Gastric-type endocervical adenocarcinoma (G-EAC) represents a rare variant of cervical mucinous adenocarcinoma that is typically unrelated to human papillomavirus (HPV) infection. G-EAC exhibits highly atypical clinical presentations and characteristics, and aggressive biological behavior often leads to challenges in timely diagnosis. Here, we present a case study involving a 74-year-old Chinese woman who experienced urinary incontinence for one month. Biopsy pathology confirmed the diagnosis of G-EAC, revealing stage IVa by imaging examinations. The patient subsequently underwent three cycles of chemotherapy, followed by adjuvant radiotherapy and surgical excision of residual tumor foci. This comprehensive treatment approach yielded a favorable survival outcome. For patients with advanced G-EAC, a multimodal therapeutic approach holds promise and warrants further exploration.

Gastric-type endocervical adenocarcinoma (G-EAC) is a rare special type of cervical mucinous adenocarcinomas, and it is reported the incidence is unrelated to human papilloma virus infection. We report a rare case of G-EAC in stumps of duplicated cervices in a 49-year-old female patient. The woman complained of post-coital bleeding. She had a didelphic uterus with a duplex cervix, and had undergone subtotal hysterectomy 16 years ago. Gynecological examination revealed a normal-appearing right cervix, but the non-dominant side of the left cervix, which was buried and covered by the side wall of the left vagina, was difficult to view. After exposing, the left side cervix presented a mature appearance which was smaller than a normal cervix. Her serum carbohydrate antigen-19-9 levels was 112.59 U/ml. The right cervix\'s cytology was normal, whereas the left cervix had unusual glandular epithelial cells. HPV testing on both cervical smears was negative. Adenocarcinoma was identified at 3, 6, 12 o\'clock at the right cervix in a colposcopy-directed punch biopsy, while no abnormality was found in the biopsy of the left cervix, nor in the curettage of the double cervices. Pelvic magnetic resonance imaging (MRI) revealed two cervical canals, with a 1.9cm×1.6cm mass inside the left cervix, and the left wall of the right cervix may be involved by the tumor of the left cervix. After much deliberation, we considered that the patient had adenocarcinoma of the left cervix stage IB1. Then, the patient underwent radical cervical resection with bilateral salpingo-oophorectomy and bilateral pelvic lymphadenectomy. Her final histopathology indicated G-EAC of the duplicated cervices. After surgery, she received concurrent chemoradiation. Currently, 29 months after the final chemotherapy was administered, the patient remains healthy. Because G-EAC with duplicated cervices is an uncommon cunning tumor with a bad prognosis, early identification and therapy are recommended to enhance the prognosis. The comprehensive evaluation of symptoms and gynecological examination with cervical cytology, colposcopy-directed punch biopsy, endocervical curettage and MRI examine together may assist in determining an accurate preoperative diagnosis.

BACKGROUND: HIK1083 and MUC6 have been used as immunohistochemical markers to differentiate gastric-type adenocarcinoma (GTAC) from other endocervical adenocarcinomas. We aimed to assess their diagnostic accuracy through a systematic review and meta-analysis.
METHODS: Three electronic databases were searched from their inception to July 2022 for all studies assessing the expression in endocervical GTAC vs other endocervical adenocarcinomas. Diagnostic accuracy was assessed as sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR), and area under the curve (AUC) on SROC curves.
RESULTS: Four studies with 343 patients were included. HIK1083 showed sensitivity= 0.64, specificity= 0.94, LR+ =8.30, LR-= 0.38, DOR= 33.36, AUC= 89.9%. MUC6 showed sensitivity= 0.51, specificity= 0.74, LR+ =1.96, LR-= 0.71, DOR= 3.48, AUC= 72.8%.
CONCLUSIONS: HIK1083 showed high specificity and low sensitivity as a marker of GTAC, with moderate overall accuracy; MUC6 showed moderate specificity and low sensitivity, with low overall accuracy.

Gastric-type endocervical adenocarcinoma (GAS) is considered a distinct and clinically important entity because it is unrelated to human papillomavirus infection and has aggressive behavior and worse clinical outcomes than the usual type of endocervical adenocarcinoma (ECA). The preoperative diagnosis of GAS is often difficult because of its nonspecific clinical manifestations and special lesion location. We report the case of a 50-year-old Chinese woman who presented with intermittent left lower abdominal pain for 1 year. Preoperative images showed left hydrosalpinx and a lesion that was mainly located in the lower part of the uterine cavity. We considered the lesion to be a polyp before surgery. During hysteroscopic surgery, we suspected that it may be a submucosal myoma. However, pathology revealed that it was a GAS. GAS may be located in the upper endocervix or even reach the uterine cavity. The appearance is occasionally similar to that of submucosal myoma, resulting in difficult preoperative diagnosis and even misdiagnosis.

BACKGROUND: We aimed to analyze the clinicopathological features and outcomes of patients with gastric-type of HPV-independent endocervical adenocarcinoma (GAS HPVI ECA), and compare them with non-GAS HPVI ECA cases.
METHODS: Thirty-eight GASs [including 17 minimal deviation adenocarcinoma (MDA), 21 non-MDA GAS] and 17 non-GAS HPVI ECAs were studied. Data of clinical features, pathological characteristics, treatment, and outcomes were evaluated.
RESULTS: The median age of patients with GAS and non-GAS HPVI ECA was 46 and 48 years, respectively (p = 0.93). Compared with non-GAS HPVI ECAs, GAS had more common complains of vaginal watery discharge (p = 0.04). GAS cases were also associated with higher clinical stage (p = 0.036), more common in deeper cervical stromal invasion (p = 0.002) and lymphoavascular invasion (p = 0.044). GAS was associated with worse median progression-free survival (PFS) (p = 0.02) and median overall survival (OS) (p = 0.03) over patients with non-GAS HPVI ECAs. MDA had similar clinical and pathological features and prognosis compared with non-MDA GAS. Of note, serum CA19-9 levels were significantly higher in GAS than that in non-GAS HPVI ECA cases.
CONCLUSIONS: GAS cases were more likely to have high risk pathological factors and poorer PFS and OS compared with non-GAS HPVI ECAs. Serum CA19-9 may be helpful for diagnosis and screening in patients with GAS.

•Vaginal adenosis is a non-obligate pre-cursor for vaginal clear cell carcinoma.•Vaginal adenosis is rare and presents with a variety of signs and symptoms.•Unclear link between adenosis and carcinoma without diethylstilbestrol exposure.•Surveillance with physical examinations, imaging and biopsies is recommended.

UNASSIGNED: Endocervical adenocarcinoma represents 20-25% of the histological types of cervical carcinoma. Gastric-type mucinous adenocarcinoma of the cervix is a rare type of cancer with aggressive behavior. This type of malignancy is not related to high-risk human papillomavirus (HPV).
UNASSIGNED: We report a 59-year-old postmenopausal woman complaining of vaginal bleeding and pelvic pain. Histological analysis of punch biopsy and endocervical curettage revealed possible endocervical mucinous adenocarcinoma, while magnetic resonance imaging (MRI) revealed a 10 × 8 cm sized cervical mass. According to oncologists, the tumor was inoperable, so the patient received 6 cycles of chemotherapeutic agents with carboplatin, paclitaxel and bevacizumab from December 2019 to March 2020. However, chemotherapy had very poor results in this patient, because the mass was increased to 24 cm in a new MRI performed after the end of chemotherapy. Finally, the patient underwent radical surgery. On histopathological examination, the surgical margin was all free from everywhere and the mass was confirmed as a gastric-type mucinous adenocarcinoma of the cervix with low differentiation.
UNASSIGNED: It is very important to have an early diagnosis of gastric-type mucinous adenocarcinoma of the cervix, as this tumor is poorly symptomatic and very aggressive. When chemotherapy is not effective, radical surgery may be a solution for better survival.

Few studies have explored HER2 status in cervical adenocarcinoma, particularly in the gastric-type adenocarcinoma (GAC), a nonhuman-papillomavirus-related subtype with poor clinical outcomes. In this study, we investigated HER2 expression and amplification by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 209 well annotated cervical adenocarcinomas diagnosed using the International Endocervical Adenocarcinoma Criteria and Classification. IHC identified HER2 protein expression in 57.4% (123/209) of adenocarcinomas, of which 62 were IHC 1+ (negative), 38 2+ (equivocal) and 23 3+ (positive). HER2 amplification was found in 13 cases (6.2%) including 10 with IHC 3+ and 3 with IHC 2+. Among all the major histotypes of cervical adenocarcinoma, HER2 amplification was most common in GAC cases with a frequency of 14.7% (5/34). Moreover, HER2 amplification was more frequently associated with 2018 International Federation of Gynecology & Obstetrics (FIGO) stage III/IV, perineural involvement and ovarian spread (p < 0.05) while IHC 3+ was more common in patients with lymphovascular invasion and ovarian involvement (p < 0.05). Survival analysis indicated that FIGO stage III/IV, GAC, and p53 overexpression were associated with poor disease-specific survival and tumor recurrence (p < 0.05). In conclusion, HER2 amplification was present in a subset of adenocarcinomas, and more common in GAC, pointing to a potential benefit from trastuzumab treatment. HER2 overexpression does not identify gene amplification status in cervical adenocarcinoma; therefore, FISH is suggested for both IHC positive and equivocal cases. Further investigation on more cases with longer follow-up times is required to consolidate these findings.

The emerging concept of gastric-type mucinous carcinoma (GAS) of the uterine cervix has been accepted worldwide because of its aggressive clinical behaviour and the absence of high-risk human papillomavirus (HPV). GAS is included as a variant of mucinous carcinoma in the 2014 World Health Organization classification, and its recognition has provoked a discussion on endocervical adenocarcinoma as a single entity such that endocervical adenocarcinoma is now divided into HPV-associated and HPV-independent groups. This article reviews historical and conceptual aspects of GAS and its precursors, starting with minimal deviation adenocarcinoma (MDA), through the ensuing confusion, up to the recent paradigm shift in cervical adenocarcinoma subclassification. The gastric immunophenotype of MDA was demonstrated by a Japanese group in 1998 using the HIK1083 antibody, which recognises gastric pyloric gland mucin, and this elucidated the pathogenesis of this particular tumour. However, this information resulted in overdiagnosis of lobular endocervical glandular hyperplasia (LEGH), first described in 1999 and which represents pyloric gland metaplasia (PGM), as malignant. In the early 2000s the relationship between MDA and LEGH/PGM became a matter of controversy. In 2007 HIK1083 immunohistochemistry extended the morphological spectrum of endocervical adenocarcinoma showing gastric differentiation beyond MDA, which resulted in the proposal of GAS as a distinct entity including MDA as its very well-differentiated subtype. GAS is now considered to be an aggressive and chemoresistant neoplasm that is not related to high-risk HPV. The LEGH/PGM-GAS sequence is currently regarded as an HPV-independent pathway of carcinogenesis. Understanding the underlying molecular events in this process is key to the development of biomarkers for early detection and molecular targeted therapy.

The current study indicates the case of intracholecystic papillary neoplasm (ICPN) protruding into the common bile duct (CBD) without superficial spread. A 58-year-old woman presented to hospital with a fever that lasted for three days. Laboratory tests revealed elevated hepatobiliary enzyme levels. CT, MRI and endoscopic ultrasonography revealed a polypoid, papillary tumor inside the gallbladder cavity, which also extended to the CBD. On peroral cholangioscopy, a papillary tumor with mucin production was found at the middle bile duct. Biliary biopsy and bile cytology indicated adenocarcinoma. Based on a diagnosis of ICPN extending to the CBD, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy and gallbladder bed resection. However, pathological examination revealed that the ICPN was confined to the gallbladder and cystic duct, whereas the CBD was tumor-free. The present case indicates that when ICPN increases in size, it may protrude into the CBD due to an increased intracholecystic pressure, which increases the risk of overestimation of tumor extension and may result in unnecessary additional bile duct resection.