Appendiceal adenocarcinoma presenting with bilateral Krukenberg tumors

Primary appendiceal malignancy metastatic to the ovaries is a condition that may mimic advanced stage ovarian cancer. This condition is rarely diagnosed preoperatively. A 52-year-old woman referred to our institution for presumed advanced stage of ovarian cancer was found to have primary appendiceal adenocarcinoma metastatic to ovaries at laparotomy. We describe the clinical course of the patient. It is important for the gynecologist-oncologist to include tumors of the appendix into the differential diagnosis of any case of ovarian tumor.     

The role of appendectomy in surgical procedures for ovarian cancer.

To assess the role of appendectomy in the surgical procedures for ovarian cancer, we evaluated retrospectively the clinical charts of 435 patients who underwent surgery after diagnosis of ovarian cancer. The appendix was removed in 160 cases and pathological examination revealed 37 with metastatic implants (23%). All the patients with appendiceal metastases showed advanced disease (stages III-IV) with an incidence of 43%. Ninety-one percent (31/34) of the tumors with appendiceal involvement at the staging operation were of the serous cell type and grade II or III. No case with early stage, right ovary carcinoma showed appendiceal metastatic foci, denying the existence of a preferential lymphatic pathway. Microscopic involvement was found only in 4 patients with advanced disease (11.7%). No intra- or postoperative complication directly related to the appendectomy was recorded. We conclude, with these results, that appendectomy should be part of the cytoreductive operation for ovarian cancer.     

Ovarian management at the time of radical hysterectomy for cancer of the cervix

Ovarian management at the time of radical hysterectomy for cervical cancer was reviewed retrospectively over a 7-year period. All patients had early-stage cancer except three who had stage IIB disease. Approximately 80% of patients had squamous cancer and 20% adenocarcinoma or adenosquamous carcinoma. The mean age was 44, and 24% of patients were 35 or younger. Ninety-nine patients had their ovaries removed. None of the ovaries contained metastatic disease including 22 patients with adenocarcinoma or adenosquamous carcinoma. Of the 17 patients with retained ovaries 14 had transposition into the paracolic gutters. Only one of the 14 patients with transposed ovaries developed symptoms of ovarian failure. No patients with retained ovaries developed metastatic disease or required reoperation secondary to new ovarian pathology. It is our opinion that normal ovaries can be preserved in young women at the time of radical hysterectomy for early cervical cancer regardless of histologic type.     

Survival and prognostic factors in patients with synchronous ovarian and endometrial cancers and endometrial cancers metastatic to the ovaries

PURPOSE: To compare the survival and prognostic factors of patients with synchronous primary ovarian and endometrial cancers, and endometrial cancers metastatic to the ovaries. PATIENTS AND METHODS: Fifty-three patients with synchronous primary ovarian and endometrial cancer and 64 patients with endometrial cancer metastatic to the ovaries were evaluated. RESULTS: Mean follow-up time was 47.2 months (18-170 months). There was no statistical difference in age, gravidity and parity between the two groups. Abnormal vaginal bleeding was the most common symptom in both groups. All patients were subjected to a surgical staging procedure. Overall survival of the synchronous group was significantly higher than that of the metastatic group (98 +/- 12 vs 59 +/- 6 months; p = 0.048). The significant prognostic factors for synchronous cancers after multivariate analysis were age, stage of ovarian cancer, grade of endometrial cancer, and adjuvant therapy status. CONCLUSION: Patients with synchronous ovarian and endometrial cancers appear to have a good prognosis and should undergo primary surgical staging since the stage of tumors is a significant prognostic factor.     

Histological Features of the Contralateral Ovary in Patients with Unilateral Ovarian Cancer: A Case Control Study

Objective.Most of the surface epithelial–stromal tumors of the ovary are thought to arise from epithelial inclusion cysts, thus these cysts, and the original surface epithelium, are precursor lesions of ovarian carcinoma.Material and methods.The histological features in contralateral ovary from 20 patients with unilateral ovarian carcinoma were compared with 20 ovaries of patients without ovarian pathology and with 12 normal ovaries of women with contralateral benign ovarian pathology.Results.Cortical invaginations were more frequent and numerous in ovaries of patients with contralateral ovarian carcinoma. The presence of cortical invaginations and epithelial inclusion cysts showed correlation in patients with cancer and in those without ovarian pathology, but there were no differences in the number of inclusion cysts when the three groups were compared. Mild cytological atypia was detected more frequently in the surface epithelium of contralateral ovaries of patients with ovarian carcinoma. Ovarian size, cortical thickness, stromal hyperplasia, psammoma bodies, and surface papillae did not show differences when comparing patients with cancer and control groups.Conclusion.Cortical invaginations, a previous step in the formation of epithelial inclusion cysts, can also play an important role in the genesis of ovarian carcinoma.     

Incidence of Ovarian Cancer in Women with Prior Hysterectomy in Japan

Objective.Our aim was to estimate the number of women in Japan in whom ovarian cancer could be prevented by performing prophylactic oophorectomy.Methods.Of 1289 women who were diagnosed clinically and histologically as having primary cancers of the ovary between 1986 and 1995, 53 (4.1%) had undergone hysterectomy with conservation of one or both ovaries. Clinical data and representative microscopic slides for these 53 cases were evaluated.Results.Hysterectomy had been performed at the age 45 or above in 28 of the 53 patients (53%). We estimated that performance of prophylactic oophorectomy in women who underwent a hysterectomy at age 45 or older would prevent 2.2% (4.1% × 0.53) of the cases of ovarian cancer in Japan, which is below the 3.3% estimated for women in other countries. The interval between the hysterectomy and the diagnosis of ovarian cancer ranged from 1 to 29 years (mean 9.9 years). Fourteen patients (26%) developed ovarian cancer within 5 years of the hysterectomy. The overall 3-year survival rate of these 53 patients was 65%, not significantly different from that for patients with ovarian cancer in the national study in Japan.Conclusions.Prophylactic oophorectomy for the prevention of ovarian cancer in Japanese women would appear to have a lesser impact than reported in other industrialized nations. The short interval between hysterectomy and the diagnosis of ovarian cancer observed in 26% of the patients suggested that ovarian cancer can develop within a few years of the visualization of apparently normal ovaries.     

Primary appendiceal cancer: gynecologic manifestations and treatment options

OBJECTIVE: To determine the presenting symptoms, gynecologic manifestations, and optimal intraoperative management of women with primary appendiceal cancer. METHODS: A multi-institutional investigation was performed to identify female patients with primary appendiceal cancer who were treated from 1990 to present. RESULTS: Forty-eight women with primary appendiceal cancer were identified from the tumor registries of participating institutions. The most common symptoms were abdominal pain (40%) and bloating (23%), but only 8% experienced rectal bleeding. Serum CEA was elevated (>2.5 U/ml) in 67% of patients, and serum Ca-125 was elevated (>35 U/ml) in 50% of patients. Thirty-one patients (65%) presented with a right adnexal or right lower quadrant mass and were operated on initially by a gynecologic oncologist. Ovarian involvement by metastatic appendiceal cancer was documented in 18 patients (38%). All of these patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and staging, but only 8 had a right hemicolectomy at the time of initial surgery. Forty-one patients (85%) presented with advanced stage appendiceal cancer (Stage III or IV) and 19 patients (46%) received postoperative chemotherapy, most commonly with a combination of 5-FU/Leukovorin. Following surgery, 22 patients (46%) experienced disease progression or recurrence, and 14 have died of disease. The most common sites of recurrence were abdominal or pelvic peritoneum (18), colon (2), and ovary (2). Patient survival was 70% at 2 years, and 60% at 5 years. CONCLUSION: Women with primary appendiceal cancer frequently present with ovarian metastases, and initial surgical intervention is often performed by a gynecologic oncologist. All patients with mucinous epithelial ovarian cancer should undergo appendectomy at the time of surgical staging. The appendix should be examined intraoperatively, and if appendiceal carcinoma is identified, a right hemicolectomy and appropriate surgical staging should be considered.     

B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125 expression

OBJECTIVE: This study characterizes the expression of the novel biomarker B7-H4 in ovarian cancer tissue, normal ovaries, and benign ovarian tumors, and evaluates its relationship to CA125. METHODS: Ovarian tissue lysates from 251 patients with ovarian carcinoma were assessed for the levels of B7-H4 and CA125 by ELISA assays. For comparison, ovarian tissues from patients with benign ovarian tumors (n=43) and patients with normal ovaries (n=32) were tested. The marker concentrations were correlated with CA125 expression, clinicopathological variables, and patient outcome. RESULTS: Using a cut-off based on the 95th percentile of B7-H4 or CA125 concentration in the control group, B7-H4 was over-expressed in 48% of patients with stage I cancer, 55% of patients with stage II cancer, and 67% of patients with late stage cancer. CA125 was elevated in 31% patients with early stage cancer. B7-H4 was elevated in tumors of 30 patients with early stage cancer that were negative for CA125. The combination of B7-H4 and CA125 identified 56 early stage cancer patients (65%) as positive. Correlation of marker expression to clinical outcome showed that high B7-H4 levels were correlated with poor prognosis. However, the effect was not significant when outcome was adjusted for other clinicopathological variables. CONCLUSION: B7-H4 expression was low in normal ovaries and in benign tumors while half of early stage and two-thirds of late stage cancers over-expressed B7-H4. The data are consistent with previous observations and support further investigation of B7-H4 in the detection of early stage ovarian cancer either alone, or in combination with CA125.     

Rate of Appendiceal Metastasis with Non-Serous Epithelial Ovarian Cancer in Manitoba

Objective

This study sought to evaluate the rate of appendiceal involvement in non-serous mucinous and endometrioid-associated epithelial ovarian cancers.

Ovarian Histopathology in Breast Cancer Patients Receiving Tamoxifen

Objective. The purpose of this study was to examine ovarian histopathology in tamoxifen-treated breast cancer patients undergoing oophorectomy.Methods. We reviewed the records and ovarian histopathology of 152 breast cancer patients who underwent oophorectomy at a single institution between January 1980 and October 1996. At the time of oophorectomy, 99 patients had never received tamoxifen, 44 patients were currently receiving tamoxifen, and 9 patients had previously received tamoxifen. Patient demographic and medical data and indication for oophorectomy were examined. Ovarian histopathology was classified as normal, functional ovarian cyst, benign ovarian tumor, endometriosis, ovarian cancer, and metastatic cancer.Results. Patient characteristics and indication for oophorectomy did not differ significantly based on tamoxifen exposure. There was no difference in the occurrence of benign ovarian tumors, functional ovarian cysts, or metastatic breast cancer based on tamoxifen exposure. Tamoxifen-treated patients were less likely to have ovarian cancer, 0 of 53 patients (95% confidence interval (CI): 0.0%, 6.7%) compared with 10 of 99 patients (95% CI: 5.0%, 17.8%) patients not receiving tamoxifen (P = 0.015). Endometriosis was slightly more common in patients currently receiving tamoxifen, but the difference was not statistically significant.Conclusions. In women undergoing oophorectomy, there was no evidence that tamoxifen exposure was associated with an increase in benign or malignant primary or metastatic ovarian neoplasm or in functional ovarian cysts. Further study is necessary to better define any association between tamoxifen and endometriosis and the effect of tamoxifen on ovarian cancer risk.     

Metastatic cancer in transposed ovaries after radical Wertheim-Meigs hysterectomy for a stage I B and II A cervical cancer

In this research work we show our and foreign experience in preserving the ovarian function in young women and cervical cancer stage I B and II A. 6 cases are quoted for the period of time from 1987 till 2003 (4 patients with ovarian metastases from our experience and 2 patients with ovarian metastases found from the greek colleagues). Histologically 3 patients were with adenosquamous metastatic cervical cancers and 3 patients with squamous metastatic cervical cancers in the region of the transposed ovaries. The metastases occurred mostly 2 to 3 years after the radical hysterectomies a modo Wertheim-Meigs. Nevertheless our experience which is connected with radical hysterectomies a modeo W. Meigs including both ovaries, we have also experience in transposing ovaries /one or both of them/. In some of them we found metastases. In our research work we found 4 cases with metastases in transposed ovaries. In these cases a chemotherapy was applied: mitomicin C, etoposide, and cysplatinum. The greek colleagues also have applied such schemes of chemotherapy. 3 from the patients had a very good effect from the chemotherapy, in 2 the recurrences have appeared 2 years after the chemotherapy, and in one case there was a very big progression of the disease, nevertheless the chemotherapy. IT is very important for the oncogynaecologist to clear up if the transposition of the ovaries is safe and effective, especially in young patients with early cervical cancer receiving postoperative radiotherapy. That is why we did this research work in order to give more light on this problem.     

Coexisting ovarian malignancy in patients with clinical stage I endometrial carcinoma

Aim

To evaluate the feasibility of ovarian preservation at the time of operation in patients with clinical stage I endometrial carcinoma.

Materials and methods

The data of 499 consecutive patients with clinical stage 1 endometrial cancer operated between January 2001 and December 2011 were retrospectively reviewed. Clinical and pathologic information and the intraoperative inspection findings of ovaries were evaluated to find the factors associated with the coexisting ovarian malignancy.

Results

The mean age of patients was 56.8?±?9.8?years. Coexisting ovarian tumors were detected in 38 patients (7.6?%), and 28 (5.6?%) of them were malignant (12 metastatic and 16 synchronous primaries). Most of the patients were postmenopausal (n?=?371, 74.3?%) and 60 (12?%) of the patients were at the age of 45?years or less. Coexisting malignancy was detected in 9?% (n?=?11) of the premenopausal patients and in 5?% (n?=?3) of the patients aged 45?years or less. Multivariate analysis revealed that serosal invasion, tubal involvement, and positive abdominal cytology were independent risk factors for coexisting ovarian malignancy. The sensitivity, specificity, positive predictive value and negative predictive value of the intraoperative examination for the diagnosis of benign/normal ovary was 99.6, 78.8, 98.5 and 92.9?%, respectively.

Conclusion

The incidence of coexisting ovarian malignancy in clinical stage I endometrial carcinoma is low. Although occult metastasis cannot be excluded at all, careful intraoperative inspection of ovaries seems valuable for the prediction of co-existing ovarian malignancy.     

Two Concurrent Cancers in a 19-Year-Old Patient: Yolk Sac Ovarian Tumor and Metastatic Gastrointestinal Tract Malignancy—Case Report

BackgroundTwo concurrent malignancies present in a young person is an extremely rare condition. Diagnoses of gastric cancer primarily concern older patients. There are very few reports of concomitant Krukenberg tumor and germ-cell ovarian malignancy.CaseA 19-year-old girl was admitted to the gynecologic oncology department with symptoms of advanced malignancy. Radiological imaging revealed disseminated neoplastic disease with bulky adnexal tumors. Cytoreductive surgery was performed, achieving no visible disease (T = 0 cm). The final pathology report confirmed metastatic mixed adenoneuroendocrine carcinoma (MANEC) in both ovaries, originating from the gastrointestinal tract. Moreover, the primary germ cell yolk sac tumor was found in the left ovary.ConclusionIn cases of concomitant gastric and ovarian tumors, metastatic disease (Krukenberg tumor) should be considered in the differential diagnosis. This concerns even adolescent patients. In particular cases, including tumors with germ cell components, primary debulking surgery is crucial for prognosis.     

Retrograde Lymphatic Spread: A Likely Route for Metastatic Ovarian Cancers of Gastrointestinal Origin

In order to outline the pathways of gastrointestinal malignancies metastasizing to the ovaries, we reviewed 103 cases of metastatic ovarian tumors, and also performed para-aortic lymph node sampling on 11 patients at operation for metastatic ovarian tumors. Of the 103 patients, 74% (26/35) with gastric cancer and 67% (45/67) with colorectal cancer had lymph node metastasis at or before the diagnosis of ovarian tumor. Intraperitoneal metastases presented in 49 and 42% of patients with gastric and with colorectal cancers, respectively. Twenty-three percent of gastric cancer patients and 25% of colorectal cancer patients presented with both lymph node and intraperitoneal metastases. The ovary was the first or among the early metastatic organs diagnosed in 51 of the 53 patients with metachronous ovarian metastases. Only 4 patients with colorectal cancer and none with gastric cancer showed parenchymal organ metastases. These 4 patients also showed intraperitoneal lesions, and 3 of these 4 patients had node metastasis. Among the 11 patients who underwent prospective para-aortic lymph node sampling during operation for the ovarian tumors, only 1 had enlarged para-aortic nodes depicted by computed tomography, 2 had grossly enlarged (≥1.5 cm) para-aortic lymph nodes noted at surgery, and 6 of the 7 patients with gastric cancer and all 3 with colorectal cancer had metastatic nodes histologically. Among the 58 nodes taken from these patients, 67% showed metastatic foci. We concluded that lymph node metastasis is frequently seen in patients with metastatic ovarian tumors of gastrointestinal origin, and hypothesized that retrograde lymphatic spread is a likely route for the metastases.     

Ovarian metastasis in women with clinical stage I endometrial carcinoma

BACKGROUND: The incidence of ovarian metastasis in women with clinical stage I endometrial carcinoma is generally reported to be 5%, leading to the practice of removing the ovaries at surgery even in young patients. METHODS: A retrospective study of 84 patients with clinical stage I endometrial cancer was carried out. Patients were excluded if the pathologic study revealed any evidence of extrauterine, apart from adnexal, spread or if the peritoneal cytology was positive. Patients with serous papillary or clear cell tumor histology were also excluded. RESULTS: Sixty-seven patients fulfilled the inclusion criteria. Only three (4%) patients were found to be in surgical stage IIIA, all three had grade 3 tumors. Of these patients, two had uterine serosal involvement and one had a microscopic tumor implant in a fallopian tube; none had ovarian metastasis. CONCLUSIONS: The risk of ovarian metastasis in women with well to moderately differentiated endometrial cancer, myometrial invasion limited to less than one half of the myometrium, negative peritoneal cytology and no evidence of metastatic lymph node spread is negligible. Young patients with a preoperative histological diagnosis of well to moderately differentiated endometrial carcinoma may be surgically staged, leaving the final decision regarding removal of the ovaries pending a thorough pathological review of the surgical specimens.     

放疗对早期子宫颈癌患者移位卵巢功能的影响

目的探讨放疗对早期(Ⅰ~Ⅱa期)宫颈癌患者移位卵巢功能的影响。方法对早期宫颈癌患者62例行广泛性全子宫切除加盆腔淋巴结切除加双侧卵巢结肠旁沟侧方移位术,术后随访患者有无绝经期症状,并测定血清中卵泡刺激素和雌二醇水平以判定卵巢功能。62例患者中, 30例未予任何放疗(G0组); 17例患者仅术前接受了A点剂量为15Gy的腔内后装治疗(G1组); 15例术后予以45~50Gy盆腔外照射(G2组),其中14例术前已接受了放疗(方法同G1组)。结果G0、G1和G2组患者卵巢功能衰竭的发生率分别为20% (6 /30)、35% (6 /17)和64% (9 /14),分别两两比较,差异均有统计学意义(P<0 01); 3组术后发生卵巢功能衰竭的患者中,其平均衰竭时间分别为15 7、12 0和9 2个月,分别两两比较,差异均有统计学意义(P<0 05)。2例(3% )发生了移位卵巢囊肿,未发现卵巢转移。结论早期宫颈癌患者术前或术后放疗均能明显引起卵巢功能衰竭,甚至卵巢移位手术本身也会影响卵巢的功能。     

Histology of Prophylactically Removed Ovaries from BRCA1 and BRCA2 Mutation Carriers Compared with Noncarriers in Hereditary Breast Ovarian Cancer Syndrome Kindreds

Objective. The literature reports conflicting studies claiming premalignant histological features in benign ovaries from women who may have hereditary predilections for ovarian carcinoma. To test the veracity of these claims, this investigation studied ovaries prophylactically removed from members of hereditary breast ovarian cancer (HBOC) syndrome families who carry BRCA1 and BRCA2 mutations and compared these with the ovaries of mutation-negative women from the same HBOC syndrome kindred.Methods. Sixty cases of women from HBOC syndrome families who had undergone prophylactic oophorectomies and whose BRCA1 and BRCA2 mutation status had been tested were selected from our database. Thirty had tested positive for BRCA1 mutations, 3 carried BRCA2 mutations, and 27 were negative for both BRCA1 and BRCA2 germline mutations. Histologic material from each case was examined by light microscopy blinded to the mutation status. Histologic features, previously reported to be possible precursor lesions for ovarian cancer, were quantified. Data from BRCA1 and BRCA2 mutation carriers were compared with those from mutation-negative cases in the direct line of genetic inheritance from the same HBOC syndrome families.Results. Statistical analysis found that a more frequent occurrence of ovarian surface micropapillae in 87% of mutation carriers compared with just 55% of mutation-negative cases was the only histologic feature which was significantly different between the two groups (P = 0.39). Cortical clefts tended to be deeper in the ovaries of mutation carriers, but this did not reach significance (P = 0.051). There were no other significant histologic differences between the ovaries removed from mutation carriers and those from noncarriers.Conclusions. The results of our large and prospectively controlled, blinded study contrast with those reported from smaller, unblinded investigations. Except for the possible biological significance of surface micropapillae on ovaries from BRCA1 and BRCA2 mutation carriers, we found no histologic evidence for a genetically determined ovarian carcinoma precursor lesion.     

Pathology of borderline (low malignant potential) ovarian tumours

Recent studies suggest that the borderline group of ovarian tumours can be subclassified into benign and malignant neoplasms. The survival for patients with serous borderline tumours confined to the ovaries is virtually 100%. Patients with serous borderline tumours with invasive peritoneal implants, and with micropapillary serous carcinomas (a distinctive neoplasm previously included in the borderline category), have a 30-40% mortality rate and therefore these tumours are classified as carcinomas. After these neoplasms are excluded, the remaining advanced stage serous borderline tumours (those with non-invasive implants) have a survival rate of nearly 100% and should be considered benign. Similarly, nearly all mucinous borderline tumours reported to display aggressive behaviour have been associated with pseudomyxoma peritonei, a condition now known to be of appendiceal origin. The remaining mucinous borderline tumours are always confined to the ovaries and have a benign behaviour. Since borderline tumours can now be classified into benign and malignant types, the category has no further utility.     

Frequent and increased expression of human METCAM/MUC18 in cancer tissues and metastatic lesions is associated with the clinical progression of human ovarian carcinoma

ObjectivesHuman METCAM/MUC18 (huMETCAM/MUC18), a cell adhesion molecule, plays an important role in the progression of several epithelial cancers; however, its role in the progression of epithelial ovarian cancers is unknown. To initiate the study we determined expression of this protein in normal and cancerous ovarian tissues, cystadenomas, metastatic lesions, and ovarian cancer cell lines.Materials and methodsImmunoblotting and immunohistochemical (IHC) methods were used to determine huMETCAM/MUC18 expression in lysates of frozen and formalin-fixed, paraffin-embedded tissue sections of normal human ovaries, and ovarian (benign) cystadenomas, carcinomas and metastatic lesions. We also determined expression levels of several downstream effectors of METCAM/MUC18 in these tissues.ResultsHuMETCAM/MUC18 levels in ovarian carcinomas and metastatic lesions were significantly higher than in normal tissues and cystadenomas. IHC results showed that expression of huMETCAM/MUC18 in normal tissues and cystadenomas was mostly absent from epithelial cells, but in carcinomas and metastatic lesions it was localized to epithelial cells. In higher pathological grades of ovarian cancer and metastatic lesions, the percentage of cells stained in IHC was increased. Thirty percent of normal tissues weakly expressed the huMETCAM/MUC18 antigen, but 70% of cancer tissues and 100% of metastatic lesions expressed the antigen. Expression levels of several downstream effectors of huMETCAM/MUC18, Bcl2, PCNA and VEGF, were elevated in cancerous tissues, however, not that of Bax. The phospho-AKT/AKT ratio was elevated in metastatic lesions.ConclusionUpexpression of huMETCAM/MUC18 may be a marker for the malignant potential of ovarian carcinomas. Progression of ovarian cancer may involve increased signaling in anti-apoptosis, proliferation, survival/proliferation pathway, and angiogenesis.