[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Female genital tract](https://durgical.com/en/general-pathology/areas/female-genital/) › High-grade serous carcinoma # High-grade serous carcinoma - Lesion The deadliest ovarian cancer usually starts in the tube, carries TP53 mutation and has spread over the abdomen by the time it causes symptoms. Updated Nov 12, 2026 ## Key points - Precursor: serous tubal intraepithelial carcinoma (STIC) in the fimbria, preceded by p53 signatures. - TP53 mutation in nearly all; BRCA1 or BRCA2 germline in a significant minority; homologous recombination deficiency predicts response to platinum and PARP inhibitors. - Gross: bilateral, solid and cystic, with surface tumour; omental cake and peritoneal nodules. - Micro: solid sheets and papillae with slit-like spaces, marked atypia, many mitoses; WT1, PAX8 positive; p53 aberrant. - CA-125 is useful to follow treatment but not as a screening test in the general population. - Risk lowered by risk-reducing salpingo-oophorectomy in carriers, opportunistic salpingectomy, oral contraceptives and parity. ## What it is High-grade serous carcinoma is the most common and most lethal ovarian cancer. Most cases begin in the fimbria of the fallopian tube as serous tubal intraepithelial carcinoma, a lesion with TP53 mutation that sheds cells onto the ovary and peritoneum. Nearly all tumours have TP53 mutations, many have defective homologous recombination (including inherited BRCA1 or BRCA2 mutations), and most are diagnosed at an advanced stage with ascites and omental disease. Removal of the tubes and ovaries in carriers and oral contraceptive use lower the risk. ## Structure - Large adnexal masses with friable papillary and solid tumour on the surface; necrosis and haemorrhage. - Peritoneum, omentum, diaphragm and bowel serosa studded with nodules; malignant ascites. - Tumour cells with large pleomorphic nuclei, prominent nucleoli and abundant mitoses; psammoma bodies may be present. ## Step by step - A TP53 mutation arises in secretory cells of the tubal fimbria (p53 signature). - The clone gains proliferative ability and forms serous tubal intraepithelial carcinoma. - Defective DNA repair, often BRCA-related, causes widespread copy-number changes. - Cells exfoliate onto the ovarian surface and peritoneum and implant. - Peritoneal spread produces ascites, omental cake and bowel obstruction; lymph nodes and the pleura are involved later. ## Markers - PAX8 - WT1 - p53 aberrant - p16 strong - CA-125 (serum) ## Clinical notes - Symptoms are vague and late: bloating, early satiety, abdominal pain, change in bowel habit; many present with ascites or a pleural effusion. - Treatment combines cytoreductive surgery and platinum chemotherapy; BRCA testing is offered to every patient and their relatives as appropriate. - Advanced stage at diagnosis is the main reason ovarian cancer has the highest mortality of gynecologic cancers. ## Memory aid High-grade serous is born in the tube, carries a broken p53, and travels by peritoneal sea to the omentum. ## Test yourself Think of the answer, then tap the question to see it. ## Where does most high-grade serous carcinoma begin? In the fimbria of the fallopian tube, as serous tubal intraepithelial carcinoma with TP53 mutation. ## Why is CA-125 not used to screen the general population? It is neither sensitive enough for early disease nor specific, being raised by endometriosis, menstruation, pregnancy and other conditions. ## Which inherited mutations raise the risk of high-grade serous carcinoma most? Germline BRCA1 and BRCA2 mutations; Lynch syndrome raises the risk of other ovarian carcinoma types. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/high-grade-serous-carcinoma/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Elsewhere in DurgiPedia - [CA-125](https://durgical.com/en/biochemistry/topics/ca-125/) - [Oncogenes and tumour suppressor genes](https://durgical.com/en/biochemistry/topics/oncogenes-and-tumour-suppressor-genes/) - [Uterine tube](https://durgical.com/en/histology/uterine-tube/) ## Connections ## Related 9 - [Low-grade serous ovarian tumours](https://durgical.com/en/general-pathology/low-grade-serous-ovarian-tumours/) - [Diseases of the fallopian tube](https://durgical.com/en/general-pathology/diseases-of-the-fallopian-tube/) - [Ovarian tumours: classification](https://durgical.com/en/general-pathology/ovarian-tumours-classification/) - [High-grade endometrial cancers: serous, clear cell, carcinosarcoma](https://durgical.com/en/general-pathology/high-grade-endometrial-cancers-serous-clear-cell-carcinosarcoma/) - [Familial breast cancer: BRCA1, BRCA2 and others](https://durgical.com/en/general-pathology/familial-breast-cancer-brca1-brca2-and-others/) - [Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis](https://durgical.com/en/general-pathology/tumour-suppressor-genes-rb-tp53-apc-brca-and-the-two-hit-hypothesis/) - [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/) - [Pathways of spread and the usual metastatic sites](https://durgical.com/en/general-pathology/pathways-of-spread-and-the-usual-metastatic-sites/) - [Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum](https://durgical.com/en/general-pathology/genomic-instability-mismatch-repair-brca-and-xeroderma-pigmentosum/) ## Related conditions 5 - [Ovarian cancer](https://durgical.com/en/conditions/ovarian-cancer/) - [Hereditary breast and ovarian cancer syndrome (BRCA1/BRCA2)](https://durgical.com/en/conditions/hereditary-breast-and-ovarian-cancer-syndrome/) - [Lynch syndrome (hereditary non-polyposis colorectal cancer)](https://durgical.com/en/conditions/lynch-syndrome/) - [Pleural effusion](https://durgical.com/en/conditions/pleural-effusion/) - [Small bowel obstruction](https://durgical.com/en/conditions/small-bowel-obstruction/) [← All of general pathology](https://durgical.com/en/general-pathology/) Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given. Sources: [Epithelial Ovarian Cancer](https://www.ncbi.nlm.nih.gov/books/NBK567760/) (StatPearls (NCBI Bookshelf), 2026); [Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (PDQ®)–Health Professional Version](https://www.cancer.gov/types/ovarian/hp/ovarian-epithelial-treatment-pdq) (National Cancer Institute, 2026); [Ovarian cancer: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/ovarian-cancer/) (MedlinePlus, US National Library of Medicine, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/high-grade-serous-carcinoma/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/high-grade-serous-carcinoma/