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Li J, Wang D, Su N, Wang M, Wang Y. Immunotherapy benefits PD‑L1‑positive gastric‑type endocervical adenocarcinoma: A multicenter, retrospective study. Mol Clin Oncol 2025; 22:46. [PMID: 40236834 PMCID: PMC11995453 DOI: 10.3892/mco.2025.2841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Accepted: 01/28/2025] [Indexed: 04/17/2025] Open
Abstract
Gastric-type endocervical adenocarcinoma (GEA) usually exhibits notable aggressiveness and resistance to current therapies. A high expression of programmed death-ligand 1 (PD-L1) was previous reported in GEA and indicated it might benefit from immunotherapy targeting programmed cell death protein 1 (PD-1)/PD-L1. In the present study, the efficacy of immunotherapy in a panel of patients with GEA was explored, aiming to provide the first-hand evidence on this topic. A total of 44 pathologically diagnosed patients with GEA were recruited from the First Affiliated Hospital of Zhengzhou University and the Cancer Hospital of Zhengzhou University. The clinical and pathological information including age, tumor stage, treatments and prognosis were retrieved from our medical records system. Kaplan-Meier analysis was conducted to evaluate the role of immunotherapy on patients' overall survival (OS) and progression-free survival (PFS). According to the treatments, patients with GEA were divided into two groups: The immunotherapy group (n=19) and the non-immunotherapy group (n=25, the control group). In the immunotherapy group, 9 patients received PD-1/PD-L1 inhibitors as part of their primary treatment, while the remaining 10 received it after tumor recurrence/metastasis. Compared with the control group, the use of immunotherapy during primary treatment significantly extended PFS (median PFS: 14 vs. 6 months, P=0.004) and OS (median OS: 24 vs. 16 months, P=0.019). However, in the 10 patients who initiated immunotherapy after tumor recurrence/metastasis, the survival benefits were only observed for OS (median OS: 33.5 vs. 16 months, P=0.013) but not PFS. Furthermore, the efficacy of immunotherapy was more significant in patients with PD-L1-positive GEA than those PD-L1-negative cases, which improved both the PFS (median PFS: 17 vs. 7 months, P=0.002) and OS (median OS: 36 vs. 16 months, P<0.001). This is the first study, to the best of our knowledge, reporting the efficacy of immunotherapy for GEA. It was demonstrated that the earlier use of PD-1/PD-L1 inhibitors was significantly associated with an improved prognosis, and PD-L1 status could predict the response of immunotherapy. These preliminary findings warrant further validations in the future.
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Affiliation(s)
- Jing Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Dian Wang
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Ning Su
- Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan 450000, P.R. China
| | - Min Wang
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Yulu Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
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Kamijo K, Miyamoto T, Oshima S, Asaka S, Shinagawa M, Sato Y, Ando H, Asaka R, Fujioka M, Uchiyama N, Yokokawa Y, Tanaka Y, Kusama Y, Takeshi U, Kobayashi Y, Shiozawa T. Extensive Pathologic Invasion and Prognostic Implication of Gastric-Type Cervical Adenocarcinoma: A Comparative Analysis With Human Papillomavirus-Associated Adenocarcinoma. Am J Surg Pathol 2025; 49:471-480. [PMID: 39981977 DOI: 10.1097/pas.0000000000002369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2025]
Abstract
Gastric-type adenocarcinoma (GAS) is the most common subtype of human papillomavirus (HPV)-independent cervical adenocarcinomas and is associated with a poor prognosis. We used a gross morphologic classification system and imaging analysis to compare the clinicopathological features of GAS and HPV-associated adenocarcinoma (HPVA) and identify factors contributing to the poor prognosis of GAS. This retrospective 2-center study analyzed 33 patients with GAS and 70 with HPVA (stages IB-IVB) who underwent surgery between 1997 and 2023. GAS had a higher rate of positive surgical margins (21.2% vs. 0%, respectively, P <0.001) and unclear tumor boundaries on gross morphologic findings (47.8% vs. 8.8%, respectively, P <0.001). Discrepancies between clinical and pathologic T classifications were more common in GAS, leading to frequent upstaging (51.5% vs. 28.6%, respectively, P =0.029). Imaging analysis revealed that GAS was associated with a smaller median tumor cell area (19.8% vs. 55.7%, respectively, P <0.001), which was significantly correlated with unclear tumor boundaries. Perineural invasion (PNI) was significantly more frequent in GAS (69.7% vs. 10.0%, respectively, P <0.001). A Kaplan-Meier analysis showed that patients with PNI had significantly poorer overall survival ( P <0.001). A Cox multivariate analysis identified an advanced pathologic stage, positive peritoneal cytology, and positive surgical margins as independent risk factors. The present results indicate that GAS has a unique "stealth" invasion pattern, possibly caused by low tumor density, leading to undetectable tumor boundaries and positive surgical margins. This suggests a greater risk of incomplete resection than HPVA, leading to a poorer prognosis.
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Affiliation(s)
- Kyosuke Kamijo
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto
- Department of Obstetrics and Gynecology, Nagano Prefectural Shinshu Medical Center, Suzaka
| | - Tsutomu Miyamoto
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto
| | - Shiori Oshima
- Department of Pathology, Nagano Red Cross Hospital
- Department of Laboratory Medicine, Shinshu University Hospital
| | - Shiho Asaka
- Department of Laboratory Medicine, Shinshu University Hospital
- Department of Laboratory Medicine and Pathology, Life Science Research Center, Nagano Children's Hospital
| | - Manaka Shinagawa
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto
| | - Yoshinori Sato
- Department of Laboratory Medicine, Shinshu University Hospital
| | - Hirofumi Ando
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto
| | - Ryoichi Asaka
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto
| | - Marina Fujioka
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto
| | - Natsuki Uchiyama
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto
| | - Yusuke Yokokawa
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto
| | - Yasuhiro Tanaka
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto
| | | | - Uehara Takeshi
- Department of Laboratory Medicine, Shinshu University School of Medicine
| | - Yaeko Kobayashi
- Department of Gynecology, Nagano Municipal Hospital, Nagano, Japan
| | - Tanri Shiozawa
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto
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3
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Himoto Y, Kido A, Yamanoi K, Kurata Y, Morita S, Kikkawa N, Fukui H, Ohya A, Iraha Y, Tsuboyama T, Ito K, Fujinaga Y, Minamiguchi S, Mandai M, Nakamoto Y. Limited diagnostic performance of imaging evaluation for staging in gastric-type endocervical adenocarcinoma: a multi-center study. Jpn J Radiol 2025; 43:810-819. [PMID: 39625593 PMCID: PMC12053355 DOI: 10.1007/s11604-024-01713-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 11/19/2024] [Indexed: 05/06/2025]
Abstract
PURPOSE The purposes of the study are to assess the diagnostic performance of preoperative imaging for staging factors in gastric-type endocervical adenocarcinoma (GEA) and to compare the performance for GEA with that of usual-type endocervical adenocarcinoma (UEA) among patients preoperatively deemed locally early stage (DLES) (< T2b without distant metastasis). MATERIALS AND METHODS For this multi-center retrospective study, 58 patients were enrolled. All had undergone MRI with or without CT and FDG PET-CT preoperatively and had been pathologically diagnosed with GEA at five institutions. Based on the medical charts and radiological reports, the diagnostic performances of preoperative imaging for the International Federation of Gynecology and Obstetrics staging factors were assessed retrospectively. Next, the imaging performance was assessed in preoperatively DLES-GEA (n = 36) and DLES-UEA (n = 136, with the same inclusion criteria). The proportions of underestimation of GEA and UEA were compared using Fisher's exact test. RESULTS Imaging diagnostic performance for GEA was limited, especially for sensitivity: parametrial invasion, 0.49; vaginal invasion, 0.54; pelvic lymph node metastasis (PELNM), 0.48; para-aortic lymph node metastasis, 0.00; and peritoneal dissemination, 0.25. Among preoperatively DLES patients, the proportions of underestimation were significantly higher in GEA than in UEA; parametrial invasion, 35% vs. 5% (p < 0.01); vaginal invasion, 28% vs. 6% (p < 0.01); PELNM, 24% vs. 6% (p < 0.05); peritoneal dissemination, 6% vs. 0% (p < 0.05). CONCLUSION At present, preoperative imaging diagnostic performance for staging factors in GEA does not meet clinical expectations, especially for sensitivity. Among patients preoperatively DLES, the proportions of underestimation in GEA were significantly higher than in UEA. Future incorporation of approaches specifically emphasizing GEA is desirable to improve imaging performance.
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Affiliation(s)
- Yuki Himoto
- Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Shogoinkawahara-Cho 54, Sakyo-Ku, Kyoto, 606-8507, Japan.
| | - Aki Kido
- Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Shogoinkawahara-Cho 54, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Koji Yamanoi
- Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yasuhisa Kurata
- Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Shogoinkawahara-Cho 54, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Nao Kikkawa
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan
| | - Hideyuki Fukui
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Ayumi Ohya
- Department of Radiology, Shinshu University School of Medicine, Nagano, Japan
| | - Yuko Iraha
- Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Okinawa, Japan
| | - Takahiro Tsuboyama
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kimiteru Ito
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan
| | - Yasunari Fujinaga
- Department of Radiology, Shinshu University School of Medicine, Nagano, Japan
| | - Sachiko Minamiguchi
- Department of Diagnostic Pathology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Masaki Mandai
- Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Shogoinkawahara-Cho 54, Sakyo-Ku, Kyoto, 606-8507, Japan
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Li J, Wang D, Duan Q, Su N, Li X, Qiu H. The efficacy of anti-angiogenic drugs in gastric-type endocervical adenocarcinoma: A retrospective study. J Obstet Gynaecol Res 2025; 51:e16247. [PMID: 39988602 DOI: 10.1111/jog.16247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 02/09/2025] [Indexed: 02/25/2025]
Abstract
OBJECTIVES Gastric-type endocervical adenocarcinoma (GEA) is a rare malignant tumor that is not associated with high-risk HPV infection, known for its high invasiveness and resistance to current treatments. This study assessed the effectiveness of anti-angiogenic regimens in real-world GEA patients. METHODS Patients with GEA were enrolled between February 2012 and March 2023, and their clinicopathological characteristics were collected from their medical records. The patients were categorized into groups based on whether they received anti-angiogenic treatments or not. Survival analysis was conducted using the Kaplan-Meier method. RESULTS A total of 43 GEA patients were enrolled in this study, with 23 cases who received anti-angiogenic drugs (nine received them as the primary treatment, 12 as first-line therapy after recurrence/metastasis, and two as second-line therapy) as the observation group. The other 20 patients who received similar treatments without the anti-angiogenic regimens serve as the control group. Compared to the control group, the addition of anti-angiogenic drugs as the primary treatment mildly extended progression-free survival (PFS) while not being statistically significant (16 months vs 11 months, p = 0.744). The negative results were also observed in 12 patients who started anti-angiogenic therapy as first-line therapy after recurrence/metastasis (8.5 months vs 9 months, p = 0.518). As for the overall survival (OS), no benefits were detected in either patients who started the anti-angiogenic therapy as primary or subsequent treatments (p = 0.499 and 0.450, respectively). CONCLUSION We firstly evaluated the efficacy of anti-angiogenic drugs in treating patients with GEA. Although with a small sample size, our preliminary results clearly proposed that the anti-angiogenic therapy failed in suppressing tumors and should not be a preferred choice for GEA. As a much rarer tumor without standard treatments, we herein warned of a pitfall for gynecologic oncologists when facing this malignancy.
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Affiliation(s)
- Jing Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Dian Wang
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Qing Duan
- Department of Gynecologic Oncology, Anyang Tumor Hospital, Anyang, Henan Province, China
| | - Ning Su
- Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan Province, China
| | - Xiufang Li
- Department of Gynecologic Oncology, Anyang Tumor Hospital, Anyang, Henan Province, China
| | - Haifeng Qiu
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
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Desravines N, Tran C, Wethington S, Williams-Brown MY. Contemporary Review of Adenocarcinoma of the Cervix. Curr Treat Options Oncol 2024; 25:1538-1549. [PMID: 39535688 DOI: 10.1007/s11864-024-01254-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/07/2024] [Indexed: 11/16/2024]
Abstract
OPINION STATEMENT Among cervical cancers, adenocarcinoma is less common than squamous cell carcinoma of the cervix; however, the incidence of these cancers is rising. The incidence has changed largely due to a shift in risk factors as well as the evolution of the diagnosis and classification of adenocarcinoma. Adenocarcinoma of the cervix is composed of a diverse group of neoplasms that can be classified by various factors. In this review article, preinvasive disease, updated classifications of adenocarcinoma, and treatment options for cervical adenocarcinoma are discussed with a focus on current and future therapies. Advances in antibody-drug conjugates (ADC) and immunotherapy have increased the treatment options available for usual-type adenocarcinoma but there is still a lack of variety of treatment options for the remaining 25% of non-usual-type adenocarcinomas.
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Affiliation(s)
- N Desravines
- Division of Gynecologic Oncology, Department of Women's Health, University of Texas at Austin Dell Medical School, Austin, TX, USA.
| | - C Tran
- Department of Women's Health, University of Texas at Austin Dell Medical School, Austin, TX, USA
| | - S Wethington
- Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - M Y Williams-Brown
- Division of Gynecologic Oncology, Department of Women's Health, University of Texas at Austin Dell Medical School, Austin, TX, USA
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Shao N. Research progress on human papillomavirus-negative cervical cancer: A review. Medicine (Baltimore) 2024; 103:e39957. [PMID: 39465870 PMCID: PMC11479510 DOI: 10.1097/md.0000000000039957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 09/16/2024] [Indexed: 10/29/2024] Open
Abstract
Cervical cancer is the fourth most common cancer in women worldwide. The vast majority of cervical cancers are associated with human papillomavirus (HPV) infection, but a small proportion of cervical cancers occur independently of HPV infection, with different subtypes having varying rates of occurrence. Despite the presence of false negatives in current testing, improving the accuracy of detection is crucial for studying the pathogenesis of HPV-negative cervical cancer and improving the prognosis of these patients. Existing research suggests that HPV-negative cervical cancer has a different pathogenesis from HPV-positive cervical cancer, although the exact mechanism is not yet clear. It is currently believed to be associated with the immune microenvironment, certain tumor gene mutations, and some long noncoding RNAs. This article provides an overview of the latest research progress on HPV-negative cervical cancer, including possible reasons, pathogenesis, pathological features, and clinical characteristics, aiming to provide new insights for diagnosis, treatment, and prognosis improvement.
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Affiliation(s)
- Ning Shao
- Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Kikkawa N, Sugawara H, Yoshida H, Kobayashi-Kato M, Tanase Y, Uno M, Ishikawa M, Kato T, Kusumoto M. Characteristics of the magnetic resonance imaging findings of cervical gastric-type adenocarcinoma. Clin Radiol 2024; 79:e1189-e1195. [PMID: 39013666 DOI: 10.1016/j.crad.2024.04.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/20/2024] [Accepted: 04/30/2024] [Indexed: 07/18/2024]
Abstract
AIMS This study identified the distinct magnetic resonance imaging findings of cervical gastric-type adenocarcinoma (GAS) that can help differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA) and reveal the radiologic-pathologic correlation. MATERIALS AND METHODS All consecutive patients with cervical GAS treated at our hospital from November 2009 to August 2021 were included. The SCC and UEA cases were considered controls. Tumor location, tumor shape, presence and size of cysts, presence of uterine fluid, and apparent diffusion coefficient (ADC) were evaluated. RESULTS Overall, 18 GAS, 55 SCC, and 23 UEA cases were evaluated. The tumor was located in the entire cervix in 13/18 GAS cases, whereas it was predominantly located in the lower cervix in 38/55 SCC cases and 14/23 UEA cases. Most GAS cases exhibited a diffuse infiltration growth pattern (17/18), whereas most SCC and UEA cases exhibited a mass-forming pattern (39/55 and 20/23, respectively). Moreover, the percentages of cases presenting microcysts or macrocysts and undergoing uterine fluid collection were significantly higher in the GAS group (14/18 and 13/18) than in the SCC and UEA groups. ADC was significantly higher in the GAS group than in the SCC group (1.092 × 10-3 vs. 0.819 × 10-3 mm2/s). CONCLUSION This study revealed that GAS is characterized by tumor presence in the entire cervix, infiltrative growth pattern, intrauterine fluid collection, and frequent microcyst or macrocyst formation. Moreover, ADC was significantly higher in the GAS group than in the SCC group.
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Affiliation(s)
- N Kikkawa
- Department of Diagnostic Radiology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
| | - H Sugawara
- Department of Radiology, IMSUT Hospital, The Institute of Medical Science, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
| | - H Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - M Kobayashi-Kato
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - Y Tanase
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - M Uno
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - M Ishikawa
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - T Kato
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - M Kusumoto
- Department of Diagnostic Radiology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
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Xiao ML, Fu L, Ma FH, Li YA, Zhang GF, Qiang JW. Comparison of MRI features among squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma, usual-type endocervical adenocarcinoma and gastric adenocarcinoma of cervix. Magn Reson Imaging 2024; 112:10-17. [PMID: 38848968 DOI: 10.1016/j.mri.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 05/21/2024] [Accepted: 06/04/2024] [Indexed: 06/09/2024]
Abstract
OBJECTIVE To compare and explore the characteristics of squamous cell carcinoma (SCC), adenocarcinoma (AC) and adenosquamous carcinoma (ASC), usual-type endocervical adenocarcinoma (UEA) and gastric adenocarcinoma (GAC) of cervix. MATERIALS AND METHODS A total of 728 cervical cancers (254 cases of AC, 252 cases of ASC, and 222 cases of SCC) confirmed by histopathology were retrospectively reviewed. Among AC, 119 UEA and 47 GAC were included. Clinical baseline data and tumor morphological features on MRI (including tumor location, shape, diameter and volume, margin, growth pattern, presence of fluid component or cyst, heterogenous and peritumoral enhancement) of all cases were collected and analyzed. The signal intensity (SI) of tumor and gluteus maximus muscle were measured and their ratios (SIR) were calculated based on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and contrast-enhanced T1WI at arterial and delay phases (A/DCE-T1WI). These clinical and MRI features were compared between SCC, AC and ASC, UEA and GAC, and the specific ones of each subtype were identified. RESULTS There was a significant difference in SCC-Ag, CA-199, CEA, ADC value, SIR-DWI, presence of intratumor cyst and peritumoral enhancement between AC and ASC; in patient age, menopausal status, International Federation of Gynecology and Obstetrics (FIGO) stage, SCC-Ag, CA-125, CA-199, CEA, tumor shape, growth pattern, margin, presence of intratumor fluid component and cyst, tumor diameter and volume, ADC value, SIR-T1WI, SIR-T2WI, and SIR-DWI between SCC and AC, as well as SCC and ASC. Also, there was a significant difference in deep stromal invasion (DSI), peritumoral and heterogenous enhancement between SCC and AC, and in SIR-ACE-T1WI between SCC and ASC. There was a significant difference in reproductive history, menopausal status, FIGO stage, CA-199, DSI, lymph node metastasis (LNM), parametrial invasion (PMI), tumor location, shape, margin, growth pattern, presence of fluid component and cyst, tumor diameter and volume, SIR-T1WI, SIR-DWI, and heterogenous enhancement between GAC and UEA. CONCLUSION The clinical and MRI features with significant differences among SCC, AC and ASC, and between UEA and GAC, can help to identify each subtype of cervical cancer.
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Affiliation(s)
- Mei Ling Xiao
- Department of Radiology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, China; Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, China
| | - Le Fu
- Department of radiology, Shanghai First Maternity and Infant Hospital, Tongji University, 536 ChangleRoad, Shanghai 200092, China
| | - Feng Hua Ma
- Departments of Radiology, Obstetrics & Gynecology Hospital, Fudan University, 128 Shenyang Road, Shanghai 200090, China
| | - Yong Ai Li
- Department of Radiology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, China
| | - Guo Fu Zhang
- Departments of Radiology, Obstetrics & Gynecology Hospital, Fudan University, 128 Shenyang Road, Shanghai 200090, China
| | - Jin Wei Qiang
- Department of Radiology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, China.
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Wang Q, Li Y, Kan G, Fu X, Wang M, Zhu J. Gastric‑type endocervical adenocarcinoma: A report of two cases. Oncol Lett 2024; 28:344. [PMID: 38872865 PMCID: PMC11170259 DOI: 10.3892/ol.2024.14477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 05/09/2024] [Indexed: 06/15/2024] Open
Abstract
Gastric-type endocervical adenocarcinoma (GEA) is an uncommon and highly aggressive malignancy, characterized by non-specific clinical manifestations. The limited number of documented cases poses significant challenges in achieving an early preoperative diagnosis. In the present study, two cases of GEA in female patients, aged 46 and 39 years, who presented with the chief complaint of profuse vaginal discharge are described. Both patients underwent a total hysterectomy and bilateral adnexectomy, leading to the definitive diagnosis of GEA through routine pathological and immunohistochemical examination. Following surgery, case one received conventional chemotherapy with paclitaxel and carboplatin, demonstrating no evidence of recurrence during a follow-up period of >2 years. At present, patient B has been followed up for >1 year without any signs of disease recurrence. Given the rarity and diagnostic challenges associated with GEA, further investigations into its pathogenesis and diagnostic modalities are warranted. Additionally, due to its poor prognosis, close surveillance is essential for monitoring potential recurrences. Reporting such cases is crucial in aiding clinicians to make accurate diagnoses and treatment decisions.
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Affiliation(s)
- Qian Wang
- Department of Ultrasound Medicine, The First People's Hospital of Linhai City, Linhai, Zhejiang 317000, P.R. China
- Department of Ultrasound Medicine, and State Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital School of Medicine Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China
| | - Yanyu Li
- Department of Ultrasound Medicine, The First People's Hospital of Linhai City, Linhai, Zhejiang 317000, P.R. China
- Department of Ultrasound Medicine, and State Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital School of Medicine Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China
| | - Guangjuan Kan
- Department of Ultrasound Medicine, and State Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital School of Medicine Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China
| | - Xiaofeng Fu
- Department of Ultrasound Medicine, and State Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital School of Medicine Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China
| | - Minyan Wang
- Department of Ultrasound Medicine, and State Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital School of Medicine Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China
| | - Jiang Zhu
- Department of Ultrasound Medicine, and State Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital School of Medicine Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China
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10
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Lee KH, Kim NI, Nam JH, Kim SS. Gastric-type adenocarcinoma of the uterine cervix presenting in urine cytology specimens: A case report and literature review. Diagn Cytopathol 2024; 52:E80-E83. [PMID: 38140795 DOI: 10.1002/dc.25268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 12/04/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023]
Abstract
Gastric-type endocervical adenocarcinoma (GEA) is a rare type adenocarcinoma of the uterine cervix that is unrelated to human papillomavirus (HPV). GEA is difficult to diagnose due to its bland-looking morphological characteristics and is therefore often underdiagnosed. Although abnormal cells may be seen on cervical cytology specimens, they are rarely diagnosed as malignant and are often classified as atypical glandular cells. As a result, GEA may be diagnosed at advanced stages, with cytology samples from other organs after it has already invaded adjacent organs. Here, we report a case of GEA diagnosed by both cytological and histological examinations of urinary bladder and uterine cervix, after being identified as a non-urothelial malignancy on a urine cytology. We also review and summarize the differential diagnoses for non-urothelial lesions, particularly for glandular lesions observed on urinary cytology specimens, as well as the cytological and histological characteristics of GEA.
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Affiliation(s)
- Kyung-Hwa Lee
- Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea
- Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea
| | - Nah Ihm Kim
- Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea
- Department of Pathology, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Jong-Hee Nam
- Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea
- Department of Pathology, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Sung Sun Kim
- Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea
- Department of Pathology, Chonnam National University Hospital, Gwangju, Republic of Korea
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11
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Xiao ML, Qian T, Fu L, Wei Y, Ma FH, Gu WY, Li HM, Li YA, Qian ZX, Cheng JJ, Zhang GF, Qiang JW. Deep Learning Nomogram for the Identification of Deep Stromal Invasion in Patients With Early-Stage Cervical Adenocarcinoma and Adenosquamous Carcinoma: A Multicenter Study. J Magn Reson Imaging 2024; 59:1394-1406. [PMID: 37392060 DOI: 10.1002/jmri.28882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 07/02/2023] Open
Abstract
BACKGROUND Deep stromal invasion (DSI) is one of the predominant risk factors that determined the types of radical hysterectomy (RH). Thus, the accurate assessment of DSI in cervical adenocarcinoma (AC)/adenosquamous carcinoma (ASC) can facilitate optimal therapy decision. PURPOSE To develop a nomogram to identify DSI in cervical AC/ASC. STUDY TYPE Retrospective. POPULATION Six hundred and fifty patients (mean age of 48.2 years) were collected from center 1 (primary cohort, 536), centers 2 and 3 (external validation cohorts 1 and 2, 62 and 52). FIELD STRENGTH/SEQUENCE 5-T, T2-weighted imaging (T2WI, SE/FSE), diffusion-weighted imaging (DWI, EPI), and contrast-enhanced T1-weighted imaging (CE-T1WI, VIBE/LAVA). ASSESSMENT The DSI was defined as the outer 1/3 stromal invasion on pathology. The region of interest (ROI) contained the tumor and 3 mm peritumoral area. The ROIs of T2WI, DWI, and CE-T1WI were separately imported into Resnet18 to calculate the DL scores (TDS, DDS, and CDS). The clinical characteristics were retrieved from medical records or MRI data assessment. The clinical model and nomogram were constructed by integrating clinical independent risk factors only and further combining DL scores based on primary cohort and were validated in two external validation cohorts. STATISTICAL TESTS Student's t-test, Mann-Whitney U test, or Chi-squared test were used to compare differences in continuous or categorical variables between DSI-positive and DSI-negative groups. DeLong test was used to compare AU-ROC values of DL scores, clinical model, and nomogram. RESULTS The nomogram integrating menopause, disruption of cervical stromal ring (DCSRMR), DDS, and TDS achieved AU-ROCs of 0.933, 0.807, and 0.817 in evaluating DSI in primary and external validation cohorts. The nomogram had superior diagnostic ability to clinical model and DL scores in primary cohort (all P < 0.0125 [0.05/4]) and CDS (P = 0.009) in external validation cohort 2. DATA CONCLUSION The nomogram achieved good performance for evaluating DSI in cervical AC/ASC. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Mei Ling Xiao
- Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, China
| | - Ting Qian
- Department of Radiology, International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Le Fu
- Department of Radiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yan Wei
- Department of Automation, Zhejiang University of Technology, Hangzhou, China
| | - Feng Hua Ma
- Department of Radiology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, China
| | - Wei Yong Gu
- Department of Pathology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, China
| | - Hai Ming Li
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yong Ai Li
- Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, China
| | - Zhao Xia Qian
- Department of Radiology, International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jie Jun Cheng
- Department of Radiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
| | - Guo Fu Zhang
- Department of Radiology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, China
| | - Jin Wei Qiang
- Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, China
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12
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Kong TW, Kim J, Son JH, Lee AJ, Yang EJ, Shim SH, Kim NK, Kim Y, Suh DH, Hwang DW, Park SJ, Kim HS, Lee YY, Yoo JG, Lee SJ, Chang SJ. Is minimally invasive radical surgery safe for patients with cervical cancer ≤2 cm in size? (MISAFE): Gynecologic Oncology Research Investigators coLLborAtion study (GORILLA-1003). Gynecol Oncol 2023; 176:122-129. [PMID: 37515926 DOI: 10.1016/j.ygyno.2023.07.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 07/10/2023] [Accepted: 07/20/2023] [Indexed: 07/31/2023]
Abstract
OBJECTIVE To identify clinicopathological factors associated with disease recurrence for patients with 2018 FIGO stage IA with lymphovascular invasion to IB1 cervical cancer treated with minimally invasive surgery (MIS). METHODS A total of 722 patients with cervical cancer between January 2010 and February 2021 were identified. Clinicopathological factors related to disease recurrence were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. To determine prognostic factors for DFS, a Cox proportional hazard regression model was used. RESULTS Of 722 patients, 49 (6.8%) experienced disease recurrence (37 pelvis, 1 para-aortic lymph node, and 11 peritoneum). Five-year DFS and OS rates were 90.7% and 98.1%, respectively. In multivariate analysis, risk factors associated with disease recurrence were residual disease in the remaining cervix (OR, 3.122; 95% CI, 1.152-8.461; p = 0.025), intracorporeal colpotomy (OR, 3.252; 95% CI, 1.507-7.017; p = 0.003), and positive resection margin (OR, 3.078; 95% CI, 1.031-9.193; p = 0.044). The non-conization group had a higher percentage of stage IB1 (77.4% vs. 64.6%; p = 0.004) and larger tumor (10 mm vs. 7 mm; p < 0.001) than the conization group. Intracorporeal colpotomy and residual disease in the remaining cervix were independent variables associated with disease recurrence in patients undergoing MIS following conization. CONCLUSION During MIS, patients with cervical cancer ≤2 cm in size can be vulnerable to peritoneal recurrences. Patients diagnosed with invasive cancer through conization often have low-risk pathological features, which may affect their survival outcomes.
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Affiliation(s)
- Tae-Wook Kong
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Jeeyeon Kim
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Joo-Hyuk Son
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - A Jin Lee
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Eun Jung Yang
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Seung-Hyuk Shim
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Nam Kyeong Kim
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Yeorae Kim
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Dong Hoon Suh
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Dong Won Hwang
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Soo Jin Park
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoo-Young Lee
- Department of Obstetrics and Gynecology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ji Geun Yoo
- Department of Obstetrics and Gynecology, Daejeon St. Mary's Hospital, The Catholic University of Korea, Daejeon, Republic of Korea
| | - Sung Jong Lee
- Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea
| | - Suk-Joon Chang
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Republic of Korea.
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Funakoshi M, Nakai G, Yamada T, Ohmichi M, Yamamoto K, Osuga K. Acute cervicitis resembling gastric-type mucinous adenocarcinoma that was definitively diagnosed by cervical conization: A case report. Radiol Case Rep 2023; 18:1767-1771. [PMID: 36923387 PMCID: PMC10009334 DOI: 10.1016/j.radcr.2023.02.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 02/03/2023] [Accepted: 02/05/2023] [Indexed: 03/06/2023] Open
Abstract
Although imaging studies are not typically performed for clinical diagnosis of cervicitis, in this case magnetic resonance imaging (MRI) was performed because a lesion with a tumor-like gross appearance was found in the uterine cervix. We present a case of cervicitis in which clinical, imaging and pathological features overlapped with those of gastric-type mucinous adenocarcinoma (GAS). The patient, a 30-year-old woman, was referred to a gynecologist with a complaint of watery vaginal discharge. On visual examination, the uterine cervix was irregularly enlarged and bled easily, suggesting cervical cancer. The next day, the patient had a fever of 39°C and blisters appeared on her vulva due to herpes simplex virus type II infection. MRI showed a diffusely enlarged cervix with poorly marginated high signal intensity on T2-weighted imaging (WI) and apparent diffusion coefficient map as well as strong enhancement on contrast-enhanced T1WI, which are findings consistent with GAS. Although a punch biopsy showed only mild atypia of the cervical glands, this was not enough to completely rule out GAS. Consequently, laser conization of the lesion was performed for definitive diagnosis, and the diagnosis of cervicitis was made. Acute cervicitis can be difficult to differentiate from GAS based on symptoms, results of cervical biopsy and MR imaging because of their overlapping features. Even when a patient presents with a lesion with tumor-like gross appearance, acute cervicitis should be included in the differential diagnosis if the result of cervical biopsy is negative, especially when accompanied by infection-like fever.
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Key Words
- ADC, apparent diffusion coefficient
- Adenocarcinoma
- DWI, diffusion-weighted imaging
- Diagnostic Imaging
- FDG, fluorodeoxyglucose
- G, gravida
- GAS, gastric-type mucinous adenocarcinoma
- HSV, herpes simplex virus
- MRI, magnetic resonance imaging
- Magnetic Resonance Imaging
- Mucinous
- P, para
- PET-CT, positron emission tomography-computed tomography
- Positron-Emission Tomography
- STD, sexually transmitted disease
- TE, echo time
- TR, repetition time
- Uterine Cervicitis
- WI, weighted imaging
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Affiliation(s)
- Mai Funakoshi
- Department of Diagnostic Radiology, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan
| | - Go Nakai
- Department of Diagnostic Radiology, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan
| | - Takashi Yamada
- Department of Pathology, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan
| | - Masahide Ohmichi
- Department of Obstetrics and Gynecology, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan
| | - Kazuhiro Yamamoto
- Department of Diagnostic Radiology, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan
| | - Keigo Osuga
- Department of Diagnostic Radiology, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan
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14
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Mori T, Kato H, Kawaguchi M, Kanayama T, Furui T, Noda Y, Hyodo F, Matsuo M. MRI characteristics for predicting histological subtypes in patients with uterine cervical adenocarcinoma. Eur J Radiol 2023; 158:110612. [PMID: 36542931 DOI: 10.1016/j.ejrad.2022.110612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 10/17/2022] [Accepted: 11/14/2022] [Indexed: 12/14/2022]
Abstract
PURPOSE To evaluate the magnetic resonance imaging (MRI) findings of uterine cervical adenocarcinoma for predicting different histological subtypes. MATERIALS AND METHODS We 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. RESULTS The 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. CONCLUSIONS Compared 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.
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Affiliation(s)
- Takayuki Mori
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan
| | - Hiroki Kato
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Masaya Kawaguchi
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan
| | | | - Tatsuro Furui
- Department of Obstetrics and Gynecology, Gifu University, Gifu, Japan
| | - Yoshifumi Noda
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan
| | - Fuminori Hyodo
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan; Institute for Advanced Study, Gifu University, Japan
| | - Masayuki Matsuo
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan
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15
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Jeon J, Park BK, Lee JW, Choi CH, Lee YY, Kim TJ, Kim BG. Invisible cervical cancers on MRI: Can the type of histology (SCC versus non-SCC) influence surgical planning? Front Oncol 2022; 12:996516. [PMID: 36568188 PMCID: PMC9773832 DOI: 10.3389/fonc.2022.996516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 11/21/2022] [Indexed: 12/13/2022] Open
Abstract
Background Invisible cervical cancers on MRI can indicate less invasive surgery. Cervical cancers consist of squamous cell carcinoma (SCC) and non-SCC, each with different long-term outcomes. It is still unclear if surgical planning should be changed according to the histologic type of cervical cancer when it is not visible on MRI. Purpose The purpose of the study was to determine if surgical planning for cervical cancer that is not visible on MRI is influenced by the histologic type. Materials and methods Between January 2007 and December 2016, 155 women had Federation of Gynecology and Obstetrics (FIGO) stage 1B1 cervical cancer that was not visible on preoperative MRI. They underwent radical hysterectomies and pelvic lymph node dissections. Among them, 88 and 67 were histologically diagnosed with SCC and non-SCC, respectively. The size of the residual tumor, depth of stromal invasion, parametrial invasion, vaginal invasion, lymphovascular invasion, and lymph node metastasis were compared between these patients using the t-test, Mann-Whitney U test, Chi-squared test, or Fisher's exact test. The recurrence-free and overall 10-year survival rates were compared between the groups by Kaplan-Meier analysis. Results The mean sizes of residual tumors were 8.4 ± 10.4 mm in the SCC group and 12.5 ± 11.9 mm in the non-SCC group (p = 0.024). The mean depth of stromal invasion in the SCC group was 12.4 ± 21.2% (0%-100%), whereas that in the non-SCC group was 22.4 ± 24.4 (0%-93%) (p = 0.016). However, there was no difference in parametrial or vaginal invasion, lymphovascular invasion, or lymph node metastasis (p = 0.504-1.000). The recurrence-free and overall 10-year survival rates were 98.9% (87/88) and 95.5% (64/67) (p = 0.246), and 96.6% (85/88) and 95.5% (64/67) (p = 0.872), respectively. Conclusions The non-SCC group tends to have larger residual tumors and a greater depth of stromal invasion than the SCC group, even though neither is visible on MRI. Therefore, meticulous care is necessary for performing parametrectomy in patients with non-SCC cervical cancer.
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Affiliation(s)
- Jungeun Jeon
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Byung Kwan Park
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jeong-Won Lee
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Chel Hun Choi
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yoo-Young Lee
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Tae-Joong Kim
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Byoungi-Gie Kim
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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16
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Ehmann S, Sassine D, Straubhar AM, Praiss AM, Aghajanian C, Alektiar KM, Broach V, Cadoo KA, Jewell EL, Boroujeni AM, Kyi C, Leitao MM, Mueller JJ, Murali R, Bhaloo SI, O'Cearbhaill RE, Park KJ, Sonoda Y, Weigelt B, Zamarin D, Abu-Rustum N, Friedman CF. Gastric-type adenocarcinoma of the cervix: Clinical outcomes and genomic drivers. Gynecol Oncol 2022; 167:458-466. [PMID: 36253302 PMCID: PMC10155605 DOI: 10.1016/j.ygyno.2022.10.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/30/2022] [Accepted: 10/03/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVES Gastric-type endocervical adenocarcinoma (GEA) is a rare form of cervical cancer not associated with human papilloma virus (HPV) infection. We summarize our experience with GEA at a large cancer center. METHODS Clinical and demographic information on all patients diagnosed with GEA between June 1, 2002 and July 1, 2019 was obtained retrospectively from clinical charts. Kaplan-Meier survival analysis was performed to describe progression-free survival (PFS) and overall survival (OS). Tumors from a subset of patients underwent next generation sequencing (NGS) analysis. RESULTS A total of 70 women with GEA were identified, including 43 who received initial treatment at our institution: of these 4 (9%) underwent surgery alone, 15 (35%) underwent surgery followed by adjuvant therapy, 10 (23%) were treated with definitive concurrent chemoradiation (CCRT), 7 (16%) with chemotherapy alone, and 3 (7%) with neoadjuvant CCRT and hysterectomy with or without chemotherapy. One-third (n = 14) of patients experienced disease progression, of whom 86% (n = 12) had prior CCRT. The median PFS and OS for patients with stage I GEA were 107 months (95% CI 14.8-199.2 months) and 111 months (95% CI 17-205.1 months) respectively, compared to 17 months (95% CI 5.6-28.4 months) and 33 months (95% CI 28.2-37.8 months) for patients with stages II-IV, respectively. On NGS, 4 patients (14%) had ERBB2 alterations, including 2 patients who received trastuzumab. CONCLUSIONS GEA is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or later. Further investigation is needed to identify the optimal management approach for this rare subtype.
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Affiliation(s)
- Sarah Ehmann
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Dib Sassine
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Alli M Straubhar
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Aaron M Praiss
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Carol Aghajanian
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Kaled M Alektiar
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Vance Broach
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Karen A Cadoo
- St. James's Hospital Dublin, Trinity St. James's Cancer Institute, Dublin 8 DO8 NHY1, Ireland
| | - Elizabeth L Jewell
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Amir Momeni Boroujeni
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Chrisann Kyi
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Mario M Leitao
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Jennifer J Mueller
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Rajmohan Murali
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Shirin Issa Bhaloo
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Roisin E O'Cearbhaill
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Kay J Park
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Yukio Sonoda
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Britta Weigelt
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Dmitriy Zamarin
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Nadeem Abu-Rustum
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Claire F Friedman
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
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17
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Giannella L, Di Giuseppe J, Delli Carpini G, Grelloni C, Fichera M, Sartini G, Caimmi S, Natalini L, Ciavattini A. HPV-Negative Adenocarcinomas of the Uterine Cervix: From Molecular Characterization to Clinical Implications. Int J Mol Sci 2022; 23:ijms232315022. [PMID: 36499345 PMCID: PMC9735497 DOI: 10.3390/ijms232315022] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 11/25/2022] [Accepted: 11/28/2022] [Indexed: 12/05/2022] Open
Abstract
Cervical cancer is the fourth most common cancer in women. It is the leading cause of female deaths in developing countries. Most of these cervical neoplasms are represented by squamous lesions. Cervical adenocarcinoma causes about a quarter of cervical cancers. In contrast to squamous lesions, cervical glandular disease is HPV-negative in about 15-20% of cases. HPV-negative cervical adenocarcinomas typically present in advanced stages at clinical evaluation, resulting in a poorer prognosis. The overall and disease-free survival of glandular lesions is lower than that of squamous lesions. Treatment options require definitive treatments, as fertility-sparing is not recommended. Moreover, the impact of HPV vaccination and primary HPV screening is likely to affect these lesions less; hence, the interest in this challenging topic for clinical practice. An updated review focusing on clinical and molecular characterization, prognostic factors, and therapeutic options may be helpful for properly managing such cervical lesions.
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Wang J, Yang Q, Wang D, Li M, Zhang N. Case Report: Gastric-Type Endocervical Adenocarcinoma Mimicking Submucosal Myoma Under Hysteroscopy. Front Med (Lausanne) 2022; 9:845445. [PMID: 35360733 PMCID: PMC8963799 DOI: 10.3389/fmed.2022.845445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 02/01/2022] [Indexed: 11/13/2022] Open
Abstract
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.
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Affiliation(s)
- Jiao Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qing Yang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Dandan Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mengyuan Li
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ningning Zhang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
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Independent validation of distinct clinicopathological features and prognosis among usual-type, mucinous-type and gastric-type endocervical adenocarcinoma categorised by new WHO classification (2020). Pathology 2022; 54:555-562. [PMID: 35346505 DOI: 10.1016/j.pathol.2021.12.301] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/20/2021] [Accepted: 12/31/2021] [Indexed: 11/22/2022]
Abstract
The new World Health Organization (WHO) classification of tumours of the female genital tract (2020) divides endocervical adenocarcinoma (EAC) into human papilloma virus (HPV)-related adenocarcinoma (HPVA) and HPV-independent adenocarcinoma (HPVI) to underscore the morphological and pathogenetic correlation. It may be potentially prognostic. In this study, we appraised the new WHO classification in an independent, single institution-based EAC cohort from China to assess the clinicopathological features and prognostic value among tumour types. Our study cohort contained 402 consecutive, surgically excised EACs consisting of 298 (74.1%) HPVA, 88 (21.9%) HPVI and 16 (4%) adenocarcinomas not otherwise specified (NOS). Usual-type (55.7%) and gastric-type adenocarcinoma (GAC) (18.2%) was the most common type in HPVA and HPVI, respectively. Block p16 staining (94.7% vs 24.4%) and HPV mRNA signal (89.4% vs 0) were more common in HPVA than in HPVI (p<0.001). HPVI or GAC were more frequently associated with prognostically adverse variables including old age, large tumour size, deep invasion of the cervical wall, high tumour stage, spread of the upper genital tract, lymphovascular invasion, and mutant-type p53 expression, compared to HPVA or mucinous/usual-type HPVA, respectively (all p<0.001). In univariate survival analysis, HPVI had a worse overall survival and higher tumour recurrence compared to HPVA (p<0.05). Mucinous-type HPVA showed a worse prognosis than usual-type HPVA, but better than GAC (p<0.001). Multivariate survival analysis demonstrated that HPVI was independently associated with a worse overall survival and tumour recurrence (p<0.05) while GAC was an adverse prognostic factor independently of FIGO stage (p<0.05). Our findings validate the value of the new WHO classification in prognostic stratification and pathogenetic correlation in EAC and its subtypes.
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Nishio S, Matsuo K, Nasu H, Murotani K, Mikami Y, Yaegashi N, Satoh T, Okamoto A, Ishikawa M, Miyamoto T, Mandai M, Takehara K, Yahata H, Takekuma M, Ushijima K. Analysis of postoperative adjuvant therapy in 102 patients with gastric-type mucinous carcinoma of the uterine cervix: A multi-institutional study. Eur J Surg Oncol 2022; 48:2039-2044. [DOI: 10.1016/j.ejso.2022.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 03/02/2022] [Accepted: 03/10/2022] [Indexed: 11/16/2022] Open
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21
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Fertility Sparing Treatment in Gastric-Type Endocervical Carcinoma. Cancers (Basel) 2021; 13:cancers13205177. [PMID: 34680326 PMCID: PMC8533748 DOI: 10.3390/cancers13205177] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Revised: 10/09/2021] [Accepted: 10/12/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Due to a trend toward late childbearing, fertility preservation has become a major issue in young patients with gynecological cancer. Surgical fertility sparing management is universally acknowledged as an acceptable option in eligible patients with cervical cancer. Excisional cone biopsy or trachelectomy are now standard surgical procedures offered to selected patients with gynecological malignancies who wish to preserve their fertility. Neoadjuvant chemotherapy followed by surgery is another therapeutic option studied currently in numerous clinical trials. However, fertility preserving treatment is generally not recommended in rare histological types of cervical cancer, including clinically aggressive gastric-type endocervical carcinoma. Due to controversies in this emerging topic, a review of literature and international database was carried out, in search of solid evidence on fertility sparing management in gastric-type endocervical carcinoma. Abstract Fertility sparing management of cancer is one of the main components of quality-of-life issues. Early-stage cervical cancer, frequently diagnosed in women of reproductive age, can potentially be treated conservatively. However, some rare histological types of cervical cancer present with aggressive clinical behavior. Particularly, in the newly introduced concept of gastric-type endocervical carcinoma, fertility sparing management is ‘a priori’ not recommended. Even so, this issue remains undocumented. For this reason, a selected review of the current literature on gastric type endocervical carcinoma was carried out through PubMed. The keywords included “gastric-type cervical cancer”, “gastric-type endocervical carcinoma”, “conservative surgery”, “conservative treatment”, “fertility sparing surgery”, “radical trachelectomy”, “laparoscopic trachelectomy”, “robotic trachelectomy”, “laparotomic trachelectomy”, “abdominal trachelectomy”, “trachelectomy”, “neoadjuvant chemotherapy”, “conisation”, and “cone resection”. A search in the European Network on Cancer, Infertility and Pregnancy (INCIP) database was performed. The rarity of gastric-type endocervical carcinoma does not allow for conclusions on fertility sparing management with solid evidence. However, diffuse character of the disease and aggressive clinical behavior contraindicate a conservative treatment in young women with gastric type cervical cancer.
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Dong Y, Lv Y, Guo J, Sun L. Minimal deviation adenocarcinoma with elevated CA19-9: A case report. World J Clin Cases 2021; 9:5999-6004. [PMID: 34368319 PMCID: PMC8316964 DOI: 10.12998/wjcc.v9.i21.5999] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 05/07/2021] [Accepted: 05/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Minimal deviation adenocarcinoma is a rare malignancy with a high rate of misdiagnosis and high aggressiveness, and its diagnosis relies on histopathology. Surgical resection is the preferred and most effective treatment, but the outcomes are often unsatisfactory.
CASE SUMMARY A 60-year-old perimenopausal woman was admitted to the hospital and found to have elevated CA19-9 on physical examination without abdominal pain or vaginal bleeding. Clinical examination and positron emission tomography/computed tomography examination were unremarkable, magnetic resonance imaging examination was suggestive of dominant cervical lesions, and methylation examination was suggestive of malignant lesions. Tissue samples were taken from the suspected cervical lesion, and the final pathologic diagnosis was minimal deviation adenocarcinoma. Based on the pathologic diagnosis of suspected minimal deviation adenocarcinoma, radical abdominal total hysterectomy, bilateral oophorectomy, and pelvic and para-aortic lymph node dissection were performed. The final histological report confirmed minimal deviation adenocarcinoma of the cervix, stage IB2, with lymph node metastasis. Minimal deviation adenocarcinoma is a tumor with aggressive clinical behavior.
CONCLUSION Patients with minimal deviation adenocarcinoma have a lower survival rate than patients with conventional human papillomavirus-related cervical adenocarcinoma. A precise preoperative pathologic diagnosis may reduce the mortality rate due to missed optimal treatment with multiple surgical interventions. To date, there is no therapeutic consensus; therefore, each case must be treated individually.
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Affiliation(s)
- Yan Dong
- Department of Clinical Medicine, Jining Medical University, Jining 272000, Shandong Province, China
| | - Ying Lv
- Department of Radiology, The Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China
| | - Jing Guo
- Department of Pathology, The Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China
| | - Lin Sun
- Department of Obstetrics and Gynecology, The Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China
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23
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Selenica P, Alemar B, Matrai C, Talia KL, Veras E, Hussein Y, Oliva E, Beets-Tan RGH, Mikami Y, McCluggage WG, Kiyokawa T, Weigelt B, Park KJ, Murali R. Massively parallel sequencing analysis of 68 gastric-type cervical adenocarcinomas reveals mutations in cell cycle-related genes and potentially targetable mutations. Mod Pathol 2021; 34:1213-1225. [PMID: 33318584 PMCID: PMC8154628 DOI: 10.1038/s41379-020-00726-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 10/28/2020] [Accepted: 10/29/2020] [Indexed: 12/20/2022]
Abstract
Gastric-type cervical adenocarcinoma (GCA) is an aggressive type of endocervical adenocarcinoma characterized by mucinous morphology, gastric-type mucin, lack of association with human papillomavirus (HPV) and resistance to chemo/radiotherapy. We characterized the landscape of genetic alterations in a large cohort of GCAs, and compared it with that of usual-type HPV-associated endocervical adenocarcinomas (UEAs), pancreatic adenocarcinomas (PAs) and intestinal-type gastric adenocarcinomas (IGAs). GCAs (n = 68) were subjected to massively parallel sequencing targeting 410-468 cancer-related genes. Somatic mutations and copy number alterations (CNAs) were determined using validated bioinformatics methods. Mutational data for UEAs (n = 21), PAs (n = 178), and IGAs (n = 148) from The Cancer Genome Atlas (TCGA) were obtained from cBioPortal. GCAs most frequently harbored somatic mutations in TP53 (41%), CDKN2A (18%), KRAS (18%), and STK11 (10%). Potentially targetable mutations were identified in ERBB3 (10%), ERBB2 (8%), and BRAF (4%). GCAs displayed low levels of CNAs with no recurrent amplifications or homozygous deletions. In contrast to UEAs, GCAs harbored more frequent mutations affecting cell cycle-related genes including TP53 (41% vs 5%, p < 0.01) and CDKN2A (18% vs 0%, p = 0.01), and fewer PIK3CA mutations (7% vs 33%, p = 0.01). TP53 mutations were less prevalent in GCAs compared to PAs (41% vs 56%, p < 0.05) and IGAs (41% vs 57%, p < 0.05). GCAs showed a higher frequency of STK11 mutations than PAs (10% vs 2%, p < 0.05) and IGAs (10% vs 1%, p < 0.05). GCAs harbored more frequent mutations in ERBB2 and ERBB3 (9% vs 1%, and 10% vs 0.5%, both p < 0.01) compared to PAs, and in CDKN2A (18% vs 1%, p < 0.05) and KRAS (18% vs 6%, p < 0.05) compared to IGAs. GCAs harbor recurrent somatic mutations in cell cycle-related genes and in potentially targetable genes, including ERBB2/3. Mutations in genes such as STK11 may be used as supportive evidence to help distinguish GCAs from other adenocarcinomas with similar morphology in metastatic sites.
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Affiliation(s)
- Pier Selenica
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- GROW School for Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Barbara Alemar
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Cathleen Matrai
- Department of Pathology and Laboratory Medicine, Weill-Cornell Medicine, New York, NY, USA
| | - Karen L Talia
- Department of Pathology, Royal Women's Hospital and VCS Foundation, Melbourne, VIC, Australia
| | - Emanuela Veras
- Department of Pathology, Sibley Memorial Hospital, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Yaser Hussein
- Department of Pathology, Morristown Medical Center, Morristown, NJ, USA
| | - Esther Oliva
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Regina G H Beets-Tan
- GROW School for Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands
| | - Yoshiki Mikami
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan
| | - W Glenn McCluggage
- Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK
| | | | - Britta Weigelt
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kay J Park
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Rajmohan Murali
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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24
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Mikami Y. Gastric-type mucinous carcinoma of the cervix and its precursors - historical overview. Histopathology 2020; 76:102-111. [PMID: 31846534 DOI: 10.1111/his.13993] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
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.
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Affiliation(s)
- Yoshiki Mikami
- Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan
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25
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Saida T, Sakata A, Tanaka YO, Ochi H, Ishiguro T, Sakai M, Takahashi H, Satoh T, Minami M. Clinical and MRI Characteristics of Uterine Cervical Adenocarcinoma: Its Variants and Mimics. Korean J Radiol 2019; 20:364-377. [PMID: 30799567 PMCID: PMC6389813 DOI: 10.3348/kjr.2018.0458] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 11/05/2018] [Indexed: 01/12/2023] Open
Abstract
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.
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Affiliation(s)
- Tsukasa Saida
- Department of Radiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
| | - Akiko Sakata
- Department of Diagnostic Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Yumiko Oishi Tanaka
- Department of Diagnostic Imaging, The Cancer Institute Hospital Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiroyuki Ochi
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Toshitaka Ishiguro
- Department of Radiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Masafumi Sakai
- Department of Radiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Hiroaki Takahashi
- Department of Radiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Toyomi Satoh
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Manabu Minami
- Department of Radiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
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26
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Omori M, Kondo T, Tagaya H, Watanabe Y, Fukasawa H, Kawai M, Nakazawa K, Hashi A, Hirata S. Utility of imaging modalities for predicting carcinogenesis in lobular endocervical glandular hyperplasia. PLoS One 2019; 14:e0221088. [PMID: 31415639 PMCID: PMC6695122 DOI: 10.1371/journal.pone.0221088] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 07/30/2019] [Indexed: 12/26/2022] Open
Abstract
Objectives To investigate the use of imaging methods for predicting carcinogenesis in lobular endocervical glandular hyperplasia (LEGH). Methods We retrospectively analyzed preoperative images on transvaginal sonography and magnetic resonance imaging (MRI) in 23 cases with histologically diagnosed LEGH. Results Shape of cervical multicystic lesions on MR images could be divided into two types the flower-type with many small cysts surrounded by larger cysts, and the raspberry-type with many tiny, closely aggregated cysts. Six (46%) of 13 cases had raspberry-type lesions that were not detected on transvaginal sonography but were seen on MRI. Adenocarcinoma in situ (AIS) was identified in 4 postmenopausal women with raspberry-type lesions during the follow-up periods. In these cases, cytologic examination by targeted endocervical sampling using sonography enabled early detection of AIS. Conclusions MRI and cytologic examination by targeted endocervical sampling may be very useful for predicting carcinogenesis in LEGH.
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Affiliation(s)
- Makiko Omori
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
- * E-mail:
| | - Tetsuo Kondo
- Department of Pathology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Hikaru Tagaya
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Yumika Watanabe
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Hiroko Fukasawa
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Masataka Kawai
- Department of Pathology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Kumiko Nakazawa
- Department of Pathology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Akihiko Hashi
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Shuji Hirata
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
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Gastric-Type Adenocarcinoma of the Uterine Cervix: Magnetic Resonance Imaging Features, Clinical Outcomes, and Prognostic Factors. Int J Gynecol Cancer 2019; 28:1203-1210. [PMID: 29683881 DOI: 10.1097/igc.0000000000001275] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
OBJECTIVE Gastric-type mucinous adenocarcinoma (GAS) of uterine cervix has been suggested as distinct clinicopathologic behavior. Our study aimed to investigate the distinguishing imaging features and clinical outcomes of GAS. METHODS Fifteen cases of GAS and 45 cases of 3:1 age-matched usual-type endocervical carcinoma (UEA) were assessed. Clinical parameters (age, tumor size, clinical stage, and time to recurrence [TTR] or death) and pathologic results confirmed by surgery were recorded. Imaging features (tumor shape, margin, presence of vaginal involvement, or cyst) on magnetic resonance T2-weighed images were evaluated by consensus reading. Parametrial invasion was assessed by 2 independent readers on a 4-point scale system. RESULTS Gastric-type mucinous adenocarcinomas were associated with a higher stage at presentation and higher rates of deep cervical stromal invasion, parametrial invasion, and lymphovascular invasion. On magnetic resonance images, GASs also demonstrated a more infiltrative shape (93.3% vs 22.2%; P < 0.001) with/without cysts, ill-defined margin (93.3% vs 31.8%; P < 0.001), endocervical location (46.7%) or extension to the entire cervix (46.7%), higher rates of vaginal involvement (40.0% vs 4.4%; P = 0.002), and higher grade of parametrial invasion by both readers (66.7% vs 22.2%; P = 0.003) compared with UEAs. Patients with GAS had a significantly shorter TTR compared with UEA cases (P < 0.001) by log-rank test. A multivariate Cox proportional hazards model revealed that an infiltrative tumor shape (hazard ratio, 5.92; P = 0.004) and stage II or greater (hazard ratio, 4.19; P = 0.011) were prognostic indicators of a shorter TTR. CONCLUSIONS Gastric-type mucinous adenocarcinoma may have characteristic imaging features and poorer outcomes compared with UEA.
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28
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Nishio S, Mikami Y, Tokunaga H, Yaegashi N, Satoh T, Saito M, Okamoto A, Kasamatsu T, Miyamoto T, Shiozawa T, Yoshioka Y, Mandai M, Kojima A, Takehara K, Kaneki E, Kobayashi H, Kaku T, Ushijima K, Kamura T. Analysis of gastric-type mucinous carcinoma of the uterine cervix — An aggressive tumor with a poor prognosis: A multi-institutional study. Gynecol Oncol 2019; 153:13-19. [DOI: 10.1016/j.ygyno.2019.01.022] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/14/2019] [Accepted: 01/22/2019] [Indexed: 11/30/2022]
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29
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Pirog EC, Park KJ, Kiyokawa T, Zhang X, Chen W, Jenkins D, Quint W. Gastric-type Adenocarcinoma of the Cervix: Tumor With Wide Range of Histologic Appearances. Adv Anat Pathol 2019; 26:1-12. [PMID: 30234500 DOI: 10.1097/pap.0000000000000216] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Gastric-type endocervical adenocarcinoma (GAS) is a recently described diagnostic entity originally characterized as a tumor with (1) voluminous cytoplasm that is (2) clear or pale eosinophilic, and (3) cells showing distinct cell borders. Since the initial tumor description there has been accumulating experience that the neoplasm, in addition to classic features, may show a wide spectrum of morphologic appearances. This paper describes and illustrates cases of GAS with focal or diffuse findings that include: densely eosinophilic cytoplasm, foamy cytoplasm, goblet cells, glands with elongated, stratified nuclei, glands with small cuboidal cells, glands with flattened cells, papillary growth, single cell infiltration and infiltration with microcystic elongated and fragmented pattern. All these patterns may bring up a differential diagnosis with other cervical malignancies such as usual, intestinal, endometrioid, clear cell, serous, and mesonephric adenocarcinoma. The paper describes the patterns of immunostaining of respective lesions that may aid in the diagnostic process and summarizes the main points of the differential diagnosis. GAS is associated with somatic and germline STK11 mutations and TP53 mutations but is invariably negative for human papilloma virus when tumor only is tested. It shows variation in incidence between countries. Awareness of the spectrum of morphologic appearances in GAS is important for accurate and confident diagnosis. Correct identification of GAS is important due to its propensity for ovarian and other distant metastases, markedly worse prognosis as compared with usual endocervical adenocarcinoma, and its relative resistance to chemotherapy.
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30
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Mucinous adenocarcinoma, gastric type of the uterine cervix: clinical features and HER2 amplification. Med Mol Morphol 2018; 52:52-59. [DOI: 10.1007/s00795-018-0202-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 07/02/2018] [Indexed: 01/25/2023]
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31
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Ohya A, Asaka S, Fujinaga Y, Kadoya M. Uterine cervical adenocarcinoma associated with lobular endocervical glandular hyperplasia: Radiologic-pathologic correlation. J Obstet Gynaecol Res 2017; 44:312-322. [PMID: 29144012 DOI: 10.1111/jog.13528] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 09/17/2017] [Indexed: 11/30/2022]
Abstract
AIM We aimed to identify the radiologic features of uterine cervical adenocarcinoma associated with lobular endocervical glandular hyperplasia (LEGH). METHODS 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. RESULTS 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. CONCLUSION On MR imaging, the most common type of adenocarcinoma with LEGH is type A; type C is difficult to diagnose as carcinoma.
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Affiliation(s)
- Ayumi Ohya
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Shiho Asaka
- Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan
| | - Yasunari Fujinaga
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Masumi Kadoya
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
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Hino M, Yamaguchi K, Abiko K, Yoshioka Y, Hamanishi J, Kondoh E, Koshiyama M, Baba T, Matsumura N, Minamiguchi S, Kido A, Konishi I. Magnetic resonance imaging findings and prognosis of gastric-type mucinous adenocarcinoma (minimal deviation adenocarcinoma or adenoma malignum) of the uterine corpus: Two case reports. Mol Clin Oncol 2016; 4:699-704. [PMID: 27123265 DOI: 10.3892/mco.2016.789] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 01/20/2016] [Indexed: 11/05/2022] Open
Abstract
Our group previously documented the first, very rare case of primary gastric-type mucinous adenocarcinoma of the uterine corpus. Although this type of endometrial cancer appears to be similar to the gastric-type adenocarcinoma of the uterine cervix, its main symptoms, appearance on magnetic resonance imaging (MRI) and prognosis have not been fully elucidated due to its rarity. We herein describe an additional case of gastric-type mucinous adenocarcinoma of the endometrium and review the relevant literature. The two cases at our institution (Kyoto University Hospital, Kyoto, Japan) involved postmenopausal women with a primary complaint of abnormal genital bleeding. Microscopic examination of the hysterectomy specimens indicated a highly differentiated mucinous adenocarcinoma with a desmoplastic stromal reaction. Immunohistochemistry for HIK1083 and/or MUC6 was positive in both cases, suggesting a gastric phenotype. Both patients were diagnosed at an advanced stage, they relapsed or recurred immediately after adjuvant chemotherapy, and eventually succumbed to the disease. The main symptom of gastric-type mucinous adenocarcinoma of the uterine cervix is watery discharge, whereas abnormal genital bleeding in addition to watery discharge is mainly observed in the mucinous type of endometrial adenocarcinoma. Cystic cavities in the tumor are present on MRI in cases of endometrial origin, and prognosis is very poor due to resistance to chemotherapy. Thus, gastric-type mucinous adenocarcinoma of the uterine endometrium exhibits a clinical behavior that is similar to tumors originating from the uterine cervix, but is associated with distinguishing clinical symptoms. The incidence of gastric-type endometrial adenocarcinoma may be higher than expected.
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Affiliation(s)
- Mayo Hino
- Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Ken Yamaguchi
- Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Kaoru Abiko
- Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Yumiko Yoshioka
- Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Junzo Hamanishi
- Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Eiji Kondoh
- Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Masafumi Koshiyama
- Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Tsukasa Baba
- Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Noriomi Matsumura
- Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Sachiko Minamiguchi
- Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Aki Kido
- Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
| | - Ikuo Konishi
- Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Kyoto 606-8507, Japan
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