The clinical significance of "squamous intraepithelial lesion of indeterminate grade" as a distinct cytologic category

The histologic and/or cytologic follow-up of 127 cases of cervical lesions termed "squamous intraepithelial lesion of indeterminate grade" (SIL) on Papanicolaou (Pap) smears by the 2001 Bethesda System was compared with 150 control cases of low-grade SIL (LSIL), high-grade SIL (HSIL), and atypical squamous cells, cannot exclude HSIL (ASC-H). A follow-up diagnosis of cervical intraepithelial neoplasia (CIN) 2 or higher was identified in 22.8% of SIL cases, which was 2.6 times higher than LSIL, 3 times lower than HSIL, and 1.5 times lower than ASC-H. A follow-up diagnosis of CIN 1 was identified in 31.5% of SIL cases, which was 2 times lower than the LSIL group, 1.5 times higher than the ASC-H cases, and 1.8 times higher than the HSIL group. We found that 22.0% of cases diagnosed as SIL were followed up by Pap smears rather than colposcopy and biopsy, compared with about 1% of LSIL and HSIL cases. Because SIL cases have a significant risk of harboring CIN 2 or greater, we recommend follow-up by colposcopy and biopsy.     

Papillary immature metaplasia of the uterine cervix: a report of 5 cases with an emphasis on the differential diagnosis from reactive squamous metaplasia, high-grade squamous intraepithelial lesion and papillary squamous cell carcinoma.

Papillary immature metaplasia (PIM) is a distinctive exophytic lesion of the uterine cervix and shares some histologic and cytologic features with ordinary squamous metaplasia (SM), atypical immature squamous metaplasia (AIM), high-grade squamous intraepithelial neoplasia (HSIL) and papillary squamous cell carcinoma (PSC). PIM has been suggested to be a subset of condyloma associated with low-risk type human papilloma virus (HPV), however, the etiologic role of HPV and biologic behavior of the disease are still elusive. We compared the clinical and histopathological findings, immunohistochemical expression of Ki-67 and p53 protein, and HPV typing of 5 cases of PIM with SM (n=9), HSIL (n=6), and PSC (n=4) to know the helpful features for the differential diagnosis. Histologically, all 5 cases showed a papillary proliferation of immature metaplastic cells involving the proximal transformation zone and endocervix. On HPV typing by polymerase chain reaction-restriction fragment length polymorphism, 2 out of 5 PIM were confirmed to have HPV 6 or HPV 11, while 2 out of 4 PSC were proved having HPV 31 and HPV 16 each. Ki-67 labeling index and mitotic index of PIM were significantly lower than those of HSIL or PSC. There were no significant differences of Ki-67 labeling index and mitotic index between PIM and SM. The expression of p53 varied among the groups and thus it was not helpful for the differential diagnosis.     

High-grade squamous intraepithelial lesions and invasive carcinoma following the report of three negative Papanicolaou smears: screening failures or rapid progression?

The cytologic smears and histopathologic specimens of 18 patients developing cervical intraepithelial neoplasia 3 (CIN3) and two developing invasive squamous carcinoma following the report of at least three negative Papanicolaou tests were studied. A median number of 9.5 smears per patient procured over a median interval of 93.5 mo were reviewed. Twenty-eight (22.7%) of 123 reportedly negative smears revealed a squamous intraepithelial lesion (SIL), 17 (13.8%) were unsatisfactory, 14 (11.4%) lacked an endocervical component, and 37 (30.1%) were classified as atypical squamous cells of undetermined significance (ASQUS) on reexamination. Fourteen (50%) of 28 smears originally misclassified as negative contained fewer than 100 SIL cells and five (17.8%) were severely inflamed. One patient whose smears were misclassified as negative had an atrophic cervix, one had SIL cells primarily in thick sheets, and two had small CIN3 cells resembling squamous metaplasia. Six patients (30%) had a single false negative smear, seven (35%) had multiple false negative smears, seven (35%) had two or more unsatisfactory smears reported as negative, seven had at least two smears lacking an endocervical component, and six had at least two smears taken during pregnancy. Thirteen patients had abnormal smears classified as ASQUS or high-grade SIL (HSIL) but never had a specimen showing only a low-grade SIL (LSIL). This study demonstrates that early signs of SIL may be difficult to recognize cytologically and that poor quality specimens and inadequate sampling may contribute to false negative diagnoses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dual sampling of the endocervix and its impact on AutoCyte Prep endocervical adequacy

We compared satisfactory for evaluation but limited by (limited by) and unsatisfactory gynecologic cytologic diagnoses for samples collected by conventional smearing with those generated with the AutoCyte Prep in a population with a historic squamous intraepithelial lesion (SIL) rate of less than 1%. Results from 18,819 AutoCyte Preps were compared with 53,835 conventional cervical smears. Furthermore, 23 women ages 18 to 65 years undergoing annual Papanicolaou tests underwent sequential sampling with the AutoCyte Prep and the Surgipath C-E brush. Comparison of the AutoCyte Prep with conventional cytologic diagnoses revealed the following: unsatisfactory rate, down 97%; limited by rate, down 67%; low-grade SIL rate, up 86%; cervical cancer rate, up 300%; and high-grade SIL rate, unchanged. Examination of unsatisfactory and limited by cases for the AutoCyte Prep showed that 88% were due to absence of endocervical cells (ECs). Dual sampling showed no improvement in EC recovery over the AutoCyte collection device. Compared with conventional Papanicolaou smears, the AutoCyte Prep significantly decreased the rate of unsatisfactory and limited by specimens while increasing low-grade SIL and cancer detection and EC recovery. The majority of limited by specimens with the AutoCyte Prep were due to absence of ECs, but use of a brush-type device for better endocervical sampling did not enhance EC recovery.     

Clinical significance of cytologic diagnosis of atypical squamous cells, cannot exclude high grade, in perimenopausal and postmenopausal women

We used cytohistologic correlation to determine the clinical significance of atypical squamous cells, cannot exclude high grade (ASC-H) in perimenopausal and postmenopausal women. A computer search identified 250 Papanicolaou smears from women older than 45 years with a diagnosis of ASC- H. Cases were considered perimenopausal (45 to < 55 years; 150 cases) and postmenopausal ((3)55 years; 100 cases). No follow-up data were available for 33 cases, which were excluded. The remaining 217 cases (perimenopausal, 127; postmenopausal, 90) had surgical or cytologic follow-up. Results of follow-up colposcopic biopsy were available for 176 (81.1%) and cytology for 41 (18.9%) women. Follow-up results were as follows: perimenopausal women, negative, 50 (39.4%); mild dysplasia (low-grade squamous intraepithelial lesion [LSIL]), 46 (36.2%); high-grade dysplasia (high-grade SIL [HSIL]); 28 (22.0%); and ASC of undetermined significance (ASC-US), 3 (2.4%); postmenopausal women, negative, 52 (58%); LSIL, 31 (34%); HSIL, 5 (6%); and ASC-US, 2 (2%). The diagnosis of ASC-H in postmenopausal women usually is associated with LSIL or a negative diagnosis on follow-up, suggesting a less aggressive surveillance and treatment regimen is needed for postmenopausal women with ASC-H.     

Atypical glandular cells of undetermined significance. Outcome predictions based on human papillomavirus testing

Cases of atypical glandular cells (AGC) diagnosed on liquid-based preparations were culled from a 3-year period. When available, residual cellular material was analyzed for human papillomavirus (HPV) by polymerase chain reaction and correlated with cytologic and histologic (biopsy) outcome. Of 178,994 cytologic cases, 187 (0.1045%) contained AGC compared with 8,740 (4.8828%) atypical squamous cells (ASC) for an AGC/ASC ratio of 0.021. HPV results and follow-up were available for 108 specimens from 106 patients. Depending on the end-point (histologic/cyto-logic), the sensitivity range of HPV testing for significant cervical disease (high-grade squamous intraepithelial lesion [SIL], adenocarcinoma in situ [ACIS], invasive carcinoma) was 83% with a specificity range of 78% to 82%, a positive predictive value of 57% to 61%, and a negative predictive value of 91% to 95%. Fifteen false-positive results included concurrent ASC or low-grade SIL, ASC on follow-up cytology, and previous ACIS with a negative follow-up cone biopsy result. Noncervical glandular neoplasia (including atypical endometrial hyperplasia) was confirmed in 13 cases (1 recurrent), only 2 of which scored positive for HPV. HPV-positive AGC has a substantially higher positive predictive value for significant disease than ASC (61% vs historic 20%) and merits consideration in the triage of patients with atypical endocervical cells not otherwise specified. However, noncervical or other HPV-negative glandular neoplasia must be considered in all patients with AGC, particularly older patients.     

Atypical immature cervical metaplasia: immunoprofiling and longitudinal outcome

Atypical proliferations of immature cervical squamous metaplasia were reviewed and correlated with p16 and Ki-67 expression to determine whether immunoprofiling could enable more conventional classification. The longitudinal outcome of atypical immature metaplasia (AIM) and predictive role of biomarker expression were also investigated. All atypias of immature squamous metaplasia in the year 2000 were reviewed and stained with p16 and Ki-67. Biomarker features were evaluated and the Ki-67 index calculated. Diagnoses were correlated with the immunoprofile of each antibody, both separately and combined. The progression to squamous intraepithelial lesion (SIL) of lesions reclassified as AIM was determined, and biomarker immunoprofiles were correlated with outcome. The 172 atypias were reviewed as 3 (1.7%) negative, 54 (31.4%) benign, 60 (34.9%) AIM, 43 (25%) low-grade SIL (LSIL), and 12 (6.9%) high-grade SIL (HSIL). HSIL correlated significantly with a combined high index (>15%) and p16 diffusely positive profile (P = .01). Benign diagnoses correlated significantly with a low index (1%-15%) and p16 negative or focal profile (P = .01). AIM and LSIL correlations were not significant, but their profiles were very variable and nearly identical. AIM was the only pathology in 43 cases, and follow-up was available for 32 (74.4%). SIL developed in 66% (50% LSIL and 16% HSIL) and p16 positivity correlated (P = .02). p16 and Ki-67 immunoprofiling are reliable in reclassifying some atypical proliferations of immature squamous metaplasia as HSIL and some as benign. The similarity between AIM and LSIL in regard to their immunoprofile as well as outcome suggests AIM is a morphological type of LSIL.     

"Low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion" is a distinct cytologic category: histologic outcomes and HPV prevalence

We examined the histologic outcomes and prevalence of high-risk human papillomavirus (HR-HPV) in women with liquid-based Papanicolaou (Pap) tests interpreted as "low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion" (LSIL-H) compared with the 2001 Bethesda System (TBS 2001) cytologic categories of LSIL, high-grade SIL (HSIL), and atypical squamous cells, cannot exclude HSIL (ASC-H). A computer search identified 426 LSIL, 86 ASC-H, 81 LSIL-H, and 110 HSIL cytologic interpretations during a 1-year period, each with up to 2 years of histologic follow-up. The risk of histologic cervical intraepithelial neoplasia (CIN) 2 or worse (CIN 2+) associated with LSIL-H (32/81 [40%]) was intermediate between LSIL (46/426 [10.8%]) and HSIL (72/110 [65.5%]), but not significantly different from ASC-H (23/86 [27%]). However, LSIL-H was more frequently associated with a definitive histologic diagnosis of any CIN (CIN 1+) than ASC-H (53/81 [65%] vs 35/86 [41%]). Moreover, the prevalence of HR-HPV was significantly greater in patients with LSIL-H than in patients with ASC-H (15/15 [100%] vs 43/73 [59%]). The histologic outcomes and HR-HPV prevalence associated with LSIL-H differ significantly from the established categories of TBS 2001 and provide evidence to support the recognition of LSIL-H as a distinct cytologic category.     

Cytologic correlates of benign versus dysplastic abnormal keratinization

The purpose of this study was to determine the cytologic and histologic features that differentiate benign from squamous intraepithelial lesion (SIL)-associated cervical abnormal keratinization, defined as hyperkeratosis, parakeratosis, or individual cell dyskeratosis. Fifty-four cervical Papanicoloau (Pap) smears that contained abnormally keratinized cells were reviewed without knowledge of the concurrent biopsy. Twenty-three Pap smears were diagnosed as SIL and the corresponding biopsy showed SIL in 21 (91%) of these cases. Of the 23 Pap smears diagnosed as negative for SIL, the corresponding biopsy in 20 cases (87%) showed benign (SIL negative) abnormal keratinization. Eight Pap smears showed squamous atypia, of these 5 showed SIL on biopsy, and the other 3 revealed benign keratinization. The Pap smear correlates of the 25 biopsies that were negative for SIL included marked hyperkeratosis (18/25–72 vs. 5/29–17% for biopsies with SIL) and regular nuclear membranes (16/18–89% cases with nucleated dyskeratotic cells vs. 5/29–17% for biopsies with SIL). The cytologic correlates of the 29 biopsies that showed SIL included irregular chromatin clumping (27/29–93% vs. 3/18–17% for biopsies without SIL), and a disorganized growth pattern (24/29–83 vs. 5/25–20% for biopsies without SIL). It is concluded that the cytologic distinction between benign and SIL-related Pap smears with abnormal keratinization can be reliably made by the degree of hyperkeratosis, nuclear chromaticity pattern and contour, and the growth pattern of the dyskeratotic cells. Diagn. Cytopathol. 1997;17:447–451. © 1997 Wiley-Liss, Inc.     

Cytologic and histologic correlation of atypical glandular cells of undetermined significance

To determine the cytologic and histologic correlation of atypical glandular cells of undetermined significance (AGUS) in Papanicolaou smears, a cytology file from January 1998 to May 1999 was reviewed. Surgical pathology files were searched to determine which patients received subsequent biopsies. One hundred thirty-two patients with AGUS were identified. Corresponding biopsies were available for 82 of these cases. AGUS has been sub-classified into 3 subtypes: 1) AGUS, favor reactive; 2) AGUS, not otherwise specified; and 3) AGUS, favor neoplasia. The pathologic findings for the respective Papanicolaou smears with the diagnosis of each subtype of AGUS through the follow-up period were as follows: benign lesions in 56.1%, 0%, and 1.2%; squamous intraepithelial lesions 2.4%, 0%, and 1.2%; glandular intraepithelial lesions 0%, 0%, and 17.1%; endometrial simple hyperplasia 1.2%, 0%, and 0%; and carcinoma 0%, 9.8%, and 11%, respectively. In conclusion, AGUS, on cervical cytologic screening, was correlated with significant pathologic findings in 41.5% of the patients (37.8% with preinvasive or invasive glandular lesions and 9.6% with combined squamous intraepithelial lesions). It is thought that intensive follow-up studies, including colposcopy, cervical biopsy, and curettage, should be recommended for complete evaluation of AGUS.     

Abnormal vaginal cytology in HIV-infected and at-risk women after hysterectomy

OBJECTIVE: To determine the frequency of and risk factors for abnormal vaginal Papanicolaou smears in HIV-infected women after hysterectomy. METHODS: Data were from the HIV Epidemiology Research (HER) study, a prospective multisite study of HIV-infected and uninfected women. Semiannual vaginal Papanicolaou smears and colposcopy data were obtained from 102 HIV-infected and 46 at-risk women who had hysterectomy either before or during the study. Analytic models used include Cox proportional hazards (women with hysterectomy during the study) and multiple logistic regressions, which corrected for repeated measures (all women). RESULTS: Among the HIV-infected women, evidence of cervical intraepithelial neoplasia before or at hysterectomy was associated with abnormal cytology during follow-up; 63% had squamous intraepithelial lesions (SIL) on vaginal Papanicolaou smears following hysterectomy. CD4 counts of <200 cells/microL at hysterectomy and HIV viral load of >10,000 copies/mL at hysterectomy were predictive of SIL vaginal cytology. Prevalent SIL vaginal cytology was associated with low CD4 count and human papillomavirus risk type. Of the 102 HIV-infected women, 16 (16%) had vaginal intraepithelial neoplasia on biopsy. CONCLUSIONS: The high rate of SIL on vaginal Papanicolaou smears and the presence of high-grade vaginal intraepithelial neoplasia among HIV-infected women after hysterectomy demonstrate the need for continued follow-up for lower genital tract lesions.     

Extensively keratinized squamous intraepithelial lesions of the cervix are difficult to grade

We tested the hypothesis that extensively keratinized squamous intraepithelial lesions (SILs) are difficult to grade precisely by identifying 100 Papanicolaou smears with a keratinizing SIL that had been originally judged difficult to grade. Of these, 65 were confirmed as low-grade SIL (LSIL) or high-grade SIL (HSIL) on subsequent biopsy. The 65 smears were reviewed independently by 3 cytopathologists who graded each case as LSIL or HSIL (by Bethesda System criteria). The accuracy of the grade was determined by the subsequent biopsy results; accuracy was compared with that of a historic control group of SILs with biopsy follow-up. In the study group, biopsies showed LSIL in 41 cases and HSIL in 24. The mean accuracy for a smear diagnosis of LSIL was 60% for the study group and 92% for the control group. For a smear diagnosis of HSIL, the accuracy was 60% for the study group and 95% for the control group. The overall kappa value for the study group confirmed poor interobserver agreement. Some keratinizing SILs are difficult if not impossible to grade precisely using standard criteria. For such lesions, the diagnosis "SIL, grade cannot be determined due to extensive keratinization" is justified.     

Atypical reparative change on cervical/vaginal smears may be associated with dysplasia

The Bethesda System for classifying cervical/vaginal smears has divided reparative changes into two categories: typical and atypical. Although atypical repair may be grouped with atypical squamous cells of unknown significance (ASCUS), this study selected cases specifically diagnosed as atypical reparative changes (ARC), which showed streaming sheets of cells and enlarged nuclei with nucleoli and anisonucleosis. Our goal was to determine the validity of grouping atypical repair with ASCUS. All cases were received by the Medical College of Virginia-Virginia Commonwealth University (MCV-VCU) pathology department in a 6-month period in 1993. Of 196 cases, 55 (28%) were biopsied within a subsequent 3–6-month period. Of these, 27 also carried a diagnosis of ASCUS (9), low-grade squamous intraepithelial lesion (LGSIL) (15), or high-grade squamous intraepithelial lesion (HGSIL) (3). The remaining 28 were presumably biopsied on the basis of clinical concern regarding a diagnosis of ARC. This group, which represents only 14% of the total with the ARC diagnosis, showed a spectrum of histologic changes from squamous metaplasia and chronic cervicitis to HGSIL. Surprisingly, 25% of these patients (7 of 28) showed changes of LGSIL or higher, including 2 (7%) showing HGSIL. This level of higher grade histologic findings justifies separation of atypical from typical repair. Although there are some cases with a significant histologic abnormality found with a cytologic diagnosis of ARC, the percentage of cases is not nearly as high as the 60% range seen associated with the diagnosis of ASCUS. Due to the lack of consensus on the clinical management of ASCUS, we find no justification to separate the diagnosis of ARC from that of ASCUS. Diagn Cytopathol 1996;14:374–379. © 1996 Wiley-Liss, Inc.     

Women with atypical glandular cells: a long-term follow-up study in a high-risk population

To determine the incidence of clinically significant lesions in high-risk patients with atypical glandular cells (AGCs) after 4 to 6 years of follow-up, we reviewed repeated Papanicolaou (Pap) test and surgical pathology results for a 3-year period for 337 patients; 62 (18.4%) had only repeated Pap smears; 84 had Pap smear and histologic evaluations. In a range of repeated Pap smears from 1 to 11 (mean, 4.2), 9 patients had persistent AGCs/atypical squamous cells; remaining Pap smears were judged normal. Histologic follow-up revealed a clinically significant lesion in 110 (40.1%) of 274 patients--low-grade squamous intraepithelial lesion (LSIL), 46; high-grade squamous intraepithelial lesion (HSIL), 47; endocervical adenocarcinoma in situ (AIS), 3; endometrial hyperplasia, 4; endocervical or endometrial adenocarcinoma, 10. Among patients with histologic follow-up, 14 lesions (12.7% of patients with clinically significant lesions) were diagnosed after a mean of 37 months (range, 21-59 months): LSIL, 7; HSIL, 4; AIS, 1; endometrial adenocarcinoma, 2. Seven patients had negative cytologic and/or histologic evaluations between the initial cytologic AGC diagnosis and the final histologic diagnosis. Patients with AGCs are at risk of harboring clinically significant uterine lesions and should be followed up for a substantial period despite initial negative findings.     

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.     

Diagnostic value of endometrium associated with papillary metaplastic changes in endometrial cytopathology

Papillary metaplastic changes especially occur in both non‐neoplastic and neoplastic endometrium. We tried to investigate to assess the relationship between endometrial cytologic diagnosis and papillary metaplasia. The material consists of 160 cases of cytologic smears obtained by direct sampling of the endometrial cavity comprising 54 cases of normal proliferative endometrium (NPE), 36 cases of glandular and stromal breakdown (EGBD), and 70 cases of endometrial hyperplasia without atypia (EH). As for the correlation between the appearance of papillary metaplasia and cytological diagnosis, a statistical significance test was performed. The material consists of 40 cases of cytologic smears examined by direct sampling of the endometrial cavity comprising 10 cases of EGBD with papillary metaplasia, 10 cases of G1 without pappilary metaplasia, 10 cases of NPE without papillary metaplasia, and 10 cases of EH without papillary metaplasia. Using the comparison between appearance of papillary metaplasia and cytological diagnosis, a significant difference was only seen in the rate of correct diagnoses in EGBD cases. The nuclear area of papillary metaplastic cells in EGBD was 888.8, G1 was 928.7, NPE was 682.0, and EH was 722.2. Significant difference was observed between ECC cells in EGBD to NPE, between papillary metaplastic cells in EGBD to EH, between G1 to NPE, or between G1 to EH. This study provides new and important information on the correlation between endometrial cytological diagnosis and papillary metaplastic changes. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Microglandular hyperplasia has a cytomorphological spectrum overlapping with atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H)

We retrospectively evaluated cytological interpretations of conventional cervical smears in 48 cases of biopsy-proven microglandular hyperplasia and compared them with 15 negative controls. A glandular pattern was noted in all 48 cases but was predominant in 73% (35/48) of the cases. Immature metaplastic pattern was present in 71% (34/48) and was predominant in 27% (13/48). These features were not observed in negative control smears. 85% of cases (41/48) were interpreted as negative for epithelial cell abnormality. Two cases with predominantly glandular pattern (6%, 2/35) were interpreted as atypical glandular cells. Five cases with predominantly immature metaplastic pattern (38%, 5/13) showed checkerboard arrangement or rows of single cells with slightly larger atypical nuclei leading to interpretation as "atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion." The metaplastic cells with normoblast-like karyorrhectic apoptotic debris confined to the nuclear area were scattered among these cells in microglandular hyperplasia with metaplastic pattern.     

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.     

Metaplastic spindle cell breast tumors arising within papillomas, complex sclerosing lesions, and nipple adenomas.

Micropapillomas/papillomas and complex sclerosing lesions of the breast have been associated with a slightly increased risk for subsequent carcinoma, although benign squamous metaplasia and reactive hypercellular stroma are seen within these lesions. There are few reports of these fibrosclerotic lesions associated with metaplastic tumors. Here we describe a series of metaplastic tumors arising within fibrosclerotic breast lesions. Thirty-three metaplastic tumors associated with fibrosclerotic lesions were selected from a breast pathology consultative practice. Relevant clinical and pathological features were reviewed. Representative sections were evaluated immunohistochemically for expression of cytokeratins, vimentin, and smooth muscle and muscle-specific actins. Both the metaplastic component (spindled and squamous cells) and the glandular elements were graded. The metaplastic tumors arose within papillomas (20 cases), complex sclerosing lesions (7 cases), both papilloma and complex sclerosing lesions (3 cases), and nipple adenoma (3 cases). A majority of the metaplastic tumors showed a dominant spindle cell component with various degrees of atypia, ranging from fibromatosis-like (16 cases) to low-grade (13 cases), intermediate-grade (2 cases), and high-grade (2 cases) fibrosarcoma phenotype. Squamous metaplasia was present in 25 cases, and low-grade glandular elements, in 21 cases. Eleven tumors had a low-grade adenosquamous growth pattern. Ductal carcinoma in situ was present in 7 cases, and invasive mammary carcinoma, in 5 cases. The very low-grade tumors were histologically similar to limited areas of stromal reaction and myofibroblastic proliferation, seen in partially sclerotic micropapillomas/papillomas and complex sclerosing lesions, but usually more cellular. Cytokeratin positivity (13+/13 tested) supports the metaplastic nature of the more plump spindled cells. The spindle cells were also positive for vimentin (8+/8 tested) and smooth muscle (2+/5 tested) and muscle-specific actins (6+/6 tested). Spindle cell metaplastic tumors, from fibromatosis-like to fibrosarcoma, may arise within a variety of fibrosclerotic breast lesions.     

经内镜逆行胰胆管造影胰胆管刷检的细胞病理学诊断

目的 探讨经内镜逆行胰胆管造影(ERCP)胰胆管刷检的细胞形态学诊断的敏感性和准确性,及其在诊断胆道和胰腺肿瘤中的作用.方法 回顾性分析长海医院2004年1月至2006年12月行ERCP胰胆管刷片细胞学检查的病例212例,对照术后病理诊断及临床最终诊断,分析胆道及胰腺肿瘤的细胞学特点及意义.结果 212例中样本满意率99%(2例无上皮细胞),细胞学报告阴性者137例,其中临床最终诊断恶性45例(阴性预告值60.2%).细胞学报告低级别异型增生者11例,临床最终诊断恶性6例(阳性预告值54.5%).细胞学报告高级别异型增生和恶性者可信性较高,高级别异型增生23例,1例失随访,临床最终诊断恶性19例(阳性预告值86.4%).细胞学报告恶性41例,临床最终诊断均为恶性(阳性预告值100%).细胞重叠、核大小不等、染色质增粗、黏附性差、坏死背景、核仁、病理性核分裂等特征具有诊断意义.结论 提高诊断效率依赖于从取材、制片、固定到阅片诊断各个环节的质量控制;区分"低级别异型增生"和"高级别异型增生",对临床实际工作的指导意义更大.