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1
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Das S, Ahlawat S, Jain P, Panda AK, Sarangi J, Joshi R, Gogi R, Jain A. Neuroendocrine Tumors of the Endometrium: a Case Series with Clinico-Pathological Analysis and Review of Literature. Indian J Surg Oncol 2025; 16:211-220. [PMID: 40114864 PMCID: PMC11920455 DOI: 10.1007/s13193-024-02047-0] [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: 04/26/2024] [Accepted: 07/21/2024] [Indexed: 03/22/2025] Open
Abstract
Neuroendocrine carcinomas are rare aggressive tumors that are either mixed with endometrial carcinomas or pure neuroendocrine carcinoma. They show at least one or two neuroendocrine markers by immunohistochemistry. Here, we describe a case series of six cases that arise from endometrium. The mean age of presentation was 57 years with the most common type being mixed endometrioid and neuroendocrine carcinoma. Immunohistochemistry showed all cases positive for Pan-cytokeratin and INSM-1 while the majority were positive for synaptophysin and chromogranin. At least two neuroendocrine markers were positive in all cases in > 20% of tumor cells. The majority of the cases presented at FIGO (International Federation of Gynecology and Obstetrics) Stage III & IV. Three patients had a recurrence, one patient had bone metastasis, one patient died, and one patient was free of disease. Four patients with Stage IV disease were not alive for more than 18 months. A multidisciplinary approach is required for these aggressive tumors for better management of patients.
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Affiliation(s)
- Sumanta Das
- Department of Pathology, Agilus Diagnostics Ltd, Fortis Memorial Research Institute, Gurugram, India
| | - Sunita Ahlawat
- Department of Pathology, Agilus Diagnostics Ltd, Fortis Memorial Research Institute, Gurugram, India
| | - Priti Jain
- Department of Pathology, Agilus Diagnostics Ltd, Fortis Memorial Research Institute, Gurugram, India
| | - Arun Kumar Panda
- Department of Pathology, Agilus Diagnostics Ltd, Fortis Memorial Research Institute, Gurugram, India
| | - Jayati Sarangi
- Department of Pathology, Agilus Diagnostics Ltd, Fortis Memorial Research Institute, Gurugram, India
| | - Rama Joshi
- Department Obstetrics and Gynecology, Fortis Memorial Research Institute, Gurugram, India
| | - Ramana Gogi
- Department of Medical Oncology, Fortis Memorial Research Institute, Gurugram, India
| | - Ashutosh Jain
- Department of Medical Oncology, Fortis Memorial Research Institute, Gurugram, India
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2
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Siu WYS, Hong MK, Ding DC. Neuroendocrine carcinoma of the endometrium concomitant with Lynch syndrome: A case report. World J Clin Cases 2023; 11:5160-5166. [PMID: 37583867 PMCID: PMC10424008 DOI: 10.12998/wjcc.v11.i21.5160] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 06/14/2023] [Accepted: 07/03/2023] [Indexed: 07/26/2023] Open
Abstract
BACKGROUND Large-cell neuroendocrine carcinoma (NEC) is an uncommon type of tumor that can occur in the endometrium. This aggressive cancer requires definitive management. Here, we describe the clinical characteristics and treatment of a postmenopausal woman with large cell NEC of the endometrium. CASE SUMMARY A 55-year-old Asian female presented with a 1-year history of postmenopausal vaginal bleeding. Transvaginal ultrasound revealed a thickened endometrium (30.2 mm) and a hypervascular tumor. Computed tomography revealed that the tumor had invaded more than half of the myometrium and spread to the pelvic lymph nodes. The tumor marker, carcinoembryonic antigen, was elevated (3.65 ng/mL). Endocervical biopsy revealed high-grade endometrial carcinoma. She underwent radical hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and bilateral pelvic and para-aortic lymph node dissection. Pathological examination revealed mixed neuroendocrine and endometrioid adenocarcinoma, pT2N0M0, grade 3, and International Federation of Gynecology and Obstetrics stage 2. Immunohistochemistry showed moderate estrogen and progesterone receptor expressions (20% and 1%, respectively), focal CD56 expression (NEC marker), positive staining for vimentin, p53 (wild type), and ki67 (90%), and loss of expression of PMS2 (Lynch syndrome marker). The patient received five cycles of cisplatin and etoposide after surgery. No recurrence was noted after 5 mo. CONCLUSION We report the characteristics and successful management of a rare case of large-cell endometrial NEC concomitant with Lynch syndrome.
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Affiliation(s)
- Wing Yu Sharon Siu
- Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Hualien 970, Taiwan
| | - Mun-Kun Hong
- Minimally Invasive Gynecology Surgery Center, Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Hualien 970, Taiwan
| | - Dah-Ching Ding
- Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Tzu Ch University, Hualien 970, Taiwan
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3
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Pang L, Chen J, Chang X. Large-cell neuroendocrine carcinoma of the gynecologic tract: Prevalence, survival outcomes, and associated factors. Front Oncol 2022; 12:970985. [PMID: 36457506 PMCID: PMC9707296 DOI: 10.3389/fonc.2022.970985] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 10/27/2022] [Indexed: 07/26/2023] Open
Abstract
BACKGROUND We aimed to assess the clinical behavior of gynecologic large-cell neuroendocrine carcinoma (LCNEC) via a retrospective analysis of data from 469 patients. METHODS Patients diagnosed with gynecologic LCNEC from 1988 to 2015 were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox hazard regression analyses were performed to assess independent predictors of overall survival (OS) and cancer-specific survival (CSS). OS and CSS were also evaluated using the Kaplan-Meier method, and the effects of different treatment regimens on prognosis were compared according to disease stage. RESULTS Cervical, ovarian, and endometrial LCNEC were observed in 169, 219, and 79 patients, respectively. The 5-year OS rates for patients with cervical, ovarian, and endometrial LCNEC were 35.98%, 17.84%, and 23.21%, respectively, and the median duration of overall survival was 26, 11, and 11 months in each group. The 5-year CSS rates for the three groups were 45.23%, 19.23%, and 31.39%, respectively, and the median duration of CSS was 41, 12, and 11 months in each group. Multivariate analysis revealed that American Joint Committee on Cancer stage, lymph node metastasis, and chemotherapy were independent prognostic factors for OS and CSS in patients with cervical LCNEC. Lymph node metastasis, surgery, and chemotherapy were independent prognostic factors for OS and CSS in the ovarian group and for OS in the endometrial group. Lymph node metastasis and surgery were also independent prognostic factors for CSS in the endometrial group. CONCLUSION Surgery alone may help to improve overall survival and CSS in patients with early-stage cervical LCNEC. In contrast, surgery+chemotherapy and surgery+radiotherapy may help to improve survival in those with early-stage ovarian and endometrial LCNEC, respectively. Regardless of subtype, comprehensive treatment involving surgery, CTX, and RT should be considered to improve prognosis in patients with advanced-stage gynecologic LCNEC.
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Affiliation(s)
- Li Pang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Jie Chen
- Centre of Journals, China Medical University, Shenyang, Liaoning, China
| | - Xiaohan Chang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
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4
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Zhang J, Pang L. Primary Neuroendocrine Tumors of the Endometrium: Management and Outcomes. Front Oncol 2022; 12:921615. [PMID: 35814474 PMCID: PMC9260008 DOI: 10.3389/fonc.2022.921615] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 05/25/2022] [Indexed: 11/24/2022] Open
Abstract
Objective To analyze clinical behavior of, optimal treatment regimens for, outcomes, and prognosis of 170 patients with neuroendocrine tumors (NETs) of the endometrium. Methods The Surveillance, Epidemiology, and End Results database was used to identify patients with endometrial NETs diagnosed between 2004 and 2015. Clinical features and treatment regimens were analyzed, and 5-year overall survival (OS) and cancer-specific survival (CSS) were compared among different stages and treatment regimens. Univariate and multivariate analyses were performed to identify independent prognostic factors associated with endometrial NETs. Finally, prognosis was compared between small- and large-cell neuroendocrine carcinoma (SCNEC and LCNEC, respectively) of the endometrium. Results There were 20, 8, 47, and 95 patients with stage I, II, III, and IV NET, respectively. The 5-year OS rates of patients in each stage were 59.86%, 42.86%, 32.75%, and 6.04%, respectively. The 5-year CSS survival rates were 59.86%, 50.0%, 38.33%, and 6.39%, respectively. In the multivariate analysis, American Joint Committee on Cancer (AJCC) stage and treatment were associated with poor OS, while AJCC stage, nodal metastasis, and treatment were associated with poor CSS. Neither pathological type nor distant metastasis was associated with prognosis. The rate of distant metastasis was significantly higher for LCNEC than for SCNEC, while 5-year OS and CSS rates were significantly lower. Conclusion Complete surgical treatment should be selected regardless of staging for patients with endometrial NETs. For early-stage disease, individualized postoperative treatment with single chemotherapy or radiotherapy may improve OS and CSS. For advanced-stage disease, comprehensive postoperative adjuvant therapy may improve OS and CSS.
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Affiliation(s)
- Jingjing Zhang
- Department of Nursing, Shengjing Hospital of China Medical University, Shenyang, China
| | - Li Pang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Li Pang,
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Du R, Jiang F, Wang ZY, Kang YQ, Wang XY, Du Y. Pure large cell neuroendocrine carcinoma originating from the endometrium: A case report. World J Clin Cases 2021; 9:3449-3457. [PMID: 34002157 PMCID: PMC8107915 DOI: 10.12998/wjcc.v9.i14.3449] [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: 12/08/2020] [Revised: 02/10/2021] [Accepted: 03/04/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Large cell neuroendocrine carcinoma (LCNEC) of the endometrium is an uncommon and highly aggressive tumor that has not been comprehensively characterized. We report a case of pure endometrial LCNEC and review the current literature of similar cases to raise awareness of the histological features, treatment, and prognosis of this tumor.
CASE SUMMARY We report the case of a 73-year-old woman who presented with irregular postmenopausal vaginal bleeding. Ultrasonography showed an enlarged uterus and a 5.1 cm × 3.3 cm area of medium and low echogenicity in the uterine cavity. Biopsy by dilatation and curettage suggested poorly differentiated carcinoma. Magnetic resonance imaging revealed a heterogeneously enhanced uterine tumor with diffuse infiltration of the posterior wall of the uterine myometrium and enlarged pelvic lymph nodes. The patient underwent a hysterectomy and bilateral adnexal resection. Gross observation revealed an ill-defined white solid mass of the posterior wall of the uterus infiltrating into the serosa with multiple solid nodules on the serous surface. Microscopically, the tumor cells showed neuroendocrine morphology (organoid nesting). Immunohistochemistry revealed the tumor cells were diffusely positive for the neuroendocrine markers CD56, chromogranin A, and synaptophysin. Thus, the tumor was diagnosed as stage IIIC endometrial LCNEC.
CONCLUSION Pathologic findings and immunohistochemistry are essential in making a diagnosis of endometrial LCNEC.
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Affiliation(s)
- Ran Du
- Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000, Shandong Province, China
| | - Feng Jiang
- Department of Thoracic Surgery, Liaocheng Tumor Hospital, Liaocheng 252000, Shandong Province, China
| | - Zheng-Yan Wang
- Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000, Shandong Province, China
| | - Yan-Qing Kang
- Department of Radiology, Liaocheng People’s Hospital, Liaocheng 252000, Shandong Province, China
| | - Xiu-Yu Wang
- Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000, Shandong Province, China
| | - Ying Du
- Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000, Shandong Province, China
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6
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Burkeen G, Chauhan A, Agrawal R, Raiker R, Kolesar J, Anthony L, Evers BM, Arnold S. Gynecologic large cell neuroendocrine carcinoma: A review. Rare Tumors 2020; 12:2036361320968401. [PMID: 33194158 PMCID: PMC7605029 DOI: 10.1177/2036361320968401] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 09/30/2020] [Indexed: 01/05/2023] Open
Abstract
Large cell neuroendocrine carcinomas (LCNEC) are rare, aggressive high-grade neuroendocrine neoplasms within the neuroendocrine cell lineage spectrum. This manuscript provides a detailed review of published literature on LCNEC of gynecological origin. We performed a PubMed search for material available on gynecologic LCNEC. We analyzed 104 unique cases of gynecologic LCNECs, of which 45 were cervical primary, 45 were ovarian, 13 were uterine, and 1 was vaginal. A total of 45 cases of cervical LCNEC were identified with a median age of 36 years. Median overall survival was 16 months. We identified 45 ovarian LCNEC cases in the published literature with a median age of 54 years. Median overall survival was 8 months. 13 LCNEC cases of uterine origin were identified; 12 out of 13 were of endometrial origin and the median age was 71 years. The majority of patients presented with Stage III/IV disease (stages I-IV were 31%, 8%, 38%, and 23%, respectively). Gynecologic LCNEC is an aggressive malignancy. Our current understanding of the disease biology is very limited. Efforts are required to better understand the genomic and molecular characterizations of gynecological LCNEC. These efforts will elucidate the underlying oncogenic pathways and driver mutations as potential targets.
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Affiliation(s)
- Grant Burkeen
- Department of Internal Medicine, University of Kentucky, Lexington, KY, USA
| | - Aman Chauhan
- Division of Medical Oncology, University of Kentucky, Lexington, KY, USA.,Markey Cancer Center, University of Kentucky, Lexington, KY, USA
| | - Rohitashva Agrawal
- Division of Medical Oncology, University of Kentucky, Lexington, KY, USA
| | - Riva Raiker
- Department of Internal Medicine, University of Kentucky, Lexington, KY, USA
| | - Jill Kolesar
- Markey Cancer Center, University of Kentucky, Lexington, KY, USA.,Department of Pharmacy Practice and Science, University of Kentucky, Lexington, KY, USA
| | - Lowell Anthony
- Division of Medical Oncology, University of Kentucky, Lexington, KY, USA.,Markey Cancer Center, University of Kentucky, Lexington, KY, USA
| | - B Mark Evers
- Markey Cancer Center, University of Kentucky, Lexington, KY, USA.,Department of Surgery, University of Kentucky, Lexington, KY, USA
| | - Susanne Arnold
- Division of Medical Oncology, University of Kentucky, Lexington, KY, USA.,Markey Cancer Center, University of Kentucky, Lexington, KY, USA
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7
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Hardy LE, Chaudry Z, Wan K, Ayres C. Primary mixed large cell neuroendocrine and high grade serous carcinoma of the endometrium. BMJ Case Rep 2020; 13:13/9/e234977. [PMID: 32878852 DOI: 10.1136/bcr-2020-234977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Endometrial large-cell neuroendocrine carcinoma admixed with a high-grade serous (HGS) adenocarcinoma is extremely rare with only one reported case in the literature. We present the second reported case in a 47-year-old woman who presented with abdominal pain, distension and loss of weight. On examination she had a fixed pelvic mass and vascular left vaginal mass. Imaging confirmed a 13 cm solid cystic rectouterine pelvic mass, omental disease and retroperitoneal lymphadenopathy. She underwent a modified posterior exenteration, partial posterior vaginectomy, omentectomy and Hartmanns procedure with suboptimal debulking. Histopathology revealed a stage 4B mixed carcinoma with large cell neuroendocrine (70%) and HGS carcinoma (30%). Eight cycles of adjuvant cisplatin and paclitaxel were given with a complete radiological and biochemical response after 7 months. Unfortunately, she developed widespread recurrence at 9 month and was offered second line chemotherapy.
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Affiliation(s)
- Liesel Elisabeth Hardy
- Gynaecology Oncology, King Edward Memorial Hospital for Women Perth, Subiaco, Western Australia, Australia .,Anatomical Pathology, PathWest Laboratory Medical WA, Nedlands, Western Australia, Australia
| | - Zia Chaudry
- Anatomical Pathology, PathWest Laboratory Medical WA, Nedlands, Western Australia, Australia.,Anatomical Pathology, King Edward Memorial Hospital for Women Perth, Subiaco, Western Australia, Australia
| | - King Wan
- Gynaecology Oncology, King Edward Memorial Hospital for Women Perth, Subiaco, Western Australia, Australia
| | - Chloe Ayres
- Gynaecology Oncology, King Edward Memorial Hospital for Women Perth, Subiaco, Western Australia, Australia
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8
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Suh DS, Kwon BS, Hwang SY, Lee NK, Choi KU, Song YJ, Kim KH. Large cell neuroendocrine carcinoma arising from uterine endometrium with rapidly progressive course: report of a case and review of literature. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2019; 12:1412-1417. [PMID: 31933957 PMCID: PMC6947078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 02/21/2019] [Indexed: 06/10/2023]
Abstract
Large cell neuroendocrine carcinoma (LCNEC) of the endometrium is a rare and highly malignant neoplasm with no characteristic findings in terms of clinical manifestations, diagnostic imaging, or pathology, and thus, the definitive preoperative diagnosis of LCNEC is difficult. A 61-year-old postmenopausal woman presented with low abdominal pain and a rapidly growing uterine mass without postmenopausal bleeding. Magnetic resonance imaging of the pelvis revealed an enlarged uterus with a 7.5 cm mass. Intraoperative frozen examination revealed a malignant tumor, and accordingly, cytoreductive surgery was performed. Microscopically, the tumor showed extensive necrosis, hemorrhage, and an organoid nesting pattern of large cells. Immunohistochemistry revealed tumor cells were diffusely positive for the neuroendocrine markers CD56 and synaptophysin. Thus the tumor was diagnosed as LCNEC of endometrium. Postoperatively, the disease pursued a progressive course and relapsed even after repeated multiple chemotherapy courses. The patient succumbed to the disease 23 months after surgery. We present a case of LCNEC of the endometrium with a high Ki-67 index that exhibited a rapidly progressive course. LCNEC should be considered when a rapidly growing uterine tumor is detected.
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Affiliation(s)
- Dong Soo Suh
- Department of Obstetrics and Gynecology, Pusan National University School of MedicineBusan, Republic of Korea
- Biomedical Research Institute, Pusan National University HospitalBusan, Republic of Korea
| | - Byung Su Kwon
- Department of Obstetrics and Gynecology, Pusan National University School of MedicineBusan, Republic of Korea
- Biomedical Research Institute, Pusan National University HospitalBusan, Republic of Korea
| | - Seo Yoon Hwang
- Department of Obstetrics and Gynecology, Pusan National University School of MedicineBusan, Republic of Korea
| | - Nam Kyung Lee
- Department of Radiology, Pusan National University School of MedicineBusan, Republic of Korea
- Biomedical Research Institute, Pusan National University HospitalBusan, Republic of Korea
| | - Kyung Un Choi
- Department of Pathology, Pusan National University School of MedicineBusan, Republic of Korea
- Biomedical Research Institute, Pusan National University HospitalBusan, Republic of Korea
| | - Yong Jung Song
- Department of Obstetrics and Gynecology, Pusan National University School of MedicineBusan, Republic of Korea
- Biomedical Research Institute, Pusan National University HospitalBusan, Republic of Korea
| | - Ki Hyung Kim
- Department of Obstetrics and Gynecology, Pusan National University School of MedicineBusan, Republic of Korea
- Biomedical Research Institute, Pusan National University HospitalBusan, Republic of Korea
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9
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Jenny C, Kimball K, Kilgore L, Boone J. Large cell neuroendocrine carcinoma of the endometrium: a report and review of the literature. Gynecol Oncol Rep 2019; 28:96-100. [PMID: 30976646 PMCID: PMC6441730 DOI: 10.1016/j.gore.2019.03.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 03/08/2019] [Indexed: 01/22/2023] Open
Abstract
Large-cell neuroendocrine tumor of the endometrium is a rare tumor type which is difficult to diagnose. Our routine tissue sampling is often non-productive and these tumors can be mistaken for other poorly differentiated carcinomas. Sites of metastatic disease sometimes confuse the identification of the primary organ, and histological diagnosis requires a choice of neuroendocrine biomarkers. In addition, there are no published diagnostic criteria for LCNEC of the endometrium and diagnostic criteria must be translated from the WHO classification of tumors of the lung. Once a diagnosis is reached, there are no large series to direct treatment. Consensus opinion appears to favor surgery for early stage disease followed by chemotherapy with etoposide and platinum-based agents. While there are many hurdles to overcome, the proper diagnosis of LCNEC of the endometrium is of utmost importance in a disease characterized by rapid progression and poor prognosis. We examine a case of large cell neuroendocrine tumor of the endometrium with rapid progression over a period of two months which precluded her planned chemotherapy.
There are 20 cases of large cell neuroendocrine tumor of the endometrium reported. It is difficult to make the diagnosis with traditional tissue sampling procedures. The prognosis is poor with disease that may progress rapidly. There may be a role for neo-adjuvant chemotherapy but this is poorly studied.
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Affiliation(s)
- Courtney Jenny
- The University of Tennessee, Knoxville, Department of Obstetrics and Gynecology and Graduate School of Medicine, United States of America
| | - Kristopher Kimball
- The University of Tennessee, Knoxville, Department of Obstetrics and Gynecology and Graduate School of Medicine, United States of America
| | - Larry Kilgore
- The University of Tennessee, Knoxville, Department of Obstetrics and Gynecology and Graduate School of Medicine, United States of America
| | - Jonathan Boone
- The University of Tennessee, Knoxville, Department of Obstetrics and Gynecology and Graduate School of Medicine, United States of America
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10
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Abstract
Neuroendocrine tumours are uncommon or rare at all sites in the female genital tract. The 2014 World Health Organisation (WHO) Classification of neuroendocrine tumours of the endometrium, cervix, vagina and vulva has been updated with adoption of the terms low-grade neuroendocrine tumour and high-grade neuroendocrine carcinoma. In the endometrium and cervix, high-grade neoplasms are much more prevalent than low-grade and are more common in the cervix than the corpus. In the ovary, low-grade tumours are more common than high-grade carcinomas and the term carcinoid tumour is still used in WHO 2014. The term ovarian small-cell carcinoma of pulmonary type is included in WHO 2014 for a tumour which in other organs is termed high small-cell neuroendocrine carcinoma. Neuroendocrine tumours at various sites within the female genital tract often occur in association with other neoplasms and more uncommonly in pure form.
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11
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Ogura J, Adachi Y, Yasumoto K, Okamura A, Nonogaki H, Kakui K, Yamanoi K, Suginami K, Koyama T, Ikehara S. Large-cell neuroendocrine carcinoma arising in the endometrium: A case report. Mol Clin Oncol 2018; 8:571-574. [PMID: 29564132 DOI: 10.3892/mco.2018.1583] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Accepted: 01/17/2018] [Indexed: 12/15/2022] Open
Abstract
Large-cell neuroendocrine carcinoma (LCNEC) of the endometrium is an extremely rare, high-grade malignant tumor. We herein report a case of a rapidly growing LCNEC arising in the endometrium. A 52-year-old woman was referred to Toyooka Hospital (Tooyoka, Japan) due to genital bleeding in February 2016. There had been no abnormalities on a regular gynecological and physical examination 3 months prior to the consultation. Imaging (computed tomography and magnetic resonance imaging) and a pelvic examination revealed a tumor sized 16.9×8.4×7.8 mm occupying the intrauterine cavity and extending into the vaginal cavity. Multiple metastatic pelvic and paraaortic lymph nodes were also identified. Continuous bleeding from the tumor was observed, and a blood examination revealed anemia, which was likely due to that bleeding. Biopsy of the tumor was performed, and large atypical cells were identified. The tumor cells were negative for cytokeratin AE1/AE3 and chromogranin A, but positive for CD56 and synaptophysin. There was also an abundance of Ki-67-positive cells in the tumor, altogether suggesting that the tumor was an LCNEC. The patient succumbed to the disease 36 days after the first consultation. Based on the findings of the present case and previously published cases, LCNECs arising in the endometrium may progress rapidly and are associated with an unfavourable outcome. LCNEC should be included in the differential diagnosis in cases of rapidly growing tumors of the uterine corpus.
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Affiliation(s)
- Jumpei Ogura
- Department of Obstetrics and Gynecology, Toyooka Hospital, Toyooka, Hyogo 668-8501, Japan.,Department of Obstetrics and Gynecology, Kyoto University, Kyoto, Kyoto 606-8501, Japan
| | - Yasushi Adachi
- Department of Diagnostic Pathology, Toyooka Hospital, Toyooka, Hyogo 668-8501, Japan
| | - Koji Yasumoto
- Department of Obstetrics and Gynecology, Toyooka Hospital, Toyooka, Hyogo 668-8501, Japan.,Department of Obstetrics and Gynecology, Kyoto University, Kyoto, Kyoto 606-8501, Japan
| | - Akiharu Okamura
- Department of Diagnostic Pathology, Kakogawa Central City Hospital, Kakogawa, Hyogo 675-8611, Japan
| | - Hirofumi Nonogaki
- Department of Obstetrics and Gynecology, Toyooka Hospital, Toyooka, Hyogo 668-8501, Japan
| | - Kazuyo Kakui
- Department of Obstetrics and Gynecology, Toyooka Hospital, Toyooka, Hyogo 668-8501, Japan.,Department of Obstetrics and Gynecology, Kyoto University, Kyoto, Kyoto 606-8501, Japan
| | - Koji Yamanoi
- Department of Obstetrics and Gynecology, Toyooka Hospital, Toyooka, Hyogo 668-8501, Japan.,Department of Obstetrics and Gynecology, Kyoto University, Kyoto, Kyoto 606-8501, Japan
| | - Koh Suginami
- Department of Obstetrics and Gynecology, Toyooka Hospital, Toyooka, Hyogo 668-8501, Japan.,Department of Obstetrics and Gynecology, Kyoto University, Kyoto, Kyoto 606-8501, Japan
| | - Takashi Koyama
- Department of Radiology, Toyooka Hospital, Toyooka, Hyogo 668-8501, Japan
| | - Susumu Ikehara
- Professor Emeritus, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
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12
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Kobayashi A, Yahata T, Nanjo S, Mizoguchi M, Yamamoto M, Mabuchi Y, Yagi S, Minami S, Ino K. Rapidly progressing large-cell neuroendocrine carcinoma arising from the uterine corpus: A case report and review of the literature. Mol Clin Oncol 2017; 6:881-885. [PMID: 28588782 PMCID: PMC5451872 DOI: 10.3892/mco.2017.1229] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 01/30/2017] [Indexed: 12/18/2022] Open
Abstract
Large-cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor. LCNECs arising from the genital organs are highly malignant and rare, with <20 cases of LCNEC developing from the uterine endometrium reported to date. We herein present the case of a patient with LCNEC of the endometrium. The patient was a 52-year-old woman, who exhibited lower abdominal pain and rapid uterine enlargement during outpatient treatment for uterine myoma. The endometrial biopsy suggested a diagnosis of poorly differentiated carcinoma or carcinosarcoma. Based on magnetic resonance imaging and positron emission tomography/computed tomography, endometrial stromal sarcoma was suspected. The serum lactate dehydrogenase level was abnormally high. Due to the suspicion of stage IIIC malignant tumor of the uterine corpus, surgery was performed. The pathological diagnosis was stage IIIC2 LCNEC of the endometrium. Recurrence occurred in the vaginal stump, and concurrent chemoradiotherapy (CCRT) was initiated 1 month after the surgery. The residual lesions markedly shrank, but metastasis to the upper abdominal region and cervix subsequently developed. CCRT was attempted, but the associated adverse effects were severe and was switched to palliative treatment. The patient eventually succumbed to the disease 309 days after surgery.
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Affiliation(s)
- Aya Kobayashi
- Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-8509, Japan
| | - Tamaki Yahata
- Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-8509, Japan
| | - Sakiko Nanjo
- Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-8509, Japan
| | - Mika Mizoguchi
- Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-8509, Japan
| | - Madoka Yamamoto
- Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-8509, Japan
| | - Yasushi Mabuchi
- Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-8509, Japan
| | - Shigetaka Yagi
- Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-8509, Japan
| | - Sawako Minami
- Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-8509, Japan
| | - Kazuhiko Ino
- Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-8509, Japan
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Ariura M, Kasajima R, Miyagi Y, Ishidera Y, Sugo Y, Oi Y, Hayashi H, Shigeta H, Miyagi E. Combined large cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium: a shared gene mutation signature between the two histological components. Int Cancer Conf J 2016; 6:11-15. [PMID: 31149461 DOI: 10.1007/s13691-016-0263-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 09/10/2016] [Indexed: 02/06/2023] Open
Abstract
A 61-year-old Japanese woman was diagnosed with FIGO Stage IB endometrioid cancer (EC) combined with large cell neuroendocrine carcinoma (LCNEC). Metastasis to the lymph nodes in the right bronchopulmonary area, mediastinum and brain were also identified. The patient eventually developed pleuritis and pericarditis carcinomatosa, and died of cancer at 51 months after surgery. Because gene aberrations in uterine neuroendocrine carcinoma are still not well understood, we examined alterations in the mutational hotspots of 50 selected cancer-associated genes. The EC and LCNEC components shared identical alterations in PTEN, PIK3CA and FGFR3. Both the EC and LCNEC components had heterozygous SBSs on CTNNB1 but at different codons (G34R in EC, and T41A in LCNEC). The altered gene signature raised a possibility that the EC and LCNEC components were derived from a common precursor lesion. The LCNEC independently obtained a significant CTNNB1 mutation and the lymph node metastasis originated from this component. Because the LCNEC component seemed to bring about the aggressive course of the disease and defined the patient outcome, further investigations are needed to elucidate the mechanism of NE carcinoma development in the endometrium.
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Affiliation(s)
- Masayo Ariura
- Department of Obstetrics and Gynecology, Yokohama Municipal Citizens Hospital, Yokohama, Kanagawa Japan
| | - Rika Kasajima
- 2Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa Japan
| | - Yohei Miyagi
- 2Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa Japan
| | - Yumi Ishidera
- Department of Obstetrics and Gynecology, Yokohama Municipal Citizens Hospital, Yokohama, Kanagawa Japan
| | - Yoshinobu Sugo
- Department of Obstetrics and Gynecology, Yokohama Municipal Citizens Hospital, Yokohama, Kanagawa Japan
| | - Yuka Oi
- Department of Obstetrics and Gynecology, Yokohama Municipal Citizens Hospital, Yokohama, Kanagawa Japan
| | - Hiroyuki Hayashi
- Molecular Pathology and Genetics Division, Yokohama Municipal Citizens Hospital, Yokohama, Kanagawa Japan
| | - Hiroyuki Shigeta
- Department of Obstetrics and Gynecology, Yokohama Municipal Citizens Hospital, Yokohama, Kanagawa Japan
| | - Etsuko Miyagi
- 3Department of Obstetrics and Gynecology, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004 Japan
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Abstract
Neuroendocrine carcinoma (NECa) of the endometrium is an uncommon tumor. In this study, we present the clinicopathologic features of 25 such cases. The patients ranged in age from 37 to 87 years (median, 57 y) and most commonly presented with vaginal bleeding. The tumors were either pure NECa (10) or mixed with other histotypes (15), most commonly endometrioid carcinoma. The NECas were large cell type (15), small cell type (4), or a mixture of both (6). NECa was underrecognized in 89% of referral/consultation cases. All tumors were positive for ≥1 neuroendocrine marker (chromogranin, synaptophysin, CD56). Additional immunohistochemical (IHC) studies were obtained in 18 cases, with positive results as follows: keratin cocktail (17), diffuse p16 (6), PAX-8 (6), CD117 (6), and TTF-1 (1). Mismatch-repair protein expression by IHC was abnormal in 8 of 18 cases (6 MLH1/PMS2 loss; 1 MSH2/MSH6 loss; 1 MSH6 loss). According to FIGO staging, cases were distributed as follows: I (6), II (2), III (10), and IV (7). All patients underwent surgical treatment, and 20 patients received adjuvant therapy. Twelve patients died of disease (mean survival 12.3 mo). Eleven patients were alive 5 to 134 months after diagnosis, including 7 who achieved a 5-year survival (3 stage I; 4 stage III). In summary, most of our endometrial NECas were large cell type, mixed with other histotypes, and underrecognized. These tumors tend to be PAX-8 negative and may be associated with microsatellite instability. The recognition of NECa may have an impact on the treatment of the patients affected by this disease. Although NECa usually has an aggressive behavior, 28% of our patients survived at least 5 years.
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A case of uterine corpus large cell neuroendocrine carcinoma showing prominent myometrial invasion without any macroscopically clear tumor formation. Int Cancer Conf J 2015; 5:13-19. [PMID: 31149416 DOI: 10.1007/s13691-015-0217-7] [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: 01/07/2015] [Accepted: 03/24/2015] [Indexed: 10/23/2022] Open
Abstract
Large cell neuroendocrine carcinoma (LCNEC) arising in the uterine corpus is a very rare. Here, we report our experience with a primary LCNEC in the uterine corpus that showed prominent myometrial invasion without exhibiting any macroscopically distinct tumor formation in the uterine cavity. The patient was a 54-year-old woman. She had a past medical history of right breast cancer and was referred to our department with irregular genital bleeding, elevated serum carcinoembryonic antigen in periodic medical examinations and computed tomography (CT) findings of uterine cavity dilation. Endometrial biopsy suggested a poorly differentiated tumor. Although magnetic resonance imaging (MRI) showed hematometra-like findings in the uterine cavity, it did not indicate any clear endometrial lesion. The myometrium was unequally thickened, and the entire muscle layer showed a high signal intensity on diffusion-weighted images. Fluorine-18-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed strong FDG accumulation in the whole uterus, and on the bottom of the uterus, there was a ring-shaped accumulation mainly in the muscle layer. The postoperative resected specimen did not show any tumor formation in the uterine cavity, whereas the myometrium was hard and thickened, and colored white overall. Histopathological examination revealed prominent myometrial invasion in most layers, cervical stromal invasion and pelvic lymph node metastasis. The diagnosis was a LCNEC of the uterine corpus, at FIGO stage IIIC1 and pT2N1M0. With these patients, we found that functional metabolic images, such as MRI diffusion-weighted images and FDG-PET/CT, were useful in identifying the lesion. Preoperatively, when a poorly differentiated tumor is estimated and characteristic myometrial invasion is suspected, the possibility of LCNEC should be considered.
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Nguyen MLT, Han L, Minors AM, Bentley-Hibbert S, Pradhan TS, Pua TL, Tedjarati SS. Rare large cell neuroendocrine tumor of the endometrium: A case report and review of the literature. Int J Surg Case Rep 2013; 4:651-5. [PMID: 23792474 DOI: 10.1016/j.ijscr.2013.04.027] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Accepted: 04/15/2013] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Large cell neuroendocrine carcinoma (LCNEC) of the endometrium is a rare malignancy with an aggressive course. Although data is limited to case reports, the prognosis appears to be poor, similar to other type II uterine cancers. A total of 12 cases of LCNEC of the uterus have been published to date. PRESENTATION OF CASE A 71 year-old woman presented with postmenopausal vaginal bleeding. Endometrial biopsy was non-diagnostic for LCNEC. She underwent surgical debulking and staging of a 22cm endometrial tumor with omental metastasis and positive lymph nodes. Her final FIGO stage was IVB. DISCUSSION We summarize all prior case reports of LCNEC of the endometrium and discuss the definition, presentation, imaging and surgical management. The pathology with immunohistochemical review, adjuvant therapy and prognosis of LCNEC of the endometrium are also reviewed. CONCLUSION Pathologic findings and immunohistochemistry are essential in making a diagnosis of LCNEC of the endometrium. Primary debulking and surgical staging is typically performed, but if a diagnosis of LCNEC can be made preoperatively with immunohistochemistry, surgeons should consider neoadjuvant chemotherapy due to its high grade histology and aggressive course. Otherwise adjuvant chemotherapy is usually given. Even with early stage disease, the prognosis seems poor. Due to the rarity of this aggressive malignancy, more data is needed to establish incidence.
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Affiliation(s)
- My-Linh T Nguyen
- Department of Obstetrics and Gyencology, New York Medical College, United States.
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