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Of all gynecologic malignancies, ovarian cancer continues to have the
highest mortality and is the most difficult to diagnose. In the United States
female population, ovarian cancer ranks fifth in absolute mortality among
cancer related deaths (13,000/yr). In most reported cases, ovarian cancer,
when first diagnosed is in stages III or IV in about 60 to 70% of patients
which further complicates treatment of the disease (Barber, 3).
Early detection in ovarian cancer is hampered by the lack of appropriate
tumor markers and clinically, most patients fail to develop significant
symptoms until they reach advanced stage disease. The characteristics
of ovarian cancer have been studied in primary tumors and in established
ovarian tumor cell lines which provide a reproducible source of tumor material.
Among the major clinical problems of ovarian cancer, malignant progression,
rapid emergence of drug resistance, and associated cross-resistance remain
unresolved. Ovarian cancer has a high frequency of metastasis yet generally
remains localized within the peritoneal cavity. Tumor development has been
associated with aberrant, dysfunctional expression and/or mutation of
various genes. This can include oncogene overexpression, amplification or
mutation, aberrant tumor suppressor expression or mutation. Also, subversion
of host antitumor immune responses may play a role in the pathogenesis of
cancer (Sharp, 77).
Ovarian clear cell adenocarcinoma was first described by Peham in 1899 as
"hypernephroma of the ovary" because of its resemblance to renal cell carcinoma.
By 1939, Schiller noted a histologic similarity to mesonephric tubules and
classified these tumors as "mesonephromas." In 1944, Saphir and Lackner described
two cases of "hypernephroid carcinoma of the ovary" and proposed "clear cell"
adenocarcinoma as an alternative term. Clear cell tumors of the ovary are now
generally considered to be of mullerian and in the genital tract of mullerian origin.
A number of examples of clear cell adenocarcinoma have been reported to arise
from the epithelium of an endometriotic cyst (Yoonessi, 289). Occasionally, a renal
cell carcinoma metastasizes to the ovary and may be confused with a primary clear
Ovarian clear cell adenocarcinoma (OCCA) has been recognized as a distinct
histologic entity in the World Health Organization (WHO) classification of ovarian
tumors since 1973 and is the most lethal ovarian neoplasm with an overall five year
survival of only 34% (Kennedy, 342). Clear cell adenocarcinoma, like most ovarian
cancers, originates from the ovarian epithelium which is a single layer of cells found on
the surface of the ovary. Patients with ovarian clear cell adenocarcinoma are typically
above the age of 30 with a median of 54 which is similar to that of ovarian epithelial
cancer in general. OCCA represents approximately 6% of ovarian cancers and bilateral
ovarian involvement occurs in less that 50% of patients even in advanced cases.
The association of OCCA and endometriosis is well documented (De La Cuesta,
243). This was confirmed by Kennedy et al who encountered histologic or intraoperative
evidence of endometriosis in 45% of their study patients. Transformation
from endometriosis to clear cell adenocarcinoma has been previously demonstrated in
sporadic cases but was not observed by Kennedy et al. Hypercalcemia occurs in a
significant percentage of patients with OCCA. Patients with advanced disease are more
typically affected than patients with nonmetastatic disease. Patients with OCCA are also
more likely to have Stage I disease than are patients with ovarian epithelial cancer in
general (Kennedy, 348).
Histologic grade has been useful as an initial prognostic determinant in some studies
of epithelial cancers of the ovary. The grading of ovarian clear cell adenocarcinoma has
been problematic and is complicated by the multiplicity of histologic patterns found in
the same tumor. Similar problems have been found in attempted grading of clear cell
adenocarcinoma of the endometrium (Disaia, 176). Despite these problems, tumor
grading has been attempted but has failed to demonstrate prognostic significance.
However, collected data suggest that low mitotic activity and a predominance of clear
cells may be favorable histologic features (Piver, 136).
Risk factors for OCCA and ovarian cancer in general are much less clear than for
other genital tumors with general agreement on two risk factors: nulliparity and family
history. There is a higher frequency of carcinoma in unmarried women and in married
women with low parity. Gonadal dysgenesis in children is associated with a higher risk
of developing ovarian cancer while oral contraceptives are associated with a decreased
risk. Genetic and candidate host genes may be altered in susceptible families. Among
those currently under investigation is BRCA1 which has been associated with an
increased susceptibility to breast cancer. Approximately 30% of ovarian
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Cancer, Clinical medicine, Health, Gynaecological cancer, RTT, Tumor markers, Gynaecology, Ovarian cancer, Surface epithelial-stromal tumor, Ovarian tumor, CA-125, Germ cell tumor
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