Download LOW MALIGNANT POTENTIAL TUMORS

LOW MALIGNANT POTENTIAL TUMORS: SHOULD THEY BE STAGED?
R.G. Moore, M.C. Simpson, K. Robison
Program in Women’s Oncology, Department of Obstetrics and Gynecology.
Women and Infants’ Hospital / Brown University
Introduction: Recently the world health organization removed tumors of low malignant
potential (LMP) or borderline ovarian tumors from the category of invasive ovarian
carcinomas. LMP tumors make up to 15% of epithelial ovarian tumors and contribute
approximately 3000 case of ovarian tumor annually(1). Patients diagnosed with LMP tumors
tend to have an excellent prognosis even when diagnosed with advanced stage disease. The
5 year survival rate for stage I and II LMP tumors is essentially 100% and is approximately
80% for advanced stage tumors(2,3). The recurrence rate of LMP tumors is typically low and
in patients that experience recurrences the time to recurrence is often 10 to 15 years from the
time of the original diagnosis. The management of LMP tumors is mostly surgical and
chemotherapy is indicated in only a few cases. Patients presenting with LMP tumors tend to
be slightly older than those presenting with benign disease but younger than patients
presenting with ovarian malignancies. Approximately 20% of patient with LMP tumors will
present with advanced stage disease(4). The surgical management of these patients should
be the same as for those patients presenting with invasive ovarian cancer.
Pathology: LMP tumors include histologic features consisting of any of the epithelial ovarian
cancer subtypes. The most common are the serous, mucinous and endometrioid histologic
subtypes. The histologic components that distinguish LMP tumors from invasive carcinomas
are mainly architectural feature such as pushing borders rather than destructive invasion.
Some of the histologic criteria used to describe LMP tumors include epithelial papilla,
complexity of the architecture, cellular stratification, mitotic activity and lack of stromal
invasion. LMP tumors are classified as LMP tumor, LMP tumors with non-invasive implants,
LMP tumors with invasive implants and micropapillary LMP tumors.
Surgical management: In general the surgical management for patients diagnosed with a
LMP tumor on intraoperative frozen section includes hysterectomy with bilateral
salpingooophorectomy. The current guidelines for LMP tumors are the same as the
recommendation for invasive ovarian malignancy and include full surgical staging with pelvic
and periaortic node dissection, omentectomy, multiple peritoneal biopsies, diaphragmatic
cytology and washings. However, the benign course that LMP tumors of the ovaries follow
allow for a wide option for the surgical management for this disease and there is some
controversy as to whether full surgical staging is necessary. Many of these tumors will be
diagnosed in patients that continue to desire future fertility or who may continue to benefit
from the hormonal contribution the ovary provides in the premenopausal age group. For
patients with stage I disease many gynecologist agree that conservative management is an
option for these patients. Analysis of GOG 72 revealed patients that underwent conservative
surgery with unilateral oophorectomy had higher recurrence rates than what was experienced
in patients treated with hysterectomy and bilateral oophorectomy. However, the survival rate
was equivalent in the two groups(2). The use of cystectomy for the treatment of LMP tumors
is also controversial. Intuitively the rate of recurrence would be higher for these patients but
there is no evidence to show a difference in overall survival. For patients with advanced
stage disease (stage II, III, and IV) in most cases a hysterectomy with bilateral
salpingooophorectomy and tumor debulking or full surgical staging is recommended.
The natural history of LMP tumors of all stages is that of a benign clinical course. Therefore,
many physicians question the value of surgical staging in this disease. Approximately 50 to
70% of serous and 75 to 100% of mucinous LMP tumors appear to be confined to the ovary
and are stage I disease(2,3). However, patients with apparent stage I disease who undergo
full surgical staging will be upstage in 20% to 47% of cases(4,5). More importantly
proponents of surgical staging argue that intraoperative frozen section may not reveal an
invasive component within an LMP tumor that is found at the time of permanent sections.
Depending on the institution LMP tumors are upgraded to an invasive carcinoma in 6% to
27% of cases(5-7). In these cases the true surgical stage would be unknown leading to a
potential second surgery or unnecessary chemotherapy.
Patients with LMP tumors with non invasive implants will benefit from aggressive surgical
debulking. About 30% of these patients will develop recurrent or progressive disease. The
median time to recurrence is just over 7 years. In a report by Gershenson et al. seventy
percent of patients that had their tissue sampled at the time of their recurrence had a low
grade serous carcinoma and 30% had a recurrence of their LMP tumor(8). Despite the
increase in recurrence and the progression to invasive cancer this patient group did not
benefit from adjuvant chemotherapy after their initial diagnosis(8). Patients with LMP tumors
with invasive implant have a similar out come as patients with non invasive implants. They
have a recurrence rate of 31%, a large number of which are low grade invasive tumors(9).
Their time to recurrence was two years, five years earlier than patients with non invasive
implants. Likewise these patients did not seem to benefit from adjuvant chemotherapy after
their initial surgery(9). Micropapillary LMP tumors present an even greater dilemma than LMP
tumors with invasive implants. These tumors have a high recurrence and progression rate
and are often associated with invasive implants. The treatment of both LMP tumors with
invasive implants and micropapillary tumors with adjuvant chemotherapy continues to be
controversial. However, many gynecologic oncologist will agree that patients with
micropapillary tumors will benefit from adjuvant chemotherapy.
Summary: The surgical management of LMP tumors of the ovary is controversial. In women
desiring future fertility conservative surgery has not been shown to decrease survival rates in
these patients. Women who present with advanced stage disease will benefit from a surgery
characteristic to that which is recommended for patients with invasive ovarian cancer.
Whether fertility sparing surgery is performed or not full surgical staging is indicated seeing
that up to 50% of patients will be up staged and up to 30% of tumors will be upgraded to
invasive ovarian malignancies.
Reference
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(2) Barnhill DR, Kurman RJ, Brady MF, Omura GA, Yordan E, Given FT et al. Preliminary analysis of the behavior of
stage I ovarian serous tumors of low malignant potential: a Gynecologic Oncology Group study. J Clin Oncol 1995;
13(11):2752-2756.
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Aust N Z J Obstet Gynaecol 1997; 37(1):100-103.
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(9) Gershenson DM, Silva EG, Levy L, Burke TW, Wolf JK, Tornos C. Ovarian serous borderline tumors with
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