Clinical impact of ERG and PTEN status in prostate cancer patients underwent radical prostatectomy.

OBJECTIVES: Phosphate and tensin homolog gene (PTEN) acts as a regulator of PI3-KAkt molecular pathway. ETS Related gene (ERG), an oncogene located in chromosome 21q22.2, is involved in prostate cancer (PCa) by serine 2 (TMPRSS2), a protein encoded by TMPRSS2 gene. The aim of this study is to evaluate the clinical impact of PTEN loss and ERG rearrangement in terms of oncologic results in patients diagnosed with localized PCa who underwent radical prostatectomy. MATERIALS AND METHODS: Prospective data were collected from a total of 74 patients who underwent open radical retropubic prostatectomy for localized PCa and immunohistochemical study was performed in tissue samples. The primary antibodies for anti-ERG antibody as well as anti-PTEN antibody were obtained from DAKO. ERG was considered positive if at least 20% of the evaluated cells were stained at least with medium intensity. PTEN protein loss was considered when the intensity of cytoplasmic and nuclear staining was mild or entirely negative across > 10% of tumor cells. RESULTS: Homogenous loss of PTEN was associated with higher clinical International Society of Urological Pathology (ISUP) grade (p = 0.018) while no statistical significant association was present regarding the presence of ERG rearrangement with either ISUPc or ISUPp. After a median follow up of 34 months, 24 patients developed biochemical recurrence. No statistical significant correlation of ERG status with biochemical recurrence was noted while PTEN was associated with biochemical recurrence development in a statistical significant way. Lastly the combination of PTEN loss with ERG rearrangement presence was detected more often in higher ISUPc and ISUPp as well as biochemical recurrence development, although in a non statistical significant way. CONCLUSIONS: Homogenous and heterogenous PTEN loss was associated with biochemical recurrence. No association of ERG and biochemical recurrence was noted. The combination of PTEN loss and ERG rearrangement presented a trend for higher ISUPc and ISUPp as well as biochemical recurrence but not in a statistical significant way.

Expression of proto-oncogene c-Myc in patients with urinary bladder transitional cell carcinoma.

BACKGROUND: c-Myc is a proto-oncogene located on human chromosome 8. It encodes a transcriptional factor which regulates the expression of approximately 10% to 15% of human genes, playing a crucial role in cell growth, differentiation, cellular metabolism, apoptosis, and cell transformation. The aim of this study is to correlate the expression of c-Myc in patients suffering from urinary bladder transitional cell carcinoma with tumor grade, stage, and lymph node metastases. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue samples were obtained from 54 consecutive patients who underwent transurethral resection of bladder tumor or radical cystectomy (RC) as treatment for urinary bladder transitional cell carcinoma. Immunohistochemistry was performed using c-Myc monoclonal antibody and c-Myc expression was then analyzed for correlation with tumor stage, grade, and lymph node metastases. RESULTS: From a total of 54 patients, 42 (77.8%) had c-Myc positive staining and 12 (22.2%) were c-Myc negative. In the c-Myc positive group, 28 patients (66.7%) had low grade tumors and 33 (78.6%) presented with non-muscle-invasive disease (p < 0.05). In the c-Myc negative group, 10 patients (83.3%) had high-grade disease and 8 (66.7%) presented with muscle-invasive disease (p < 0.05). Lymph node metastases were evaluated in 17 patients who underwent RC. Of these, 5 had lymph node metastases, 4 of whom had c-Myc negative staining (p < 0.05). CONCLUSIONS: In our study, c-Myc negative staining was associated with higher grade and higher stage disease. On the contrary, most c-Myc positive tumors were low grade and non-muscle-invasive disease. In patients who underwent RC, c-Myc negative staining was associated with lymph node metastases.

Distinctive features of pancreatic neuroendocrine neoplasms exhibiting an increment in proliferative activity during the course of the disease.

PURPOSE: Neuroendocrine neoplasms (NENs) differ in their biological behavior and growth potential in a way that can be predicted using histological classification and grading systems. A subset of pancreatic NENs (pNENs) may develop a more aggressive phenotype during the course of the disease, associated with an increase in the Ki-67 proliferation index (PI). The purpose of the study was to present the clinical characteristics of these patients. METHODS: Using re-biopsy of growing lesions, we investigated the increase in Ki-67 PI sufficient to change initial grading (G). RESULTS: Of 264 patients with well differentiated (WD) pNENs who showed progressive disease during follow-up, 15 (6%) exhibited an increase in Ki-67 PI at a median time 36.8 (9.3-255.8) months. All neoplasms had WD-morphology: five had G1 (Ki-67 median value 1%), nine G2 (median value 5%), one G3 (25%) grades. Upon change of Ki-67 PI, 3 patients had G2 (8%) and 12 G3 (57.5%) NENs, while all retained their WD-morphology. At last follow-up, eight patients were alive with a median overall survival (OS) of 52.5 (9.5-264.3) months. Μedian OS was shorter in patients who had a change in Ki-67 PI before 36 months compared to those who had a change of Ki-67 PI at a later stage (27.5 95%CI: 11.88-43.06 vs. 120.87 95%CI: 96.05-145.69; log-rank p = 0.018). CONCLUSIONS: During the course of their disease, 6% patients with progressive pNENs develop an increase in Ki-67 PI resulting in an increase in grading status while maintaining their morphology. This process is associated with worse OS when it occurs at an early stage.

Giant Cell Tumor of Tendon Sheath Developed over Chimeric-Free Latissimus Dorsi and Serratus Anterior Muscle Flaps.

This article describes a rare case of giant cell tumor of the tendon sheath (GCTTS) that was developed over the substance of chimeric-free latissimus dorsi and -serratus -anterior muscle flaps performed for lower limb reconstruction. To our knowledge, development of GCTTS over a free flap is first described in the literature. A 71-year-old -woman was presented with a large protuberant ulcerated tumor mass that was developed over the substance of chimeric free muscle flaps at the foot and ankle. We performed an extensive tumor resection, and the pathology report confirmed the presence of a primary giant cell tumor. The patient was advised to have a below-knee amputation. However, the patient refused the amputation, and 4 months later, she was presented with a metastatic mass proximally at the upper thigh. We believe that the GCTTS was associated with the chronic inflammation of the soft tissue and bones along with the recurrent episodes of infection, mainly due to proteus mirabilis and proteus syndrome (PS). PS may lead to the development of malformations and overgrowth of different tissues in unusual locations. In cases resistant to antibiotics, the radical surgical debridement should be considered as the most effective treatment.

Imaging and Cytopathological Criteria Indicating Malignancy in Mucin-Producing Pancreatic Neoplasms: A Series of 68 Histopathologically Confirmed Cases.

OBJECTIVES: This study aims to evaluate the performance of clinical, imaging, and cytopathological criteria in the identification of high-grade dysplasia/carcinoma (HGD/Ca) in pancreatic mucin-producing cystic neoplasms. METHODS: Sixty-eight consecutive, histopathologically confirmed mucin-producing cystic neoplasms, evaluated by endoscopic ultrasound-guided fine-needle aspiration, were enrolled; specifically, 39 branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), 21 main duct IPMNs, and 8 mucinous cystic neoplasms. The associations between HGD/Ca in histopathology and findings of endoscopic ultrasound and cytology, demographic, lifestyle, and clinical parameters were evaluated, separately in IPMNs and mucinous cystic neoplasms. RESULTS: Age 65 years or more was associated with HGD/Ca in IPMNs. In BD-IPMNs, cyst diameter 3 cm or greater (sensitivity, 68.8%; specificity, 65.2%), a mural nodule (sensitivity, 56.3%; specificity, 78.3%), main pancreatic duct diameter 5 to 9 mm (sensitivity, 50.0%; specificity, 87.0%), and suspicious cytology (sensitivity, 81.3%; specificity, 100%) signaled the presence of HGD/Ca. Similarly, in main duct IPMNs, suspicious cytology predicted HGD/Ca with high sensitivity (88.9%) and excellent specificity (100%). Regarding cytopathological criteria, in BD-IPMNs, HGD/Ca was associated with a high nuclear/cytoplasmic ratio, background necrosis, presence of papillary structures, hypochromatic nuclei, hyperchromatic nuclei, and major nuclear membrane irregularities (thickening and/or indentations). CONCLUSIONS: Clinical, imaging, and cytopathological criteria are useful in the identification of HGD/Ca in IPMNs.

Identification of a novel mutation of the PRKAR1A gene in a patient with Carney complex with significant osteoporosis and recurrent fractures.

OBJECTIVE: Carney complex (CNC) is a rare autosomal dominant multiple neoplasia syndrome characterized by the presence of endocrine and non-endocrine tumors. More than 125 different germline mutations of the protein Kinase A type 1-α regulatory subunit (PRKAR1A) gene have been reported. We present a novel PRKAR1A gene germline mutation in a patient with severe osteoporosis and recurrent vertebral fractures. DESIGN: Clinical case report. CASE REPORT: A 53-year-old male with a medical history of surgically removed recurrent cardiac myxomas was evaluated for repeated low-pressure vertebral fractures and severe osteoporosis. Physical examination revealed spotty skin pigmentation of the lower extremities and papules in the nuchal and thoracic region. The presence of hypercortisolism due to micronodular adrenal disease and the history of cardiac myxomas suggested the diagnosis of CNC; the patient underwent detailed imaging investigation and genetic testing. METHODS: Standard imaging and clinical testing; DNA was sequenced by the Sanger method. RESULTS: Sequence analysis from peripheral lymphocytes DNA revealed a novel heterozygous point mutation at codon 172 of exon 2 (c.172G>T) of the PRKAR1A gene, resulting in early termination of the PRKAR1A transcript [p.Glu58Ter (E58X)]. CONCLUSION: We report a novel point mutation of the PRKAR1A gene in a patient with CNC who presented with significant osteoporosis and fractures. Low bone mineral density along with recurrent myxomas should point to the diagnosis of CNC.

Primary lymphoma of the spermatic cord: a case report and review of the literature.

Primary lymphomas of the spermatic cord are extremely rare. To date, only 15 cases have been reported in the international literature. Herein, we report a new case of a primary lymphoma of the spermatic cord. A 73-year-old patient presented at the Urology Department, complaining of bilateral painful masses at the inguino-scrotal region. A computed tomography scan revealed spermatic cord tumor. A right inguinal orchidectomy was performed in order to establish a definitive diagnosis. Macroscopically, the tumor was restricted to the spermatic cord area, leaving unaffected the testis and the epididymis. The histopathological and immune-histological evaluation has indicated a diffuse large B-cell lymphoma. Postoperatively, the patient was investigated thoroughly but no further signs of the disease were found.