A combined molecular-pathologic score improves risk stratification of thyroid papillary microcarcinoma.

BACKGROUND: Thyroid papillary microcarcinoma (TPMC) is an incidentally discovered papillary carcinoma that measures ≤1.0 cm in size. Most TPMCs are indolent, whereas some behave aggressively. The objective of the study was to evaluate whether the combination of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and specific histopathologic features allows risk stratification of TPMC. METHODS: A group aggressive TPMCs was selected based on the presence of lymph node metastasis or tumor recurrence. Another group of nonaggressive tumors included TPMCs matched with the first group for age, sex, and tumor size, but with no extrathyroid spread. A molecular analysis was performed, and histologic slides were scored for multiple histopathologic criteria. A separate validation cohort of 40 TPMCs was evaluated. RESULTS: BRAF mutations were detected in 77% of aggressive TPMCs and in 32% of nonaggressive tumors (P = .001). Several histopathologic features differed significantly between the groups. By using multivariate regression analysis, a molecular-pathologic (MP) score was developed that included BRAF status and 3 histopathologic features: superficial tumor location, intraglandular tumor spread/multifocality, and tumor fibrosis. By adding the histologic criteria to BRAF status, sensitivity was increased from 77% to 96%, and specificity was increased from 68% to 80%. In the independent validation cohort, the MP score stratified tumors into low-risk, moderate-risk, and high-risk groups with the probability of lymph node metastases or tumor recurrence in 0%, 20%, and 60% of patients, respectively. CONCLUSIONS: BRAF status together with several histopathologic features allowed clinical risk stratification of TPMCs. The combined MP risk stratification model was a better predictor of extrathyroid tumor spread than either mutation or histopathologic findings alone.

Carcinomas of Distal Fallopian Tube and Their Association with Tubal Intraepithelial Carcinoma: Do They Share a Common "Precursor" Lesion? Loss of Heterozygosity and Immunohistochemical Analysis Using PAX 2, WT-1, and P53 Markers.

As the role of distal fallopian tube as organ of serous carcinogenesis is emerging, additional literature on the role of tubal intraepithelial carcinoma (TIC) as a precursor lesion in a subset of primary peritoneal serous carcinomas (PPSC is emerging as well. TIC although fallopian tube in origin can be genetically related to ovarian/peritoneal carcinomas. The role of PAX2 in primary fallopian tube carcinomas (PFTC)/PPSC is yet to be defined. The aim of our study was to understand if the biologic properties of tumors arising in the distal fallopian tube that remain as PFTC are different when they seed on to the peritoneal surface (PPSC). A panel of 6 polymorphic microsatellite markers corresponding to p53, PAX2, and WT1 tumor suppressor genes were studied. Invasive carcinomas as well as TIC arising in the distal fallopian tube when remain as PFTC appears to exhibit different LOH patterns in comparison to PPSC. PAX 2 LOH patterns might represent a "hidden PAX 2 signature" analogous to p53 signatures. PAX 2 might be an emerging marker for detection of early serous carcinomas particularly in BRCA + women.

Classical-type invasive lobular carcinoma with HER2 overexpression: clinical, histologic, and hormone receptor characteristics.

The majority of invasive lobular carcinomas (ILCs) express estrogen receptor (ER) and progesterone receptor (PR) but lack ERBB2 (HER2) amplification. HER2 overexpression is traditionally considered to occur in the pleomorphic variant of ILCs. We describe 12 cases of classical-type ILCs with HER2 overexpression in a 3-year period. All tumors displayed the characteristic morphologic features of classical ILC with uniform cells and discohesive growth patterns. The lobular phenotype was confirmed by the absence of E-cadherin staining. Multiple variables regarding clinical, histologic, and hormone receptor characteristics of tumors were evaluated and compared with a set of HER2- classical ILCs. The study identified 2 main pathologic features associated with HER2 overexpression in classical type ILC: histiocytoid morphologic features and absence of PR expression. ER is still expressed in HER2+ classical ILCs, although the level of expression is significantly reduced compared with the HER2- cases. The implications of the findings are discussed.

Primary epithelioid hemangioendothelioma of the kidney and penis.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of low malignant potential most commonly found in the lung, liver, and soft tissues. Here we describe the very rare presentations of primary EHE in the kidney and on the penis. One patient is a 59-year-old man with a renal lesion found incidentally on surveillance radiography, and the other is a 26-year-old man with an asymptomatic subdermal glanular lesion. Both were treated surgically via open partial nephrectomy and partial penectomy, respectively. Surgery is standard treatment, and close clinical follow up is necessary due to the unpredictable nature of EHE.

Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation.

Androgens exert growth inhibitory effects on estrogen receptor and progesterone receptor-negative breast cancer cell lines that show androgen receptor expression. These laboratory findings may be translated into inexpensive alternative therapies for hormone receptor-negative invasive breast cancers. Our aim was to systematically evaluate androgen receptor expression by immunohistochemistry in invasive breast cancers. Androgen receptor (clone AR441, Dako) expression was analyzed on 189 well-characterized consecutive invasive breast carcinomas represented with threefold redundancy on tissue microarrays. Androgen receptor expression was semi-quantitated using a histochemical score-like method and a score >10 was considered positive. Of the 189 consecutive invasive breast cancers, 151 (80%) were positive and 38 (20%) were negative for androgen receptor. The majority (95%) of estrogen receptor-positive tumors were also androgen receptor positive. Of the estrogen receptor-negative tumors, androgen receptor reactivity was seen in 3 of 30 (10%) triple-negative cases and in 5/8 (63%) estrogen receptor-negative/progesterone receptor-negative/HER2+ cases. Six of eight estrogen receptor-negative/androgen receptor-positive cases showed apocrine differentiation. Androgen receptor expression in estrogen receptor-positive cases was associated with smaller tumor size (P=0.0001), lower Nottingham grade (P=0.002) and less frequent tumor cell necrosis (P=0.0001). Androgen receptor expression in estrogen receptor-negative tumors was associated with lower Nottingham grade (P=0.005) and apocrine differentiation (P=0.039). In conclusion, most estrogen receptor-positive breast tumors also express androgen receptor. Androgen receptor expression in estrogen receptor-negative/progesterone receptor-negative/HER2+ tumors (which commonly show apocrine differentiation) and a subset of triple - negative apocrine tumors suggest that these tumors together comprises the 'molecular apocrine' group described previously. However, these findings should be further confirmed on larger series of triple-negative and estrogen negative/progesterone negative/HER2+ tumors. Androgen receptor-targeted therapy in estrogen/progesterone receptor-negative tumors may provide an inexpensive alternative to usual high-dose chemotherapy with or without trastuzumab.

Multivessel off-pump revascularization in patients with significant left main coronary artery stenosis: early and midterm outcome analysis.

BACKGROUND: The presence of significant left main stenosis (> or =50%) has been considered a relative contraindication to the use of off-pump coronary artery bypass (OPCAB) stemming from well-documented hemodynamic perturbations during the displacement of the heart. We examined our experience with patients with critical left main stenosis (LMS) to assess the safety and feasibility of OPCAB in this subgroup. METHODS: Our prospectively updated database was queried to identify all patients with severe left main disease who underwent isolated coronary revascularization between January 1, 1999 and May 31, 2002. This query yielded 234 on-pump and 420 off-pump patients with significant LMS whose clinical information was retrospectively reviewed. RESULTS: The groups were well matched with regard to gender, left ventricular function, surgical priority, and severity of angina. The conventional coronary artery bypass (CABG) group was significantly younger than the OPCAB group and had a higher incidence of a previous myocardial infarction. Patients in the CABG cohort were more likely than OPCAB patients to remain ventilated after 24 hours, require placement of intraoperative or postoperative intraaortic balloon pump, or suffer from postoperative renal failure. There was a decrease in mortality (6.4% vs. 1.9%; p = 0.006) when CPB was eliminated. Intermediate term survival analysis revealed a significant survival benefit in the off-pump group (p = 0.007). CONCLUSIONS: Multivessel off-pump revascularization in patients with severe left main disease is a safe and effective alternative to conventional bypass grafting and conveys a survival benefit.

Is off-pump revascularization better for patients with non-dialysis-dependent renal insufficiency?

BACKGROUND: Renal dysfunction is a well-recognized complication following coronary artery bypass grafting (CABG). Coronary revascularization without cardiopulmonary bypass (CPB) has been shown to minimize renal injury in patients with normal preoperative renal function who undergo elective procedures. The purpose of this study was to define the effect of an off-pump revascularization strategy on the incidence of postoperative renal failure and survival of patients with preexisting renal dysfunction. METHODS: From January 1, 1999, to December 1, 2002, a total of 371 patients were identified as having a preoperative creatinine concentration greater than or equal to 1.5 mg/dL. This number included 291 patients who did not need hemodialysis or peritoneal dialysis to support renal function. These patients were subdivided into those undergoing traditional CABG with CPB (103 patients) and those undergoing off-pump revascularization (188 patients) whose demographic, operative, and outcome information was retrospectively reviewed and compared. RESULTS: The off-pump cohort was older than the on-pump cohort (70 +/- 9.6 versus 66 +/- 10.9 years; P =.002), had a lower prevalence of previous myocardial infarction (35% versus 50%; P =.008), and had a modestly higher mean left ventricular ejection fraction (0.47 +/- 0.01 versus 0.43 +/- 0.01; P =.017). Otherwise the groups were well matched. The mean preoperative serum creatinine and creatinine clearance values were not significantly different (1.8 +/- 0.5 versus 1.9 +/- 0.6 mg/dL [ P =.372] and 45.1 +/- 15.5 versus 46.8 +/- 17.2 mL/min [ P =.376] for the off-pump and on-pump cohorts, respectively). There was a significant reduction in postoperative renal failure (17% versus 9% of patients; P =.020) and need for new dialysis (10% versus 3% of patients; P =.022) when CPB was eliminated. Intermediate-term survival analysis revealed a survival benefit for the off-pump group (70% versus 57%) at 42 months, although this value did not reach statistical significance ( P =.143). CONCLUSION: The results of this study suggested that patients with preoperative non-dialysis-dependent renal insufficiency have more favorable outcome when revascularization is done off pump. Avoidance of CPB results in (1) a reduction in the incidence of postoperative renal failure; (2) a reduction in the need for new dialysis; and (3) improved in-hospital and midterm survival.