Diagnosis Of Adenocarcinoma In Situ Research Articles

Stereologic consequences of iatrogenic collapse: The morphology of adenocarcinoma in situ overlaps with invasive patterns. Proposal for a necessary modified classification of pulmonary adenocarcinomas

Recognizing non-invasive growth patterns is necessary for correct diagnosis, invasive size determination and pT-stage in resected non-small cell lung carcinoma. Due to iatrogenic collapse after resection, the distinction between adenocarcinoma in-situ (AIS) and invasive adenocarcinoma may be difficult. The aim of this study is to investigate the complex morphology of non-mucinous non-invasive patterns of AIS in resection specimen with iatrogenic collapse, and to relate this to follow-up.The effects of iatrogenic collapse on the morphology of collapsed AIS were simulated in a mathematical model. Three dimensional related criteria applied in a modified classification, using also cytokeratin 7 and elastin as additional stains, in two independent retrospective cohorts of primary pulmonary adenocarcinomas ≤3 cm resection specimen with available follow-up information.The model demonstrated that infolding of alveolar walls occurs during iatrogenic collapse and lead to a significant increase in tumor cell heights in maximal collapse areas, compared to less collapsed areas. The morphology of infolded AIS overlaps with patterns described as papillary and acinar adenocarcinoma according to the WHO classification, necessitating an adaptation.The modified classification incorporates recognition of iatrogenic and biologic collapse, tangential cutting effect true invasion and surrogate markers of invasion i.e. grey zone, covering a multilayering falling short of micropapillary, cribriform and solid alveolar filling growth. The use of elastin and CK7 staining aids in the morphologic recognition of iatrogenic collapsed AIS and the distinction from invasive adenocarcinoma. Out of a total of 70 resection specimens 1 case was originally classified as AIS and 9 were reclassified as iatrogenic collapsed AIS. Patients with collapsed AIS showed a 100 % recurrence-free survival after a mean follow-up time of 69.5 months.With the current WHO classification, AIS is overdiagnosed as invasive adenocarcinoma due to infolding. The modified classification facilitates the diagnosis of AIS.

Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience

ObjectiveHysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. MethodsA retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. Results121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. ConclusionOur study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

Endocervical adenocarcinoma in situ-from Papanicolaou test to hysterectomy: a series of 74 cases.

Endocervical adenocarcinoma in situ (AIS) is not always identified on cervical Papanicolaou (Pap) test cytology because the Pap test has relatively low sensitivity for the diagnosis endocervical glandular lesions. We performed a retrospective study to determine the relative sensitivity of different diagnostic approaches, including Pap tests, cervical biopsy and/or endocervical curettage, loop electrosurgical excision procedure (LEEP), and hysterectomy specimens. Cases of endocervical AIS diagnosed from August 2005 to January 2019 were retrieved from our institution's pathology databases, and their clinicopathologic features were reviewed. A total of 74 patients with endocervical AIS with or without concurrent squamous intraepithelial lesions or cervical neoplasms were identified. Their mean age at diagnosis was 39.9 years. More than one half of the cases of AIS were not detected from screening Pap tests but were diagnosed during histologic examination of cervical biopsy or endocervical curettage, LEEP, or cone biopsy specimens (~66%). Only a few patients had had a definitive diagnosis of AIS from the Pap tests (10.8%). Other abnormal glandular cytology included atypical glandular cells, not otherwise specified (16.2%), atypical glandular cells favoring neoplasia (5.4%), and atypical glandular cells suspicious for malignancy (1.3%). Abnormal squamous cytology was common in the study population (54%), with high-grade squamous intraepithelial lesion the most common finding (30%). AIS was diagnosed in 31 of 42 cervical biopsies or curettages, with 16 cases an incidental finding and 15 cases confirming previous abnormal glandular cytology. In addition, AIS was identified in 51 of 53 LEEPs. Approximately 41.5% of those undergoing LEEP had a previous diagnosis of AIS, and 54.7% of the cases were incidental findings. More than one half of the AIS cases harbored significant concurrent cervical lesions, including 26.7% with high-grade squamous intraepithelial lesion, 5.7% with low-grade squamous intraepithelial lesion, 1.9% with invasive squamous cell carcinoma, 20.9% with invasive adenocarcinoma, and 6.7% with microinvasive adenocarcinoma. Our results have demonstrated that the ability to detect AIS with routine screening Pap testing or biopsy/curettage has variable efficacy depending on the screening methods. Given the relatively low combined sensitivity of Pap testing and biopsy/endocervical curettage in the diagnosis of AIS, all LEEPs and cervical cone biopsies performed for squamous cell abnormalities should be thoroughly evaluated for glandular lesions.

Without mandatory high-risk HPV co-testing, are we inadequately screening for adenocarcinoma of the cervix?

Objectives: High-risk human papillomavirus (hrHPV) is an important co-factor in the development of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the cervix. Screening with the Papanicolaou test is more effective for SCC compared to AC, creating a missed opportunity for early detection if hrHPV co-testing is not performed. We sought to evaluate the effect of HPV status, as well as other risk factors, on the development of adenocarcinoma in situ (ACIS) and AC. Methods: We conducted a single-institution, retrospective case-control study. Cases consisted of women diagnosed with ACIS or AC of the cervix between 2007-2017. Controls consisted of patients without the diagnosis of ACIS or AC, randomly selected from a pool of potential control patients via a random number generator, with a cases to control ratio of 1:3. Univariable tests were applied on the basis of whether the variable of interest was distributed normally (ie, t test, analysis of variance) test with a 0.05 two-sided significance level. Results: A total of 118 cases (47 AC and 71 ACIS) and 289 controls were identified for inclusion in this study. The average age was 42.5 years (cases 39.7, controls 34.3, p=0.0001). 29% of AC patients were post-menopausal at time of diagnosis (14/47), 17% ACIS (12/71) and 33% controls (97/289) (p=0.0215). 34% of AC patients (16/47) and 24% of ACIS patients (17/71) had a significant smoking history compared to 18% of controls (53/289), (p=0.0309). 29% AC and 49% ACIS (35/71) patients had a co-existing preinvasive squamous a lesion at time of diagnosis compared to 26% of controls (76/289), (p=0.0024). Nulliparity was not significantly associated with AC/ACIS vs. controls (p=0.0696). 86% of AC patients (31/36) and 91% ACIS (63/69) were hrHPV positive at the time of diagnosis compared to 28% of controls (83/279) (p Conclusions: Patients with AC and ACIS were significantly more likely to be pre-menopausal, a current or former smoker, and have a co-existing HSIL/LSIL lesion. High-risk HPV status was positive in 90% of AC/ACIS patients whereas Pap cytology was normal in 26% of ACIS/AC patients preceding diagnosis. Pap cytology with mandatory hrHPV co-testing may be more effective screening for early detection of AC/ACIS. Download : Download high-res image (203KB) Download : Download full-size image

Can computed tomography differentiate adenocarcinoma in situ from minimally invasive adenocarcinoma?

BackgroundGiven the subtle pathological signs of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), effective differentiation between the two entities is crucial. However, it is difficult to predict these conditions using preoperative computed tomography (CT) imaging. In this study, we investigated whether histological diagnosis of AIS and MIA using quantitative three‐dimensional CT imaging analysis could be predicted.MethodsWe retrospectively analyzed the images and histopathological findings of patients with lung cancer who were diagnosed with AIS or MIA between January 2017 and June 2018. We used Synapse Vincent (v. 4.3) (Fujifilm) software to analyze the CT attenuation values and performed a histogram analysis.ResultsThere were 22 patients with AIS and 22 with MIA. The ground‐glass nodule (GGN) rate was significantly higher in patients with AIS (p < 0.001), whereas the solid volume (p < 0.001) and solid rate (p = 0.001) were significantly higher in those with MIA. The mean (p = 0.002) and maximum (p = 0.025) CT values were significantly higher in patients with MIA. The 25th, 50th, 75th, and 97.5th percentiles (all p < 0.05) for the CT values were significantly higher in patients with MIA.ConclusionsWe demonstrated that quantitative analysis of 3D‐CT imaging data using software can help distinguish AIS from MIA. These analyses are useful for guiding decision‐making in the surgical management of early lung cancer, as well as subsequent follow‐up.

Personalized Medicine and Cervical Screening: Development of Individualized Quantitative Risk Assessments for Cervical Adenocarcinoma and Adenocarcinoma in situ

Introduction: Cervical screening has decreased the incidence of cervical carcinoma around the world primarily by preventing cervical squamous carcinoma, with significantly less measurable protective benefits in prevention of cervical adenocarcinoma. In this study, we apply Bayesian modeling of cervical clinical, screening, and biopsy data from a large integrated health system to explore the feasibility of calculating personalized risk assessments on screened system patients for subsequent histopathologic diagnoses of invasive cervical adenocarcinoma (AdCa) or cervical adenocarcinoma in situ (AIS). Materials and Methods: Diagnoses of cervical AIS or AdCa rendered between 2005 and 2018 were identified in our large health system database with 1,053,713 cytology results, 354,843 high-risk (hr) human papillomavirus (HPV) test results, and 99,012 cervical histopathologic results. Using our continuously updated Bayesian cervical cancer screening model which includes clinical data, cervical screening results, and cervical biopsy results, we projected quantitative estimates of patients’ 5-year cumulative risk for cervical AIS or AdCa. Results: 161 patients were identified with AIS (ages 17–75, mean 37 years), and 99 patients had diagnoses of cervical AdCa (ages 26–91, mean 48 years). Quantitative Bayesian 5-year cumulative risk projections for diagnoses of cervical AdCa or AIS in patients with different cervical screening test and biopsy histories were determined. The highest patient risk projections for subsequent cervical AdCa and/or AIS histopathologic diagnoses were associated with prior cervical screening test results of HPV-positive atypical glandular cells. Prior squamous cytologic abnormalities were associated with lower risk estimates. Prior histopathologic diagnoses of squamous abnormalities also influenced quantitative risk. A prior histopathologic diagnosis of AIS was associated with a very low risk of subsequent AdCa, consistent with effective excisional treatment. AdCa risk was greatest in women aged 30–65 years with prior CIN3 biopsy results, whereas AIS risk was greatest in women <30. Conclusion: Prevention of cervical AdCa in screened patients remains a major challenge for cervical screening. Individualized risk projections for cervical glandular neoplasia reflecting patient age, prior cervical screening test results, and prior cervical biopsy history are feasible using Bayesian modeling of health system data.

Cytology and curetting diagnosis of endocervical adenocarcinoma

Papanicolaou testing is effective in identifying squamous intraepithelial lesions of the cervix. Endocervical adenocarcinoma (EAC) and adenocarcinoma in situ (AIS) are far less commonly identified. Endocervical curettings (ECCs) are usually obtained after colposcopic biopsy, sample the endocervical canal, and aid in the detection of endocervical glandular lesions. Here, we examine the utility of Papanicolaou testing and endocervical curetting for detecting AIS and EAC. Cases from 2007 to 2019 with a histologically confirmed diagnosis of AIS and EAC were identified and the clinical data and diagnostic material, including the cytology and surgical specimens, obtained. A total of 108 cases of AIS and EAC were identified, Papanicolaou tests were performed in 97 of these cases, and ECC in 87. AIS or EAC were detected in 46.4% of Papanicolaou tests; 41.4% of ECC showed AIS or EAC. A total of 92.7% of cases were positive for high-risk human papillomavirus (HPV) and concurrent squamous intraepithelial lesion was present in 53.3% of cases. AIS or EAC were more commonly identified in cases without concurrent squamous intraepithelial lesions. Papanicolaou testing and endocervical curettings have a low detection rate for AIS and EAC. The majority of AIS and EAC cases test positive for high-risk HPV. Papanicolaou test and ECC show different detection rates and are complementary tools in patients with AIS and EAC. In some settings, an ECC can increase the diagnostic sensitivity and specificity of the pathologic diagnosis.

Serum von Willebrand factor for early diagnosis of lung adenocarcinoma in patients with type 2 diabetes mellitus.

BACKGROUNDThe elevation of plasma von Willebrand factor (vWF) has been proposed to be a predictor of lung cancer. Type 2 diabetes mellitus (T2DM) causes endothelial activation, resulting in the secretion of vWF. However, the role of vWF in patients with T2DM complicated with lung cancer remains unclear.AIMTo investigate the clinical value of serum vWF as a tumor marker in patients with T2DM combined with lung adenocarcinoma in situ (AIS).METHODSThis study enrolled 43 patients with T2DM combined with lung AIS (T2DM + AIS group), 43 patients with T2DM alone (T2DM group), 43 patients with lung AIS alone (AIS group), and 43 healthy volunteers (control group). The serum levels of vWF, insulin-like growth factor 1, and insulin-like growth factor binding protein 3 were determined. Multiple linear stepwise regression was performed to determine the correlations among variables.RESULTSSerum concentration of vWF in the T2DM + AIS group was significantly higher than those in the T2DM, AIS, and control groups (P < 0.05). Serum vWF levels in the T2DM and AIS groups were significantly higher than that in the control group (P < 0.05). There was no significant difference in serum vWF level between the T2DM and AIS groups. In the T2DM + AIS group, serum vWF was independently associated and positively correlated with serum levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 (P < 0.05).CONCLUSIONSerum vWF level may represent a novel biomarker for the early diagnosis of lung AIS.

Endocervical adenocarcinoma in situ with ovarian metastasis: a case report

Background: Ovarian metastases, which may simulate primary ovarian neoplasms, can occur in advanced stage primary cervical adenocarcinoma (AC). However, such tumors are very rarely observed in cases of endocervical adenocarcinoma in situ (AIS) with early or even no obvious signs of tumor invasion. Case: We present a case of ovarian metastasis occurring in a 37-year-old triparous premenopausal woman with a diagnosed case of endocervical AIS. The patient presented with a rapidly growing and painful abdominal mass 22 months after a cold knife cone biopsy and 19 months after a simple extrafascial hysterectomy. She was subsequently treated with a combination of surgery and chemotherapy and is currently free of disease seven years after the initial diagnosis of endocervical AIS lacking unequivocally recognizable stromal invasion. Conclusion: Endocervical AIS with early or even no obvious detectable invasion may spread to the ovaries, but this situation is exceptionally rare. We propose that, in such cases, ovary sparing surgery is justifiable for initial treatment. Medical care strategies for patients affected by rare diseases largely depend on experience gained from reported cases in published literature, this is what compelled us to report this particular case.

P1.17-43 Sublober Resection for Adenocarcinoma in Situ Diagnosed by Intraoperative Frozen Sections

The establishment of sublobar resection procedures for non-small cell lung cancer is expected. Many groups have suggested adenocarcinoma in situ (AIS) to be a potential indication for sublobar resection. From 2012 to 2016, 80 patients (23 men and 57 women; median age, 70 years; range 40-86) diagnosed with adenocarcinoma in situ from intraoperative frozen sections, and underwent sublobar resection or lobectomy at our institution. Of these, 74 patients received sublobar resection and 6 patients underwent lobectomy. for adenocarcinoma in situ. We evaluate the predictive value of the intraoperative pathologic examination for AIS diagnosis, and overall survival, disease-free survival, and cancer-specific survival. Permanent pathologic examination revealed 61patients had AIS, 17 patients had minimally invasive adnocarcinoma and 2 patients had invasive adnocarcinoma. The predictive value of intraoperative pathologic examination for AIS diagnosis was 79.3%. During a median 48-month follow-up, there were 1 cancer unrelated deaths. The 5-year overall survival rate was 98.8%. The disease-free survival rate and the 5-year cancer-specific survival rate were 100%. The results of our retrospective study indicate that an intraoperative pathologic diagnosis of AIS is strongly predictive and allows for an intraoperative decision to perform a sublobar resection in these patients.

Cervical Screening Results Leading to Detection of Adenocarcinoma in Situ of the Uterine Cervix

Background:Adenocarcinoma in situ (AIS) of the uterine cervix is a preinvasive lesion of the invasive adenocarcinoma. We analyzed the cervical screening results leading to detecting the AIS lesions including the co-existence of AIS lesions with high-grade squamous intra-epithelial lesions (HSIL) and invasive carcinoma. Methods:Women who were diagnosed and received treatment for AIS at Chiang Mai University Hospital between January 1, 2007 and August 31, 2016 were retrospectively reviewed. The inclusion criteria were the women who had pathological diagnosis of AIS obtained from cervical punch biopsy or excisional cone biopsy with either loop electrosurgical excision procedure (LEEP) or cold-knife conization (CKC). The patient characteristics, diagnostic work-up and treatment details were reviewed, including the cervical screening results prior to the diagnosis of cervical AIS, pathologic results of excisional cone biopsy and hysterectomy specimens.Results:During the study period, 75 women with AIS pathology undergoing excisional cone biopsy with either LEEP (n=62) or CKC (n=13) were identified. The abnormal cytologic screening leading to detection of AIS was the squamous cell abnormality accounting for 57.3%. Abnormal glandular cytology accounted for 37.3%. The most common abnormal cervical screening results was HSIL cytology (n = 25) followed by AIS cytology (n = 13). Normal cytology was noted in 4 women in whom 3 were positive for HPV 18 and 1 had AIS on the endocervical polyp. AIS coexisted with HSIL and invasive carcinoma were detected in cone biopsy specimens in 21 (28%) and 29 (38.7%) patients, respectively. Conclusion:The majority of cervical screening results leading to detection of cervical AIS was the squamous cell abnormality accounting for 57.3% in which, HSIL cytology was the most common. Abnormal glandular cytology accounted for only 37.3%. Diagnostic cone excision is recommended if AIS lesion is noted in cervical biopsy specimen since nearly 40% have coexisting invasive lesions.

Challenges in the Pap diagnosis of endocervical adenocarcinoma in situ

Recognition of adenocarcinoma in situ (AIS) in cervical cytology is challenging. We calculated the sensitivity and accuracy of Papanicolaou (Pap) tests obtained within 1 year of a histologic diagnosis of AIS from 2007 to 2016. We also correlated it with the coexistence of squamous lesions, calculated the interobserver agreement, and compared these measures with those of endocervical adenocarcinoma (ECCA). We correlated AIS detection with high-risk human papillomavirus (hrHPV) status. Of 72 patients with histologic AIS and 48 patients with ECCA, 92% and 87.5%, respectively, had abnormal Pap test results. A glandular abnormality was detected in 44.4% of the AIS and 77.1% of the ECCA cases. Complete cytohistologic concordance was reached in 8.3% of AIS and 22.9% of ECCA cases. In addition, 27.8% of AIS and 6.3% of ECCA cases were diagnosed on Pap as a high-risk squamous abnormality. Concurrent squamous lesions were present in 79.2% of patients with AIS and 29.2% of patients with ECCA. The Paps from the AIS and ECCA cases were diagnosed as pure squamous abnormalities in 47.2% and 10.4% of cases, respectively. In the AIS cases, interobserver agreement was substantial for detection of any high-risk cytologic abnormality (kappa = 0.67) and fair for detection of any glandular abnormality (kappa = 0.34). Among the 26 patients with AIS tested for hrHPV, 92% had positive results and 8% had negative results. The cytologic sensitivity for the detection of AIS remains low. It is directly related to the coexistence of squamous lesions. Cytology and hrHPV as stand-alone screening tests fail in the early detection of a small proportion of glandular lesions, although combined testing will improve their detection rates.

Is a 5-mm diameter an appropriate cut-off value for the diagnosis of atypical adenomatous hyperplasia and adenocarcinoma in situ on chest computed tomography and pathological examination?

Preinvasive lesions, such as atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS), usually appear as pure ground-glass nodules (pGGNs) on thin-section computed tomography (TSCT). AAH is usually less than 5 mm wide on imaging and pathological examinations. We aimed to determine whether a 5-mm cut-off value was appropriate for the diagnosis of AAH and AIS. We retrospectively analyzed the performance of TSCT in evaluating 80 pathologically confirmed preinvasive lesions (33 AAH lesions in 31 patients and 47 AIS lesions in 45 patients). We compared the following characteristics between the AAH and AIS groups: lesion diameter, density, rim, lobulation, spiculation, vacuole sign, aerated bronchus sign, pleural indentation sign, and pathological findings. All 80 lesions appeared as pGGNs. On TSCT, the average diameter of AAH lesions (6.0±1.64 mm) was significantly smaller than that of AIS lesions (8.7±3.16 mm; P<0.001). The area under the curve (AUC) for diameter was 0.792, and the best diagnostic cut-off value was 6.99 mm. On gross pathological examination, the average diameter of AAH lesions (4.6±1.99 mm) was significantly smaller that of AIS lesions (6.8±2.06 mm; P<0.001). The AUC was 0.794, and the best diagnostic cut-off value was 4.5 mm. The vacuole sign was common in AIS (P=0.021). AAH did not significantly differ from AIS (P>0.05) in terms of average CT value, uniformity of density, morphology, rim, lobulation, spiculation, pleural indentation sign, and aerated bronchus sign. Lesion size and the vacuole sign were beneficial in the diagnosis of AAH and AIS. The vacuole sign was common in AIS. The best diagnostic cut-off value of nodular diameter for differentiating between AAH and AIS was 6.99 mm on TSCT and 4.5 mm on gross pathology.

Clinical significance of loop electrosurgical excisional procedure in diagnosis and treatment of cervical adenocarcinoma in situ and invasive cervical adenocarcinoma

Objective: To evaluate the accuracy of colposcopic biopsy on diagnosis of cervical adenocarcinoma in situ (AIS) and the clinical significance of loop electrosurgical excisional procedure (LEEP) on diagnosis and treatment of AIS and invasive adenocarcinoma. Methods: All medical records of 193 patients diagnosed as AIS by colposcopic biopsy and (or) AIS or invasive adenocarcinoma diagnosed by LEEP conization from Jan. 2015 to Dec. 2016 in Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed. The final diagnosis was based on colposcopic biopsy or LEEP or the highest grade of pathological diagnosis after hysterectomy. Results: In the 193 patients, 155 cases were finally diagnosed as AIS and 38 cases as invasive adenocarcinoma by histopathologic examination. Among the 155 AIS patients, 21.9% (34/155) had positive cone margins, in which 26 patients had hysterectomy, 30.8% (8/26) had residual disease in hysterectomy specimens; 78.1% (121/155) had negative cone margins, 68 patients with negative margins had hysterectomy and 5.9% (4/68) had residual disease, which was significantly lower than that with positive margins (χ(2)=10.46, P=0.001) . One hundred and twenty from one hundred ninty-three (62.3%, 120/193) with AIS were detected by colposcopy. Pathological diagnosis of 50.8% (98/193) cases were upgraded after LEEP conization. Conclusions: Colposcopy is indispensable for the diagnosis of AIS, but accurate diagnosis should be made by LEEP. LEEP is capable of detecting AIS or cervical adenocarcinoma that was misdiagnosed by colposcopy, which is a pivotal method for accurate diagnosis. The margin status of LEEP is important for patients in choosing further hysterectomy, but the presence of cervical adenocarcinoma should always be aware of.

Advance in Diagnose and Treatment Strategies of Adenocarcinoma in Situ

肺原位腺癌（adenocarcinoma in situ, AIS）于2011年在肺腺癌国际多学科分类中新增，2015版世界卫生组织（World Health Organization, WHO）肺肿瘤分类中补充，由于AIS处于肺腺癌发展的早期阶段，加深对其病理、诊断、鉴别与治疗策略等方面的认识，对改善肺腺癌的治疗预后具有重要意义。本综述将对目前AIS的发生发展、病理特征、鉴别诊断和治疗策略等方面的研究做一系统回顾，旨在为AIS的进一步研究提供理论基础。

Tissue-based Immunohistochemical Biomarker Accuracy in the Diagnosis of Malignant Glandular Lesions of the Uterine Cervix: A Systematic Review of the Literature and Meta-Analysis.

Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the published data. This systematic review and meta-analysis was performed to investigate the sensitivity and specificity of immunohistochemistry biomarkers in the tissue-based diagnosis of cervical adenocarcinoma histotypes compared with normal endocervix and benign glandular lesions. The systematic review and meta-analysis used a PICOT framework and QUADAS-2 to evaluate the quality of included studies. The literature search spanned 40 years and ended June 30, 2015. Abstracts of identified records were independently screened by 2 of the authors who then conducted a full-text review of selected articles. Sensitivity and specificity of immunohistochemistry expression in malignant glandular lesions of the cervix classified per WHO 2003 compared with 5 benign comparators (normal/benign endocervix, and benign endocervical, endometrioid, gastric, and mesonephric lesions) were calculated. Of 902 abstracts screened, 154 articles were selected for full review. Twenty-five articles with results for 36 biomarkers were included. The only biomarker with enough studies for a meta-analysis was p16 and the definition of positive p16 staining among them was variable. Nevertheless, any positive p16 expression was sensitive, ranging from 0.94 to 0.98 with narrow confidence intervals (CIs), for adenocarcinoma in situ (AIS) and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical and endometrioid lesions. Specificity for AIS and mucinous adenocarcinomas was also high with narrow CIs compared with benign endocervical lesions. The specificity was high for AIS, 0.99 (0.24, 1.0), and mucinous adenocarcinoma, 0.95 (0.52, 1.0), compared with normal/benign endocervix but with wider CIs, and low with very wide CIs compared with benign endometrioid lesions: 0.31 (0.00, 0.99) and 0.34 (0.00, 0.99), respectively. Results from single studies showed that p16, p16/Ki67 dual stain, ProExC, CEA, ESA, HIK1083, Claudin 18, and ER loss in perilesional stromal cells were useful with high (≥0.75) sensitivity and specificity estimates in ≥1 malignant versus benign comparisons. None of the biomarkers had highly useful sensitivity and specificity estimates for AIS, mucinous adenocarcinomas, or minimal deviation adenocarcinoma/gastric adenocarcinoma compared with benign gastric or mesonephric lesions or for mesonephric carcinoma compared with normal/benign endocervix, benign endocervical, endometrial, or mesonephric lesions. Any expression of p16 supports a diagnosis of AIS and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical lesions. The majority of studies did not separate mosaic/focal p16 staining from diffuse staining as a distinct pattern of p16 overexpression and this may have contributed to the poor performance of p16 in distinguishing AIS and mucinous adenocarcinomas from benign endometrioid lesions. Single studies support further investigation of 8 additional biomarkers that have highly useful sensitivity and specificity estimates for ≥1 malignant glandular lesions compared with ≥1 of the 5 benign comparators.

Preinvasive and Invasive Cervical Adenocarcinoma: Preceding Low-Risk or Negative Pap Result Increases Time to Diagnosis.

The aims of the study were to investigate screening histories of women with adenocarcinoma in situ (AIS) and adenocarcinoma (AdCa) of the cervix and to further evaluate screening for glandular disease. Screening histories were retrospectively collected for patients with AIS or AdCa at a single large-volume academic institution from 2005 to 2015. Fisher exact and Wilcoxon rank sum tests were used to compare AIS with AdCa patient characteristics, distribution of preceding Pap (i.e., trigger Pap) results, and high-risk human papillomavirus testing. The association between Pap result and time to diagnosis was evaluated. Eighty-seven cases, 50 AIS and 37 AdCa, met study criteria; median age was 31 and 43 years, respectively. Among the AIS cohort, 52.0% had a negative or low-risk trigger Pap result versus 24.3% of those with AdCa (p = .001). The time to diagnosis of AIS ranged from 8.4 to 18.8 weeks for those with high- versus low-risk or negative trigger Pap results, respectively (p = .002). The time to diagnosis of AdCa ranged from 14.6 to 44.7 weeks for those with high- versus low-risk or negative trigger Pap results, respectively (p = .003). Among those with high-risk human papillomavirus testing, 89.7% tested positive at the time of trigger Pap with 100% positivity among those with low-risk or negative trigger Pap results. Cervical AIS and AdCa affect many young nulliparous women and commonly preceded by low-risk or negative Pap testing. The interval to diagnosis increases with low-risk and negative Pap results, and therefore, further investigation into optimal screening for glandular lesions is needed.

Long-Term Follow-Up Results From Women With Cervical Adenocarcinoma In Situ Treated by Conization

Cervical adenocarcinoma in situ (AIS) is the precursor to adenocarcinoma, and early management will often prevent the occurrence of invasive adenocarcinoma. Conservative treatment with conization has been proposed for the initial treatment for cervical AIS. To evaluate the risk of residual/recurrent disease after conization, we investigated the long-term follow-up results for patients with cervical AIS treated by conization. One hundred thirty-six patients with a biopsy diagnosis of cervical AIS followed by conization were followed up with cytologic, histologic, and human papillomavirus testing. The rate of residual AIS in the following hysterectomy was significantly increased in patients with positive margins on the conization (48.6%, 17/35) compared to patients with negative margins (0/30). No significant disease was identified in patients treated by hysterectomy as primary treatment. More importantly, only 2 patients with conization as primary management had adenocarcinoma or focal AIS, respectively, during a long-term follow-up period (mean, 45 mo). However, one of them had positive margin on the conization and did not proceed to further treatment. The other one had negative margin on the conization but only had focal AIS on the hysterectomy. Human papillomavirus-positive rate showed no significant difference between patients treated by conization and patients treated by hysterectomy during the long-term follow-up. Therefore, if a negative resection margin is achieved, conservative management with conization and careful surveillance is suitable for patients with cervical AIS and desire for future childbearing.

Potential Effects of Updated Pap Test Screening Guidelines and Adenocarcinoma In Situ of the Cervix

To review cases of adenocarcinoma in situ (AIS) at our institution to examine how updated guidelines affect the timing of diagnosis. We identified patients with AIS diagnosed between 1998 and 2010 using the International Classification of Diseases, 9 Revision, Clinical Modification, code 233.1. Diagnosis was confirmed by pathology review. We abstracted demographic data, dysplasia history, and modalities utilized for diagnosis and treatment. We identified 242 patients who met selection criteria. Two hundred eight (86%) had Pap test abnormalities at presentation. One hundred thirty-seven out of 208 (66%) patients with abnormal Pap test results had a squamous, rather than glandular, abnormality. The mean time from abnormal Pap test to diagnosis of AIS was 29 months in patients older than 30 years and was 21 months in patients 30 years or younger. In patients younger than 21 years, 16 out of 17 had abnormal screening Pap test results showing squamous lesions. Their subsequent treatment for squamous dysplasia ultimately led to the diagnosis of AIS. : Updated screening guidelines may prevent the expeditious diagnosis of AIS in females younger than 21 years and those aged 21-29 years, many of whom had normal Pap test results within 3 years of diagnosis. II.

Cervical Adenocarcinoma in Situ: Update and Management

Adenocarcinoma in situ (AIS) of the uterine cervix is caused by infection with high-risk human papillomavirus and is the recognized precursor of invasive adenocarcinoma of the cervix. Because most AIS lesions are caused by HPV 16/18 infection, prophylactic HPV vaccination is an important step toward prevention of AIS, potentially reducing the incidence of invasive adenocarcinoma. Nonetheless, at the moment the incidence of AIS and invasive adenocarcinoma continues to increase, especially among young women when fertility preservation is an issue. Both diagnosis and treatment of AIS is challenging, because AIS lesions frequently extend into the endocervical canal, making detection and complete excision difficult. Hysterectomy remains the standard treatment for AIS. Selected patients, who wish to preserve fertility, with clear margins and negative ECC after initial conization are potential candidates for conservative treatment. If margins are involved after initial conization or ECC results are positive, the risk of residual or recurrent AIS and invasive adenocarcinoma of the cervix is considerably high. In these women, repeat surgery should be performed. For women, who do not undergo hysterectomy, long-term follow-up is recommended.