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Mucinous tumors represent a spectrum within ovarian tumors, comprising 15% of all ovarian neoplasms. They are less common than their serous counterparts. There are some interesting associations with these tumors and Peutz-Jeghers syndrome. In addition, there may be co-existing Brenner tumors or a dermoid cyst, usually with benign mucinous cystadenomas.

Like serous tumors of the ovary, the critical question which must be answered by the pathologist is whether stromal invasion is present, making the tumor a carcinoma. Most investigators suggest that invasion should be diagnosed only in the presence of the following:

Nuclei of the lining cells are stratified to four layers or more
Cribriform pattern or presence of stroma-free papillae

These criteria are applicable only for intestinal type borderline tumors. Mullerian type tumors, on the other hand, may show cellular stratification up to 20 layers.

Benign cystadenomas 3-5th decades 85%
Borderline malignancy 4-7th decades 6-10%
Cystadenocarcinomas 4-7th decades 5-10%

Associated with all mucinous tumors are occasional stromal nodules usually composed of a high grade carcinoma. Occasional, these mural nodules may resemble a sarcoma. These nodules are sharply demarcated. In spite of the ominous histologic appearance, the prognosis for these patients is unchanged from the primary tumor prognosis.

The pathologist must differentiate these tumors from endometrioid carcinomas. Since squamous differentiation is very rare in mucinous tumors, this feature would favor an endometrioid carcinoma. In addition, some metastatic adenocarcinomas to the ovary may be difficult to exclude. Features favoring a metastasis inlcude metastatic implants on the surface of the ovary and prominent vascular invasion. There may be a mixture of mucinous epithelial types and more goblet cells in primary mucinous tumors.


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Ovarian Mucinous Tumors Associated With Mature Cystic Teratomas: Morphologic and Immunohistochemical Analysis Identifies a Subset of Potential Teratomatous Origin That Shares Features of Lower Gastrointestinal Tract Mucinous Tumors More Commonly Encountered as Secondary Tumors in the Ovary.

*Departments of Pathology and Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD †PhenoPath Laboratories, Seattle, WA §Department of Pathology, Virginia Mason Medical Center, Seattle, WA ‡Department of GYN and Breast Pathology, AFIP, Washington, DC ∥Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC.


Am J Surg Pathol. 2007 Jun;31(6):854-869. Abstract quote

Most primary ovarian mucinous tumors are of surface epithelial-stromal origin and exhibit diffuse expression of cytokeratin 7 (CK7) combined with variable expression of cytokeratin 20 (CK20); this immunoprofile distinguishes them from most lower gastrointestinal tract tumors secondarily involving the ovaries.

The uncommon ovarian mucinous tumors of germ cell (teratomatous) origin have not been extensively evaluated to determine the utility of these markers and other markers of intestinal differentiation for distinguishing these tumors from metastatic gastrointestinal tract mucinous tumors. Immunohistochemical expression of CK7, CK20, CDX2, and villin was assessed in 44 ovarian mucinous tumors associated with a mature cystic teratoma.

All cases lacked evidence of a nonovarian primary mucinous tumor. All mucinous tumors were unilateral; 6 cases had bilateral teratomas. All tumors displayed gastrointestinal-type mucinous differentiation, with epithelium that was commonly goblet cell-rich or hypermucinous; 21 were associated with pseudomyxoma ovarii and 3 of these had pseudomyxoma peritonei. Tumor architecture ranged from purely cystadenomatous (n=24), to proliferative (n=13), to carcinomatous (n=6); some tumors had admixtures of these patterns. One tumor had a goblet cell carcinoidlike pattern with pseudomyxoma ovarii. Three carcinomas had a signet ring cell component. Cystadenomatous tumors without pseudomyxoma ovarii (n=15) exhibited all possible CK7/CK20 coordinate expression profiles with nearly equal frequency. All proliferative tumors without pseudomyxoma ovarii (n=8) expressed CK7, most often in combination with CK20 expression. All cystadenomatous and proliferative tumors with pseudomyxoma ovarii (n=9 and n=5) were CK7-/CK20+. All carcinomatous tumors had pseudomyxoma ovarii; 3 were CK7-/CK20+, 2 were CK7+/CK20+, and 1 was CK7+/CK20-. The presence of pseudomyxoma ovarii was significantly associated with a CK7-/CK20+ profile (86% with pseudomyxoma ovarii vs. 13% without, P<0.0001), CDX2 positivity (79% vs. 0%, P<0.0001), and villin positivity (57% vs. 5%, P=0.0009). A subset of mucinous tumors associated with mature cystic teratomas exhibiting morphologic and immunohistochemical features of lower intestinal tract-type mucinous tumors may be teratomatous in origin. In practice, the more common diagnosis of secondary involvement by a lower intestinal tract mucinous tumor should be addressed in the pathology report and in subsequent clinical evaluation; interpretation as a true primary ovarian mucinous tumor of teratomatous origin can be considered as an alternative diagnosis when evaluation and follow-up fail to identify a nonovarian source of the mucinous tumor.

Those tumors having CK7 expression with or without CK20 expression may be derived from upper gastrointestinal tract-type or sinonasal-type teratomatous elements but could be independent tumors of surface epithelial-stromal origin.


Heterogeneous genetic alterations in ovarian mucinous tumors: Application and usefulness of laser capture microdissection

Yukio Takeshima, MD
Vishwa Jeet Amatya, MBBS
Yutaka Daimaru, MD
Fumio Nakayori, BS
Tomohiro Nakano, CT
Kouki Inai

Hum Pathol 32:1203-1208. Abstract quote

Histologic observation of ovarian mucinous tumors suggests that there is a multistep transition through the accumulation of genetic alterations.

We analyzed loss of heterozygosity (LOH) and replication error (RER) on TP53 and D17S855 as well as K-ras point mutations of the heterogeneous histologic areas of the same tumor in 26 cases of ovarian mucinous tumor. The laser capture microdissection (LCM) technique has been applied to the study of K-ras point mutation in 10 cases. As for genetic alterations for LOH or RER on TP53 and D17S855, 2 (1 borderline tumor and 1 carcinoma) of 14 cases and 4 (1 borderline tumor and 3 carcinomas) of 12 cases, respectively, showed genetic heterogeneities in different histologic areas. Six (2 borderline tumors and 4 carcinomas) of 18 cases showed heterogeneity of K-ras point mutation in the different histologic areas of the same tumor, and 5 (1 cystadenoma with Brenner tumor component, 2 borderline tumors, and 2 carcinomas) of 10 cases showed heterogeneous K-ras mutation pattern in the same tumor when the LCM technique was used. Atypical areas tended to show K-ras point mutations frequently. Out of 3 cases of mixed mucinous cystadenoma and Brenner tumor, 1 case showed K-ras point mutation in the Brenner tumor area but not in the area of mucinous cystadenoma.

These preliminary results suggest that a subset of ovarian mucinous tumors occur through multistep carcinogenesis and show that LCM is useful for molecular pathologic studies.


Benign cystadenomas

Multilocular and may grow to 30 cm or more
Thin walls with thick to watery mucinous fluid
Bilateral <5%

Epithelial lining resembles endocervical epithelium and less commonly intestinal epithelium with goblet cells
Borderline malignancy Papillae with solid areas
Necrosis and hemorrhage
Mullerian type tumors are usually unilocular
Bilateral 5-10%

Two histologic types:

Mullerian (Endocervical)-Papillae resembling serous borderline tumors with endocervical lining
May have extensive cellular stratification
Extensive acute inflammation

Intestinal-85-90% of tumors
Papillae uncommon and if present tend to be filiform and branching
Nuclear stratification usually less than 4 layers

Cystadenocarcinomas Papillae with solid areas
Necrosis and hemorrhage
Bilateral 5-10% but mullerian type tumors are more often bilateral than intestinal type (40% vs 6%)

May vary from solid to cystic areas and mullerian or intestinal differentiation usually cannot be discerned

Invasion into the underlying stroma


Endocervical-like Mucinous Borderline Tumors of the Ovary: A Clinicopathologic Analysis of 31 Cases.

Rodriguez IM, Irving JA, Prat J.

Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
Am J Surg Pathol. 2004 Oct;28(10):1311-8. Abstract quote  

Ovarian mucinous borderline tumors are divided into two morphologic groups: endocervical-like and intestinal type, the latter comprising the majority of cases.

Thirty-one endocervical-like ovarian mucinous borderline tumors (ELMBTs) were reviewed and evaluated for the presence of intraepithelial carcinoma and microinvasion. Intraepithelial carcinoma was identified in 13% and stromal microinvasion in 23% of cases. All but 1 patient were stage I. Follow-up information was available for 21 patients; all were alive with no evidence of disease at a mean follow-up interval of 5.7 years. Six of 8 patients with ELMBT containing foci of microinvasion and/or intraepithelial carcinoma and for whom follow-up was available were alive with no evidence of disease at a mean follow-up interval of 6.6 years.

These results indicate that ELMBTs, specifically those exhibiting intraepithelial carcinoma and microinvasion, are tumors associated with an excellent prognosis. The frequency of occurrence and criteria for the diagnosis of intraepithelial carcinoma and microinvasion in ELMBT are discussed.

Mucinous Tumors of the Ovary A Clinicopathologic Study of 196 Borderline Tumors (of Intestinal Type) and Carcinomas, Including an Evaluation of 11 Cases With `Pseudomyxoma Peritonei'

Kenneth R. Lee, M.D.; Robert E. Scully, M.D.

From the Department of Pathology, Brigham and Women's Hospital, and the James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Boston, Massachusetts, U.S.A.

Am J Surg Pathol 2000;24:1447-1464 Abstract quote

Mucinous ovarian neoplasms other than cystadenomas and adenofibromas have been classified as either borderline tumors or carcinomas for many years. Borderline tumors have been subdivided more recently into endocervical-like (mullerian) and intestinal forms. Such a distinction is rarely made in the mucinous carcinoma category. We did not encounter a pure endocervical-like carcinoma in the present series. Criteria for distinguishing an intestinal-type mucinous borderline tumor from a mucinous carcinoma have been controversial.

In this study of 164 mucinous borderline tumors of intestinal type and 32 mucinous carcinomas, the former were further subdivided into 74 cases with epithelial atypia only and 90 with focal intraepithelial carcinoma.

Of the 67 stage I tumors in the borderline (with atypia) category, all 49 with follow-up data were clinically benign; in the seven cases that had been designated stage III, the intraoperative appearance was that of ``pseudomyxoma peritonei,'' which was fatal in four cases. Most of these tumors, however, were probably metastatic to the ovary rather than truly primary borderline tumors, although failure to examine the appendix in six cases compromised their interpretation.

All 90 mucinous borderline tumors that had foci of intraepithelial carcinoma were recorded as stage I, but two of the 69 patients with follow-up data (3%) had fatal recurrences. Both of these tumors were incompletely staged, however, and one had ruptured intraoperatively. Thirty-two invasive carcinomas were subdivided into 12 expansile and 20 infiltrative subtypes; within the latter category seven tumors were only microinvasive. All 12 carcinomas with only expansile invasion were stage I; none of the 10 with follow-up data recurred. All seven microinvasive infiltrative carcinomas were stage I; none of the five with follow-up data recurred. One of five patients with stage I infiltrative carcinomas that were more than microinvasive and were adequately followed had a fatal recurrence, but staging had been incomplete in that case. Seven of the remaining eight infiltrative carcinomas were higher than stage I; five of the six (83%) with follow-up data persisted or recurred and were fatal.

Considering all stages, increasing tumor grade in the carcinoma category correlated with an unfavorable outcome. However, grade did not influence prognosis in stage I carcinomas. Among 13 stage I cases in all categories with either preoperative or intraoperative tumor rupture and follow-up data, one recurred, a tumor in the borderline with intraepithelial carcinoma category. ``Pseudomyxoma peritonei'' is an ill-defined term and should not be used as a pathologic diagnosis.

The presence of mucin in the abdominal cavity requires careful histologic evaluation to characterize it for prognostic purposes. Adequate and sometimes extensive sampling of mucinous ovarian tumors, the appendix and the peritoneum in cases of ``pseudomyxoma peritonei'' is necessary to achieve an accurate diagnosis and prognosis.


Squamous predominance in mixed-epithelial papillary cystadenomas of borderline malignancy of mullerian type arising in endometriotic cysts: a study of four cases.

Nagai Y, Kishimoto T, Nikaido T, Nishihara K, Matsumoto T, Suzuki C, Ogishima T, Kuwahara Y, Hurukata Y, Mizunuma M, Nakata Y, Ishikura H.


Am J Surg Pathol 2003 Feb;27(2):242-7 Abstract quote

Mixed-epithelial papillary cystadenoma of borderline malignancy of mullerian type (MEBMM) is composed of a mixture of mullerian epithelial types, such as mucinous, serous, endometrioid, and squamous.

Four cases of MEBMM with squamous overgrowth (MEBMMSO) were reviewed. The patients' median age was 56 years, and all cases were unilateral. The clinical stages were Ia (two cases), Ic (one case), and IV based on the presence of tumor cells in pleural fluid (one case). No recurrence was seen in three of the cases. In one of those three cases, there was no recurrence after undergoing surgery only; in the other two of those three cases, there was no recurrence after undergoing surgery and receiving postoperative chemotherapy. In the single case that was at stage IV at initial presentation, a recurrent MEBMMSO nodule was found at a second look 17 months after the initial surgery.

In terms of gross findings, all of the tumors were cystic with intracystic papillary fronds. In addition, old endometriotic lesions lined the cysts. The tumors were mainly composed of a proliferation of squamous-type epithelium, with minor foci containing a mixture of other mullerian-type epithelia, especially mucinous. Intraepithelial infiltration by neutrophilic leukocytes was prominent. The differential diagnosis of MEBMMSO includes proliferating Brenner tumors.


Sarcoma-Like Mural Nodules in Mucinous Cystic Tumors of the Ovary Revisited: A Clinicopathologic Analysis of 10 Additional Cases
Sílvia Bagué, M.D.; Ingrid M. Rodríguez, M.D.; Jaime Prat, M.D., F.R.C.Path.

Am J Surg Pathol 2002; 26(11):1467-1476 Abstract quote

Ten mucinous cystic ovarian tumors that contained sarcoma-like mural nodules are described. The nodules were studied by conventional and immunohistochemical methods.

The sarcoma-like mural nodules occurred predominantly in middle-aged women, were multiple and sharply demarcated from the adjacent mucinous tumor, had small size, and exhibited a heterogeneous cell population. Distinction of these lesions from true sarcomatous nodules and foci of anaplastic carcinoma is important because of the worse prognosis of the two latter tumors compared with the favorable behavior of the sarcoma-like mural nodules.

Six of the eight patients with follow-up information were alive and clinically free of recurrence at a mean follow-up interval of 12 years. Two patients died of other causes (thyroid and breast carcinomas).

The nature of the nodules is not clear. Sarcoma-like mural nodules probably represent a reactive and self-limited phenomenon within a neoplasia. Their coexpression of vimentin and cytokeratins is consistent with an origin from submesothelial mesenchymal cells, which undergo partial transformation into epithelial cells.


Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: atypical proliferative (borderline) tumors, intraepithelial, microinvasive, and invasive carcinomas.

Shappell HW, Riopel MA, Smith Sehdev AE, Ronnett BM, Kurman RJ.

Am J Surg Pathol 2002 Dec;26(12):1529-41 Abstract quote

Ovarian endocervical-type (mullerian) mucinous tumors and tumors composed of a mixture of endocervical-type mucinous, serous, endometrioid, squamous, and indifferent cells with abundant eosinophilic cytoplasm reported to date have been primarily limited to borderline and microinvasive types, with only one report of a disease-related death.

The clinicopathologic features of 54 endocervical-type and mixed cell-type mucinous tumors, defined as tumors with papillary architecture resembling serous tumors but containing endocervical-type mucinous epithelium, were evaluated. Thirty-four tumors (64%) were classified as atypical proliferative (borderline) tumors based on the absence of stromal invasion and the absence of micropapillary architecture measuring >5 mm. Five tumors (9%) qualified as intraepithelial carcinoma based on the presence of marked cytologic atypia or a complex cribriform growth pattern involving the epithelium covering the surface of papillae or lining cystic spaces. Eight tumors (15%) with stromal invasion </=5 mm were classified as microinvasive carcinoma. Seven tumors (13%) with either stromal invasion (five tumors) or micropapillary architecture measuring >5 mm (two tumors) were classified as carcinoma. Sixteen tumors (30%) were bilateral, and endosalpingiosis was identified in 41% of cases. Serous-type differentiation was present in all cases.

Of the 29 patients with atypical proliferative tumors, intraepithelial carcinomas, and microinvasive carcinomas for whom follow-up was available, there were no disease-related deaths. In contrast, of the seven patients whose tumors had either stromal invasion or micropapillary architecture >5 mm, two stage III patients died of disease (one with frank invasion and one with a micropapillary tumor that lacked stromal invasion). One other stage III patient with a noninvasive micropapillary carcinoma was alive with disease at 84 months. The remaining four patients (three stage I and one stage III) were alive with no evidence of disease.

In summary, most endocervical-type atypical proliferative tumors are stage I and benign. The presence of either intraepithelial carcinoma or microinvasion has no adverse effect on behavior. Rare endocervical-type mucinous tumors demonstrate histologically malignant features and aggressive behavior that warrant designation as carcinoma.

As with serous tumors, micropapillary architecture without frank invasion in endocervical-type mucinous tumors is associated with disease recurrence and death when presenting as advanced-stage disease. All the tumors in this study were composed of a heterogeneous population of cells, consisting mainly of serous (ciliated) and endocervical-type mucinous cells. In addition, they all contained endometrioid-type cells, hobnail cells, and indifferent cells with abundant eosinophilic cytoplasm to a varying degree. Accordingly, it appears that tumors that feature endocervical-type mucinous cells are rarely if ever pure but almost invariably of mixed cell type.

Despite containing mucinous epithelium, the papillary architecture, serous-type differentiation, association with endosalpingiosis, frequent bilaterality, size, and clinical behavior of endocervical-type mucinous tumors closely resemble serous tumors. We therefore recommend the term "seromucinous" for these tumors, which acknowledges both their serous and mucinous features.


Ovarian yolk sac tumor associated with endometrioid carcinoma and mucinous cystadenoma of the ovary.

Lopez JM, Malpica A, Deavers MT, Ayala AG.

Ann Diagn Pathol. 2003 Oct;7(5):300-5. Abstract quote  

The clinicopathologic and immunohistochemical findings of an unusual case of ovarian yolk sac tumor associated with endometrioid carcinoma and mucinous cystadenoma of the ovary are reported. The tumor was detected in a 51-year-old postmenopausal woman who presented with abdominal swelling and a pelvic mass.

The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy. The tumor was confined to the right ovary and measured 16.0 cm in greatest dimension. Microscopic examination revealed that the tumor had a yolk sac component associated with an endometrioid carcinoma, grade I, and a mucinous cystadenoma. A background of atypical endometriosis was noted. Immunoperoxidase studies showed that the yolk sac component stained diffusely with a cytokeratin cocktail and was focally positive for alpha-fetoprotein. It was negative for keratin 7. In contrast, the endometrioid carcinoma stained positive for keratin 7 in addition to the cytokeratin cocktail, but was negative for alpha-fetoprotein.

After surgery, the patient received three cycles of chemotherapy. However, the disease progressed and the patient died 10 months after the diagnosis of the ovarian tumor.




Immunohistochemical expression of CDX2 in primary ovarian mucinous tumors and metastatic mucinous carcinomas involving the ovary: comparison with CK20 and correlation with coordinate expression of CK7.

[1] 1Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA [2] 2Department of Gynecology & Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.


Mod Pathol. 2006 Nov;19(11):1421-8. Epub 2006 Sep 15 Abstract quote

Recent studies have demonstrated conflicting results regarding the value of CDX2 for distinguishing primary ovarian mucinous tumors from metastatic mucinous carcinomas in the ovary. Utility of coordinate expression of cytokeratins 7 and 20 is restricted to distinction of ovarian mucinous tumors from lower gastrointestinal tract metastases and data comparing coordinate expression of all three markers is limited.

Immunohistochemical studies were performed to compare expression of CDX2 and cytokeratin 20, both markers of intestinal differentiation, in conjunction with coordinate expression of cytokeratin 7, in 90 mucinous tumors involving the ovary: 42 primary ovarian mucinous tumors (31 atypical proliferative (borderline) mucinous tumors (gastrointestinal type), 11 mucinous carcinomas) and 48 metastatic mucinous carcinomas of upper (pancreaticobiliary tract: 14; stomach: five) and lower (colon and rectum: 25; appendix: four) gastrointestinal tract origin. Primary ovarian tumors expressed CDX2 (40%) less frequently than cytokeratin 20 (83%) (P<0.0001). CDX2 expression in primary ovarian tumors (40%) was lower than CDX2 expression in metastatic carcinomas of both upper (74%; P=0.016) and lower gastrointestinal tract origin (90%; P<0.0001). Cytokeratin 20 expression was similar in primary ovarian tumors (83%) and metastases of upper (89%; P=0.071) and lower gastrointestinal tract origin (93%; P=0.29).

Thus, as a single marker CDX2 offers some advantage over cytokeratin 20 because it is less frequently positive in primary ovarian tumors. In the almost universally cytokeratin 7-positive primary ovarian tumors and metastases of upper gastrointestinal tract origin, CDX2 coordinate expression was less common in primary ovarian tumors (36%) than in metastases of upper gastrointestinal tract origin (63%) (P=0.022) whereas cytokeratin 20 coordinate expression was identical in both tumor types (79%). In the almost universally cytokeratin 7-negative metastases of lower gastrointestinal tract origin, coordinate expression of CDX2 (83%) and cytokeratin 20 (86%) were equivalent (P=1.00). CDX2 was comparable to cytokeratin 20 in distinguishing metastases of lower gastrointestinal tract origin (usually cytokeratin 7-negative and CDX2/cytokeratin 20 positive) from primary ovarian tumors and metastases of upper gastrointestinal tract origin (usually cytokeratin 7-positive and CDX2/cytokeratin 20 variable). CDX2 provided some advantage over cytokeratin 20 for distinguishing primary ovarian mucinous tumors from metastases of upper but not lower gastrointestinal tract origin; however, the advantage in the former was limited due to the occurrence of shared coordinate expression profiles in both tumor types.

Cytokeratin 7 provides the predominant discriminatory value among these markers yet is limited to distinction of primary ovarian tumors from metastases of lower gastrointestinal tract origin.



Am J Surg Pathol 2000;24:1447-1464.

Presence of one of the following strongly suggests and the presence of two or more establishes the diagnosis of metastasis to the ovary

  Recent history or operative finding of GI, pancreatic, or biliary tract mucinous adenocarcinoma
  Parenchymal liver metastases and/or mesenteric lymph node metastases (except in cases of extensive intra-abdominal disease)
  Bilateral ovarian parenchymal involvement
  Multiple distinct nodules in ovarian tumors
  Vascular space invasion within ovary
  Lack of staining for cytokeratin 7
Benign appearing, borderline-appearing, or both with dissecting mucin present in the abdominal cavity

If a mucinous tumor is found in the appendix, it should be considered primary and staged according to the criteria similar to those used for primary intestinal tumors in general

The ovarian tumor(s) should be considered metastatic.

  If the ovarian tumor is bilateral, or unilateral in the absence of an accompanying dermoid cyst, it should be considered metastatic from the appendix unless removal of the latter followed by step sectioning of the entire organ for microscopic examination fails to reveal a mucinous tumor
  If the ovarian tumor is unilateral and associated with a dermoid cyst in the absence of any evidence of an appendiceal tumor, the ovarian tumor should be considered primary
  Ovarian tumor should be considered primary if the appendix has been removed previously and showed no gross or microscopic evidence of a mucinous tumor, and there was no evidence of mucin in the abdominal cavity at the time of the appendectomy

In evaluating involvement of the peritoneum, mucinous ascites and superficial organizing intra-abdominal mucin that contains tumor cells should not be considered peritoneal spread of tumor.

In such cases if the ovarian tumor is judged to be primary, it should be placed in the FIGO Ic (TNM TIc category) in the absence of more advanced disease; if an intestinal tumor is judged to be primary, on the other hand, the tumor should be placed in the TNM T4 stage.

Dissecting mucin with fibrosis makes an ovarian tumor FIGO stage 2 or 3 (TNM T2 or T3); if an intestinal tumor is judged primary, the presence of dissecting mucin with fibrosis makes it TNM stage 4.

  The presence or absence of cells in the peritoneal biopsy specimens, and if cells are present, whether they appear benign, borderline (atypical), or malignant should be noted in the pathology report
Cytokeratins 7 and 20 in Primary and Secondary Mucinous Tumors of the Ovary: Analysis of Coordinate Immunohistochemical Expression Profiles and Staining Distribution in 179 Cases.

Departments of *Pathology daggerGynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD double daggerPhenoPath Laboratories, Seattle, WA section signArmed Forces Institute of Pathology (Department of GYN and Breast Pathology); (Current address: Dr Wheeler, Quest Diagnostics, Inc, Las Vegas, NV) parallelWashington Hospital Center (Department of Pathology), Washington, DC.


Am J Surg Pathol. 2006 Sep;30(9):1130-1139. Abstract quote

Coordinate expression profiles for cytokeratins 7 and 20 (CK7 and CK20) are useful for distinguishing certain types of adenocarcinomas but use for distinction of primary and secondary mucinous tumors in the ovary is limited due to the existence of a number of tumor types exhibiting overlapping CK7/CK20 immunoprofiles; the use of staining distribution patterns in the distinction of tumors with shared profiles has not been evaluated in detail.

We report analysis of both coordinate expression profiles and staining distribution in 179 rigorously classified mucinous tumors in the ovary, including 53 primary tumors [35 atypical proliferative (borderline) mucinous tumors of gastrointestinal type and 18 invasive mucinous carcinomas] and 126 secondary tumors [28 colorectal adenocarcinomas, 54 appendiceal tumors (23 adenocarcinomas, 31 low-grade adenomatous mucinous tumors associated with pseudomyxoma peritonei), 14 pancreatic adenocarcinomas, 8 endocervical adenocarcinomas, 5 gastric adenocarcinomas, 4 gallbladder/biliary tract adenocarcinomas, and 13 adenocarcinomas of unknown primary sites). A CK7/CK20 immunoprofile was the most common profile in primary ovarian tumors (74%), upper gastrointestinal tract tumors (78%), and endocervical tumors (88%) but was occasionally observed in lower intestinal tract tumors (colorectal: 11%; appendiceal: 13% of low-grade tumors, 35% of carcinomas). A CK7/CK20 immunoprofile was the most common profile in lower intestinal tract tumors (79%) and was uncommon in upper gastrointestinal tract tumors (9%), rarely seen in primary ovarian tumors (4%), and not seen in endocervical tumors. A CK7/CK20 profile was observed in some primary ovarian (23%), upper gastrointestinal tract (13%), and endocervical tumors (13%) but not in lower intestinal tract tumors.

For CK7 tumors, staining distribution was very frequently diffuse (>50% of tumors cells positive) in primary ovarian, upper gastrointestinal tract, and endocervical tumors, whereas staining distribution was often focal (<50% of tumors cells positive) when present in colorectal and appendiceal carcinomas but not in low-grade appendiceal tumors.

For CK20 tumors, staining distribution was variable but often focal in primary ovarian tumors and nonlower intestinal tract tumors, whereas the pattern was almost always diffuse in lower intestinal tract tumors. Immunohistochemical staining distribution can supplement CK7/CK20 coordinate expression profiles to distinguish subsets of primary ovarian and metastatic lower intestinal tract mucinous tumors having overlapping immunoprofiles but neither coordinate expression profiles nor staining distribution distinguishes primary ovarian tumors from the nonlower intestinal tract metastases.

Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis.

Seidman JD, Kurman RJ, Ronnett BM.

Am J Surg Pathol. 2003 Jul;27(7):985-93 Abstract quote

Mucinous carcinomas are reported to comprise 6-25% of ovarian carcinomas (mean 12%), but recent refinements in the interpretation of histologic features of noninvasive and metastatic mucinous carcinomas suggest that this may be an overestimate. Mucinous carcinomas in the ovaries are commonly metastatic, but the proportion of primary versus metastatic mucinous carcinomas in unselected patients is unknown.

To evaluate the histologic-type distribution of ovarian surface epithelial carcinomas, a consecutive series of 124 ovarian carcinomas was reviewed using uniform current criteria. Microinvasive and intraepithelial carcinomas and carcinomas arising in germ cell and stromal tumors were excluded. To evaluate the proportions of primary and metastatic tumors among the mucinous carcinomas, 52 consecutive mucinous carcinomas from nonreferral patients were reviewed. Three of 124 primary ovarian carcinomas were pure mucinous carcinomas (2.4%). Among 52 cases of mucinous carcinomas in the ovaries, 40 (77%) were metastatic and 12 (23%) were primary. Among the 12 primary mucinous tumors, three were atypical proliferative mucinous tumors with microinvasion and nine were invasive mucinous carcinomas. Among the 40 metastatic mucinous tumors, 18 (45%) were from the gastrointestinal tract, 8 (20%) were pancreatic, 7 (18%) were gynecologic malignancies (5 cervical, 2 endometrial), 3 (8%) were from the breast, and 4 (10%) were of unknown primary site.

A simple rule that classifies all bilateral mucinous carcinomas as metastatic, unilateral mucinous carcinomas <10 cm as metastatic, and unilateral mucinous carcinomas >/=10 cm as primary correctly classified 90% of the neoplasms. This algorithm for distinguishing primary and metastatic mucinous carcinomas in the ovary can be used at the time of intraoperative consultation to guide surgical management.

After careful exclusion of noninvasive, microinvasive, and metastatic tumors, pure mucinous adenocarcinoma primary in the ovary appears to be substantially less common than previously reported.

The distinction between primary and metastatic mucinous carcinomas of the ovary: gross and histologic findings in 50 cases.

Lee KR, Young RH.


Am J Surg Pathol 2003 Mar;27(3):281-92 Abstract quote

The gross and routine microscopic features of 25 stage I primary mucinous ovarian carcinomas without clinical evidence of recurrence and 25 mucinous carcinomas metastatic to the ovaries were compared.

Findings that were frequent in the latter and strongly favored a metastasis were: 1) bilaterality, 2) microscopic surface involvement by epithelial cells (surface implants), and 3) an infiltrative pattern of stromal invasion. Findings that were less frequent but present exclusively or almost exclusively in metastatic carcinomas were: 1) a nodular invasive pattern, 2) ovarian hilar involvement, 3) single cell invasion, 4) signet-ring cells, 5) vascular invasion, and 6) microscopic surface mucin. Findings that were frequent in, and strongly favored, primary ovarian carcinoma were: 1) an "expansile" pattern of invasion and 2) a complex papillary pattern.

Findings that were less frequent but also favored a primary tumor were: 1) size >10 cm, 2) a smooth external surface, 3) benign-appearing and borderline-appearing areas, 4) microscopic cystic glands, and 5) necrotic luminal debris. Findings that did not distinguish the tumors were: 1) a cystic gross appearance, 2) gross solid, papillary, necrotic, or hemorrhagic areas, 3) nature of cyst contents (mucinous vs nonmucinous), 4) stromal mucin (pseudomyxoma ovarii), 5) cribriform, villous, or solid growth patterns, 6) focal area resembling typical colonic carcinoma, 7) goblet cells, or 8) tumor grade. Primary and metastatic mucinous ovarian carcinomas can be distinguished from each other in the great majority of cases based solely on their conventional histopathologic findings.

Careful gross evaluation is also important with special attention paid to the external surface of the ovarian tumor(s) to detect abnormalities that have the features of surface implants on microscopic evaluation.

Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary.

Park SY, Kim HS, Hong EK, Kim WH.

Center for Colorectal Cancer, Center for Gastric Cancer, and Department of Pathology, National Cancer Center, Goyang, Gyeonggi, Korea and the Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.


Hum Pathol 2002 Nov;33(11):1078-85 Abstract quote

The expressions of cytokeratin (CK) 7 and 20 have been studied in various primary and metastatic carcinomas, and their determination may help distinguish the site of origin of metastatic carcinomas. However, little is known about the factors that determine variations in their expression patterns in primary gastric and colorectal carcinomas.

We investigated the expressions of CK7 and CK20 in 289 cases of gastric carcinoma and 225 cases of colorectal carcinoma using a tissue microarray. To evaluate CK7 and CK20 expression patterns of ovarian metastases from gastric or colorectal carcinomas, 54 cases of metastatic carcinomas to the ovary were examined. It was found that 71% (207 of 289) of the gastric carcinomas stained positively for CK7, whereas only 9% (21 of 225) of the colorectal carcinomas proved to be CK7 positive, and that 41% (117 of 289) of the gastric carcinomas and 73% (165 of 225) of the colorectal carcinomas were CK20 positive.

The proportion of CK7+/CK20- was highest in the gastric carcinomas at 46% (132 of 289), and was independent of the histologic classification of Lauren (46% of the intestinal type, 45% of the diffuse type). The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histologic grade and location of the tumor. CK7-/CK20+ had the greatest proportion (68%) in colorectal carcinomas, and this was dependent on the tumor's histologic grade (75% of low-grade versus 52% of high-grade) and location (46% of right-sided versus 76% of left-sided). Moreover, 42% (18 of 43) of gastric carcinomas metastatic to the ovary were CK7+/CK20-, whereas 19% (8 of 43) were CK7-/CK20+. All colorectal cancers metastatic to the ovary were CK7-/CK20+, except 1 case that was CK7-/CK20-.

In conclusion, the CK7 and CK20 expression patterns in primary gastric carcinomas vary considerably, and those in colorectal carcinomas are associated with histologic grade and tumor location. The CK7-/CK20+ expression pattern is specific for metastatic colorectal carcinomas to the ovary, but has low predictability for colorectal origin in metastatic ovarian carcinoma.


Invasion patterns in stage I endometrioid and mucinous ovarian carcinomas: a clinicopathologic analysis emphasizing favorable outcomes in carcinomas without destructive stromal invasion and the occasional malignant course of carcinomas with limited destructive stromal invasion.

Chen S, Leitao MM, Tornos C, Soslow RA.

1Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Mod Pathol. 2005 Jul;18(7):903-11. Abstract quote  

Stage I, low-grade endometrioid and mucinous ovarian carcinomas have an excellent prognosis. Published data have suggested that destructive stromal invasion, a relatively uncommon finding in these tumors, is a poor prognostic factor.

We investigated this by studying all FIGO stage I, grades 1 and 2 (of 3) endometrioid and mucinous ovarian carcinomas that were surgically staged at the Memorial Sloan-Kettering Cancer Center from 1980 to 2000. We undertook a careful review of all available slides using current diagnostic criteria and correlated histopathologic indices with clinical outcome data. Cases studied included 13 endometrioid ovarian carcinomas (stage IA, eight; stage IC, five) and six intestinal mucinous ovarian carcinomas (stage IA, three; stage IC, three).

All of the tumors contained areas of expansile invasion, greater than that acceptable for microinvasion, and were thus diagnosed as carcinomas instead of borderline tumors. Nevertheless, nearly all demonstrated borderline tumor (noninvasive) components. Six tumors contained at least one focus of destructive stromal invasion (two endometrioid and four mucinous ovarian carcinomas). Four additional cases showed a focus suspicious for but not diagnostic of destructive invasion ('indeterminate for destructive invasion') (two endometrioid and two mucinous ovarian carcinomas). Follow-up data were available for 17 patients. The median follow-up was 81 months (range, 9-161 months). In all, 14 patients were alive with no evidence of disease (expansile invasion alone, eight; destructive stromal invasion, four; and indeterminate for destructive invasion, two). Three patients died of their disease (destructive stromal invasion, two; and indeterminate for destructive invasion, one). The size, number, and nuclear grade of destructive stromal invasion foci did not appear to have an impact on survival in this relatively limited number of patients.

Outcome data in patients with stage I, low-grade endometrioid and mucinous ovarian carcinomas without destructive stromal invasion indicate that these tumors have a very limited malignant potential. The literature has not documented recurrences in this setting when the staging has been complete, the sampling adequate, and the cytologic features no more than grade 2, and metastasis to the ovary has been excluded. In contrast, carcinomas harboring even limited foci of destructive stromal invasion, although frequently cured surgically, can pursue a malignant clinical course.
Mucinous Tumors of the Ovary
A Clinicopathologic Analysis of 75 Borderline Tumors (of Intestinal Type) and Carcinomas

Ingrid M. Rodríguez, M.D. ; Jaime Prat, M.D. , F.R.C.Path.

From the Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.


Am J Surg Pathol 2002;26:139-152 Abstract quote

With the exception of benign cystadenomas, mucinous ovarian tumors are rare and heterogeneous neoplasms. They have been classified as either borderline tumors or carcinomas for almost 30 years. Subsequently, the borderline tumors have been subclassified into endocervical-like and intestinal types. The diagnostic criteria for distinguishing borderline tumors of the intestinal type from mucinous carcinomas have varied, making difficult the interpretation of prognostic information. More recently, a further subdivision of the former tumors into forms with only epithelial atypia and variants with focal intraepithelial carcinoma has been proposed.

Consequently, in this study of 41 mucinous borderline tumors of intestinal type and 34 mucinous carcinomas, the former were also subdivided into 30 cases with mild to moderate atypia only and 11 with areas of intraepithelial carcinoma.

All 30 purely borderline tumors were stage I tumors, and all 15 with follow-up information (including one case with microinvasion) were clinically benign. All 11 mucinous borderline tumors that had foci of intraepithelial carcinoma were also stage I neoplasms, and none of the eight patients with follow-up data (including one with microinvasive carcinoma) recurred.

Thirty-four invasive carcinomas were subclassified into 15 expansile and 19 infiltrative subtypes. All 15 carcinomas with only expansile invasion were stage I; none of the 11 with follow-up data recurred. Three of nine patients with stage I infiltrative carcinomas with follow-up information had a fatal recurrence. Eight of the remaining 10 infiltrative carcinomas had extended beyond the ovary at the time of diagnosis (stages II and III); of the six patients with follow-up data, four died of tumor and two were alive with disease.

In stage I carcinomas nuclear grade and tumor rupture correlated with unfavorable prognosis, but less than infiltrative invasion. However, all three fatal tumors were infiltrative carcinomas that had ruptured, and two contained grade 3 malignant nuclei.

Combination of infiltrative invasion, high nuclear grade, and tumor rupture is a strong predictor of recurrence for stage I mucinous ovarian tumors. Among the 19 infiltrative tumors, 13 contained foci of anaplastic carcinoma. Of the seven patients with stage I tumors and follow-up data, only one patient whose tumor had ruptured intraoperatively had a fatal recurrence. The presence of anaplastic components in stage Ia (intact) carcinomas did not have an adverse effect in their outcome, even when the undifferentiated carcinomatous elements appeared in the form of mural nodules.

TREATMENT Dependent upon the stage

Am J Surg Pathol 2000;24:1447-1464.
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