/or finger-like TDCs. On histological evaluation of SCBs, 16 of 17 (94.1%) patients with cytological diagnoses of HSIL-EGI and 17 of 40 (42.5%) patients with cytological diagnoses of HSIL exhibited EGI (P < 0.001, sensitivity: 48.5%, specificity: 95.8%, positive predictive value: 94.1%, negative predictive value: 57.5% and accuracy: 68.4%). For the patient with a cytological diagnosis of HSIL-EGI but without histological confirmation, the transformation zone was included partially in the SCB. Histologically, none of the 57 cases exhibited AIS.
Table 1: Cytological features of HSIL-EGI on Pap smears

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   Discussion Top


It has been demonstrated that EGI was a significant factor correlating with a positive endocervical margin and residual/recurrent disease in women with CIN who did not undergo hysterectomy. The reported success rates in treating dysplasia by LEEP biopsy range from 60 to 95%. [16],[17],[18],[19],[20] It has been demonstrated that after LEEP, EGI was predictive of residual/recurrent dysplasia. [1],[2],[3] Livacy et al.[3] found an association between EGI and recurrent dysplasia independent of margin status in LEEP cones. Patients with negative margins and positive EGI had approximately twofold higher recurrence rates than patients with negative margins and negative gland involvement. Some authors report increased failure rates in treatment with LEEP attributed to the smaller size of LEEP versus conventional cold-knife conization specimens. [21],[22] However, Sun et al.[23] concluded that EGI and the depth of conization were significant factors that correlated with positive cone margins. In addition, several authors report an increased failure rate using cryotherapy when the endocervical glands were involved in CIN. [3] Therefore, information concerning gland involvement should influence patient management; the option of deeper conization may have advantages over LEEP or cryotherapy to ensure negative margins for suitable patients. [1],[2],[3],[4],[5],[6],[7],[8]

Some authors have described the criteria for the cytological diagnosis of HSIL-EGI and confirmed the effectiveness of their criteria. [9],[10],[11],[12] However, the results of two of these authors differed from those of the others; they did not confirm the increased frequency of EGI on SCBs of patients with cytological HSIL-EGI diagnoses. [13],[14] Selvaggi [9],[11] defined the cytological criteria of HSIL-EGI with a particular emphasis on patterns A and B. Round to oval "syncytial" clusters with smooth cellular borders, central whorling and peripheral flattening of small dysplastic cells were designated as "pattern A," and sheets of abnormal columnar vacuolated cells with peripheral palisades and nuclear pseudostratification were designated as "pattern B." We actually experienced difficulty in understanding and recognizing the cell clusters of patterns A and B. Instead, we used two more simple TDCs, which were mentioned by Drikoningen et al.[10] and Levine et al.[13] as follows: the first was a TDC with attached benign endocervical cells [10] and the second one was a finger-like TDC covered with intact epithelium on most sides, which represents the finger-like invaginations of the endocervical glandular area involved by HSIL. [13] In the present study, the required and consistent findings for the cytological diagnosis of HSIL-EGI were atypical squamous cells with definite HSIL features, at least one of two simple-type TDCs and the absence of cytological findings of AIS. As the HSIL descends into the crypt, it displaces the benign endocervical epithelium, which may be seen attached to the atypical squamous cell clusters on the cytological examination. Finger-like TDCs with smooth contours might be observed in the Pap smears when the cytobrush removes fragments of tissue including endocervical crypts and accompanying dysplastic tissue. Differential diagnosis from AIS was possible in most cases if diagnostic criteria were strictly applied. None of these TDCs showed cell polarity and/or glandular openings. Cell patterns including those of strips, cell rosettes, feathering and cigar-shaped nuclei, which are unique to AIS, were not observed. Furthermore, normal endocervical cells were predominant, while in AIS, normal endocervical cells are usually scant. When in doubt, one has to consider that AIS occurs less frequently than HSIL. [10] On histological evaluation of SCBs, 16 of 17 (94.1%) patients with cytological diagnosis of HSIL-EGI exhibited EGI. However, 17 of 40 (42.5%) patients with cytological diagnosis of HSIL exhibited EGI on histological evaluation of SCBs (P < 0.001, sensitivity: 48.5%, specificity: 95.8%, positive predictive value: 94.1%, negative predictive value: 57.5% and accuracy: 68.4%). According to our study results, the cytological diagnosis of HSIL-EGI has disadvantages of low sensitivity and negative predictive value, with a high frequency of false-negative diagnoses. We feel that the limited and difficult sampling of endocervical crypts for cytological examination was responsible for these results. All cervical samples were obtained with a cytobrush. The highest yield of endocervical cells has been found for the cytobrush among various cell collection devices. [24],[25],[26],[27] However, during cytological sampling without special attention to deep endocervical sampling, endocervical glandular invaginations may not be available for the cytological evaluation.

In conclusion, diagnosis of HSIL-EGI may be possible on Pap smears with a high positive predictive value and specificity but with low sensitivity, possibly due to cytological sampling limitations. To clarify the results of the present study, more extensive studies with a particular emphasis on the sampling of the endocervical glandular area for cytological evaluation of the cervix are needed.

 
   References Top

1.Savage EW, Matlock DL, Salem FA, Charles EH. The effect of endocervical gland involvement on the cure rates of patients with cervical intraepithelial neoplasia undergoing cryosurgery. Gynecol Oncol 1982;14:194-8.  Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.Demopoulos RI, Horowitz LF, Vamvakas EC. Endocervical gland involvement by cervical intraepithelial neoplasia grade III. Predictive value for residual and/or recurrent disease. Cancer 1991;68:1932-6.  Back to cited text no. 2
[PUBMED]    
3.Livasy CA, Maygarden SJ, Rajaratnam CT, Novotny DB. Predictors of recurrent dysplasia after a cervical loop electrocautery excision procedure for CIN-3: a study of margin, endocervical gland, and quadrant involvement. Mod Pathol 1999;12:233-8.  Back to cited text no. 3
[PUBMED]    
4.Nagi CS, Schlosshauer PW. Endocervical glandular involvement is associated with high-grade SIL. Gynecol Oncol 2006;102:240-3.  Back to cited text no. 4
[PUBMED]  [FULLTEXT]  
5.Kalogirou D, Antoniou G, Karakitsos P, Botsis D, Kalogirou O, Giannikos L. Predictive factors used to justify hysterectomy after loop conization: increasing age and severity of disease. Eur J Gynaecol Oncol 1997;18:113-6.  Back to cited text no. 5
[PUBMED]    
6.Lu CH, Liu FS, Tseng JJ, Ho Es. Predictive factors for residual disease in subsequent hysterectomy following conization for CIN III. Gynecol Oncol 2000;79:284-8.  Back to cited text no. 6
[PUBMED]  [FULLTEXT]  
7.Moore BC, Higgins RV, Laurent SL, Marroum MC, Bellitt P. Predictive factors from cold knife conization for residual cervical intraepithelial neoplasia in subsequent hysterectomy. Am J Obstet Gynecol 1995;173:361-6.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.Lu CH, Liu FS, Kuo CJ, Chang CC, Ho ES. Prediction of persistance or recurrence after conization for cervical intraepithelial neoplasia III. Obstet Gynecol 2006;107:830-5.  Back to cited text no. 8
[PUBMED]    
9.Selvaggi SM. Cytologic features of squamous cell carcinoma in situ involving endocervical glands in endocervical cytocrush specimens. Acta Cytol 1994;38:687-92.  Back to cited text no. 9
[PUBMED]    
10.Drikoningen M, Meertens B, Lauweryns J. High grade squamous intraepithelial lesion (CIN 3) with extension into endocervical clefts. Difficulty of cytologic differentiation from adenocarcinoma in situ. Acta Cytol 1996;40:889-94.  Back to cited text no. 10
    
11.Selvaggi SM. Cytologic features of high-grade squamous intraepithelial leisons involving endocervical glands on ThinPrep cytology. Diagn Cytopathol 2002;26:181-5.  Back to cited text no. 11
[PUBMED]  [FULLTEXT]  
12.Thiryayi SA, Marshall J, Rana DN. Differentiating between endocervical neoplasia and high grade squamous intraepithelial lesions in endocervical cryopts: cytological features in ThinPrep and SurePath cervical cytology samples. Diagn Cytopathol 2009;37:315-9.  Back to cited text no. 12
[PUBMED]  [FULLTEXT]  
13.Levine PH, Wiasman J, Mittal K. Significance of the cytologic diagnosis of endocervical glandular involvement in high-grade squamous intraepithelial leesions. Diagn Cytopathol 2002;26:217-21.  Back to cited text no. 13
    
14.Van Hoeven KH, Hanau CA, Hudock JA. The detection of endocervical gland involvement by high grade squamous intraepithelial lesions in smears prepared from endocervical brush specimens. Cytopathology 1996;7:310-5.  Back to cited text no. 14
[PUBMED]    
15.Solomon D, Nayar R, editors. The Bethesda system for reporting cervical cytology. New York: Springer; 2004.  Back to cited text no. 15
    
16.Gold M, Dunton CJ, Murray J, Macones G, Hanau C, Carlson JA Jr. Loop electrocautery excision procedure: therapetic effectiveness as an ablation and a conization equivalent. Gynecol Oncol 1996;61:241-4.  Back to cited text no. 16
[PUBMED]  [FULLTEXT]  
17.Luesley DM, Cullimore J, Redman CW, Lawton FG, Emens JM, Rollason TP, et al. Loop diathermy excision of the cervical transformation zone in patients with abnormal cervical smears. BMJ 1990;300:1690-3.  Back to cited text no. 17
[PUBMED]  [FULLTEXT]  
18.Wright TC Jr, Gagnon S, Richar RM, Ferenczy A. Treatment of cervical intraepithelial neoplasia using the loop electrocautery excision procedure. Obstet Gynecol 1992;79:173-8.  Back to cited text no. 18
    
19.Alvarez RD, Helm CW, Edwards RP, Naumann RW, Partridge EE, Shingleton HM, et al. Prospective randomized trial of LLetz versus laser ablation in patients with cervical intraepithelial neoplasia. Gynecol Oncol 1994;52:175-9.  Back to cited text no. 19
[PUBMED]  [FULLTEXT]  
20.Oyesanya OA, Amerasinghe C, Manning EA. A comparison between loop diathermy conization and cold-knife conization for management of cervical dysplasia associated with unsatisfactory colposcopy. Gynecol Oncol 1993;50:84-8.  Back to cited text no. 20
[PUBMED]  [FULLTEXT]  
21.Linares AC, Storment J, Rhodes-Morris H, Malpica A, Mitchell MF. A comparison of three cone biopsy tecniques for evaluation and treatment of squamous intraepithelial lesions. J Gynecol Tech 1997;3:151-6.  Back to cited text no. 21
    
22.Krebs HB, Pastore L, Helmkamp BF. Loop electrosurgical excision procedures for cervical dysplasia: experience in a community hospital. Am J Obstet Gynecol 1993;169:289-93.  Back to cited text no. 22
[PUBMED]    
23.Sun XG, Ma SQ, Zhang JX, Wu M. Predictors and clinical significance of the positive cone margin in cervical intraepithelial neoplasia III patients. Chin Med J 2009;122:367-72.  Back to cited text no. 23
[PUBMED]  [FULLTEXT]  
24.Murata PJ, Johnson RA, McNicoll KE. Controlled evaluation of implementing the Cytobrush tecnique to improve Papanicolaou smear quality. Obstet Gynecol 1990;75:690-5.  Back to cited text no. 24
[PUBMED]    
25.Lai-Goldman M, Nieberg RK, Mulcahy D, Wiesmeier E. The cytobrush for evaluating routine cervicovaginal-endocervical smears. J Reprod Med 1990;35:959-63.  Back to cited text no. 25
[PUBMED]    
26.Martin-Hirsch P, Lilford R, Jarvis G, Kitchener HC. Efficacy of cervical-smear collection devices: a systematic and meta-analysis. Lancet 1999;354:1763-70.  Back to cited text no. 26
[PUBMED]  [FULLTEXT]  
27.Kohlberger PD, Stani J, Gitsch G, Kieback DG, Breitenecker G. Compararive evaluation of seven collection devices for cervical smears. Acta Cytol 1999;43:1023-6.  Back to cited text no. 27
[PUBMED]    

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Correspondence Address:
G Kir
Sinpas Aqua Manors Sitesi D-18, Alemdag cd., Yukari Dudullu Umraniye, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9371.97152

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