Serous carcinomas represent the vast majority of primary ovarian malignant tumors (75–80 %) and are composed of columnar cells with cilia. They are subdivided into high-grade and low-grade serous carcinomas [1, 4].

High-grade serous carcinomas (HGSC) account for 85–90 % of serous carcinomas and 70 % of ovarian surface epithelial carcinomas. This is the ovarian carcinoma subtype that most people have in mind when talking about “ovarian cancer” and account for most deaths due to ovarian cancer. HGSC is a disease of elderly patients with a mean age of 64 years. This carcinoma is bilateral in 60 % of cases and is detected in advanced stage in more than 80 % of cases. HGSC is very large cystic and solid tumor with frequent areas of hemorrhage and necrosis. Morphologically, the cells form papillae, solid masses, or slit-like spaces with high-grade nuclear atypia and more than 12 mitoses per 10 high-power fields. Immunohistochemical findings show CK7, PAX8, and WT1 positivity, while CK20 is negative. HGSC show TP53 mutation in more than 96 % of cases with protein overexpression detected by immunohistochemical analyses. Transitional cell carcinoma is a rare variant of ovarian high-grade carcinoma (3 %) showing a papillary pattern seen in urothelial carcinomas. Most tumors show an admixture of HGSC. They have the same immunoprofile than HGSC; thus, the new WHO classification considers this type of carcinoma to be a variant of HGSC [1]. HGSC are genomically instable and aneuploid. Around 10 % of patients with HGSC have a germ line BRCA1 or BRCA2 mutations. Moreover, sporadic tumors show BRCAness phenotype with BRCA loss by somatic mutation (3 %) or promoter hypermethylation (11 %) of BRCA genes [5]. HGSC were thought to drive from surface epithelium without a known precursor according to incessant ovulation theory. However, pathological studies on prophylactic bilateral salpingo-oophorectomies in patients with germ line BRCA mutations have demonstrated occult intraepithelial serous carcinomas in 17 % of cases, mostly located in the fimbriated end of the fallopian tube [6]. This serous tubal intraepithelial carcinoma (STIC) showed the same TP53 mutation profile than invasive ovarian carcinoma in patients with BRCA mutation, indicating that it might represent the precursor of ovarian serous carcinomas. STIC was also detected in 60 % of sporadic ovarian and peritoneal carcinomas with the same TP53 mutational profile [7], in favor of a direct relationship between a noninvasive lesion in the fallopian tube and an invasive carcinoma in the ovary or the peritoneum.

Low-grade serous carcinoma (LGSC) is less common, representing 10–15 % of serous carcinomas and <5 % of all ovarian carcinomas. It occurs at a younger age than HGSC (mean 43 versus 64 years). It is associated with a serous borderline tumor (60 %) or represents the recurrent lesion seen after a diagnosis of borderline serous tumor (75 %). It is composed of papillae or micropapillae without nuclear atypia and with few mitoses. They are slow-growing tumors with 10-year survival rate of 50 % (overall survival 82 months) and a relative insensitivity to chemotherapy. LGSC’s immunoprofile is comparable to HGSC, but there is no TP53 mutation in these tumors, so there is no P53 overexpression by immunohistochemistry. LGSC are genetically stable and diploid tumors [8]. They show KRAS (mutation exon 12 % or 13 % in 19 % of cases), BRAF mutation V600E (5–38 %), or ERBB2 mutation (6 % of cases) that are mutually exclusive [9, 10]. It has however been shown that BRAF mutation (V600E) is more frequent in serous borderline tumors (28–48 %) as compared to LGSC (5–38 %) [11, 12].

Endometrioid carcinomas account for 10 % of all ovarian carcinomas and are mostly unilateral (60 %) solid masses with smooth outer surface. They are composed of glands resembling endometrial epithelium and may be associated (23–42 %) with ovarian or pelvic endometriosis. They show CK7, PAX8, hormone receptor (estrogen and progesterone) positivity and are WT1 and CK20 negative, helping in their distinction from serous and colonic carcinomas, respectively. They are graded into three grades according to the FIGO system, based on the presence of solid areas and the nuclear atypia. Grade 3 tumors tend to show TP53 mutations and may be difficult to distinguish from HGSC. Genotypically, endometrioid carcinomas show molecular abnormalities seen in their endometrial counterpart with CTNNB-1(48 %), PIK3CA (20 %), PTEN (20 %), and ARID1A (30 %) mutations. These tumors are the subtype of ovarian carcinomas most often seen in patients with LYNCH syndrome. Sporadic cases also show microsatellite instabilities (hypermethylation of MLH1 promoter) in a number of cases [13, 14]. The same mutations (PTEN and ARID1A) have been detected in the carcinoma and adjacent endometriosis cysts, indicating that endometriosis might be the precursor for endometrioid ovarian carcinomas.

Also, pure endometrioid mesenchymal and mixed epithelial/mesenchymal tumors, reminiscent of those seen in the uterine corpus, are seldom encountered in the ovary.

Mixed epithelial/mesenchymal tumors are biphasic tumors with a sarcomatous component and a benign or malignant epithelial component. The latter is used to subdivide these mixed tumors into adenosarcomas and carcinosarcomas (malignant mixed mullerian tumor/MMMT) (see also below), respectively. MMMT is a tumor of elderly women seen usually in patients over 60 years old. It is a very high-grade and aggressive neoplasm, often detected at a high stage with extra-ovarian spread and a median survival of less than 24 months [15]. The epithelial component is usually of high-grade serous, endometrioid, and/or clear cell carcinoma. The sarcomatous component may be homologous or heterologous with rhabdomyosarcoma, chondro- or osteo- or liposarcomatous elements.

Primary mucinous carcinomas are of intestinal type (containing goblet cells) and comprise only 2–3 % of ovarian carcinomas. They are unilateral, stage I (75–80 %), large (18–22 cm), and multicystic tumors filled with mucus. They often contain solid areas. Histologically, they are composed of cysts and glands of varying size, with a confluent pattern and back-to-back glands. Complex papillary architecture is also seen. The cells are tall, columnar, and stratified with basophilic cytoplasm containing mucin. Invasive mucinous carcinomas are subclassified into expansile and infiltrative type. The expansile-type mucinous carcinomas are stage I disease with a very good prognosis and are composed of confluent glands and a papillary pattern, seen mostly in younger patients. Infiltrative-type mucinous carcinomas have a destructive invasion pattern with desmoplastic stromal reaction and are more likely to have extra-ovarian spread [16, 17]. Mucinous adenocarcinomas may be graded according to their nuclear features [18]. On immunohistochemical study, ovarian mucinous carcinomas show diffuse CK7 positivity, while CK20 is usually less diffusely positive. Hormone receptors (estrogen and progesterone), WT1, and PAX8, are usually negative. Mucinous carcinomas arise from a mucinous borderline tumor. Thus, mucinous ovarian tumors show often a heterogeneous pattern with coexisting areas of mucinous cystadenoma, mucinous borderline tumor, and mucinous adenocarcinoma. Their diagnosis requires a thorough sampling with 2 blocks per cm of tumor.

The major difficulty in the diagnosis of mucinous ovarian tumor is their distinction from a metastasis from gastrointestinal or pancreatobiliary tract tumor. The bilaterality, a multinodular pattern in the ovary, a small size (usually less than 10 cm), ovarian surface involvement, and a massive disorganized pattern of invasion are characteristics seen in metastatic tumors. Appendicectomy and a clinical assessment of the gastrointestinal tract is useful in case of a mucinous carcinoma in the ovary.

Molecular biology in mucinous ovarian carcinoma shows KRAS mutations codons 12 and/or 13 in 68–86 % of cases. An identical mutational profile in different areas from benign (55 %) to borderline (73 %) and malignant (86 %) of the same tumor in 12/15 cases supports the morphological continuum of tumor progression in ovarian mucinous tumors [19]. Amplification of HER2 gene has been shown in 18 % of carcinomas and 6 % of borderline tumors. HER2 amplification and KRAS mutation are mutually exclusive (5.6 % show both abnormalities). HER2 amplification or KRAS mutation seem to be associated with decreased in recurrence and death when compared with double-negative tumors (34 %) [20]

This variant has been added to the new WHO classification 2014 [1], while it was described as endocervical mucinous carcinoma in the previous WHO classification 2003. Morphologically, this rare variant of ovarian carcinoma is composed of a mixture of serous- and endocervical-type mucinous cells with foci of endometrioid and squamous differentiation. The mean age is 45 years and it is seldom seen in elderly patients. This tumor is often associated with endometriosis that may represent its precursor. When stage I, the tumor has a good prognosis, while half of patients with advanced disease died because of their tumor [21]

Clear cell carcinomas (CCC) represent 6 % of all ovarian carcinomas in western countries but 15–25 % of carcinomas in Japan. They are most often diagnosed at low stage (I/II) (49 % versus 17 % for HGSC). They occur at a younger age than HGSC (55 years versus 64 years). Less than 10 % of cases are seen in the fourth decade, and most patients are 50–70 years old. They seem to have a worst prognosis with 5-year survival rate of 60 % versus 80 % for HGSC. However, when looking at stage I disease only, the prognosis is similar to HGSC at the same stage (85 % versus 86 % for HGSC). CCC show a low response to platinum/taxane therapy (11–45 %) [22].

The majority (99 %) of ovarian clear cell tumors are carcinomas and clear cell adenofibromas or borderline tumors are exceptional lesions (<1 %). The tumor is predominantly solid and unilateral (98 % of stage I cases), with a yellow cut surface. The tumor is composed of papillae with a hyalinized core and solid, tubulo-cystic, and glandular pattern. The cells are large with a clear or eosinophilic cytoplasm. The nuclei are pleomorphic, irregular, and hyperchromatic, but the mitotic index might be lower than what one could expect from the nuclear atypia.