Cytology and high risk HPV testing in cervical cancer screening program: Outcome of 3-year follow-up in an academic institute.

BACKGROUND: Combination of cervical cytology and high-risk human papillomavirus (HR-HPV) testing, co-testing, has been increasingly used in screening cervical cancers. The present study summarized the outcome of co-testing by reviewing 3-year clinical and pathological follow-up information. METHODS: Patients were retrospectively identified via computerized search and were grouped based on the cytologic diagnosis and HR-HPV status as negative for intraepithelial lesion or malignancy (NILM)/HPV-, NILM/HPV+, atypical squamous cells of undetermined significance (ASC-US)/HPV-, ASC-US/HPV+, low grade squamous intraepithelial lesion (LSIL)/HPV-, LSIL/HPV+, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H)/HPV-, ASC-H/HPV+, high grade squamous intraepithelial lesion (HSIL)/HPV-, and HSIL/HPV+. The patients' pertinent past medical history and follow-up information were analyzed. RESULTS: During 3-year follow-up period, histologically proven HSIL was found in 5 of 1565 (0.3%) patients with NILM/HPV-, 7 of 141 (5.0%) with NILM/HPV+, 2 of 502 (0.4%) with ASC-US/HPV-, 30 of 274 (10.9%) with ASC-US/HPV+, 1 of 81 (1.2%) with LSIL/HPV-, 28 of 159 (17.6%) with LSIL/HPV+, 3 of 18 (16.7%) with ASC-H/HPV-, 34 of 69 (49.3%) with ASC-H/HPV+, 7 of 7 (100%) with HSIL/HPV-, and 35 of 56 (62.5%) HSIL/HPV+. In reviewing 12 HSIL cases that were originally diagnosed as NILM, 7 remained as NILM, and the other 5 were reclassified as 1 HSIL, 1 ASC-H, and 3 ASC-US, respectively. In 18 HSIL cases with negative HR-HPV, 12 patients had a prior history of positive HR-HPV testing and/or positive p16 IHC stain in the follow-up cervical biopsy. CONCLUSION: HR-HPV testing plays an important role in cervical cancer screening by identifying HSIL in patients with ASC-US, LSIL, and NILM. Co-testing is an optimal method to identifying the patients with higher risk for developing cervical abnormalities.

Fatal aortic pseudoaneurysm from disseminated Mycobacterium kansasii infection: case report.

Mycobacterium kansasii is a photochromogenic, slow-growing mycobacterium species that can cause pulmonary infection in patients with predisposing lung diseases, as well as extrapulmonary or disseminated disease in immunosuppressed patients. We describe a patient with a myelodysplastic syndrome, disseminated M kansasii infection, and ruptured aortic aneurysm. He had a recent diagnosis of mycobacterium cavitary lung lesions and was transferred to our facility for possible surgical intervention of an aortic aneurysm. Few hours after admission, the patient suddenly collapsed and died despite resuscitation efforts. A complete autopsy was performed and showed ruptured ascending aortic pseudoaneurysm with hemopericardium, disseminated necrotizing and nonnecrotizing granulomas with acid-fast bacilli in the aortic wall, lungs, heart, liver, spleen, and kidneys. Further genetic studies were consistent with monocytopenia and mycobacterial infection syndrome.

BRAF mutations in metastatic malignant melanoma: comparison of molecular analysis and immunohistochemical expression.

Melanoma is a complex genetic disease, and multiple genetic alterations have been reported to play a role during disease progression. The dysregulation of BRAF signaling has been shown to affect many molecules that promote the continual progression of melanoma. Oncogenic BRAF expression plays a vital role in promoting cell invasion and metastasis in melanoma. It is also associated with poor prognosis in metastatic melanoma. About 40% to 60% of cutaneous melanomas have BRAF mutations, and 90% of the mutations involve a specific substitution at codon 600 (BRAF V600E). In this study, we compared BRAF (V600E) mutation detection by molecular analysis with BRAF expression by immunohistochemical (IHC) analysis using 2 different antibodies. A total of 25 metastatic malignant melanomas were included in this study. 10 of the 25 (40%) cases were positive by molecular analysis using the COBAS 4800 BRAF V600 Real-time PCR assay, and 18 of the 25 (72%) cases were positive by IHC analysis with 2 different antibodies. All positive cases by molecular analysis were positive by both IHC stains (100%). No false negatives were obtained with either IHC stain. Eight of the 25 (32%) were false-positive by both IHC stains. This study demonstrates that IHC analysis is a very sensitive test for evaluation of BRAF mutations in metastatic malignant melanoma and may be useful as an initial screening test.

Human epidermal growth factor receptor 2 expression in urothelial carcinoma of the renal pelvis: correlation with clinicopathologic parameters.

The significance of human epidermal growth factor receptor 2 (HER2) overexpression in breast cancer is well established, and these patients are subsequently treated with Trastuzumab. Although HER2 expression in urothelial carcinoma of the urinary bladder has also been recently characterized, it has not been well studied in urothelial carcinoma of the renal pelvis. We investigated the relationship between HER2 overexpression in urothelial carcinoma of the renal pelvis and clinicopathologic parameters. Forty six cases were identified. HER2 overexpression was present in 34/46 (74%) cases. Mean patient age with HER2 overexpression was 68 years (range: 42-87 years). There was a male predominance with 28/34 (82%) patients. High grade urothelial carcinoma was present in 32/34 (94%) cases and 2/34 (6%) cases had low grade urothelial carcinoma. Pathologic staging was as follows; 9/34 (26%) cases were pTa, 10/34 (29%) cases were pT1, 2/34 (6%) cases were pT2, 12/34 (35%) cases were pT3, and 1/34 (3%) cases was pT4. An inverted growth pattern was present in 23/46 (50%) cases. HER2 overexpression was present in 15/23 (65%) cases of urothelial carcinoma with an inverted growth pattern. Our study showed that HER2 overexpression is more common in male patients with high grade urothelial carcinoma, especially those with an inverted growth pattern. It is highly conceivable that patients with urothelial carcinoma of the renal pelvis may be further stratified based on HER2 overexpression, and may also be potential candidates for Trastuzumab therapy in the neoadjuvant or adjuvant setting.

Immunohistochemical Investigation of BRAF p.V600E mutations in thyroid carcinoma using 2 separate BRAF antibodies.

BACKGROUND: Approximately 45% of papillary thyroid carcinomas harbor BRAF p.V600E mutations and current practice algorithms endorse molecular testing for BRAF p.V600E. We assessed the utility of immunohistochemistry to detect BRAF p.V600E mutations in thyroid carcinomas using 2 separate BRAF monoclonal antibodies: one that detects both mutant and wild-type protein (pan-BRAF) and another that detects only the mutant protein (mut-BRAF). METHODS: We selected 41 formalin-fixed paraffin-embedded thyroid carcinomas (29 papillary, 1 follicular, 7 medullary, and 4 anaplastic) from 37 thyroidectomies and 4 fine-needle aspirations. Immunohistochemistry was performed using a pan-BRAF (clone EP152Y) or a mut-BRAF (clone VE1) monoclonal antibody. Tumors were considered positive if >10% of neoplastic cells showed moderate (2+) or strong (3+) cytoplasmic staining. BRAF p.V600E mutations were confirmed by molecular pyrosequencing, the gold standard for statistical analysis. RESULTS: pan-BRAF reactivity was observed in 80.5% (n=33) of cases: 34.1% (n=14) harbored BRAF p.V600E mutations and 46.3% (n=19) were wild type. mut-BRAF reactivity was observed in 46.3% (n=19) of cases: 34.1% (n=14) harbored BRAF p.V600E mutations and 12.2% (n=5) were wild type. The pan-BRAF antibody detected 14 more false positives (specificity: 29.6%, PPV: 42.4%) compared with the mut-BRAF antibody (specificity: 61.5%, PPV: 73.7%), but both antibodies detected the same 5 false positives. No false negatives were detected with either antibody (sensitivity and NPV 100.0% for both). CONCLUSIONS: The suboptimal specificity and PPV limits the diagnostic utility of both antibodies to reliably detect BRAF p.V600E mutations in thyroid carcinoma. However, both antibodies provide excellent sensitivity and NPV and either could be used to exclude BRAF wild-type thyroid carcinomas before molecular testing.

Expression of MLH1 and MSH2 in urothelial carcinoma of the renal pelvis.

In this study, we investigated microsatellite instability in urothelial carcinoma of the renal pelvis by lack of immunohistochemical staining for MLH1 and MSH2. The study included 44 cases of urothelial carcinoma of the renal pelvis obtained from radical nephroureterectomy specimens at our institution. We evaluated the loss of nuclear immunohistochemical staining of MLH1 and MSH2. Eight of 44 (18 %) patients had negative MLH1 expression and 25/44 (57 %) patients had negative MSH2 expression. Six of 8 (75 %) patients with negative MLH1 expression were male and 2/8 (25 %) patients were female. Nineteen of 25 (75 %) patients with negative MSH2 expression were male, and 6/25 (24 %) patients were female. Seven of 8 (88 %) cases with negative MLH1 expression were high-grade urothelial carcinoma, and 21/25 (84 %) cases with negative MSH2 expression were high-grade urothelial carcinoma. Twenty-one of 44 (48 %) cases had an inverted growth pattern, of which 3/21 (14 %) cases had negative MLH1 expression and 14/21 (67 %) cases had negative MSH2 expression. Our study showed that microsatellite instability based on negative expression of MLH1 and MSH2 was more common in male patients with high-grade urothelial carcinoma. There is a strong correlation between inverted growth pattern and negative MSH2 expression. Microsatellite instability testing should be performed in patients with upper urinary tract carcinoma and may have prognostic value.

Schistosomiasis of the prostate: a case report.

BACKGROUND: Schistosomiasis with involvement of the prostate is relatively uncommon and is rarely diagnosed in needle core biopsies. CASE: A 45-year-old, African American man who had recently returned from the Middle East presented with hematospermia of unknown etiology. He also had an elevated PSA level and a positive family history of prostate cancer. Prostate needle core biopsies were obtained. On microscopy he had multiple foci of acute and chronic inflammation. In other foci, Schistosoma haematobium ova were identified in the absence of a host inflammatory response. All his biopsies were negative for carcinoma. A diagnosis of schistosomiasis of the prostate was made. CONCLUSION: Schistosomiasis should be considered in the differential diagnosis of parasitic diseases involving the prostate, especially in patients who live in or have recently visited endemic regions.

BCA2 is differentially expressed in renal oncocytoma: an analysis of 158 renal neoplasms.

The distinction between renal oncocytoma and renal cell carcinoma, especially chromophobe renal cell carcinoma and clear cell carcinoma with oncocytic features, is important due to the different biologic potentials of these tumors. RING E3 ligases have the subject of intense studies for their roles in many diseases including cancer and as potential therapeutic targets. All RING E3 ligases, including BCA2, contain a consensus protein sequence that would complex two or more zinc ions in the expressed protein. Identification of which ubiquitin ligases specifically affect distinct cellular processes is essential to the development of targeted therapeutics in these tumors. The ubiquitin-proteasome system regulates the turnover of proteins that have essential roles in the cell cycle, apoptosis, DNA damage repair, and in protein trafficking, which makes this pathway a target for oncogenic events. In this study, we investigated expression of BCA2 in renal oncocytoma and renal cell carcinoma. A total of 158 patients were included in the study. Our study has shown that 114/114 (100 %) cases of renal cell carcinoma were negative for BCA2. All 38 (100 %) cases of renal oncocytoma were positive for BCA2, and 6/6 (100 %) cases designated as oncocytic neoplasm which favor oncocytoma were also positive for BCA2. This is the first study to date evaluating the expression of BCA2 in renal oncocytoma. BCA2 could serve as a marker that may be utilized in the distinction between renal oncocytoma and its mimickers.