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Large intestine polyps are commonly found during colonoscopies. Pedunculated colon polyps can be totally removed using an endoscopic invasive technique. A problem arises when the pendulated polyp contains cancerous infiltration. The aim of the article was a presentation of the clinical decision process concerned with the presence of cancer invasion tissue within colorectal polyps. Review of literature source and presentation of histological sample photography. A correct interpretation of the pathomorphological protocol is crucial for the therapeutic decision, which should be consistent with the actual recommendations of gastroenterological societies. Local treatment is considered as complete when the adenocarcinoma is well or moderately differentiated without any microinvasion of blood and lymphatic vessels and the resection margin is more than 1 mm from the cancer tissue infiltration. In the contemporary clinical practice patients with a colon polyp require rational clinical decisions, which are based on the actual recommendations.

Myoepithelial carcinoma of salivary glands is an underrecognized and challenging entity with a broad morphologic spectrum, including an EWSR1-rearranged clear cell variant. Myoepithelial carcinoma is generally aggressive with largely unknown genetic features. A retrospective review of Salivary Gland Tumor Registry in Pilsen searching for the key words "clear cell myoepithelial carcinoma," "hyalinizing clear cell," and "clear cell malignant myoepithelioma" yielded 94 clear cell myoepithelial carcinomas (CCMCs) for molecular analysis of EWSR1 rearrangement using fluorescence in situ hybridization (FISH). Tumors positive for EWSR1 gene rearrangement were tested by next-generation sequencing (NGS) using fusion-detecting panels. NGS results were confirmed by reverse-transcription polymerase chain reaction or by FISH. Twenty-six tumors originally diagnosed as CCMC (26/94, 27.6%) revealed split signals for EWSR1 by FISH. Six of these tumors (6/26, 23%) displayed amplification of the EWSR1 locus. Fifteen cases were analyzable by NGS, whereas 9 were not, and tissue was not available in 2 cases. None of the CCMCs with EWSR1 rearrangements detected by FISH had an EWSR1 fusion transcript. Fusion transcripts were detected in 6 cases (6/15, 40%), including LIFR-PLAG1 and CTNNB1-PLAG1, in 2 cases each, and CHCHD7-PLAG1 and EWSR1-ATF1 fusions were identified in 1 case each. Seven cases, including those with PLAG1 fusion, were positive for PLAG1 rearrangement by FISH, with notable exception of CHCHD7-PLAG1, which is an inversion not detectable by FISH. One single case with EWSR1-ATF1 fusion in NGS showed ATF1 gene rearrangement by FISH and was reclassified as clear cell carcinoma (CCC). In addition, another 4 cases revealed ATF1 rearrangement by FISH and were reclassified as CCC as well. Moreover, 12/68 (17%) CCMCs with intact EWSR1 gene were selected randomly and analyzed by NGS. PLAG1 fusions were found in 5 cases (5/12, 41.6%) with LIFR (2 cases), FGFR1 (2 cases), and CTNNB1 (1 case) as partner genes. Overall, PLAG1 gene rearrangements were detected in 10/38 (26%) tested cases. None of the tumors had SMARCB1 loss by immunohistochemistry as a possible explanation for the EWSR1 abnormalities in FISH. Novel findings in our NGS study suggest that EWSR1-FISH positive CCMC is a gene fusion-driven disease with frequent oncogenic PLAG1 fusions, including LIFR-PLAG1 and CTNNB1-PLAG1 in most cases. Productive EWSR1 fusions are found only in a minority of EWSR1-ATF1-rearranged cases, which were in part reclassifiable as CCCs. Detectable EWSR1-FISH abnormality in CCMCs without gene fusion perhaps represents a passenger mutation with minor or no oncologic effect.

Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture–based next generation sequencing (NGS). Of the 182 tumors, 8 were ALK positive by IHC. Further analysis using hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion in one case of intraductal carcinoma. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2 and ALK. ALK rearrangements are a rare entity in salivary gland carcinomas. We identified a potentially targetable novel ALK fusion in an intraductal carcinoma of minor salivary glands.

Intratumoral heterogeneity of breast cancer remains a major challenge in successful treatment. Failure of cancer therapies can also be accredited to inability to systemically eradicate cancer stem cells (CSCs). Recent evidence points to the role of epithelial-mesenchymal transition (EMT) in expanding the pool of tumor cells with CSCs features. Thus, we assessed expression level as well as heterogeneity of CSCs markers in primary tumors (PT), lymph node metastasis (LNM), and circulating tumor cells (CTCs)–enriched blood fractions in order to correlate them with signs of EMT activation as well as clinicopathological data of breast cancer patients. Level of CSCs markers (ALDH1, CD44, CD133, OCT-4, NANOG) and EMT markers was quantified in PT (N=107), LNM (N=56), and CTCs-enriched blood fractions (N=85). Heterogeneity of CSCs markers expression within each PT and LNM was assessed by calculating Gini Index. Percentage of ALDH1-positive cells was elevated in PT in comparison to LNM (P = .005). However, heterogeneity of the four CSCs markers: ALDH1 (P = .019), CD133 (P = .009), OCT-4 (P = .027), and CD44 (P < .001) was decreased in LNM. Samples classified as mesenchymal (post-EMT) showed elevated expression of CSCs markers (OCT-4 and CD44 in PT; OCT-4 in LNM; ALDH1, OCT-4, NANOG, CD44 in CTCs). Patients with mesenchymal-like CTCs had worse prognosis than patients with epithelial-like or no CTCs (P = .0025). CSCs markers are enriched in PT, LNM, and CTCs with mesenchymal features, but their heterogeneity is decreased in metastatic lymph nodes. Mesenchymal CTCs phenotype correlates with poor prognosis of the patients.

The etiology of sarcoidosis is unknown, but microbial agents are suspected as triggers.We sought to identify bacterial, fungal, or viral lineages in specimens from patients with sarcoidosis enriched relative to control subjects using metagenomic DNA sequencing. Because DNA from environmental contamination contributes disproportionately to samples with low authentic microbial content, we developed improved methods for filtering environmental contamination.We analyzed specimens from subjects with sarcoidosis (n = 93), control subjects without sarcoidosis (n = 72), and various environmental controls (n = 150). Sarcoidosis specimens consisted of two independent sets of formalin-fixed, paraffin-embedded lymph node biopsies, BAL, Kveim reagent, and fresh granulomatous spleen from a patient with sarcoidosis. All specimens were analyzed by bacterial 16S and fungal internal transcribed spacer ribosomal RNA gene sequencing. In addition, BAL was analyzed by shotgun sequencing of fractions enriched for viral particles, and Kveim and spleen were subjected to whole-genome shotgun sequencing.In one tissue set, fungi in the Cladosporiaceae family were enriched in sarcoidosis compared with nonsarcoidosis tissues; in the other tissue set, we detected enrichment of several bacterial lineages in sarcoidosis but not Cladosporiaceae. BAL showed limited enrichment of Aspergillus fungi. Several microbial lineages were detected in Kveim and spleen, including Cladosporium. No microbial lineage was enriched in more than one sample type after correction for multiple comparisons.Metagenomic sequencing revealed enrichment of microbes in single types of sarcoidosis samples but limited concordance across sample types. Statistical analysis accounting for environmental contamination was essential to avoiding false positives.

Aim The aim of the study was to assess the watch&wait strategy for management of patients with close surgical margin after conservative parotidectomy due to early low/intermediate grade parotid carcinoma. Patients and methods Out of 78 patients operated on due to primary parotid gland cancer we selected 32 patients with a history of parotidectomy, and preservation of 7th nerve, with negative (≥1 mm), but close (≤5 mm) surgical margin and who did not receive supplementary radiotherapy due to other indications. Margins ranged from 1 to 3 mm (in 27 cases it was 1 mm, in 3 cases – 2 mm and in 2 cases – 3 mm), average 1.2 mm. The patients underwent further clinical-histological analysis. Results 3 of 32 (9.38%) patients experienced a local recurrence 36, 53 and 56 months post-surgery. The 5-year disease-free survival (DFS) was 90.6%. Recurrences were treated surgically, followed by radiotherapy, which resulted in an overall survival of 107, 104 and 104 months. One patient died 72 months after surgery due to non-oncological causes. The 10-year disease-free survival (DFS) was 96.3%. The 3 patients with recurrence of cancer had histological diagnosis of epithelial-myoepithelial carcinoma LG, with a margin of 2, 1 and 3 mm, respectively. There were no other distinctive features. Conclusion The watch&wait strategy with intensive follow-up seems justified in cases of close margin after excision of I/LG T1/T2 parotid tumors. EMC should be considered as a neoplasm associated with higher risk of recurrence.

Rationale: Etiology of sarcoidosis remains unknown, although it is strongly suggested that it develops in response to infectious factors in genetically predisposed individuals, hence expression of FcγRII and -III in sarcoid granuloma should differ from foreign body granuloma, being non-infectious in origin. Objective: FcγRs are key players in the afferent and efferent immune response. They trigger complexed antigens and opsonised microbes phagocytosis. During inflammation evoked by infectious factors number of activating FcγRIIA and FcγRIIIA increase, while number of inhibitory FcγRIIB remain at the same level. It cause lowering to the signalling threshold for antibody-mediated cell activation during inflammation. Methods: Formalin-fixed, paraffin-embedded skin samples with sarcoid non-caseating granulomas were retrieved from 28 newly diagnosed patients with cutaneous sarcoidosis and from 14 patients with foreign body granuloma in the skin. Diagnosis of SA was confirmed retrospectively by analysis of clinical and pathological databases. FcγR expression was assessed by immunohistochemistry and modified H-score was used to determine their expression by 2 senior pathologists. Measurements and Main Results: Increased expression of membranous FcγRIIa (p Conclusions: Increased number of activating receptors, coexisting with not increased number of inhibitory FcγRIIb in SA strongly supports its infecfectious etiology.

The most recent classification of the lung cancer expanded the diagnostic criteria of its histological subtypes and included its immunophenotypic profile. We performed the study to compare the reliability of selected markers in high-grade non-small cell lung carcinoma (NSCLC) in the oligobiopsies with the matched postoperative samples. We evaluated expression of p40, p63, TTF1, cytokeratin 5/6, cytokeratin 7, napsin A, desmoglein 3, desmocollin 3 and mucin secretion as detected by mucicarmine staining. The study cohort included 123 cases of poorly-differentiated NSCLC. The tissue oligobiopsy material was available in 38 cases. Tissue microarrays (TMAs) from all postoperative cases were constructed. Comparing the immunophenotype between postsurgical samples and oligobiopsies we found an almost perfect agreement for most of performed IHC reactions. The highest concordance of results was found for desmoglein 3, CK7, and p40, whereas the lowest – for desmocollin 3. Immunoprofile of the oligobiopsies corresponded well to that in the resection specimens. The most useful markers in poorly differentiated ADs are: TTF1 and napsin A, and for non-keratinizing SCCs: p40, p63, CK5/6 and desmoglein 3.

The present study was undertaken to evaluate real probability and pattern of cervical occult lymph node metastases (OLNM) in primary parotid carcinoma (PPC). We carried out a retrospective analysis of 66 patients treated in years 1992–2010 due to PPC, who underwent elective neck dissection (END). In search of risk factors for OLNM, we analysed the following parameters: age, sex, pT-Status, tumour size, skin invasion, facial nerve palsy, tumour fixation, extraparotid extension, localization, grade, histology, intra/periparotid LN metastases (IPLNM). OLNM was observed in 30.3% of patients. In a univariate analysis statistical significance was found for IPLNM, extraparotid extension and high risk histology. A multivariate analysis showed statistical significance only for the first variable. The most common location of cervical OLNM was level II (80%), then III (45%) and V (30%). In a compilation of our own material with data from the literature (5 series), we obtained a group of 80 patients with OLNM, selected out of 650 patients with cN0 (12.3%). The proportion of metastases to particular levels was the following: 69%—II, 22.5%—III, 20%—I,16%—V, 7.5%—IV. END should be carried out in case of all T3/T4a carcinomas with minimal range of levels II and III. Removal of levels Ib and Va is recommended as well. In the T1/T2 carcinomas with high grade/high risk histology, END should be performed including levels II and III.

Metastatic tumors involving salivary glands arising from the non-head and neck area are very rare. Renal cell carcinoma (RCC) is known for its high propensity for metastasis to unusual localizations. RCC metastasis to the maxillofacial area is an uncommon event (16%), but metastasis to salivary glands is extremely rare. We report a series of 9 such cases retrieved from two institutions. The group included 6 females and 3 males. The age at diagnosis ranged from 60 to 97 years (mean 72.6 years). The tumors involved the parotid gland in 7 cases, and the submandibular and small salivary gland of the oral cavity in 1 case each. The size of tumors ranged from 0.4 to 5 cm. Total parotidectomy with selective neck dissection was performed in 4 cases, while superficial parotidectomy was performed in 1 case and simple resection in 3 cases. Histologically, all the tumors were clear cell renal cell carcinomas, and therefore the differential diagnosis mainly included clear cell variants of salivary gland carcinomas. The parotid gland was the initial manifestation of renal malignancy in 4 of the cases, while in the remaining 5 cases a history of RCC had been known. The salivary gland involvement developed from 11 months to 13 years after the time of diagnosis of the primary tumor. In 2 cases it was the first site of dissemination. Pathologists need to maintain a high index of suspicion for the possibility of metastasis when confronted with oncocytic or clear cell neoplasms developing in salivary glands. RCC, although rare, should be included in this differential diagnosis.

Bones are the most common metastatic site of relapse in breast cancer patients and the prediction of bone metastases (BM) risk might prompt developing preventive and therapeutic strategies. The aim of the study was to correlate imumohistochemical (IHC) expression of selected proteins in primary breast cancer with the occurrence of BM. We analyzed expression of proteins potentially associated with BM in primary tumors of 184 patients with metastatic breast cancer (113 with- and 71 without BM). Expression of estrogen receptor (ER) in primary tumor was more common in patients with- compared to those without BM (74 vs. 45 % respectively, p = 0.0001), whereas in this subset less common was expression of parathyroid hormone related protein receptor type 1 (16 vs. 34 %, respectively, p = 0.007) and cytoplasmic expression of osteopontin (OPNcyt; 1.9 vs. 14 %, respectively, p = 0.002). The relationship between expression of ER and OPNcyt and the occurrence of BM was confirmed in the multivariate analysis. The ER-positive/OPNcyt negative phenotype was significantly more common in patients with- compared to those without BM (75 and 25 %, p

This study examines the presence of the EWSR1 rearrangement in a variety of clear cell salivary gland carcinomas with myoepithelial differentiation. A total of 94 salivary gland carcinomas with a prominent clear cell component included 51 cases of clear cell myoepithelial carcinomas de novo (CCMC), 21 cases of CCMCs ex pleomorphic adenoma (CCMCexPA), 11 cases of epithelial-myoepithelial carcinoma (EMC), 6 cases of EMC with solid clear cell overgrowth, and 5 cases of hyalinizing clear cell carcinoma of minor salivary glands. In addition, 10 cases of myoepithelial carcinomas devoid of clear cell change and 12 cases of benign myoepithelioma were included as well. All the tumors in this spectrum were reviewed, reclassified, and tested by fluorescence in situ hybridization (FISH) for the EWSR1 rearrangement using the Probe Vysis EWSR1 Break Apart FISH Probe Kit. The EWSR1 rearrangement was detected in 20 of 51 (39%) cases of CCMC, in 5 of 21 (24%) cases of CCMCexPA, in 1 of 11 (9%) cases of EMC, and in 4 of 5 (80%) cases of hyalinizing clear cell carcinoma. The 25 EWSR1-rearranged CCMCs and CCMCexPAs shared similar histomorphology. They were arranged in nodules composed of compact nests of large polyhedral cells with abundant clear cytoplasm. Necrosis, areas of squamous metaplasia, and hyalinization were frequent features. Immunohistochemically, the tumors expressed p63 (96%), cytokeratin CK14 (96%), and S100 protein (88%). MIB1 index varied from 10% to 100%, with most cases in the 20% to 40% range. Clinical follow-up information was available in 21 cases (84%) and ranged from 3 months to 15 years (mean 5.2 y); 4 patients were lost to follow-up. Ten patients are alive with no evidence of recurrent or metastatic disease in the follow-up period from 3 months to 15 years (mean 5 y), 3 patients are alive with recurrent and metastatic disease, and 8 died of disseminated cancer 9 months to 16 years after diagnosis (mean 6 y). Lymph node metastasis appeared in 5 patients within 5 months to 4 years after diagnosis (mean 22 mo), distant metastases were noted in 7 patients with invasion of orbit (2 cases), and in 1 case each metastasis to the neck soft tissues, liver, lungs, mediastinum, and thoracic vertebra was noted. We describe for the first time EWSR1 gene rearrangement in a subset of myoepithelial carcinomas arising in minor and major salivary glands. The EWSR1-rearranged CCMC represents a distinctive aggressive variant composed predominantly of clear cells with frequent necrosis. Most EWSR1-rearranged CCMCs of salivary glands are characterized by poor clinical outcomes.

Background: Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, wellcharacterized cohort of these tumors. Materials and methods: 182 salivary gland carcinomas were tested for ALK positivity by immunohistochemistry using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture based next generation sequencing (NGS). Results: Of the 182 tumors, 8 were ALK positive. Further analysis showed ALK amplification in one case of intraductal carcinoma/low grade cribriform cystadenocarcinoma (LGCCC). Hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2. Conclusion: We identified a potentially targetable novel ALK fusion in an intraductal carcinoma/LGCCCC of minor salivary glands.

Intratumor heterogeneity implies heterogeneous protein function, facilitating tumor adaptation which results in therapeutic failure. We hypothesized that tumor heterogeneity at protein level may influence the course of the disease. As a single biopsy might not represent the full biologic complexity of the tumor, we have analyzed immunohistochemically four different cores obtained from each primary tumor within the cohort of 364 patients with endometrial cancer (EC). The following proteins were examined: estrogen receptor 1 (ESR1), progesterone receptor, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, receptor tyrosine-protein kinase erbB-3, v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4, phosphatidylinositol-4,5-bisphosphate 3-kinase, phosphorylated v-akt murine thymoma viral oncogene homolog 1, v-myc avian myelocytomatosis viral oncogene homolog, DNA topoisomerase II alpha 170 kDa (TOP2A), cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein p53, RAD21 homolog, S. pombe, and runt-related transcription factor 1. Particularly strong correlation was found between TOP2A and CDKN2A heterogeneity and higher stage of the disease (P = .0002 and P = .0003, respectively). Most correlations with clinicopathologic data were observed for ESR1 heterogeneity that correlated with non-endometrioid carcinomas (P=.02), higher stage (P=.005), grade (P=.01), and the presence of metastases (P = .01). Thirty-nine (11.0%) patients were classified as “globally heterogeneous”. Cumulative tumor heterogeneity strongly correlated with the presence of metastases, higher stage, and higher grade of the disease (all P b .05). It also carried negative prognostic value (P=.0008). We show that the degree of heterogeneity in EC might serve as a clinically valid molecular marker.

Whilst the role of eukaryotic translation initiation factors (eIFs) has already been investigated in several human cancers, their role in endometrial cancer (EC) is relatively unknown. In the present retrospective study, 279 patients with EC (1180 samples) were included (mean age: 63.0 years, mean follow-up: 6.1 years). Samples were analysed for expression of 7 eIFs subunits (eIF2&alpha, eIF3c, eIF3h, eIF4e, eIF4g, eIF5, eIF6) through immunohistochemistry and western blotting. Fifteen samples of healthy endometrium served as controls. Density and intensity were assessed and mean combined scores (CS) calculated for each patient. Upon immunohistochemistry, median eIF5 CS were significantly higher in EC as compared with non-neoplastic tissue (NNT, p &lt, 0.001), whilst median eIF6 CS were significantly lower in EC (p &lt, 0.001). Moreover, eIF5 (p = 0.002), eIF6 (p = 0.032) and eIF4g CS (p = 0.014) were significantly different when comparing NNT with EC grading types. Median eIF4g CS was higher in type II EC (p = 0.034). Upon western blot analysis, eIF4g (p &lt, 0.001), peIF2&alpha, (p &lt, 0.001) and eIF3h (p &lt, 0.05) were significantly overexpressed in EC, while expression of eIF3c was significantly reduced in EC as compared with NNT (p &lt, 0.001). The remaining eIFs were non-significant. Besides tumour stage (p &lt, 0.001) and patient&rsquo, s age (p &lt, 0.001), high eIF4g CS-levels were independently associated with poor prognosis (HR: 1.604, 95%CI: 1.037&ndash, 2.483, p = 0.034). The other eIFs had no prognostic significance. Notably, the independent prognostic significance of eIF4g was lost when adding tumour type. Considering the difficulties in differentiating EC type I and II, eIF4g may serve as a novel prognostic marker indicating patient outcome.

Background There are no clinically useful biomarkers predictive of brain metastases (BM) in breast cancer. In this study, we investigated the correlation between expression of selected proteins in the primary tumor and the risk of BM in patients with metastatic breast cancer (MBC). Methods The study included 198 MBC patients (96 with and 102 without BM). Using tissue microarrays derived from the primary tumor, we assessed by immunohistochemical expression of ER, PR, HER2, Ki-67, CK5/6, EGFR, HER3, CXCR4, Rad51, E-cadherin, and claudin 3 and 4. Results Ki-67 ≥14% (hazard ratio [HR] 2.76; P P = 0.014) and ER-negativity (HR 1.72; P = 0.029) were associated with increased risk of BM in the multivariate analysis. A three-biomarker profile including ER, Ki-67 and Rad51 vs. other subtypes combined yielded an HR of 4.43 ( P Conclusions ER-negativity, cytoplasmic expression of Rad51 and high Ki-67 are associated with increased risk of BM.

The molecular background of endometrial cancer (EC) has not been fully elucidated. In the present study, we developed a quantitative PCR (qPCR) platform to examine the gene dosages of the potential molecular markers MGB1, TOP2A, ERBB1-4, MYC, CCND1, ESR1 and PI3K. The platform was applied in samples collected from 157 EC patients (stage I-IV) to verify its clinical utility and to examine the diagnostic and prognostic significance of the analysed biomarkers. The gene dosage pattern of the ERBB family and its downstream effectors PI3K and MYC showed particularly strong correlations with clinicopathological data. The ERBB PI3K/Akt pathway was upregulated in 31 (20%) of 156 cases. Activation of the ERBB PI3K/Akt pathway was positively correlated with a higher stage (p=0.001), higher grade (p=0.001), histological type II disease (p=0.0003) and metastases (p=0.02). The implemented hierarchical clustering revealed that cluster 2 was characterised by high copy numbers of the studied genes. Cluster 2 was associated with shorter overall survival (p=0.05). The platform was found to be a fast and simple method for direct analysis of the genes involved in uterine carcinogenesis, making it feasible for EC biology characterisation.

Parotid gland metastases from distant malignant tumors are uncommon (0.16–4%). The distinction between primary and metastatic tumors in salivary gland is of special importance for therapy and prognosis. For the treatment of this metastasis, parotidectomy, radiation, chemotherapy, and hormone therapy were performed. The authors presented the case of distant metastasis to the parotid gland; a 59-year-old woman with breast cancer and metastases to the parotid gland 12 years after surgery. Because immunohistochemical analysis in our case had revealed the tumor to be positive for estrogen and progesterone receptors we continued to administer postoperatively hormonotherapy. The prognosis of patients presenting with metastatic deposits in parotid gland from a distant primary tumor is usually poor. The long-term prognosis is influenced by the histological type, location, and staging of the primary tumor type and steroid receptors – positive and HER2 overexpression. Adjuvant hormonotherapy is an effective treatment, which prolongs survival in women with hormone receptor-positive breast cancer.

Introduction: We revealed that mycobacterial heat shock proteins being implicated in forming immune complexes (CIs) can induce an immune response in sarcoidosis (SA). The immunocomplexemia in our SA patients with Stage I/II, not with Stage III/IV, may be a result of monocytes disorder of abilities to phagocytosis/clearance CIs, which rely on the function of receptors for Fc fragment of immunoglobulin G (FcγR) and for complement (CR). A stimulation of FcγRIIa, encoded by FCGR2A gene, can impact the CR3 function, which may cause a decreased affinity of this FcγR to ICs and their decreased clearance. Aim/Materials/Methods: Therefore, we evaluated the FcγRIIa and CR3R expression on blood monocytes, and polymorphism of FCGR2A gene in 114 SA patients and 148 healthy volunteers, using flow cytometry and PCR-SSP. Results: Our study revealed significantly increased expression of FcγRIIa and unchanged C3R on monocytes in SA patients with Stage I/II vs. Controls. Analysis of H131R polymorphism of FCGR2A gene revealed a significantly increased occurrence of 131HH and decreased frequency of 131HR in Stage III of SA vs. controls, with increased affinity of FcγRIIa to CIs and increased clearance of CIs. In SA patients with Stages I/II, we revealed a significantly decreased percentage of 131HH genotype of FCGR2A and a significant increase in an occurrence of 131HR heterozygotes in Stage I/II vs. Stage III/IV. Conclusions: Thus, H131R polymorphism of FCGR2A may cause of disorder of function of FcγRIIa with subsequent unchanged CR3 expression and decreased affinity of FcγRIIa to CIs and their decreased clearance with following immunocomplexemia in our SA patients with Stage I/II. Study was founded by grant no.02-127/07/232.

Thyroid transcription factor-1 (TTF-1) is a marker of tumors of pulmonary and thyroid origin, and its expression practically excludes diagnosis of Merkel cell carcinoma (MCC). However, TTF-1 expression in combined MCC was recently reported. PAX5 is a marker of B-cell origin that is also expressed in most classical MCC cases; however, its expression was not described in combined MCC. The authors decided to evaluate the expression of both these markers in a group of 5 combined MCCs (2 with invasive squamous cell carcinoma, 2 with squamous cell carcinoma in situ, and 1 with basal cell carcinoma). Expression of TTF-1 was found in 4 of 5 cases; in 3 cases, the marker was shown in the MCC component (weakly in 2 cases and strongly in 1 case), whereas the non-MCC component presented TTF-1 expression in 2 cases. A weak-to-moderate immunoreactivity for PAX5 was identified in all cases of the MCC component but in none of the non-MCC component. The results show that the expression of TTF-1 is a frequent finding in combined MCC and can be present in the neuroendocrine component, which differs from the conventional MCC. In contrast, PAX5 expression pattern is similar to that of the classical MCC.

Background: About 10–30% of breast cancer patients will develop brain metastases. In untreated patients with brain metastases the median survival is 1–2 months, and in those undergoing palliative radiotherapy — 3–6 months. The mechanism of brain metastases remains largely unknown. The identification of molecular markers might help in selecting high risk patients, and enable active surveillance, prevention and early treatment. The aim of this study was to analyze predictive value of expression of selected tumor proteins for the risk of brain metastases in breast cancer patients. Material and methods: This study included 198 advanced breast cancer patients treated between 2001 and 2007 in 11 oncology centers in Poland, including 96 woman with and 102 without overt brain metastases, respectively. The median age at diagnosis in these two groups was 52 and 60 years, respectively, with 52% and 32% of patients being premenopausal. Stage at diagnosis was similar in both groups and ductal carcinoma was a dominant histological type (76% and 86% of cases, respectively). Immunohistochemistry was performed on formalin-fixed paraffin embedded microarray cores derived from the primary tumor. Expression analysis included ER, PR, HER2, Ki67, CK5/6, EGFR, HER3, CXCR4, RAD51, E-cadherin, and claudin 3 and 4. Cox regression model was used to estimate the relative risk of brain metastases. Results: Expression of HER2, CK5/6, EGFR, RAD51 (both cytoplasmatic and nuclear staining), CXCR4 (cytoplasmatic staining) and Ki67 ≥14%, as well as ER or PR negativity was associated with increased risk of brain metastases in the univariate analysis (Table 1). Of those, Ki67 ≥14% (HR 2.76 [95%CI 1.70–4.48]; p < 0.001), cytoplasmatic expression of double strand DNA repair gene RAD51 (HR 1.87 [95%CI 1.14–3.08]; p = 0.014) and ER negativity (HR 1.72 [95%CI 0.36–0.94]; p = 0.029) were found to be significantly related to the risk of brain relapse in the multivariate analysis. Four molecular profiles composed of the latter three markers were created, of which a profile including ER, Ki67 and RAD51 was associated with the highest risk of brain metastases (HR 4.43 [95%CI 2.69–7.27]; p < 0.001). Molecular subtype analysis showed the highest risk of BM in the ER/PR/ HER2-negative (triple negative) subset (HR 1.21 [95%CI 1.11–1.32]; p < 0.001). Conclusion: Expression of proteins related to high tumor proliferation, DNA repair and ER negativity is associated with increased risk of brain metastases in breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-09.

Background. Bones constitute the most frequent localization of distant failure in breast cancer patients. Treatment of bone metastases is virtually palliative, but in a proportion of patients can effectively prolong survival and improve quality of life. Currently, there are no effective strategies to prevent bone dissemination with systemic adjuvant therapies. Thus, better molecular selection and identification of patients who have particularly high risk of skeletal metastases may facilitate designing future clinical trials. In this study we analyzed expression of selected tumor proteins potentially associated with skeletal metastases in breast cancer patients. Patients and methods. The study group included 184 metastatic breast cancer patients; 113 with clinically diagnosed bone metastases and 71 with exclusively other sites of metastases, respectively. In all patients, using tissue microarrays technology, IHC expression of the following proteins was evaluated in the primary tumor: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, cyclooxygenase 2 (COX2), chemokine receptor CXCR4, osteopontin (OPN), calcium sensing receptor (CaSR), cytokeratins 5/6 (CK5/6) and parathyroid hormone-related protein receptor 1 (PTHrPR1). Additionally based on ER/PR, HER2 and Ki67 expression, following molecular breast cancer subtypes were selected: luminal A, luminal B HER2-negative, luminal B HER2-positive, nonluminal HER2-positive and triple negative. Results. Median survival in patients with bone vs. other site of metastases was 56 vs. 37 months respectively (p = 0.0098). ER expression was more common in patients who did, compared with those who did not develop bone metastases (74.% vs. 45% respectively; p = 0.0001), whereas cytoplasmic overexpression of OPN (1.9% vs. 14% respectively; p = 0.002) and PTHrPR1 (16% vs. 34% respectively; p = 0.007) was more common in patients with other sites of metastases. The impact of ER and cytoplasmic OPN expression on the risk of bone dissemination was confirmed in the multivariate analysis (Table 1). Luminal A breast cancer subtype (43% vs. 23% respectively; p = 0.009) and luminal B HER2-positive (16% vs. 4.9%, respectively; p = 0.032) were more common among patients with bone dissemination, whereas triple negative tumors prevailed in patients with other sites of metastases (16% vs. 38%; p = 0.002). Median survival of patients with luminal A subtype was significantly longer than that with remaining subtypes (67 vs. 38 months respectively; p = 0.0004). Conclusions. These results suggest that ER expression and lack of OPN expression are independent factors predicting increased risk of bone dissemination in breast cancer patients. Bone metastases are specifically associated with luminal A and luminal B HER2-positive subtypes. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-03.

Acquired ichthyosis is a known paraneoplastic sign of lymphoproliferative malignancies, but ichthyosiform eruption can also constitute a rare atypical variant of mycosis fungoides. Ichthyosiform mycosis fungoides differs from acquired ichthyosis associated with mycosis fungoides in histopathology. Histological pictures of paraneoplastic ichthyosis usually do not show any aspect related to malignancy in the skin. In both cases thinning of the granular layer and decrease of filaggrin in that layer are observed. We describe here 2 patients with mycosis fungoides, who were treat ed in the Department of Dermatology, the first one with ichthyosiform mycosis fungoides and the other one with acquired ichthyosis with coexisting mycosis fungoides.

Orbital tumor is a rare presentation of lymphoma. Unspecific symptoms, local infiltration, chronic progression may mimic other more common orbital diseases and often make the diagnosis difficult. We report a case of orbital non-Hodgkin lymphoma initially diagnosed as Graves’ disease. A 65-year-old woman was admitted to the Department of Endocrinology with a diagnosis of a left eye tumor. On admission, apart from the tumor, exophthalmos and the upper eyelid proptosis were present. The lesion had been observed for two years before hospitalization. Due to the muscle infiltration, as detected on computed tomography scanning and magnetic resonance imaging, Graves’ disease was suggested. The thyroid function was normal. Further diagnosis performed during hospitalization revealed lymphoplasmacytic lymphoma. Lymphoma may manifest as a localized orbital tumor without extraorbital or constitutive symptoms. Rare orbital diseases, among others lymphoproliferations, should be taken into account in the differential diagnosis of exophthalmos.

Malignant acanthosis nigricans is a rare paraneoplastic skin syndrome mostly associated with gastric adenocarcinoma. Florid cutaneous papillomatosis and tripe palms syndrome are considered to be abortive clinical variants of acanthosis nigricans. Clinical manifestations include pruritic, hyperkeratotic and hyperpigmented plaques with a subsequent formation of velvety papillomas in the involved areas. This case report describes an unusual case of the patient diagnosed with a combination of malignant acanthosis nigricans, florid cutaneous papillomatosis and tripe palms syndrome associated with gastric adenocarcinoma.

Studies on the influence of long-lasting hyperthyroidism on enzyme activities and total protein level in the blood plasma of adult Leghorn hens showed that: 1. Protein level during whole experimental period showed inconsiderable variability irrespective of T4 dose. 2. Activity of aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) increased. Changes were dependent on T4 dosage level. 3. T4 had no effect on activity of aldolase.

Background Endometrial cancer (EC) is a hormone-related disease, showing highly diverse features of ER/PR/HER2 status-based molecular subtypes. Long noncoding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) has recently emerged as a key molecule in many cancers, triggering epithelial-mesenchymal transition (EMT)–mediated cancer stem cell (CSC) formation, but little is known about its significance in EC. Thus, we aimed to investigate the clinical significance of HOTAIR itself in different molecular subtypes of EC and possible links between HOTAIR, EMT and CSC-related markers. Methods The study group included 156 consecutive, stage I-IV EC patients treated between 2000 and 2010. ER, PR and HER2 protein expression were examined by immunohistochemistry (IHC) on tissue microarrays. RT-qPCR was used to analyze the expression levels of HOTAIR, EMT-related genes – SNAIL and SLUG – and the CSCs marker CD133. Results Molecular subtypes, defined as ER/PR+HER2+, ER/PR+HER2-, ER-PR-HER2+ and ER-PR-HER2-, occurred in 40.2%, 52.3%, 4.7% and 1.9% of cases, respectively. The expression of HOTAIR did not differ between the subtypes, but high HOTAIR expression correlated with shorter overall survival (p = 0.04) in the entire group. The expression levels of HOTAIR, SNAIL, SLUG and CD133 were similar in defined EC molecular subtypes. Conclusions Our data do not confirm the role of HOTAIR in EMT-mediated CSC formation in EC. Neither does the diversity of EC molecular subtypes influence these processes. But HOTAIR expression could serve as an independent prognostic factor in EC. The clinical importance of the above discoveries requires further studies.

ETV6 gene abnormalities are well described in tumor pathology. Many fusion partners of ETV6 have been reported in a variety of epithelial and hematological malignancies. In salivary gland tumor pathology, however, the ETV6-NTRK3 translocation is specific for mammary analogue secretory carcinoma (MASC), and has not been documented in any other salivary tumor type. The present study comprised a clinical and molecular analysis of 25 cases morphologically and immunohistochemically typical of MASC. They all also displayed the ETV6 rearrangement as visualized by fluorescent in situ hybridization but lacked the classical ETV6-NTRK3 fusion transcript by standard reverse-transcriptase-polymerase chain reaction. In 4 cases, the classical fusion transcript was found by more sensitive, nested reverse-transcription-polymerase chain reaction. Five other cases harbored atypical fusion transcripts as detected by both standard and nested reverse-transcription-polymerase chain reaction. In addition, fluorescent in situ hybridization with an NTRK3 break-apart probe was also performed; rearrangement of NTRK3 gene was detected in 16 of 25 cases. In 3 other cases, the tissue was not analyzable, and in 2 further cases analysis could not be performed because of a lack of appropriate tissue material. Finally, in the 4 remaining cases whose profile was NTRK3 split-negative and ETV6 split-positive, unknown (non-NTRK) genes appeared to fuse with ETV6 (ETV6-X fusion). In looking for possible fusion partners, analysis of rearrangement of other kinase genes known to fuse with ETV6 was also performed, but without positive results. Although numbers were small, correlating the clinico-pathologic features of the 4 ETV6-X fusion tumors and 5 MASC cases with atypical fusion transcripts raises the possibility of that they may behave more aggressively.

The aim the study was to compare two groups of endometrial cancer patients (below and above 45 years of age) in the aspect of clinicopathological and molecular data.The study encompassed 456 primary tumour samples retrospectively collected from a cohort of endometrial cancer patients, primarily treated by surgery Molecular analysis covered: copy number variations of 10 genes (TOP2A, ERBB1, ERBB2, ERBB3, ERBB4, MYC, CCND1, ESR1, PIK3CA, RAD21) analyzed by quantitative PCR; mRNA expression of 6 genes (SCGB2A2, RAD27, RUNX1, SNAI1, SNAI2, PROM1) analyzed with the use of reverse transcription quantitative PCR; protein expression analysis of 8 markers (PGR, ESR1; ERBB1, ERBB2, ERBB3, ERBB4, TOP2A, pAKT1) performed with the use of immunohistochemistry.The younger group of patients was characterized by less frequent hypertension (p0.00007), less frequent myometrial infiltration (p=0.002) and longer overall survival (p=0.003). Apart from RAD21 gene aberrations, which were more frequent in younger patients (p=0.02), the study revealed no statistically significant differences between the groups.The study showed no molecular differences in the profile of younger and older endometrial cancer patients. Data on both the prognostic and predictive significance of RAD21 in endometrial cancer are still insufficient. The clinical profile of younger patients with endometrial carcinoma was slightly better when compared to elderly patients. Younger patients were characterized by longer overall survival.

Epithelial-mesenchymal transition (EMT) was shown to enhance metastatic abilities of cancer cells, but it remains elusive in clinical samples. Moreover, EMT is rarely studied in lymph node metastases (LNM), thus limiting our understanding of its role outside of the primary tumors (PT). We collected a set of samples including triplets - PT, circulating tumor cells (CTCs)-enriched blood samples and LNM from 108 early breast cancer patients. With immunohistochemistry we analyzed levels of EMT effectors – E-cadherin, vimentin and N-cadherin in LNM, central areas and margins of PT. Additionally, expression of EMT core regulators TWIST1, SNAI1, SNAI2 was measured with RT-qPCR. Patients with E-cadherin loss had CTCs in 45% of the cases in comparison to 23% with normal E-cadherin level (P = 0.05). Mesenchymal phenotype of CTCs-enriched blood fractions was five-times more frequent in patients with E-cadherin loss in PT compared to PT with normal E-cadherin levels (P = 0.01). Epithelial/mesenchymal status of matched samples at different stages of dissemination was frequently discordant, especially for pairs involving CTCs, indicating high plasticity of tumor cells. LNM showed increased expression of TWIST1, SNAI1, SNAI2 accompanied by decreased Ki67 labeling index, with median Ki67 of 15% in PT and 10% in LNM (P = 0.0002). Our findings demonstrate that E-cadherin loss, not only in PT margin, might lead to seeding of especially malignant CTCs with mesenchymal phenotype. In comparison to PT, cells in LNM re-express E-cadherin, upregulate EMT transcription factors and reduce cell division rate, which could be viewed as their long-term survival strategy.

Extranodal marginal zone lymphoma (EMZL, MALT lymphoma) and carcinoid are neoplasms occurring most frequently in the gastrointestinal tract and respiratory system. Although each of them occurs relatively frequently and separately, the simultaneous appearance of these two neoplasms is exceptionally rare, and only a few cases in the gastrointestinal tract have been described so far. We report a case of a 70-year-old female with the simultaneous presence of MALT lymphoma and tumorlet in the middle lobe of the right lung. To the best of our knowledge, this is the first report of such a collision tumor at the same anatomical site.

Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are presumed to be key conditions for malignancy. Data concerning their role in endometrial cancer (EC) are scarce. We aimed to investigate the possible link between EMT and CSCs markers in EC samples.The study encompassed 156 primary tumour samples. Using RT-qPCR, we analyzed the expression of EMT-related genes, SNAIL and SLUG, and the CSCs marker CD133.SNAIL and SLUG correlated with each other (R=0.33; p=0.00003). All the studied genes were expressed in both normal and malignant endometrial tissue. Decreased SNAIL expression was found to correlate with post-menopausal status (p=0.002). Decreased SLUG expression was associated with shorter overall survival (p=0.01).SLUG expression could serve as a prognostic factor in EC. No correlation between the expression of EMT and CSCs markers was found, suggesting there to be no association between the EMT and CSC phenotype in endometrial cancer.

Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor resembling secretory carcinoma of the breast characterized by strong S-100 protein, mammaglobin, and vimentin immunoexpression and which harbors a t(12;15) (p13;q25) translocation resulting in ETV6-NTRK3 fusion product. Histologically, conventional MASC displays bland histomorphology and a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogenous or bubbly secretions. Colloid-like secretory material stains positively for periodic acid-Schiff with and without diastase as well as for Alcian Blue. We present for the first time, 3 patients with MASC of the parotid gland in which high-grade (HG) transformation developed in each case characterized by an accelerated clinical course and poor outcome. The HG component revealed strong membrane staining for EGFR and β-catenin, cytoplasmic/nuclear staining for S-100 protein, and nuclear staining for cyclin-D1, whereas HER-2/neu was absent. Analysis for the presence of the ETV6-NTRK3 fusion transcript revealed positivity in both HG and low-grade component of MASC in 2 of the 3 studied cases. The tumor in case 2 was negative in both its elements for the t(12;15) translocation, but ETV6 gene rearrangement was detected in both components in all 3 cases. Analysis of TP53 and CTNNB1 gene mutations in the HG component of MASCs as well as detection of copy number aberration of EGFR and CCND1 gene did not harbor any abnormalities. All 3 patients with HG-transformed MASC died of disseminated disease within 2 to 6 years after diagnosis. Recognizing HG-transformed MASC and testing for ETV6 rearrangement may be of potential value in patient treatment, because the presence of the ETV6-NTRK3 translocation may represent a therapeutic target in MASC.

Background Salivary gland neoplasms represent a heterogeneous group of benign and malignant tumors that comprise 6% of all head and neck cancers. Due to their low incidence, these tumors are poorly understood and remain a diagnostic and therapeutic challenge. Methods Out of 182 analyzed salivary gland tumors with various histologies, eight were positive for ALK immunohistochemistry. The cut-off was 15% positive cells in either membranous, nuclear or cytoplasmic compartments. The ALK positive tumors were first subjected to FISH analysis. Subsequently, these tumors were analyzed using hybrid capture based next generation sequencing to confirm possible ALK gene fusions or copy number alterations, and to detect additional genomic alterations of clinical relevance. Results An in-depth genomic analysis of the samples resulted in the detection of inactivating mutations in BRAF (p.D594N) and TP53 (p.C238S), as well as amplifications of ERBB2 and ALK. Strikingly, a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion was detected in a patient with adenocarcinoma not otherwise specified. This tumor was FISH positive and 100% of cells showed strong membranous staining for ALK. MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion resulted in the retention of the kinase domain of ALK and the coiled-coil domain of MYO18A. Similarly to other ALK fusions, we hypothesize that the coiled-coil domain of MYO18A mediates the dimerization and activation of MYO18A-ALK, thereby resulting in an overexpression of constantly activated ALK. Conclusion Using hybrid capture based next generation sequencing, we identified in salivary gland tumors numerous genomic alterations in therapeutically relevant genes and a novel gene fusion (MYO18A-ALK). Patients harboring this fusion may potentially benefit from treatment with ALK inhibitors. Citation Format: Hanna Majewska, Judith Müller, Sotirios Lakis, Piotr Czapiewski, Adam Gorczyński, Mariola Iliszko, Alena Skalova, Rafal Dziadziuszko, Jacek Jassem, Wojciech Biernat, Roopika Menon, Johannes M. Heuckmann, Lukas C. Heukamp. Genomic profiling of salivary gland tumors identifies novel and targetable alterations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3190.

The article describes a case of a 15-year old boy after a head contusion with a five-month history of headaches and two seizure episodes. MR imaging revealed a partly solid and partly cystic cortical-subcortical tumour within the precentral gyrus with post-contrast enhancement. The patient underwent gross total resection of the lesion. Histologically the neoplasm was composed of pseudopapillary gliovascular structures surrounded by solid glioneuronal tumour areas. The expression of GFAP and nestin characterized the central parts of the tumour. Moreover the immunolabelling for synaptophysin, neurofilaments, Olig2 and NCAM was present in the peripheral part of the lesion. The neoplasm was consistent with a papillary glioneuronal tumour - one of the new entities in the last WHO CNS tumour classification.

e16539 Background: Endometrial cancer (EC) is the most frequent malignancy of the female genital tract, with approximately 88,068 cases registered each year in the European Union. Discoveries of re...

e16540 Background: Dysregulation of the ERBB signaling network occurs in many human cancers and is associated with more aggressive tumor behavior and poor outcome. The data about the status of the ...

This paper presents the results of bulk wave transmission investigation in a wide band SAW filter designed on 128/spl deg/ YX LiNbO/sub 3/. Bulk wave transmission in the filter was investigated in both frequency and time domain. Fourier transform and windowing techniques were used to identify the most important bulk wave modes and their contribution to the frequency response of the device. The influence of the substrate backside grooving on bulk wave propagation was examined. Application of grooving significantly reduces the level of bulk wave modes bouncing off the backside of the substrate. As a result substantial improvement in stopband rejection was obtained. It was found that in the devices with their backside grooved one of the most prominent bulk waves is the longitudinal wave travelling directly between the IDTs of the filter. The longitudinal wave limits the rejection in the upper stopband to approx. 40 dB.

Studies on the influence of repeated injections of L-thyroxine on enzyme activity and total protein level in the blood plasma of White Rock and Sussex hens have shown that: 1. The total protein level in both races decreased significantly. 2. Activity of aldolase increased in White Rock hens while in Sussex hens it increased considerably only after the last injection. 3. Activity of alanine aminotransferase did not change in White Rock hens and increased in the blood plasma of Sussex hens. 4. In both races, the activity of aspartate aminotransferase increased initially and changed after L-thyroxine injection. 5. Activity of alkaline phosphatase increased in White Rock hens, while in Sussex hens it decreased. 6. Statistically significant differences between activities of examined enzymes in both races after L-thyroxine administration were found.

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumour that harbours the recurrent ETV6-NTRK3 translocation. This is the first series of MASC cases identified in the historic cohort of carcinomas of salivary glands with clinical/pathological correlation and follow-up data. We reviewed 183 primary carcinomas of major and minor salivary glands resected at the Medical University of Gdansk, Poland, between 1992 and 2012. Based on morphology and immunohistochemistry, cases suspicious for MASC were selected, and the diagnosis was confirmed by fluorescence in situ hybridization (FISH) for ETV6 rearrangement and by RT-PCR for the ETV6-NTRK3 fusion transcript. Seven carcinomas met the criteria of MASC, as they exhibited a typical appearance with solid/microcystic and papillary architecture and intraluminal secretions, and cells completely devoid of basophilic cytoplasmic zymogen granules indicative of true acinar differentiation. The only paediatric case was an unencapsulated tumour composed of macrocystic structures covered by a mostly single but, focally, double layer of cells with apocrine morphology. In all cases, the neoplastic cells revealed immunoreactivity for S100, mammaglobin, cytokeratin CK7, CK8, STAT5a and vimentin. FISH for ETV6 gene rearrangement was positive in six out of seven cases, and RT-PCR was positive in three cases. MASC is a new entity of malignant epithelial salivary gland tumours not included in the 2005 WHO Classification of Head and Neck Tumours. There is a growing body of evidence that it is not as rare as was assumed, as is also indicated by our series (3.8 %). In most cases, MASC shares some microscopic features with AciCC, adenocarcinoma/cystadenocarcinoma NOS and low-grade MEC. In rare cases, MASC with high-grade transformation may mimic the morphological appearances of high-grade salivary gland malignancies, such as salivary duct carcinoma.

Reassessment of histological specimens of salivary gland carcinomas is associated with a change of primary diagnosis in a significant number of patients. The authors evaluated the relation between reclassification/verification of histological diagnosis and the clinical course of parotid gland carcinomas. Histological and immunohistochemical examinations of 111 specimens of parotid gland carcinomas operated on during the years 1992-2010 were revised and in some cases supplemented with cytogenetic tests (FISH), to verify the diagnosis and potentially reclassify the tumours. Analysis of the clinical documentation and follow-up data of patients whose diagnosis was changed was then carried out. The prognostic factors taken into account in the evaluation of the clinical course included the T and N stage, the tumour grade and the extent of resection. The primary diagnosis was changed on review in 28 patients (25.2 %). In 16 patients, the change involved a different histological type of cancer. In six cases, what was thought to be a primary salivary gland cancer was reclassified as a secondary tumour. In four other cases, the change was made from a malignant to a benign tumour and in one case to a non-neoplastic lesion (necrotizing sialometaplasia). Additionally, in two patients with carcinoma ex pleomorphic adenoma, the malignant component was found to be of in situ type. A potentially atypical clinical course was observed in 4 out of 28 patients whose diagnosis was changed. In the case of 2 patients, the course of disease was more aggressive (dissemination, death) than predicted and less aggressive in rest of the patients. Histological reclassification/verification of parotid gland carcinomas can explain the cause of an atypical clinical course in some patients and sometimes enables doctors to implement a change in therapy.

1. 1. Quails hatched from eggs incubated at physiological temperature (37.5°C—normal quails) and elevated (39.3°C—warm quails) were injected with l -thyroxine (T4) at dose 600 μg per kg of body wt, every 48 hr for 17 days. 2. 2. After last injection of hormone the total protein level in the blood plasmaa as well as activities of the following enzymes in liver homogenates were detemined: phosphoglucomutase (PGM), glucosephosphate isomerase (GPI), phosphofructokinase (PFK), aldolase (ALD) and lactate dehydrogenase (LDH). 3. 3. The total protein level in the blood plasma was lowered in quails injected with l -thyroxine. Simultaneously, significant increase of the activity of PGM, GPI and PFK was observed. 4. 4. The activity of these enzymes increased up to 138.4;181.0 and 290% of the control in warm quails and 142.1;175.3 and 137.5% of the control in normal quails, respectively. 5. 5. The activity of lactate dehydrogenase in T4-treated quails changed slightly, while the activity of aldolase lowered below the control activity in normal quails and increased up to 163.7% of the control in T4-treated warm quails.