Glandular Atypia Research Articles

Reclassification and analysis of clinical significance of atypical glandular cells on ThinPrep using Bethesda 2001: Geneva experience.

The category "atypical glandular cells" (AGC) in The Bethesda System (TBS) 2001 represents equivocal glandular atypia. The objective was to determine the clinical significance of diagnosing AGC using new TBS 2001 on Thin-Prep. There is scant information on the diagnosis of AGC and its outcome on ThinPrep using TBS 2001. 174 "ThinPrep" Pap tests reported as atypical glandular cells of unknown significance (AGUS) using TBS 1991 during the period (2001-2004) were reclassified using AGC subcategories of TBS 2001. Follow-up histology was correlated with AGC subcategories of TBS 2001 and in women <40 and >or=40 years of age. The mean AGC rate significantly decreased from 0.7% to 0.3%. (p <0.02). The frequency of clinically significant lesions on followup was higher with AGC diagnosis (51%, 21/41) than AGUS diagnosis (36%, 37/103). It was significantly higher for atypical endocervical cells favouring neoplasia (AEC-FN) (67%, 4/6) and AGC with concurrent squamous intraepithelial lesions (SIL) (67%, 8/12) than for the atypical endocervical cells, not otherwise specified (AECNOS) subcategory (12.5%, 2/16). All clinically significant lesions were high grade squamous intraepithelial lesions (HSIL) in women <40 years but in women >or=40 years, the majority (70%) were glandular. In categories atypical glandular cells favouring neoplasia (AGC-FN) and atypical endometrial cells (AEMC) all women had clinically significant glandular lesions. AEC-FN, AGC-FN, AEMC and AGC with concurrent SIL subcategories represented high risk diagnoses. The sequence of further investigations may vary by age and presence of postmenopausal bleeding.

O‐5 Reporting profile review post LBC conversion

This study was undertaken by a pathology network providing cervical cytology screening services across two trusts, using SurePath LBC technology. The aim of this study was to establish if LBC screening results and histological correlation was in concordance with the pilot sites findings, with particular reference to glandular atypia. All the data was extrapolated from the Apex database for the specified times using Cognos. Data from Jan to Dec 2004 (last complete year conventional cytology) and Jan to Dec 2006 (first complete year LBC) have been used in this study.In summary from 2004 to 2006 we found: A reduction in the inadequate rate to 1.1% Low‐grade rates remained stable 4.9% High grade grades increased by 45% (PPV 84%) Glandular neoplasia increased by 75% with a PPV for endocervical origin of 92% and for endometrial cell origin of 43% Borderline endocervical rates remained stable 0.036% (PPV 50%)The PPV of endometrial glandular neoplasia was disappointing and possibly reflects increased endometrial sampling, reduced adherence to mid‐cycle sampling, and our lack of experience, resulting in poor endometrial interpretation. In conclusion, our data produced a different profile to the pilot sites with increase high grade and ? Glandular neoplasia reporting, but with a significant overcall in endometrial glandular neoplasia.

S-100A4 Protein and Mesothelin Expression in Dysplasia and Carcinoma of the Extrahepatic Bile Duct

We evaluated the expression of S100A4 protein and mesothelin in dysplasia and carcinoma of the extrahepatic bile duct (EBD) and their potential use as adjuncts for differentiating carcinomatous and significant high-grade dysplastic epithelium from reactive or inflammatory glandular atypia of the EBD. We used immunohistochemical analysis on formalin-fixed tissue sections from 10 cases of carcinoma, 6 cases of high-grade dysphasia (HGD), 4 cases of low-grade dysplasia (LGD), and 10 cases of benign or reactive or inflammatory epithelium from the EBD. Expression of S100A4 protein was observed in 8 invasive carcinomas (80%), 5 HGD/carcinoma in situ cases (83%), and 0 LGDs. Mesothelin was expressed in 5 (50%) of 10 adenocarcinomas, 1 (17%) of 6 HGD/adenocarcinoma in situ cases, and 0 LGDs. No case of normal or reactive epithelium was positive for S100A4 protein or mesothelin. Mesothelin has moderate sensitivity and high specificity, whereas S100A4 protein is sensitive and specific for the identification of carcinoma and HGD of the EBD. S100A4 protein alone or combined with mesothelin can be used as an adjunct in differentiating carcinomatous and significant high-grade dysplastic epithelium from LGD and reactive or inflammatory glandular atypia of the EBD.

Psammoma bodies in cervicovaginal cytology specimens: A clinicopathological analysis of 31 cases

Background. Psammoma bodies in cervicovaginal cytology specimens are associated with malignant and benign conditions. Few studies have evaluated which features distinguish patients with underlying malignancy from those with benign conditions. Methods. Pathology files were searched for cervicovaginal specimens having psammoma bodies. The cytology specimen was assessed for the background, glandular atypia, squamous atypia, and presence of non-psammomatous calcifications. Clinical data was obtained from chart review. Results. Nineteen women (mean age 42.7 years) had benign outcomes. None had signs or symptoms suggesting malignancy. None had highly atypical or malignant appearing glandular cells. Twelve women had malignant neoplasms (mean age 56 years), including 6 with recurrent disease. Four women without prior malignancy had worrisome signs including bleeding or mass. All six women with prior malignancy had signs of recurrent disease. All specimens contained highly atypical or malignant glandular cells. Conclusions. The only cytologic feature predictive of outcome was the presence of highly atypical gladular cells in the specimen ( P = 0.001), but these cells may be few. Women with underlying malignancy were older than those with benign outcome ( P = 0.014) and more likely to be postmenopausal ( P = 0.05). Women with malignancy had signs that warranted additional investigation whereas those with benign outcome were usually asymptomic ( P = 0.001).

CD10, Actin, and Vimentin Expression in Breast Phyllodes Tumors Correlates with Tumor Grades of the WHO Grading System

The discrimination of borderline from malignant primary breast phyllodes (PT) tumor is still unclear. We studied 22 PT cases to investigate the immunohistochemical expression (staining of stromal CD10, SMA [smooth muscle actin], and vimentin) as well as the features of focal glandular atypia to determine whether these correlated with the histopathologic grading system. In our results, the stromal staining of CD10 was positive in 4 of 6 malignant and 2 of 5 borderline PT cases, but negative in all benign PT cases. Stromal actin and intraglandular vimentin-expressive tumor cells were found in 5 of 6 malignant PT cases but not in borderline and benign PT cases. There is a significant difference in the panel of stromal CD10, actin, and vimentin expression between borderline and malignant PT (p<0.05). Besides, the progression of malignant potential breast phyllodes tumor may cause glandular epithelium atypia with loss of polarity.

Current practice of diagnosis and reporting of prostatic intraepithelial neoplasia and glandular atypia among genitourinary pathologists

The criteria for diagnosing prostatic intraepithelial neoplasia (PIN) and lesions suspicious for cancer are described in the literature. However, it is unknown how these are applied in practice by experts in genitourinary (GU) pathology. A questionnaire was sent to 93 GU pathologists in countries around the world with the purpose of surveying current practices. The response rate was 69% including 40 North American pathologists and 24 from other continents. For preneoplastic lesions, the term PIN was universally endorsed by the respondents. PIN was graded by 83%, usually as low/high-grade PIN (LGPIN/HGPIN) or as HGPIN only. Most respondents would usually not report lesions that may qualify for LGPIN. A majority (81%) did not specify architectural patterns of PIN. With both HGPIN and invasive cancer present, 69% would still mention HGPIN. Among the diagnostic criteria for HGPIN were any nucleoli visible (52%), or nucleoli seen in at least 10% of cells (33%). However, 56% would diagnose HGPIN in the absence of prominent nucleoli, most commonly based on prominent pleomorphism, marked hyperchromasia or mitotic figures. The number of cores involved with HGPIN was specified by 50%. Lesions suspicious for but not diagnostic of carcinoma were reported by 45% as atypia, atypical glands or suspicious for cancer and by 42% as atypical small acinar proliferation. The degree of suspicion was further defined by 41%. Our survey data may serve as a guideline to general pathologists on how to diagnose and report atypia and PIN in prostate biopsies.

Effect of Probiotics and Triple Eradication Therapy on the Cyclooxygenase (COX)‐2 Expression, Apoptosis, and Functional Gastric Mucosal Impairment in Helicobacter pylori‐Infected Mongolian Gerbils

Helicobacter pylori infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis that mimics H. pylori-positive patients developing gastric ulcer and gastric cancer, but the effect of probiotic therapy on functional aspects of this infection remains unknown. We compared the effects of intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) colony forming units/ml) with or without triple therapy including omeprazole, amoxicillin, and tinidazol or probiotic bacteria Lacidofil. Histology of glandular mucosa, the viable H. pylori, and density of H. pylori colonization were evaluated. The gastric blood flow was measured by H2-gas clearance method; the plasma gastrin and gastric luminal somatostatin were determined by RIA and expression of cyclooxygenase (COX)-2 and apoptotic Bax and Bcl-2 proteins were evaluated by Western blot. The gastric H. pylori infection was detected in all animals by histology and H. pylori culture. Basal gastric acid was significantly reduced in H. pylori-infected animals but not in those with triple therapy or Lacidofil. Early lesions were seen already 4 weeks upon H. pylori inoculation and consisted of chronic gastritis and glandular atypia associated with typical regenerative hyperplasia and increased mitotic activity and formation of apoptotic bodies. The H. pylori infection was accompanied by the fall in gastric blood flow, the marked increase in plasma gastrin, the significant fall in gastric somatostatin levels and Bcl-2 protein expression, and the rise in expression of COX-2 and Bax proteins. These mucosal changes were counteracted by the triple therapy and Lacidofil. H. pylori infection in gerbils, associated with regenerative hyperplasia of glandular structure, results in the suppression of gastric secretion, overexpression of COX-2, and enhancement in apoptosis and impairment of both, gastric blood flow and gastrin-somatostatin link that were reversed by anti-H. pylori triple therapy and attenuated by probiotics.

Glandular Atypia In Cervical Smear: Cytohistologic And Clinical Correlation

The purpose of this study was to audit and analyse all the cases of Glandular Atypia reported by cervical cytology. The cytological features were correlated with histopathology diagnosis and subsequent follow up of these patients. Design: A retrospective case note based study from January 1995 through December 1999, identifying all patients with cervical smears reported as Glandular Atypia. Their subsequent colposcopic examination, treatment, final diagnosis and follow up were retrieved from the notes. Results: Of the 78 women with Glandular Atypia reported in their cervical smear, the mean age was 38.6 years and 21 (27%) were nulliparous. The median follow up of these women was 18 months. On further investigation 4 cases were diagnosed to have endocervical adenocarcinoma, three cases of squamous cell carcinoma of the cervix and three cases of endometrial adenocarcinoma. One case of microinvasive adenocarcinoma of the cervix was diagnosed. Collectively 11 cases (14%) were malignant in 78 cases. Seven cases (8.9%) were diagnosed as Cervical Glandular Intraepithelial Neoplasia (CGIN) and 38 cases (48.7%) of cervical intraepithelial Neoplasia (CIN) with or without involvement of the cervical glands. Eight cases (10.2%) were diagnosed as chronic cervicitis and two cases of cervical endometriosis. Three cases (3.8%) only were normal following investigations. Conclusion: This retrospective study suggested that a diagnosis of Glandular Atypia in the cervical smears correlated with clinically significant lesions in the majority of cases.CIN and CGIN were the most common lesions identified. Close follow up with Colposcopy and both cytobrush and spatula cytology is recommended in-patients where CGIN has been diagnosed and treated by local ablation or excision without hysterectomy.

Atypical glandular cells: improvement in cytohistologic correlation by the 2001 Bethesda system

The objective of this article was to evaluate clinical significance of glandular atypia on Papanicolaou smear, to compare the Bethesda system (TBS) 2001 with the 1991 revision, and to determine whether there is any improvement in the cytohistologic correlation by the new system. Cytology files of 18,955 patients were reviewed for diagnosis of atypical glandular cells of undetermined significance (AGUS), and histopathology files were searched. Cervical smears of these patients were reclassified according to TBS 2001. Of the 18,955 specimens, 89 (0.46%) were diagnosed as AGUS. Of these 89 women, 76 (85.3%) accepted the follow-up protocol of our hospital. In reevaluation according to TBS 2001, 31 specimens were reevaluated as atypical glandular cells (AGC) and 3 were reevaluated as adenocarcinoma in situ, 8 as AGC with concomitant squamous cell abnormalities, 1 as atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesions, and 33 as negative. Thirty-one (93.9%) of these 33 negative cases were in the AGUS-reactive category in the initial examination. The difference between the rates of the malignant pathologies in the AGUS (25%, 19/76) and in the AGC (42.8%, 18/42) categories was significant (chi(2)= 4.0, P= 0.04). The new terminology of AGC is more likely to suggest a clinically significant lesion than TBS 1991. Repeated cytologic testing during follow-up seems to be unacceptable.

Resultados de una serie de 6000 pacientes con biopsia transrectal ecodirigida de próstata: Parte I: Anatomía patológica, tacto rectal, ecografía transrectal y PSA

To analyze the results of transrectal ultrasound (TRUS) guided biopsy of the prostate in 6000 patients, and their relation to common-use clinical parameters.We collected PSA, digital rectal examination, TRUS characteristics, and pathology report in a data- base including 6000 patients who underwent sextant TRUS biopsy from 1994 to December 2002. 861 of them underwent more than one biopsy, accounting for a total of 7127 biopsies. Sextant biopsy with samples from the most lateral portions of the prostate was the standard procedure so that they included peripheral zone only. We analyze pathological results and their relation with clinical variables.Total percentage of cancer in biopsy samples was 42.6%, with 39.1% in the first biopsy. Overall, repeated biopsies resulted in a 3.5% diagnostic yield increase. PIN or focal glandular atypia were detected in 2.0% and 2.1% of the cases respectively. The percentage of patients with Gleason score =<6 increased from 41.8% in the first biopsy to 70% in the third. Similarly, single core involvement increased from 21.% to 65%. Digital rectal examination and presence of hypoechogenic nodules specificity were 82.6 and 78.2% respectively. The incidence of prostate cancer with PSA between 4 and 10 ng/ml was 29.6%, 16.7% in those with PSA lower than 4 ng/ml.TRUS biopsy of the lateral prostatic areas offers a good diagnostic yield in comparison with most series of extensive biopsies. The sensitivity of TRUS has decreased but it maintains a high specificity which should not be forgotten when planning the TRUS strategy

Minimally Invasive Video-Assisted Thyroidectomy: One Year Initial Experience

Barrett's oesophagus predisposes to adenocarcinoma. However, most patients with Barrett's oesophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and the subjective assessment of dysplasia. We investigated whether a non-endoscopic device, the Cytosponge, could be coupled with clinical and molecular biomarkers to identify a group of patients with low risk of progression suitable for non-endoscopic follow-up.In this multicentre cohort study (BEST2), patients with Barrett's oesophagus underwent the Cytosponge test before their surveillance endoscopy. We collected clinical and demographic data and tested Cytosponge samples for a molecular biomarker panel including three protein biomarkers (P53, c-Myc, and Aurora kinase A), two methylation markers (MYOD1 and RUNX3), glandular atypia, and TP53 mutation status. We used a multivariable logistic regression model to compute the conditional probability of dysplasia status. We selected a simple model with high classification accuracy and applied it to an independent validation cohort. The BEST2 study is registered with ISRCTN, number 12730505.The discovery cohort consisted of 468 patients with Barrett's oesophagus and intestinal metaplasia. Of these, 376 had no dysplasia and 92 had high-grade dysplasia or intramucosal adenocarcinoma. In the discovery cohort, a model with high classification accuracy consisted of glandular atypia, P53 abnormality, and Aurora kinase A positivity, and the interaction of age, waist-to-hip ratio, and length of the Barrett's oesophagus segment. 162 (35%) of 468 of patients fell into the low-risk category and the probability of being a true non-dysplastic patient was 100% (99% CI 96–100) and the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 0% (0–4). 238 (51%) of participants were classified as of moderate risk; the probability of having high-grade dysplasia was 14% (9–21). 58 (12%) of participants were classified as high-risk; the probability of having non-dysplastic endoscopic biopsies was 13% (5–27), whereas the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 87% (73–95). In the validation cohort (65 patients), 51 were non-dysplastic and 14 had high-grade dysplasia. In this cohort, 25 (38%) of 65 patients were classified as being low-risk, and the probability of being non-dysplastic was 96·0% (99% CI 73·80–99·99). The moderate-risk group comprised 27 non-dysplastic and eight high-grade dysplasia cases, whereas the high-risk group (8% of the cohort) had no non-dysplastic cases and five patients with high-grade dysplasia.A combination of biomarker assays from a single Cytosponge sample can be used to determine a group of patients at low risk of progression, for whom endoscopy could be avoided. This strategy could help to avoid overdiagnosis and overtreatment in patients with Barrett's oesophagus.Cancer Research UK.

The Relationship of Glands to Thick-Wall Blood Vessels as a Marker of Invasion in Endocervical Adenocarcinoma

The recognition of early invasion in endocervical adenocarcinomas can be difficult. We evaluated the proximity of endocervical glands and their pattern of infiltration in relation to thick-wall blood vessels as potential markers of invasion in a series of invasive endocervical adenocarcinomas removed by cone biopsy or hysterectomy. Routinely stained slides were examined from 50 invasive endocervical adenocarcinomas (37 of usual type and 13 of minimal deviation type), 26 noninvasive lesions (14 cases of adenocarcinoma in situ, 7 cases of hyperplasia, 4 cases of tunnel clusters, 1 adenomyoma), and 20 normal cervices, including 7 with deep nabothian cysts. The range of vessel wall thickness using an ocular micrometer was recorded in each specimen. A blood vessel with a wall > or =36-microm thick was defined as thick-walled. Both the blood vessel wall thickness and distance to the closest gland was recorded for each case. The median distance from a thick-wall blood vessel to a gland in the invasive tumors was 30 microm compared with 168 microm in the noninvasive group. In both groups, the measured blood vessel wall had a median thickness of 42 microm. The pattern of infiltration of glands around the thick-wall vessels was classified as "circumferential," in which multiple glands circumferentially enveloped the vessel, or "molded," in which single or multiple distorted glands were molded around the vessel. The circumferential and molded patterns were identified in 35 (70%) and 10 (20%) of 50 invasive adenocarcinomas, respectively. Of the 26 lesions in the noninvasive group, only 3 (6%) had a circumferential pattern and none had a molded pattern. Importantly, none of the cases in the noninvasive group showed either pattern in the presence of glandular atypia. In conclusion, close proximity of glands to thick-wall blood vessels (distance from the closest gland to a thick-wall vessel less than or equal to the thickness of the vessel wall) seems to be a useful feature in the diagnosis of invasive endocervical adenocarcinoma. This feature, in combination with certain glandular growth patterns and cytologic atypia, can be highly suggestive, if not diagnostic, of invasive carcinoma.

SCHISTOSOMA COLITIS

Schistosomiasis is a major source of morbidity and mortality for developing countries in Africa, South America, the Caribbean, the Middle East, and Asia. Tourism and immigration result in schistosomiasis cases presenting in the developed world. It is a human disease syndrome caused by infection from one of several species of parasitic trematodes of the genus Schistosoma. The adult flukes lay large numbers of eggs in the walls of the intestines or bladder, some of which flow through the bloodstream to the liver eliciting an inflammatory response in those regions. We present a case of Schistosoma Colitis which is uncommonly seen in the United States. A 48 year-old male, an immigrant from Brazil, presented with 4 days of severe, intermittent cramping abdominal pain located in the epigastrium and left-lower quadrant. It was associated with nausea, subjective fevers and intermittent non-bloody watery diarrhea. On examination, he was febrile to 100.1F, tachycardic at 102 beat per minute, and tachypneic at 24 breaths per minute. His blood pressure was 111/67. He had epigastric and left-lower quadrant tendernes with presence of guarding but no rebound tenderness. He had no rectal mass palpable and was guaiac negative. Laboratory data on presentation revealed WBC of 12.2 TH/UL with 10.4% eosinophils. CT scan of the abdomen and pelvis showed wall thickening throughout the colon with sparing of the sigmoid. The patient was initially treated with intravenous Flagyl, ampicillin and gentamicin. The stool studies including fecal leucocytes, C. difficile, ova and parasites were normal. Colonoscopy revealed mild edema and patchy erythema throughout the colon. Random biopsies from the colon showed moderately active, chronic colitis with reactive glandular atypia. Schistosome eggs were present in the mucosa. Rectal biopsy revealed similar findings. The patient was then started on Praziquantel 1200 mg QID for 3 days with good response. Schistosoma colitis is an unsual etiology of abdominal pain in the nonendemic areas. It is estimated that 400,000 immigrants from endemic regions may harbor the infection. Exposure to schistosomiasis is a health hazard for U.S. citizens who travel to endemic areas. Hence, we need to be aware of it in our differential when evaluating patients with abdominal pain who are from or have recently travelled to an endemic area.

An audit of cervical smears reported to contain atypical glandular cells.

The terminology and classification system for the reporting of cervical smears is currently under review. However, evidence on which to base the reporting of atypical cervical glandular cells is lacking. This audit of glandular atypia reporting in cervical smears provides evidence to support a three-tier sub-classification system for cervical glandular atypia. The three sub-classifications are distinct with respect to their positive predictive values and to the cell type of the abnormality as confirmed by histology and therefore relate to further clinical investigation.

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.

P16INK4a is a useful marker for the diagnosis of adenocarcinoma of the cervix uteri and its precursors: an immunohistochemical study with immunocytochemical correlations.

p16 is a tumor suppressor gene that plays a central role in the regulation of the cell cycle. In squamous cervical cancers, overexpression of p16 is induced by HPV and associated with the carcinogenesis of cervical epithelia. The aim of this study was to determine whether immunostaining of p16 is useful in detecting adenocarcinomas of the cervix uteri in histologic and cytologic routine specimens. A total of 45 surgical specimens, including 18 cases of invasive carcinoma, 8 cases of adenocarcinoma in situ, 4 cases of endocervical glandular atypia (cervical glandular intraepithelial neoplasia), and 15 reactive lesions of the endocervical glands were immunostained using a specific anti-human p16 monoclonal antibody (clone E6H4, mtm laboratories AG, Heidelberg, Germany). Furthermore, immunocytochemical analysis was performed on 10 preoperative ThinPrep cytologic samples with abnormal glandular cells and compared with the human papillomavirus status as assessed with the Hybrid Capture II test. p16 was detected immunohistochemically in all 26 cases of adenocarcinoma of the cervix uteri, including 18 invasive and 8 in situ carcinomas. Only a focal expression was evidenced in the four specimens with endocervical glandular atypia, and no reaction was found in reactive lesions. Also, the immunocytochemical analysis on the 10 ThinPrep specimens evidenced a strong expression of p16 in neoplastic endocervical cells. In all cases this was associated with a high-risk HPV-positive typing. p16 is a useful marker for the detection of the adenocarcinoma of the cervix uteri and its precursors. The immunocytochemical detection on ThinPrep specimens may contribute to an early detection of endocervical lesions.

Adénocarcinome in situ de l’endocol : difficultés du diagnostic cyto-histologique

In situ adenocarcinoma is regarded as the precursor of invasive adenocarcinoma. It is asymptomatic and early diagnosis relies solely on cytopathologist. It is usually discovered on a cone for squamous CIN. When diagnosis is made by biopsy, conisation is required to exclude invasive adenocarcinoma. Lesion is histologically caracterised by epitheliomatous transformation of endocervical glands without invasion of the chorion. By the appearance of glandular cells, different histological varieties are described. They have no influence on the pronostic. Several benign lesions may mimic adenocarcinoma : tubar metaplasia, glandular atypia due to inflammation or irradiation, mesonephric remnants and microglandular hyperplasia. Precursor lesions (atypical hyperplasia, glandular dysplasia, CIGNI and II) are badly morphologically defined. Preferential location of in situ adenocarcinoma is the transformation zone. Because of this topography, if the surgical margins are disease free, conisation alone may be adequate therapy. HPV infection (mainly HPV 18) are incriminated in its pathogenesis.

Significance of AGUS Pap Smears in Pregnant and Postpartum Women

To study the clinical significance of atypical glandular cells of undertermined significance (AGUS) in pregnant and postpartum women. We evaluated 35 women who were pregnant (30) or within three months postpartum (5) and had a cytologic diagnosis of AGUS. Twenty-seven (77%) patients had follow-up: 17 (63%) patients underwent colposcopic examination and biopsy, and 10 (37%) had repeat Pap smears. Eight patients were lost to follow-up. Five (29.4%) patients had a squamous intraepithelial lesion (SIL), including three high grade and two low grade, on subsequent biopsy. The remaining (70.6%) patients had benign pathology, which included 5 chronic cervicitis, 4 endocervical and/or endometrial polyps, 2 Arias-Stella reaction and 1 microglandular hyperplasia. Among the patients with repeat Pap smears, two had persistent AGUS/atypical squamous cells of undetermined significance, the remaining cases were within normal limits. Pregnancy-related changes may present with glandular atypia. In addition, about one-third of pregnant and postpartum women with a diagnosis of AGUS had SIL on subsequent biopsy; that rate is similar to that in nonpregnant women. Therefore, pregnant women with a cytologic diagnosis of AGUS should be followed closely.

Clinical significance of atypical glandular cells of undetermined significance in postmenopausal women

Glandular atypia in Papanicolaou (Pap) smears from postmenopausal women is encountered frequently. This finding can be the result of artifactual alterations such as drying artifacts and inflammatory changes or may represent a squamous or glandular, preneoplastic or neoplastic process. Therefore, it is important to determine the clinical implication of a diagnosis of atypical glandular cells of undetermined significance (AGUS) in postmenopausal patients. A total of 30,036 Pap smears were obtained from postmenopausal women between 1995 and 1997. Among these smears, 154 (0.51%) had a diagnosis of AGUS. Follow-up was available for 133 patients (86.4%); 110 patients (82.7%) had histologic follow-up (including cervical biopsy, endocervical [EC] curettage, and/or endometrial [EM] biopsy) and 23 patients (17.3%) had repeat smears. Thirty-six of 110 patients (32.7%) were found to have a clinically significant lesion (defined as a preneoplastic or neoplastic, glandular or squamous lesion) on subsequent histologic follow-up. Nineteen patients (53%) had glandular lesions (15 EM adenocarcinoma [ACA] cases, 2 EC ACA cases, 1 EC adenocarcinoma is situ case, and 1 EM hyperplasia case). Seventeen patients (47%) had a squamous intraepithelial lesion (SIL) (6 cases of low-grade SIL, 9 cases of high-grade [HGIL], and 2 cases of squamous cell carcinoma). Among those patients with repeat Pap smears, five patients had persistent AGUS/atypical squamous cells of undetermined significance and one patient had an SIL. The incidence of AGUS among postmenopausal patients was similar to that of the general population (0.51% vs. 0.56%; P > 0.05). A significant percentage of these patients were found to have a clinically significant lesion on subsequent follow-up. Furthermore, a majority of these lesions were ACA (53%) or HGSIL (26%). The findings of the current study strongly suggest the need for the close follow-up of postmenopausal patients with a diagnosis of AGUS. Cancer (Cancer Cytopathol)

Management of women with minor abnormalities of the cervix detected on screening: a qualitative study

To examine the consistency of decisions by pathology staff and general practitioners in managing women in whom minor cervical abnormalities are detected by screening, with current National Health and Medical Research (NHMRC) Council guidelines, and to look at reasons for inconsistencies. Qualitative interview study. 14 pathology staff (12 pathologists and two cytoscientists) from 10 of the 17 laboratories providing cervical cytology services in Victoria, and a sample of 22 GPs from metropolitan and rural locations in Victoria. Comparison of management practice with NHMRC guidelines; reasons for current decision-making practice. Most pathologists provided more cautious recommendations for minor abnormalities of the cervix than the NHMRC recommendations in all reporting categories except human papillomavirus. Pathologists had concerns about the appropriateness of the NHMRC recommendations, particularly for glandular atypia, lack of an endocervical component and inflammatory smears, where they believed that the NHMRC recommendations were not well supported by evidence. GPs generally followed the recommendations of their laboratories. Medicolegal concerns were a major influence on clinical decisions for both pathologists and GPs, and have contributed to the development of cautious management practice. Reporting and management practice of pathologists and GPs reflects the ambiguity of minor cervical abnormalities that the NHMRC guidelines fail to highlight. Many pathologists and GPs are reluctant to follow NHMRC guidelines because they believe they are inadequate for some minor cervical abnormalities. The cervical screening guidelines should be reviewed according to the NHMRC guidelines for developing clinical practice guidelines, to promote consistent practice based on an up-to-date, accurate evidence base.