**2.1 Pathology of ovarian high-grade serous carcinomas**

These tumours are large, exophytic and usually bilateral with solid and papillary growth patterns and fluid-containing cysts. Necrosis is not uncommon and extraovarian affected sites can be observed. Occasionally a small tumour nodule can be found at the distal part of the fallopian tube fimbria.

Microscopically, HGSCs are heterogeneous tumours displaying solid, papillary, glandular and/or cribriform architectural patterns, sometimes with slit-like spaces. Recently, two histotypes have been observed, the classic type and the SET type (solid pseudoendometrioid and transitional variant) [5]. Classic type HGSCs exhibit papillary, micropapillary and solid growth patterns. The neoplastic cells demonstrate large pleomorphic nuclei with prominent nucleoli, high mitotic activity (>5 mitoses/mm2 ) including atypical mitoses and presence of multinucleated cells. SET type HGSCs are characterised by solid sheets of neoplastic cells mimicking endometrioid and/or transitional cell carcinomas, sometimes with bizarre cytologic features. Occasionally a micropapillary pattern can be seen and areas with geographical necrosis can be also found. These tumours are associated with a high number of tumour infiltrating lymphocytes (TILs) [5, 26]. SET pattern is more commonly correlated with germline and/or somatic *BRCA1/2* mutations [26] and is more sensitive to chemotherapy and PARP inhibitors.

Based on *BRCA* mutation status, histomorphological patterns (classic vs. SET), STIC presence and clinical outcome, two categories of HGSC can be identified: (1) BRCA-mutated tumours exhibiting SET morphology, absence of STIC lesions, more common in young patients, more chemosensitive and responsive to PARP inhibitors with favourable prognosis and (2) tumours without *BRCA* genomic alterations displaying classic morphology, presence of STIC lesions, more common in old aged patients and less responsive to chemotherapy with unfavourable clinical outcome [26, 27].

The WHO 2020 classification introduces specific criteria for site assignment of HGSCs origin (fallopian tube, ovary, tubo-ovarian or peritoneal) **Table 1** [5]. According to these criteria, 80% of the cases are of tubal origin, whereas peritoneal


### **Table 1.**

*Criteria for assigning primary site in high grade serous carcinomas.*

origin should be considered only after careful exclusion of STIC and absence of ovarian involvement.
