Microinvasive Squamous Carcinoma Research Articles

Conservative treatment of microinvasive squamous cell carcinoma of the cervix stage IA1: Defining conization height to an optimal oncological outcome.

ObjectiveThis paper searches an ideal cone height for stage definition and safe treatment of cervical microinvasive squamous carcinoma stage IA1 (MIC IA1), avoiding excessive cervix resection, favoring a future pregnancy.MethodsA retrospective study was performed involving 562 women with MIC IA1, from 1985 to 2013, evaluating cone margin involvement, depth of stromal invasion, lymph vascular invasion, conization height, and residual uterine disease (RD). High-grade squamous lesions or worse detection was considered recurrence. Univariate and multivariate regression analyses were performed, including age, conization technique (CKC, cold-knife, or ETZ, excision of transformation zone), and pathological results. Conization height to provide negative margins and the risk of residual disease were analyzed.ResultsConization was indicated by biopsy CIN2/3 in 293 cases. Definitive treatments were hysterectomy (69.8%), CKC (20.5%), and ETZ (9.7%). Recurrence rate was 5.5%, more frequent in older women (p = 0.030), and less frequent in the hysterectomy group (p = 0.023). Age ≥40 years, ETZ and conization height are independent risk factors for margin involvement. For ages <40 years, 10 mm cone height was associated with 68.6% Negative Predictive Value (NPV) for positive margins, while for 15 mm and 25 mm, the NPV was 75.8% and 96.2%, respectively. With negative margins, the NPV for RD varied from 85.7–92.3% for up to 24 mm cone height and 100% from 25 mm.ConclusionConization 10 mm height for women <40 years provided adequate staging for almost 70%, with 10% of RD and few recurrences. A personalized cone height and staging associated with conservative treatment are recommended.

Hypercalcemia with invasive pulmonary papillomatosis and microinvasive squamous carcinoma

Juvenile respiratory papillomatosis is a rare pediatric disease in which benign papillomata develop in the respiratory tract, most commonly involving the larynx and tracheobronchial tree. Invasive pulmonary papillomatosis is an aggressive form in which the papillomata extend into the lung parenchyma. We report a case of a 22-year-old man with a long-standing juvenile respiratory tract papillomatosis, initially diagnosed at age 2, who subsequently developed invasive pulmonary papillomatosis and underwent partial surgical resection for his pulmonary disease. Hypercalcemia complicated the patient’s final hospitalizations. HPV typing performed on a laryngeal papilloma was positive for HPV 6/11. The lobectomy specimen revealed malignant transformation of invasive pulmonary papillomatosis characterized by the presence of microinvasive nests of squamous carcinoma. Immunohistochemical stain for parathyroid hormone on the invasive component was negative. Eventually, the patient succumbed to his disease and while the family refused post-mortem examination, Positron Emission Tomography (PET) performed during the patient’s terminal course suggested the possibility of metastasis to liver and periaortic lymph nodes. There was no evidence of bony metastasis.

Analysis of the risk factors of residual lesions after conization and prognosis of multifocal micro-invasive squamous cell cervical carcinoma treated with different types of surgery.

The aim of the present study was to evaluate the residual lesions after conization and the clinical outcome of patients with multifocal micro-invasive squamous cell cervical carcinomas (MMSCCs) treated with different surgical strategies. A retrospective study was carried out in 98 patients with MMSCCs diagnosed by conization and treated between January 2010 and December 2016 in 2 institutions. The patients underwent further different surgeries as therapeutic conization, extrafascial hysterectomy (ES), modified radical hysterectomy (MRH), radical hysterectomy (RH) with or without pelvic lymph node dissection (PLND) and regular follow-up. The clinicopathological characteristics of all of the patients were recorded. The risk factors of residual lesions and that of the recurrence were also analyzed in the present study. The logistic regression analysis revealed that cone margins (P=0.001) were correlated with residual disease after conization whereas parameters including age, gravidity, parity, menopause, stage, LVSI and the number of lesions were not predictors of residual lesions. The cone margin status also indicated the incidence of residual disease as follows: The risk of residual disease was lower with a negative margin when compared with the margin with micro-invasive carcinoma [MIC; odds ratio (OR)=0.064, P=0.012] and was lower in margin with a high-grade intraepithelial lesion than the margin with MIC (OR=0.297, P=0.287). The Cox regression analysis revealed that there were no significant correlations between the following surgery scales and postoperative recurrences, nor were any significant correlations found between the recurrences and the gravidity and parity, postmenopausal state, stage, residual disease after conization, margin status, LVSI and number of lesions (P>0.05). Positive cone margin was the only predictive factor for residual disease in patients with MMSCCs. There were no significant correlations between the surgical scales and postoperative recurrences. This result may be due to the excellent prognosis of MICs despite multiple lesions, regardless the treatment.

Should we be bothered with asymptomatic endocervical polyps in perimenopausal women

Cervical polyps are defined as focal hyperplastic protrusions of endocervical folds with an incidence of 1%-10%. The majority of endocervical polyps are benign and the incidence of high-grade squamous intraepithelial lesion (HSIL) or carcinoma is relatively rare (1: 1000). Endocervical polyps are mostly incidentally discovered, however the most frequent symptoms are post-coital, postmenopausal or intermenstrual bleeding and/or profuse discharge. Here, we present a perimenopausal women with an asymptomatic polyp, later to be diagnosed with cervical carcinoma. A 46-year-old woman applied to our outpatient clinic without any complaint. The examination revealed a 2.3x2 cm cervical polyp with a slim pedincule. An immediate cervical polypectomy was performed and histopathological examination was resulted as HSIL. The patient then underwent cold-knife conization and endocervical curettage (ECC). The excized cone material’s histopathology was consistent with the polyp and the cervical lesion was continous at the surgical borders. ECC was positive for cervical intraepithelial changes. A type 1 hysterectomy was carried out. The definitive pathological diagnosis was microinvasive squamous carcinoma. Accummulating literature advises against routine polypectomy, despite the possibility of displasia in cervical polyps. Various clinical aspects, such as symptoms, age, menopausal status, cytological and colposcopic findings have been evaluated in conjunction with this common entity. In conclusion, the gen- eral notion that symptomatic polyps over 5 mm should be evaluated may be cost-effective, but will not discern cases of polyp associated operable microin-vasive /invasive cervical carcinomas.

Abstract A55: Mapping the airways: The fate of bronchial epithelium in long term heavy smokers

Abstract Introduction: Although tumors of the bronchi account for a large percentage of the lung cancer burden, little is known about the status of the bronchial epithelium prior to transformation into invasive carcinoma. This report describes in situ cellular changes that occur in the central airways (bronchi and bronchioles) of long term heavy smokers screened by fluorescence bronchoscopy through the Colorado SPORE in Lung Cancer and includes results of recent intensive evaluation of selected sites of high grade lesions. Methods: Current and former tobacco smokers with a history of more than twenty pack years were asked to undergo fluorescence and white light bronchoscopy. Patients enrolled in clinical trials were offered follow-up bronchoscopy. Over 8900 bronchoscopic biopsies were obtained at abnormal or predetermined bronchial sites from 1373 subjects under IRB approved protocols between Jan-1993 and July-2014. Multiple same site biopsies were obtained from 290 individual. Biopsies from each site were serially sectioned, examined a multiple levels to identify abnormal epithelium throughout the biopsy tissue and graded for dysplasia on the 8 point scale of the WHO atlas, edition IV. Diagnostic H&amp;E images were archived in a digital repository that could be accessed through a digital tool, the Bronchial Map which allows for side by side comparison of digital images from different times and anatomical sites. Changes in histology score were quantified by subtracting later scores from earlier scores at same site. Clonality was assessed by TP53 sequencing in selected cases. Results: Squamous dysplasia of variable grade was found at 36% of sampled bronchial sites. In contrast to low grade lesions or normal epithelium, higher grade dysplasia often progressed or persisted. Persistent squamous dysplasia was associated with the development of squamous carcinoma (P&amp;lt;0.0001) but invasive carcinoma was rarely observed to develop at specific sites under observation. Four intensively followed cases illustrate the variable and unpredictable outcome of squamous dysplasia: Case 1. Fatal squamous carcinoma developed at a biopsy site that had exhibited grade 5 (moderate) dysplasia 14 years earlier. Case 2. Dysplasia grade improved following irradiation for an adjacent microinvasive squamous carcinoma. Case 3. High grade dysplasia (CIS) with a twice documented TP53 mutation was observed at the left upper lobe and was stable for several years under observation. An invasive squamous carcinoma with a different TP53 mutation subsequently developed on the right and proved fatal. Case 4. A high grade dysplastic lesion has intermittently persisted for several year without progressing to invasive carcinoma. Conclusions: 1. Squamous dysplasia is frequent and often persistent in the airways of heavy tobacco smokers 2. High grade dysplasia may persist for many years without progression to invasive carcinoma 3. Persistent dysplasia is associated with incident squamous carcinoma but the site of associated invasive tumor is frequently distant and unpredictable 4. Early intervention in progression of squamous lesions may require a combination of local and systemic treatment Supported by SPORE in Lung Cancer grant NCI CA580187 Citation Format: Wilbur A. Franklin, Daniel T. Merrick, Kathryn D. Matney, Robert Keith, Mormita Ghosh, Ichiro Nakachi, York E. Miller. Mapping the airways: The fate of bronchial epithelium in long term heavy smokers. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A55.

Performance of HPV DNA testing in the follow-up after treatment of high-grade cervical lesions, adenocarcinoma in situ (AIS) and microinvasive carcinoma.

BackgroundOver the last two decades it has become clear that distinct types of human papillomavirus (HPV), the so-called high-risk types (hrHPV), are the major cause of cervical cancer. The hrHPV-DNA testing has shown excellent performance in several clinical applications from screening to the follow-up of conservatively treated patients.MethodsWe conducted a systematic review of the recent literature on the performance of HPV DNA testing in follow-up after treatment of high-grade cervical lesions, adenocarcinoma in situ, and microinvasive carcinoma compared to Pap smear cytology.ResultsObservational studies have demonstrated that the high risk hrHPV-DNA test is significantly more sensitive (95%) compared to follow-up cytology(70%) in detecting post-treatment squamous intraepithelial high-grade lesions. Moreover, in patients treated conservatively for cervical adenocarcinoma in situ, the hrHPV-DNA test is the most significant independent predictor of recurrent disease or progression to invasive cancer, and the combination of viral DNA testing and cytology reaches 90% sensitivity in detecting persistent lesions at the first follow-up visit and 100% at the second follow-up visit. The cause of microinvasive squamous cervical carcinoma is increasingly treated with conservative therapies in order to preserve fertility, and an effective strategy allowing early detection of residual or progressive disease has become more and more important in post-treatment follow-up. Primary results seem to indicate that the median time for viral clearance is relatively longer compared with patients treated for CIN and suggest a prolonged surveillance for these patients. However, the potential clinical value of HPV-DNA testing in this clinical setting needs to be confirmed by further observations.ConclusionsThe excellent sensitivity, negative predictive value, and optimal reproducibility of the hrHPV DNA testing, currently is considered a powerful tool in the clinicians’ hands to better manage post-treatment follow-up either in cervical squamous lesion or in situ adenocarcinoma.

Cervical microinvasive squamous carcinoma during pregnancy: observation and outcome of pregnancy with planned delayed treatment

To evaluate the maternal and fetal outcomes of planned delay in treatment for cervical microinvasive squamous cancer during pregnancy. A prospective study of pregnant women was done from August 1, 2007 to May 31, 2010. Pregnant women who had not been carried out cervical cytological screening within one year were got thin-prep cytology test (TCT) screening at their initial prenatal visit. Patients with abnormal cytological results were performed colposcopic examination and directed biopsy. Women with cervical microinvasive cancer were followed up every 8 to 12 weeks. If lesion progression were suspected, compared with previous image, repeated biopsy directed by colposcopy should be performed. Once worsening invasive cancer was confirmed, the pregnancy should be terminated timely. All patients should be reevaluated 6 to 12 weeks postpartum with repeated colposcopic examination and biopsy. All mothers were performed cold knife conization (CKC) at 6 to 12 weeks postpartum. We totally diagnosed 17 cases cervical microinvasive squamous carcinoma during pregnancy. The positive rate is 6.2/10 000 (17/27 230). After informed consent, 15 pregnant women decided to delay treatment until fetal maturation. The mean gestational age of initial diagnosis was (19.3 ± 5.9) weeks. The women were followed up 2 to 4 times during pregnancy. Only 1 patient was verified lesion progression by directed biopsy at 34 weeks and delivered by cesarean section. The progression rate during pregnancy was 1/15. The mean delivered time was (37.1 ± 1.8) weeks (ranged from 34 to 40 weeks). The mean diagnosis-to-delivery interval was (18.4 ± 5.2) weeks. All patients were delivered by cesarean section and all newborns had good outcomes. Finally we confirmed 1 case with cervical cancer stage Ia2, 11 cases with stage Ia1, 3 cases with cervical intraepithelial neoplasia (CIN) III by pathological diagnosis after CKC during 6 to 12 weeks postpartum. All cases were disease free after follow-up ranged from 22 to 48 months. It is necessary to perform TCT screening for pregnant women who have not been carried out cervical cytology screening within 1 year. If cervical microinvasive squamous cancer were suspected during pregnancy, in order to achieve fetal maturity it is acceptable for the women who desired pregnancy to delay treatment under closely monitoring until postpartum.

Human Papillomavirus Detection by PCR Assay in a Large Series of High-Grade Squamous Intraepithelial Lesions with Cytohistological Correlation and Follow-Up

Objective: High-grade squamous intraepithelial lesions (HSIL) are the precursors of invasive cervical carcinomas and are generally associated with the integration of mucosotropic human papillomavirus (HPV) DNA into the host cell genome. Detection of HPV is easy to perform nowadays, even in laboratories with limited technological capacity, and follow-up procedures for patients with HSIL are well established. Study Design: HPV detection was performed in a large group of patients with HSIL, and results were correlated with cytological, histological, and colposcopic findings. Discrepancies were examined and discussed. Results: Conventional Papanicolaou (Pap) screening detected 446 HSIL (0.20%) in 218,906 cervical smears. HPV detection by PCR was positive in 339/358 (94.7%) patients. The strains involved were: HPV 16 in 180 patients (53.1%), HPV 18 in 35 (10.3%), HPV 31/33 in 27 (8%), HPV 6/11 in 10 (2.96%), and an unidentified type in 73 (30%). For the last 97 patients (2006–2007), HPV typing was expanded with the following results: HPV 52 was detected in 9 patients (9.2%), HPV 58 in 6 (6.1%), HPV 51 in 4 (4.1%), HPV 68 in 2 (2.0%), and HPV 39 in 1 (1.0%). The number of nonidentified patients dropped to 9 (9.4%); in addition, 14/97 (14.4%) patients were infected with 2 or more viral types. Finally, 19 (5.3%) patients were HPV negative. Colposcopy revealed minor changes in 59 patients (17.3%), major changes in 264 (77.6%), and normal findings in 17 (5.1%). A biopsy was taken in 331/446 patients, and the diagnosis of HSIL or overt malignancy was histologically confirmed in 281 (84.9%) patients: CIN II in 46, CIN III in 224, and histologically upgraded in 11 (6 microinvasive squamous carcinomas, 1 squamous carcinoma, 2 in situ endocervical adenocarcinomas, and 2 microinvasive endocervical adenocarcinomas). Thirty-five patients (10.6%) were downgraded to CIN I and 15 (4.5%) patients had a negative biopsy. Follow-up in the negative-biopsy patients confirmed the existence of SIL in 11 patients [1 HSIL and 10 low-grade squamous intraepithelial lesions (LSIL)] while 4 were considered false positives (atrophic changes, 2; reactive changes, 2). After treatment, 31/331 (9.36%) patients displayed recurrence (HSIL in 29 and LSIL in 2). The viral strains involved in patients with recurrence were HPV 16 in 16 patients (51.6%); HPV 18 in 4 (12.9%); HPV 16 and 18 in 1 (3.2%); HPV 31 in 1 (3.2%); HPV 52 in 1 (3.2%); HPV 18, 31, and 58 in 1 (3.2%); HPV 68 in 1 (3.2%); HPV 51 and 73 in 1 (3.2%), and an unidentified type in 5 (16.1%). Follow-up in 14/19 HSIL and HPV-negative patients confirmed the existence of cervical pathology. Conclusions: HPV detection improves diagnostic sensitivity and provides an ideal tool for monitoring the response to treatment in HSIL patients. The pathogenic relevance of HPV strain 18 may be greater than previously assumed.

ETS-1 proto-oncogene as a key newcomer molecule to predict invasiveness in laryngeal carcinoma

ETS-1 protein is one of the key regulators in tumor invasion and progression. We aimed to evaluate the role of ETS-1 in the invasiveness and progression of laryngeal squamous carcinoma, as well as to determine the correlations between clinicopathological characteristics and expression of this molecule. We assessed the levels of ETS-1 in a total of 96 laryngeal specimens of varying degrees of dysplasia, microinvasive squamous carcinoma (8), and invasive squamous carcinoma (60), using normal mucosal epithelium (10) as a positive control. The relationship between ETS-1 expression and clinicopathological parameters of laryngeal carcinoma was also analyzed. We found a significantly higher ETS-1 expression in invasive laryngeal squamous cell carcinomas than in dysplasia ( P < 0.001). A correlation between ETS-1 expression scores and grade was detected – T factor, stage, cartilage invasion, lymph node metastasis, as well as depth of invasion in laryngeal tumors. Our study is the first to demonstrate that ETS-1 expression is significantly increased in invasive carcinoma, but it is absent in low-moderate grade laryngeal dysplasia and non-neoplastic laryngeal mucosa. This data suggest that ETS-1 expression may play an important role in tumor invasion, and may function in the initiation of the invasive process in laryngeal squamous cell carcinoma.

Microinvasive squamous carcinoma (FIGO stage IA1) of the cervix: are there colposcopic criteria for the diagnosis?

The purpose of this study was to evaluate colposcopic sensitivity in the diagnosis of microinvasive squamous carcinoma of the cervix. We conducted a cross-sectional study in 151 patients from 1991-2008. The colposcopic findings of microinvasion suspicion were described by the International Federation for Cervical Pathology and Colposcopy in 2003. There has been colposcopic suspicion of invasion in 35 patients, which represents a sensitivity of 23%. The major colposcopic findings that were observed in the transformation zone included acetowhite epithelium in 21% (32/151 patients), coarse punctuation in 19% (29/151 patients), coarse mosaic in 17% (26/151 patients), and atypical vessels in 3.9% (6/151 patients). Suspicion of microinvasion was found in 14.5% of unsatisfactory colposcopy and in 8.6% of satisfactory colposcopy. The sensitivity of colposcopy in the diagnosis of microinvasive carcinoma of the cervix was low. Colposcopy plays an important role in directing the biopsy to the most suspicious area. The definitive diagnosis of microinvasive squamous carcinoma is established only by histologic study.

Clinical study on cervix biopsy guided by colposcopy in diagnosis of cervical diseases in pregnant women

To investigate the value and safety of biopsy guided by colposcopy in diagnosis of cervical diseases in pregnant women. From Aug. 2007 to Feb. 2009, 17 828 pregnant women who receive antenatal examination underwent cervical cytological screening thinprep cytology test (TCT) in Beijing Obstetrics and Gynecology Hospital. If abnormal cytological results were found, those pregnant women were administered by colposcopic examination and biopsy after they signed informed consent. (1) TCT: the abnormal TCT results of 1502 pregnant women (8.425%, 1502/17 828) were found in 17 828 cases. (2) Colposcopic examination: two hundred and four pregnant women underwent colposcopic examination. The rate of satisfied colposcopic imaging was 92.6% (189/204), colposcopic examination identified 125 cases with cervical inflammation or cervical intraepithelial neoplasia (CIN)I, 25 cases with CINII and 54 cases with CINIII or microinvasive squamous carcinoma (MIVC) of squamous cervical carcinoma (SCC). (3) The results of biopsy guided by colposcopy: among 204 cases, it was found 33 cases with cervical inflammation or wart, 95 cases with CINI, 28 CINII, 36 cases with CINIII and 12 cases with MIVC. (4) The rate of concordance: compared with biopsy pathologic examination, colposcopy examination found 113 cases with cervical inflammation and CINI, the rate of concordance was 90.4% (113/125). And 54 cases with CINIII or SCC diagnosed by colposcopy examination, however biopsy pathologic examination confirm 23 cases with CINIII and 10 cases with SCC at stage Ia, the concordance rate was 61% (33/54). (5) Complication: eight (3.9%, 8/204) pregnant women underwent cervical wound suturing due to continuous bleeding after colposcopy exam or biopsy. No other complications were recorded. It is necessary that TCT should be performed in pregnant women without cytological screening within one year. Colposcopic examination and biopsy were indicated if pregnant woman with abnormal cytological result were found. Pregnant women with cervicitis or CINI diagnosed by colposcopy should be followed up. If pregnant woman was suspected with CINII or advanced disease, biopsy guided by colposcopy should be performed.

Simultaneous squamous carcinoma involving the fallopian tube and the uterine cervix

Primary fallopian tube carcinoma are extremely rare and are most commonly of serous or endometrioid type. Primary squamous cell carcinomas are exceptional with only three cases reported in the English literature. We present the case of a 43-year-old woman operated for cervical carcinoma. Histologic examination, showed a squamous cell carcinoma of cervix with post operative discovery of a concomitant microinvasive squamous carcinoma of fallopian tube developing on high grade dysplasia and in situ carcinoma lesions. Clinico-pathological features of fallopian tube carcinoma, in general, and squamous carcinoma, in particular, will be discussed.

The risk of residual neoplasia in women with microinvasive squamous cervical carcinoma and positive cone margins

The risk of residual neoplasia in women with microinvasive squamous cervical carcinoma and positive cone margins

The risk of residual neoplasia in women with microinvasive squamous cervical carcinoma and positive cone margins

The objective was to evaluate the prevalence and factors affecting residual disease in women with cervical microinvasive carcinoma (MIC) with positive cone margins for high-grade lesions and invasive carcinoma. We reviewed histopathology slides of 129 women with MIC who had high-grade lesions or invasive carcinoma at cone margins. These patients underwent hysterectomy following cone biopsy between January 1994 and June 2004. Of the 129 patients, 77 (59.7%) had residual disease in the hysterectomy specimens, in which 57 (44.2%) had residual high-grade lesions. Twenty patients (15.5%) had residual invasive carcinoma: 18 were microinvasive and 2 were invasive. Factors significantly affecting the risk of residual disease included positive postconization endocervical curettage (P= 0.001), positive cone margins for invasive carcinoma (P= 0.003), and depth of stromal invasion >1 mm (P= 0.014). Cox proportional hazards analysis revealed positive cone margins for invasive carcinoma as significant predictor of residual invasive disease (hazard ratio, 3.22; 95% CI 1.21-8.60, P= 0.019) In summary, patients with MIC and positive cone margins for high-grade lesions or invasive carcinoma are at high risk of residual neoplasia. Repeat cone biopsy should be performed to determine exactly the severity of lesion before planning treatment.

Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive squamous cell carcinoma of the uterine cervix

Maspin is a serine protease inhibitor with tumor suppression activity. It is expressed in normal breast and prostate tissue but is downregulated or absent in breast and prostate tumors. Recent reports have shown that decreased expression is associated with a greater propensity for metastasis in oral squamous cell carcinomas. We know that some high-grade cervical intraepithelial neoplasia progress to invasive carcinomas while others either persist at the same degree of atypia or regress. The pattern of maspin expression in cervical intraepithelial neoplasia-grade 3, microinvasive squamous carcinomas and overtly invasive squamous cell carcinomas of the uterine cervix was studied to determine the relationship between the extent of maspin expression and the progression of cervical intraepithelial neoplasia to squamous cell carcinoma. In total, 36 cases were evaluated: 18 cases of cervical intraepithelial neoplasia-grade 3, seven cases of microinvasive squamous cell carcinoma and 11 cases of invasive squamous cell carcinoma. A monoclonal antibody was used on paraffin-embedded tissues. Immunoreactivity was scored semiquantitatively using a scale of 0–3. The sums of the scores of the different groups were compared using the Mann–Whitney U-test. A significant decrease in maspin scores was noted between cervical intraepithelial neoplasia-grade 3 vs invasive squamous cell carcinoma (P<0.005), microinvasive squamous cell carcinoma vs invasive squamous cell carcinoma (P<0.05), and cervical intraepithelial neoplasia-grade 3 vs tumor emboli (P<0.005). Although not statistically significant, scores of cervical intraepithelial neoplasia-grade 3 associated with invasive squamous cell carcinoma were lower compared to that cervical intraepithelial neoplasia-grade 3 without invasive squamous cell carcinoma. These findings suggest that maspin likely plays a role in disease progression from in situ to invasive carcinoma. Virtual absence of maspin immunopositivity in tumor emboli indicates that maspin may also play a role in metastasis.

Topical 5-Fluorouracil in the Management of Extensive Anal Bowen's Disease: A Preferred Approach

An alternative approach to anal Bowen's disease was investigated. The use of topical 5 percent 5-fluorouracil for large lesions and surgical excision of small lesions were evaluated. A prospective study was undertaken for anal Bowen's disease in 11 patients over a six-year period. Before therapy all patients underwent anal mapping biopsy and colonoscopy. For one-half circumferential disease or greater, patients underwent topical 5 percent 5-fluorouacil therapy for 16 weeks. For smaller involvement, wide surgical excision was performed. All patients underwent anal mapping biopsy one year after completion of therapy. Of 11 patients, 8 (5 male) received 16 weeks of topical 5 percent 5-fluorouacil therapy. Three patients (3 female) underwent surgical excision for localized disease. All but one patient, who was HIV positive, were free of Bowen's disease one year after completion of therapy. One patient underwent total excision of a residual microinvasive squamous carcinoma after circumferential Bowen's disease had resolved. One patient received eight additional weeks of topical 5-fluorouacil therapy for incomplete resolution. All patients were followed yearly, with a mean follow-up of 39 months and a range of 12 to 74 months. There have been no recurrences. There were no long-term side effects or morbidity from topical 5-fluorouacil or local excision. All colonoscopies were normal. Topical 5 percent 5-fluorouacil therapy is a safe and effective method to treat anal Bowen's disease. Wide local excision is appropriate for smaller, isolated areas of disease. Anal Bowen's disease was not associated with colonic or other neoplasms.

Microinvasive squamous carcinoma of the cervix: treatment modalities.

Patients with FIGO stage IA1 squamous cell carcinoma of the cervix can be treated conservatively with simple hysterectomy or, if young and desiring to preserve their fertility, with conization only, provided surgical margins are free of dysplasia or invasive disease. When the surgical margins are involved a repeat conization should be performed. Patients with FIGO stage IA2 or stage IA1 carcinoma with extensive lymph vascular space invasion benefit from a modified radical hysterectomy with pelvic lymph node dissection. If preservation of fertility is an issue, then conization with extraperitoneal or laparoscopic pelvic lymphadenectomy can be performed. Alternatively, radical trachelectomy with pelvic lymphadenectomy may be a safer procedure. Individualization of therapy based on an exhaustive pathological evaluation of an adequate cone biopsy specimen is of paramount importance for treatment planning and disease control.

How significant is a cervical smear showing glandular dyskaryosis?

Objective: To evaluate the incidence, outcome and predictive value of cytology showing glandular dyskaryosis. Participants: Fifty-seven women with a smear diagnosis of glandular dyskaryosis registered between January 1997 and December 2001. Setting: Colposcopy and cytopathology units in a large district general hospital. Results: Sixty smears in 57 women showing glandular dyskaryosis were identified from a cohort of 135,120 smears, giving an incidence of 0.05%. Hospital records were available for 50 women. Final diagnosis included 13 cases of cervical glandular intraepithelial neoplasia (CGIN), 4 microinvasive cervical adenocarcinomas, 2 undifferentiated tumours, 1 microinvasive squamous carcinoma, 21 cases of CIN and 13 cases of endometrial pathology (8 endometrial cancers). Twelve women had coexistent squamous and glandular disease. Forty-five out of 50 women had significant pathology (positive predictive value 90%). Colposcopy was seen to be of limited value in assessment of smears showing glandular dyskaryosis. Only 1 out of 13 glandular lesions was diagnosed by colposcopy. Conclusion: Smears showing glandular dyskaryosis are associated with significant pathology in 90% of cases and malignancy in 32% of cases. Hence, women with a smear showing glandular dyskaryosis should be referred urgently to a colposcopy clinic and flagged up as suspected cancer. Glandular dyskaryosis should be included in the national referral criteria for suspected gynaecological cancer.

Microinvasive squamous carcinoma of the cervix: treatment modalities

Patients with FIGO stage IA1 squamous cell carcinoma of the cervix can be treated conservatively with simple hysterectomy or, if young and desiring to preserve their fertility, with conization only, provided surgical margins are free of dysplasia or invasive disease. When the surgical margins are involved a repeat conization should be performed. Patients with FIGO stage IA2 or stage IA1 carcinoma with extensive lymph vascular space invasion benefit from a modified radical hysterectomy with pelvic lymph node dissection. If preservation of fertility is an issue, then conization with extraperitoneal or laparoscopic pelvic lymphadenectomy can be performed. Alternatively, radical trachelectomy with pelvic lymphadenectomy may be a safer procedure. Individualization of therapy based on an exhaustive pathological evaluation of an adequate cone biopsy specimen is of paramount importance for treatment planning and disease control.

Proliferative epidermal lesions associated with anogenital Paget's disease.

A series of 35 cases of Paget's disease (PD) of the vulva and perianal area were studied to characterize the spectrum of proliferative epidermal lesions that occur in this rare disease but generally have been overlooked. The study group consisted of 8 men and 27 women with a median age of 66 years. Nineteen patients (54%) had one or more benign proliferative epidermal lesions, including 7 of 22 patients (32%) with vulvar PD and 12 of 13 patients (92%) with perianal PD. Two patients also had malignant squamous cell neoplasms. Three categories of epidermal hyperplasia were identified: (1) squamous hyperplasia NOS (34%), (2) fibroepithelioma-like hyperplasia (32%), and (3) papillomatous hyperplasia (29%). Small nests of hyperplastic squamous cells protruding into the dermis simulated microinvasive squamous carcinoma in three of these cases. None of the nine papillomatous hyperplasias tested for HPV by in-situ hybridization were positive. The squamous hyperplasia NOS and the papillomatous hyperplasia did not show a predilection for an anatomic site. In contrast, fibroepithelioma-like hyperplasia occurred in 69% of perianal PD compared with only 9% of vulvar cases. There was no association between the type of epidermal hyperplasia and the presence of a regional internal cancer. Two patients with vulvar PD had malignant squamous lesions, including one with squamous cell carcinoma in-situ (CIS) of classic type and one patient with invasive squamous cell carcinoma (InvSCC); the latter also had invasive PD. The malignant squamous component in both patients was positive for HPV 16/18, whereas the associated Paget's cells were HPV-negative. The finding of fibroepithelioma-like hyperplasia in the anogenital skin should prompt a thorough search for Paget' s cells. Papillomatous hyperplasia may be misinterpreted as condyloma acuminatum when Paget's cells are few in number and have koilocytotic-like vacuolar change or for warty (condylomatous) carcinoma when pseudoinvasive foci are present. When Paget's cells are florid and diffusely infiltrate an acanthotic epidermis, classic CIS may be misdiagnosed. Cytokeratin 7 immunostain is an excellent marker for intraepithelial and invasive Paget's cells that aids in their distinction from hyperplastic and malignant squamous cells.