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Background

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.

TUMOR TYPE AGE OF PRESENTATION PERCENTAGE OF TUMORS
Benign cystadenomas 3-5th decades 85%
Borderline malignancy 4-7th decades 6-10%
Cystadenocarcinomas 4-7th decades 5-10%

 

PATHOGENESIS CHARACTERIZATION

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.

 

TUMOR TYPE GROSS APPEARANCE HISTOLOGIC APPEARANCE
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

 

HISTOPATHOLOGY CHARACTERIZATION

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.

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.

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.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
Carcinomas

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
NOTE:

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

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
HISTOPATHOLOGY
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.

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


Commonly Used Terms

Ovaries
Serous tumors of the ovary


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Last Updated 2/28/2002

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