Discriminating POMNs from MMTs is one of the problematic issues facing the pathologist in their practice and it is a crucial decision as respective management is totally different. Patients with POMNs have a better prognosis and usually do not require adjuvant chemotherapy [18,19,20], whereas patients with MMTs involving the ovary have a poor prognosis and may need systemic treatment.
The most popular panels used to discriminate POMNs from MMTs are CK7, CK20 and CDX2. CK7 was positive in 86% of POMNs, while 33% were positive for CK20 and CDX [6]. Vang et al. [4] showed that CK20 can be expressed in 83% of POMNs in both focal and diffuse patterns, while CDX2 was expressed in 40% of the cases. However, colonic carcinoma and appendiceal tumors are positive for CK7 in about 35% [21] and 31% of cases [12], respectively. CK20 is positive in colonic cancer in 66%–92% of cases [4]. Our study showed similar results: CK7 was the most sensitive and the second-most specific immunohistochemical marker for POMNs, with a sensitivity of 78.0% and a specificity of 87.5%. In contrast, CK7 expression in colonic and appendiceal tumors had 12.5% sensitivity and 22.0% specificity. CK20 was positive in 87.5% of colonic and appendiceal tumors and in 24.0% of POMNs.
CDX2 is typically expressed in a strong diffuse pattern in colorectal and appendiceal adenocarcinomas, with sensitivity of 100% [15], in contrast to their analogs in the upper GI and ovaries, where it is expressed focally. Vang et al. [7] showed that 40% of POMNs were positive for CDX2, while Strickland et al. [15] showed that 50% of ovarian mucinous adenocarcinomas were positive for CDX2. Furthermore, combined use of CDX2 with CK7 can help in this differential diagnosis, as 60% of the primary ovarian mucinous tumors are (CK7+, CDX2−, in contrast to mucinous adenocarcinomas of the lower gastrointestinal tract, where 83% of cases are (CK7−, CDX2+) [4, 7, 22]. In our study, CDX2 was positive in 14.0% of POMNs, and comparatively, in 88.0% of colonic and appendiceal tumors. CDX2 was the most sensitive marker (91.7%) for colonic and appendiceal tumors.
SATB2 is expressed by lower gastrointestinal normal epithelium, as well as by primary and metastatic CRC [13, 14]. In CRC, sensitivity for SATB2 is analogous with CK20 and CDX2, for which rates of positivity range from 85%–93% [13, 14, 23]. Staining for SATB2 is useful in ovarian tumors with morphologic evidence of intestinal differentiation, or with expression of CDX2 or CK20, as most cases (98%) are typically negative [24]. In our study, SATB2 was positive in 2.0% of POMNs compared to in 52.8% of colonic and appendiceal tumors. Appendiceal tumors showed more positivity for SATB2 (77.8%) in comparison to colonic tumors (49.2%), making it a useful maker in discriminating POMNs from appendiceal and colonic tumors. The percentage of positivity in our study was lower than in the literature and this might be due to the use of a different antibody.
PAX8 is a sensitive and specific marker for tumors of Müllerian origin [8] but it is less commonly expressed in ovarian mucinous tumors, with a range therein from 0% to 70% [6, 8, 10,11,12]. This discrepancy in the results is most likely due to the use of anti-PAX8 rabbit polyclonal antibody instead of using the monoclonal anti-PAX8 antibody (mAb) [10, 11]. Recent studies by Hu et al. [11] and Strickland et al. [12] showed that PAX8 (mAb) is expressed in 53% and 70% of POMNs, respectively. Yet, Chu et al. [22] found that PAX8 positivity was mainly seen in mucinous tumors from the female genital tract. That said, PAX8 is uniformly negative in GITs as shown by Peiguo et al. [22]. Similarly, in our study, all colonic and appendiceal tumors were negative for PAX8. However, PAX8 was positive in 32.0% of POMNs in our study, which is lower than that reported by Hu et al. [11] and Strickland et al. [12].
In conclusion, the most sensitive marker for POMNS is CK7 (78.0%), whereas the most specific is PAX8 (100%). Regarding mucinous tumors arising from the colon and appendix, the most sensitive marker is CDX2 (91.7%), while the most specific is SATB2 (98.0%). Therefore, adding PAX8 and SATB2 to the panel of immunostains for differentiating mucinous tumors will be of great benefit. If the tumor is positive for PAX8, it is most likely to be of ovarian origin. On the other hand, positivity for SATB2 is most likely of colonic/appendiceal tumors.