Uterine Cervical Adenocarcinoma Research Articles

Concordance Between Biopsy and Resection Diagnoses of Uterine Cervical Adenocarcinoma According to the Updated World Health Organization 2020 Classification: A Multi-Institutional Study Elucidating Real-World Practice in Japan.

Endocervical adenocarcinoma is divided into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) in the 5h edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphological criteria used for biopsy specimens in real-world practice remains undetermined. To validate the utility of the 5th edition of the WHO classification for biopsy samples, focusing on its diagnostic criteria with the aid of ancillary studies. We retrieved 217 cases of endocervical adenocarcinoma from 6 institutions, in which glass slides of both biopsy and resection specimens were available for review. Concordance between the biopsy and resection specimen diagnoses was evaluated. For discordant diagnoses, an algorithmic approach with ancillary studies proposed by the international group was applied to confirm their utility to improve the accuracy of biopsy diagnosis. The biopsy diagnosis matched the resection specimen diagnosis in 197 cases (concordance rate, 91%; κ = 0.75). The concordance rate was significantly higher for HPVA than HPVI (95% versus 81%, P = .001). There were no significant differences in the proportions of HPVA and HPVI or the accuracy of biopsy diagnosis between the participating institutions. All 19 discordant cases with unstained glass slides available were accurately recategorized as HPVA or HPVI using HPV in situ hybridization; p16 immunohistochemistry was positive in 3 of 9 cases of gastric-type HPVI that were negative by in situ hybridization. The 5th edition of the WHO criteria for biopsy diagnosis of endocervical adenocarcinoma distinguishes HPVA from HPVI well when ancillary studies are adequately applied.

Radixin modulates the plasma membrane localization of CD47 in human uterine cervical adenocarcinoma cells

Despite the dramatic success of immune checkpoint blockers in treating numerous cancer cell types, current therapeutic modalities provide clinical benefits to a subset of patients with cervical cancers. CD47 is commonly overexpressed in a broad variety of cancer cells, correlates with poor clinical prognosis, and acts as a dominant macrophage checkpoint by interacting with receptors expressed on macrophages. It allows cancer cells to escape from the innate immune system and hence is a potential therapeutic target for developing novel macrophage checkpoint blockade immunotherapies. As the intracellular scaffold proteins, ezrin/radixin/moesin (ERM) family proteins post-translationally regulate the cellular membrane localization of numerous transmembrane proteins, by crosslinking them with the actin cytoskeleton. We demonstrated that radixin modulates the plasma membrane localization and functionality of CD47 in HeLa cells. Immunofluorescence analysis and co-immunoprecipitation assay using anti-CD47 antibody showed the colocalization of CD47 and all three ERM families in the plasma membrane, and the molecular interactions between CD47 and all three ERM. Interestingly, gene silencing of only radixin, reduced the CD47 plasma membrane localization and functionality by means of flow cytometry and phagocytosis assay but had little influence on its mRNA expression. Together, in HeLa cells radixin may function as a principal scaffold protein responsible for the CD47 plasma membrane localization.

MRI characteristics for predicting histological subtypes in patients with uterine cervical adenocarcinoma

PurposeTo evaluate the magnetic resonance imaging (MRI) findings of uterine cervical adenocarcinoma for predicting different histological subtypes. Materials and methodsWe retrospectively analyzed MRI findings of 76 consecutive patients with histopathologically-confirmed uterine cervical adenocarcinoma undergoing preoperative MRI examination. An experienced pathologist classified the histological subtypes based on World Health Organization’s 2020 classification and into human papillomavirus (HPV)-associated adenocarcinomas (HPVAs, n = 54) (usual type and variants) and HPV-independent adenocarcinomas (HPVIs, n = 22) (gastric type adenocarcinoma (GAS), clear cell type, and other types). Different MRI variables were compared quantitatively and qualitatively between HPVA and HPVI and between GAS and non-GAS tumor types. ResultsThe maximum tumor diameter was significantly greater in HPVIs than HPVAs (41.9 ± 18.6 vs 32.7 ± 15.6 mm; p < 0.05). Heterogeneous enhancement on fat-suppressed gadolinium-enhanced T1-weighted images was more frequently seen in HPVIs than HPVAs (62 % vs 15 %; p < 0.01) and in GASs than non-GASs (78 % vs 16 %; p < 0.01). Also, infiltrative growth pattern (58 % vs 20 %; p < 0.05) and intratumoral cyst formation (83 % vs 47 %) (p < 0.05) were more frequent in GASs than non-GASs. ConclusionsCompared with HPVAs, HPVIs tend to have a larger tumor size with heterogeneous enhancement, of which GASs frequently show infiltrative growth patterns with intratumoral cyst formation and heterogeneous enhancement.

Aberrant expression of claudin-6 contributes to malignant potentials and drug resistance of cervical adenocarcinoma.

Recent studies have revealed that aberrant expression of tight junction (TJ) proteins is a hallmark of various solid tumors and it is recognized as a useful therapeutic target. Claudin‐6 (CLDN6), a member of the family of TJ transmembrane proteins, is an ideal therapeutic target because it is not expressed in human adult normal tissues. In this study, we found that CLDN6 is highly expressed in uterine cervical adenocarcinoma (ADC) and that high CLDN6 expression was correlated with lymph node metastasis and lymphovascular infiltration and was an independent prognostic factor. Shotgun proteome analysis revealed that cell‐cell adhesion‐related proteins and drug metabolism‐associated proteins (aldo‐keto reductase [AKR] family proteins) were significantly increased in CLDN6‐overexpressing cells. Furthermore, overexpression of CLDN6 enhanced cell‐cell adhesion properties and attenuated sensitivity to anticancer drugs including doxorubicin, daunorubicin, and cisplatin. Taken together, the results indicate that aberrant expression of CLDN6 enhances malignant potentials and drug resistance of cervical ADC, possibly due to increased cell‐cell adhesion properties and drug metabolism. Our findings provide an insight into a new therapeutic strategy, a CLDN6‐targeting therapy, against cervical ADC.

Nomograms for predicting the survival rate of stage T1−T2 uterine cervical adenocarcinoma patients after hysterectomy

To explore factors associated with the overall survival (OS) and cancer-specific survival (CSS) of patients with stage T1–T2 uterine cervical adenocarcinoma (UAC) after hysterectomy and develop nomogram models to predict their prognosis. The data of stage T1–T2 UAC patients after hysterectomy, diagnosed from 2004 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database, were retrieved and divided into a training cohort (n = 2103) and internal validation cohort (n = 1052). Another dataset of eligible patients (n = 107) diagnosed from 2013 to 2019 at the Fujian Maternal and Child Health Hospital was retrieved as the external validation set. Nomograms were developed by the results of univariate and multivariate Cox regression models of OS and CSS. C-index, calibration curve, receiver operating characteristic (ROC) curve and area under the curve (AUC) value were used to assess the prediction model. Age, race, marital status, tumor grade, T stage, tumor size and number of positive lymph nodes were identified as independent prognostic factors for OS and CSS. The number of primary tumors was a specific influencing factor for OS, and postoperative radiotherapy was a beneficial factor for CSS. The C-indexes of OS and CSS nomograms constructed in this study in the training cohort were 0.825 (0800–0.850) and 0.820 (0.789–0.851), higher than the 0.701 (0.671–0.731) and 0.735 (0.702–0.768) of the International Federation of Gynecology and Obstetrics (FIGO) stage, p &lt; 0.001. The prediction ability of the nomogram models was successfully validated in both the internal and external validation cohorts. The established nomogram models had high prediction accuracy for predicting the OS and CSS of stage T1–T2 UAC patients after hysterectomy and were superior to the FIGO stage. They could help clinicians accurately predict patients’ prognoses and select the best treatment plan.

The role of human papillomavirus deoxyribonucleic acid for distinguishing between cervical adenocarcinoma and endometrial adenocarcinoma

HIGHLIGHTS1. Determining primary tumor between uterine cervical adenocarcinoma and endometrial carcinoma is often complicated due to the lack of specimen or overlapped histological and morphological spectrum.2. The distinction between endometrial and endocervical adenocarcinoma preoperatively is important because the treatment is different.3. The samples from each group are tested for HPV DNA using PCR method.4. High risk HPV infected patients have a higher probability to become uterine cervical adenocarcinoma.5. HPV DNA test has a role for distinguishing between uterine cervical adenocarcinoma and endometrial carcinoma. ABSTRACTObjectives: To analyze the role of HPV DNA for distinguishing between uterine cervical adenocarcinoma and endometrial adenocarcinoma.Materials and Methods: This was a case control study using paraffin block samples from uterine cervix adenocarcinoma and endometrial adenocarcinoma operation at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. Each group was tested for HPV DNA using PCR method. Sample size was 18 in each group.Results: A total of 36 samples fulfilled the inclusion criteria in this study. Each group comprised 18 samples. There were 83.3% of uterine cervical adenocarcinoma and 11.1% of endometrial adenocarcinoma that revealed high risk HPV. Chi-Square test result found significant correlation between high risk HPV and uterine cervical adenocarcinoma (p&lt;0.05) with Odds Ratio (OR) 40.00 (CI 95%).Conclusion: There was a significant correlation between high risk HPV and uterine cervix adenocarcinoma. High-risk HPV infected patients had a risk to suffer from uterine cervical adenocarcinoma compared to those with endometrial adenocarcinoma. HPV DNA test had a role for distinguishing between uterine cervical adenocarcinoma and endometrial adenocarcinoma.

Regulatory roles of claudin-1 in cell adhesion and microvilli formation

Aberrant expression of tight junction proteins has recently been focused on in the cancer research field. We previously showed that claudin-1 is aberrantly expressed from an early stage of uterine cervical adenocarcinoma and contributes to malignant potentials. To elucidate the molecular mechanisms underlying tumor-promoting roles of claudin-1, we established and analyzed claudin-1 knockout cells. Knockout of claudin-1 suppressed conventional tight junctional functions, barrier and fence functions, and expression of cell adhesion-associated proteins including E-cadherin. Comparative proteome analysis revealed that expression of claudin-1 affected expression of a wide range of proteins, especially proteins that are associated with cell adhesion and actin cytoskeleton remodeling. Interactome analysis of the identified proteins revealed that E-cadherin and focal adhesion kinase play central roles in the claudin-1-dependently affected protein network. Moreover, knockout of claudin-1 significantly suppressed microvilli formation and activity of Ezrin/Radixin/Moesin. Taken together, the results indicate that expression of claudin-1 affects not only conventional tight junction function but also expression and activity of a wide range of proteins, especially proteins that are associated with cell adhesion and actin cytoskeleton remodeling, to contribute to malignant potentials and microvilli formation in cervical adenocarcinoma cells.

Development and validation of a novel nomogram to predict cancer-specific survival in patients with uterine cervical adenocarcinoma.

BackgroundThe treatment strategies and prognostic factors for uterine cervical adenocarcinoma (UAC) primarily refer to that for squamous cell carcinoma (SCC). However, the biological behavior, treatment outcomes of UAC differ from that of SCC. This study aimed to develop and validate a prognostic nomogram for predicting the probability of 3- and 5-year cancer-specific survival (CSS) in patients with UAC.MethodsA total of 8,991 UAC patients from the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. Patients diagnosed between 1988 and 2010 (n=5,655) were enrolled for model development and internal validation, and those diagnosed between 2011 and 2016 (n=3,336) were used for temporal validation. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to select predictors of CSS. Cox hazard regression analysis was used to construct the model, which was presented as a static nomogram and web-based dynamic nomogram. The nomogram was internally validated using the bootstrap resampling method and underwent temporal validation.ResultsTumor grade, stage T, stage N, stage M, tumor size, and surgery of the primary site were identified as independent prognostic factors for CSS and subsequently incorporated into construction of the nomogram. The nomogram could accurately predict 3- and 5-year CSS with an optimism adjusted c-statistic of 0.90 [95% confidence intervals (CI): 0.89–0.91] and 0.89 (95% CI: 0.88–0.91) after internal validation, respectively; while, after temporal validation, the statistics were 0.89 (95% CI: 0.87–0.91) and 0.88 (95% CI: 0.83–0.94), respectively. The internal and temporal calibration plots demonstrated good consistency between the predicted and observed values of CSS. Based on the model, the cases were stratified into high- and low-risk groups. The Kaplan-Meier plot showed that high-risk patients exhibited significantly poorer survival than those at low risk (P<0.0001). The prediction model exhibited a good discriminative ability and an optimal accuracy.ConclusionsIn the form of a static nomogram or an online calculator, an effective and convenient nomogram was developed and validated to help clinicians quantify the risk of mortality, make personalized survival assessments, and create optimal treatment plans for UAC patients.

Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas

The association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV− groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV− group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV− group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.

Aberrant expression of junctional adhesion molecule-A contributes to the malignancy of cervical adenocarcinoma by interaction with poliovirus receptor/CD155.

Recent studies have shown that aberrant expression of tight junction proteins (TJP) contributes to malignant potential of various cancers. In the present study, we investigated the expression of junctional adhesion molecule‐A (JAM‐A), one of the transmembrane TJP, in uterine cervical adenocarcinoma and the significance of its expression for malignancy. Immunohistochemistry on human surgical specimens showed that JAM‐A was aberrantly expressed in neoplastic regions including adenocarcinoma in situ (AIS). Knockout of JAM‐A significantly suppressed cell proliferation and colony‐forming and migration abilities. We also showed that an antibody specific to an extracellular region of JAM‐A reduced cell proliferation ability and that loss of JAM‐A increased drug sensitivity of cervical adenocarcinoma cells. Based on a comprehensive proteome analysis, we found that poliovirus receptor (PVR/CD155) was regulated by JAM‐A and formed a physical interaction with JAM‐A. In human surgical specimens, PVR/CD155 expression was significantly correlated with some clinicopathological features and prognosis of cervical adenocarcinoma. Interestingly, most of the PVR/CD155‐positive cases expressed a high level of JAM‐A, and patients with the expression pattern of PVR/CD155 positive/JAM‐A high had significantly shorter periods of relapse‐free survival (P = .00964) and overall survival (P = .0204) than those for the other patients. Our observations suggest that aberrant expression of JAM‐A promotes malignancy of uterine cervical adenocarcinoma by regulation of PVR/CD155, and JAM‐A is therefore a potential therapeutic target for this malignancy.

Protein overexpression of c-MET has a significant impact on survival in patients with uterine cervical adenocarcinoma

Protein overexpression of c-MET has a significant impact on survival in patients with uterine cervical adenocarcinoma

Aldolase A promotes epithelial-mesenchymal transition to increase malignant potentials of cervical adenocarcinoma.

Recent studies have revealed that metabolic reprogramming is closely associated with epithelial‐mesenchymal transition (EMT) during cancer progression. Aldolase A (ALDOA) is a key glycolytic enzyme that is highly expressed in several types of cancer. In this study, we found that ALDOA is highly expressed in uterine cervical adenocarcinoma and that high ALDOA expression promotes EMT to increase malignant potentials, such as metastasis and invasiveness, in cervical adenocarcinoma cells. In human surgical specimens, ALDOA was highly expressed in cervical adenocarcinoma and high ALDOA expression was correlated with lymph node metastasis, lymphovascular infiltration, and short overall survival. Suppression of ALDOA expression significantly reduced cell growth, migration, and invasiveness of cervical cancer cells. Aldolase A expression was partially regulated by hypoxia‐inducible factor‐1α (HIF‐1α). Shotgun proteome analysis revealed that cell‐cell adhesion‐related proteins were significantly increased in ALDOA‐overexpressing cells. Interestingly, overexpression of ALDOA caused severe morphological changes, including a cuboidal‐to‐spindle shape shift and reduced microvilli formation, coincident with modulation of the expression of typical EMT‐related proteins. Overexpression of ALDOA increased migration and invasion in vitro. Furthermore, overexpression of ALDOA induced HIF‐1α, suggesting a positive feedback loop between ALDOA and HIF‐1α. In conclusion, ALDOA is overexpressed in cervical adenocarcinoma and contributes to malignant potentials of tumor cells through modulation of HIF‐1α signaling. The feedback loop between ALDOA and HIF‐1α could become a therapeutic target to improve the prognosis of this malignancy.

Positive staining of the immunoligand B7-H6 in abnormal/transformed keratinocytes consistently accompanies the progression of cervical cancer

BackgroundB7-H6 has been revealed as an endogenous immunoligand expressed in a variety of tumors, but not expressed in healthy tissues. Heretofore, no studies have been reported describing B7-H6 in women with cervical cancer. To investigate this question, our present study was conducted.ResultsThis retrospective study comprised a total of 62 paraffinized cervical biopsies, which were distributed in five groups: low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), squamous cervical carcinoma (SCC), uterine cervical adenocarcinoma (UCAC), and a group of cervicitis (as a control for non-abnormal/non-transformed cells). Cervical sections were stained by immunohistochemistry to explore the expression of B7-H6, which was reported according to the immunoreactive score (IRS) system. We observed a complete lack of B7-H6 in LSIL abnormal epithelial cells. Interestingly, B7-H6 began to be seen in HSIL abnormal epithelial cells; more than half of this group had B7-H6 positive cells, with staining characterized by a cytoplasmic and membranous pattern. B7-H6 in the SCC group was also seen in the majority of the sections, showing the same cytoplasmic and membranous pattern. Strong evidence of B7-H6 was notably found in UCAC tumor columnar cells (in 100% of the specimens, also with cytoplasmic and membranous pattern). Moreover, consistent B7-H6 staining was observed in infiltrating plasma cells in all groups.ConclusionsB7-H6 IRS positively correlated with disease stage in the development of cervical cancer; additionally, B7-H6 scores were found to be even higher in the more aggressive uterine cervical adenocarcinoma, suggesting a possible future therapeutic target for this cancer type.

Elevated expression of G protein-coupled receptor 30 (GPR30) is associated with poor prognosis in patients with uterine cervical adenocarcinoma.

Uterine cervical adenocarcinoma has a worse prognosis than that of squamous cell carcinoma and useful diagnostic and prognostic markers are needed. Estrogen is one of the key regulators of several cancers, however, the estrogen signaling has not been focused on in cervical adenocarcinoma. Here, we shows expression profile of classical estrogen receptor (ER) and a novel membrane type estrogen receptor, G protein-coupled receptor 30 (GPR30), in surgical specimens (n=53). GPR30 was strongly expressed on the cell membrane and in the cytoplasm in adenocarcinoma in situ (AIS) and adenocarcinoma, and its expression was especially strong at the invasion front in most of the cases of GPR30-positive adenocarcinoma. Nuclear staining of ER was strong in non-neoplastic glands, whereas it was almost absent in most of the AIS and adenocarcinoma cases. There was a weak but statistically significant negative correlation between immunoreactivity of GPR30 and that of ER in cervical AIS and adenocarcinoma lesions (Spearman's correlation, r=-0.324, p=0.017). ROC curve analysis revealed that immunoreactivity of GPR30 successfully distinguished neoplasms from non-neoplastic glands with high specificity (100%) and sensitivity (75.5%). GPR30 positivity was significantly correlated with histological type (p=0.009), tumor diameter (p=0.003), tumor size (p<0.001), lymphovascular infiltration (p=0.005) and UICC stage (p<0.001). ER expression was correlated only with tumor factor (p=0.047). GPR30-high patients had poor prognosis with a significantly shorter overall survival (OS) period (p=0.0309). GPR30 expression is a potential diagnostic and prognostic marker.

Postirradiation PD-L1 expression is a predictor of an improved prognosis after carbon ion radiotherapy for uterine cervical adenocarcinoma

Postirradiation PD-L1 expression is a predictor of an improved prognosis after carbon ion radiotherapy for uterine cervical adenocarcinoma

Clinical and MRI Characteristics of Uterine Cervical Adenocarcinoma: Its Variants and Mimics.

Adenocarcinoma currently accounts for 10–25% of all uterine cervical carcinomas and has a variety of histopathological subtypes. Among them, mucinous carcinoma gastric type is not associated with high-risk human papillomavirus (HPV) infection and a poor prognosis, while villoglandular carcinoma has an association with high-risk HPV infection and a good prognosis. They show relatively characteristic imaging findings which can be suggested by magnetic resonance imaging (MRI), though the former is sometimes difficult to be distinguished from lobular endocervical glandular hyperplasia. Various kinds of other tumors including squamous cell carcinoma should be also differentiated on MRI, while it is currently difficult to distinguish them on MRI, and HPV screening and pathological confirmation are usually necessary for definite diagnosis and further patient management.

Role of Magnetic Resonance Imaging in distinguishing the origin of adenocarcinoma at the junction of the lower uterine segment and endocervix

Objective: To evaluate Magnetic Resonance Imaging (MRI) at 3.0T in differential diagnosis of the origin of adenocarcinoma at the junction of the lower uterine segment and endocervix. Methods: 71 patients with adenocarcinoma at the junction of the lower uterine segment and endocervix were retrospectively collected. Pelvic MR examinations, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences, were performed within 2 weeks before surgery. MR images were analyzed and measured by two radiologists, including the location of the tumor center, the enhancement pattern, the anterior and posterior diameters, the left and right diameters, the upper and lower diameters, and the apparent diffusion coefficient (ADC) of the tumor. Immunohistochemical method was used as gold standard in distinguishing cervical adenocarcinoma and uterine adenocarcinoma. Results: The upper and lower diameters of uterine adenocarcinoma were [(5.80±2.31) cm], significantly larger than those of cervical adenocarcinoma [(4.16±2.17) cm, P=0.009]. Using 4.5cm as the best cutoff point value, the sensitivity and specificity in distinguishing uterine adenocarcinoma and cervical adenocarcinoma were 68.4% and 65.4%, respectively. According to the location of tumor center, the sensitivity and specificity were 84.2% and 73.1%, respectively. Using tumor enhancement pattern as the criterion, the sensitivity and specificity of diagnosing uterine adenocarcinoma and cervical adenocarcinoma were 68.4% and 80.8% respectively. Conclusions: MRI has certain clinical value in evaluating the origin of adenocarcinoma at the junction of the lower uterine segment and endocervix. The lesions can be diagnosed according to the main location, the characteristics of dynamic enhancement and the growth pattern of the tumor.

Metastatic Adenocarcinoma to the Uterine Cervix Versus Primary Cervical Adenocarcinoma

Abstract Adenocarcinoma metastases to the cervix can originate from the endometrium, the upper müllerian tract, or from extramüllerian sites such as the gastrointestinal and pancreatobiliary tract, bladder, breast, lung, or even the salivary gland. In some cases, the metastatic lesions have signet-ring morphology, infiltrative pattern, and/or extensive lymphovascular spread. In others, however, the distinction between a primary cervical lesion and a metastasis to the cervix is more challenging because metastases may mimic endocervical adenocarcinoma in situ by colonizing the native endocervical mucosa through intraepithelial spread. Careful morphologic interpretation, combined with immunohistochemistry, human papillomavirus molecular testing, and clinical correlation, is required in order to arrive at the correct diagnosis.

Tumor-associated CD204+ M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma.

Uterine cervical adenocarcinoma is rare, but its prevalence has increased. To improve outcomes and ensure the suitability of recent immunotherapies, the aim of this study was to evaluate the clinicopathological impact of the tumor immune microenvironment of uterine cervical adenocarcinoma. We investigated 148 adenocarcinoma cases, including 21 cases of adenocarcinoma in situ (AIS) and 127 cases of invasive adenocarcinoma, using immunohistochemistry to detect tumor‐infiltrating immune cells and the expression of programmed cell death 1 ligand‐1 (PD‐L1) and p16 on tumor cells. We then carried out correlation and survival analyses. The density of immune cells and expression levels were compared between the tumor cell nest and stroma and between AIS and invasive adenocarcinoma using digital image analysis. A higher density of tumor‐infiltrating CD204+ M2 macrophages was significantly associated with shorter disease‐free survival, although no other tumor‐infiltrating immune cells were prognostic, including CD4+, CD8+, FOXP3+, and PD‐1+ lymphocytes and CD68+ macrophages. The density of stroma‐infiltrating lymphocytes and macrophages was significantly higher in invasive adenocarcinoma than in AIS. The density of tumor‐infiltrating lymphocytes in p16‐expressing human papillomavirus (HPV)‐positive tumors was significantly higher than that in HPV‐negative tumors. The HPV status was not associated with patient outcome. Expression of PD‐L1 on tumor cells was found only in invasive adenocarcinoma cases (17.3%). A higher density of stroma‐infiltrating lymphocytes and macrophages was found in PD‐L1‐positive tumors than in negative tumors. Patients with PD‐L1‐positive tumors tended to experience longer survival. It is suggested that tumor‐infiltrating CD204+ M2 macrophages may predict poor prognoses in patients with cervical adenocarcinoma.

Uterine cervical adenocarcinoma associated with lobular endocervical glandular hyperplasia: Radiologic-pathologic correlation.

We aimed to identify the radiologic features of uterine cervical adenocarcinoma associated with lobular endocervical glandular hyperplasia (LEGH). We retrospectively analyzed magnetic resonance (MR) images and pathologic findings of eight patients who underwent preoperative MR imaging followed by surgical resection and who were pathologically diagnosed with adenocarcinoma (except for adenocarcinoma in situ) associated with LEGH. We assessed the following MR findings: multicystic component (MC), solid component (SC), signal intensity of SC on diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) map, and radiological stage (r-stage) based on the FIGO classification. A pathologist reevaluated the pathological stage (p-stage) according to the FIGO classification. We correlated the MR findings with the pathologic features. Eight patients were classified into the following three types based on the MR findings: type A, MC and SC; type B, only SC; and type C, only MC. In the five patients with type A, diffusion restriction (DR) was seen on DWI and the ADC map. In 80% of type A cases, the r-stage matched the p-stage. In the one patient with type B, DR was not seen on DWI or the ADC map, and the r-stage matched the p-stage. In the remaining type C cases, DR was not seen on DWI or the ADC map, and the r-stage was underestimated compared with the p-stage. On MR imaging, the most common type of adenocarcinoma with LEGH is type A; type C is difficult to diagnose as carcinoma.