Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.

Context: Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. Objective: To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. Design: MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Patients: Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Main Outcome Measure: Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Results: Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. Conclusion: MMT appears to convey longer survival in ATC among patients with stage IVA/B disease.

Riedel's thyroiditis association with IgG4-related disease.

CONTEXT: IgG4-positive (+) plasma cells have been reported in both Riedel's thyroiditis (RT) and Hashimoto's thyroiditis (HT). These cells are the hallmark of IgG4-related disease (IgG4-RD). OBJECTIVE: We sought to determine whether RT is part of IgG4-RD spectrum. DESIGN, SETTING AND PATIENTS: This was a case-control study performed at a tertiary medical centre. We included RT cases from the period 1958 to 2008 that had sufficient paraffin-embedded tissue for IgG4 immunostaining. Controls were patients with HT, age and gender matched, with similar pathology criteria. MAIN OUTCOME MEASURE: The main outcome measures were the intensity of the IgG4 staining and the clinical and histological correlates with IgG4-RD. RESULTS: Six pairs of RT and HT were analysed. The mean age was 44·7 years. In both groups, 5/6 cases had positive IgG4 staining. The mean number of IgG4 + cells/ HPF, normalized to the degree of inflammation, was 3·2 ± 3·0 SD (RT) vs 0·9 ± 0·7 (HT), P = 0·15, for fibrotic areas and 2·1 ± 2·3 SD vs 1·0 ± 0·8 (P = 0·39) for areas with lymphoid aggregates. We found the number of IgG4 +  cells in RT to be inversely correlated with the duration of disease (P = 0·046). Three RT cases had associated comorbidities from the IgG4-RD spectrum while none of the HT cases had such conditions. CONCLUSIONS: Riedel's thyroiditis is a component of IgG4-RD with the density of the IgG4 +  lymphocytic infiltrate being time dependent. In this small study, we did not identify differences in IgG4 infiltration between RT and HT, minimizing the utility of this marker in RT diagnosis.

Association of BRAF V600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers.

BACKGROUND: Studies have demonstrated an association of the BRAF(V600E) mutation and microRNA (miR) expression with aggressive clinicopathologic features in papillary thyroid cancer (PTC). Analysis of BRAF(V600E) mutations with miR expression data may improve perioperative decision making for patients with PTC, specifically in identifying patients harboring central lymph node metastases (CLNM). METHODS: Between January 2012 and June 2013, 237 consecutive patients underwent total thyroidectomy and prophylactic central lymph node dissection (CLND) at four endocrine surgery centers. All tumors were tested for the presence of the BRAF(V600E) mutation and miR-21, miR-146b-3p, miR-146b-5p, miR-204, miR-221, miR-222, and miR-375 expression. Bivariate and multivariable analyses were performed to examine associations between molecular markers and aggressive clinicopathologic features of PTC. RESULTS: Multivariable logistic regression analysis of all clinicopathologic features found miR-146b-3p and miR-146b-5p to be independent predictors of CLNM, while the presence of BRAF(V600E) almost reached significance. Multivariable logistic regression analysis limited to only predictors available preoperatively (molecular markers, age, sex, and tumor size) found miR-146b-3p, miR-146b-5p, miR-222, and BRAF(V600E) mutation to predict CLNM independently. While BRAF(V600E) was found to be associated with CLNM (48% mutated in node-positive cases vs. 28% mutated in node-negative cases), its positive and negative predictive values (48% and 72%, respectively) limit its clinical utility as a stand-alone marker. In the subgroup analysis focusing on only classical variant of PTC cases (CVPTC), undergoing prophylactic lymph node dissection, multivariable logistic regression analysis found only miR-146b-5p and miR-222 to be independent predictors of CLNM, while BRAF(V600E) was not significantly associated with CLNM. CONCLUSION: In the patients undergoing prophylactic CLNDs, miR-146b-3p, miR-146b-5p, and miR-222 were found to be predictive of CLNM preoperatively. However, there was significant overlap in expression of these miRs in the two outcome groups. The BRAF(V600E) mutation, while being a marker of CLNM when considering only preoperative variables among all histological subtypes, is likely not a useful stand-alone marker clinically because the difference between node-positive and node-negative cases was small. Furthermore, it lost significance when examining only CVPTC. Overall, our results speak to the concept and interpretation of statistical significance versus actual applicability of molecular markers, raising questions about their clinical usefulness as individual prognostic markers.

Minimal extrathyroid extension in papillary thyroid carcinoma does not result in increased rates of either cause-specific mortality or postoperative tumor recurrence.

BACKGROUND: This study assessed the influence of extrathyroid extension (EE) on cause-specific mortality (CSM) and tumor recurrence (TR) in patients treated for papillary thyroid carcinoma (PTC). METHODS: We studied outcome in 3,524 patients with PTC without distant metastases at diagnosis. CSM and TR were investigated in 422 patients with gross EE (GEE) or microscopic EE (MEE). RESULTS: The 30-year CSM rate for GEE of 25% was 12-fold greater (P < .001) than 2% seen with surgically intra-thyroid tumors (SIT); no patient who underwent MEE died of PTC. No difference (P = .36) existed in CSM rates between 127 MEE and 3,102 microscopically intra-thyroid tumors (MITs). The 20-year TR rate for GEE was 43% versus 12% with SIT (P < .001). Analyzing only 2,067 pN0 tumors, we found that GEE patients had greater TR rates (all sites), compared with SIT or MEE (P < .001). When 44 MEE were compared with 1,941 MIT cases, TR (all sites) rates were not different (P = .74). In patients aged >45 with tumors <41 mm, 20-year TR rates for MIT (stages I/II) and MEE (stage III) were not different at 4.7% and 3.8% (P = .71). CONCLUSION: MEE without concomitant GEE did not increase rates of either CSM or TR in PTC. Accordingly, these results raise concerns regarding current AJCC staging recommendations.

Prevalence of parathyroid carcinoma in 348 patients with multiple endocrine neoplasia type 1 - case report and review of the literature.

OBJECTIVE: To report the prevalence of parathyroid carcinoma (PC) in patients with multiple endocrine neoplasia type 1 (MEN1) and review of the literature. BACKGROUND: Primary hyperparathyroidism (PHP) is the most common manifestation of MEN1. The occurrence of PC in patients with MEN1 is rare and the literature regarding the clinical manifestations - including the prevalence of the disease - is scarce. CONTEXT: Single tertiary care centre experience from 1977 to 2013. DESIGN: Electronic search of the medical records to identify a cohort of patients with MEN1. Literature review based on current case reports. PATIENTS: Single case of PC in a cohort of 348 patients with MEN1. Ten cases of PC in patients with MEN1 reported in the literature. MEASUREMENT: Clinical features of PC in patients with MEN1. RESULTS: The prevalence of PC in 348 patients with MEN1 was found to be 0·28% (95% CI, 0-1·4%). Based on the current published cases of PC in patients with MEN1, 54·5% were women, mean age at diagnosis was 48·3 years, and the serum PTH concentrations at least four times the upper limit of the reference range in 73% of the cases. CONCLUSION: PC in patients with MEN 1 is rare with a prevalence of 0·28%, and the clinical features are similar to PC in patients without MEN1.

The Value of Repeat Thyroid Fine-Needle Aspiration Biopsy in Patients with a Previously Benign Result: How Often Does It Alter Management?

BACKGROUND: Thyroid nodules are prevalent and mostly benign, being present in up to 67% of the population when assessed by ultrasound. Due to the variable diagnostic performance of ultrasound-guided fine-needle aspiration biopsy (USFNA) of the thyroid and the possibility of a false-negative result, current clinical guidelines recommend ultrasonographic follow-up of benign thyroid nodules. The objective of this study was to evaluate the clinical relevance of a repeat fine-needle aspiration (rFNA) in patients with an initial benign fine-needle aspiration biopsy (iFNA). METHODS: A retrospective review was conducted of medical records of patients seen at the Mayo Clinic between January of 2003 and December of 2013 who had undergone rFNA of a nodule with benign iFNA. The outcome measured was the result of the rFNA and histopathological correlation, when available. RESULTS: Three hundred and thirty-four nodules with benign iFNA underwent rFNA during the 10-year study period. The rFNA was most commonly reported as benign (85.3%), followed by suspicious (7.2%), nondiagnostic (5.7%), and malignant (1.8%). The rFNA changed clinical management in 9.5% of the cases. The prevalence of thyroid malignancy ranged from 4.1% to 1.2% based on the gold standard used (histology vs. long-term follow-up, 4.0 ± 2.3 years). CONCLUSION: In the majority of patients with a benign iFNA, results of the rFNA were unchanged. However, in a small group of patients, the rFNA may differ from the initial results, and alter management. Even so, the prevalence of malignancy remains very low, ranging from 1.2% to 4.1% depending on the gold standard.

The diagnostic utility of combination of HMGA2 and IMP3 qRT-PCR testing in thyroid neoplasms.

The diagnosis of malignant thyroid tumors in some cytologic and histologic specimens remains challenging. High-mobility group A2 (HMGA2) expression and insulin-like growth factor II mRNA-binding protein-3 (IMP3) expression were evaluated by relative quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The aim of this study was to evaluate whether the combination of HMGA2 and IMP3 qRT-PCR was diagnostically useful in differentiating benign from malignant thyroid neoplasms. Fine-needle aspiration (FNA) specimens from 120 patients including 56 benign lesions and 64 carcinomas were used. The available 80 corresponding formalin-fixed paraffin-embedded (FFPE) thyroid tissues from 66 patients were also included in this study. HMGA2 and IMP3 expression levels were detected by qRT-PCR and reported as relative fold change after normalizing with a calibrator. The diagnostic utilities of HMGA2 and IMP3 qRT-PCR tests were evaluated individually and in combination. In FNA specimens, HMGA2 and IMP3 expression was consistently higher in thyroid malignancies compared with benign lesions in all subgroups except in Hürthle cell tumors. After exclusion of Hürthle cell tumors, the sensitivity was 90.2% for HMGA2, 88.2% for IMP3, and 98% for HMGA2+IMP3; the specificity was 97.1% for HMGA2, 79.4% for IMP3, and 79.4% for HMGA+IMP3. qRT-PCR data showed similar results in FFPE tissues: the sensitivity was 84.2% for HMGA2, 85.7% for IMP3, and 94.7% for HMGA2+IMP3; the specificity was 96.9% for HMGA2, 91.2% for IMP3, and 90.6% for HMGA2+IMP3. qRT-PCR data were concordant between FNA and FFPE samples for HMGA2 (97.4%) and IMP3 (96.9%). The results indicate that HMGA2 qRT-PCR with high specificity may be a useful ancillary technique to assist in the classification of difficult thyroid specimens, excluding Hürthle cell tumors. The HMGA2 and IMP3 qRT-PCR combination model with increased sensitivity and negative predictive value (96.4%) may be useful in screening thyroid cytology specimens.

Review of our experience with neuroblastoma and ganglioneuroblastoma in adults.

BACKGROUND: Neuroblastomas and ganglioneuroblastomas (NB/GNB) are malignant tumors that rarely occur in adults. Their disease progression and appropriate treatment are unclear. METHODS: All adults (age ≥18 years) were evaluated for histologically confirmed NB/GNB within our institution. Data were collected via chart review and direct patient contact. RESULTS: From 1980 to 2009, a total of 15 adult patients with NB/GNB were evaluated: six men (mean age 23 years, range 19-33 years) and nine women (mean 34 years, range 20-66 years). Their overall average age at diagnosis was 30 years. Tumor-related symptoms occurred in ten patients: Pain (abdominal 3, back 2, pelvic 1, groin 1) was more common than a mass (abdominal 2) or dysmenorrhea (1). Five patients had tumors found incidentally by computed tomography (4) or chest radiography (1). Primary tumor origins were in the pelvis (4), mediastinum (3), abdomen (2), adrenal gland (2), retroperitoneum (2), and mixed locations (2). Altogether, 12 patients underwent surgical resection (biopsy in 3; resections of R0 in 5, R1 in 3, R2 in 4). Ten underwent chemotherapy. Histology showed four GNBs and 11 NBs. Five patients with stage I disease survived a mean of 21 years (range 10-40 years). Two are alive today. Three stage III patients died at 2, 6, and 9 years after diagnosis (mean 5.7 years). Six of seven patients (one was lost to follow-up) with initial stage IV neuroblastoma died within 5 years (mean 2.7 years). NB and GNB patients had similar survivals. CONCLUSIONS: Adult-onset NB/GNB is rare. Symptoms appear to occur later when incurable stage IV disease is detected. Complete surgical resection can lead to long-term, disease-free survival in stage I patients.

Comparison of urine cytology and fluorescence in situ hybridization in upper urothelial tract samples.

BACKGROUND: The cytologic diagnosis of urothelial carcinoma (UC) of the upper urothelial tract (UT) is challenging. Using the UroVysion probe set adds diagnostic value for the detection of bladder cancer in voided urine. In instrumented UT specimens, the authors encountered positive UT cytology and fluorescence in situ hybridization (FISH) cases that did not demonstrate subsequent UT carcinoma. METHODS: The performance of cytology and FISH in the presence or absence of concomitant bladder cancer within 2 years was compared in 61 patients (112 samples) from 2003 through 2009. The mean follow-up was 3.2 years. The authors also compared the performance of near-tetrasomy versus hypertetrasomy. Biopsy confirmation of UTUC in 21 patients was considered the gold standard. RESULTS: Cytology alone was found to be poorly sensitive (38%) but highly specific (89%) for the detection of UTUC. FISH was found to increase the sensitivity of cytology and decrease specificity. Tetrasomy FISH resulted in many false-positive cases. Other false-positive FISH results were likely due to the presence of bladder cancer cells contaminating the UT specimen. CONCLUSIONS: Caution should be used when evaluating instrumented urine specimens of the UT from patients with a previous history of bladder carcinoma, and tetrasomy FISH results should not be interpreted as abnormal because it significantly lowers the specificity of the test. The combination of cytology and FISH appears to have good specificity while maintaining good sensitivity in evaluating UTUC when using modified scoring criteria for the appropriate patient population.

p300 acetyltransferase regulates androgen receptor degradation and PTEN-deficient prostate tumorigenesis.

Overexpression of the histone acetyltransferase p300 is implicated in the proliferation and progression of prostate cancer, but evidence of a causal role is lacking. In this study, we provide genetic evidence that this generic transcriptional coactivator functions as a positive modifier of prostate tumorigenesis. In a mouse model of PTEN deletion-induced prostate cancer, genetic ablation of p300 attenuated expression of the androgen receptor (AR). This finding was confirmed in human prostate cancer cells in which PTEN expression was abolished by RNA interference-mediated attenuation. These results were consistent with clinical evidence that the expression of p300 and AR correlates positively in human prostate cancer specimens. Mechanistically, PTEN inactivation increased AR phosphorylation at serine 81 (Ser81) to promote p300 binding and acetylation of AR, thereby precluding its polyubiquitination and degradation. In support of these findings, in PTEN-deficient prostate cancer in the mouse, we found that p300 was crucial for AR target gene expression. Taken together, our work identifies p300 as a molecular determinant of AR degradation and highlights p300 as a candidate target to manage prostate cancer, especially in cases marked by PTEN loss.

Prostate cancer Ki-67 (MIB-1) expression, perineural invasion, and gleason score as biopsy-based predictors of prostate cancer mortality: the Mayo model.

OBJECTIVE: To determine the role of cellular proliferation and other biopsy-based features in the prediction of prostate cancer mortality. PATIENTS AND METHODS: Between 1993 and 2012, our institution has performed quantitation of prostate cancer DNA ploidy and Ki-67 (MIB-1) on most prostate cancer needle biopsy specimens. The outcomes of 451 consecutive patients with biopsy-proven cancer treated by radical prostatectomy between January 24, 1995, and December 29, 1998, without neoadjuvant hormonal therapy were assessed. Clinical and biopsy information obtained before radical prostatectomy was placed in multivariate Cox proportional hazards regression models to predict local or systemic progression and cancer-specific death. Predictive ability was evaluated using a concordance index. RESULTS: With a median follow-up of 12.9 years, 46 patients experienced local or systemic progression, and 18 patients died of prostate cancer. On multivariate analysis, the biopsy features of Ki-67 expression, perineural invasion, and Gleason score were associated with local or systemic progression. Ki-67 expression, perineural invasion, and Gleason score were associated with cancer-specific death with a concordance index of 0.892. After adjusting for perineural invasion and Gleason score, each 1% increase in Ki-67 expression was associated with a 12% increased risk of cancer-specific death (P<.001). Ki-67 expression alone was a strong predictor of cancer-specific outcomes and improved the predictive ability of currently used algorithms. CONCLUSION: This study documents that long-term prostate cancer outcomes are best estimated with a combination of Gleason score, perineural invasion, and Ki-67 expression. Given its low cost, rapid assessment, and strong predictive power, we believe that adding Ki-67 expression to perineural invasion and Gleason score at biopsy should be considered a standard by which all new biomarkers are compared before introducing them into clinical practice.

Human Calmodulin-Like Protein CALML3: A Novel Marker for Normal Oral Squamous Mucosa That Is Downregulated in Malignant Transformation.

Oral cancer is often diagnosed only at advanced stages due to a lack of reliable disease markers. The purpose of this study was to determine if the epithelial-specific human calmodulin-like protein (CALML3) could be used as marker for the various phases of oral tumor progression. Immunohistochemical analysis using an affinity-purified CALML3 antibody was performed on biopsy-confirmed oral tissue samples representing these phases. A total of 90 tissue specimens were derived from 52 patients. Each specimen was analyzed in the superficial and basal mucosal cell layers for overall staining and staining of cellular subcompartments. CALML3 was strongly expressed in benign oral mucosal cells with downregulation of expression as squamous cells progress to invasive carcinoma. Based on the Cochran-Armitage test for trend, expression in the nucleus and at the cytoplasmic membrane significantly decreased with increasing disease severity. Chi-square test showed that benign tissue specimens had significantly more expression compared to dysplasia/CIS and invasive specimens. Dysplasia/CIS tissue had significantly more expression than invasive tissue. We conclude that CALML3 is expressed in benign oral mucosal cells with a statistically significant trend in downregulation as tumorigenesis occurs. CALML3 may thus be a sensitive new marker for oral cancer screening.

Does BRAF V600E mutation predict aggressive features in papillary thyroid cancer? Results from four endocrine surgery centers.

BACKGROUND: Existing evidence is controversial regarding the association between BRAF mutation status and aggressive features of papillary thyroid cancer (PTC). Specifically, no study has incorporated multiple surgical practices performing routine central lymph node dissection (CLND) and thus has patients who are truly evaluable for the presence or absence of central lymph node metastases (CLNMs). METHODS: Consecutive patients who underwent total thyroidectomy and routine CLND at 4 tertiary endocrine surgery centers were retrospectively reviewed. Descriptive and bivariable analyses examined demographic, patient, and tumor-related factors. Multivariable analyses examined the odds of CLNM associated with positive BRAF status. RESULTS: In patients with classical variant PTC, bivariate analysis found no significant associations between BRAF mutation and aggressive clinicopathologic features; multivariate analysis demonstrated that BRAF status was not an independent predictor of CLNM. When all patients with PTC were analyzed, including those with aggressive or follicular subtypes, bivariate analysis showed BRAF mutation to be associated with LNM, advanced American Joint Committee on Cancer (AJCC) stage, and histologic subtype. Multivariable analyses showed BRAF, age, size, and extrathyroidal extension to be associated with CLNM. CONCLUSION: Although BRAF mutation was found to be an independent predictor of central LNM in the overall cohort of patients with PTC, this relationship lost significance when only classical variant PTC was included in the analysis. The usefulness of BRAF in predicting the presence of LNM remains questionable. Prospective studies are needed before BRAF mutation can be considered a reliable factor to guide the treatment of patients with PTC, specifically whether to perform prophylactic CLND.

Symptomatic amyloid goiters: report of five cases.

BACKGROUND: Massive amyloid deposition in the thyroid to the point of goiter formation is rare. Here we describe the clinical presentation and outcomes of five patients with amyloid goiter (radiographically confirmed goiter in the context of tissue-proven thyroid amyloidosis) encountered in the past 23 years at our institution. METHODS: Mayo Clinic archives were searched between 1987 and 2010 for a diagnosis of "thyroid amyloidosis," "amyloid deposits," "amyloid deposition," or "liquid chromatography consistent with amyloid." Inclusion criteria were symptomatic thyromegaly; tissue confirmation of thyroid enlarged by amyloid deposits; and radiologic confirmation of thyroid enlargement. RESULTS: Five patients were identified who met all inclusion criteria. Amyloid goiter etiology included both primary and secondary amyloidosis, and the goiters ranged in weight from 50 to 130 g each. Diagnosis was made by fine-needle aspiration biopsy with Congo red staining and, if needed, spectrophotometry. All five patients had histories of persistent hoarseness for several years before presentation with compressive symptoms referable to their enlarging thyroids, and all had some degree of thyroid dysfunction (both hypothyroidism and hyperthyroidism) by the end of our follow-up period, which ranged from 5 months to 13 years. Two patients underwent surgical interventions, two were managed conservatively, and in one, the goiter shrank after systemic therapy for amyloidosis. CONCLUSIONS: Our clinical observations suggest slower goiter progression and a higher prevalence of thyroid dysfunction than previously thought.

Application of vibro-acoustography in prostate tissue imaging.

PURPOSE: To evaluate the potential of the imaging modality vibro-acoustography (VA) for imaging of the prostate. METHODS: Excised cadaver prostate specimens were embedded in tissue mimicking gel to simulate the properties of surrounding soft tissues. The samples were imaged at various depths using a laboratory prototyped VA imaging system. The recorded signals were used for offline processing and image reconstruction. In a selected subgroup of tissue samples, conventional ultrasound (B-mode) and x-ray imaging were performed for further analysis, evaluation, and validation of the VA images. RESULTS: The imaging results of prostate tissue samples indicate the capability of VA imaging to detect prostatic nodules and lesions. In the prostate sample with an adenocarcinoma, the lesion appears with a clear contrast with respect to its surrounding tissue. The VA images could also identify the presence of calcifications deep inside the prostate tissue. Further, quantifications of the imaging results demonstrate that VA imaging has higher sensitivity to detect the calcifications compared to conventional ultrasound imaging. VA is also capable of visualizing prostatic tissue structures and in some cases can identify the anatomical zones. More specifically, the observed higher texture level in peripheral zones demonstrates the ability of VA to differentiate between prostatic anatomical zones. CONCLUSIONS: Imaging results of ex vivo prostate tissues, reveals the potency of VA as a promising tool to detect abnormalities, delineate tissue structures and anatomical zones, and locate calcifications. The results of this pilot study suggest that in vivo VA imaging of the prostate may be of clinical utility.

Risks and benefits of parathyroid fine-needle aspiration with parathyroid hormone washout.

OBJECTIVE: To describe the experience with parathyroid fine-needle aspiration (FNA) and parathyroid hormone (PTH) washout at Mayo Clinic Rochester, Rochester, Minnesota. METHODS: We retrospectively reviewed all parathyroid FNA procedures performed at Mayo Clinic Rochester between January 2000 and December 2007. Clinical, biochemical, and imaging information, parathyroid FNA procedure, and cytology, surgical, and pathology reports were reviewed, and descriptive statistics, sensitivity, specificity, and positive predictive values are presented. RESULTS: During the study period, 75 parathyroid FNAs were performed on 74 patients. Cytology results were available for 74 of 75 procedures, with only 31% interpreted as parathyroid cells. PTH washout was performed in 67 patients (91%). Parathyroid FNA with PTH washout had a sensitivity of 84%, specificity of 100%, positive predictive value of 100%, and accuracy of 84%. At the time of surgical treatment, 2 patients were noted to have an inflammatory response from the parathyroid FNA biopsy, 1 had a parathyroid abscess, and 2 had a hematoma. In 3 of these 5 patients, the necessary conversion of a minimally invasive surgical procedure to the standard surgical approach prolonged the surgical time. CONCLUSION: Parathyroid FNA with PTH washout had a superior performance in comparison with parathyroid scanning or ultrasonography alone. The main limitations of parathyroid FNA with PTH washout are (1) the need for initial identification of a potential parathyroid adenoma by ultrasonography and (2) the number of false-negative results. Parathyroid FNA resulted in complications affecting the surgical procedure in 3 patients.

FOXL2 mutations in granulosa cell tumors occurring in males.

CONTEXT: Granulosa cell tumors comprise less than 5% of ovarian tumors in women and are much rarer in men, with only about 20 cases reported, to our knowledge. Recently, a somatic mutation of FOXL2 was reported in virtually all adult-type granulosa cell tumors in women. OBJECTIVE: To investigate FOXL2 mutations in granulosa cell tumors occurring in males. DESIGN: Five cases of an adult-type granulosa cell tumor from males were selected from the files of the Mayo Clinic. Nine other testicular tumors (1 juvenile granulosa cell tumor, 5 Leydig cell tumors, and 3 Sertoli-Leydig cell tumors) were evaluated for comparison. Inhibin immunostain was performed in all cases. DNA was extracted from formalin-fixed, paraffin-embedded tissue, followed by polymerase chain reaction and direct sequencing of FOXL2. RESULTS: All 5 cases had classic histopathologic features of the adult-type granulosa cell tumor. Inhibin was diffusely positive in all cases. FOXL2 402C→G (C134W) was identified in 40% (2 of 5) of the male, adult-type granulosa cell tumors. Of the 2 tumors positive for the mutation, 1 occurred in the testis of a man, and the other one affected the abdominal ovaries of a phenotypically male patient. All other testicular tumors were negative for the mutation. CONCLUSIONS: The FOXL2 402C→G (C134W) mutation is also present in adult-type granulosa cell tumors occurring in men, although in a smaller proportion when compared with the rates reported in women. FOXL2 mutational analysis can be a helpful in the diagnosis of granulosa cell tumors of the testis.

Shared gene expression alterations in prostate cancer and histologically benign prostate from patients with prostate cancer.

Prostate cancer (PCa) field effect alterations provide important clues regarding the initiation of these tumors and suggest targets for prevention or biomarkers for early detection. However, biomarkers of PCa field effects that have passed independent validation are lacking, largely because these alterations are subtle and difficult to distinguish from unrelated small changes in gene expression. We hypothesized that shared expression alterations in PCa and benign prostates containing PCa (BPCs) would have a higher potential for independent validation than alterations identified in BPCs alone. Expression analyses were performed on 37 PCas and 36 unmatched BPCs and were contrasted with 28 benign prostates (BPs) from patients free of PCa. Most of the protein-coding genes and nonexonic RNAs selected according to the hypothesis were validated by quantitative RT-PCR in an independent set of 51 BPCs and BPs. A statistical model based on two markers distinguished BPCs from BPs in the RT-PCR set and in an external microarray (area under the curve = 0.84 and 0.90, respectively). In addition, genes with predominant expression in stroma were identified by expression profiling of pure stroma and epithelial cells. Pathway analysis identified dysregulated platelet-derived growth factor receptor signaling in BPC stroma. These results validate our approach for finding PCa field effect alterations and demonstrate a PCa transcriptome fingerprint in nonneoplastic cells in prostates containing cancer.