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Shi SY, Li YA, Qiang JW. Multiparametric MRI-based radiomics nomogram for differentiation of primary mucinous ovarian cancer from metastatic ovarian cancer. Abdom Radiol (NY) 2025; 50:1018-1028. [PMID: 39215773 DOI: 10.1007/s00261-024-04542-y] [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: 07/01/2024] [Revised: 08/15/2024] [Accepted: 08/16/2024] [Indexed: 09/04/2024]
Abstract
OBJECTIVE To develop a multiparametric magnetic resonance imaging (mpMRI)-based radiomics nomogram and evaluate its performance in differentiating primary mucinous ovarian cancer (PMOC) from metastatic ovarian cancer (MOC). METHODS A total of 194 patients with PMOC (n = 72) and MOC (n = 122) confirmed by histology were randomly divided into the primary cohort (n = 137) and validation cohort (n = 57). Radiomics features were extracted from axial fat-saturated T2-weighted imaging (FS-T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced T1-weighted imaging (CE-T1WI) sequences of each lesion. The effective features were selected by minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) regression to develop a radiomics model. Combined with clinical features, multivariate logistic regression analysis was employed to develop a radiomics nomogram. The efficiency of nomogram was evaluated using the receiver operating characteristic (ROC) curve analysis and compared using DeLong test. Finally, the goodness of fit and clinical benefit of nomogram were assessed by calibration curves and decision curve analysis, respectively. RESULTS The radiomics nomogram, by combining the mpMRI radiomics features with clinical features, yielded area under the curve (AUC) values of 0.931 and 0.934 in the primary and validation cohorts, respectively. The predictive performance of the radiomics nomogram was significantly superior to the radiomics model (0.931 vs. 0.870, P = 0.004; 0.934 vs. 0.844, P = 0.032), the clinical model (0.931 vs. 0.858, P = 0.005; 0.934 vs. 0.847, P = 0.030), and radiologists (all P < 0.05) in the primary and validation cohorts, respectively. The decision curve analysis revealed that the nomogram could provide higher net benefit to patients. CONCLUSION The mpMRI-based radiomics nomogram exhibited notable predictive performance in differentiating PMOC from MOC, emerging as a non-invasive preoperative imaging approach.
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Affiliation(s)
- Shu Yi Shi
- Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, China
- Department of Radiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yong Ai Li
- Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, China
- Department of Radiology, Changzhi People's Hospital, Changzhi, Shanxi, China
| | - Jin Wei Qiang
- Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, China.
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Gupta S, Ahuja S, Kalwaniya DS. Immunohistochemistry Markers in Ovarian and Fallopian Tube Neoplasms: a Comprehensive Review. Indian J Surg Oncol 2024; 15:465-480. [PMID: 39328739 PMCID: PMC11422544 DOI: 10.1007/s13193-024-02049-y] [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: 06/09/2024] [Accepted: 07/22/2024] [Indexed: 09/28/2024] Open
Abstract
Immunohistochemistry (IHC) has emerged as a crucial tool in diagnosing and managing ovarian cancer, offering invaluable insights into tumor biology and guiding therapeutic decisions. The intricate histopathological landscape of ovarian cancer presents challenges in accurate diagnosis and classification. IHC offers a complementary approach, aiding in the characterization of tumor subtypes, prognostication, and prediction of treatment response. By targeting specific biomarkers, IHC enables the identification of diverse histological features and molecular alterations associated with ovarian malignancies. The integration of IHC into routine diagnostic workflows enhances diagnostic accuracy, aids in the subclassification of ovarian tumors, and facilitates personalized treatment strategies. Emphasis is placed on the judicious selection of antibody panels tailored to specific clinical scenarios, ensuring optimal utilization of resources and minimizing diagnostic pitfalls. Overall, this review underscores the pivotal role of IHC in refining the diagnosis, prognostication, and management of ovarian cancer, highlighting its significance in the era of precision medicine. By leveraging the molecular insights provided by IHC, clinicians and pathologists can optimize patient care and improve outcomes in ovarian cancer management.
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Affiliation(s)
- Sumedha Gupta
- Department of Obstetrics and Gynaecology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
| | - Sana Ahuja
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
| | - Dheer Singh Kalwaniya
- Department of Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
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Tan JKT, Wong JSM, Seo CJ, Lim C, Zhu HY, Ong CAJ, Chia CS. Incidence and outcomes of delayed presentation and surgery in peritoneal surface malignancies. Front Oncol 2023; 13:1137785. [PMID: 37324005 PMCID: PMC10265672 DOI: 10.3389/fonc.2023.1137785] [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: 01/04/2023] [Accepted: 05/18/2023] [Indexed: 06/17/2023] Open
Abstract
Background Peritoneal surface malignancies (PSM) present insidiously and often pose diagnostic challenges. There is a paucity of literature quantifying the frequency and extent of therapeutic delays in PSM and its impact on oncological outcomes. Methods A review of a prospectively maintained registry of PSM patients undergoing Cytoreductive Surgery and Hyperthermic Intra-peritoneal Chemotherapy (CRS-HIPEC) was conducted. Causes for treatment delays were identified. We evaluate the impact of delayed presentation and treatment delays on oncological outcomes using Cox proportional hazards models. Results 319 patients underwent CRS-HIPEC over a 6-years duration. 58 patients were eventually included in this study. Mean duration between symptom onset and CRS-HIPEC was 186.0 ± 37.1 days (range 18-1494 days) and mean duration of between patient-reported symptom onset and initial presentation was 56.7 ± 16.8 days. Delayed presentation (> 60 days between symptom onset and presentation) was seen in 20.7% (n=12) of patients and 50.0% (n=29) experienced a significant treatment delay of > 90 days between 1st presentation and CRS-HIPEC. Common causes for treatment delays were healthcare provider-related i.e. delayed or inappropriate referrals (43.1%) and delayed presentation to care (31.0%). Delayed presentation was a significantly associated with poorer disease free survival (DFS) (HR 4.67, 95% CI 1.11-19.69, p=0.036). Conclusion Delayed presentation and treatment delays are common and may have an impact on oncological outcomes. There is an urgent need to improve patient education and streamline healthcare delivery processes in the management of PSM.
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Affiliation(s)
- Jun Kiat Thaddaeus Tan
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
| | - Jolene Si Min Wong
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Chin Jin Seo
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Cindy Lim
- Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore, Singapore
| | - Hong-Yuan Zhu
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
| | - Chin-Ann Johnny Ong
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Institute of Molecular and Cell Biology, A*STAR Research Entitie, Singapore, Singapore
| | - Claramae Shulyn Chia
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
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Subhan A, Attia SA, P Torchilin V. Targeted siRNA nanotherapeutics against breast and ovarian metastatic cancer: a comprehensive review of the literature. Nanomedicine (Lond) 2021; 17:41-64. [PMID: 34930021 DOI: 10.2217/nnm-2021-0207] [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] [Indexed: 12/29/2022] Open
Abstract
Metastasis is considered the major cause of unsuccessful cancer therapy. The metastatic development requires tumor cells to leave their initial site, circulate in the blood stream, acclimate to new cellular environments at a remote secondary site and endure there. There are several steps in metastasis, including invasion, intravasation, circulation, extravasation, premetastatic niche formation, micrometastasis and metastatic colonization. siRNA therapeutics are appreciated for their usefulness in treatment of cancer metastasis. However, siRNA therapy as a single therapy may not be a sufficient option for control of metastasis. By combining siRNA with targeting, functional agents or small-molecule drugs have shown potential effects that enhance therapeutic effectiveness. This review addresses multidrug resistance and metastasis in breast and ovarian cancers and highlights drug-delivery strategies using siRNA therapeutics.
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Affiliation(s)
- Abdus Subhan
- Department of Chemistry, ShahJalal University of Science & Technology, Sylhet 3114, Bangladesh
| | - Sara Aly Attia
- Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA
| | - Vladimir P Torchilin
- Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.,Department of Oncology, Radiotherapy & Plastic Surgery, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991, Russia
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de Malet A, Svrcek M, Kerbaol A, Theou-Anton N, Granier S, Dokmak S, Paye F, André T, de Mestier L, Cros J, Hammel P. Ovarian metastases of pancreatic adenocarcinoma: clinical presentation, role of surgery, and potential value of the mutational profile for the differential diagnosis with primary mucinous ovarian carcinoma. Ther Adv Med Oncol 2021; 13:17588359211053412. [PMID: 34721673 PMCID: PMC8554549 DOI: 10.1177/17588359211053412] [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: 06/03/2021] [Accepted: 09/27/2021] [Indexed: 11/21/2022] Open
Abstract
Background: Ovarian metastases (OM) of pancreatic adenocarcinoma (PA) (OM-PA) can mimic primary ovarian mucinous carcinoma (POMC) on imaging and histology. These metastases are often symptomatic and not highly chemosensitive, so that oophorectomy may be considered. Aims: The aims of this study were to compare the characteristics of OM-PA and POMC, and discuss the role of surgery. Patients and Methods: Clinical, imaging, and histological data of patients with OM-PA and POMC (2000–2017) in three tertiary centers were reviewed. Twenty-six genes were analyzed by next generation sequencing (NGS) on both primary PA and OM-PA. Results: Twenty-two women with OM-PA (n = 13, 11 with surgical resection) or POMC (n = 9) were selected. OM-PA were smaller than POMC (p = 0.02); imaging, histological, and immunohistochemistry data did not clearly differentiate OM-PA from POMC in 12 of 22 cases (54%). Seven PA/OM-PA pairs were analyzed, and a concordant KRAS mutation was identified in all cases. In four OM-PA, concordant mutations were also found in TP53 (n = 3), SMAD4 (n = 1), MET (n = 1), and PDGFRA (n = 1) genes. The aim of oophorectomy in 11 OM-PA was for antalgic (n = 6) or curative (n = 5) intent. Pain improved in 4/6 of the former patients, but 2/6 had significant morbidity, and 2/6 died of rapid tumor progression. After oophorectomy, median progression-free and overall survivals were 6 (0–11) and 8 months (1–131), respectively. Conclusion: Analysis of mutation profiles in both primary PA and ovarian tumors, especially KRAS, can help to determine the pancreatic origin of OM-PA. Surgical resection of OM-AP in highly selected patients may improve pelvic symptoms but may also cause significant morbidity. The benefit to survival requires further studies.
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Affiliation(s)
- Alice de Malet
- Digestive and Medical Oncology, Paul Brousse Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université of Paris Saclay, Villejuif, France
| | - Magali Svrcek
- Department of Pathology, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université Paris-Sorbonne, Paris, France
| | - Anne Kerbaol
- Radiology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université de Paris, Clichy, France
| | - Nathalie Theou-Anton
- Biochemistry and Genetics, Bichat Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université de Paris, Paris, France
| | - Sandra Granier
- Digestive and Medical Oncology, Paul Brousse Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université of Paris Saclay, Villejuif, France
| | - Safi Dokmak
- Digestive Surgery, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris (AP-HP), Université de Paris, Clichy, France
| | - François Paye
- Digestive Surgery, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université Paris-Sorbonne, Paris, France
| | - Thierry André
- Digestive Oncology, Saint-Antoine Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université Paris-Sorbonne, Paris, France
| | - Louis de Mestier
- Gastroenterology-Pancreatology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université de Paris, Clichy, France
| | - Jérôme Cros
- Pathology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université de Paris, Clichy, France
| | - Pascal Hammel
- Digestive and Medical Oncology, Paul Brousse Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Université of Paris Saclay, 12 avenue Paul Vaillant-Couturier, 94800 Villejuif, France
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Kwon DH, Malpica A, Zaleski M, Euscher ED, Ramalingam P. Immunohistochemical Loss of DPC4 in Tumors With Mucinous Differentiation Arising in or Involving the Gynecologic Tract. Int J Gynecol Pathol 2021; 40:523-532. [PMID: 33405429 DOI: 10.1097/pgp.0000000000000754] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
DPC4 immunohistochemistry (IHC) is usually part of the work-up of mucinous neoplasms in the ovary where the distinction between an ovarian primary and metastatic pancreaticobiliary adenocarcinoma (PanACa) must be made. Although DPC4 IHC is lost in about 55% (46%-61%) of PanACas and typically retained in most primary ovarian mucinous neoplasms, no study has evaluated the expression of this marker in a large cohort of neoplasms arising in or involving gynecologic (GYN) organs. In this study, we retrospectively analyzed the expression of DPC4 IHC in a total of 251 tumors and lesions related to the GYN tract in which DPC4 IHC stain was performed during the initial pathology evaluation. Of these, 138 were primary GYN tumors and lesions, 31 were metastatic GYN tumors involving non-GYN sites, and 83 were metastatic non-GYN tumors involving the GYN tract. We identified 27 cases with loss of DPC4 IHC expression of which 20 cases met the inclusion criteria (i.e. clinical information was available to determine the site of tumor origin). We observed that loss of DPC4 nuclear expression was most commonly seen in tumors of endocervical origin (n=7), of which 5 were gastric-type cervical adenocarcinomas (GCxACa) and 2 were usual-type cervical adenocarcinomas, either primary or metastatic. This was followed by tumors of the pancreaticobiliary tract (n=5), ovary (n=2), and appendix (n=1). In addition, 1 gastric-type vaginal adenocarcinoma (GVaACa) also showed loss of DPC4. Our findings indicate that in female patients with mucinous neoplasms involving the ovary or other sites, with loss of DPC4 by IHC, and negative pancreaticobiliary imaging, the possibility of an occult GCx/GVaACa, and rarely an ovarian primary must be considered.
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Affiliation(s)
- Dong Hyang Kwon
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Ovarian Metastasis from Pancreatic Ductal Adenocarcinoma. World J Surg 2021; 45:3157-3164. [PMID: 34236477 DOI: 10.1007/s00268-021-06209-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) has a high propensity for systemic dissemination. Ovarian metastases are rare and poorly described. METHODS We identified PDAC cases with ovarian metastasis from a prospectively maintained registry. We reported on the association between outcomes and clinicopathologic factors. Recurrence-free (RFS) and overall survival (OS) were calculated using Kaplan-Meier analysis. RESULTS Twelve patients with PDAC and synchronous or metachronous ovarian metastases were identified. Nine patients (75%) underwent pancreatectomy for localized PDAC and developed metachronous ovarian recurrence. The median OS for all patients was 25.4 (IQR:15.4-82.9) months. For the nine patients with metachronous ovarian metastasis, the median RFS and OS were 14.2 (IQR:7.2-58.3) and 44.6 (IQR:18.6-82.9) months, respectively. Nodal disease, poor grade, vascular invasion in the pancreatic primary, and bilateral ovarian disease tended to confer worse outcomes. CONCLUSION Patients with resected PDAC and ovarian recurrence tend to have a comparable disease course to more common patterns of recurrence. Primaries with nodal disease, poorer grade, vascular invasion, and bilateral ovarian disease were indicative of more aggressive disease biology. The ideal management remains largely unknown, and future collaborative efforts should optimize therapeutic strategies.
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Das G, Sridevi V, Natarajan M. A Tertiary Cancer Center Experience of 52 Cases of Primary Ovarian Mucinous Adenocarcinomas. South Asian J Cancer 2020; 9:90-92. [PMID: 33354551 PMCID: PMC7745751 DOI: 10.1055/s-0040-1721211] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Background
Primary mucinous epithelial ovarian adenocarcinoma (mEOC) constitutes a small percentage (2–5%) of ovarian cancer. Our aim is to understand the clinicopathological characteristics and survival results of patients with mEOC after a long-term follow-up.
Materials and Methods
This is a retrospective study of primary mEOC cases treated at a tertiary cancer center in India, from January 1, 2005, to December 31, 2012.
Results
Out of 958 malignant ovarian tumors, 52 (5.43%) were mucinous adenocarcinoma. Nearly 71.2% of cases were of early-stage disease, and the remaining were of advanced-stage disease. After a follow-up period of 63 months (range: 1–138 months), the 5-year actuarial overall survival for stages I, II, III, and IV was 92.5, 70, 38.5, and 0%, respectively. Among advanced-stage tumors, half of them progressed without undergoing cytoreductive surgery and died.
Conclusion
Most of the mEOC cases present in early stages and have good clinical outcome. Patients with advanced-stage disease do not respond well to standard chemotherapy regimens in use and have poor survival figures. The use of primary cytoreduction should be considered in the place of interval cytoreduction for advanced mEOC.
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Affiliation(s)
- Gaurav Das
- Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
| | - V Sridevi
- Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India.,Division of Gynecologic Oncology, Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
| | - Mohanaraj Natarajan
- Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
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Wang SD, Zhu L, Wu HW, Dai MH, Zhao YP. Pancreatic cancer with ovarian metastases: A case report and review of the literature. World J Clin Cases 2020; 8:5380-5388. [PMID: 33269273 PMCID: PMC7674732 DOI: 10.12998/wjcc.v8.i21.5380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 08/30/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pancreatic cancer with ovarian metastases is rare and easily misdiagnosed. Most patients are first diagnosed with ovarian cancer. We report a rare case of ovarian metastases secondary to pancreatic adenocarcinoma. We also review the literature to analyze the clinical characteristics of, diagnostic methods for, and perioperative management strategies for this rare malignancy.
CASE SUMMARY A 48-year-old woman with an abdominal mass presented to our hospital. Computed tomography revealed lesions in the pancreas and lower abdomen. Radiological examination and histological investigation of biopsy specimens revealed either an ovarian metastasis from a pancreatic neoplasm or two primary tumors, with metastasis strongly suspected. The patient simultaneously underwent distal pancreatectomy plus splenectomy by a general surgeon and salpingo-oophorectomy with hysterectomy by a gynecologist. Histological examination of the surgical specimen revealed a pancreatic adenocarcinoma (intermediate differentiation, mucinous) and a metastatic mucinous adenocarci-noma in the ovary.
CONCLUSION For this rare tumor, surgical resection is the most effective treatment, and the final diagnosis depends on tumor pathology.
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Affiliation(s)
- Shun-Da Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Liang Zhu
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Huan-Wen Wu
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Meng-Hua Dai
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Yu-Pei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
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Eymerit-Morin C, Brun JL, Vabret O, Devouassoux-Shisheboran M. [Borderline ovarian tumours: CNGOF Guidelines for clinical practice - Biopathology of ovarian borderline tumors]. GYNECOLOGIE, OBSTETRIQUE, FERTILITE & SENOLOGIE 2020; 48:629-645. [PMID: 32422414 DOI: 10.1016/j.gofs.2020.05.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVES Ovarian borderline tumors (OBT) represent a heterogeneous group of lesions with specific management for each histological subtype. Thus, the correct histological diagnosis is mandatory. MATERIAL AND METHODS References were searched by PubMed from January 2000 to January 2018 and original articles in French and English literature were selected. RESULTS AND CONCLUSIONS OBT should be classified according to the last WHO classification. Any micro-invasion (foci<5mm) or microcarcinoma (foci<5mm with nuclear atypia and desmoplastic stromal reaction) should be indicated in the pathology report. In case of serous OBT, variants (classical or the micropapillary/cribriform) should be indicated (grade C). The peritoneal implants associated with OBT, should be classified as invasive or noninvasive, according to the extension into the underlying adipous tissue. If no adipous tissue is seen the term undetermined should be used (grade B). In case of mucinous OBT bilateral and/or with peritoneal implants or peritoneal pseudomyxoma a search for primitive gastrointestinal, appendiceal or biliopancreatic tumor should be performed (grade C). In case of OBT, a thorough sampling of the tumor is recommended, with 1 block/cm and 2 blocks/cm in case of mucinous OBT, serous OBT micropapillary variant, OBT with intraepithelial carcinoma or/and micro-invasion. Peritoneal implants should be examined in toto. Omentum without macroscopic lesion should be sampled in 4 to 6 blocks (grade C). In case of ovarian cyst suspicious for OBT, fine needle aspiration is not recommended (grade C). In case of ovarian tumor suspicious for OBT, intraoperative examination should be performed by a gynecological pathologist (grade C).
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Affiliation(s)
- C Eymerit-Morin
- Service d'anatomie et cytologie pathologiques, hôpital Tenon, HUEP, UPMC Paris VI, Sorbonne université, 4, rue de la Chine, 75020 Paris, France; Institut de pathologie de Paris, 35, boulevard Stalingrad, 92240 Malakoff, France
| | - J L Brun
- Service de chirurgie gynécologique, centre Aliénor d'Aquitaine, hôpital Pellegrin, 33076 Bordeaux, France; Société française de gynécopathologie, 94410 Saint Maurice, France
| | - O Vabret
- Service de chirurgie gynécologique, centre Aliénor d'Aquitaine, hôpital Pellegrin, 33076 Bordeaux, France
| | - M Devouassoux-Shisheboran
- Institut de pathologie multi-sites, hospices civils de Lyon, centre hospitalier Lyon Sud, centre de biologie et pathologie Sud, 165, chemin du Grand-Revoyet, 69495 Pierre-Bénite, France; Société française de gynécopathologie, 94410 Saint Maurice, France.
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Novel classification of ovarian metastases originating from colorectal cancer by radiological imaging and macroscopic appearance. Int J Clin Oncol 2020; 25:1663-1671. [PMID: 32494980 DOI: 10.1007/s10147-020-01717-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 05/26/2020] [Indexed: 10/25/2022]
Abstract
BACKGROUND Diagnosis of secondary ovarian tumors originating from colorectal cancer has previously been based upon history of malignancy and radiological findings of bilateral masses with a "stained glass appearance." The purpose of this study was to perform a detailed investigation of the radiological and macroscopic features of ovarian metastases originating from colorectal cancer, which remain to be fully characterized. METHODS Study participants were 48 consecutive patients with ovarian metastases from colorectal cancer who underwent resection of ovarian tumors at the National Cancer Center Hospital between August 1998 and January 2019. Ovarian tumors were classified into subgroups using computed tomography (CT), magnetic resonance imaging (MRI), and macroscopic appearance. RESULTS CT/MRI findings and macroscopic appearance were classified into the following four types: type 1 (oval, homogeneous-solid) (n = 5); type 2 (heterogeneous-solid, small in size with multinodular surface) (n = 3); type 3 (solid-cystic, predominantly solid) (n = 18); and type 4 (cystic-solid, multilocular with solid components) (n = 22). Type 1 mimics Krukenberg tumors, type 2 mimics ovarian metastases from breast cancer, type 3 mimics primary ovarian endometrioid cancer, and type 4 mimics primary ovarian mucinous cancer, with a "stained glass appearance". Twenty-eight (58%) patients had bilateral metastases. Eleven patients (23%) underwent hysterectomy and/or pelvic lymph node dissection in addition to ovarian resection. CONCLUSION We introduced a novel classification system for ovarian metastases originating from colorectal cancer, which may be beneficial for assessing ovarian metastases from colorectal cancer and avoiding unnecessary surgery due to misdiagnosis of primary ovarian tumors.
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A Comprehensive Review of Biomarker Use in the Gynecologic Tract Including Differential Diagnoses and Diagnostic Pitfalls. Adv Anat Pathol 2020; 27:164-192. [PMID: 31149908 DOI: 10.1097/pap.0000000000000238] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Morphologic (ie, hematoxylin and eosin) evaluation of the Mullerian tract remains the gold standard for diagnostic evaluation; nevertheless, ancillary/biomarker studies are increasingly utilized in daily practice to assist in the subclassification of gynecologic lesions and tumors. The most frequently utilized "biomarker" technique is immunohistochemistry; however, in situ hybridization (chromogenic and fluorescence), chromosomal evaluation, and molecular analysis can also be utilized to aid in diagnosis. This review focuses on the use of immunohistochemistry in the Mullerian tract, and discusses common antibody panels, sensitivity and specificity of specific antibodies, and points out potential diagnostic pitfalls when using such antibodies.
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Kajiyama H, Suzuki S, Utsumi F, Nishino K, Niimi K, Mizuno M, Yoshikawa N, Kawai M, Oguchi H, Mizuno K, Yamamuro O, Shibata K, Nagasaka T, Kikkawa F. Epidemiological overview of metastatic ovarian carcinoma: long-term experience of TOTSG database. NAGOYA JOURNAL OF MEDICAL SCIENCE 2019; 81:193-198. [PMID: 31239587 PMCID: PMC6556446 DOI: 10.18999/nagjms.81.2.193] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Malignant ovarian neoplasm is one of the most lethal malignancies among cancers of the female reproductive system. Occasionally, these tumors originate from non-ovarian organs as metastatic lesions since the ovary is a frequent metastatic target of many cancers. However, there limited clinical information on metastatic ovarian carcinoma (MOC) and its hallmarks are unknown. During the period of 1986–2015, 4,284 patients with malignant ovarian neoplasm were identified using the Tokai Ovarian Tumor Study Group (TOTSG) database. Of these, excluding borderline malignant tumor, 3,478 patients with malignant ovarian cancer were extracted. The pathological slides were evaluated under central pathological review. Among them, a total of 143 (4.1%) patients with MOC were identified. The median age of patients with MOC was 54 (29–82) years. The most and second most frequent original tumors were colorectal (43%, N=62) and gastric (29%, N=42) carcinoma, respectively. The rates of carcinoma of the appendix, breast, and pancreas were 8, 6, and 4%, respectively. This is the one of the largest studies clarifying the rates of MOC among malignant ovarian neoplasms. Although the rate is low, we should keep in mind that MOC, particularly from colorectal and gastric cancer should be considered when encountering clinical practice of ovarian cancer.
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Affiliation(s)
- Hiroaki Kajiyama
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shiro Suzuki
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Fumi Utsumi
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kimihiro Nishino
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kaoru Niimi
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mika Mizuno
- Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Nobuhisa Yoshikawa
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Michiyasu Kawai
- Department of Obstetrics and Gynecology, Toyohashi Municipal Hospital, Toyohashi, Japan
| | - Hidenori Oguchi
- Department of Obstetrics and Gynecology, Toyota Memorial Hospital, Toyota, Japan
| | - Kimio Mizuno
- Department of Obstetrics and Gynecology, Nagoya First Red-cross Hospital, Nagoya, Japan
| | - Osamu Yamamuro
- Department of Obstetrics and Gynecology, Nagoya Second Red-cross Hospital, Nagoya, Japan
| | - Kiyosumi Shibata
- Department of Obstetrics and Gynecology, Bantane Hospital, Fujita Health University, Nagoya, Japan
| | - Tetsuro Nagasaka
- Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Fumitaka Kikkawa
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Biolchini F, Castro Ruiz C, Pavesi E, Musci G, Zizzo M, Ugoletti L, Annessi V. Diagnostic challenges in synchronous ovarian metastasis from rectal cancer: A case report. Medicine (Baltimore) 2019; 98:e17782. [PMID: 31689847 PMCID: PMC6946346 DOI: 10.1097/md.0000000000017782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 09/05/2019] [Accepted: 10/03/2019] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Ovarian metastases from rectal cancer are infrequent; thus it might be hard to diagnose and treat them. Our study introduces a challenging case which highlights our method in addressing such an issue. PATIENTS CONCERNS A 74-year-old woman was admitted to our Unit showing abdominal pain, vomit, and a gross abdominal mass located in the right iliac fossa and mesogastrium. Oncological markers recorded following abnormalities: carbohydrate antigen 19.9 (Ca19.9) = 453.40 U/mL, carbohydrate antigen 125 (Ca125) = 88.3 U/mL. DIAGNOSIS Such a metastatic tumor being difficult to diagnose, we could not achieve a precise preoperative diagnosis. We entered the operating room with a histologic diagnosis that was highly suspicious of colon adenocarcinoma. During surgery, frozen section analysis was positive for primary ovarian cancer. Thanks to the immunohistochemistry test on the histologic specimen, which might be very helpful in diagnosing such metastatic tumor, final pathology report documented ovarian metastasis from rectal cancer. INTERVENTIONS We performed total hysterectomy with bilateral salpingo-oophorectomy and low anterior resection of the rectum with a terminal colostomy. Adjuvant chemotherapy was administered for 6 months using FOLFOX plus panitumumab in first-line therapy. OUTCOME At 8 months from surgery, during follow-up, a local pelvic progression of disease was detected, leading to second-line chemotherapy treatment. CONCLUSION Correct differential diagnosis between primary and metastatic ovarian tumors is paramount in choosing the best treatment which leads to the best possible outcome. In ovarian metastatic tumors, immunohistochemistry could represent an optimal diagnostic tool.
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Affiliation(s)
| | | | - Erica Pavesi
- Department of General Surgery, Chirurgia Area Nord
| | | | - Maurizio Zizzo
- Surgical Oncology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
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Moro F, Pasciuto T, Djokovic D, Di Legge A, Granato V, Moruzzi MC, Mancari R, Zannoni GF, Fischerova D, Franchi D, Scambia G, Testa AC. Role of CA125/CEA ratio and ultrasound parameters in identifying metastases to the ovaries in patients with multilocular and multilocular-solid ovarian masses. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2019; 53:116-123. [PMID: 29978587 DOI: 10.1002/uog.19174] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/24/2018] [Revised: 06/21/2018] [Accepted: 07/01/2018] [Indexed: 06/08/2023]
Abstract
OBJECTIVES To investigate ultrasound features and the best cut-off value of the cancer antigen 125/carcinoembryonic antigen (CA125/CEA) ratio to discriminate ovarian metastases from benign and primary malignant ovarian neoplasms in two selected groups of morphological ovarian masses, namely multilocular masses with five or more locules and multilocular-solid masses. METHODS Patients with multilocular (five or more locules) or multilocular-solid ovarian masses, operated on within 3 months of ultrasound examination, and with tumor markers (CEA and CA125) available at diagnosis, were identified retrospectively from three ultrasound centers. The masses were described using the International Ovarian Tumor Analysis (IOTA) terminology. Ultrasound and clinical characteristics were compared between those with an ovarian neoplasm (including benign and primary malignant neoplasms) and those with an ovarian metastasis. Receiver-operating characteristics curve (ROC) analysis was used to evaluate the ability of CA125, CEA and CA125/CEA to differentiate between ovarian neoplasms and ovarian metastases, and their predictive performance was assessed. RESULTS In total, 350 (88.4%) patients with an ovarian neoplasm (including 99 benign, 43 borderline and 197 primary epithelial ovarian carcinomas, seven malignant rare tumors and four other types of invasive ovarian tumor) and 46 (11.6%) patients with an ovarian metastasis were analyzed. On ultrasound examination, ovarian neoplasms were smaller than ovarian metastases (median largest diameter, 97 (range, 20-387) mm vs 146 (range, 43-259) mm, respectively; P < 0.0001) and presented with a lower number of cysts with > 10 locules (18.9% vs 54.3%; P < 0.0001). ROC curve analysis showed that the best cut-off value of CEA for distinguishing between ovarian neoplasms and ovarian metastases was 2.33 ng/mL. The predictive performance of this CEA cut-off value was: area under the curve (AUC), 0.791 (95% CI, 0.711-0.870); accuracy, 73.7%; sensitivity, 73.1%; specificity, 78.3%; positive predictive value (PPV), 96.2%; and negative predictive value (NPV), 27.7%. The best cut-off value of CA125/CEA for distinguishing between ovarian neoplasms and ovarian metastases was 11.92. The predictive performance of this CA125/CEA cut-off value was: AUC, 0.758 (95% CI, 0.683-0.833); accuracy, 79.8%; sensitivity, 82.3%; specificity, 60.9%; PPV, 94.1%; and NPV, 31.1%. CONCLUSIONS CA125/CEA ratio and CEA alone did not show any significant difference in their ability to distinguish between ovarian neoplasms (including benign and malignant) and ovarian metastases in masses with multilocular and those with multilocular-solid morphology. Therefore, in this morphological subgroup of ovarian masses, CEA alone is sufficient to differentiate between ovarian neoplasms and ovarian metastases. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
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Affiliation(s)
- F Moro
- Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - T Pasciuto
- Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - D Djokovic
- Istituto di Ginecologia e Ostericia Università Cattolica del Sacro Cuore, Rome, Italy
| | - A Di Legge
- Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - V Granato
- Istituto di Ginecologia e Ostericia Università Cattolica del Sacro Cuore, Rome, Italy
| | - M C Moruzzi
- Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
- Gynecological Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - R Mancari
- Preventive Gynecology Unit, Division of Gynecology, European Institute of Oncology, Milan, Italy
| | - G F Zannoni
- Institute of Histopathology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - D Fischerova
- Gynecological Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - D Franchi
- Preventive Gynecology Unit, Division of Gynecology, European Institute of Oncology, Milan, Italy
| | - G Scambia
- Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - A C Testa
- Istituto di Ginecologia e Ostericia Università Cattolica del Sacro Cuore, Rome, Italy
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Hu J, Khalifa RD, Roma AA, Fadare O. The pathologic distinction of primary and metastatic mucinous tumors involving the ovary: A re-evaluation of algorithms based on gross features. Ann Diagn Pathol 2018; 37:1-6. [PMID: 30179792 DOI: 10.1016/j.anndiagpath.2018.07.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 07/12/2018] [Indexed: 12/13/2022]
Abstract
The problems associated with the pathologic distinction of primary ovarian mucinous tumors from their metastatic counterparts are well-recognized. Herein, we systematically evaluate a variety of gross parameters to determine the combination of features that most optimally separate primary from secondary mucinous ovarian tumors, and to address the tumor types that are most frequently associated with exceptions. 129 consecutive mucinous tumors involving the ovary formed the study set, including 61 primary mucinous tumors (16 carcinomas, 45 borderline tumors), and 68 metastatic carcinomas (21 colon; 28 appendix; 5 breast; 3 lung; 3 pancreas; 3 cervix; 1 bladder; 4 stomach). Consistent with prior studies, we found that as compared with metastases, primary ovarian mucinous tumors tend to be larger, more frequently unilateral and were more likely to be predominantly cystic and devoid of surface nodules. 41 of the 68 cases in the metastatic group showed intraperitoneal disease, as compared with only 3 of the 61 cases in the primary group (p < 0.0001). In 21% (14/68) of the metastatic group, the ovarian tumor was the first clinical indication of the primary tumor, and 82% of those cases were of gastrointestinal tract primary; this group of cases showed significantly larger tumors than ovarian tumors for patients with an established diagnosis of cancer. Receiver operating curve analyses showed that a tumor size cut off of <13 cm for metastatic disease yielded the maximal area under the curve of 0.877 (sensitivity 80%; specificity 80%); the most frequent exception to the size cut off of <13 cm for metastases was colorectal carcinoma, 30% of which were ≥13 cm. An algorithm whereby a tumor ≥13 cm is considered primary unless it displays surface nodules or bilaterality, and a tumor <13 cm is considered metastatic unless it is unilateral, correctly classified 94% (64/68) of the metastatic tumors and 98% (60/61) of the primary tumors. 3 of the 4 incorrectly classified cases in the metastatic group had intraperitoneal disease. We conclude that gross features are very useful in the distinction of primary from metastatic mucinous tumors in the ovary, and the presence of intraperitoneal disease provides additional diagnostic information. Although algorithms such as the one described herein are imperfect classifiers, they do provide baseline information on which additional findings, including microscopic features, can be added to ultimately provide the most accurate diagnostic classification.
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Affiliation(s)
- Jingjing Hu
- Department of Pathology, University of California San Diego, San Diego, CA, United States of America
| | - Raji D Khalifa
- Department of Pathology, University of California San Diego, San Diego, CA, United States of America
| | - Andres A Roma
- Department of Pathology, University of California San Diego, San Diego, CA, United States of America
| | - Oluwole Fadare
- Department of Pathology, University of California San Diego, San Diego, CA, United States of America.
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17
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Sonkusare S, Vishwanath S, Kaur P, Murthi P, Krishnapriya. Occult Gallbladder Carcinoma Presenting as a Primary Ovarian Tumour: a Case Report and Review of Literature. Indian J Surg Oncol 2018; 9:618-621. [PMID: 30538402 DOI: 10.1007/s13193-018-0786-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 07/13/2018] [Indexed: 01/30/2023] Open
Abstract
The ovary is a common site of metastasis from various organs. However, little is known about gallbladder carcinoma metastasising to the ovaries and presenting as a primary ovarian tumour. We report a case of a metastatic gallbladder carcinoma which mimicked a primary ovarian tumour in a 31-year-old woman who presented with menstrual symptoms and an ovarian mass without obvious signs and symptoms related to gallbladder carcinoma. Postoperatively histopathological examination diagnosed primary ovarian germ cell tumour for further chemotherapy. However, postoperative re-evaluation with radiology suggested the possibility of a primary gallbladder carcinoma. Exact diagnosis could only be made after repeat histopathological evaluation of the ovarian mass.
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Affiliation(s)
- Shipra Sonkusare
- 1Department of Obstetrics and Gynaecology, K.S. Hegde Medical Academy, Mangalore, 575018 India
| | - S Vishwanath
- 2Department of Surgical Oncology, K.S. Hegde Medical Academy, Mangalore, 575018 India
| | - Prabhneet Kaur
- 1Department of Obstetrics and Gynaecology, K.S. Hegde Medical Academy, Mangalore, 575018 India
| | - Pujitha Murthi
- 1Department of Obstetrics and Gynaecology, K.S. Hegde Medical Academy, Mangalore, 575018 India
| | - Krishnapriya
- 1Department of Obstetrics and Gynaecology, K.S. Hegde Medical Academy, Mangalore, 575018 India
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18
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Matias-Guiu X, Stewart CJR. Endometriosis-associated ovarian neoplasia. Pathology 2017; 50:190-204. [PMID: 29241974 DOI: 10.1016/j.pathol.2017.10.006] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 10/10/2017] [Accepted: 10/11/2017] [Indexed: 12/13/2022]
Abstract
This article reviews the most relevant pathological and molecular features of ovarian tumours that are associated with endometriosis. Endometriosis is a common condition, affecting 5-15% of all women, and it has been estimated that 0.5-1% of cases are complicated by neoplasia. The most common malignant tumours in this setting are endometrioid adenocarcinoma and clear cell adenocarcinoma, each accounting for approximately 10% of ovarian carcinomas in Western countries. A minority of cases are associated with Lynch syndrome. These carcinomas are often confined to the ovaries at presentation in which case they have relatively favourable outcomes. However, high-stage tumours, particularly clear cell carcinomas, generally have a poor prognosis and this partly reflects relative resistance to current treatment. Histological diagnosis is straightforward in the majority of cases but some variants, for example endometrioid carcinomas with sex cord-like appearances or oxyphil cells, may create diagnostic difficulty. Similarly, clear cell carcinomas can show a range of architectural and cytological patterns that overlap with other tumours, both primary and metastatic, involving the ovaries. Endometriosis-associated borderline tumours are less common, and they often show mixed patterns of differentiation (seromucinous tumours). Atypical endometriosis may represent an intermediate step in neoplastic progression and some of these lesions demonstrate immunohistological and molecular alterations similar to those observed in endometriosis-related tumours. ARID1A mutations are relatively common in all of these tumours, but each has additional characteristic molecular alterations which are likely to be of increasing clinical relevance as targeted therapies are developed. Less is known of the pathogenesis of rarer endometriosis-associated ovarian tumours including endometrioid stromal sarcoma, mesodermal (Müllerian) adenosarcoma, and carcinosarcoma. This article also briefly reviews the issue of synchronous endometrioid carcinomas of the endometrium and the ovary, including the most recent developments on pathogenesis.
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Affiliation(s)
- Xavier Matias-Guiu
- Department of Pathology, Hospital U Arnau de Vilanova and Hospital U de Bellvitge, IDIBELL, IRBLleida, University of Lleida, and CIBERONC, Spain
| | - Colin J R Stewart
- Department of Histopathology, King Edward Memorial Hospital, Perth, and School for Women's and Infants' Health, University of Western Australia, Perth, WA, Australia.
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Lobo J, Machado B, Vieira R, Bartosch C. The challenge of diagnosing a malignancy metastatic to the ovary: clinicopathological characteristics vary and morphology can be different from that of the corresponding primary tumor. Virchows Arch 2016; 470:69-80. [PMID: 27757533 DOI: 10.1007/s00428-016-2029-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 08/29/2016] [Accepted: 10/04/2016] [Indexed: 10/20/2022]
Abstract
An accurate diagnosis of metastases to the ovary is essential for adequate patient management. The aim of this retrospective study was to characterize clinicopathological features of metastatic malignancies that presented as an ovarian mass and compare them with their corresponding primary tumors. We reviewed clinical files and histological material of 120 patients with metastases to the ovary, diagnosed in our center between 2000 and 2014. Metastases were diagnosed before (18 %), synchronously (33 %), or after (49 %) the primary tumor was identified; 25 % were single, 40 % were unilateral; 47 % were ≥13 cm. Most originated from the gastrointestinal tract (73 %), followed by breast (13 %), and female reproductive organs (10 %). Gross features varied with primary tumor site. Metastases from gastrointestinal malignancies were significantly larger and frequently showed necrosis. Metastases to the appendix were cystic (94 %), and almost all metastases to the stomach (96 %) and breast (87 %) were solid. The predominant histological pattern was discordant in 44 % cases, mostly due to cystic changes in ovarian metastases which were observed across several histological types. Other metastases showed a predominant histological pattern which was present only focally in the primary tumor. Metastases showed significantly more edema, necrosis, and hemorrhage, but less lymphovascular invasion and inflammatory infiltrate than the corresponding primary tumors. Metastases to the ovary present highly variable clinicopathological features which frequently differ from those of the corresponding primary tumor. A metastasis should always be considered in the differential diagnosis of an ovarian mass. All clinical, imaging, macroscopic, and histological aspects must be taken into account to establish a correct diagnosis which is essential for adequate treatment.
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Affiliation(s)
- João Lobo
- Department of Pathology, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.,Cancer Biology and Epigenetics Group, Research Center (CI-IPOP), Portuguese Oncology Institute of Porto, Porto, Portugal.,Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira, 4050-313, Porto, Portugal
| | - Bianca Machado
- Department of Pathology, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal
| | - Renata Vieira
- Department of Pathology, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal
| | - Carla Bartosch
- Department of Pathology, Portuguese Oncology Institute-Porto, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. .,Cancer Biology and Epigenetics Group, Research Center (CI-IPOP), Portuguese Oncology Institute of Porto, Porto, Portugal. .,Department of Pathology and Oncology, Medical Faculty, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
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Survival of Patients With Mucinous Ovarian Carcinoma and Ovarian Metastases: A Population-Based Cancer Registry Study. Int J Gynecol Cancer 2016; 25:1208-15. [PMID: 25978291 DOI: 10.1097/igc.0000000000000473] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES Patients with mucinous ovarian carcinoma (MOC) generally have a favorable prognosis, although in advanced stage, prognosis is significantly worse compared to patients with serous ovarian carcinomas (SOCs). This might be due to the difficulties in distinguishing MOC from metastatic tumors. In the current study, we investigate prognosis of MOC compared to other types of ovarian cancer and to synchronous metastases to the ovary (sMO). MATERIALS AND METHODS Age, laterality, International Federation of Gynecology and Obstetrics stage, tumor grade, treatment, and survival were extracted from the Eindhoven Cancer registry for all patients diagnosed with ovarian carcinomas or sMO between 1990 and 2012. Five-year survival analysis and Cox proportional hazards analysis were conducted. RESULTS A total of 3556 patients with primary ovarian carcinoma (of which 474 mucinous) and 289 with sMO were identified. In advanced stage, 5-year survival of patients with MOC was comparable to survival of patients with sMO (11% vs 11%, P = 0.32) and decreased compared to patients with SOC (26%, P < 0.01). For MOC, there was no clinically significant effect on 5-year survival of either debulking (12% vs 8%, P < 0.01) or chemotherapy (12% vs 10%, P = 0.02). CONCLUSIONS Patients with advanced stage MOC have a worse prognosis than advanced stage SOC. Survival is almost identical to that of patients with sMO. Effects of chemotherapy and debulking are limited in patients with MOC, which may be explained by suboptimal treatment due to the admixture of metastases in advanced stage MOC. Methods to differentiate between primary MOC and metastatic disease are needed to provide optimal treatment and insight in prognosis.
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21
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Xu W, Rush J, Rickett K, Coward JIG. Mucinous ovarian cancer: A therapeutic review. Crit Rev Oncol Hematol 2016; 102:26-36. [PMID: 27083591 DOI: 10.1016/j.critrevonc.2016.03.015] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Revised: 03/01/2016] [Accepted: 03/09/2016] [Indexed: 12/18/2022] Open
Abstract
Mucinous ovarian cancer represents approximately 3% of epithelial ovarian cancers (EOC). Despite this seemingly low prevalence, it remains a diagnostic and therapeutic conundrum that has resulted in numerous attempts to adopt novel strategies in managing this disease. Anecdotally, there has been a prevailing notion that established gold standard systemic regimens should be substituted for those utilised in cancers such as gastrointestinal (GI) malignancies; tumours that share more biological similarities than other EOC subtypes. This review summarises the plethora of small studies which have adopted this philosophy and influenced the design of the multinational GOG142 study, which was ultimately terminated due to poor accrual. To date, there is a paucity of evidence to support delivering 'GI style' chemotherapy for mucinous ovarian cancer over and above carboplatin-paclitaxel doublet therapy. Hence there is an urge to develop studies focused on targeted therapeutic agents driven by refined mutational analysis and conducted within the context of harmonised international collaborations.
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Affiliation(s)
- Wen Xu
- Mater Health Services, Raymond Terrace, Brisbane, QLD 4101, Australia
| | - Jack Rush
- School of Medicine, University of Queensland, St Lucia, QLD 4072, Australia
| | - Kirsty Rickett
- UQ/Mater McAuley Library, The University of Queensland Library, Brisbane 4101, Australia
| | - Jermaine I G Coward
- Mater Health Services, Raymond Terrace, Brisbane, QLD 4101, Australia; School of Medicine, University of Queensland, St Lucia, QLD 4072, Australia; Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102, Australia.
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22
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Güth U, Arndt V, Stadlmann S, Huang DJ, Singer G. Epidemiology in ovarian carcinoma: Lessons from autopsy. Gynecol Oncol 2015; 138:417-20. [PMID: 26005053 DOI: 10.1016/j.ygyno.2015.05.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Accepted: 05/13/2015] [Indexed: 11/24/2022]
Abstract
OBJECTIVE We challenge epidemiologic knowledge regarding ovarian carcinoma (OC) by bridging the gap between clinical and autopsy data. METHODS Autopsy reports, histological slides and clinical files from 660 patients in whom OC was diagnosed from 1975-2005 were studied (autopsy cohort, n=233; Clinical Cancer Registry from the local gyneco-oncologic center, n=427). RESULTS Out of the autopsy cohort, we identified four distinct subgroups of patients: 1) OC was diagnosed before autopsy, n=156 (67.0%). 2) OC was an incidental finding, n=16 (6.8%). 3) The ovarian tumors were not primary OC but rather metastases from other primary tumors; this revised diagnosis was first made by using current histopathological knowledge/techniques, n=24 (10.3%). 4) Death was directly due to OC in its final stage and OC was first diagnosed by autopsy, n=37 (15.9%); when these cases were added to the Clinical Cancer Registry to an adjusted OC incidence model, the autopsy cases comprised 8.8% of the adjusted cohort and almost doubled the percentage of oldest patients (≥80 years at diagnosis) from 4.9% to 9.3% (p=0.013). CONCLUSIONS Epidemiological data from the 1970s-1990s may overestimate true incidence because up to 10% of carcinomas in the ovary were not properly classified. Patients who were first diagnosed with OC by autopsy comprise a distinct subgroup. These are patients who have not been seen by specialized oncologists and thus play no role in their perception of the disease. Nevertheless, these cases have impact on prevalence and incidence data of OC and in an era of reduced autopsy rates will probably be overlooked.
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Affiliation(s)
- Uwe Güth
- Cantonal Hospital Winterthur, Department of Gynecology & Obstetrics, Brauerstrasse 45, CH-8401 Winterthur, Switzerland; University Hospital Basel (UHB), Department of Gynecology and Obstetrics, Spitalstrasse 21, CH-4031 Basel, Switzerland.
| | - Volker Arndt
- National Institute for Cancer Epidemiology and Registration (NICER), c/o University of Zurich, Epidemiology, Biostatistics and Prevention Institute. Seilergraben 49, CH-8001 Zürich, Switzerland
| | - Sylvia Stadlmann
- Kantonsspital Baden AG, Institute of Pathology, CH-5404 Baden, Switzerland; University Hospital Basel of Basel, Institute of Pathology, Schönbeinstrasse 40, CH-4031 Basel, Switzerland
| | - Dorothy Jane Huang
- University Hospital Basel (UHB), Department of Gynecology and Obstetrics, Spitalstrasse 21, CH-4031 Basel, Switzerland
| | - Gad Singer
- Kantonsspital Baden AG, Institute of Pathology, CH-5404 Baden, Switzerland; University Hospital Basel of Basel, Institute of Pathology, Schönbeinstrasse 40, CH-4031 Basel, Switzerland
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Horn LC, Einenkel J, Handzel R, Höhn AK. [Morphology of secondary ovarian tumors and metastases]. DER PATHOLOGE 2015; 35:336-47. [PMID: 24859239 DOI: 10.1007/s00292-014-1907-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The distinction between primary and secondary (metastatic) ovarian tumors is essential for the selection of appropriate surgical interventions, chemotherapeutic treatment and prognostic evaluation for the patient. Metastatic tumors of the ovary range between 5 % and 30 %. The majority of ovarian metastases in Europe and North America derive from colorectal (25-50 %) and breast cancers (8-25 %). A major issue is the differential diagnosis of mucinous tumors. Major features favoring metastasis include bilaterality, size < 10 cm, ovarian surface involvement, extensive intra-abdominal spread, and infiltrative growth within the ovary involving the corpus albicans and corpora lutea. An algorithm using bilaterality and tumor size (cut-off 10 cm) allows correct categorization in approximately 85 % of the cases. Although immunohistochemistry (especially CK7 and CK20 in mucinous tumors) using a panel of antibodies plays a valuable role and is paramount in the diagnosis, the results must be interpreted with caution and within the relevant clinical and histopathological context. It is necessary to note that the correct diagnosis of ovarian metastases always needs interdisciplinary and multidisciplinary approaches.
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Affiliation(s)
- L-C Horn
- Abteilung Mamma-, Gynäko- & Perinatalpathologie, Institut für Pathologie, Department für Diagnostik, Universitätsklinikum Leipzig AöR, Liebigstr. 24, 04103, Leipzig, Deutschland,
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24
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Hariprasad G, Hariprasad R, Kumar L, Srinivasan A, Kola S, Kaushik A. Apolipoprotein A1 as a potential biomarker in the ascitic fluid for the differentiation of advanced ovarian cancers. Biomarkers 2013; 18:532-41. [PMID: 23902290 DOI: 10.3109/1354750x.2013.822561] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
CONTEXT Primary ovarian cancer and ovarian metastasis from non-ovarian cancers in advanced stage are closely mimicking conditions whose therapeutics and prognosis are different. OBJECTIVE To identify biomarkers that can differentiate the two variants of advanced ovarian cancers. METHODS Gel-based proteomics and antibody-based assays were used to study the differentially expressed proteins in the ascitic fluid of fourteen patients with advanced ovarian cancers. RESULTS Programmed Cell Death 1-Ligand 2, apolipoprotein A1, apolipoprotein A4 and anti-human fas antibody are differentially expressed proteins. CONCLUSIONS Apolipoprotein A1 with a 61.8 ng/ml cut-off is a potential biomarker with the best differentiating statistical parameters.
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Affiliation(s)
- Gururao Hariprasad
- Department of Biophysics, All India Institute of Medical Sciences , Ansari nagar, New Delhi, 110029 , India
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Losito NS, Scaffa C, Cantile M, Botti G, Costanzo R, Manna A, Franco R, Greggi S. Lung cancer diagnosis on ovary mass: a case report. J Ovarian Res 2013; 6:34. [PMID: 23663245 PMCID: PMC3660167 DOI: 10.1186/1757-2215-6-34] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Accepted: 04/18/2013] [Indexed: 01/20/2023] Open
Abstract
Metastatic neoplasms to the ovary often cause diagnostic problems, in particular those large ovarian masses mimicking primary tumors. Most of these tumors arise from digestive system or breast, while 37-year-old woman diagnosed as right adnexal complex mass, with a subpleural nodule in the apical part of the left lower lobe, at preoperative chest computed tomography scan. The patient underwent total abdominal hysterectomy with right salpingo-oophorectomy (ovarian mass 220 × 200 mm), total omentectomy, left ovarian biopsy, peritoneal random biopsies, and peritoneal washings for cytology. Pathologic and immunohistochemical examination of ovarian specimen suggested morphology and expression of metastatic lung adenocarcinoma with an intense positivity for Thyroid Transcriptional Factor-1 (TTF-1) and Cytokeratin 7 (CK7) staining. Fine needle biopsy of the lung nodule found epithelioid like malignant cells, confirming the diagnosis of an ovarian metastasis from a primary lung cancer. This report focused on the clinical and pathologic diagnostic challenge of distinguishing secondary from primary ovarian neoplasms. Issues on useful immunohistochemical stains are also discussed.
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Affiliation(s)
- Nunzia Simona Losito
- Department of Surgical Pathology, National Cancer Institute "G, Pascale", Naples, Italy.
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Di Marco M, Vecchiarelli S, Macchini M, Pezzilli R, Santini D, Casadei R, Calculli L, Sina S, Panzacchi R, Ricci C, Grassi E, Minni F, Biasco G. Preoperative gemcitabine and oxaliplatin in a patient with ovarian metastasis from pancreatic cystadenocarcinoma. Case Rep Gastroenterol 2012; 6:530-7. [PMID: 22949893 PMCID: PMC3433024 DOI: 10.1159/000341513] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
We describe a case of clinical benefit and partial response with gemcitabine and oxaliplatin (GEMOX) in a young patient with ovarian metastasis from cystadenocarcinoma of the pancreas. A young woman complained of abdominal pain and constipation. Computed tomography (CT) and magnetic resonance imaging scans disclosed two bilateral ovarian masses with pancreatic extension. She underwent bilateral ovarian and womb resection. During surgery peritoneal carcinosis, a pancreatic mass and multiple abdominal lesions were found. The final diagnosis was mucinous pancreatic cystadenocarcinoma with ovarian and peritoneal metastases. She started chemotherapy with GEMOX (gemcitabine 1,000 mg/m(2)/d1 and oxaliplatin 100 mg/m(2)/d2 every 2 weeks). After 12 cycles of chemotherapy a CT scan showed reduction of the pancreatic mass. She underwent distal pancreatic resection, regional lymphadenectomy and splenectomy. Pathologic examination documented prominent fibrous tissue and few neoplastic cells with mucin-filled cytoplasm. Chemotherapy was continued with gemcitabine as adjuvant treatment for another 3 cycles. There is currently no evidence of disease. As reported in the literature, GEMOX is associated with an improvement in progression-free survival and clinical benefit in patients with advanced pancreatic cancer. This is an interesting case in whom GEMOX transformed inoperable pancreatic cancer into a resectable tumor.
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Affiliation(s)
- Mariacristina Di Marco
- Department of Hematology and Oncological Sciences 'L. & A. Seràgnoli', University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
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Zikan M, Fischerova D, Pinkavova I, Dundr P, Cibula D. Ultrasonographic appearance of metastatic non-gynecological pelvic tumors. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2012; 39:215-225. [PMID: 21845744 DOI: 10.1002/uog.10068] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/22/2011] [Indexed: 05/31/2023]
Abstract
OBJECTIVE To describe the ultrasound (sonomorphologic and vascular) characteristics of metastatic non-gynecological pelvic tumors, and to identify ultrasound characteristics typical of the most common non-gynecological pelvic tumors. METHODS In 92 patients with a pelvic mass who had undergone ultrasound examination with subsequent surgery or tru-cut biopsy revealing a metastatic non-gynecological tumor origin, we analyzed retrospectively the sonomorphologic and vascular parameters. All parameters were evaluated for the whole group of non-gynecological tumors as well as separately for each specific tumor type. The findings were compared with those from 100 women with epithelial ovarian cancer. RESULTS We found that CA 125, size of tumor, echogenicity, homogeneity of solid portion, mobility, and presence of ovarian crescent sign, parenchymal metastases and suspicious necrosis were individual statistically significant discriminators (P < 0.01) between the metastatic non-gynecological tumor group and the epithelial ovarian cancer group. CONCLUSIONS Metastatic non-gynecological tumors in the pelvis have a significantly different sonomorphologic pattern compared with primary epithelial ovarian cancer. This pattern is dependent on the primary origin of the tumor. Doppler parameters, however, cannot differentiate between primary ovarian cancer and metastatic non-gynecological tumors.
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Affiliation(s)
- M Zikan
- Gynecologic Oncology Center, Department of Obstetrics and Gynecology, Charles University, Prague, First Medical Faculty and General Teaching Hospital, Prague, Czech Republic.
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Abstract
Recent years have seen a dramatic change in the pathological approach to ovarian mucinous neoplasms. A substantial proportion of tumours previously considered to be ovarian primaries actually represent secondary ovarian involvement by tumours elsewhere in the body. Two major categories of tumour have completely disappeared from the diagnostic spectrum: ovarian ‘borderline’ mucinous tumour associated with pseudomyxoma peritonei, and widely disseminated mucinous carcinomas. The emergent picture of true ovarian primary carcinoma of pure mucinous morphology is that this is a rare malignancy that is low grade and low stage at presentation in the vast majority of cases, with a very low likelihood of aggressive clinical behaviour. A large volume of literature has appeared concerning the pathological distinction of primary from metastatic ovarian mucinous neoplasms in view of the dramatically different prognosis and treacherously similar morphology. Clinicopathological parameters useful in the distinction of primary from metastatic mucinous ovarian carcinomas are reviewed. Major features favouring metastases are bilaterality, size <10 cm, surface involvement, extensive intra-abdominal spread and an extensive infiltrative pattern with desmoplasia. Two morphological patterns essentially exclude ovarian origin: colloid and signet ring carcinomas. Features favouring primary ovarian origin are unilaterality, large size >12 cm, smooth external surface and association with other ovarian pathology. An admixture of benign, borderline and malignant patterns in the same tumour favour primary origin, but can be misleading as a ‘maturation’ pattern in metastases can result in the same appearance.
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Zaino RJ, Brady MF, Lele SM, Michael H, Greer B, Bookman MA. Advanced stage mucinous adenocarcinoma of the ovary is both rare and highly lethal: a Gynecologic Oncology Group study. Cancer 2011; 117:554-62. [PMID: 20862744 PMCID: PMC3010456 DOI: 10.1002/cncr.25460] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2010] [Revised: 04/06/2010] [Accepted: 04/14/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND Primary mucinous adenocarcinomas of the ovary are uncommon, and their biological behavior is uncertain. Retrospective studies have suggested that many mucinous carcinomas initially diagnosed as primary to the ovary have in fact metastasized from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. METHODS A phase 3 trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were reclassified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared within the groups and with that of patients with serous carcinomas. RESULTS Forty-four cases were classified as mucinous adenocarcinoma upon review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high, with unanimity of opinion in 30 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, P < 0.001). CONCLUSION Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary.
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Affiliation(s)
- Richard J Zaino
- Division of Anatomic Pathology, Hershey Medical Center, Medical Center of Pennsylvania State University, Hershey, Pennsylvania 17033, USA.
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Verleye L, Ottevanger PB, Kristensen GB, Ehlen T, Johnson N, van der Burg MEL, Reed NS, Verheijen RHM, Gaarenstroom KN, Mosgaard B, Seoane JM, van der Velden J, Lotocki R, van der Graaf W, Penninckx B, Coens C, Stuart G, Vergote I. Quality of pathology reports for advanced ovarian cancer: are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial. Eur J Cancer 2010; 47:57-64. [PMID: 20850296 DOI: 10.1016/j.ejca.2010.08.008] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2010] [Revised: 08/06/2010] [Accepted: 08/10/2010] [Indexed: 11/19/2022]
Abstract
OBJECTIVE To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant chemotherapy and interval debulking surgery. METHODS Four hundred and seventy nine pathology reports from 40 institutions in 11 different countries were checked for the following quality indicators: macroscopic description of all specimens, measuring and weighing of major specimens, description of tumour origin and differentiation. RESULTS All specimens were macroscopically described in 92.3% of the reports. All major samples were measured and weighed in 59.9% of the reports. A description of the origin of the tumour was missing in 20.5% of reports of the primary debulking group and in 23.4% of the interval debulking group. Assessment of tumour differentiation was missing in 10% of the reports after primary debulking and in 20.8% of the reports after interval debulking. Completeness of reports is positively correlated with accrual volume and adversely with hospital volume or type of hospital (academic versus non-academic). Quality of reports differs significantly by country. CONCLUSION This audit of ovarian cancer pathology reports reveals that in a substantial number of reports basic pathologic data are missing, with possible adverse consequences for the quality of cancer care. Specialisation by pathologists and the use of standardised synoptic reports can lead to improved quality of reporting. Further research is needed to better define pre- and post-operative diagnostic criteria for ovarian cancer treated with neoadjuvant chemotherapy.
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Pictorial essay: multimodality imaging of metastases from pancreatic ductal adenocarcinoma. Clin Imaging 2010; 34:277-87. [DOI: 10.1016/j.clinimag.2009.06.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2009] [Accepted: 06/20/2009] [Indexed: 11/24/2022]
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Kir G, Gurbuz A, Karateke A, Kir M. Clinicopathologic and immunohistochemical profile of ovarian metastases from colorectal carcinoma. World J Gastrointest Surg 2010; 2:109-16. [PMID: 21160859 PMCID: PMC2999225 DOI: 10.4240/wjgs.v2.i4.109] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2009] [Revised: 01/28/2010] [Accepted: 02/04/2010] [Indexed: 02/06/2023] Open
Abstract
Metastasis of colorectal adenocarcinoma of the ovary is not an uncommon occurrence and ovarian metastases from colorectal carcinoma frequently mimic endometrioid and mucinous primary ovarian carcinoma. The clinical and pathologic features of metastatic colorectal adenocarcinoma involving the ovary is reviewed with particular focus on the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasm. Immunohistochemical stains that may be useful in the differential diagnosis of metastatic colorectal tumors to the ovary and primary ovarian tumors are detailed.
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Affiliation(s)
- Gozde Kir
- Gozde Kir, Department of Pathology, Umraniye Education and Research Hospital, Umraniye, Istanbul 34766, Turkey
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Falchook GS, Wolff RA, Varadhachary GR. Clinicopathologic features and treatment strategies for patients with pancreatic adenocarcinoma and ovarian metastases. Gynecol Oncol 2008; 108:515-9. [PMID: 18164378 DOI: 10.1016/j.ygyno.2007.11.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2007] [Revised: 11/09/2007] [Accepted: 11/15/2007] [Indexed: 12/29/2022]
Abstract
BACKGROUND Ovarian metastases from pancreatic adenocarcinoma are uncommon and data on the clinical features, treatment, and survival of patients with pancreatic adenocarcinoma with ovarian metastases is limited. The purpose of this study is to define the clinical characteristics and treatment strategies for this patient population. METHODS We reviewed the charts of 18 patients with pancreatic adenocarcinoma with ovarian metastasis who had presented to The University of Texas M. D. Anderson Cancer Center from 1985 to 2005. RESULTS Of the 18 patients diagnosed with pancreatic adenocarcinoma and ovarian metastases, 8 (44%) presented with ovarian metastases initially and a pancreatic primary tumor became apparent only on further imaging or during surgery. On pathology review, the primary pancreatic cancers (5 out of 18) and ovarian metastases (8 out of 16) showed mucinous characteristics. Patients who underwent resection of their ovarian metastases followed by chemotherapy had a trend of longer median survival compared to patients who received chemotherapy alone without resection of the ovarian metastases (16.5 vs. 8.5 months, respectively; p=0.28). Patients who responded to chemotherapy had a trend of longer survival compared to nonresponders (19 vs. 6 months, respectively; p=0.1). No responses were observed in the ovarian metastases to chemotherapy alone. CONCLUSIONS Primary pancreatic adenocarcinoma with synchronous ovarian metastases may present initially as symptomatic ovarian masses and they commonly have mucinous histologic characteristics. Surgical resection of ovarian metastases may play an important palliative role in the treatment of symptomatic patients with good performance status and lead to longer survival.
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Affiliation(s)
- Gerald S Falchook
- University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA
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Intrahepatic cholangiocarcinoma metastatic to the ovary: a report of 16 cases of an underemphasized form of secondary tumor in the ovary that may mimic primary neoplasia. Am J Surg Pathol 2008; 31:1788-99. [PMID: 18043033 DOI: 10.1097/pas.0b013e3180674ded] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The potential for adenocarcinoma metastatic to the ovary to mimic primary mucinous neoplasms is a well-known issue to surgical pathologists, most of the recent literature emphasizing pancreatic and various other origins for the ovarian metastases. Although an origin in the gallbladder or extrahepatic bile ducts is acknowledged for some cases little information exists on tumors originating within the intrahepatic bile ducts. Sixteen cases of this type were retrieved from the surgical pathology files of the Chiang Mai University Hospital between January 1992 and December 2006. The patients ranged from 38 to 74 years (mean 52). Thirteen presented with nonspecific pelvic symptoms similar to primary ovarian neoplasms. The hepatic tumors were radiologically detected before the ovarian lesion in 2 cases. Hepatic and ovarian masses were simultaneously detected by preoperative radiologic studies or at exploratory laparotomy in 10 cases. In the remaining 4 cases, the hepatic lesions were detected postoperatively. There were a total of 26 metastatic ovarian lesions which included 22 clinically recognized ovarian masses (range 3 to 20 cm, mean 11.8 cm). Bilateral involvement was present in 10 cases (62%) and unilateral involvement in 6 (38%). The cut surfaces of the 22 grossly enlarged ovaries were predominantly solid in 5, solid-cystic in 10, and multicystic in 7. Microscopically, surface implants were observed in 80% of tumors, multinodular growth in 48%, and infiltrative stromal invasion (including microinvasionlike foci as it would be applied if the tumors were primary) in 86%. The neoplastic epithelium typically formed glands that ranged from small to large and cystically dilated, but small clusters of cells and individual cells were also seen. The epithelium ranged from tall, columnar, and mucinous in appearance to cuboidal or flattened and nonspecific. The tumors most closely mimicked primary mucinous neoplasms although a resemblance to other mullerian neoplasms was also seen. Foci often mimicked mucinous borderline tumors of typical type or with intraepithelial carcinoma and benign-appearing mucinous epithelium was seen in 62% of tumors. Immunohistochemical studies in 15 cases showed a positive reaction for cytokeratin 7 in all and for cytokeratin 20 in 5 cases. Intrahepatic cholangiocarcinoma should be included in the list of origins of possible ovarian metastatic tumors that mimic primary ovarian mucinous neoplasia, particularly in parts of the world where cholangiocarcinoma of the liver is relatively common.
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Testa AC, Mancari R, Di Legge A, Mascilini F, Salutari V, Scambia G, Ferrandina G. The 'lead vessel': a vascular ultrasound feature of metastasis in the ovaries. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2008; 31:218-221. [PMID: 18254156 DOI: 10.1002/uog.5251] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
OBJECTIVE To investigate, in a series of metastatic and primary invasive ovarian lesions examined by color Doppler, the prevalence of a main peripheral vessel penetrating into the central part of the ovarian mass with a tree-shaped morphology, defined as the 'lead vessel'. METHODS This was a retrospective study of 31 patients with histopathologically confirmed metastatic involvement of the ovary and 106 patients with confirmed primary invasive ovarian carcinoma, who had undergone standardized ultrasound examination, with established definitions of ultrasound characteristics. We retrieved sonographic images and videoclips, focusing on the detection of the lead vessel. RESULTS The presence of the lead vessel was detected in 11/31 (35.4%) metastatic ovarian tumors, and in only two (0.01%) cases of primary ovarian carcinoma (P = 0.0001). At color Doppler analysis, metastatic ovarian lesions were characterized by significantly lower pulsatility index (P = 0.0001) and resistance index (P = 0.0001) values, and significantly higher peak systolic velocity (P = 0.0002) and time-averaged maximum velocity (P = 0.04) values, when compared with primary ovarian carcinomas. The lead vessel was detected in 11/21 (52%) solid metastatic lesions and in no cases of multilocular or multilocular-solid lesions (P = 0.008). CONCLUSION The lead vessel is a novel sonographic feature of vascular morphology in solid ovarian metastases. The more frequent observation of this feature in metastatic ovarian tumors compared with primary invasive ovarian carcinomas warrants further investigation in order to explore its potential role in the diagnosis of metastatic ovarian masses.
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Affiliation(s)
- A C Testa
- Gynecologic Oncology Unit, Catholic University of Sacred Heart, Largo A. Gemelli 8, Campobasso, Rome, Italy.
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Güth U, Huang DJ, Bauer G, Stieger M, Wight E, Singer G. Metastatic patterns at autopsy in patients with ovarian carcinoma. Cancer 2007; 110:1272-80. [PMID: 17634950 DOI: 10.1002/cncr.22919] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND Previously published studies concerning autopsy findings in ovarian cancer failed to consider the broad differences in factors that influence the course of disease. Furthermore, those studies were conducted when the currently accepted standards in diagnostics and therapy had not been fully established. The objective of the current study was to determine the frequency and sites of metastases in patients with ovarian cancer with particular attention to the clinical course and therapy. METHODS Autopsy reports, histologic slides, and clinical files from 197 patients who died of ovarian carcinoma between 1975 and 2005 were studied. The distribution of metastatic sites (19 different organ sites) and metastatic patterns, with particular attention to clinical course (age, length of survival) and therapy (surgical treatment with curative intention, different chemotherapy regimens), were analyzed. RESULTS Overall, 66.3% of patients had metastases to sites outside the abdominopelvic cavity. Patients who were aged >70 years, who had a disease duration <or=6 months, or who had received either no treatment or treatment without curative intention more often had metastases limited to the abdominopelvic cavity. This pattern of spread was observed most frequently in patients who had received current chemotherapy regimens (odds ratio, 3.5; P = .002). Compared with patients who had received chemotherapy according to previous standards, these patients showed a significantly increased incidence of liver metastases (P < .001). CONCLUSIONS Autopsy data may yield important information concerning the metastatic potential of a malignancy and may assist physicians in making clinical management decisions. The results from the current indicated that declining autopsy rates during the last decades have limited the ability of physicians to evaluate the impact of new therapy regimens on the frequency and distribution of metastases through postmortem examination.
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Affiliation(s)
- Uwe Güth
- Department of Gynecology and Obstetrics, University Hospital Basel, Basel, Switzerland.
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Primary Appendiceal Malignancy Mimicking Advanced Stage Ovarian Cancer. Taiwan J Obstet Gynecol 2007; 46:304-7. [DOI: 10.1016/s1028-4559(08)60042-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Testa AC, Ferrandina G, Timmerman D, Savelli L, Ludovisi M, Van Holsbeke C, Malaggese M, Scambia G, Valentin L. Imaging in gynecological disease (1): ultrasound features of metastases in the ovaries differ depending on the origin of the primary tumor. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2007; 29:505-11. [PMID: 17444565 DOI: 10.1002/uog.4020] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2023]
Abstract
OBJECTIVE To describe the gray-scale and color Doppler ultrasound findings of metastatic tumors in the ovary according to the origin of the primary tumor. METHODS Information was retrieved retrospectively from 67 patients who had undergone preoperative transvaginal gray-scale and color Doppler ultrasound examination and who were found subsequently to have metastatic tumors in their ovaries. In all women the ultrasound information had been collected prospectively using a standardized examination technique and predefined definitions of ultrasound characteristics. Stored ultrasound images were used only to describe retrospectively the external surface of the metastatic tumors. Information on presenting symptoms and on whether the patient had been treated for a malignancy in the past was retrieved retrospectively from patient records. RESULTS Most (95%) ovarian metastases were solid, multilocular-solid or multilocular. Almost all (38/41, 93%) metastases that derived from the stomach, breast, lymphoma or uterus were solid, while most (16/22, 73%) metastases deriving from the colon, rectum, appendix or biliary tract were multilocular or multilocular-solid (P<0.0001). Metastases that derived from the colon, rectum, appendix or biliary tract were larger compared with those from the stomach, breast, lymphoma or uterus (median maximum diameter, 122 (range, 16-200) mm vs. 71 (range, 27-170) mm, P=0.02). In addition, irregular external borders were more common (19/22 (86%) vs. 19/41 (46%), P=0.002), as were papillary projections (6/22 (27%) vs. 2/41 (5%), P=0.011). They also appeared to be less vascularized, with 64% (14/22) manifesting moderate-to-abundant vascularization at color Doppler examination in comparison to 88% (36/41) of the ovarian metastases from stomach, breast, lymphoma or uterus (P=0.024). CONCLUSION Ovarian metastases derived from lymphoma or from tumors in the stomach, breast and uterus are solid in almost all cases, whereas those derived from the colon, rectum or biliary tract manifest more heterogeneous morphological patterns, most being multicystic with irregular borders.
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Affiliation(s)
- A C Testa
- Gynecologic Oncology Unit, Catholic University of Sacred Heart, Rome, Italy, and Department of Obstetrics and Gynecology, University Hospitals KU Leuven, Belgium.
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Lerwill MF, Young RH. Ovarian metastases of intestinal-type gastric carcinoma: A clinicopathologic study of 4 cases with contrasting features to those of the Krukenberg tumor. Am J Surg Pathol 2006; 30:1382-8. [PMID: 17063077 DOI: 10.1097/01.pas.0000213256.75316.4a] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Ovarian metastases of intestinal-type gastric adenocarcinomas are rare, and information on them is very limited compared with that on signet-ring cell carcinomas that result in the Krukenberg tumor. Four cases are reported herein. The patients averaged 55 years of age. In 3 patients, the ovarian metastases were identified several to 21 months after the diagnosis of the gastric primary, and the tumors were synchronous in the fourth. Two tumors were bilateral, 1 unilateral, and for 1, the laterality was unknown. The ovarian tumors were characteristically solid and cystic, with multinodular growth in 2. In 2 cases, the ovarian tumors had a pseudoendometrioid morphology with tubulo-glandular, cribriform, and papillary patterns; they also had focal trabecular and insular patterns. Prominent necrosis was present, including segmental and intraluminal "dirty" necrosis. In the other 2 cases, the ovarian tumors had a mucinous appearance, 1 being dominantly cystic with occasional goblet cells and the other with prominent foveolar-type cells. Nuclei ranged from deceptively bland to highly atypical. Surface implants were identified in 2 cases. Two ovarian tumors examined expressed cytokeratin 7 and 20 but not estrogen receptor. Three patients with follow-up information all died within 1 year of the ovarian metastases. Although information is limited, our results suggest that metastatic spread to the ovary by intestinal-type gastric adenocarcinoma is usually seen in patients older than those with Krukenberg tumors, with a known history of gastric carcinoma, and with concomitant widespread disease. Involvement of the ovary by intestinal-type gastric carcinoma produces a microscopic picture distinctly different from that of a Krukenberg tumor. These metastatic intestinal-type tumors may be confused with metastases from other gastrointestinal sites that are more frequently the cause of pseudoendometrioid or mucinous metastases, and like such tumors may be confused with primary ovarian endometrioid and mucinous neoplasms.
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Affiliation(s)
- Melinda F Lerwill
- James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Department of Pathology, Harvard Medical School, Boston, MA 02114, USA.
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N/A, 马 向, 付 静, 余 力. N/A. Shijie Huaren Xiaohua Zazhi 2006; 14:3333-3334. [DOI: 10.11569/wcjd.v14.i34.3333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Young RH. From krukenberg to today: the ever present problems posed by metastatic tumors in the ovary: part I. Historical perspective, general principles, mucinous tumors including the krukenberg tumor. Adv Anat Pathol 2006; 13:205-27. [PMID: 16998315 DOI: 10.1097/01.pap.0000213038.85704.e4] [Citation(s) in RCA: 126] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
This review considers historical aspects of metastatic tumors to the ovary, general principles that aid in their evaluation, and metastatic mucinous tumors, including the Krukenberg tumor. The historical timeline on the Krukenberg tumor dates back to the legendary Sir James Paget and the story is followed through the well-known, albeit flawed, contribution of Friedrich Krukenberg and others who have contributed important papers over the years, including the overlooked contribution of the French investigator Gauthier-Villars. Knowledge of metastatic colorectal carcinoma is traced back to the famed British surgeon Sir John Bland-Sutton and followed through to more recent contributions, including the important one of Lash and Hart. Contributions on mucinous tumors conclude the historical perspective, note being made of the recent evidence suggesting that the long held contention of Dr Robert E. Scully that ovarian mucinous tumors in patients with pseudomyxoma peritonei usually originate from the appendix is correct. The section on general principles highlights the many clinical, gross, microscopic, and special techniques such as immunohistochemistry that may aid in determining that an ovarian tumor is metastatic with emphasis on the first 3 mentioned aspects. Problematic features such as a tendency for metastatic tumors to be cystic, even when the primary tumors are not, and for many metastatic tumors to mature in the ovary (so-called maturation phenomenon), are emphasized. Of the many helpful findings that resolve the problem, the characteristic features of surface implants are highlighted. The contribution on the Krukenberg tumor reviews the varied microscopy of this tumor pointing out that the well-known pattern of signet-ring cells in a cellular stroma, albeit characteristic, is often not striking and frequently overshadowed by other microscopic features. The latter include, in many cases, a rather unique microcystic pattern. The final portion of the essay reviews mucinous tumors of non-Krukenberg type, beginning with those that originate from the appendix. The appendiceal neoplasms have distinctive features in most cases being particularly well differentiated, and this is also seen in their ovarian metastases. Other mucinous tumors that commonly simulate closely metastatic neoplasms, include those from the pancreas in particular, but also diverse other sites, are then reviewed.
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Affiliation(s)
- Robert H Young
- James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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Heinzelmann-Schwarz VA, Scolyer RA, Scurry JP, Smith AN, Gardiner-Garden M, Biankin AV, Baron-Hay S, Scott C, Ward RL, Fink D, Hacker NF, Sutherland RL, O'Brien PM. Low meprin alpha expression differentiates primary ovarian mucinous carcinoma from gastrointestinal cancers that commonly metastasise to the ovaries. J Clin Pathol 2006; 60:622-6. [PMID: 16822880 PMCID: PMC1955076 DOI: 10.1136/jcp.2005.034223] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Currently, no specific immunohistochemical markers are available to differentiate primary mucinous epithelial ovarian cancer (MOC) from adenocarcinomas originating at other sites that have metastasised to the ovary, which may have an impact on patient management and prognosis. AIM To investigate the expression of two intestinal markers, galectin 4 and meprin alpha, in mucinous carcinomas of the ovary and gastrointestinal tract. METHODS Using immunohistochemical analysis, the expression of galectin 4 and meprin alpha was investigated in 10 MOCs and in 38 mucinous adenocarcinomas of colon, pancreas, stomach and appendix, the most common sites of origin of ovarian metastases. RESULTS Total cytoplasmic galectin 4 expression was relatively consistent between the different carcinomas. Membranous meprin alpha expression was significantly lower in MOCs compared with gastrointestinal carcinomas. Moreover, meprin alpha expression showed greater discrimination between the ovarian and gastrointestinal carcinomas than the cytokeratins CK7 and CK20, the current standard immunohistochemical markers used to determine the tissue origin of mucinous carcinomas involving the ovaries. CONCLUSIONS Meprin alpha is a useful additional marker in differentiating primary from secondary mucinous adenocarcinomas of the ovary.
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Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, Scurry JP, Scolyer RA, Smith AN, Bali A, Bergh PV, Baron-Hay S, Scott C, Fink D, Hacker NF, Sutherland RL, O'Brien PM. A distinct molecular profile associated with mucinous epithelial ovarian cancer. Br J Cancer 2006; 94:904-13. [PMID: 16508639 PMCID: PMC2361366 DOI: 10.1038/sj.bjc.6603003] [Citation(s) in RCA: 87] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of ovarian cancer. To determine the genetic basis of MOC and to identify potential tumour markers, gene expression profiling of 49 primary ovarian cancers of different histological subtypes was performed using a customised oligonucleotide microarray containing >59 000 probesets. The results show that MOC express a genetic profile that both differs and overlaps with other subtypes of epithelial ovarian cancer. Concordant with its histological phenotype, MOC express genes characteristic of mucinous carcinomas of varying epithelial origin, including intestinal carcinomas. Differences in gene expression between MOC and other histological subtypes of ovarian cancer were confirmed by RT–PCR and/or immunohistochemistry. In particular, galectin 4 (LGALS4) was highly and specifically expressed in MOC, but expressed at lower levels in benign mucinous cysts and borderline (atypical proliferative) tumours, supporting a malignant progression model of MOC. Hence LGALS4 may have application as an early and differential diagnostic marker of MOC.
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Affiliation(s)
- V A Heinzelmann-Schwarz
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
- Division of Gynecology, University Hospital Zurich, Switzerland
| | - M Gardiner-Garden
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
| | - S M Henshall
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
| | - J P Scurry
- South Eastern Area Laboratory Service, Prince of Wales Hospital, Randwick, NSW 2031, Australia
| | - R A Scolyer
- Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
| | - A N Smith
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
| | - A Bali
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
| | - P Vanden Bergh
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
| | - S Baron-Hay
- Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
| | - C Scott
- Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
| | - D Fink
- Division of Gynecology, University Hospital Zurich, Switzerland
| | - N F Hacker
- Gynaecological Cancer Centre, Royal Hospital for Women, Randwick, NSW 2031, Australia
| | - R L Sutherland
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
| | - P M O'Brien
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
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McCluggage WG, Young RH. Immunohistochemistry as a diagnostic aid in the evaluation of ovarian tumors. Semin Diagn Pathol 2006; 22:3-32. [PMID: 16512597 DOI: 10.1053/j.semdp.2005.11.002] [Citation(s) in RCA: 108] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Aspects of immunohistochemistry (IHC), which are useful in the diagnosis of ovarian tumors (mostly neoplasms but also a few tumor-like lesions), are discussed. The topic is first approached by considering the different growth patterns and cell types that may be encountered. Then a few other specific situations in which IHC may assist are reviewed. Selected findings largely, or only, of academic interest are also mentioned. One of the most common situations in which IHC may aid is in the evaluation of tumors with follicles or other patterns which bring a sex cord-stromal tumor into the differential. The distinction between a sex cord tumor and an endometrioid carcinoma with sex-cord-like patterns may be greatly aided by the triad of epithelial membrane antigen (EMA), inhibin, and calretinin, the latter two being typically positive and EMA negative in sex cord tumors, the converse being typical of endometrioid carcinoma. It should be emphasized that granulosa cell tumors may be inhibin negative and, albeit less specific, calretinin is more reliable in evaluating this particular issue. Lack of staining for inhibin and calretinin may also be supportive in leading to consideration of diverse other neoplasms that may form follicles, including metastatic tumors as varied as carcinoid and melanoma. The well-known staining of the latter neoplasm for S-100 protein and HMB-45 may be very helpful in evaluating melanomas with follicular or other unusual patterns, a challenging aspect of ovarian tumor interpretation. The most common monodermal teratoma, struma ovarii, usually has an overt follicular pattern and is easily recognized, but recognition of unusual appearances ranging from oxyphilic to clear cell to various patterns of malignant struma may be greatly aided by a thyroglobulin or TTF 1 stain. IHC for neuroendocrine markers may assist in the diagnosis of primary and metastatic carcinoid tumor. The broad differential diagnosis of glandular neoplasms with an endometrioid-pseudoendometrioid morphology, or mucinous cell type, has been the subject of much exploration in recent years, particularly the distinction between primary and metastatic neoplasms. The well-known CK7 positive, CK20 negative phenotype of primary endometrioid carcinoma, and the converse profile in most metastatic large intestinal adenocarcinomas with a pseudoendometrioid morphology, has been much publicized but albeit an appropriate supportive adjunct in many cases, exceptions from the typical staining pattern may be encountered. It is even less helpful in the case of primary versus metastatic mucinous neoplasia. Evaluation of the expression of mucin gene products has shown mixed, essentially unreliable, results. Experience with other new markers, such as CDX-2, villin, beta catenin, and P504S (racemase), is limited but is in aggregate promising with regard to providing some aid in this area. The rare differential of metastatic cervical adenocarcinoma versus primary ovarian mucinous or endometrioid carcinoma may be aided by strong p16 staining of the former. Staining for alpha-fetoprotein may aid in confirming the diagnosis of endometrioid-like (and hepatoid) variants of yolk sac tumor. Ependymoma of the ovary may also have an endometrioid-like glandular pattern, but positive stains for glial fibrillary acidic protein contrast with the negative results in others neoplasms with a similar pattern. Immunostains may be very helpful in the evaluation of oxyphilic tumors and tumor-like lesions and in some unusual forms of clear cell neoplasia, such as clear cell struma, both subjects being reviewed herein. Immunostains may highlight both the presence and extent of epithelial cells in a variety of circumstances, including microinvasive foci in cases of serous borderline tumors and mucinous carcinomas, and in determining the extent of carcinoma cells and reactive cells within mural nodules of mucinous neoplasms. As in tumor pathology in general, various markers may be crucial in the diagnosis of small round cell tumors of the ovary, and familiar markers of epithelial, lymphoid, leukemic, and melanocytic neoplasms may assist in the analysis of high grade tumors with a poorly differentiated carcinoma, lymphoma-granulocytic sarcoma, malignant melanoma differential. The evaluation of ovarian cystic lesions may be aided by thyroglobulin or TTF 1 (cystic struma), glial fibrillary acid protein (ependymal cysts), and inhibin-calretinin (follicle cysts and unilocular granulosa cell tumors). Stains for trophoblast markers may occasionally aid in the evaluation of germ cell tumors, although routine stains should usually suffice; they may be of academic interest in confirming trophoblastic differentiation in some high grade surface epithelial carcinomas.
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Affiliation(s)
- W Glenn McCluggage
- Department of Pathology, Royal Group of Hospitals Trust, Belfast, Northern Ireland.
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Khunamornpong S, Suprasert P, Pojchamarnwiputh S, Na Chiangmai W, Settakorn J, Siriaunkgul S. Primary and metastatic mucinous adenocarcinomas of the ovary: Evaluation of the diagnostic approach using tumor size and laterality. Gynecol Oncol 2005; 101:152-7. [PMID: 16300822 DOI: 10.1016/j.ygyno.2005.10.008] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2005] [Revised: 10/07/2005] [Accepted: 10/07/2005] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To evaluate the usefulness of the recently proposed algorithm (Seidman JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol 2003; 27: 985-93 [5]) that classifies mucinous adenocarcinomas of the ovary as primary when they were unilateral > or =10 cm and as metastatic when they were unilateral <10 cm or bilateral. METHODS Malignant ovarian neoplasms, which were resected in Chiang Mai University Hospital between 1992 and 2003, were histologically reviewed. Mucinous adenocarcinomas involving the ovary were identified. The medical records and radiologic materials were reviewed in correlation with the pathologic features to identify the primary site. RESULTS There were 74 cases of mucinous adenocarcinomas; 16 were primary ovarian; 52, metastatic; and 6 of indeterminate primary site (primary versus metastatic). Primary mucinous adenocarcinomas had a mean size of 16.4 cm and bilateral involvement in 13%. Metastatic mucinous adenocarcinomas had a mean size of 11.7 cm and bilateral involvement in 77%. Excluding the 6 tumors of indeterminate primary site, the proposed algorithm correctly classified primary and metastatic tumors in 84% of 68 cases. Of 21 unilateral mucinous adenocarcinomas > or =10 cm, 62% were primary ovarian. Of 5 unilateral tumors <10 cm, 80% were metastatic. Of 42 bilateral mucinous adenocarcinomas, 95% were metastatic. CONCLUSION The algorithm provided high accuracy in the overall prediction of primary and metastatic mucinous adenocarcinomas of the ovary, with major strength in the identification of metastatic tumors by bilaterality or size <10 cm. However, the prediction of primary mucinous adenocarcinomas by unilaterality and size > or =10 cm was less reliable than previously reported. Due to the overlapping features between primary and metastatic tumors and the higher frequency of the latter, the possibility of metastases should always be borne in mind in the evaluation of mucinous adenocarcinomas of the ovary.
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Affiliation(s)
- Surapan Khunamornpong
- Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
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