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Glandular Lesions of the Endocervix

Pitfalls in Diagnosis

Marilyn Betchley
Senior Cytotechnologist
ClinPath Laboratories
Adelaide, Australia 5000

There are a number of conditions which need to be considered in the differential diagnosis of AIS and Invasive lesions of the endocervix. These include the following:

Post Cone Biopsy Smears

A cone biopsy shortens the endocervical canal allowing easier access to endometrial cells. Post cone biopsy smears may contain cells from this region and these cells are referred to as lower uterine segment or LUS cells. The cytological features of LUS cells have been described (de Peralta-Venturino et al, 1995; Lee 1993) and are outlined as follows:

lus1 Presence of long tubular, branching glands embedded in loose monomorphic stroma. This appearance is best appreciated on low power magnification.

lus2 Presence of glandular cells of endometrial origin showing round nuclei, finely granular chromatin and nuclear crowding. Nucleoli are inconspicuous.

Occasional peripheral palisading of cells is noted and glandular openings are often visible.

Presence of stromal cells showing uniform round to spindle shaped nuclei, fine granular chromatin and scant cytoplasm. Peripheral cells are loosely attached and appear 'strung out'.

It is important to exercise caution in examining post cone smears especially in women who have had a previous diagnosis of adenocarcinoma. Residual tumour may be present and careful scrutiny is required to differentiate abnormal from LUS cells.

Sampling of lower uterine cells

Vigorous sampling of the endocervical canal in women who have no history of cone biopsy or other surgery may also yield cells with cytological features of LUS cells. Use of special sampling instruments, such as the cytobrush, to collect cells from the endocervical canal has meant that on occasions cells from further up the endocervical canal are collected and smeared for examination. Appreciation of the cytological features of LUS cells is essential to avoid misdiagnosis.


Endometriosis was originally thought to be a rare lesion but recent reports have suggested an incidence as high as 2.4% in some series. Previous trauma to the cervix, for example surgery, has been implicated as a contributor to the condition (Hanau et al, 1997). The presence of aberrant endometrial glands and stroma on a cervical smear can present diagnostic difficulties. Clusters of cells with the cytological appearance described for LUS cells may be present and mimic a glandular abnormality.

Tubal Metaplasia

This refers to the replacement of normal endocervical glandular epithelium by foci of benign epithelium resembling that of normal fallopian tube epithelium. These foci consist of:

Ciliated cells: the cells possess uniform, large and round nuclei which are basally located within the cytoplasm. The nuclei exhibit moderate hyperchromasia. The cells present as crowded sheets with a smooth cytoplasmic border, terminal bars and cilia.

Non-ciliated secretory cells: these cells have uniform, large and round nuclei with fine to moderately granular chromatin. Pale cytoplasm is evident and the cells have peripherally located nucleoli.

Peg/intercalated cells: these small oval cells with hyperchromatic nuclei are dispersed infrequently throughout the group.

The cytology of tubal metaplasia has been described in the literature (Novotny et al, 1992; Ismail 1991; Hirschowitz et al, 1992; Ducatman et al, 1993).

Microglandular Endocervical Hyperplasia (MEH)

Microglandular endocervical hyperplasia is a localised proliferation of endocervical cells which can mimic adenocarcinoma. The lesion usually occurs in younger women and has been described in association with oral contraceptive use and pregnancy. Although the histological features of MEH have been well described, the cytological characteristics are ill defined. The predominant cellular findings are nuclear enlargement and hyperchromasia, a finely distributed chromatin pattern and nuclear crowding. The cytoplasm is usually abundant and finely vacuolated. Degenerative features can present diagnostic difficulties and reparative changes have been described in a significant proportion of cases and resulted in a false positive diagnosis (Selvaggi and Haefner, 1997).

Cervical Intraepithelial Neoplasia (CIN) involving glands

CIN-3 involving glands needs to be distinguished from glandular lesions. Two types of patterns are seen (Selvaggi 1994).

Pattern A is typified by round to oval clusters of cells with smooth cell borders. Cells at the periphery are flattened whereas cells in the centre show a spindle or whorling arrangement.

Pattern B is characterised by sheets of columnar cells with peripheral palisading and nuclear pseudostratification which can mimic AIS. Some sheets show benign endocervical cells along one edge and it is easy to mistake the whole group as being of endocervical origin.

Reactive and Inflammatory Changes

The cells seen in repair and inflammatory conditions may mimic a glandular abnormality specifically invasive adenocarcinoma of the endocervix. The cells shed in sheets, strips and rosettes. Nuclei may be large with coarse chromatin and nucleoli. However, the cells seen in reactive conditions are usually monolayered with abundant cytoplasm. There is no stratification or 'feathering' of nuclei.

Cells with marked nuclear enlargement, hyperchromasia and prominent nucleoli may be seen in polyps. It is important to obtain clinical information in these situations and appraise cytological criteria for AIS with care (Nasu et al, 1993; Cooper 1995; Pacey 1991).

Click here to view a table summarising the main cytological features helful in distinguishing AIS from other entities.


  • Cooper P. Glandular Neoplasms of the Uterine Cervix. Chapter 31. Diagnostic Cytopathology by Winifred Gray. 1995.
  • Ducatman et al. Tubal Metaplasia: A Cytologic Study with Comparison to other Neoplastic and Non- Neoplastic conditions of the Endocervix. Diagn Cytopathol. 1993 9:98-105.
  • Hanua et al. Cervical Endometriosis. A Potential Pitfall in the Evaluation of Glandular cells in Cervical Smears. Diagn Cytopathol.1997 16: 274- 280.
  • Hirschowitz et al. Cytologic changes Associated with Tubo-Endometroid Metaplasia of the Uterine Cervix. Cytopathol. 1994. 5: 1-8.
  • Ismail SM. Cone Biopsy Causes cervical Endometriosis and Tubo-Endometroid metaplasia of the Uterine Cervix. Cytopathol. 1994. 18:107-114.
  • Lee KR. Comparative Cytological Features of Adenocarcinoma In Situ of the Uterine Cervix. Acta Cytol. 1991 35:117-124.
  • Nasu et al. Endocervical Glandular Atypia and Adenocarcinoma: A Correlation of Cytology and Histology. Int.J.Gynaecol. Pathol. 1993 12:208-127.
  • Novotny et al. Tubal Metaplasia. A frequent Potential Pitfall in the Cytological Diagnosis of Endocervical Glandular Dysplasia on Cervical Smears. Acta Cytol. 1992 36:1-9.
  • Pacey NF. Glandular Neoplasms of the Uterine Cervix. Chapter 10. Comprehensive Cytopathology by Marluce Bibbo. 1991.
  • de Peralta-Venturino et al. Endometrial Cells of the "Lower Uterine Segment" (LUS) in Cervical Smears obtained by Endocervical Brushings: A Source of Potential Diagnostic Pitfall. Diagn Cytopathol. 1995 12:263-271.
  • Selvaggi S. Cytologic Features of Squamous Cell Carcinoma in Situ Involving Endocervical Glands in Endocervical Brush Specimens. Acta Cytol. 1994 38:687-692.
  • Selvaggi S, Heafner . Microglandular Endocervical Hyperplasia and Tubal Metaplasia. Pitfalls in the Diagnosis of Adenocarcinoma on Cervical Smears. Diagn Cytopathol. 1997 16:168-173.


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