Carmela Iglesias

PTOV1 Expression Predicts Prostate Cancer in Men with Isolated High-Grade Prostatic Intraepithelial Neoplasia in Needle Biopsy

Purpose: To analyze the expression of PTOV1 in high-grade prostatic intraepithelial neoplasia (HG-PIN) and to explore its usefulness to predict prostate cancer in patients with isolated HG-PIN in needle biopsy (prostate needle biopsy). Experimental Design: PTOV1 expression in HG-PIN lesions from 140 patients was analyzed by immunohistochemistry in a semiquantitative manner (Histo-score). HG-PIN derived from 79 radical prostatectomies for prostate cancer and from 11 cistoprostatectomies for bladder cancer without prostate cancer were used as positive and negative controls, respectively. Fifty patients with HG-PIN without concomitant cancer at their first prostate needle biopsy were chosen as the study group. Patients were followed by a mean of 2.5 repeated prostate needle biopsies (1-5), during a mean period of 12.4 months (1-39). Results: PTOV1 expression in HG-PIN from radical prostatectomies showed a significantly higher Histo-score (162.6) compared with specimens from cistoprostatectomies (67.0). In the study group, PTOV1 expression was significantly higher in samples with cancer in the follow-up (11 patients, 22%) compared with samples in which cancer was not detected (151.4 versus 94.6). PTOV1 expression was the only independent predictor of cancer in the multivariate analysis and the area under the curve was 0.803 (95% confidence interval, 0.728-0.878). A threshold of 100 for PTOV1 expression provided 90.9% sensitivity, 51.3% specificity, 34.5% positive predictive value, and 95.2% negative predictive value. Conclusions: PTOV1 is overexpressed in HG-PIN associated with cancer and is a potential marker for studying the carcinogenesis and progression of prostate cancer. Prostate needle biopsy with PTOV1 expression in HG-PIN above a threshold of 100 should be repeated immediately for the likely presence of undiagnosed cancer.

Concordance study between one-step nucleic acid amplification and morphologic techniques to detect lymph node metastasis in papillary carcinoma of the thyroid

Tumor resection in papillary thyroid carcinoma (PTC) is often accompanied by lymph node (LN) removal of the central and lateral cervical compartments. One-step nucleic acid amplification (OSNA) is a polymerase chain reaction-based technique that quantifies cytokeratin 19 (CK19) messenger RNA copies. Our aim is to assess the value of OSNA in detection of LN metastases in PTC, in comparison with imprints and microscopic analysis of formalin-fixed, paraffin-embedded (FFPE) tissue. A total of 387 LNs from 37 patients were studied. From each half LN, 2 imprints were taken and analyzed with hematoxylin and eosin (H&E) and CK19 immunostaining. One half of the LN was submitted to OSNA and one half to FFPE processing and H&E and CK19 staining. For concordance analysis, every single LN was considered as a case. A group of 11 cases with discordant results between OSNA and H&E/CK19 FFPE sections were subjected to additional FFPE serial sectioning and H&E and CK19 staining. We found a high degree of concordance between the assays used, with sensitivities ranging from 0.81 to 0.95, and specificities ranging from 0.87 and 0.98. OSNA allowed upstaging of patients from pN0 to pN1, in comparison with standard pathologic analysis. Identification of a metastatic LN with more than 15000 CK19 messenger RNA copies predicted the presence of a second LN with macrometastasis (<5000 copies). In summary, the study shows that OSNA application in sentinel or suspicious LN may be helpful in assessing nodal status in PTC patients.

Successful treatment with GEMOX in patient with metastatic pancreatic adenosquamous carcinoma

BACKGROUND Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic cancer characterized by a dual histological component and aggressive behavior. This form is not well known, its histogenesis is uncertain, and there are different opinions on the diagnostic histopathological criteria. The differential diagnosis with more common ductal adenocarcinoma, squamous cell carcinoma, squamous or adenosquamous metastases is complex. The available therapies do not improve the poor prognosis and it is difficult to find long-term survivors (more than 1 year), even after demolitive surgery with complementary therapies. CASE REPORT We report a case of advanced PASC with excellent progression-free survival and overall survival, 20 months and 29 months, respectively. Furthermore, an almost complete response was obtained to first-line chemotherapy with gemcitabine/oxaliplatin (GEMOX) followed by maintenance gemcitabine. CONCLUSION GEMOX followed by gemcitabine as maintenance could be an effective treatment for this pancreatic entity. Further reports are needed to confirm this outcome.

Detection of Thyroid Papillary Carcinoma Lymph Node Metastases Using One Step Nucleic Acid Amplification (OSNA): Preliminary Results

ABSTRACT Purpouse: One Step Nucleic Acid Amplification (OSNA) has been previously proposed for the diagnosis of lymph node metastases (LNMs) from several malignant conditions by quantifying the number of copies of cytokeratin 19 mRNA. Our aim was to evaluate the results obtained by OSNA in the lymph nodes of patients with papillary thyroid carcinoma (PTC) by comparing our results with the findings observed using standard pathological examination. Materials and Methods: Fifty human lymph nodes (from five patients with diagnosed PTC) were studied. Each node was divided into two: one half was used for molecular study (“OSNA-node”), and the other half was used for conventional staining with hematoxylin and eosin (“HE-non-OSNA node”). Three cytological imprints using Papanicolaou and May-Grunwald-Giemsa strains were obtained from both node halves. The results from each technique were compared, and ROC analysis was performed. Results: The OSNA study showed 22 positive samples for LNM (44%), which demonstrate a high concordance rate with the results observed using conventional pathological examination (cytology of “OSNA-node” and HE of “Non-OSNA node”) with specificity and sensitivity values greater than 86% and 89%, respectively. However, both comparisons differed in the number of copies of mRNA as the best cut-off (260 copies in the first case and 93 in the second case). Conclusions: The OSNA results for the detection of LNM in patients with PTC are comparable with those observed using conventional techniques. However, its quantitative nature could be useful to more accurately detect lymph node involvement.

Increased Global DNA Hypomethylation in Distant Metastatic and Dedifferentiated Thyroid Cancer

Context Global DNA hypomethylation is a major event for the development and progression of cancer, although the significance in thyroid cancer remains unclear. Therefore, we aimed to investigate its role in thyroid cancer progression and its potential as a prognostic marker. Methods Global hypomethylation of Alu repeats was used as a surrogate marker for DNA global hypomethylation, and was assessed using the Quantification of Unmethylated Alu technique. Mutations in BRAF and RAS were determined by Sanger sequencing. Results Ninety primary thyroid tumors were included [28 low-risk differentiated thyroid cancer (DTC), 13 pediatric DTC, 33 distant metastatic DTC, 7 poorly differentiated thyroid cancer (PDTC), and 9 anaplastic thyroid cancer (ATC)], as well as 24 distant metastases and 20 normal thyroid tissues. An increasing hypomethylation was found for distant metastatic DTC [median, 4.0; interquartile range (IQR), 3.1 to 6.2] and PDTC/ATC (median, 9.3; IQR, 7.0 to 12.1) as compared with normal thyroid tissue (median, 2.75; IQR, 2.30 to 3.15), whereas low-risk and pediatric DTC were not affected by hypomethylation. Alu hypomethylation was similar between distant metastases and matched primary tumors. Within distant metastatic DTC, Alu hypomethylation was increased in BRAF vs RAS mutated tumors. Kaplan-Meier and Cox regression analyses showed that thyroid cancer-related and all-cause mortality were associated with tumor hypomethylation, but this association was lost after adjustment for thyroid cancer risk category. Conclusion Distant metastatic DTC, PDTC, and ATC were increasingly affected by global Alu hypomethylation, suggesting that this epigenetic entity may be involved in thyroid cancer progression and dedifferentiation.

Cytology of Head and Neck Lesions

The correct cytological discrimination between benign and malignant lesions is the first invaluable point for the adequate clinical and/or surgical management of head and neck lesions. This chapter offers a detailed and specific overview of both the common and rare benign and malignant lesions of the head and neck district. We deem the increasing role of cytology in some areas, such as nasal, sinonasal, oropharyngeal, major and minor salivary glands, and odontogenic, offering specific diagnostic features in a territory that has been mainly and largely diagnosed from a histological perspective. A specific section underlines the cytological features of head and neck cystic lesions, and a focused attention is directed to the cytological evaluation of benign and malignant mesenchymal and lymphoid lesions. Furthermore, the growing number of different cytological methods (i.e., conventional cytology, liquid-based cytology, and cell blocks) is highlighted mainly because of the application of ancillary techniques such as immunocytochemistry, flow cytometry and molecular analysis. A final detailed section points to all the possible and different benign and malignant thyroid lesions which are assessed with both conventional and liquid-based cytology. The conclusive point is a discussion about the problem of reporting thyroid diagnoses as emerged in the different thyroid classification systems used. All of these critical limits are analyzed in detail in the present chapter with appropriate references and pertinent illustrations. In this regard and taken together both all the advantages and the pitfalls and drawbacks, cytology might be the first and worldwide diagnostic tool in achieving a correct diagnosis and guiding the most appropriate management.

Dos casos de sarcoma de partes blandas de presentación insólita, con dificultades para el diagnóstico (El hombre de Estambul. Una situación bastante habitual: no reconocer una lesión porque no está en el lugar «adecuado»)

Resumen Para un patologo preparado, reconocer un tumor cuando presenta la morfologia caracteristica y esta en su localizacion habitual es facil. Pero cuando se presenta en un lugar insolito y ademas la biopsia para diagnostico es pequena, es facil caer en un error de orientacion y, aunque a veces las tecnicas auxiliares nos puedan ayudar, en algunas ocasiones no se concreta el diagnostico hasta que una biopsia completa o la extirpacion del tumor nos permiten ver la totalidad de la lesion, con la sobrecarga de tiempo, riesgo para el paciente y gasto economico que ello conlleva. El Prof. Rosai describe esta situacion con la historia que contaba Lauren V. Ackerman y que titulo «El hombre de Estambul»: el empecinamiento en no reconocer un tumor porque no esta en «su» lugar. Aportamos dos casos de sarcomas de partes blandas que se presentaron en localizaciones que podriamos llamar «invertidas»: un sarcoma sinovial mandibular y un mioepitelioma maligno yuxtaarticular en un dedo del pie y exponemos las dificultades que presentaron para su diagnostico inicial.