Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life and accounts for 3-5% of all paediatric renal neoplasms. To further understand the morphological variants of MN, we identified 19 cases of MN (five classic, eight cellular and six mixed) and examined each case for markers known to be important in urogenital embryological development (PAX8, WT1 and RCC), stem cell associated markers (Oct 4, CD34 and c-kit), muscle/myofibroblastic markers (muscle specific actin, calponin and h-caldesmon), aberrant transcription factors, cell cycle regulation and other oncogenic proteins (p16, cyclin D1 and beta-catenin). Fluorescence in situ hybridisation (FISH) testing for ETV6-NTRK3 gene fusion/rearrangement revealed further differentiation between the subtypes with ETV6-NTRK3 gene fusion detected in 0/5 of the classic MN, 8/8 of the cellular MN and 5/6 of the mixed MN cohorts, respectively. Our results conclude that cyclin D1 and beta-catenin may be useful markers for differentiating between cellular MN and classic MN when the histology is not conclusive. The absence of expression of stem cell markers and markers involved in urogenital development suggests that MN is not a nephroma and most likely represents a soft tissue tumour, with congenital infantile fibrosarcoma representing cellular MN with a predilection to arise in the kidney. In addition, the immunophenotype and genetic fingerprint of mixed MN most likely represents a heterogenous group of tumours that are mostly cellular type, with areas that are phenotypically less cellular.

Renal oncocytosis is a rare pathological condition characterised by the presence of multiple oncocytic tumours with a spectrum of histological features ranging from renal oncocytoma, hybrid oncocytic tumour and rarely chromophobe renal cell carcinoma, sometimes overlapping. Here we retrospectively analysed histological, immunohistochemical (IHC), and cytogenetic features of 42 lesions in 11 patients with renal oncocytosis, not associated with Birt-Hogg-Dubé syndrome. The histology of all the lesions was blindly reviewed by three dedicated genitourinary pathologists. IHC for cytokeratin 7 (CK7) and fluorescence in situ hybridisation (FISH) for copy number variation of chromosomes 1, 6, 7 and 17 were performed in all 42 nodules. Among the 42 lesions 36 (85.7%) were histologically renal oncocytomas, two (4.76%) 'hybrid oncocytic tumours' (HOT), one (2.4%) clear cell renal cell carcinoma (ccRCC), one (2.4%) papillary renal cell carcinoma (pRCC), one typical angiomyolipoma (2.4%), and one mixed epithelial/stromal tumour of the kidney (2.4%). FISH analysis confirmed the histological diagnosis of all the lesions. We show that most patients with renal oncocytosis harbour benign or low malignant potential tumours that can be treated conservatively.

Distal extrahepatic bile duct (EBD) carcinoma is a rare but highly aggressive malignant neoplasm. Some in vitro studies have shown that EGFR and PI3K-Akt pathway play an important role in the carcinogenesis of bile duct carcinoma. The aim of the present study is to investigate the expression of EGFR, p-AKT, and COX-2 and the mutation of PIK3CA in distal EBD carcinoma and evaluate the association with clinicopathological factors. Ninety cases of distal extrahepatic bile duct (EBD) carcinoma specimens were studied. Immunohistochemistry (IHC) using antibodies against EGFR, p-AKT, and COX-2 was performed on TMA blocks. The PIK3CA mutation was evaluated using the PNAClamp Detection Kit from DNA samples extracted from formalin fixed, paraffin embedded tissue. EGFR expression of distal EBD carcinomas was 61.9%, 26.2%, 6.0% and 6.0% in the negative, weakly positive, moderately positive, and strongly positive groups, respectively. Positive EGFR expression showed significant relationships with high T stage (p = 0.024). In Kaplan-Meier analysis, EGFR expression was associated with shorter cancer-specific overall survival (p = 0.005). Multivariate analysis also showed that moderate or strong (2+ or 3+) EGFR expression was a significant prognostic factor in distal EBD carcinoma: HR 5.286; p = 0.001. Ninety cases of EBD carcinoma tissue were analysed for hotspot mutations (exon 9 and 20) in the PIK3CA gene. Only one mutation was detected: a missense mutation of H1047 at exon 20. The expression levels of p-AKT and COX-2 showed no association with any clinicopathological parameters, including survival rate. Moderate and strong EGFR expressions demonstrate a direct link to poor prognosis. Although further study is warranted to understand the clinicopathological significance, our finding suggests EGFR is a useful prognostic marker of patients with distal EBD carcinoma. A low prevalence of PIK3CA mutation exists in the distal EBD carcinoma of Korean patients, indicating that mutation screening may not be useful in determining prognosis or in formulating a treatment response to targeted inhibition in Korea.

Atypical ductal hyperplasia (ADH) and lobular carcinoma in situ (LCIS) may be associated with a relatively high incidence of invasive carcinoma and ductal carcinoma in situ (DCIS) on immediate excision when found on core needle biopsy of the breast. However, the long term significance of ADH and LCIS in a breast core needle biopsy is not as well characterised. We reviewed the results of all breast core needle biopsies with a diagnosis of ADH or LCIS and immediate excision from the years 2000-2004, and correlated the results with long term clinical follow-up. Of 175 biopsies with ADH, 53 (30.3%) had carcinoma (8 invasive, and 45 DCIS) at the time of immediate re-excision. Of 69 biopsies with LCIS, three (4.3%) had carcinoma (2 invasive, and 1 DCIS) at the time of immediate re-excision. A total of 14 (11.5%) patients with ADH and benign re-excisions developed invasive carcinoma (12) or DCIS (2) on follow-up. A total of 17 (25.8%) patients with LCIS and benign re-excisions developed invasive carcinoma (13) or DCIS (4) on follow-up. The risk of invasive carcinoma or DCIS on immediate re-excision was significantly higher for women with ADH than LCIS (p<0.001). Women with LCIS developed significantly more invasive carcinomas and DCIS than women with ADH on long term follow-up (p=0.01). Compared to women with fibrocystic changes (FCC) on core needle biopsy, the risk of developing invasive carcinoma or DCIS was significantly higher for women with ADH and benign initial re-excisions (95% CI 1.092-7.297, p=0.03), and women with LCIS and benign re-excisions (95% CI 3.028-18.657, p<0.001). Overall, 67/175 (38.3%) women with ADH and 20/69 (29.0%) women with LCIS on core needle biopsy either had carcinoma at the time of the biopsy or later developed carcinoma. Significantly more women with LCIS developed invasive carcinoma or DCIS than women with ADH on long term follow-up. The relative risk for ADH and LCIS on core biopsy with a negative excision compared with FCC was similar to that reported in the literature (ADH 1-7×, LCIS 3-19×).

We sought to investigate the frequency of mutations in epidermal growth factor receptor (EGFR) and Kirsten-RAS (KRAS) by each pathological subtype for patients with resected pulmonary adenocarcinoma as defined by the IASLC/ATS/ERS classification. Histological examination determined the predominant subtype according to the IASLC/ATS/ERS classification. EGFR and KRAS mutations were determined by high-resolution melting and Sanger sequencing. Clinical data were collected from medical records and clinicians. The 178 consecutive patients consisted of 48% males, median age 68 years (range 20-87) and smoking history 78%. The tumour stage was I in 62%, II in 18% and III in 20%. The mutation rates were: EGFR 30%; KRAS 28%. The rate of EGFR mutations in the acinar predominant reference group (n=76), was 37%. The solid predominant subtype showed significantly fewer EGFR mutations [3/33 (9%), odds ratio 0.17 (0.05-0.61), p=0.007]. No differences in mutation rate were observed in other subtypes. No association was found between KRAS mutations and predominant histological subtype. Advanced stage and solid predominant subtype were negative prognostic factors. EGFR mutations can be present in adenocarcinoma of any predominant subtype, however rarely in solid predominant tumours. No association was found between KRAS mutation and the predominant histological subtype.

Steroid hormones have been shown to play a role in gastric carcinogenesis. Large amounts of steroid hormones are locally produced in the peripheral tissues of both genders. Type 5 of 17β-hydroxysteroid dehydrogenase, encoded by the AKR1C3 gene, plays a pivotal role in both androgen and estrogen metabolism, and its expression was found to be deregulated in different cancers. In this study we measured AKR1C3 transcript and protein levels in nontumoral and primary tumoral gastric tissues, and evaluated their association with some clinicopathological features of gastric cancer (GC). We found decreased levels of AKR1C3 transcript (p < 0.0001) and protein (p = 0.0021) in GC tissues compared with the adjacent, apparently histopathologically normal, mucosa. Lower levels of AKR1C3 transcript were observed in diffuse and intestinal types of GC, whereas AKR1C3 protein levels were decreased in tumors with multisite localization, in diffuse histological type, T3, T4, and G3 grades. We also determined the effect of the histone deacetylase inhibitor sodium butyrate (NaBu) on AKR1C3 expression in EPG 85-257 and HGC-27 GC cell lines. We found that NaBu elevates the levels of both AKR1C3 transcript and protein in the cell lines we investigated. Together, our results suggest that decreased expression of AKR1C3 may be involved in development of GC and can be restored by NaBu.

Histologically confirmed small cell lung cancer associated with Cushing's syndrome and elevated amylase is rarely described in the literature. We present a case of a 63-year-old patient admitted to cardiology department due to shortness of breath, exhaustion, palpitations and nausea. Elevated values of troponin and electrocardiography suggested that he could have acute coronary syndrome. According to the radiologist's opinion, plane lung radiography was normal. Elevated level of amylase was found in both serum (3802 U/L, normal range 28-100) and urine (12012 U/L, normal range 0-450 U/L), as well as elevated sodium (156 mmol/L, normal range 137-147 mmol/L), hyperglycemia (12 mmol/L, normal range 3.8-6.1 mmol/L) and lowered serum potassium (1.7 mmol/L, normal range 3.5-5.3 mmol/L). Computerized tomography (CT) of the abdomen revealed a tumor of the left adrenal gland and enlargement of the right adrenal gland with normal structure of the pancreas. During hospitalization, the patient had blood while coughing and CT scan of the lungs showed a tumor 48x38x51 mm in size localized in the laterobasal segment of the left lung with mediastinal lymphadenopathy. He also had bilateral pleural effusions with signs of pulmonary embolism, which explained elevated troponin values. Biopsy confirmed microcellular lung carcinoma and tumor cells were diffusely positive for TTF-1 and focally for CK7, expressing markers of neuroendocrine differentiation (chromogranin +++, synaptophysin +++, NSE ++). Since neuroendocrine tumor was confirmed and the patient had low potassium and high glucose, hypercortisolism was suspected. High morning cortisol (1784 mmol/L, normal range 171-536) and unsuppressed ACTH (214 pg/L, < 60), as well as a high level of chromogranin (1339 µg/L, < 65) were determined. During hospital stay, the patient developed heart and respiratory failure and died in the second week of hospitalization.

The verified presence of a glioblastoma multiforme (GBM) tumor in the motor area of the brain, in a patient lacking preoperative neurological deficit, offers no certainty that the tumor can be radically removed without the possibility of causing postoperative motor deficit. We present a series of 60 patients hospitalized at the Clinical Department of Neurosurgery, Clinical Center of Serbia in Belgrade between October 2011 and February 2015, harboring tumors located within and in the vicinity of the motor zone of the brain. By using Karnofsky's index (KI), the pre- and postoperative conditions of the patients were evaluated. Regarding electrical stimulation of the motor cortex, significantly lower values of the electrical current intensity, frequency, and pulse wave duration (p < 0.01) were needed for triggering motor response in case of GBM tumor compared to a slowly growing tumor (low-grade). Patients with low-grade gliomas (LGG) had statistically significantly higher KI values pre- and postoperatively than patients with GBM (p < 0.01). Using electrical stimulation of the cortex, a higher grade of resection of LGG could be achieved as compared with the group presenting with GBM (χ² = 5.281; df = 1; p < 0.05). Our findings and review of the results reported by other authors underline the necessity of routine application of electrical stimulation of the cerebral cortex in order to identify the primary motor field (M1).

microRNAs (miRNA) are involved in many biological processes. They repress target gene expression and play a vital role in breast invasive carcinoma (BRCA). Although many miRNAs are identified to be aberrantly expressed in BRCA and deemed as tumor markers, only sporadic individual studies report their target genes and the pathways involved.

Accurate assessment of characteristics of tumor and portal vein tumor thrombus is crucial in the management of hepatocellular carcinoma.

It has previously been reported that a general risk model, Estimation of Physiologic Ability and Surgical Stress (E-PASS), and its modified version, mE-PASS, had a high predictive power for postoperative mortality and morbidity in a variety of gastrointestinal surgeries. This study evaluated their utilities in proximal biliary carcinoma resection.