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OVARIAN CARCINOMAS
2% of all women. Incidence increasing to 4% in 20 years. 18,000 new cases of ovarian carcinoma yearly (23% of all GYN cancers); 11,400 deaths yearly due to ovarian carcinoma (47% of GYN cancer deaths).
Embryological origins:
4th Week: GERM CELLS migrate to the genital ridge, where they induce a proliferation of the underlying NONSPECIFIC MESENCHYME into SPECIALIZED GONADAL STROMA within the covering invested by COELOMIC EPITHELIUM. These are the cancer cell lines:
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II. Germ Cell Tumors
A. Teratoma
1. Mature teratoma
a. solid adult teratoma
b. dermoid cyst
c. struma ovarii
d. malignant Neoplasm’s arising from mature cystic teratoma
2. Immature teratoma (partially differentiated teratoma)
B. Dysgerminoma
C. Embryonal carcinoma
D. Endodermal sinus tumor
E. Choriocarcinoma
F. Gonadoblastoma
III. Specialized Gonadal Stroma
A. Granulosa-theca tumors
1. Granulosa tumor
2. Thecoma
B. Sertoli-Leydig tumors
1. Arrhenoblastoma
2. Sertoli tumor
C. Gynandroblastoma
D. Lipid-cell tumors
IV. Nonspecific Mesenchyme
A. Fibroma, hemangioma, leiomyoma, lipoma
B. Lymphoma
C. Sarcoma
V. Neoplasms Metastatic to the Ovary
A. GI tract (Krukenberg)
B. Breast
C. Endometrium
D. Lymphoma
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I. Coelomic Epithelium
A. Serous tumor
B. Mucinous tumor
C. Endometrioid tumor
D. Mesonephric (clear cell) tumor
E. Brenner tumor
F. Undifferentiated carcinoma
G. Carcinosarcoma and mixed
mesodermal tumor |
BORDERLINE TUMORS OF OVARY Not benign because there is cytologic and architectural atypia e.g. nuclear hyperchromasia, enlargement and pleomorphism, prominent nucleoli and increased mitotic activity. Can see necrosis, inflammation and psammoma bodies, frequent tufting, stratification and complex papillary architecture. Can recur.
Not malignant because there is no stromal invasion in the ovaries , despite severe atypia and frequent mitosis. Can be seen in ovaries with benign and malignant elements.
Risk factors : Pregnancy reduces-OR.54 with P2 and ,37 with P4 children, ocp >5 years reduces risk by 25% and for 10 years by 50%. Breast feeding
Work-up: Sonogram - complex cysts are usually seen with intracystic papillation, mural nodules, some septa. Get Ca125 and CEA.
Serous Epithelial Carcinoma, LMP, comprise 50%
a. stratification of epithelial lining of papillae to 4mm or less cell layers
b. papillary projections, tufts from epithelial linings of papillae, individual cells
c. Intra-epithelial carcinoma: cribiform area > 4mm. If >4mm treat as invasive primary.
Mucinous Epithelial Carcinoma, LMP, comprise 30%
a. papillary structure + solid thickening 25‑50%
b. epithelial stratification of 2‑3 layers
c. rarely bilateral (5%). Think invasive carcinoma if bilateral.
Can see pseudomyxoma ovarii. Do appendectomy and run bowel for all mucinous pathology. Can see intraepithelial carcinoma if >4 layers thick.confluence or thick stratification. Borderline are typical to mild atypical or intraepithial carcinoma, or intraglandular mucinous carcioma, or cribiform less tha 10 mm2. Usually unilateral, but bilateral can be primary or metastatic. 98% survive stage I but only 35%survive higher stages especially when metastatic deposits are invasive--treat these as malignant and invasive. Rupture does not increase recurrence. Higher stage--think appendix and pseudomyxoma peritonei. See filiform papillae (little storma).or sever nuclear atypia with marked nuclear stratification >4 cells height. Many goblet cells and AMF’s. Gland mucus can rupture into stroma with histiocytic response.
Endometrioid Epithelial Carcinoma, LMP, very rare
can see atypical endometrioid hyperplasia in glands with stroma
endometriosis seen adjacent, or elsewhere in pelvis
often seen with unopposed estrogen or obesity.
Implants - 20% metastatic to abdominal surfaces. Resect these implants, not peel off, to see if invasive.
Therapy For Borderline Ovarian Tumors
| Stage IA: |
Fertility desired: LMP or grade 1 and appears Stage IA, do USO, only and get frozen section. Do washings, nodes, omentectomy, appendectomy, biopsy contralateral ovary if pathologist cannot rule out grade 1 invasive cancer.
May need to return for TAH-BSO if biopsies show Grade 2 or Stage II or higher.
Fertility not desired- TAH-BSO and frozen section for possible staging.
Chemotherapy is not helpful. .5% recurrence |
Stage II-IV: TAH-BSO, Debulking, Staging: omentectomy, appendectomy, nodes.
Resect all mets to make sure they are not invasive, which would indicate chemotherapy. |
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No residual—observe and reassure.
Bulky residual--observe. Small possibility of transition into invasive over time, so try to resect all.
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| Recurrence: Debulking laparotomy. Pathology to see if recurrence is higher grade and to
improve disease-free interval. If still LMP then follow. If invasive then
chemotherapy with Tax and CBDCA |
Prognosis
168 cases of Stage I serous LMP tumors from the series above there were two recurrences, both in the preserved ovary. Many of higher stages whose tumors persist were still clinically well, without progression or symptoms.
Of 234 mucinous LMP tumors in Stage I, 9 recurred and all died of disease. Approximately 40% of Stage III mucinous LMP tumors die (pseudomyxoma peritonei occurs from ruptured appendix). Remove appy, and all peritoneal lesions.
| If metastases are not invasive: |
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When mets are invasive: |
| Stage |
survival |
survival |
|
Stage |
survival |
survival |
| I |
98 |
99 |
|
I |
98 |
99 |
| II |
95 |
] |
|
II |
95 |
|
| III |
56 |
]92 |
|
III |
56 |
|
| IV |
40 |
] |
|
IV |
40 |
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MALIGNANT EPITHELIAL OVARIAN NEOPLASMS
| Risk: |
<2% lifetime risk but usually ages 50 - 60 years |
| Factors: |
Obesity. Age. Industrial countries. O.C.'s: .6 relative risk No virus
implicated. Low parity. Delayed childbirth.
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| Symptoms:: |
None. Bloating, dyspepsia, constipation, tenesmus, pressure symptoms -
25% see LMD for above, must are "observed"
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| Signs: |
Increased abdominal girth, ascites, mass, postmenopausal palpable ovary, obstruction of GI tract
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| Staging: |
Surgical. Determines type of therapy. |
The FIGO Staging for Primary Carcinoma of the Ovary (1985)
Stage I: Growth limited to the ovaries.
Stage Ia Growth limited to one ovary; no ascites. No tumor on the external surface; capsule intact.
Stage Ib Growth limited to both ovaries: no ascites. No tumor on the external surfaces; capsules intact.
Stage Ic Tumor either stage Ia or Ib but with tumor on surface of one or both ovaries, or with capsule ruptured; or with ascites present containing malignant cells or with positive peritoneal washings.
Stage II: Growth involving one or both ovaries with pelvic extension.
Stage IIa Extension and/or metastases to the uterus and/or tubes.
Stage IIb Extension to other pelvic tissues.
Stage IIc Tumor either stage IIa or IIb. but with tumor on surface of one or both ovaries: or with capsule(s) ruptured; or with ascites present containing malignant cells or with positive peritoneal washings.
Stage III: Tumor involving one or both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal or inguinale nodes. Superficial liver metastasis equals stage III. Tumor is limited to the true pelvis but with histologically proven malig-nant extension to small bowel or omentum.
Stage IIIa Tumor grossly limited to true pelvis with negative nodes but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces.
Stage IIIb Tumor of one or both ovaries with histologically confirmed implants of abdominal peritoneal surfaces none exceeding 2 cm in diameter. Nodes are negative.
Stage IIIc Abdominal implants greater than 2 cm in diameter and/or positive retroperitoneal or inguinale nodes.
Stage IV: Growth involving one or both ovaries, with distant metastases. If pleural effusion is present, there must be positive cytology. Parenchymal liver metastases equal stage IV.
Stage of Carcinomas of the Ovary by Histologic Subtype: Percentage in Each Stage
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Mucinous |
Endometrioid |
Clear Cell |
Serous Undiff |
Cases |
All |
| Stage |
(N = 123) |
(N = 205) |
(N = 63) |
(N = 283) |
(N = 155) |
(N = 829) |
| I |
19.1 |
50.8 |
47.6 |
35.2 |
57.1 |
26.5 |
| II |
23.0 |
28.7 |
24.5 |
25.5 |
25.4 |
29.2 |
| III |
43.1 |
13.9 |
21.2 |
27.6 |
7.9 |
26.5 |
| IV |
14.8 |
6.5 |
6.7 |
11.7 |
9.5 |
17.7 |
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Aure et al, 1971. |
Invasive Mucinous destructive stromal invasion SPREAD:
Intestinal type Infiltrative - always see intraepithelial, can see invasion into stroma.
Microinvasive act like borderline. Any stage over I see stroma invasion
Stage I 10% recur.
Expansile confluent nests of glands with almost no stroma. Can see broad areas of cribiform.
Endocrvical mucinous type are more bilateral (40%) 20% with endometriosis, smaller, more unilocular, with gross evidence of papillae. See mucoid polypoid projections into cyst. With endocervical mucinous highlystratified >4 up to 10 to 20 cells thick cells. Papillae are covered with cellslymphocytic infiltrate. Cells Note no deaths or recurrencess. Rarely spread as discreet glands or lymph nodes
If mucinous high stage rule out high stage. Multinodular, surface implants on ovary, ovary with lymphatic invasion by tumor. (rarelys ee vsi in primary ovary)
Mechanism of spread:
- Intra abdominal currents allow cytologic seeding to follow flow clockwise:
- Pelvis: right gutter to right hemidiaphragm through Bochdalek's foramina
surface of small bowel, liver, and omentum
- Lymphatic: through peri Aortic nodes to mediastinum to supraclavicular
to lung
- Hematogenous: rare
SURGICAL MANAGEMENT AND STAGING:
| Vertical Incision |
| Opening cytology: 20% of Stage I/II Positive. |
| |
30% are upstaged at re-exploration because of spread to para-aortic nodes, pelvic
nodes, cul-de-sac, diaphragm, omentum. |
| Run large and small bowel. |
| Omentum: 25% of Stage I and II Positive |
| Pelvic and para-aortic nodes--45% occult positives. 3-6% of Stages I/II are positive. |
Debulk all tumor. >75% of patients can be meticulously debulked to zero by GYN Oncologist when previous surgeon referred as non-debulkable. TAH-BSO, Infracolic omentectomy is standard. Do lymphadenectomy if well debulked, or to complete debulking. If cannot reduce bulk safely then relieve impending problems: i.e., remove large masses, relieve bowel obstructions, avoid future bowel obstructions.
ChemoTherapy for invasive epithelial carcinoma of the ovary:
Usually carboplatin with Taxol for 6 courses. Follow CA-125 and do clinical exam to r/o progression on chemo.
Second Look: Not standard. The procedure requires a methodical, meticulous exploration of the abdomen and pelvis, with four-quadrant peritoneal cytology specimens, biopsy of all lesions, all sites where residual left (must study original surgical report), resection of all adhesions, removal of omental pedicles, resection of ovarian pedicles with peritoneum. Resection or biopsy of cul-de-sac peritoneum, bowel adhesions, and peritoneal patches from paracolic gutters. Selective dissection of pelvic and aortic lymph nodes if not done previously. Appendectomy, if not already done. Removal of residual uterus, tubes, and ovaries. Resection of all residual carcinoma.
Four types:
1. Interval Primary debulking: Debulking of patients with a large tumor bulk who could not or were not debulked initially. Given after two or three courses of chemotherapy.
2. Interval Recurrence debulking: Debulking of patients who progress (new mass grows) during initial platinum containing chemotherapy regimens. Rarely appropriate or indicated as prognosis very poor.
3. Classic Second look: Procedure does not prolong life and has no indication currently. Useful in protocols to assess disease status. Also useful if patient did not have all indicated procedures prior to initiating chemotherapy. Goal is to determine if patient appears to be disease-free in order to stop therapy. Eligible patients must have no evidence of tumor by CT, sono, or MRI, and a negative CA-125.
4. Resection of post-chemo recurrent mass: Can debulk again if recur more than six months since completion of chemo and tumor initially responsive to chemo. Not appropriate if none of the available chemotherapeutic regimens are effective for ovarian tumors, or if recurrence occurs in less than six months after completion of chemotherapy because prognosis poor. Don't operate unless there is reasonable chemo plan available, but do relieve obstructions, paliate pain.
Therapy for recurrent tumor: If patient was originally sensitive to cisplatin, can give this in higher doses. Intraperitoneal chemotherapy may hold promise for the future; studies underway now. Resistance modifiers should be considered.
METASTATIC DISEASE TO OVARY
Get good history, while ruling out metastatic disease carefully. Always rule out met if high stage mucinous. All ages 29-89, bilateral, cystic, ovaries. Do very thorough exploratory laparotomy.
Colon
Gastric
Breast
Pancreas
Appendix
Pseudomyxomatous Peritonei Carcinoma
Clinical condition of gelatinous mucin filling peritoneal cavity mucinous implantsa and fibrous adhesion.
Associated witth appendix, ovary, intestine, bile duct and pancreas.
Histogenesis: peritoneal metaplasia
Rupture of ovarian cyst with implantation
Now believed a form of metastasis sites of peritonal fliud accumulates in right hemidiaphragm and in pelvis.
Clinical symptoms distension, age mid 50 acute appendix anorexia and early satiety from gastric compression.
Micro: see much mucin without mucin cells or with a scanty epitheliom showing low grade atypia = low grade adenomucinosis. Or see mucin with abundant epitheliom showing high grade atypical peritoneal mucinous carcinomatosis see inflammatory reaction with lymphocytes. If see clusters of signet ring then think adencatcinomma.
Pseudomyxoma ovarii-conditin limited to ovary
Pseudo mycoma peritonei usually with appy adenomss, possibley with high grade dysplasia (ACIS) or lwo grade adeno carcinoma or high grade carcinoma. Very rare because high grade grow so fast causing mortality.
Appendix
is usually the origin of PMP. Whatever we see in the ovary is secondary involvement, synchronous tumors. Bilateral ovarian tumors are usually met of PMP and havepredomonant surface involvement. Can see separate tumor if ovarian tumor is large, if thre is benign mucinous.
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