Surgical Stage I high-grade ovarian cancer: is adjuvant chemotherapy warranted?

OBJECTIVE: To review the results of patients with high-grade Stage I ovarian cancer managed without adjuvant treatment. MATERIALS AND METHODS: A retrospective chart review identified patients with newly diagnosed Stage I high-grade ovarian cancer, who underwent comprehensive surgical staging. RESULTS: Thirty-three patients with FIGO surgical Stage I high-grade ovarian cancer were identified. After a median follow-up of 40 months, nine patients (27%) recurred. The median time to recurrence was 19 months. Of the nine patients with recurrences, four (44%) are alive with disease, three (33%) patients have no evidence of disease, and two have died of disease (22%). The two- and five-year overall survival is 100% and 90%, respectively. CONCLUSIONS: It would appear the recurrence rates of Stage I high risk epithelial ovarian cancer completely staged, without adjuvant treatment are comparable to those of treatment arms reported in the literature. A proportion of these patients can be salvaged at recurrence, yielding a high overall survival.

Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer.

BACKGROUND: The histology and grade of endometrial cancer are important predictors of disease outcome and of the likelihood of nodal involvement. In most centres, however, surgical staging decisions are based on a preoperative biopsy. The objective of this study was to assess the concordance between the preoperative histology and that of the hysterectomy specimen in endometrial cancer. METHODS: Patients treated for endometrial cancer during a 10-year period at a tertiary cancer centre were identified from a prospectively collected pathological database. All pathology reports were reviewed to confirm centralised reporting of the original sampling or biopsy specimens; patients whose biopsies were not reviewed by a dedicated gynaecological pathologist at the treating centre were excluded. Surgical pathology data including histology, grade, depth of myometrial invasion, cervical stromal involvement and lymphovascular space invasion (LVSI) as well as preoperative histology and grade were collected. Preoperative and final tumour cell type and grade were compared and the distribution of other high-risk features was analysed. RESULTS: A total of 1329 consecutive patients were identified; 653 patients had a centrally reviewed epithelial endometrial cancer on their original biopsy, and are included in this study. Of 255 patients whose biopsies were read as grade 1 (G1) adenocarcinoma, 45 (18%) were upgraded to grade 2 (G2) on final pathology, 6 (2%) were upgraded to grade 3 (G3) and 5 (2%) were read as a non-endometrioid high-grade histology. Overall, of 255 tumours classified as G1 endometrioid cancers on biopsy, 74 (29%) were either found to be low-grade (G1-2) tumours with deep myometrial invasion, or were reclassified as high-grade cancers (G3 or non-endometrioid histologies) on final surgical pathology. Despite these shifts, we calculate that omitting surgical staging in preoperatively diagnosed G1 endometrioid cancers without deep myometrial invasion would result in missing nodal involvement in only 1% of cases. CONCLUSIONS: Preoperative endometrial sampling is only a modest predictor of surgical pathology features in endometrial cancer and may underestimate the risk of disease spread and recurrence. In spite of frequent shifts in postoperative vs preoperative histological assessment, the predicted rate of missed nodal metastases with a selective staging policy remains low.

Interobserver agreement for endometrial cancer characteristics evaluated on biopsy material.

A shift toward a disease-based therapy designed according to patterns of failure and likelihood of nodal involvement predicted by pathologic determinants has recently led to considering a selective approach to lymphadenectomy for endometrial cancer. Therefore, it became critical to examine reproducibility of diagnosing the key determinants of risk, on preoperative endometrial tissue samples as well as the concordance between preoperative and postresection specimens. Six gynaecologic pathologists assessed 105 consecutive endometrial biopsies originally reported as positive for endometrial cancer for cell type (endometrioid versus nonendometrioid), tumor grade (FIGO 3-tiered and 2-tiered), nuclear grade, and risk category (low risk defined as endometrioid histology, grade 1 + 2 and nuclear grade <3). Interrater agreement levels were substantial for identification of nonendometrioid histology (κ = 0.63; SE = 0.025), high tumor grade (κ = 0.64; SE = 0.025), and risk category (κ = 0.66; SE = 0.025). The overall agreement was fair for nuclear grade (κ = 0.21; SE = 0.025). There is agreement amongst pathologists in identifying high-risk pathologic determinants on endometrial cancer biopsies, and these highly correlate with postresection specimens. This is ascertainment prerequisite adaptation of the paradigm shift in surgical staging of patients with endometrial cancer.

Androgenetic complete mole with trisomy 13: report of a case with microsatellite genotyping and review of the literature.

Hydatidiform moles are gestational diseases with abnormal development of the villous trophoblast and characterized by an excess of paternal to maternal genetic material. Complete moles are usually diploid and androgenetic, and are thought to develop after the fertilization of an "empty ovum" by either a haploid spermatozoon or two spermatozoa. We report a case of a complete mole in which fluorescence in situ hybridization (FISH) incidentally disclosed trisomy 13. Microsatellite genotyping showed a single allele at each of the markers tested on the chorionic villi, and comparison with parental peripheral blood specimens revealed that the markers were all of paternal origin. These results confirmed the paternal origin of all three copies of chromosome 13, and the isodisomy for each chromosome was consistent with duplication of a monospermic fertilization event and subsequent non-disjunction. To the best of our knowledge, this is the only case of an androgenetic complete mole with trisomy 13 described in the scientific literature. We present a review of the literature and hypothesize that the trisomy 13 in our case likely resulted from non-disjunction of chromosome 13.

Sentinel lymph node biopsy vs. pelvic lymphadenectomy in early stage cervical cancer: is it time to change the gold standard?

OBJECTIVE: To compare the incidence of pelvic lymph node metastases in early stage cervical cancer patients undergoing sentinel lymph node biopsy (SLN) to a matched cohort undergoing pelvic lymphadenectomy. METHODS: All patient data were entered prospectively into an ongoing cervical cancer database. Since April 2004, 87 patients with FIGO stage IA/B1 cervical cancer underwent SLN detection with identification of bilateral SLN. This cohort (cases) was compared to a matched group of patients who underwent complete pelvic lymphadenectomy (controls). The groups were matched 3:1 for tumour size (+/-5 mm), histology, depth of invasion (+/-2 mm), and presence of capillary lymphatic space invasion (CLS). Descriptive statistics were calculated for all variables of interest. The association between cases and controls and lymph node metastases was carried out using a conditional logistic regression analysis. RESULTS: 81 women in the SLN cohort were matched with 1 control, 72 cases with 2 controls, and 65 cases with 3 controls. Among cases, 14 (17%) had pelvic lymph nodes metastases vs. 15 (7%) in the controls (p=0.0059, odds ratio= 2.8, 95% CI=1.3-5.9). Among the 14 cases of SLN metastases, 11 were detected by frozen section and 3 were detected on final paraffin sectioning. All were detected by H and E stains. The size of the SLN metastases ranged from less than 1 mm to 8 mm. CONCLUSIONS: Sentinel lymph node biopsy in early cervical cancer is a more sensitive procedure in detecting pelvic lymph node metastases compared to complete lymphadenectomy.

Intraoperative margin assessment of the radical trachelectomy specimen.

OBJECTIVE: To summarize our experience in the frozen section (FS) assessment of the trachelectomy surgical margin. METHODS: All surgeries from 1994 to 2007 were performed by one surgeon. The FS examination was consistently carried out by a group of gynecologic pathologists according to the protocol described in details in this article. Cases were retrieved from the pathology files and the slides were reviewed by two pathologists. RESULTS: 132 patients were identified with complete pathology records. They ranged from 17 to 46 years old (median 31). Surgeries were performed for clinical Stages 1A (n=39) and 1B (n=93) tumors (63 adenocarcinoma, 59 squamous cell carcinoma, 7 adenosquamous and 3 others). In 78 cases, no residual tumor was seen in the trachelectomy specimens as it was resected by the preceding LEEP or cone. The margin was reported as negative in 123, suspicious in 3 and positive in 6 cases. It was revised in 16 cases (6 positive, 2 suspicious and 8 negative but <5 mm). Final margin assessment agreed with the FS diagnosis in 130 (98.5%) and showed interpretational overcall in 2 cases (1.5%); only one of which resulted in a revised margin. No false negative intraoperative assessment was found. CONCLUSIONS: We describe our FS protocol and summarize our data. This protocol is reliable since none of the patients was under-treated.

Radical vaginal trachelectomy vs. radical hysterectomy for small early stage cervical cancer: a matched case-control study.

OBJECTIVE: To determine the efficacy and outcome from radical vaginal trachelectomy (RVT) compared to a matched group of patients undergoing radical hysterectomy for small early stage cervical cancer. METHODS: All patient data were entered prospectively. Patients wishing preservation of fertility with cervical cancer, tumor <2 cm, and not meeting the definition of microinvasive cancer were offered RVT. The outcomes were compared to a matched group of patients who underwent radical hysterectomy for stage IA/IB cervical cancer. Groups were matched 1:1 for age (+/-5 years), tumor size (+/-1 mm), histology, grade, depth of invasion (+/-1 mm), presence of capillary lymphatic space invasion, pelvic lymph node metastasis, and adjuvant radiotherapy. RESULTS: A total of 137 patients underwent RVT between 1994 and 2007. Of them, 90 patients were successfully matched. Median tumor size was microscopic. Moreover, 43% and 49% were squamous and had adeno/adenosquamous histology. Median depth of invasion was 3.1 mm. Capillary lymphatic space invasion was present in 68% of cases. Of the tumors, 60% were grade 1, 29% were grade 2, and 11% were grade 3. After a median follow-up of 51 and 58 months, 5 and 1 recurrences were diagnosed in the RVT and radical hysterectomy groups, respectively. Five-year recurrence-free survival rates were present in 95% and 100% of the groups, respectively (p=0.17). In addition, 3 and 1 deaths occurred in the RVT and radical hysterectomy groups, resulting in 5-year survival rates of 99% and 100%, respectively (p=0.55). CONCLUSIONS: RVT seems to be the procedure of choice for women with small early stage cervical cancers wishing to preserve fertility.

Immunohistochemical characterization of endocervical papillary serous carcinoma.

Endocervical adenocarcinomas are rare and aggressive neoplasms. Papillary serous endocervical adenocarcinomas are the rarest form of endocervical adenocarcinomas. This tumor exhibits morphologic similarities to its counterparts commonly seen in the endometrium, fallopian tubes, ovaries, and peritoneum, which are known to have an aggressive behavior. Because of the rarity of this tumor, little is known about its immunophenotyping. In this study, we included ten cases of papillary serous carcinomas arising from the uterine cervix (PSCC) diagnosed in the absence of a primary endometrial malignancy. We studied their immunohistochemical profile, using a panel of antibodies against Ki67, bcl-2, p53, carcinoembryonic antigen (CEA), and CD10, and compared them to 20 consecutive cases of cervical adenocarcinoma of conventional cell subtypes (CAC) (15 mucinous, 3 adenosquamous, and 2 endometrioid). Immunostaining was recorded semiquantitatively. Patients with PSCC ranged in age from 27 to 79 years (mean = 51.6 +/- 19.1), while the conventional cell subtypes control group were 28-90 years old (mean = 47.5 +/- 16.9). Only p53 and CEA immunostaining significantly correlated with the PSCC morphology (P= 0.001 and P= 0.016, respectively) as shown by Cochran-Mantel-Haenszel Statistics (Modified Ridit Scores). PSCC is a distinctive immunophenotypic subtype of endocervical adenocarcinoma with significantly higher p53 and lower CEA reactivity than other more common histologic subtypes.

What are the CD34+ cells in benign peripheral nerve sheath tumors? Double immunostaining study of CD34 and S-100 protein.

To determine whether CD34 expression in nerve sheath lesions was found in a unique cell population or in a subset of nerve sheath cells, we performed double immunohistochemical staining using a standard avidinbiotin complex method with 2 separate color developing systems. We studied 40 neurofibromas and 16 neurilemomas. All lesions strongly expressed S-100 in nuclei and cytoplasm. CD34 was detected in cells having ameboid dendritic cytoplasm present in greatest numbers in Antoni B zones of neurilemomas, myxoid zones of neurofibromas, at the periphery of lobules in both tumor types, and condensed in apposition to perineurium. The CD34+ cells also were detected in normal nerves. They were infrequent in Antoni A zones of neurilemomas. No dual S-100 and CD34 expression was seen. This double immunostaining confirms the presence of a CD34-reactive non-Schwannian cell type in these neural neoplasms. As the CD34+, S-100-negative cell population is present also in normal nerves and infrequently seen in the areas of cellular neoplastic Schwann cells, CD34+, S-100-negative cells in peripheral nerve sheath tumors most likely are nonneoplastic and may have a supportive function.