Around 80% of mucinous carcinomas of the ovary are metastatic, with approximately 80% of primary tumors being stage I. The most frequent primary sites that metastasize to the ovary are: 45% from the gastrointestinal tract, 20% from the pancreas, 18% from the cervix and endometrium, and 8% from the breast [17,18]. It is agreed that diagnosing primary MOC requires careful pathological assessment as it is histologically very similar to other mucinous carcinomas, especially colorectal carcinoma (CRC). Recognizing the microscopic features and understanding the immunohistochemistry (IHC) profile of MOC are essential to reach a definitive diagnosis, which results in delivering proper treatment and an accurate prognosis.

MOC is usually a heterogeneous tumor. It encompasses benign, borderline, and carcinoma components, which indicate a stepwise progression to carcinoma. The diagnosis of an invasive carcinoma requires the detection of stromal invasion of more than 5 mm or more than 10 mm². Invasion less than these measurements is classified as “micro-invasion” with a borderline mucinous tumor. MOC is typically the intestinal type, but the endocervical type may develop infrequently [19,20,21]. According to the growth and invasion pattern, Lee and Schully classified MOC into expansile and infiltrative subtypes [22]. The expansile subtype has no destructive stromal invasion, but exhibits confluent or complex malignant glands (back to back glands) with or without minimal intervening stroma exceeding a 10 mm² area or >3 mm each of two linear dimensions. The infiltrative type has stromal invasion in the form of glands, cell clusters, or individual cells, unsystematically infiltrating the stroma and often associated with a desmoplastic stromal reaction [20,21,22,23]. In 2014, the World Health Organization (WHO) adopted Lee and Schully’s classification for MOC.

Certain histological features are suggestive for metastatic mucinous carcinoma. In general, mucinous carcinomas are categorized into cystic and colloid type, based on intracellular or extracellular mucin localization. Ovarian and pancreatic cystic mucinous carcinomas contain a large amount of intracellular mucin (>50%) in at least 90% of tumor cells. On the other hand, colloid mucinous carcinomas arising from the gastrointestinal tract, lung, breast, and skin are associated with abundant extracellular mucin accounting for 50% or more tumor volume [6]. Seidman et al. proposed an algorithm based on tumor size and laterality to distinguish between MOC and metastatic mucinous carcinoma. Tumors that were ≥10 cm and unilateral were primary MOCs 82% of the time. Unilateral tumors <10 cm were metastatic 87% of the time. Bilateral tumors <10 cm were metastatic in 92% of cases and when bilateral and ≥10 cm they were metastatic in 95% of cases [4,24]. Therefore, the possibility of metastatic mucinous carcinoma should always be considered, even in the case of a unilateral tumor. Moreover, features that suggest that metastatic disease is more likely are [25,26,27]:

• Bilateral disease;
• Ovarian surface involvement;
• Extracellular mucin localization;
• Destructive stromal invasion;
• Nodular growth pattern;
• Hilar involvement;
• Vascular invasion;
• Signet ring cells;
• Extensive necrosis.

In addition to the microscopic features, IHC staining plays an essential role in distinguishing MOC from other possible diagnoses. MOC typically shares positive IHC patterns for CK20, CEA, Ca19-9, and CDX2 with metastatic CRC. Nevertheless, CK7 is mostly positive in MOC and negative in CRC. Table 1 summarizes the IHC profile for MOC and metastatic mucinous carcinoma [11,19,28,29]. The standard IHC profile for MOC is CK7 +, CK20 +/−, CDX2 +/−, PAX8 −, WT1 −, ER −, PR −, and SATB2 – [29].