Endocervical Glandular Dysplasia Research Articles

Detection of occult endocervical glandular dysplasia in cervical conization specimens for squamous lesions

The aim of this work was to evaluate the incidence of occult cervical glandular intraepithelial neoplasia (CGIN) and adenocarcinoma of the cervix (AC) in women treated with CO2-laser conization for cervical intraepithelial neoplasia (CIN) or squamocellular cervical cancer (SCC).The medical records of all women with a histological diagnosis of squamous lesions of the uterine cervix (persistent CIN1, CIN2, CIN3 and SCC) who were subsequently treated with CO2-laser conization at our institution, during the period from January 1991 to December 2014, were analyzed in a retrospective case series.Among the 1004 women fulfilling the study inclusion/exclusion criteria, 77 cases (7.7%) of occult glandular lesions (CGIN and AC) were detected on the final cone specimen (48 cases of occult low-grade cervical glandular intraepithelial neoplasia (LCGIN), 25 cases of occult high-grade cervical glandular intraepithelial neoplasia (HCGIN), and four cases of occult “usual-type” AC). No difference in the mean age between women diagnosed with occult glandular lesions and women without occult glandular lesions on the final specimen emerged (39.1±9.3 vs 38.4±9.4, p=0.5).In women with occult LCGIN on cone specimen, mean follow-up of 48 months was reported (range 7–206 months) and no cases of progression to HCGIN or AC were observed.In conclusion, a relatively high rate of occult glandular lesions was found in women treated for squamous lesions. The natural history of CGIN is still uncertain and, in particular, there are some controversies as to whether LCGIN is a precursor lesion of HCGIN or AC. In this context the role of pathologists become very important since the appropriate diagnosis of these lesions could have potential implications in the clinical management of these patients.

Evolution of the Incidence of Cervical Cancer Among Hispanics and Asians in California Between 1990 and 2004

Purpose/Objective(s): This study aimed to evaluate the evolution of the invasive cervical cancer (CCa) incidence among Hispanics and Asians in California. Materials/Methods: Using data from the California Cancer Registry, comprising four of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program registries, information on all primary CCa diagnosed in California from January 1, 1990, through December 31, 2004 was obtained. We analyzed the influence of ethnicity and nativity on the evolution of CCa incidence. Results: Among the 22,189 CCa cases diagnosed between 1990 and 2004, 50% were non-Hispanic white (NHW), 39% Hispanic and 11% Asian women. Among Hispanic and Asian women, 74% were foreign-born (FB). For the entire population, 70% were squamous cell carcinoma (SCC), 19% adenocarcinoma and 11% other histologies. Compared to NHW, there was a higher incidence of CCa in United States born Hispanics and FB Hispanics, Japanese, Filipino and Korean women (Incidence rate ratio [IRR]; 95% CI: 1.6 [1.5-1.7], 2.6 [2.5-2.7], 1.4 [1.2-1.7], 1.5 [1.4-1.6],and 1.8 [1.6-2.1], respectively). However, FB-South Asian, FB-Chinese and US-born Japanese had lower rates than NHW (IRR (95% CI): 0.8 (0.7-1.0), 0.9 (0.8-1.0), 0.6 (0.5-0.7), respectively). From 1990 to 2004, the incidence of CCa declined significantly for all groups of women except for United States-born Asian for whom the incidence remained stable (average percent of change [APC] were 2.44, 1.40 [1990-2002], 4.64 and 7.32 [1994-2004] for NHW, United States and FB-Hispanics and FBAsians, respectively). There was a reduction of the SCC incidence for all groups of women (APC: 6.37 [1990-1994] and 5.03 [1997-2004], 5.15 [1990-1995] and 9.84 [2000-2004], 5.07, 3.62, 8.07 [19932004] for NHW, United States-and FB-Hispanics, United States and FBAsian, respectively). The incidence of adenocarcinoma did not show a significant decrease with the exception of FB-Asian women, which showed a significant decrease for adenocarcinoma (APC: 3.95 [1990 -2004]). Local and regional disease declined significantly over the 14 years period for NHW, FB-and United States-born Hispanics and FB-Asian (APC: 2.58, 4.39, 12.42 [2000-2004], 5.62 for local disease and 2.06, 3.96, 2.27 and 6.73 for regional disease respectively). The incidence of distant disease has only decreased significantly in FBHispanics and FB-Asian (APC: 5.71 and 4.40, respectively). Conclusions: The incidence of CCa declined in NHW, Hispanics and Asian women in California from 1990 through 2004. The SCC incidence declined and the adenocarcinoma incidence remained stable. This difference between these histologies could be caused by less sensitivity for detecting endocervical glandular dysplasia and adenocarcinoma than for detecting squamous malignancy with pap smear. Author Disclosure: M. Froment: None. A. Roux: None. M.C. DeRouen: None. S.L. Gomez: None. E.A. Kidd: None.

Diverse glandular pathologies coexist with high‐grade squamous intraepithelial lesion in cyto‐histological review of atypical glandular cells on ThinPrep specimens

To identify in cytology, high-grade squamous intraepithelial lesions with endocervical glandular extension in cases previously diagnosed as atypical glandular cells (AGC), analyse possible reasons for the diagnostic pitfall and document the frequency of glandular pathology coexisting with high-grade cervical intraepithelial lesion in histology. Thirty-nine ThinPrep cervical smear (Pap) tests reported as AGC of undetermined significance and showing high-grade lesions on histology [cervical intraepithelial neoplasia (CIN) 2 or 3, endometrial or extrauterine adenocarcinoma] were reviewed retrospectively to identify the cases of high-grade squamous intraepithelial lesion with endocervical glandular extension, using the Bethesda 2001 system. Cyto-histological correlation was performed. A high frequency of diverse glandular pathologies coexisted with high-grade cervical intraepithelial lesions on histology. This included endocervical glandular extension in 63%, benign glandular pathology in 33% and pre-neoplastic or malignant glandular pathology (endocervical glandular dysplasia, adenocarcinoma in situ and metastatic breast carcinoma) in 17% cases. On cytology, the sensitivity was 40%, specificity was 80% and positive predictive value was 86% for endocervical gland extension in high-grade squamous intraepithelial lesions. Special efforts to recognize endocervical glandular extension in high-grade squamous intraepithelial lesions and glandular neoplasia coexisting with squamous intraepithelial lesions from the heterogeneous category of AGC can contribute to increasing the diagnostic accuracy. The identification of endocervical glandular extension on cervical cytology would alert the gynaecologist to perform a thorough assessment of the endocervix during colposcopy. This could also help to decide on the need to perform deeper conization rather than loop electrosurgical excision procedure to ensure negative margins when colposcopic biopsy shows CIN 2 or 3.

Utility of p16INK4a, CEA, Ki67, P53 and ER/PR in the Differential Diagnosis of Benign, Premalignant, and Malignant Glandular Lesions of the Uterine Cervix and Their Relationship with Silverberg Scoring System for Endocervical Glandular Lesions

Early detection of premalignant and malignant glandular lesions of the uterine cervix and their distinction from benign mimics is crucial but sometimes difficult. In this study, we investigated utility of expression of p16, CEA, Ki67, p53 and ER/PR in evaluating the benign, premalignant, and malignant glandular lesions of the uterine cervix. A total of 35 cervical cone or LEEP cases were collected including 14 adenocarcinoma in situ (AIS), 7 endocervical glandular dysplasia (EGD), and 14 benign mimics (BM). A histological score for each case according to the criteria proposed by Silverberg group was assigned independently by 4 pathologists. Formalin-fixed, paraffin-embedded sections were immunostained with p16, CEA, p53, Ki67, and ER/PR. Immunoreactivity was scored based on intensity (0 = none, 1 = mild, 2 = moderate, 3 = marked) and percentage of cells staining (0 = <1%,1 = 2-10%, 2 = 11-40%, 3 = >40%). A comparison of histological scores and immunoscores in 3 diagnostic categories was analysed. The histological scores assigned independently by 4 pathologists were all equal or above 6 for AIS, between 3 and 5 for EGD, and equal or below 3 for BM. There was increased expression of p16 and CEA in EGD compared with BM (P < 0.05), with further increase in expression of these markers in AIS compared with EGD (P < 0.05). Ki67 expression was significantly increased in AIS compared to EGD (P < 0.05) as well as compared to BM (P < 0.05). Ki67 expression was only slightly increased in EGD as compared to BM. There was a loss of ER/PR in cervical AIS, but not in EGD. Our results indicate that the Silverberg scoring system is a useful tool in differential diagnosis of cervical glandular lesions for increased diagnostic accuracy and interobserver agreement. Most cervical glandular lesions can be differentiated by using a combination of histological scores with a panel of immunomarkers.

Endocervical glandular lesions: A diagnostic approach combining a semi-quantitative scoring method to the expression of CEA, MIB-1 and p16

To investigate whether combining a semi-quantitative scoring method with the immunohistochemical expression of CEA, MIB-1 and p16, would improve the diagnostic accuracy of endocervical glandular lesions. The hematoxylin and eosin-stained sections of 95 cervical biopsies were examined by 4 different observers and were grouped into three categories, benign, dysplasia and adenocarcinoma in situ, depending on the degree of nuclear stratification, nuclear atypia and the number of mitosis and apoptotic figures. Each case was also stained immunohistochemically with antibodies against CEA, Ki-67 (MIB-1) and p16. Staining was graded as negative, weak and positive. The accuracy of the scoring method alone was compared to the accuracy of combining the score with the immunostaining results. Using the semi-quantitative scoring system, most of the cases that were initially diagnosed as atypical hyperplasia or tuboendometrial metaplasia fell into the benign category. This scoring system discriminates effectively (Kruskal-Wallis, p<0.001) between the three categories (benign, endocervical glandular dysplasia and adenocarcinoma in situ). When analyzing the immunohistochemical score, only Ki-67 staining seems to be effective mostly in discriminating between normal glands or glands with atypical hyperplasia and epithelial glandular dysplasia. Ki-67, CEA and p16 failed to discriminate between tuboendometrial metaplasia and epithelial glandular dysplasia. Combining the semi-quantitative scoring system with the immunohistochemical results discriminates between the three categories equally well as the semi-quantitative scoring system alone (Kruskal-Wallis, p<0.001). Nevertheless, the proportion of cases that were classified similarly to the prestudy diagnosis was higher when the combined score was used. Combining a semi-quantitative scoring scheme with the immunohistochemical expression of CEA, MIB-1 and p16 seems to be of value in classifying some endocervical glandular lesions.

A cytohistologic study of atypical glandular cells detected in cervical smears during cervical screening tests in Iran

Atypical glandular cells (AGC) often cause diagnostic uncertainty in cervicovaginal smears. To determine the incidence of significant pathologies associated with AGC on Papanicolaou test, AGC smears were correlated with subsequent biopsy diagnoses. A retrospective review of archives of our cytology files for cervicovaginal smears diagnosed as AGC from April 1998 to March 2001 was performed. In 9390 cervicovaginal smears, AGC were reported in 76 (0.81%) cases, with histologic follow-up in 42 patients (55.3%). Twenty-two patients (52.4%) had preneoplastic or neoplastic, squamous, or glandular lesions on histologic examination. Among them were cervical intraepithelial neoplasia, basal cell abnormality of undetermined significance, cervical adenocarcinoma, endometrial hyperplasia or adenocarcinoma, vaginal adenocarcinoma, endocervical glandular dysplasia, metastatic breast carcinoma, and simple nonvillous trophoblastic tissue. Therefore, presence of AGC in cervical smears may exhibit a spectrum of findings, ranging from benign/reactive changes to squamous or glandular premalignancy or malignancy. A majority of these lesions are squamous dysplasia, and a significant number of patients had glandular malignancy. The results of the current study underline the importance of follow-up for patients with the diagnosis of AGC. To our knowledge, this is the first report in Iran showing the significance of AGC diagnosis.

Evaluation of p16 INK4a and pRb expression in cervical squamous and glandular neoplasia

p16 INK4a is known to play a critical role as a negative regulator of cell cycle progression and differentiation by controlling the activity of the tumor-suppressor protein pRb. The present study evaluated the expression of p16 INK4a and pRb in cervical squamous and glandular neoplasia. Immunohistochemical staining was performed for p16 INK4a and pRb in formalin-fixed, paraffin-embedded tissue sections of the uterine cervix using an indirect immunoperoxidase method. p16 INK4a staining was detected in 7 of 108 sections (6.5%) of normal squamous mucosa, in scattered ciliated columnar cells in 33 of 88 sections (37.5%) of normal endocervical glands, in 9 of 30 sections (30%) with Nabothian cysts, and in 4 of 4 areas (100%) of tubal metaplasia. In contrast, strong p16 INK4a staining was found in 13 of 18 cases (72.2%) of cervical intraepithelial neoplasia (CIN) I and in all cases of CIN II/III (n = 46), squamous cell carcinoma (n = 18), endocervical glandular dysplasia (n = 10), adenocarcinoma in situ (n = 23), and invasive adenocarcinoma (n = 12). pRb expression was detected in each diagnostic category; however, the proportion of pRb-positive cells was relatively decreased in high-grade premalignant and malignant lesions of the squamous and endocervical mucosa and showed a generally inverse correlation with the expression of p16 INK4a at the tissue level. These findings confirm a correlation between the expression of p16 INK4a and pRb in cervical neoplasias and indicate that p16 INK4a is a specific marker for premalignant and malignant lesions of the squamous and endocervical mucosa.

Is electrosurgical loop excision with negative margins sufficient treatment for cervical ACIS?

Objectives. A recent clinical practice guideline supports the conservative management of adenocarcinoma in situ of the cervix (ACIS) diagnosed or suspected before treatment. However, patients may be diagnosed with unsuspected ACIS found in a loop electrosurgical excisional procedure (LEEP) specimen done for squamous dysplasia. To assess the outcome in this group of patients, we retrospectively analyzed all our cases of cervical ACIS and endocervical glandular dysplasia (EGD) to determine if LEEP was sufficient treatment. Study Method. A retrospective review of all patients treated for ACIS–EGD from 1990 to 2003 at Kingston General Hospital Colposcopy Clinic was undertaken. Sixty patients were identified. Results. Of the 60 patients, 31 were diagnosed with ACIS–EGD only from the LEEP specimen. Twenty-two patients had ACIS and nine had EGD. Seven had further surgical procedures (five hysterectomies and two cold knife cone biopsies CKC) for positive LEEP margins. All seven of these specimens were disease free. Three of 31 LEEP patients were not compliant with colposcopic follow up. The remaining 28 patients were followed in our colposcopy clinic or by their family doctor for 6–107 months (median: 42; mean: 51) and have remained free of persistent or recurrent ACIS–EGD. Conclusion. Colposcopic follow-up with cytology and endocervical curettage (ECC) is acceptable for patients with ACIS–EGD found unexpectantly in LEEP specimens with negative margins. This is an alternative to proceeding to repeat LEEP, cold-knife conization, or simple hysterectomy, especially in patients desiring conservative management or preservation of fertility. Patients with positive margins, however, require further histologic evaluation.

Apoptosis, proliferation, and expression of p53 and bcl-2 in endocervical glandular intraepithelial lesions and invasive endocervical adenocarcinoma.

We evaluated apoptosis, proliferation, and p53 and bcl-2 expression in a spectrum of intraepithelial and invasive endocervical glandular lesions currently recognized by the World Health Organization as adenocarcinoma in situ, lesions with atypia "less than adenocarcinoma in situ" (endocervical glandular dysplasia and endocervical glandular atypia), and invasive adenocarcinoma. Aside from nuclear atypia, increased mitotic activity and apoptosis are consistent and closely correlated morphologic features of endocervical adenocarcinoma in situ. Apoptotic bodies and mitotic figures were counted in 32 examples of normal endocervical glands, 35 of endocervical glandular atypia, 30 of endocervical glandular dysplasia, 34 of adenocarcinoma in situ, and 30 of invasive adenocarcinoma. These results were correlated with immunohistochemical staining for MIB1, bcl-2, and p53 performed on 20 examples of each. Mitotic counts, p53 expression, and bcl-2 expression all increased significantly and in proportion to the degree of atypia in the spectrum of endocervical lesions. Apoptotic body counts and MIB1 expression also increased significantly with increasing atypia, but showed higher levels in adenocarcinoma in situ than in invasive adenocarcinoma. Apoptosis correlates with proliferation as measured by mitotic counts and MIB1, and also with p53 and bcl-2 expression. Apoptosis appears to be an important mechanism in the pathogenesis of endocervical glandular lesions and may be useful as an aid in their evaluation and diagnosis.

Proposal of a new scoring scheme for the diagnosis of noninvasive endocervical glandular lesions.

The differential diagnosis of endocervical glandular lesions can be very difficult, and the interobserver agreement on borderline cases can be low. We are proposing a new scoring system to aid in the reproducibility of the diagnosis of noninvasive endocervical glandular lesions. The total of 67 diagnostically difficult cases were independently reviewed by five pathologists. After the completion of the first round review, a consensus diagnosis was reached for each lesion by all participants. This consensus diagnosis was used as the reference diagnosis. According to the consensus, the lesions included 21 benign/reactive conditions, 7 endocervical glandular dysplasias, and 39 adenocarcinomas in situ. During the second round review, all cases were assessed using the new scoring scheme, according to which separate scores from 0 to 3 were given to each lesion for: 1) nuclear atypia, 2) stratification, and 3) sum of mitoses/apoptoses (counted in the two most active glands, and the average number used). These three scores were then added to result in the total score (0-3 = benign; 4-5 = endocervical glandular dysplasia; 6-9 = adenocarcinoma in situ). Complete agreement between all observers in the first round review was seen in 35 of 67 cases (52.2%), kappa = 0.565. This agreement improved in the second round with the use of the scoring scheme: 52 of 67 cases (77.6%), kappa = 0.705. If the benign and endocervical glandular dysplasia diagnostic categories were combined, the overall agreement in the second round review would be 63 of 67 cases (94%), meaning that the scheme affords accurate distinction between adenocarcinoma in situ and lesser lesions. We propose applying this new scoring scheme to the diagnosis of noninvasive endocervical glandular lesions to improve interobserver agreement. The use of this scheme will result in more consistency of data in series from different institutions and will allow uniformity on the issue of adenocarcinoma in situ precursor lesions.

Symposium part 3: Should pathologists diagnose endocervical preneoplastic lesions "less than" adenocarcinoma in situ?: Point.

The insufficient state of knowledge concerning the biology of endocervical glandular lesions is compounded by the lack of universal diagnostic criteria for recognizing endocervical glandular dysplasia. This study addressed the issue of diagnostic reproducibility of noninvasive endocervical glandular lesions and tested the proposed new scoring scheme designed to improve this reproducibility. We have shown that the application of this scheme has significantly improved interobserver agreement in all diagnostic categories. Moreover, the results of this study lend support to the recommendation not to diagnose endocervical glandular dysplasia in the clinical setting, although this category can be still reliably separated out for research purposes. Application of our scoring scheme will bring uniformity to the diagnosis of noninvasive endocervical glandular lesions and allow the study of a precursor to endocervical adenocarcinoma

Human papillomavirus 16/18 expression of endocervical glandular lesions: relationship with p53 and MIB-1 Expressions.

The pathogenesis of endocervical glandular lesions are not clearly understood. The aims of this study are to evaluate the etiologic role of human papillomavirus (HPV) 16/18 and the relationship of HPV 16/18, p53 and MIB-1 expressions in endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS) and adenocarcinoma. The materials included 14 endocervical adenocarcinoma and 5 AIS and 18 high grade EGD and 39 low grade EGD. Immunohistochemistry for p53 and MIB-1, and in situ PCR for HPV 16/18 were done. HPV 16/18 positivity was 84.2%, 16.7% and 17.9% in malignant glandular lesion (adenocarcinoma and AIS), high grade EGD and low grade EGD, respectively. P53 protein expression rates of malignant glandular lesions, high grade EGD and low grade EGD were 31.6%, 11.1%, and 0%, respectively. High MIB-1 labelling index was found in 73.7% of malignant glandular lesions, but in only 5.7% and 3.6% of high and low grade EGD, respectively. There were statistically significant differences in HPV 16/18, p53 and MIB-1 expressions between malignant endocervical glandular lesions and EGD, but no significant difference in p53 and MIB-1 expressions in relation to HPV 16/18 expression. In malignant endocervical glandular lesions, HPV 16/18 infection may be a major causative factor, but not be related to p53 and MIB-1 expressions.

Superficial Endometriosis of the Uterine Cervix

Twenty cases of superficial endometriosis of the uterine cervix that occurred in patients from 20 to 51 (mean 37.1) years of age are described. The majority of the cases were seen in consultation and were usually referred because of diagnostic problems; endocervical glandular dysplasia, adenocarcinoma in situ, or rarely invasive adenocarcinoma were a frequent consideration of the contributor. The endometriosis was almost always an incidental microscopic finding. The endometriotic foci were usually confined to the superficial third of the cervical wall, but in one case there was also involvement of the middle third of the cervical wall. Deep cervical endometriosis was not present in any case. The endometriotic glands were typically evenly spaced and were surrounded at least focally by endometriotic stroma in all cases. The endometriotic stromal cells, however, were significantly obscured by inflammatory cells (two cases), inflammatory cells and hemorrhage (two cases), hemorrhage (four cases), and in one case by smooth muscle metaplasia causing initial failure to recognize the stromal component of the process. The presence of mitotic figures in the glandular epithelium contributed to an initial diagnosis of a premalignant or malignant glandular lesion being made or seriously entertained in 10 cases. Awareness that mitotic figures may be conspicuous in endometriosis from women of reproductive age, the usually bland cytologic features of the endometriotic epithelium, and the presence of associated endometrial stromal cells all facilitate establishing the correct diagnosis.

Use of Monoclonal Antibody MIB-1 in Differential Diagnosis of Uterine Cervical Glandular Neoplasm

This study was undertaken to evaluate the significance of MIB-1 immunoreactivity in the discrimination of differential diagnosis of benign cervical lesion, endocervical glandular dysplasia, and endocervical adenocarcinoma on formalin-fixed, paraffinembedded tissue. Fifty-two cases were selected from the pathology files of Korea University Hospital from 1994 to 1998 and were composed of 25 cases of endocervical adenocarcinoma, including three cases in which squamous cell carcinoma coexists; six cases of endocervical glandular dysplasia associated with squamous cell carcinoma or cervical intraepithelial neoplasia (CIN); and 21 cases of chronic endocervicitis. Immunohistochemical staining for MIB-1 was performed after microwave treatment on formalin-fixed, paraffin-embedded tissue sections. MIB-1 expression was evaluated according to the labeling indexes. The labeling indexes were calculated for 52 specimens by means of image analysis (Quantification of Proliferation Index). The results are as follows; There was diffuse strong MIB-1 reactivity in endocervical adenocarcinoma (labeling index 37.6-61.4%, mean 54.9%), moderate spotty reactivity in endocervical glandular dysplasia (labeling index 27.9-42.6%, mean 35.1%), and minimal to focal reactivity in chronic endocervicitis (labeling index 0-24.4%, mean 5.2%). Significant differences in MIB-1 labeling indexes existed among the chronic endocervicitis group, the endocervical glandular dysplasia group, and endocervical adenocarcinoma group. In conclusion, MIB-1 immunostaining is of value in the differential diagnosis among benign cervical lesions, endocervical glandular dysplasia, and endocervical adenocarcinoma.

Immunohistochemical Demonstration of Aberrant Glycosylation and Epidermal Growth Factor Receptor in Tubal Metaplasia of the Uterine Cervix

Tubal metaplasia (TM) of the uterine cervix may be confused with endocervical glandular dysplasia or adenocarcinoma of the uterine cervix in histologic specimens. TM is characterized histologically by architecturally normal endocervical glands containing ciliated or clear cells, nonciliated cells, and intercalated or peg cells, resembling normal tubal mucosa. Although several characteristics of TM are still undetermined, TM is considered a benign lesion. In this study, the expressions of epithelial-specific antigen (ESA), epidermal growth factor receptor (EGFR), and fucosyl SSEA1 (Ley) antigens were examined by an immunohistochemical method in 14 cases of TM in the uterine cervix (5 with normal endocervix, 5 with endocervical glandular dysplasia, 3 with adenocarcinomain situ,and 1 with microinvasive adenocarcinoma). In the normal endocervical cells, expression of the EGFR antigen was rarely observed in the cytoplasm, and ESA staining was generally restricted to the basolateral membrane. Leyexpression was occasionally observed in the cytoplasm of subcolumnar reserve cells. On the other hand, expression of EGFR, ESA, and Leywas observed in the cytoplasm of TM as well as in adenocarcinomas of the uterine cervix. These results suggest that TM in the uterine cervix might possess a neoplastic character.

Distribution of Epithelial-Specific Antigen in Uterine Cervix with Endocervical Glandular Dysplasia

The natural history of cervical adenocarcinoma is largely unknown, and whether endocervical glandular dysplasia is a precursor lesion to malignant tumor formation is a controversial issue. The aim of this study was to clarify the relationship of endocervical glandular dysplasia to the uterine endocervical adenocarcinoma. Thirty-one cases of glandular abnormalities of the uterine cervix were identified histologically from January 1984 to April 1992. These included 11 cases of endocervical glandular dysplasia, 5 cases of adenocarcinomain situ,4 cases of microinvasive adenocarcinoma, and 11 cases of invasive adenocarcinoma. The immunohistochemical localization of epithelial-specific antigen (ESA) was examined in these cases of endocervical glandular dysplasia and related lesions, and was compared to 10 normal endocervical specimens. ESA immunoreactivities were usually present in the basolateral membrane of endocervical cells in the normal endocervix. However, the expressions of ESA were increasing from the basolateral membrane to the diffuse cytoplasmic membrane, along with the malignant transformation of the endocervical cells, in 6 of 11 cases with glandular dysplasia, in 9 of 9 cases within situand microinvasive adenocarcinomas, and in 11 of 11 cases with invasive adenocarcinomas. This finding indicates that ESA is a useful marker for endocervical glandular dysplasia and related lesions with malignant transformation, and suggests that endocervical glandular dysplasia may be a precursor lesion to uterine cervical adenocarcinomas.

A Clinicopathologic Study of Glandular Dysplasia of the Cervix

With the increasing incidence of cervical adenocarcinoma there is a growing interest in the detection and treatment of glandular precursors. A major obstacle to this research is that endocervical glandular dysplasia (EGD) is rare and infrequently reported. From a study of 30 patients it appears that EGD often occurs with concomitant squamous dysplasia and also benign and preinvasive glandular changes in the cervix and endometrium. If EGD is detected on cervical biopsy hysteroscopy, dilatation and curettage and cone biopsy should be performed.

Glandular Lesions of the Cervix

To determine the validity and reproducibility of various cytologic criteria as discriminators between different glandular lesions of the cervix. Seventy-three cervicovaginal smears with glandular lesions and a documented histologic and/ or clinical correlation were studied. The lesions included reactive changes, low grade glandular intraepithelial lesion (LGIL) (encompassing endocervical glandular dysplasia), high grade glandular intraepithelial lesion (HGIL) (encompassing adenocarcinoma in situ) and invasive adenocarcinoma (IA). Twenty-three cytologic criteria were used to evaluate the smears, and the results were scored and statistically analyzed. Reactive lesions consistently showed well-defined cell borders, normal nuclear/cytoplasmic (N/C) ratio, minimal or absent nuclear overlapping, round to oval nuclei with fine chromatin and prominent nucleoli. HGIL (adenocarcinoma in situ) showed feathered edges, rosettes, cell strips, increased N/C ratio, elongated nuclei, marked nuclear overlapping and nuclei with hyperchromatic, coarse chromatin. IA shared features with HGIL but had a greater tendency to show a dirty background, single cells, mitotic figures, nuclear pleomorphism and large nucleoli. Logistic regression studies indicated that the presence of mitotic figures, a dirty background and single cells increases the odds ratio for predicting invasion. LGIL showed features similar to those of high grade lesions, but the changes were more subtle. These lesions were also less cellular and less likely to show cell strips, feathered edges and rosettes. Similar to HGIL and IA, LGIL showed nuclear overlapping, increased N/C ratio, oval to elongated nuclei and nuclear hyperchromasia. There is overlap between the cytologic criteria for the various glandular lesions of the cervix. However, some of these criteria can consistently distinguish clinically significant lesions from reactive benign changes seen in the glandular epithelium.

Artifactual endocervical atypia induced by endocervical brush collection.

The cytologic distinctions between artifactual atypia induced by endocervical brush collection, endocervical glandular repair, and endocervical glandular dysplasia or neoplasia are often difficult. This difficulty is amplified by the lack of accepted cytologic criteria for endocervical glandular dysplasia, and the fact that earlier studies defining the significant cytologic features of endocervical adenocarcinoma in situ and endocervical adenocarcinoma (endocervical neoplasia) utilized a swab for endocervical cell retrieval. With the almost universal adoption of the endocervical brush, it is important to redefine those cytologic characteristics that differentiate true endocervical glandular dysplasia or neoplasia from reactive or reparative processes and instrument artifact. From our data, it appears that the classically described cytologic discriminators between a negative smear and smears of endocervical dysplasia or neoplasia are basically unchanged with some minor modifications for endocervical brush-collected samples.

Human papillomavirus DNA in glandular lesions of the uterine cervix.

To assess the role of human papillomavirus in the pathogenesis of adenocarcinoma in situ, endocervical glandular dysplasia (a presumed precursor of adenocarcinoma) and endocervical glandular epithelial giant cell change. Viral detection was carried out using an in situ hybridisation technique on paraffin wax sections. Biotinylated probes for human papillomavirus types 6/11, 16/18, 31/33/35 were used with a colorimetric detection system. Nine out of 21 (43%) cases of adenocarcinoma in situ contained human papillomavirus types 16/18, one of which was also positive for 31/33/35. Ten cases of glandular dysplasia and four cases of glandular epithelial multinucleation did not react with the probes used. These results indicate that while adenocarcinoma in situ is strongly associated with human papillomavirus infection, endocervical glandular dysplasia and glandular epithelial multinucleation are probably not associated with the virus.