The distinction of ovarian clear cell carcinomas (CCCs) from high-grade serous carcinomas (HG-SCs) is sometimes a diagnostic challenge. With the recognition that CCCs respond poorly to conventional chemotherapy there are efforts to initiate clinical trials for CCC, making accurate diagnosis critical. The purpose of this study was to test and validate a set of antibodies that could aid in the diagnosis of CCC, using a series of cases from different centers in North America. Using a test set of 133 CCCs, we identified the following markers: Cyclin E, estrogen receptor, hepatocyte nuclear factor (HNF)-1beta, Ki-67, p21, p53, and Wilms tumor (WT)1 that show significant discrimination from 200 HG-SCs. For validation, these markers were characterized on an independent set of 104 CCCs from 3 other centers. There were no significant differences in expression of these 7 markers between the independent test and validation sets of CCC. Combining all CCC cases (N=237), HNF-1beta showed the highest sensitivity (82.5%) and specificity (95.2%) for CCC, and WT1 for HG-SC (sensitivity: 79.9%, specificity: 97.4%). A diagnostic panel consisting of WT1, ER, and HNF-1beta demonstrated nearly identical performance as a panel using all 7 markers in distinguishing CCCs from HG-SCs, correctly classifying 84% of cases. Three percent of cases were misclassified and 13% carried an uninformative triple negative immunophenotype. CCCs show a distinct, reproducible immunophenotype, compared with HG-SCs, and a panel of 3 immunomarkers can serve as a diagnostic aid in problematic cases.

Uterine leiomyosarcomas (Ut-LMSs) are aggressive tumors with an overall poor prognosis (15% to 25% 5-year survival rate). However, patients with stage I Ut-LMSs are reported to have a relatively better outcome when compared with the overall group with a 5-year survival rate ranging from 25% to 75%. The purpose of this study was to evaluate the histopathologic parameters that may impact outcome in stage I Ut-LMSs. Twenty-seven patients with stage I Ut-LMSs were identified from the files of 5 tertiary care hospitals between 1974 and 2006. Tumors were primarily staged based on pathologic information, supplemented with radiologic findings (10 cases) and clinical records (1 case). Patients with stage I tumors with no additional clinical or radiologic staging information were included in the study if no recurrence was documented after 6 months from the initial staging operation (16 cases). Clinicopathologic parameters that were statistically evaluated included age [mean, 54 y (37 to 73)], tumor size [mean, 9.5 cm (5.5 to 16)], cell type (17 spindled, 5 epithelioid, 2 myxoid, and 3 mixed), mitotic activity [mean count, 24 (4 to 69)/10 high-power fields], marked cytologic atypia (26 of 27 cases), tumor cell necrosis (12 of 27 cases), and lymphovascular invasion (6 of 27 cases). Follow-up was available for all the patients. Poor outcome was defined when patients either died of disease or were alive with disease. Overall, accounting for any length of follow-up, 16 of 27 (59%) patients with stage I Ut-LMSs had poor outcome; 7 died of disease (mean follow-up, 13 mo) and 9 were alive with disease (mean follow-up, 31 mo). The remaining 11 patients were alive and well with a mean follow-up of 48 months. However, at 2 years of follow-up by univariate analysis, only nonspindle morphology (P<0.0183) and diffuse high-grade cytologic atypia (P<0.02) were statistically associated with poor outcome. No statistically significant association with survival was identified by univariate analysis when evaluating mean age, mean tumor size, presence of tumor cell necrosis, mean mitotic count, or lymphovascular invasion. In conclusion, stage I leiomyosarcoma is associated with poor prognosis. No conclusive differences were observed among different clinicopathologic parameters and prognosis, although it seemed that spindle cell morphology and diffuse high-grade cytologic atypia were associated with longer overall survival and higher death rates, respectively.

No abstract

We investigated the risk associated with variants in three genes involved in estrogen biosynthesis, CYP11A1, CYP17A1, and CYP19A1, in the population-based case control study of Estrogen, Diet, Genetics, and Endometrial Cancer. This study was conducted in New Jersey in 2001-2006 with 417 cases and 402 controls. For CYP11A1, there was no association between the number of [TTTTA] n repeats (D15S520) and risk. For CYP17A1, risk was somewhat lower among women with the C/C genotype at T-34C (rs743572) (adjusted OR=0.65, 95% CI 0.41-1.02). For CYP19A1, risk was lower among women homozygous for the 3-base pair deletion (rs11575899) in exon 4 (adjusted OR=0.44, 95% CI 0.26-0.76), while the number of [TTTA] n repeats was not significantly related to risk: the adjusted OR for n=7/7 repeats vs n>7/>7 repeats was 0.81 (95% CI 0.54-1.23). In stratified analyses, results for CYP19A1 were stronger among women with higher (>27.4) body mass index: for the homozygous deletion, OR=0.30 (95% CI 0.15-0.62); for the n=7/7 genotype, OR=0.49 (95% CI 0.26-0.93). The interaction between the n=7/7 genotype and BMI was statistically significant (p=0.01). The insertion/deletion variant in CYP19A1 appears to be related to risk of endometrial cancer; risk associated with variants in this gene may vary according to BMI.

Density of Merkel cells in peri-lesional epidermis was 0.2-0.3%. No merkel cells were detected in the BCC. BEP overlying dermatofibromas showed an obvious increase in CK 20 stained Merkel cells. The difference was statistically significant (P < 0.02) CONCLUSIONS: We report a significant increase in CK20 stained Merkel cells in BEP overlying dermatofibromas as compared to BCC. CK20 antibody staining for Merkel cells can be used as an adjunct method to differentiate BEP overlying dermatofibromas from BCC. Mahmoodi M, Asad H, Salim S, Kantor G, Minimo C. Anti-CK20 staining of Merkel cells helps differentiate basaloid proliferations overlying dermatofibromas from basal cell carcinoma.

Background: The presence of tactile corpuscle-like structures in Schwannomas, Neurofibromas and Neuroid Intradermal Melanocytic Nevi is well-documented. We report a case describing the presence of such structures in the lamina propria of grossly normal gastric mucosa.

#1002 The GeneSearch™ Breast Lymph Node (BLN) Assay (Veridex, LLC) has been FDA approved to detect metastases &gt; 0.2 mm in the sentinel lymph nodes (SLNs) of breast cancer patients and has been in clinical use in our institute for 11 months. This assay gives a qualitative (negative/positive) result by applying cutoff values to the cycle times (Ct) of the two mRNA markers analyzed: mammaglobin (MG) (cutoff value = 31 Cts) and cytokeratin 19 (CK19) (cutoff value = 30 Cts). This is the first study to evaluate if the quantitative Ct values of MG and CK19 can be used to estimate probable size of nodal metastases.&#x2028; To date 184 patients have been tested using the BLN Assay during its clinical use at Morton Plant Hospital. An additional 172 patients were tested with the BLN Assay at our institute during investigational studies. In both cases, the SLNs of breast cancer patients were divided into ∼2 mm pieces. Alternating pieces were homogenized and were processed intra-operatively. The other pieces of the SLN were used for permanent section H&E analysis. The patient was considered H&E positive when a metastasis &gt; 0.2 mm was identified. During clinical use, same-surgery complete axillary dissection was performed when the assay was positive (n = 34).&#x2028; Performance of the assay's qualitative result against permanent section H&E on adjacent node pieces was similar for the two groups (total N = 356), for a total sensitivity of 96% (81/84), specificity of 93% (254/272), and overall agreement of 94%. The marker Ct values correlated with metastases size as determined by H&E in adjacent node pieces (r = 0.74 for MG and 0.72 for CK19, p &lt; .0001). The lower the Ct values, the greater the likelihood of macrometastases reported by H&E, as described in Table 1. For example if CK19 is &lt;21.0 and MG is &lt; 25.0, there is 100% chance for H&E positivity in the SLNs, with the majority being macrometastases.&#x2028; &#x2028; Additionally, BLN Assay Ct values in the SLN were predictive of metastases in the non-SLN nodes. For example, of the 12 patients who had a SLN with CK19 &lt; 24 Cts, 9 (75%) had H&E positive non-SLNs. For the same 12 patients, SLNs were H&E positive (5 macrometastases, 5 micrometastases, and 2 reported as &gt; 0.2 mm).&#x2028; The BLN Assay's high intra-operative qualitative performance minimizes the need for second surgeries for complete axillary dissections. Results from this investigational study examining the marker Ct values suggest that the assay may provide valuable individual tumor volume data intra-operatively or post-operatively. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1002.

Whether profound carcinoembryonic antigen (CEA) elevations, such as > 20 times the upper limit of normal, are of diagnostic use remain unknown. Herein, we present a case of a 55-year-old female with profound serum CEA elevation and multiple pelvic masses but with no evidence of a primary gastrointestinal tumor following upper endoscopy and colonoscopy. Subsequent immunostaining of resected pelvic masses confirmed adenocarcinoma of colorectal origin. This case report highlights the possible diagnostic role of profound CEA elevation, particularly in cases of unknown primary tumors.