Mini-symposium: pathology of the ovaryMucinous tumours of the ovary
Introduction
Like many forms of ovarian neoplasia, mucinous tumours exhibit a remarkable clinicopathological spectrum. They are most often diagnosed in the fourth to sixth decades of life, but they can be seen at any age and are the most common surface epithelial tumour of children and adolescents. The category includes mucinous cystadenomas (Figure 1), which although benign can be huge and significantly symptomatic; borderline tumours of low malignant potential; and carcinomas that range in behaviour from relatively indolent to highly aggressive. A morphological continuum exists from mucinous cystadenoma to mucinous carcinoma, and epithelium that varies from benign to borderline to frankly malignant is frequently found within a single tumour. Because of this continuum, drawing the line between these three major categories of neoplasia can be problematic. Even within the carcinoma group itself, there is a great diversity of appearance and behaviour, which can be considered in three main categories:
- 1
Tumours with expansile invasion and a good prognosis; with rare exceptions;
- 2
Well- to moderately-differentiated tumours with destructive invasion and an associated drop-off in prognosis, but one which is still generally favourable when the tumours are stage I;
- 3
High-grade adenocarcinomas, including some with an anaplastic component that, particularly when high-stage, can be rapidly fatal.
Another diagnostic challenge is presented by metastatic mucinous tumours from a variety of sites as they may be grossly indistinguishable from primary ovarian neoplasms. The overlap extends treacherously to microscopic evaluation, although well-sampled tumours will usually give clues to their true nature. The extent to which this is a common problem in ovarian tumor pathology interpretation has only been emphasized in the last decade or so.
In this review, we will focus on practical aspects of pathological evaluation and new information regarding mucinous tumours of the ovary. The emphasis will be on primary mucinous cystic neoplasms, but we will also discuss the diagnostic problems that metastatic mucinous carcinomas may pose. Other ovarian neoplasms that are not considered fundamentally mucinous but which can have mucinous cells of varying prominence will be briefly considered. The reader is referred to a number of excellent sources in the recent literature regarding ovarian mucinous tumours,1, 2, 3, 4, 5, 6 and as thorough literature reviews are available in those citations, our referencing herein will be selective. The original reports cited, and many others in the reference lists of those papers, provide detailed information on survival figures that will not be repeated here in a contribution intended to provide, with the aid of liberal use of illustrations, a guide to practical diagnostic issues. The role of immunohistochemistry in evaluating mucinous tumours has been much investigated in recent years and the reader is referred to reviews of that topic.7, 8, 9 From the viewpoint of daily practice, however, there are still relatively few firm aids provided by this technique. Traditional careful gross and routine microscopic evaluation, aided in some cases by due note of the clinical background, will yield the correct interpretation in the vast majority of cases.
Section snippets
Classification
A major change that has occurred relatively recently is the subdivision of mucinous tumours into those of intestinal and Müllerian types. This division was prompted by the seminal observations of Rutgers and Scully10 that borderline forms of these two categories have striking differences.11, 12, 13, 14 In contrast to intestinal-type tumours, Müllerian borderline tumours are typically lined by endocervical-like mucinous cells and often have distinctive polygonal cells with eosinophilic
Intestinal-type tumours
It has long been recognized that ovarian tumours can have intestinal-type epithelium as evidenced by the presence of goblet cells and argentaffin cells (Figure 2). Recent studies using modern techniques, particularly immunohistochemistry, have lent further support to the occurrence of intestinal-type differentiation in primary ovarian mucinous neoplasms.17 Enteric-type epithelium may rarely be associated with interesting clinical manifestations, such as the Zollinger-Ellison syndrome (Figure 3).
Müllerian mucinous tumours
That some mucinous tumours are Müllerian rather than intestinal-type has only recently been appreciated and dates essentially from the description of Müllerian mucinous borderline tumours by Rutgers and Scully in 1988.10 Perhaps somewhat enigmatically, it is within the category of borderline tumours that the Müllerian mucinous neoplasms have particularly distinctive features. In our opinion, Müllerian mucinous cystadenomas can also be recognized. We prefer the designation ‘Müllerian’ to
Mural nodules
Occasional mucinous cystic tumours (benign, borderline and carcinomatous) are noteworthy for having discrete nodules within their walls, so-called mural nodules.23, 24, 25, 26, 27 These nodules may be quite variable in appearance. Sometimes they represent discrete foci of conventional carcinoma arising in an otherwise benign or borderline tumour. In other cases, there may be remarkable appearances ranging from sarcoma-like mural nodules containing mitotically-active mixtures of plump
Metastatic mucinous tumours
One of the most important advances in our knowledge of mucinous ovarian neoplasia in the last few decades has been the appreciation that metastatic mucinous carcinoma in the ovary may simulate primary mucinous neoplasia to a quite striking degree.29 Many reports and reviews have discussed this problem, dating back to a small series of metastatic pancreatic carcinoma cases reported in 1989.30 Pancreatic carcinoma remains in our experience the prototypical neoplasm that may be the responsible
Other primary ovarian tumours with a mucinous component
A diverse number of primary ovarian neoplasms other than those that are generally considered ‘mucinous tumours of the ovary’ may have mucinous epithelium60 (Table 2). They include not only carcinomas in the surface epithelial group that are of mixed cell type but also neoplasms in the mixed mesodermal category, both the adenofibroma–adenosarcoma group and the more common malignant mixed mesodermal tumour. However, mucinous epithelium in these latter tumours occurs less frequently than
References (63)
- et al.
Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament
(1998) - et al.
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”
Am J Surg Pathol
(2000) - et al.
Primary ovarian mucinous cystadenocarcinomas. A clinicopathologic study of 49 cases with long-term follow-up
Am J Surg Pathol
(1998) - et al.
Evaluation of diagnostic criteria and behavior of ovarian intestinal-type mucinous tumors. Atypical proliferative (borderline) tumors and intraepithelial, microinvasive, invasive, and metastatic carcinomas
Am J Surg Pathol
(1999) - et al.
Mucinous tumors of the ovary. A clinicopathologic analysis of 75 borderline tumors (of intestinal type) and carcinomas
Am J Surg Pathol
(2002) Mucinous tumors of the ovary: a review
Int J Gynecol Pathol
(2005)- et al.
Immunohistochemistry as a tool in the differential diagnosis of ovarian tumors: an update
Int J Gynecol Pathol
(2004) - et al.
Metastatic neoplasms involving the ovary: a review with an emphasis on morphological and immunohistochemical features
Histopathology
(2005) - et al.
Immunohistochemistry as a diagnostic aid in the evaluation of ovarian tumors
Semin Diagn Pathol
(2005) - et al.
Ovarian mullerian mucinous papillary cystadenomas of borderline malignancy. A clinicopathologic analysis
Cancer
(1988)