Curr Oncol Rep (2014) 16:389

DOI 10.1007/s11912-014-0389-x

GYNECOLOGICAL CANCERS (N REED, SECTION EDITOR)

Mucinous Tumors of the Ovary: Current Thoughts

on Diagnosis and Management
Jubilee Brown & Michael Frumovitz

Published online: 29 April 2014

# Springer Science+Business Media New York 2014

Abstract Mucinous tumors of the ovary represent a spectrum or tumor reduction, and adjuvant chemotherapy for all but
of neoplastic disorders, including benign mucinous early stage disease, usually with a taxane and a platinum
cystadenoma, pseudomyxoma peritonei, mucinous tumors of agent. Clinical decision making and prognostic information
low malignant potential (borderline), and invasive mucinous have been determined by pooling aggregate data from all
ovarian carcinoma. These tumors are related closely to each epithelial cancer subtypes, including serous, mucinous,
other and are distinct from other histologic subtypes of epi- endometrioid, clear cell, Brenner, mixed, and undifferentiated
thelial ovarian neoplasms from a clinical, histologic, and histologies. Mucinous ovarian carcinoma (mOC), however,
molecular standpoint. A continuum appears to be present from represents less than five percent of all epithelial ovarian ma-
benign to borderline to malignant, which is different from lignancies, and, until recently, the subtleties of this histologic
other types of epithelial ovarian cancer. Mutational profiles subtype were lost in the larger framework of investigating
are also distinct, as KRAS mutations are common, but p53 epithelial ovarian cancers as a whole [1].
and BRCA mutations are infrequent. These characteristics Beginning in 2004, however, the profile of mOC began to
lead to specific biologic behavior and guide both clinical emerge as a separate entity, with a specific clinical presenta-
management and research efforts in patients with mucinous tion and biological behavioral pattern [2]. It appeared that
ovarian tumors. outcomes were worse when mOCs were compared with all
other epithelial ovarian cancers, leading to further research
Keywords Mucinous . Mucinous tumor . Gynecologic and a body of work that has shown mucinous tumors of the
cancers . Gynecologic cancer . Ovary . Carcinoma . Tumor . ovary to be quite distinct from other forms of epithelial ovar-
Borderline . Pseudomyxoma . Neoplasm . Mucinous ovarian ian neoplasms. This article will examine the epidemiology,
tumors . Oncology clinical presentation, biologic behavior, pathologic character-
istics, molecular signatures, and research efforts aimed at
better understanding and improving the outcomes for women
Introduction with mucinous ovarian tumors.

Historically, all epithelial ovarian cancers have been treated in

a similar fashion, with upfront debulking surgery, staging and/ Epidemiology

Mucinous tumors represent a spectrum of malignant behavior,

This article is part of the Topical Collection on Gynecological Cancers and have benign, borderline, and invasive histologic variants.
J. Brown (*) : M. Frumovitz Among benign ovarian neoplasms, mucinous cystadenomas
Department of Gynecologic Oncology and Reproductive Sciences, account for approximately 10-15 % of all cases [3, 4]. Bor-
The University of Texas M.D. Anderson Cancer Center, 1155
derline tumors, or tumors of low malignant potential (LMP
Herman Pressler Blvd, Unit 1362, P.O. Box 301439, Houston,
TX 77030-1439, USA tumors), may be more common than invasive primary mucin-
e-mail: jbbrown@mdanderson.org ous ovarian carcinomas, and comprise up to 67 % of mucin-
M. Frumovitz ous neoplasms that are not considered strictly benign [5].
e-mail: mfrumovitz@mdanderson.org Pathologic criteria are crucial in making the correct diagnosis,
389, Page 2 of 9 Curr Oncol Rep (2014) 16:389

and classification systems have been an area of debate, so Clinical Presentation

making these epidemiologic determinations has been difficult
[6]. The clinical features of mucinous ovarian neoplasms are dis-
Each year, the projected United States statistics for tinct from their other epithelial counterparts, and certain char-
incidence and mortality of specific malignancies are re- acteristics are typical for primary mucinous ovarian neo-
leased. For 2013, the projected incidence of ovarian plasms. These include symptoms at presentation, rate of
cancer is 22,240 cases and the projected mortality is bilaterality, stage at diagnosis, potential for lymphatic dissem-
14,030 cases. However, this comprises all ovarian malig- ination, and serum tumor markers; such characteristics have
nancies, including epithelial, germ cell, and sex cord- lead to specific surgical recommendations.
stromal tumors, and does not specify the subtype of
histology within the heading of ovarian cancer [7]. Esti-
mates of the frequency of primary mOC range from 6- Symptoms at Presentation
25 %, but a systematic review to exclude tumors of low
malignant potential and metastatic lesions from gastroin- Mucinous cystadenomas usually occur as a large,
testinal, pancreatic, or other gynecologic primary tumors multiloculated cystic mass with mucus-containing fluid [14].
suggests that the true percentage of ovarian carcinomas These tumors occur most commonly in women in their
represented by primary mucinous tumors is substantially twenties to forties, but occurrences in adolescent and even
less, at 2.4 % [8]. Another study by Shimada et al. [9] premenarchal girls, as well as postmenopausal patients, have
corroborated these findings, and a careful pathologic been documented [15]. The mean size at presentation is
review of 1,400 ovarian cancer cases resulted in reclas- 18 cm, and mucinous tumors can become extremely large
sification of most patients initially thought to have pri- and fill the entire abdominopelvic cavity, occasionally pre-
mary invasive mucinous ovarian cancer; this percentage senting with ureteral obstruction or abdominal compartment
declined from 16 % to 4.9 %, with the remainder syndrome [16–18]. The large size can itself sometimes sug-
reclassified as having mucinous intraepithelial carcinoma, gest a mucinous histology.
borderline tumor, or metastatic disease from a non- When determining the primary or metastatic nature of the
ovarian origin. mucinous neoplasm, size and laterality can suggest the tumor
This low frequency is confirmed by evaluating the percent- origin, as primary tumors tend to be larger and unilateral,
age enrollment on clinical trials represented by mucinous compared with metastatic lesions. The mean size of primary
carcinomas of the ovary. For example, in Gynecologic Oncol- mOCs has been documented as 16-20 cm (range, 5-48 cm),
ogy Group (GOG) trial 111 (cisplatin and cyclophosphamide compared with 11-12 cm (range, 2-24 cm) for metastatic
vs. cisplatin and paclitaxel), only 3.4 % of the patients enrolled cancers. This is not pathognomonic, however, as 32-48 % of
(14 of 410) had mucinous tumors [10]. In intergroup trial IV- metastatic tumors are over 10 cm [8, 19].
10 (cisplatin and cyclophosphamide vs. cisplatin and pacli-
taxel), 4.4 % of the patients enrolled (30 of 680) had mucinous
tumors [11]. Subsequently, GOG trial 132 (cisplatin vs. pac- Rate of Bilaterality
litaxel vs. cisplatin and paclitaxel) enrolled 2.6 % of the
patients (16 of 614) with mucinous tumors [12]. Finally, Most mucinous tumors are unilateral, especially when primar-
GOG trial 182 compared standard-of-care paclitaxel and ily ovarian in origin. A large retrospective series and a SEER
carboplatin to four other platinum-based regimens as adjuvant database analysis have both shown that 79 % of mucinous
chemotherapy in women with stage III or IVepithelial ovarian tumors are unilateral [16, 20]. In the SEER database analysis,
cancer. Of 4312 patients enrolled with primary epithelial 21.3 % of women with primary mOCs had bilateral involve-
ovarian cancer, only 1.6 % (71 of 4312) had primary mOC ment (355 of 1,665 women), significantly less than in serous
[13]. ovarian cancers, in which 57.5 % of women had bilateral
Despite the low percentage of patients with epithelial involvement (4,289 of 7,453 women). Similarly, borderline
ovarian cancer who have a primary mOC, the conclusions mucinous ovarian tumors were less likely bilateral (7 %) than
drawn from these randomized studies have been applied to their serous borderline counterparts (29.8 %) [20].
mOCs until recently. This phenomenon is problematic for When comparing primary versus metastatic mucinous car-
all rare tumors, as rare tumors are lumped together with cinomas, primary mOCs were much less likely to be bilateral
more common tumors regardless of real differences. While (0-17 %) than mucinous tumors metastatic to the ovary (75-
this would be acceptable if the clinical behavior and treat- 77 %) [8, 19, 21]. Based on these findings of large, unilateral
ment response mirrored more common histologies, they do tumors favoring a primary ovarian origin, Seidman et al., has
not, and should be studied separately and treated different- proposed an algorithm incorporating these two factors. In their
ly [1]. series, a unilateral tumor greater than 10 cm correctly
Curr Oncol Rep (2014) 16:389 Page 3 of 9, 389

predicted primary ovarian origin in 82 % of cases. In patients Surgical Recommendations

with bilateral tumors less than 10 cm, metastatic disease was
correctly predicted in 95 % of cases [8]. Others have since The gold standard for the treatment of any suspected ovarian
validated this approach [21]. mass includes intact removal of the involved adnexa with
intraoperative pathology evaluation [30–32]. This has histori-
cally implied laparotomy, total hysterectomy, bilateral salpingo-
Stage at Diagnosis oophorectomy, and staging procedure including lymphadenec-
tomy. There are many nuances to the appropriate surgical
In contrast to serous ovarian carcinomas, in which only 4 % of management of the patient with a mucinous ovarian tumor,
patients are stage I at diagnosis, 83 % of mOCs are stage I at and close inspection of the upper and lower gastrointestinal
the time of diagnosis [22]. Thus, only 17 % of patients with tract should always be performed in the event of a suspected
mOCs are stage II or higher. primary mOC, as primary tumors are relatively rare [32].
Since most mucinous tumors of the ovary are large, most
surgeons will perform an exploratory laparotomy with remov-
Potential for Lymphatic Dissemination al of the involved adnexa. If the patient is post-menopausal, a
total hysterectomy and bilateral salpingo-oophorectomy may
Multiple authors have confirmed that a mucinous tumor gross- be considered regardless of the histology. However, many
ly limited to the ovary will not have occult lymph node patients are premenopausal, and the unilateral nature of most
metastasis. Of 146 total patients in three series with borderline mucinous tumors, whether benign, borderline, or invasive
or invasive mOC that appeared to be confined to the ovary at primary ovarian cancers, allow fertility preservation with con-
the time of surgery, none had lymphatic metastases [23–25]. servation of the normal appearing uterus and contralateral
All of these patients underwent lymphadenectomy as part of ovary in apparent early stage disease [14, 32–35]. Since most
their staging procedures, and none were found to have lymph patients do have early stage disease, this is not an uncommon
node disease. In contrast, 10 % of patients with apparent stage situation.
I serous carcinoma of the ovary have been reported to have When the surgeon enters the abdomen, care should be
occult nodal metastasis at the time of diagnosis [26]. There- taken to remove the involved ovary intact without spillage
fore, it is not necessary to perform pelvic and/or para-aortic of the mucinous contents, as rupture of a stage I mOC may
lymphadenectomy as part of the staging procedure in patients increase its potential for recurrence [36]. Benign mucinous
with primary mOC grossly limited to the ovary [25]. ovarian cystadenomas are by definition confined to the ovary,
and no further procedure is required. While appendectomy
was previously performed for any ovarian tumor with mucin-
Tumor Markers ous histology, including benign lesions, current data support
not performing an appendectomy as long as the appendix
Carcinoembryonic antigen (CEA) is the most useful serum appears normal and there is no evidence of pseudomyxoma
tumor marker to identify mOC preoperatively and to follow peritonei [37].
the progress of a patient with mOC post-operatively. Though The abdomen and pelvis should be meticulously explored
it is widely used in the detection and surveillance of gastroin- and any abnormal area should be noted. If the tumor appears
testinal carcinomas, CEA is elevated in almost one third of all to be widespread, the surgeon should determine whether the
ovarian carcinomas. It is much more likely to be elevated in disseminated disease is resectable, either to a level of less than
mOCs than in nonmucinous ovarian carcinomas (88 % vs. one centimeter - historically considered “optimal” - or prefer-
19 %) [27, 28]. ably to no gross residual disease left at the completion of
Other biomarkers have been investigated as potentially surgery. If this is possible, then every effort should be made
useful in the differentiation of mucinous from other types of for maximal debulking surgery; widespread disease does man-
epithelial ovarian cancers. Immunoassay evaluation of 58 date removal of the contralateral ovary and the uterus. If total
serum biomarkers in patients with serous, mucinous, clear gross surgical resection is not possible, then consideration
cell, and endometrioid ovarian carcinomas revealed signifi- should be given to alleviating patient symptoms, e.g., bowel
cant differences in levels between serous and mucinous ovar- resection for an impending obstruction, and stopping the
ian carcinomas in ten biomarkers. While serous tumors had procedure in favor of chemotherapy [32, 38].
elevated CA125, follicle-stimulating hormone, luteinizing Intraoperative determination of the exact degree of patho-
hormone, and SMRP levels, mucinous tumors had higher logic abnormality is difficult, as these tumors are often quite
levels of CA72-4, matrix metalloproteinase-9, CD40L, large, intraoperative sectioning is by definition limited to a
insulin-like growth factor-binding protein-1, few areas of the tumor, and the differences between benign,
myeloperoxidase, and tissue plasminogen activator-1 [29]. borderline, and invasive carcinomas are subtle. Additionally,
389, Page 4 of 9 Curr Oncol Rep (2014) 16:389

the determination of a primary versus metastastic mucinous in hospital stay, earlier return to work, less pain, and less blood
tumor can be difficult [1, 39]. Therefore, the surgeon is often loss that characterize minimally invasive surgery [42]. Of
faced with making decisions about the extent of surgery with course, such procedures require a skilled minimally invasive
incomplete knowledge of the tumor histology. Since these surgeon, and if intraperitoneal spill is deemed likely, the
tumors are often early stage and unilateral, a patient in her surgeon should immediately convert to a laparotomy.
reproductive years with disease apparently confined to one
ovary can undergo fertility-sparing surgery with no adverse
effect on her prognosis [33–35]. Every patient with either
borderline or invasive components identified, however, Biologic Behavior
should undergo a staging procedure to exclude the possibility
of occult extraovarian disease, as this would change the prog- The biologic behavior of mucinous ovarian tumors depends
nosis and recommended adjuvant therapy. Staging in patients on the specific histologic variant and stage. Intraepithelial
with mucinous tumors includes a thorough evaluation of the (non-invasive) mOC, FIGO stage I, has a recurrence rate of
peritoneal cavity with sampling of any suspicious areas, pelvic only 5.8 % [36]. Patients with stage I invasive mOC have a 5-
washings, peritoneal biopsies, and infracolic omentectomy year survival rate of 91 %, whereas patients with advanced-
[32]. Sampling of the pelvic and para-aortic lymph nodes is stage tumor usually die of disease [16].
not warranted and should not be considered as part of the As a histologic group independent of stage, the prognosis
staging procedure, based on the zero incidence of nodal me- for primary mOCs is better than that of its serous counterparts,
tastases in these patients. Any enlarged lymph node, however, due in large part to the high frequency of mucinous tumors
should be sampled [25]. It should be noted that the need for being stage I at the time of diagnosis [22]. The average overall
staging in patients with borderline mucinous tumors is con- survival for over 6,000 women in the Swedish Family Center
troversial [40]; however, given the difficulty of definitively Database was just 34 months for patients with serous subtypes
excluding invasion at the time of intraoperative pathologic compared with 70 months for women with mucinous subtypes
evaluation and the substantial likelihood of a permanent diag- [43].
nosis being rendered as invasive disease, staging without When considered stage for stage, however, women with
lymph node sampling appears to be a low risk procedure with advanced stage mOCs do significantly worse than women
the potential to avoid another operation pending a final diag- with other histologic subtypes of advanced stage ovarian
nosis of invasive disease. cancer. In 2004, Hess et al., evaluated outcomes of stage III
As the use of minimally invasive surgery has increased and and IV patients with ovarian cancer who had undergone
the scope of indications has broadened, minimally invasive primary cytoreductive surgery followed by adjuvant therapy
surgery has been increasingly used for the management of with a platinum agent. The matched cohort included 27 pa-
patients with mucinous ovarian tumors, even when they are tients with mOC and 54 patients with non-mucinous ovarian
quite large. Multiple reports exist of the safe and feasible cancer (2:1 match). Histologic grade, stage, optimal vs. sub-
removal of mucinous tumors laparoscopically, with several optimal debulking status, chemotherapy regimen, and length
techniques reported to effect removal without spillage of the of follow-up were no different between groups. However, the
cyst contents [41, 42]. Morcellation in the peritoneal cavity or progression-free survival (PFS) for patients with mucinous
contamination of the peritoneal cavity and/or trocar sites ovarian cancer was 5.7 months, compared to 14.1 months
should be absolutely avoided. The mass, once detached, for patients with non-mucinous ovarian cancer (p<0.001).
should be placed into an intraperitoneal specimen bag, and Overall survival (OS) was also worse for patients with ad-
the edges of the bag drawn up through one abdominal inci- vanced stage mOC (12.0 months) compared with non-
sion, which can be enlarged. Once the mass is in this way mucinous ovarian cancer (36.7 months) (p<0.001) [2].
isolated from the skin, subcutaneous tissues, and peritoneal These observations have been supported by Winter et al.
cavity by its placement in the bag, it can be drained with a [44], who reviewed the data from six phase III trials of
large bore spinal needle attached to a syringe or with a suction adjuvant chemotherapy with cisplatin and paclitaxel conduct-
device without risking peritoneal contamination. Alternative- ed by the Gynecologic Oncology Group in women with stage
ly, a laparoscopic needle can be used to decompress a cyst, III epithelial ovarian cancer after primary debulking surgery,
which is thought to be benign, to allow its placement into a both optimal and suboptimal. Only 2 % of the 1,895 patients
laparoscopic specimen bag with subsequent removal as de- had mOC, but their PFS was 10.5 months compared to
scribed. This does risk spillage and should be used with 16.9 months for women with serous tumors, yielding a rela-
caution. Potential advantages to minimally invasive surgery tive risk of progression of 2.18 for women with mOC
include limiting the abdominal opening to several small inci- (p<0.001). The difference in OS was also significant, as
sions rather than the xiphoid to pubis incision often required women with mOC had a median OS of 14.8 months compared
for large mucinous neoplasms, with the concomitant decrease to 45.2 months for women with serous ovarian cancer,
Curr Oncol Rep (2014) 16:389 Page 5 of 9, 389

yielding a relative risk of death from mucinous cancer of 4.14

(p<0.001).
The reason for such poor relative outcomes appears to be
related to the frequency of platinum resistance in women with
mucinous ovarian cancers. As noted, patients with early stage
disease who do not require chemotherapy do well; conversely,
patients with advanced stage disease who require chemother-
apy in principle do relatively poorly [1]. Multiple authors have
shown mOCs to be platinum resistant. Shimada et al. [9]
found a lower response rate to platinum-based chemotherapy;
the response rate among 24 women with mOC was 12.5 %,
compared to 67.7 % among 189 women with serous ovarian Fig. 1 10x H&E image showing intraepithelial carcinoma with stratified
carcinoma. Additionally, Pectasides et al. [45] performed a 1:2 atypical nuclei with increased mitoses. Cytoplasm has decreased mucin.
matched study among women with advanced stage ovarian (Credit: Elizabeth Euscher, MD)
cancer who had received platinum-based chemotherapy with-
in the Hellenic Cooperative Oncology Group. The response parenchyma (see Fig. 2). The infiltrative pattern demonstrates
rate for 47 women with primary mOC was 38.5 % compared small glands, nests or individual cells infiltrating the stroma,
with 70 % for 94 women with serous histology. Survival and tends to be more aggressive in clinical behavior than the
differences were not significant. expansile type (see Fig. 3) [36, 47].
Platinum resistance appears to extend to the recurrent set- The distinction between these entities is subtle, and within
ting. In a retrospective review of recurrent, platinum-sensitive one neoplasm, variations in degree of malignancy can be seen.
epithelial ovarian carcinomas, patients with mucinous histol- Benign cystadenomas, LMP tumors, and invasive mucinous
ogy were less likely to respond to platinum-based regimens carcinomas can coexist in close proximity (see Fig. 4). This
compared to patients with non-mucinous histology (36 % vs. may suggest a continuum from benign to borderline to inva-
63 %, p=0.04). Similarly, PFS after recurrence was 4.5 months sive disease. Practically, coexistence of these forms may make
for patients with mucinous histology, compared to 8 months frozen section diagnosis difficult, as only a limited number of
for patients with non-mucinous histology (p=0.03); OS was sections can be evaluated intraoperatively, and these tumors
17.9 months for the patients with mucinous carcinomas, com- may be quite large [1, 6]. Additionally, this may contribute to
pared to 28.8 months for patients with non-mucinous carci- inaccuracies in the diagnosis, as a small focus of invasive
nomas (p=0.003) [46]. carcinoma may be overlooked amid a large neoplasm [6].
The determination between primary mOC and mucinous
tumors metastatic from other sites may be difficult. The most
Pathologic Characteristics common primary sites for mucinous carcinomas metastatic to
the ovary are gastrointestinal, pancreas, cervix, breast, and
Ovarian mucinous neoplasms consist of borderline tumors uterus [8]. Certain histological features can favor the diagnosis
(tumors of low malignant potential, or LMP tumors), of primary mucinous carcinoma over metastatic disease, but
intraepithelial (non- invasive) carcinoma, and invasive carci- discordant or overlapping features may prevent a definitive
noma. The World Health Organization criteria for the diagno- diagnosis. Primary mOC is favored by coexistent LMP and
sis of intestinal-type mucinous borderline tumor include the benign components, an expansile, or confluent, pattern of
following elements: tumors contain cystic spaces lined by
gastrointestinal-type mucinous epithelium with stratification
and may form filiform papillae with at least minimal stromal
support; nuclei are slightly larger than those seen in
cystadenomas; mitotic activity is present; goblet cells and
sometimes Paneth cells are present, but stromal invasion is
absent [6]. Cases with marked cytologic atypia in the absence
of stromal invasion represent intraepithelial carcinoma (see
Fig. 1) [1]. The diagnosis of invasive mucinous carcinoma
requires stromal invasion measuring more than 5 mm or more
than 10 mm2 is detected. Invasive mucinous carcinoma is
subdivided into expansile (confluent) type and infiltrative type
[1]. The expansile, or confluent, type has a confluent glandular Fig. 2 4x H&E image with expansile invasion on permanent section.
growth pattern without intervening normal ovarian (Credit: Elizabeth Euscher, MD)
389, Page 6 of 9 Curr Oncol Rep (2014) 16:389

adenocarcinoma metastatic to the ovary and primary mucin-

ous adenocarcinoma since both are usually progesterone re-
ceptor negative and estrogen receptor variable (either nega-
tive, weak and diffuse, or strong and focally positive). The
latter have weak/diffuse or strong/focal staining [48]. Addi-
tionally, the presence of mesothelin, fascin, and prostate stem
cell antigen (PSCA) favor a pancreatic primary metastatic to
the ovary, while the presence of Dpc4 expression favors an
ovarian primary [49]. When differentiating mucinous ovarian
primary cancers from breast metastases, CK7 and CK20 will
usually be positive for ovarian primaries, while only CK7 will
Fig. 3 10x H&E image with infiltrative invasion; small clusters of cells be positive in metastatic breast malignancies; breast cancers
float in irregular cleft-like spaces. (Credit: Elizabeth Euscher, MD) will usually be positive for estrogen receptors and gross cystic
disease fluid protein (GCDFP)-15, but mucinous ovarian pri-
invasion, and other ovarian pathology, such as a mural nodule, maries will not [50].
Brenner tumor, or teratoma. Metastatic disease is supported by
the following findings: a prominent desmoplastic response,
nodular pattern of invasion, small clusters of tumor cells
Molecular Signatures
within corpora lutea or albicantia, numerous pools of mucin
dissecting the ovarian stroma (i.e., pseudomyxoma ovarii)
Certain genetic mutations have been identified which charac-
without a coexistent ovarian teratoma, extensive signet-ring
terize mOCs. KRAS mutations occur within the RAS family
cell pattern, ovarian surface involvement, vascular invasion, of G proteins, which signal cell division; such mutations
hilar involvement, and an extensive infiltrative pattern of
stimulate cell growth and are significantly increased in mu-
invasion [14, 19].
cinous ovarian tumors, including mucinous cystadenomas,
Immunohistochemistry may also be useful in determining LMP tumors, and invasive adenocarcinomas [51–53].
primary versus metastatic mOC. Primary mOCs often dem-
BRCA1 and BRCA2 mutations, genetic alterations in specific
onstrate CK7 and CK20 positivity, while colorectal primaries
tumor suppressor genes that occur in many hereditary and
are usually positive only for CK20 [1]. Colorectal cancers also some sporadic cases of breast and ovarian cancer, do not
express racemase and β-catenin but primary mOCs do not. In
appear to be present in most cases of mOCs. Among patients
situ hybridization for HPV may be useful in confirming an
with known BRCA mutations, only 2 % are of mucinous
endocervical primary mucinous carcinoma metastatic to the histology [54, 55]. Mutations in the p53 tumor suppressor
ovary. Diffuse immunostaining of P16 may suggest
gene are less frequent in mOCs than serous ovarian cancers;
endocervical origin, but this is only useful in cases of well
mutations in p53 have been found in almost 60 % of serous
differentiated adenocarcinoma, with the caveat that high grade tumors but only 16 % of mucinous tumors [56]. Clear sepa-
ovarian mucinous or endometrioid adenocarcinomas can dem-
ration has also been seen in the gene expression profiling
onstrate p16 positivity [1]. Estrogen and progesterone recep-
between serous and mOCs [57, 58].
tors do not help distinguish between endocervical
Immunohistochemical studies have been used to character-
ize mucinous ovarian tumors. Mucinous tumors are more
likely than serous tumors to express E-cadherin (62 % vs.
4 %, p<0.001) and less likely to stain positive for N-cadherin
(8 % vs. 68 %, p<0.001) [59]. Other differences have been
identified in the matrix metalloproteinases, p53, cadherin,
CA125, and WT-1, among others [60–62]. Together, such
molecular signatures suggest that mOCs are a separate entity
with a pathogenesis different from other histologic subtypes of
ovarian cancer.

Research Efforts
Fig. 4 20x H&E image (same focus as the 10x); higher power view
showing prominent nucleoli and coarse chromatin. Atypia similar to the
intraepithelial carcinoma in the glands directly above the focus of inva- Since the pathogenesis and biologic behavior differ substan-
sion. (Credit: Elizabeth Euscher, MD) tially from non-mucinous histologies of ovarian cancer,
Curr Oncol Rep (2014) 16:389 Page 7 of 9, 389

investigators worldwide have started to propose clinical trials Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
that are specific to mOCs.
of the authors.
In the preclinical arena, multiple primary mOC cell lines
have been treated with various cytotoxic chemotherapeutic
agents, alone and in combination. As might be expected, all
five cell lines were resistant to cisplatinum, carboplatin, and
taxanes administered as single agents. Some cell lines showed References
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