Atypical endocervical glandular cells: Accuracy of cytologic diagnosis

Atypical cells thought to be of endocervical glandular origin often cause diagnostic uncertainty in cervicovaginal smears. For this reason consecutive cases of endocervical glandular atypia diagnosed in smears were correlated with subsequent biopsy diagnoses and then retrospectively reviewed. Smears were originally diagnosed as “mild glandular atypia, probably reactive” or “severe glandular atypia, suggestive of adenocarcinoma in situ” (AIS). Biopsy follow-up was obtained on 34 of 58 patients diagnosed with severe endocervical glandular atypia. Nine patients (26%) had AIS, three with concomitant high-grade squamous intraepithelial lesions (HSIL) and two with invasive adenocarcinoma. Eighteen patients (53%) had HSIL only. Seven had benign changes. Of 152 patients diagnosed with mild glandular atypia, biopsy follow-up was obtained on 40. One patient had AIS; 14 (35%) had HSIL; one had low-grade SIL (LSIL); and 24 (60%) had benign changes. Blinded review of these smears yielded results similar to those in the biopsy follow-up, that is, the prediction of AIS on smears included most cases of AIS, some invasive adenocarcinomas, a significant number of HSIL cases and a few benign lesions. A review diagnosis of “reactive glandular cells” proved to be HSIL in 31% of cases and AIS in one case. We conclude that patients with a diagnosis of severe glandular atypia in smears may prove to have AIS or invasive adenocarcinoma, but often have HSIL without concomitant AIS. In addition, although “reactive” glandular atypia in smears usually reflects a benign condition, a significant minority of such patients prove to have HSIL. © 1995 Wiley-Liss, Inc.     

Adenocarcinoma in colonic brushing cytology: High-grade dysplasia as a diagnostic pitfall

Cytologic evaluation of brushing specimens obtained from the colon may be useful in the diagnosis of neoplastic and inflammatory lesions, as previous studies have reported favorable sensitivity and specificity figures for this procedure. In this study, we report our experience with 80 colonic brushings examined over a 5-yr period. Thirty cases received an atypical or malignant cytologic diagnosis. Nineteen of 20 cases diagnosed cytologically as adenocarcinoma revealed adenocarcinoma on biopsy; one case showed only adenomatous epithelium on biopsy and subsequent resection. Cases diagnosed cytologically as "atypical" or "adenomatous" showed adenocarcinoma, adenoma, and inflammatory conditions upon biopsy. Slides from 30 atypical/malignant cases were retrospectively reviewed for a number of cytomorphologic features and were correlated with the histologic diagnosis. Cases from histologically confirmed adenocarcinoma tended to show greater degrees of altered nuclear polarity, nuclear pleomorphism, membrane irregularities, and chromatin pattern alterations than those from histologically proven adenomatous or inflammatory lesions. The most likely cause of a false-positive diagnosis in this setting is sampling of an adenoma with high-grade dysplasia which fails to meet histologic criteria for adenocarcinoma (invasion of the underlying muscularis mucosae). Thus, in the second part of the study, we examined histologic sections from surgically excised adenomas to determine the frequency with which profound nuclear atypia is at least focally present, potentially resulting in a false-positive cytology diagnosis upon brushing. Slides from 51 cases were reviewed; cytologic atypia beyond that typically observed in adenomas was not observed in 43% of cases. However, profound nuclear atypia was present in 6% of cases; cytologic evaluation of a brushing specimen from these lesions may have resulted in a false-positive diagnosis of adenocarcinoma, despite the histologic diagnosis of adenoma with severe dysplasia. The remaining cases demonstrated intermediate degrees of atypia. These findings serve to quantitate the frequency with which cytohistologic discrepancies might be expected for mass lesions of the colon.     

Microglandular endocervical hyperplasia and tubal metaplasia: Pitfalls in the diagnosis of adenocarcinoma on cervical smears

The detection of atypical glandular cells of undetermined significance (AGUS) has risen recently due to the use of new endocervical canal sampling devices, in particular the cytobrush. From April 1993–June 1994, a diagnosis of AGUS ranging from adenocarcinoma in situ (AIS) to invasive adenocarcinoma was initially made on cervical smears from 6 women for whom histologic follow-up data were available. The purpose of this study was to determine if benign cervical glandular lesions can be reliably distinguished from adenocarcinoma on cytology. Review of the smears and histologic slides from 3 patients showed microglandular endocervical hyperplasia on cervical cone specimens. Cervical smears from 2 of these patients showed clusters of small-to-medium-sized cells with nuclei containing coarse, granular chromatin and prominent nucleoli. Cytoplasmic vacuoles and engulfment of neutrophils were present, findings suggestive of endometrial adenocarcinoma. The third patient's smear showed clusters of large cells with ample, vacuolated cytoplasm and vesicular nuclei containing prominent nucleoli, findings suggestive of endocervical adenocarcinoma, In 3 cases evaluated by cervical conization, histologic slides showed tubal metaplasia. The cervical smears showed clusters and sheets of cells with round-to-oval-shaped nuclei containing evenly distributed, finely granular chromatin and inconspicuous nucleoli. Pseudoglandular formation was present in 2 cases, a finding suggestive of AIS. Since the cytologic features of microglandular endocervical hyperplasia and tubal metaplasia overlap those of adenocarcinoma, a differential diagnosis is prudent on cytologic smears of AGUS. Diagn. Cytopathol. 16:168–173, 1997. © 1997 Wiley-Liss, Inc.     

Atypical reactive proliferation of endocervix: a common lesion associated with endometrial carcinoma and likely related to prior endometrial sampling.

We describe a common, but hitherto not well described, reactive change of the endocervical surface epithelium, commonly seen in association with endometrial carcinoma, and which we term 'atypical reactive proliferation'. This lesion, especially when florid, has the potential to be misinterpreted as a manifestation of a stage 2A endometrial cancer (endocervical glandular involvement). We examined the cervical sections in 80 consecutive hysterectomy specimens of endometrial cancer. In 22 cases (27.5%), there was cervical involvement by tumour and these cases were excluded from further analysis. Of the remaining cases, atypical reactive proliferation involved the endocervical surface in 40 of 58 (69%) cases, although the degree of abnormality varied widely between individual cases. Histological features characteristic of atypical reactive proliferation (not all features were present in each case) included nuclear stratification and multilayering with short micropapillary processes, squamoid change, hobnail cells and mild cytological atypia. Other features present in some cases were surface erosion, clearing of the cytoplasm, fibrin deposition, an inflammatory cell infiltrate and fibrosis of the subepithelial tissue. In 20 control cases, comprising hysterectomy specimens for benign conditions, similar changes were not seen. Vimentin immunohistochemistry was undertaken in eight cases in which atypical reactive proliferation was particularly florid. Five cases were completely negative and three exhibited very focal positivity. Atypical reactive proliferation involving the endocervical surface is commonly seen in association with endometrial cancer and has the potential to be misinterpreted as endocervical involvement by tumour. Although this could represent a reactive change associated with the presence of an endometrial cancer, we feel atypical reactive proliferation is most likely a reactive/reparative response to recent endometrial biopsy or curettage. The vimentin-negative immunophenotype may be of value in cases where the uterine carcinoma is endometrioid in type as these neoplasms are generally vimentin positive.     

Litigation cells: their incidence and classification in gynecologic smears

"Litigation cells" are defined as benign cells which may mimic dysplasia or cancer and might be used by plaintiffs' witnesses to imply that the cytotechnologist or pathologist "missed" cells of dysplasia or cancer. We reviewed 180 cervical smears from 166 patients who had hysterectomy for benign leiomyomas. All smears were performed within 12 months prior to hysterectomy. None of the uteri contained dysplasia or cancer on histologic examination. 90.6% of smears reviewed had at least one cell or cell group with atypia mimicking dysplasia or cancer. These "litigation cells" were classified as follows: parabasal cells, metaplastic squamous cells, degenerated endocervical cells, reactive endocervical cells, endometrial cells, neutrophils, histiocytes, and air-dried cells. Diseases mimicked by these cells included squamous cell carcinoma, high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, adenocarcinoma, and glandular dysplasia. These "litigation cells" can be correctly classified by experienced cytotechnologists and cytopathologists and recognized as benign. We recommend that in all cases of alleged malpractice against cytotechnologists and/or pathologists the smears should be reviewed by a panel of individuals trained and experienced in cytopathology. The smears should be reviewed without knowledge of the clinical outcome and in an environment that simulates the normal screening practice.     

Cervical glandular atypia associated with squamous intraepithelial neoplasia: a premalignant lesion?

Recent studies have described premalignant changes in the endocervical epithelium, but morphological criteria for the diagnosis of cervical glandular atypia of lesser severity than adenocarcinoma in situ have not been established. Adenocarcinoma in situ is often associated with cervical intraepithelial neoplasia (CIN). The endocervical mucosa in 105 cases of CIN grade III was evaluated and compared with that of 100 controls. Sixteen cases of cervical glandular atypia and one case of adenocarcinoma in situ were identified, and it was possible to discriminate between these and a range of benign glandular lesions. Interestingly, the control series included two patients with cervical glandular atypia, one of whom on review had had a cone biopsy for CIN. The progression of cervical glandular atypia through adenocarcinoma in situ to invasive adenocarcinoma is known, but the natural history of cervical glandular atypia is as yet uncertain.     

Two cases of adenocarcinoma in situ arising in lobular endocervical glandular hyperplasia indicating localization of mucin on the cluster surface as an early cytological finding of malignant transformation

Lobular endocervical glandular hyperplasia (LEGH) is an endocervical glandular hyperplastic lesion containing pyloric gland‐like mucin, and has recently been recognized as a precursor lesion of malignant glandular lesions of the endocervix. The pyloric gland‐like mucin contained in LEGH and gastric‐type adenocarcinoma is observed as golden‐yellowish by Papanicolaou staining. However, to our knowledge, the chronological course of the endocervical cytology of LEGH, eventually resulting in malignancy, has never been demonstrated to date. Here, we report two cases of gastric‐type adenocarcinoma in situ (AIS) arising in LEGH, together with an analysis of their cytological course. In both cases, localization of mucin on the surface of glandular cell clusters was observed prior to nuclear atypia in endocervical cytology. In addition, the diagnosis of gastric‐type AIS arising in LEGH was confirmed by pathological diagnosis of hysterectomy specimens in both cases. Histologically, all glandular cells of the LEGH without nuclear atypia contained a large amount of PAS‐positive mucin. On the other hand, in atypical glandular cells, localization of the mucin on the luminal surface was observed, although mucin was abundant throughout the cytoplasm in some areas. Our cases show the course of acquirement of cytological atypia of LEGH, and indicate the significance of localization of mucin on the surface of glandular cell clusters as an early finding of the malignant transformation of LEGH in endocervical cytology. Our results indicate that the distribution of mucin in glandular cells should be analyzed together with nuclear atypia in the endocervical cytology of suspected cases of LEGH.     

Cytologic atypia associated with microglandular hyperplasia

Although it has long been known that microglandular hyperplasia (MGH) may be associated with cytologic atypia in cervical smears, the cytomorphology of MGH has not been described in great detail. To clarify its cytomorphology, Pap smears obtained from biopsy proven cases of MGH over a 3-yr period were reviewed. Of 122 smears containing endocervical cells, 34 (28%) showed striking glandular abnormalities. In two cases, adenocarcinoma and adenocarcinoma in situ were falsely suggested and a high grade squamous intraepithelial lesion (HGSIL-CIN III) was not confirmed in a conization specimen which showed only low grade SIL and MGH. Review of six cytologic diagnoses of HGSIL (CIN III) unconfirmed on biopsy suggested overcalls related to MGH related atypia in five. Cytologic features of MGH, therefore, may occasionally result in erroneous interpretations of HGSIL as well as glandular neoplasia. Although these changes may be striking, comparison with glandular atypia not associated with MGH shows that they are not entirely specific. © 1994 Wiley-Liss, Inc.     

Morphology of bronchial epithelium adjacent to adenocarcinoma of the lung

Gross unremarkable bronchi and bronchioles from 22 lobectomy specimens containing primary adenocarcinoma were examined microscopically. Sections were taken from the segment containing the carcinoma and compared with sections taken from uninvolved segments in the same specimen to examine for premalignant lesions. The average tumor size was 3.75 cm (1.5 to 11 cm). The average age of patients was 60.4 yr (29 to 79 yr); 13 were men and nine were women; all were smokers, and the average was 44.1 pack-years (20 to 100 pack-years). Six of the specimens (27%) showed no histologic changes. Focal squamous metaplasia was identified in nine specimens (41%), but in four of the nine (44%), it was not seen in the carcinogenic segment. Focal goblet cell metaplasia was seen in six specimens (27%), but in two of the six (33%), it was not in the carcinogenic segment. Focal basal cell hyperplasia was seen in two specimens (9%) within both the carcinogenic segment and elsewhere. A single focus of mild epithelial dysplasia was found in each of two specimens (9%), but these foci were not in the carcinogenic segment. Focal epithelial regeneration was noted in three specimens (14%), but two of these (66) were not in the carcinogenic segment. Such microscopic abnormalities of respiratory epithelium are associated with cigarette smoking, and each is a potentially premalignant change; however, our study demonstrated no histologically identifiable changes in the respiratory epithelium that consistently mark for premalignant atypia in the lung adenocarcinoma.     

Immunohistochemical localization of cdc6 in squamous and glandular neoplasia of the uterine cervix

CONTEXT: Cdc6 has been extensively studied as a marker for cellular proliferation that is expressed during the normal cell cycle. Recent studies indicate that Cdc6 may be a marker for cervical intraepithelial neoplasia (CIN) and carcinoma; however, the histologic distribution of Cdc6 has not been explicitly defined. Expression of Cdc6 in the endocervical mucosa also remains unexplored. OBJECTIVE: The goal of the current study was to evaluate the distribution of Cdc6 protein, MIB-1 protein, and human papillomavirus (HPV) DNA in a broad range of cervical tissues, including normal, potentially premalignant, and malignant lesions of the ectocervical and endocervical mucosa. METHODS: We used an indirect immunoperoxidase method to stain formalin-fixed, paraffin-embedded tissues and frozen tissues, including biopsy and hysterectomy specimens, for Cdc6 and MIB-1 proteins, and we used in situ hybridization to detect HPV DNA in a subset of cases. RESULTS: Cdc6 staining was exclusively nuclear and was present in both squamous and glandular epithelial cells of histologic sections. Cdc6 staining was rarely present in specimens of normal cervical squamous mucosa (2/84, 2.4%) or in specimens with squamous metaplasia (3/59, 5.1%) and was not detected in normal endocervical glands (0/84). Staining was present in most cases of CIN I (31/48, 65%). Staining was present in the majority of cases of CIN II (25/28, 89%) and in all cases of CIN III (36/36) and squamous cell carcinomas (34/34). The proportion of cells staining for Cdc6 increased with the grade of dysplasia, and the proportion of stained cells in squamous cell carcinomas was similar to that in lesions of high-grade dysplasia. Cdc6 staining was present in the majority of cases in glandular lesions including adenocarcinoma in situ (11/14, 79%) and adenocarcinoma (8/10, 80%). The histologic distribution of Cdc6-immunoreactive cells was similar to that of cells with a strong signal for HPV DNA, but Cdc6 protein and HPV DNA did not colocalize at the level of individual cells. CONCLUSION: Cdc6 expression is a marker for high-grade cervical squamous and glandular dysplasia and carcinoma and is associated with HPV infection. The mechanistic basis of the association between HPV infection and Cdc6 immunopositivity remains to be determined but may represent either up-regulation of Cdc6 expression or stabilization of the Cdc6 protein.     

Mucinous metaplasia to neoplastic lesions in endometrial samples with cytohistologic correlation

Seven cases of endometrial mucinous metaplasia and five of well-differentiated mucinous adenocarcinoma of the endometrium were studied. Cytologic specimens were obtained by Isaacs endometrial sampler, avoiding endocervical contamination. The histologic diagnosis between the intermediate type of mucinous metaplasia and the well-differentiated mucinous adenocarcinoma posed no problems. DNA analyses of the histologic samples showed a euploid pattern in benign and intermediate types of metaplasia, while well-differentiated mucinous adenocarcinoma showed a hyperdiploid pattern. The cytologic diagnosis of benign mucinous metaplasia should be suggested in the presence of abundant mucinous cells in endometrial samples in the absence of nuclear abnormalities.     

Morphologic changes in the endometrium associated with the use of the mirena coil: a retrospective study of 106 cases

This study outlines the histologic changes seen in 106 endometrial specimens after use of the Mirena coil (levonorgestrel) and compares these changes with previous studies. The variables assessed include nature of the endometrial glands, metaplastic glandular changes, nuclear atypia, hobnail change, and endometrial hyperplasia. Stromal changes include pseudodecidualization, mucinous change, ulceration, and infiltration by granulocytes, neutrophils, and plasma cells, and stromal hyaline nodules, a feature not described previously. Additional changes include superficial micropapillary change, infarcted decidua, dystrophic calcification, hemosiderophages, polypoid indentations, cervical microglandular hyperplasia and endocervical pseudodecidualization. These variables are compared with a similar previous study. Significant differences in the incidence of glandular metaplasia, dystrophic calcification, plasma cell infiltrates, hemosiderophages, and presence of nuclear atypia are noted. With increased use of the Mirena coil, histopathologists need to be aware of the characteristic and constant endometrial changes due to progestogenic and mechanical effects, despite a wide variation in the duration of usage.     

Cytologic features of pancreatic intraepithelial neoplasia and pancreatitis: Potential pitfalls in the diagnosis of pancreatic ductal carcinoma

Fine‐needle aspiration (FNA) has played a significant role in the diagnosis of pancreatic masses but false‐positive diagnoses occur. The Anatomic Pathology files were searched for FNAs of pancreas with subsequent resections. FNAs with a diagnosis of positive for or suspicious for adenocarcinoma followed by a benign resection specimen were reviewed and the surgical pathology and cytology findings correlated. Six cases had a cytologic diagnosis of adenocarcinoma or suspicious for adenocarcinoma but resection specimens were benign. In two cases, a non‐invasive intraductal papillary mucinous neoplasm (IPMN) without significant dysplasia was present surrounded by foci of pancreatic intraepithelial neoplasia (PanIN). In both cases, the degree of atypia within the IPMN was less than that seen cytologically. The nuclear features of the PanIN overlapped those seen in the smears. In two cases, a neuroendocrine neoplasm was present accompanied by multifocal PanIN. The cytologic features of the neuroendocrine neoplasm did not correlate with the material cytologically diagnosed as adenocarcinoma. The cytologically atypical epithelium was similar to the PanIN. Two diagnoses of adenocarcinoma were made cytologically but the pancreatectomy specimens revealed pancreatitis with reactive atypia. Cytologic diagnosis of pancreatic adenocarcinoma has high specificity. Six cytologic misdiagnoses of adenocarcinoma occurred in 105 patients. The cytologic features of these misdiagnoses correlated with histopathologic changes of intermediate to high‐grade PanIN or marked reactive atypia in severe pancreatitis. PanIN may be an under recognized, but significant source of false‐positive results. Diagn. Cytopathol. 2011. © 2010 Wiley‐Liss, Inc.     

Endometrial brush biopsy (Tao brush). Histologic diagnosis of 200 cases with complementary cytology: an accurate sampling technique for the detection of endometrial abnormalities

We examined 200 cases of endometrial brush biopsy (EBB) using the Tao brush and correlated findings with histologic findings from subsequent dilatation and curettage (D&C) or hysterectomy specimens. Diagnosis by EBB relied mainly on histologic evaluation of H&E-stained tissue sections and was complemented by additional cytologic smear examination. EBB correctly detected the following cases: endometrioid adenocarcinoma, 3; complex hyperplasia with atypia, 1; simple hyperplasia without atypia (SH), 2; and benign endometrium, 177. In 3 cases the diagnosis of atrophic endometrium was made by EBB; corresponding D&C specimens were nondiagnostic. Five cases of SH were interpreted by EBB as proliferative endometrium, and 13 endometrial polyps were not identified by EBB. Nine samples were nondiagnostic. Sensitivity and specificity were 100% for detecting atypical hyperplasia and carcinoma. However, it was difficult for EBB to distinguish SH from disordered proliferative endometrium or to diagnose endometrial polyps. We found that diagnosis by EBB is reproducible; a second pathologist blinded to histologic follow-up correctly identified all adenocarcinoma/atypical hyperplasia cases. EBB is an accurate, safe, and easy procedure that is well tolerated by patients and should be considered in the initial evaluation of high-risk outpatients.     

Interobserver variation in the diagnosis of adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix

To examine the interobserver agreement level of the histological diagnosis of adenoma malignum (ADM), 52 proliferative endocervical glandular lesions were evaluated independently by four observers (A to D), each of whom is in charge of gynecological pathology at a different hospital. The correlation of diagnosis by each observer with patient outcome was also examined for 19 of these lesions. When the diagnoses were categorized into benign lesions including hyperplasias, ADM, and common types of adenocarcinoma, consistent diagnoses among all observers were achieved for only 12 lesions (23%), with a slight level of interobserver agreement (kappa=0.115). The points of disagreement were as follows: (i) whether proliferative endocervical glandular lesions preserving lobular structures were diagnosed as benign or as ADM; and (ii) whether proliferative endocervical glandular lesions with a discrete area of obvious adenocarcinoma were diagnosed as ADM or as common-type adenocarcinoma. The mortality rates of patients with ADM diagnosed by observers A, B, C, and D were 60% (3 of 5), 25% (3 of 12), 14% (1 of 7), and 13% (2 of 15), respectively. Therefore, ADM diagnosed by observers A and B was frequently lethal, whereas ADM diagnosed by observers C and D was mostly non-lethal and might contain benign lesions. The diagnosis of ADM covered various spectra of proliferative endocervical glandular lesions among the observers. Disagreement in the diagnosis was suggested to derive largely from the absence of consensus criteria for differential diagnosis among benign hyperplastic lesions, ADM, and common adenocarcinoma, and from differences in the observers' interpretations about cellular atypia and invasion.     

Intranuclear cytoplasmic inclusion is a significant diagnostic feature for the differentiation of lobular endocervical glandular hyperplasia from minimal deviation adenocarcinoma of the cervix

Lobular endocervical glandular hyperplasia (LEGH) is a cervical lesion with pyloric gland metaplasia. Minimal deviation adenocarcinoma (MDA) is an extremely well differentiated form of endocervical adenocarcinoma (AC). To date, it is difficult to differentiate LEGH from MDA because they share similar clinical, radiological, and immunohistochemical features. Furthermore, the cytological features of LEGH and MDA have not been well defined. In the present study, we describe the cytological features of LEGH and MDA. We reviewed 24 cases of LEGH (18 pure and six mixed forms) and four MDA cases of the cervix. A total of 40 cytologic smears from 28 patients were reviewed. Abundant yellow mucin was frequently present in both LEGH and MDA; however, an INCI was found in 22 of the 24 LEGH cases and it was not found in either MDA or adenocarcinoma cells associated with LEGH. Neither cell atypia nor architectural distortion was observed in LEGH. In MDA, slight cellular atypia, three dimensional, irregular cell clustering, and prominent nucleoli were observed. The presence of an INCI is a good parameter for the diagnosis of LEGH. Cytology is an effective aid in the differentiation of LEGH from MDA.     

Cytologic features of endocervical glandular lesions: comparison of SurePath, ThinPrep, and conventional smear specimen preparations

The cytologic features of endocervical neoplasia have been well-described for conventional and ThinPrep, but not for SurePath, methods. This study is designed to ascertain if cytological features are similar in SurePath specimens. Conventional, ThinPrep and SurePath specimens with either endocervical adenocarcinoma in situ or invasive endocervical adenocarcinoma were evaluated for architectural and cytological features previously described for endocervical neoplasia. A generalized linear model was used to assess the differences of ordinal multinomial data. Of 18 evaluated, the only features showing statistical differences were architectural: large groups of cells and single cells were more frequent in SurePath preparations and conventional smears. Feathering was more frequently noted in conventional smears. Individual cytological features were identical across all groups. Mitoses and apoptotic debris were seen with equal frequency in all preparations. The architectural and cytologic features of endocervical glandular neoplasia in liquid-based specimens show only subtle architectural differences when compared with conventional smears. Keeping these differences in mind, virtually the same criteria can be used to identify endocervical glandular lesions in all three specimen types.     

Endocervical adenocarcinomas associated with lobular endocervical glandular hyperplasia: a report of four cases with histochemical and immunohistochemical analyses.

We report on four cases of endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia using histochemical and immunohistochemical analyses. The patients ranged in age from 59 to 67 years (mean 62 years). Chief complaints were watery vaginal discharge in two cases, genital bleeding in one and no subjective symptoms in one. Cytological examinations of the cervical smears revealed adenocarcinoma cells and benign-looking glandular cells with intracytoplasmic golden-yellow mucin in all cases. Radical hysterectomy was performed in three patients, and simple total hysterectomy was performed in one. From surgical specimens, three tumors were diagnosed as mucinous adenocarcinoma and one was adenocarcinoma in situ. All adenocarcinomas were located proximally on the cervix, and did not involve the transformation zone. Adjacent to carcinoma tissues in the cervix, lobular endocervical glandular hyperplasia was detected. The cells of lobular endocervical glandular hyperplasia were dominantly positive with neutral mucin, and immunohistochemistry revealed that these cells had prominent pyloric gland mucin (HIK1083). Focal immunopositivity for pyloric mucin was also observed in three adenocarcinomas. Either CEA or p53 were immunopositive in all adenocarcinomas and negative in the tissues of lobular endocervical glandular hyperplasia. Histopathological features of the present cases suggest that some endocervical adenocarcinomas may originate from lobular endocervical glandular hyperplasia.     

Reproducible and clinically meaningful differential diagnosis is possible between lobular endocervical glandular hyperplasia and 'adenoma malignum' based on common histopathological criteria

The aim of the present study was to determine if the differential diagnosis between lobular endocervical glandular hyperplasia (LEGH) and minimal deviation adenocarcinoma (MDA), or 'adenoma malignum', is reproducible when clear criteria for these two lesions are given. A total of 44 proliferative endocervical glandular lesions were collected, for which differential diagnosis from MDA was considered to be necessary. Seven observers independently classified these 44 lesions into LEGH, LEGH with adenocarcinoma in situ (AIS), MDA, or common cervical adenocarcinoma, according to the following criteria: LEGH was non-invasive proliferation of endocervical glandular cells without any obvious adenocarcinoma component. MDA was very well-differentiated endocervical-type mucinous adenocarcinoma composed mostly of LEGH-looking glands but containing the component of obviously invasive adenocarcinoma. LEGH with AIS was defined as continuous coexistence of LEGH and AIS. Among these four diagnostic categories, the interobserver agreement level was substantial (kappa = 0.618). The level increased to almost perfect (kappa = 0.928) between the group of non-invasive lesions consisting of LEGH and LEGH with AIS and the other group of invasive lesions comprising MDA and common adenocarcinoma. When the modal diagnosis was adopted as the final diagnosis for individual lesions, the 5 year survival rate of patients after surgery was 100% for the non-invasive lesions but only 54% for the invasive lesions (P < 0.01). It is clearly shown that reproducible differential diagnosis is possible between LEGH, LEGH with AIS, and MDA and that such a differentiation is clinically meaningful.     

Intraepithelial neoplasia mimicking microinvasive squamous-cell carcinoma in endocervical brushings.

The interpretation of endocervical brush specimens requires familiarity with the various benign, atypical, dysplastic, and invasive neoplastic changes in cells located in the endocervical canal. There are several pitfalls in the cytologic evaluation of brush specimens that may result in diagnostic difficulty and error. We report seven cases of high-grade squamous intraepithelial lesions that were sampled by endocervical brushing and confirmed by cone biopsy or hysterectomy in which the cytologic changes in the Papanicolaou smears mimicked those of microinvasive squamous-cell carcinoma. The cells in the smears were compared with those in the tissue sections to determine their sites of origin. Results of this study indicate that cells with features fulfilling the criteria for microinvasive carcinoma were found primarily in brushing smears and corresponded with the features of cells involving the endocervical glands rather than those in the surface epithelium. We conclude that the criteria that have been promulgated for the cytologic diagnosis of microinvasive squamous-cell carcinoma have limited value in the examination of endocervical brush specimens.