Morphology of adenocarcinoma in situ and microinvasive adenocarcinoma of the uterine cervix. A cytologic and ultrastructural study

Adenocarcinoma in situ (AIS) and microinvasive adenocarcinoma of the uterine cervix and normal endocervical columnar epithelium were studied by cytology, morphometry and electron microscopy to identify differentiating features and to ascertain the cellular origin of cervical adenocarcinoma. Smears from AIS showed the characteristic cytology, consisting of glandular rosettes, palisading and crowded sheets; most nuclei had a relatively uniform oval shape. Smears from microinvasive adenocarcinoma showed more crowded sheets, with enlarged, round and irregular-shaped nuclei and prominent oval nucleoli. These nuclear features were confirmed by the morphometric results. Ultrastructurally, reserve cells in the normal tissues contained tonofibers and secretory granules and showed squamous and adenomatous features. The ultrastructural features of microinvasive adenocarcinoma were similar to those of well-differentiated invasive adenocarcinoma. The cells from both contained tonofibers and secretory granules. These findings suggested that the reserve cell is the cell of origin for cervical adenocarcinoma.     

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions
This paper reports the cytological findings based on air-dried smears in a retrospective series of 143 cases of endocervical adenocarcinoma, combined adenocarcinoma-squamous carcinoma and adenosquamous carcinoma drawn from the files of the BC Cancer Registry. Cervical cytology smears were available before biopsy in 131 patients, but in 18 cases the cytology showed no abnormality. Malignant changes or high-grade atypia of glandular and/or squamous cells (defined as moderate or severe dyskaryosis) were detected in 103 cases. In 46 cases, only a high-grade squamous abnormality was detected. Low-grade glandular and/or squamous lesions were detected in nine cases and one showed atypical endometrial-type glands. The cervical smears of 64 cases were reviewed in detail to determine the important cytomorphological criteria of in situ and invasive adenocarcinoma in air-dried smears, the technique used for preparing PAP smears in British Columbia. Endocervical cells were absent in four cases. Numerous (>10) groups of glandular cells were present in 51 cases. Important clues to the diagnosis of adenocarcinoma included crowding of nuclei, stratification of nuclei, loss of polarity, syncytial balls and papillary groups of glandular cells, nuclear enlargement, nuclear pleomorphism, and the presence of free-lying atypical glandular cells. Nuclear hyperchromatism, chromatin pattern, nuclear borders, nuclear membranes, and numbers and morphology of nucleoli were not helpful criteria in our material. Criteria enabling reliable distinction between in situ and invasive adenocarcinoma and/or mixed adenocarcinoma-squamous carcinoma could not be established.     

Atypical glandular cells of undetermined significance on cervical smears. A study with cytohistologic correlation.

OBJECTIVE: The incidence of endocervical adenocarcinoma has increased steadily over the past two decades. Since the Bethesda System was introduced, the diagnosis of atypical glandular cells of undetermined significance (AGUS) has also risen and now accounts for 0.46-1.83% of all cervical (Pap) smears. The purpose of this study was to evaluate the significance of a diagnosis of AGUS using cytohistologic correlation. STUDY DESIGN: A retrospective review of archival material from 1993 through 1996 identified 64 patients who had smears diagnosed as AGUS and had a subsequent surgical biopsy. The smears were reviewed and cytologic features analyzed and correlated with the histologic diagnosis. RESULTS: On biopsy, 3 (5%) of the 64 cases showed endocervical adenocarcinoma in situ (AIS) (1 case with invasive adenocarcinoma also), 14 (22%) had a benign glandular lesion (endocervical polyp, tubal metaplasia, microglandular hyperplasia, reactive changes), 35 (54%) had squamous intraepithelial lesion (SIL) (15 diagnosed on the original smear), and 12 (19%) had no abnormality. Among the cytologic criteria evaluated, feathering (P = .01), palisading (P < .001) and chromatin clearing (P = .002) were shown to have a significant association with the histopathologic diagnosis of AIS/adenocarcinoma. These features were also useful in distinguishing AIS/adenocarcinoma from SIL and benign glandular changes from AIS/adenocarcinoma but not benign/reactive glandular changes from SIL. CONCLUSION: A diagnosis of AGUS correlated with a clinically significant lesion in the majority of cases. Squamous dysplasia (SIL) was the most common lesion identified. The presence of feathering, nuclear palisading and chromatin clearing increased the likelihood of a histologic diagnosis of AIS/adenocarcinoma.     

The cytologic diagnosis of adenocarcinoma in situ of the cervix uteri and related lesions. II. Microinvasive adenocarcinoma

Criteria for the cytologic diagnosis of microinvasive adenocarcinoma of the cervix have not been previously established. Such cytologic criteria were evolved through the detailed analysis of cervical smears from 40 histologically confirmed cases. The cellular features of cervical adenocarcinoma in situ (AIS) were always associated with microinvasion. Syncytia of glandular cells, small cells in very crowded sheets and papillary groupings of cells, when seen in conjunction with AIS, were suggestive of microinvasion. Dissociation of cells was common. Nuclear pleomorphism with an irregular chromatin pattern and inconspicuous-to-prominent nucleoli was frequently present. In some cases, a tumor diathesis was seen in the smear background. Using these criteria, our predictive accuracy for diagnosing microinvasive cervical adenocarcinoma is improving steadily and now approaches 50%. Ongoing investigation of these cases must include a diagnostic come biopsy to further improve the predictive accuracy for this lesion.     

Atypical glandular cells of undetermined significance in cervical smears after conization. Cytologic features differentiating them from adenocarcinoma in situ

OBJECTIVE: To evaluate the cytologic features of atypical glandular cells of undetermined significance (AGUS) smears following conization through a comparison with adenocarcinoma in situ (AIS) smears. STUDY DESIGN: Fifty cervical smears, diagnosed as AGUS based on groups of crowded glandular cells that raised the possibility of AIS, from 38 patients who had conization and 24 AIS smears, histologically confirmed, from 17 patients were reviewed. Subsequent follow-up biopsies or hysterectomies in 38 patients were evaluated. RESULTS: Nuclear atypia was a more reliable feature than architectural structure in differentiating postcone effect from AIS on cytology. The predominant cytologic features of the postcone smears were crowded glandular cells with a high nuclear/cytoplasmic ratio and relatively small, hyperchromatic nuclei with rather finely granular and uniformly dispersed chromatin, less distinct nuclear membranes, less frequent mitosis and presence of endometrial-type stromal cells in the background. The architecture of the crowded cells in the postcone smears was sometimes similar to that of AIS. No AIS or high grade squamous intraepithelial lesion histology was encountered in follow-up biopsies or hysterectomy specimens. CONCLUSION: The cytologic features distinguishing AGUS from AIS may be helpful in identifying the postcone effect. Since it is important to avoid miscalling the postcone effect as AIS, it is recommended that one check for a previous history of a cone biopsy.     

Endocervical glandular neoplasia and its mimics in ThinPrep Pap tests. A descriptive study.

OBJECTIVE: To document the cytologic features of endocervical adenocarcinoma in situ (AIS) and invasive endocervical adenocarcinoma as observed in ThinPrep slides and to compare these features with those that have been described for conventional smears. STUDY DESIGN: Six cases of endocervical AIS and three cases of invasive adenocarcinoma were evaluated with respect to 3 low-power and 14 high-power features. All cases were biopsy proven. Glandular "look-alikes" (tubal metaplasia, n = 3; florid repair, n = 3; sampling of lower uterine segment, n = 1) were also examined. RESULTS: All cases of AIS contained dark groups and sheets at screening power. At higher power, nuclear detail was extremely well visualized. All cases had crowding, continuous depth of focus, variability of nuclear size and shape within groups, irregular nuclear membranes, uniformly stippled chromatin and at least occasional single atypical cells. Only one case lacked nucleoli. Traditional features (strips, feathering, rosettes and mitoses) were observed about as frequently as in conventional smears. Invasive lesions had many of the same features, with relatively more inflammation and lysed blood. Nonneoplastic look-alikes could be distinguished from neoplasms using traditional criteria. CONCLUSION: In this small study, AIS and invasive endocervical adenocarcinoma maintained the features previously described for conventional smears. Improved visualization of nuclear detail may allow the application of additional criteria, such as irregular nuclear membranes and the more consistent presence of nucleoli, for distinguishing glandular neoplasms from their look-alikes.     

Guest Lecture 8.45–9.30 Monday 15 September 2003 Endocervical Adenocarcinoma and its Precursors

The incidence of malignant and pre‐malignant endocervical glandular lesions is increasing. Part of this is an apparent increase due to a reduction in the number of invasive cervical squamous carcinomas but there is evidence that there is a real increase in malignant and pre‐malignant endocervical glandular lesions. Different terminologies are in use in the UK where the term cervical glandular intraepithelial neoplasia (CGIN) is commonly used and the rest of the world where pre‐malignant lesions are classified as glandular dysplasia and adenocarcinoma in situ (AIS) (WHO classification). It is well established that high‐grade CGIN (AIS in WHO terminology) is a precursor lesion of cervical adenocarcinoma but it is controversial whether a recognizable precursor to high grade CGIN (namely low‐grade CGIN) exists and criteria for diagnosing this are poorly established and poorly reproducible. Most cases of CGIN are of usual or endocervical type but other morphological subtypes described include endometrioid, intestinal, tubal and stratified mucinous intraepithelial lesion (SMILE). The presence of skip lesions and lesions high up the endocervical canal has been overemphasised in CGIN with most cases occurring close to the transformation zone. Treatment is on an individualized basis but local excision with negative margins and close cytological follow‐up may be employed. There is evidence in the literature that early invasive adenocarcinomas behave in a similar fashion to early invasive squamous carcinomas and that, on selected occasions, conservative therapy can be safely undertaken. However, further studies are needed to ascertain the behaviour and natural history of early invasive cervical adenocarcinoma. In 10%–15% of cases it may be impossible to ascertain whether a malignant endocervical glandular lesion is invasive or in situ. There are many benign mimics of CGIN and adenocarcinoma, including tuboendometrial metaplasia (TEM), endometriosis and microglandular hyperplasia (MGH). Although careful morphological examination usually allows confident distinction of these lesions, a panel of immunohistochemical stains including MIB1, bcl2 and p16 may assist.     

Quantitative CT Analysis of Pulmonary Ground-Glass Opacity Nodules for the Distinction of Invasive Adenocarcinoma from Pre-Invasive or Minimally Invasive Adenocarcinoma

Objectives

We aimed to analyze the CT findings of ground-glass opacity nodules diagnosed pathologically as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma in order to investigate whether quantitative CT parameters enable distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma.

Methods

We reviewed CT images and pathologic specimens from 191 resected ground-glass opacity nodules with little or no solid component at CT. Nodule size, volume, density, mass, skewness/kurtosis, and CT attenuation values at the 2.5^th–97.5^th percentiles on histogram, and texture parameters (uniformity and entropy) were assessed from CT datasets.

Results

Of 191 tumors, 38 were AISs (20%), 61 were MIAs (32%), and 92 (48%) were invasive adenocarcinomas. Multivariate logistic regression analysis helped identify the 75^th percentile CT attenuation value (P = 0.04) and entropy (P<0.01) as independent predictors for invasive adenocarcinoma, with an area under the receiver operating characteristic curve of 0.780.

Conclusion

Quantitative analysis of preoperative CT imaging metrics can help distinguish invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma.     

Endocervical atypical glandular cells of undetermined significance. I. Morphometric and cytologic characterization of cases that "cannot rule out adenocarcinoma in situ"

OBJECTIVE: To determine whether evaluating morphologic features through morphometry and cytology can lead to a more-satisfactory characterization of endocervical atypical glandular cells of undetermined significance (AGUS) cases that "cannot rule out adenocarcinoma in situ" (AIS). STUDY DESIGN: Fifty-seven endocervical AGUS cases showing incomplete criteria of AIS were morphometrically compared to five smears with normal endocervical columnar cells (ECC) and to five histologically confirmed endocervical adenocarcinoma cases. For each atypical nucleus, the area and shape were measured. Twenty-five cytologic criteria were used to review the AGUS and neoplastic smears. RESULTS: AGUS nuclei showed an intermediate value in terms of area and shape as compared to the values of normal and neoplastic nuclei. In particular, AGUS nuclear enlargement (136.626 micron 2) was about twice the area of normal nuclei and half the value of the area of neoplastic nuclei (P < .0000). AGUS nuclei also had the greatest variability in size and shape, indicating that anisonucleosis may be a morphologic discriminator of endocervical AGUS. The cytologic features useful in discriminating AGUS from neoplastic smears were: presence of normal ECCs, singly or in sheets (P < .001); absence of necrosis (P < .001); bare atypical cells (P < .001); papillary groups (P < .01); anisonucleosis (P < .05); irregular chromatin distribution (P < .05); and hyperchromasia (P < .01). CONCLUSION: Morphometry and cytology led to a better characterization of endocervical AGUS cases that "cannot rule out AIS."     

Endocervical glandular cell abnormalities in conventional cervical smears: evaluation of the performance of cytomorphological criteria and HPV testing in predicting neoplasia

Objective:  To analyse the correlation between cytomorphological criteria in smears with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) and human papillomavirus (HPV) reflex test results with different neoplastic histological diagnoses, particularly to distinguish between glandular and squamous neoplasia.
Methods:  A series of 155 women with glandular abnormalities in their conventional cervical smears was included: 106 with AGC, 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) and 14 with AIS. Two reviewers evaluated 35 cytomorphological criteria and hybrid capture II (HCII) was performed in all cases. Colposcopy was carried out in all cases and biopsy in 126/155. For statistical purposes, predictive values and odds ratio (OR) were calculated, followed by chi-square automatic interaction detection.
Results:  Histology detected 56 cases of squamous and 17 of glandular intraepithelial or invasive neoplasia. Predictive values of the papillary groups and feathering criteria for glandular neoplasia were, respectively, 80.0% and 73.3%. Feathering was the criterion with the highest OR for distinguishing glandular from squamous neoplasia and also for distinguishing between glandular and non-neoplastic diagnosis. Rosettes and pseudostratified strips did not perform as well. Multivariant Classification and Regression Trees analysis identified feathering as the best criterion for distinguishing between glandular, squamous and non-neoplastic diagnoses regardless of HPV status.
Conclusions:  Feathering was the best criterion for predicting glandular neoplasia.     

The cytologic diagnosis of adenocarcinoma in situ of the cervix uteri and related lesions. III. Pitfalls in diagnosis

Potential pitfalls in the cytologic diagnosis of adenocarcinoma in situ (AIS) of the cervix are illustrated by the presentation of three cases of benign cervical lesions initially diagnosed as AIS: cervical endometriosis, tubal metaplasia of the endocervix and changes due to a previous biopsy. The differential diagnosis of endocervical glandular abnormalities is discussed.     

The Cytological Features of Invasive Adenocarcinoma of the Cervix Uteri

Seventy cases of invasive adenocarcinoma of the uterine cervix were predicted on cytological grounds and confirmed by histopathology. The cervical smears from these cases were further analysed and classified into well and poorly differentiated adenocarcinoma on the basis of the pattern of the cells in the smear and their nuclear detail. Using this method of analysis it is possible to increase the accuracy of cytology for the diagnosis of adenocarcinoma of the uterine cervix.     

Clinico-cytological study of uterine papillary serous carcinoma

OBJECTIVE: The aim of this study was to determine whether or not we could distinguish uterine papillary serous carcinoma (UPSC) from other types of endometrial cancer by cytology. METHODS: We examined the cytological findings of the endometrium from five cases with UPSC and compared them with 10 cases with endometrioid adenocarcinoma, grade 1 (G1). A morphometric analysis was performed. Cytological samples from the cervix and ascites of the patients with UPSC were also reviewed. RESULTS: All five patients had FIGO stage III and IV tumours. Three patients died of the disease and two are still alive with disease. The tumour cells of UPSC tended to be shed in papillary clusters with a tumour diathesis. Psammoma bodies were seen only in UPSC. The frequency of irregular-shaped nuclei, membrane thickness and eccentric nuclei in UPSC was higher than in G1. The chromatin pattern was coarsely granular, and both anisonucleosis and bare nuclei were prominent in UPSC. Cytomorphometrically, the maximum diameter of the nuclei in UPSC was significantly greater than that in G1. The nucleoli were also more often seen in UPSC than in G1. The findings of the nuclei and nucleoli in the cervical and peritoneal fluid cytology closely resembled those in endometrial smears. The features of the cervical smears and peritoneal fluid cytology were different from those of endometrial cytology regarding clear background and small clusters of cells. CONCLUSION: As the endometrial cytology findings accurately suggested the histological diagnosis of UPSC, the diagnosis of UPSC was confirmed in this study by endometrial cytology. The cytological diagnosis of UPSC should be based on the findings of tumour diathesis, psammoma bodies and papillary clusters composed of tumour cells with enlarged nuclei and numerous nucleoli.     

Increased diagnostic accuracy of atypical glandular cells in cervical liquid‐based cytology using cell blocks

E. K. J. Risse, J. P. Holierhoek, E. M. Meijer‐Marres, E. Ouwerkerk‐Noordam and M. E. Boon Increased diagnostic accuracy of atypical glandular cells in cervical liquid‐based cytology using cell blocks Objective: The purpose of this study was to reduce the number of diagnoses of atypical glandular cells (AGC). Residual material from the cervical ThinPrep® samples (Hologic, Marlboruogh, MA, USA) was used for cell blocks (CB) and immunohistochemistry (IHC). Methods: In 2007 there were 87 patients (0.12% of tests) with AGC on liquid‐based cytology (LBC) in the Leiden Cytology and Pathology Laboratory (LCPL) using the Bethesda System 2001 (TBS). CB with IHC was used for 26 of these cases. The vials still containing the brush (Cervex‐Brush^® Combi) were placed in a shaker for 10 minutes to dislodge the material trapped between the bristles. The residual sampling fluid was used to prepare paraffin sections (Shandon Cytoblock^®) stained with Papanicolaou and immunostaining. Results: Four of five cases with AGC not otherwise specified (NOS) were diagnosed with CB/IHC as benign mimics (endometrium, tubal metaplasia, follicular cervicitis, microglandular hyperplasia) and one of four with AGC‐favour neoplasia (FN) (endocervical polyp). In one of five cases with AGC‐NOS and in two of seven with AGC‐FN, CIN3 was found on subsequent histological biopsy. Of six cases diagnosed as adenocarcinoma in situ (AIS) on LBC with CB/IHC the diagnosis was confirmed in four; one was adenocarcinoma and one glandular atypia. Of eight cases diagnosed as adenocarcinoma on cytology and CB/IHC, the diagnosis was confirmed in three. The other five cases were found to be one each of AIS, squamous cell carcinoma, CIN3, CIN2 with glandular atypia, and cervical endometriosis. Conclusions: By reducing the number of benign mimics of AGC, we achieved a high proportion (16/26; 61.5%) of neoplastic or preneoplastic lesions (glandular or squamous) on histological outcome potentially avoiding colposcopy. Histological biopsy verification by the gynaecologist is needed for final diagnosis of AGC‐FN, AIS and adenocarcinoma.     

Systems biology analysis reveals new insights into invasive lung cancer

Background

Adenocarcinoma in situ (AIS) is a pre-invasive lesion in the lung and a subtype of lung adenocarcinoma. The patients with AIS can be cured by resecting the lesion completely. In contrast, the patients with invasive lung adenocarcinoma have very poor 5-year survival rate. AIS can develop into invasive lung adenocarcinoma. The investigation and comparison of AIS and invasive lung adenocarcinoma at the genomic level can deepen our understanding of the mechanisms underlying lung cancer development.

Results

In this study, we identified 61 lung adenocarcinoma (LUAD) invasive-specific differentially expressed genes, including nine long non-coding RNAs (lncRNAs) based on RNA sequencing techniques (RNA-seq) data from normal, AIS, and invasive tissue samples. These genes displayed concordant differential expression (DE) patterns in the independent stage III LUAD tissues obtained from The Cancer Genome Atlas (TCGA) RNA-seq dataset. For individual invasive-specific genes, we constructed subnetworks using the Genetic Algorithm (GA) based on protein-protein interactions, protein-DNA interactions and lncRNA regulations. A total of 19 core subnetworks that consisted of invasive-specific genes and at least one putative lung cancer driver gene were identified by our study. Functional analysis of the core subnetworks revealed their enrichment in known pathways and biological progresses responsible for tumor growth and invasion, including the VEGF signaling pathway and the negative regulation of cell growth.

Conclusions

Our comparison analysis of invasive cases, normal and AIS uncovered critical genes that involved in the LUAD invasion progression. Furthermore, the GA-based network method revealed gene clusters that may function in the pathways contributing to tumor invasion. The interactions between differentially expressed genes and putative driver genes identified through the network analysis can offer new targets for preventing the cancer invasion and potentially increase the survival rate for cancer patients.

     

Aspiration cytology of the oncocytic variant of papillary adenocarcinoma of the thyroid gland

OBJECTIVE: To study the cytologic features of the oncocytic variant of papillary adenocarcinoma of the thyroid gland to distinguish this subtype from other oncocytic lesions of the thyroid. STUDY DESIGN: We reviewed the smears from aspiration biopsies of 6 proven cases of oncocytic variant of papillary adenocarcinoma and compared their cytologic features with smears from 19 oncocytic follicular neoplasms (11 adenocarcinomas and 8 adenomas). Smears were stained with a modified Giemsa stain (Diff-Quik). RESULTS: All smears were cellular. Colloid was variable but more abundant in cases of the oncocytic variant of papillary adenocarcinoma. The cells in papillary adenocarcinoma had round to ovoid, overlapped nuclei; prominent intranuclear inclusions; and "grooves." Nucleoli were generally absent. In oncocytic follicular neoplasms, the cells had round nuclei and prominent nucleoli. Nuclear inclusions and grooves were seen but were not as prevalent as in papillary adenocarcinomas. CONCLUSION: The oncocytic variant of papillary adenocarcinoma of the thyroid gland can be distinguished from other oncocytic lesions by fine needle aspiration biopsy, whereas the absence of prominent nucleoli in oncocytes favors the diagnosis of an oncocytic papillary adenocarcinoma.     

Glandular lesions of the cervix on thin-layer Pap tests. Validity of cytologic criteria used in identifying significant lesions

OBJECTIVE: To determine the cytologic features that are most helpful in characterizing significant glandular lesions of the cervix observed on the ThinPrep (TP) Pap test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) and to compare these features with those published for conventional smears. STUDY DESIGN: Thirty-nine TP preparations with cytologic evidence of glandular lesions of the cervix and histologic and/or clinical correlation were studied. These lesions included (1) 11 cases of benign/reactive conditions; (2) 10 cases of adenocarcinoma in situ (AIS), of which 1 had both AIS and carcinoma in situ; (3) 1 case of invasive adenocarcinoma; (4) 15 cases of squamous intraepithelial lesions and squamous cell carcinoma, including 4 with glandular involvement, and (5) 2 cases of adenosquamous cell carcinoma. These cases were reviewed by the first author without knowledge of the histologic diagnosis. Twenty-five previously published cytologic criteria were used to evaluate glandular cells on TP slides. Statistical analysis was performed using Fisher's exact test to determine the significance of the features studied. RESULTS: All glandular lesions had cytologic features on TP similar to those previously described on conventional smears. However, TP slides demonstrated enhanced nuclear features but less-preserved architectural patterns. Reactive lesions showed minimal overlapping without hyperchromasia or mitotic figures and with normal nuclear/cytoplasmic ratios. AIS and invasive adenocarcinoma cases had similar features. Increased cellularity and overcrowding were prominent, whereas feathering, rosettes and cell strips were present but subtle. CONCLUSION: Glandular lesions of the cervix on TP slides shared many of the characteristic features reported for conventional smears. However, nuclear details were more pronounced in TP slides, while architectural patterns, although present, were relatively subtle.     

Distribution of human papillomavirus types in different histological subtypes of cervical adenocarcinoma

Little information is available regarding distribution of HPV types in different histological subtypes of adenocarcinoma (AC). Thus, in this study we examined the frequency of high-risk (hr) HPV types in AC, adenocarcinoma in situ (AIS) and adenosquamous carcinoma (ADSQ). A total of 102 cases of primary cervical adenocarcinoma (26 AIS and 76 invasive AC) obtained from pathology files from 1995-2006 were histologically subtyped. Our results demonstrated that endocervical type occupied the major subtype of AC (22/66) followed by ADSQ (17/66) where as in the group of AIS endocervical type (12/23) was followed by intestinal type of AIS (7/23). Successful DNA extraction was obtained in 89 samples; 81 out of 89 (91.0%) tested positive for HPV DNA. The prevalence of HPV DNA in AIS, AC and ADSQ was 91.3% (21/23), 90.9% (60/66) and 94.1% (16/17), respectively. We found HPV 18 type to be the most predominant type in AIS (11/21) and AC (17/60) followed by HPVof undeternmined type in AIS (3/21) and HPV 16 in AC (9/60) as the sole viral type. HPV 18 was most frequently detected type in all histological subtypes of AIS and AC. We have detected HPV DNA in all 5 samples of clear cell carcinoma (CCC), although other studies have reported a highly variable prevalence of HPVDNA in CCC. The most prevalent HPV type in ADSQ was HPV-16 followed by HPV 33 as single type. The observed overall predominance of HPV 18 in AIS (chi(2) = 6.109, p< or = 0.025) and AC (chi(2) = 8.927, p< or =0.01) as well as of HPV 16 in ADSQ (chi(2) = 10.164, p < or = 0.01) was statistically significant. Our data revealed statistically significant predominance of single hrHPV infections in AIS (16/21; chi(2) = 11.523, p < 0.001) and AC (37/60; X2 = 6.533, p < 0.025) whereas multiple hrHPV infections were more abundant in AC comparing to AIS (23/81and 5/81, respectively; chi(2) = 13.989, p< or =0.001).     

Glassy-cell carcinoma of the uterine cervix. Cytopathologic and histopathologic study of five cases

The cytopathologic and histopathologic findings are presented for five cases of glassy-cell carcinoma. The cytology was characterized by tumor cells arranged predominantly in syncytial-like aggregates. The cells had moderate amounts of amphophilic cytoplasm, which was often finely granular. The nuclei were relatively large and had predominantly finely granular chromatin, with prominent nucleoli in about half of the nuclei. A tumor diathesis was present in three cases. Cytologically, glassy-cell carcinoma is most likely to be confused with large-cell nonkeratinizing carcinoma and with atypical reparative cells. Histologically, it was characterized by cells with moderate amounts of finely granular cytoplasm, well-defined cytoplasmic boundaries, vesicular nuclei and large nucleoli. Although this tumor has an alleged aggressive clinical behavior and lack of response to therapy, two of the patients survived for more than ten years. More cases need to be studied in order to ascertain whether this neoplasm is a variant of cervical carcinoma with a distinct morphology and clinical course or is just a pattern of cervical adenocarcinoma, as has been suggested.