A Skálová

Charles University in Prague, Praha, Praha, Czech Republic

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Publications (108)229.67 Total impact

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    ABSTRACT: Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.
    Nature Genetics 09/2014; · 35.21 Impact Factor
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    ABSTRACT: This review concentrates on the most important developments since the WHO classification of 2005. In particular, the identification of specific translocations is revolutionising the way salivary tumours are considered and will have a major impact on future diagnostic practice. This is true so far in four malignancies: mammary analogue secretory, mucoepidermoid, adenoid cystic and hyalinising clear cell carcinomas. In each, the gene rearrangement is found in 80 % or more of cases. Two 2014 publications have added further possible candidates with molecular abnormalities to the list (cribriform adenocarcinoma of the tongue and minor salivary glands and epithelial-myoepithelial carcinoma), but these findings have yet to be confirmed by other investigators. The advances in molecular pathology have also allowed re-evaluation of the morphology; for example, it is now realised that the histological spectrum of hyalinising clear cell carcinoma includes intracellular mucin in over half of cases, as well as tumours with only scanty clear cells. In a separate development, it is now proposed that salivary duct carcinoma can be subdivided along molecular lines, in ways analogous to breast cancer, suggesting new therapeutic prospects in an otherwise highly aggressive malignancy.
    Virchows Archiv : an international journal of pathology. 08/2014;
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    ABSTRACT: Polymorphous low-grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of minor salivary gland (CAMSG) are low-grade carcinomas arising most often in oral cavity and oropharynx, respectively. Controversy exists as to whether these tumors represent separate entities or variants of one spectrum, as they appear to have significant overlap, but also clinicopathologic differences. As many salivary carcinomas harbor recurrent translocations, paired-end RNA sequencing and FusionSeq data analysis was applied for novel fusion discovery on two CAMSGs and two PLGAs. Validated rearrangements were then screened by fluorescence in situ hybridization (FISH) in 60 cases. Histologic classification was performed without knowledge of fusion status and included: 21 CAMSG, 18 classic PLGA, and 21 with "mixed/indeterminate" features. The RNAseq of 2 CAMSGs showed ARID1A-PRKD1 and DDX3X-PRKD1 fusions, respectively, while no fusion candidates were identified in two PLGAs. FISH for PRKD1 rearrangements identified 11 additional cases (22%), two more showing ARID1A-PRKD1 fusions. As PRKD2 and PRKD3 share similar functions with PRKD1 in the diacylglycerol and protein kinase C signal transduction pathway, we expanded the investigation for these genes by FISH. Six additional cases each showed PRKD2 and PRKD3 rearrangements. Of the 26 (43%) fusion-positive tumors, there were 16 (80%) CAMSGs and 9 (45%) indeterminate cases. A PRKD2 rearrangement was detected in one PLGA (6%). We describe novel and recurrent gene rearrangements in PRKD1-3 primarily in CAMSG, suggesting a possible pathogenetic dichotomy from "classic" PLGA. However, the presence of similar genetic findings in half of the indeterminate cases and a single PLGA suggests a possible shared pathogenesis for these tumor types.
    Genes Chromosomes and Cancer 06/2014; · 3.55 Impact Factor
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    ABSTRACT: Sclerosing polycystic adenosis (SPA) of salivary glands is a tumorous lesion of salivary glands, with clinical presentation of a slow-growing mass characterized by a combination of histological features some of which are reminiscent of mammary fibrocystic disease. SPA is mostly unifocal, but rarely may be multifocal and/or bilateral. Recurrences have been reported in up to 19% of cases. Although originally considered pseudoneoplastic, the occurrence of “dysplasia” and carcinoma in situ of ductal epithelium, and recent evidence of clonality suggest a possible neoplastic nature. Herein we describe, for the first time, two cases of SPA in two sisters (7 and 33 years old). The younger patient experienced multiple recurrences. This is the first report of familial occurrence of SPA, suggesting a possible genetic background.
    Pathology - Research and Practice 01/2014; · 1.21 Impact Factor
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    ABSTRACT: There is a subgroup among head and neck squamous cell carcinomas, which is etiologically linked to the infection of high-risk human papillomavirus (HPV). In recent studies, HPV related squamous cell carcinomas have been placed in a separate group because of their different epidemiology, distinctive histopathological characteristics, therapeutic response and clinical outcome. The reported prevalence of high-risk HPV in head and neck tumors varies in different studies. This fact occurs mainly due to the absence of a widely accepted consensus for HPV detection in head and neck malignancies. We present a methodological algorithm for detection of biologically relevant HPV infection: a combination of an immunohistochemical staining of the p16 protein - a surrogate marker for a transforming HPV infection, and a molecular genetic identification of HPV DNA by three different polymerase chain reactions (PCR). The study group consisted of 41 patients with a tumor in head and neck region. A verification of detection of biologically relevant HPV infection has been performed in 10 available samples using an alternative approach, which comprised the detection of RNA transcript of HPV by reverse transcription followed by PCR (RT-PCR), and further in situ hybridization (ISH) with a commercial high-risk HPV probe. We have found a high correlation between HPV DNA detection using triple-PCR approach and strong diffuse positivity of the p16 protein (correlation coefficient 0.94) and have confirmed the validity of this algorithm. In 94 % of HPV related squamous cell carcinomas HPV type 16 was detected. In one case HPV type 33 was identified. That is in agreement with earlier published data. A more appropriate alternative method for the detection of biologically relevant- transforming HPV infection seems to be RT-PCR, which proved 100 % agreement with the original methodological approach of p16 determination and PCR status. Interpretation of the ISH has been complicated by frequent nonspecific staining of the sample and its routine usage in the diagnostic algorithm of our laboratory is currently not feasible.Keywords: HPV - squamous cell carcinoma - head and neck tumors - p16.
    Ceskoslovenska patologie 12/2013; 49(1):29-34.
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    ABSTRACT: Recent research suggests that multinodular recurrent pleomorphic adenoma (PA) might result from cell migration through lymphatics. Lymphangiogenesis in malignancies is mediated by vascular endothelial growth factors C and D (VEGF-C/D). We studied the expression of VEGF-C/D in PA by immunohistochemistry as well as lymphatic vessel density (LVD). In 6 non-recurrent, 4 primary-to-recur, and 10 recurrent PAs, VEGF-C/D expression was assessed by immunohistochemistry. Staining was scored in terms of staining intensity (0 = absent to 3 = strong), and the percentage of positive tumor cells (scored as 0 (0-19 %), 1 (20-39 %), 2 (40-50 %), and 3 (60-100 %)) and a sum score were calculated. Intra- and peritumoral LVD was assessed by counting of LV after immunostaining, using the D2-40 antibody. All but one sample were VEGF-C negative. The differences in VEGF-D expression between non-recurrent, primary-to-recur, and recurrent PAs were not significant (p > 0.05). VEGF-D expression did not correlate with peritumoral LVD (p > 0.05). Our study revealed a significant difference between intra- and peritumoral LVD values when comparing individual and all sample groups (p = 0.01). The lack of VEGF-C expression and of significant differences in VEGF-D expression and peritumoral LVD between patients with non-recurrent, primary-to-recur, and recurrent PAs does not support the lymphangiogenic local spread hypothesis.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 11/2013; · 2.68 Impact Factor
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    ABSTRACT: 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.
    The American journal of surgical pathology 10/2013; · 4.06 Impact Factor
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    ABSTRACT: The recurrent translocations t(11;19) and t(11;15) resulting in CRTC1-MAML2 or CRTC3-MAML2 fusion oncogenes, respectively, are identified in a large proportion of mucoepidermoid carcinomas (MECs) of the salivary gland and have impact on prognosis. However, there are conflicting data on the specificity of this translocation, in particular, on its putative occurrence in Warthin tumor (WT) of the parotid gland as reported in few previous cases. It was speculated that extensive squamous metaplasia could explain the presence of t(11;19) translocation in a subset of WTs. We evaluated 76 salivary gland tumors, including 16 cases of metaplastic WT and 8 cases of pleomorphic adenoma (PA) with squamous and/or mucinous metaplasia, extensive enough morphologically to mimic MEC. Detection of CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts and MAML2 gene break was performed using nested reverse transcription-polymerase chain reaction and fluorescence in situ hybridization (FISH), respectively. None of 16 analyzed metaplastic WTs showed positivity for fusion transcripts CRTC1-MAML2 or CRTC3-MAML2, and none showed rearrangement of the MAML2 gene by FISH. Similarly, we did not detect these transcripts or break of MAML2 gene in any case of PA with extensive squamous/mucinous metaplasia. For comparison, 40 cases of low-grade MEC were also evaluated. CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts were detected in 17 and 5 cases, respectively. The FISH method using break-apart probe demonstrated the MAML2 gene rearrangement in 25 cases of low-grade MEC. In contrast to low-grade MEC, neither metaplastic WTs nor metaplastic PAs harbored translocations t(11;19) and anticipated t(11;15) resulting in CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts, respectively, and/or MAML2 gene rearrangement.
    The American journal of surgical pathology 10/2013; · 4.06 Impact Factor
  • Alena Skalova
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    ABSTRACT: Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor with ETV6 translocation. Akin to secretory breast cancer, MASC expresses S-100 protein, mammaglobin, vimentin, and harbors a t(12;15) (p13;q25) translocation which leads to ETV6-NTRK3 fusion product. Histologically, MASC displays a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogeneous or bubbly secretions. Colloid-like secretory material stains positive for periodic acid-Schiff (PAS) with and without diastase and for Alcian blue. The cells of MASC are devoid of PAS-positive secretory zymogen granules. These features help to exclude the most important differential diagnostic considerations, namely acinic cell carcinoma, low-grade cribriform cystadenocarcinoma, cystadenocarcinoma (not otherwise specified), and low-grade mucoepidermoid carcinoma. To date the presence of the ETV6-NTRK3 fusion gene has not been demonstrated in any other salivary gland tumor than MASC. It is likely that MASC is more common than currently recognized and with further studies, the clinical need for molecular studies of the ETV6-NTRK3 fusion may diminish. However, molecular testing is recommended at this time to arrive at the diagnosis of MASC.
    Head and Neck Pathology 07/2013;
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    ABSTRACT: Mammary analog secretory carcinoma (MASC) of salivary glands is a recently described neoplasm with favorable outcome. We describe 2 cases of MASC occurring in a 34-year-old female and a 58-year-old male, both presenting with a swelling of upper lip and right parotid gland, measuring 15 and 20mm, respectively. Without adjuvant treatment, both patients have been free of disease for 15 months and 12 months since the operation. Microscopically, both tumors were cystic and showed tubular and cystopapillary architecture. The tumor cells had round to oval nuclei and eosinophilic cytoplasm. Presence of eosinophilic material was evident within cystic spaces. Immunohistochemically, both tumors expressed cytokeratins (CK), CK7, CK8, CK18, epithelial membrane antigen, vimentin, S-100 protein, mammaglobin, and STAT5a (signal transducer and activator of transcription 5a). Interestingly, both tumors showed variable expression of basal/myoepithelial markers. In one case, we observed diffuse expression of calponin and focal expression of p63 whereas expression of CD10 was absent. In the second case, the staining of calponin was negative, but there was focal expression of both p63 and CD10. Both neoplasms harbored the ETV6-NTRK3 fusion transcript as proved by RT-PCR. Although previously reported only rarely, we conclude that MASC may show expression of basal/myoepithelial markers.
    Pathology - Research and Practice 01/2013; · 1.21 Impact Factor
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    ABSTRACT: Background. Tumor-related high risk human papillomaviruses (HPV) 16 and 18 have been repeatedly detected in head and neck cancers, particularly, they are well known risk factors in squamous cell carcinoma of the oropharyngeal and tonsillar region. Little is known, however, about the possible role of HPV in salivary gland tumors.Methods. Fifty-five cases of benign and malignant salivary gland tumors were tested using p16 immunohistochemistry followed by HPV DNA polymerase chain reaction (PCR) using SPF, CPSGB, GP5+/GP6+ primers, and type specific primers for HPV 16, 18, 31, 33, 35, 45 in the cases with strong immunohistochemical expression for p16 protein (score 3+).Results. Only 5 tumors of 55 (9 %) were completely devoid of any p16 staining, and in 10 cases (18 %), less than 25 % of tumor cells stained (score 1+). In the majority of cases (35 of 55; 64 %) there was a patchy nuclear and cytoplasmic strong staining in 26 to 50 % of tumor cells (score 2+). In five cases (9 %), strong nuclear and cytoplasmic staining in more than 51% of tumor cells was detected (score 3+). However, none of the p16-positive cases showed any evidence of high-risk HPV by PCR.Conclusions. The results of the study indicate that HPV, in particular oncogenic types 16 and 18, are not involved in the etiology of benign and malignant epithelial tumors of salivary glands. Therefore, it is likely that salivary gland tumors belong to the category of tissues in which the p16 positive immunohistochemistry is not biologically relevant to the oncogenic role of HPV infection. Keywords: salivary gland tumor - HPV - human papilloma virus - p16 immunohistochemistry - PCR.
    Ceskoslovenska patologie 01/2013; 49(2):72-75.
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    ABSTRACT: Lipomatous neoplasms of the salivary glands are rare. Their wide histologic spectrum has not been sufficiently studied. We collected 31 fat-containing salivary gland lesions excluding pleomorphic adenoma and myoepithelioma with lipometaplasia. There were 19 male and 12 female patients aged 7 to 89 years (mean, 53 y). Tumors originated in the parotid (n=29) and the submandibular (n=2) gland. On the basis of the proportion and distribution of adipose tissue and the epithelial type, tumors could be categorized into 3 main groups: ordinary lipoma (n=20) identical to soft tissue lipoma but located within the salivary gland, oncocytic lipoadenoma (n=6) composed predominantly of oncocytes with variable fatty component, nononcocytic sialolipoma (n=4) composed of lobular fatty tissue (≥70%) with evenly distributed normal salivary tissue recapitulating the composition of normal salivary glands and microcystic lipoadenoma (n=1) composed of cystic ducts admixed with adipose tissue. The mean tumor size was 3.3, 3.8, and 2.9 cm for lipoma, oncocytic lipoadenoma, and nononcocytic sialolipoma, respectively. Associated diseases included Madelung disease with bilateral atypical lipomatous tumors of the neck and bilateral parotid lipoma (1), oncocytic lipoadenoma after irradiation for sinonasal adenocarcinoma (1), and periparotideal lipoma excised years before oncocytic lipoadenoma (1) and nononcocytic sialolipoma (1). No recurrence was recorded at a mean follow-up of 72 months (range, 6 to 184 mo). Sebaceous islands were seen in 5/6 oncocytic lipoadenomas and in 2/4 sialolipomas. Periductal inflammation/fibrosis was common in sialolipoma and oncocytic lipoadenoma. This study demonstrates the wide morphologic spectrum of fatty salivary gland lesions. Oncocytic lipoadenoma is an epithelial-predominant tumor that is distinct from the fat-dominated nononcocytic sialolipoma, but the 2 types seem to merge in some cases.
    The American journal of surgical pathology 12/2012; · 4.06 Impact Factor
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    ABSTRACT: The diagnosis of pleomorphic adenoma (PA) of salivary glands is usually straightforward posing few diagnostic problems for the general surgical histopathologist. The purpose of our investigation was to present a series of 22 cases of PA of major salivary glands, each of which contained small foci of tumor within vascular spaces. This feature has previously been described very rarely in PA and may represent a significant diagnostic pitfall. The patients included 12 women and 10 men, ranging in age at diagnosis from 17 to 82 years. Histopathologically, all 22 tumors displayed the features of PA with mixed epithelial and myoepithelial growth patterns and chondromyxoid areas. None of these neoplasms showed any cytologic evidence of malignancy. In all cases, there were multiple dilated thin-walled and/or muscular thick-walled blood vessels containing small intraluminal collections of neoplastic cells with or without myxoid stromal components. The intravascular tumor cells expressed cytokeratins, and in some cases they were also immunoreactive for S-100 protein, GFAP, D2-40, and p63 protein. The intravascular location of the neoplastic cells was confirmed by CD31, CD34, and factor VIII-related antigen immunostains. Reaction for D2-40 was negative in the endothelium of the involved vessel in all cases, confirming that they were vascular rather than lymphatic channels. Seven patients (36%) underwent fine-needle aspiration biopsy 25 days to several years before excision of the tumor. Follow-up of the patients in our series revealed no cases of recurrence or metastasis (range, 6 mo to 9.5 y; mean 3.8 y; median 3.5 y). The biological significance of intravascular tumor in PA is not clear, but there is growing evidence that it is an innocuous phenomenon that might be related to artifactual spillage caused by tumor injury presumably by either fine-needle aspiration or intraoperative trauma.
    The American journal of surgical pathology 11/2012; 36(11):1674-1682. · 4.06 Impact Factor
  • A Skálová, P Andrle, L Hostička, M Michal
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    ABSTRACT: Pleomorphic adenoma is the most common salivary gland tumor, characterized by a complex biphasic proliferation of epithelial and myoepithelial cells intermingled with a mezenchymal component with frequent metaplastic changes and protean histomorphology of the cells. This review describes several unusual histological findings in pleomorphic adenoma that may mimic malignancy, and therefore they represent a diagnostic pitfall. Intravascular invasion of tumor cells is generally suspicious of malignancy; however, intravascular tumor deposits may be rarely found within the capsule of clinically benign salivary pleomorphic adenomas. It is important not to render a malignant diagnosis in such neoplasms, in the absence of other evidence of malignancy. Pleomorphic adenomas, particularly of minor glands of palate, may contain large areas of squamous and mucinous metaplasia suspicious of mucoepidermoid carcinoma (MEC). In contrast to MEC, metaplastic pleomorphic adenomas do not harbour the distinctive translocations t(11;19) and t(11;15), they are not invasive, in contrast they reveal at least focally myxochondroid stroma. Cribriform structures in pleomorphic adenoma may mimic adenoid cystic carcinoma. Oncocytic metaplasia in cellular rich pleomorphic adenoma/myoepithelioma may be associated with significant nuclear polymorphism and hyperchromasia suspicious of malignancy. The most common pitfall in diagnosis of pleomorphic adenoma is so called "atypical PA" that must be distinguished from early malignant transformation to in situ-carcinoma ex pleomorphic adenoma. Keywords: salivary gland - pleomorphic adenoma - pitfall - metaplasia - intravascular tumor deposits - atypical - carcinoma ex pleomorphic adenoma.
    Ceskoslovenska patologie 10/2012; 48(4):179-83.
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    ABSTRACT: The aim of the study was to further elucidate the immunohistochemical and genetic characteristics of cribriform adenocarcinoma of minor salivary glands (CAMSG). The study comprised five CAMSG from two males and three females, aged 21-72 years. Four tumors were localized at the base of tongue and one in the floor of mouth. At the time of diagnosis, four tumors had metastasised to regional lymph nodes. After tumor resection, two patients were treated by radiotherapy and one by chemoradiotherapy. During the follow-up (median 14 months), two patients developed lymph node metastasis. Microscopically, all tumors showed cribriform, papillary, follicular, and microcystic growth patterns. The tumor cells displayed vesicular nuclei with intranuclear grooves. Immunohistochemically, all tumors showed expression of cytokeratin (CK) 7, CK8, CK18, vimentin, smooth muscle actin, calponin, S-100 protein, and p16 protein. In addition, we observed expression of galectin-3, CK19, and HBME-1, but not of thyroglobulin and TTF-1. No mutations of RET, BRAF, K-RAS, H-RAS, and N-RAS proto-oncogenes were detected. However, in RET proto-oncogene, we found polymorphisms Gly691Ser (exon 11) and Ser904Ser (exon 15) in one case, p.Leu769Leu (exon 13) in one case, and variant p.IVS14-24 G/A of intron 14 in two cases, and in H-RAS proto-oncogene we found polymorphism 81 T-C (exon 1) in three cases. Thyroglobulin and TTF-1 are the only useful markers in the differential diagnosis between CAMSG and papillary thyroid carcinoma as both tumors may express galectin-3, CK19, and HBME-1. The RET, H-RAS, and N-RAS proto-oncoogenes are not mutated in CAMSG.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 09/2012; · 2.68 Impact Factor
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    ABSTRACT: The review summarizes the new findings in salivary gland pathology with particular reference to molecular genetic developments. In particular, newly recognized entities and specific chromosomal translocations associated with salivary gland carcinomas are discussed. Firstly, there are three types of salivary gland carcinomas which harbour important oncogenic translocations: mucoepidermoid carcinoma with the translocation t(11; 19)(q21; p13) CRTC1-MAML2 (as well as several other less frequent ones), adenoid cystic carcinoma with the translocation t(6; 9)(q22–23; p23–24) MYB-NFIB, and the recently described entity of mammary analogue secretory carcinoma (MASC) characterized by the translocation t(12; 15)(p13; q25) ETV6-NTRK3. Secondly, sclerosing polycystic adenosis was described in 1996 as possibly a salivary counterpart to benign fibrocystic disease of the breast, but recent molecular evidence of clonality suggests it is neoplastic in nature. Finally, new molecular developments in salivary duct carcinoma and molecular mechanisms responsible for high grade transformation and tumour progression in other neoplasms will be addressed.
    Diagnostic Histopathology. 09/2012; 18(9):388–396.
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    ABSTRACT: The review summarizes the new findings in salivary gland pathology with particular reference to molecular genetic developments. In particular, newly recognized entities and specific chromosomal translocations associated with salivary gland carcinomas are discussed. Firstly, there are three types of salivary gland carcinomas which harbour important oncogenic translocations: mucoepidermoid carcinoma with the translocation t(11; 19)(q21; p13) CRTC1-MAML2 (as well as several other less frequent ones), adenoid cystic carcinoma with the translocation t(6; 9)(q22–23; p23–24) MYB-NFIB, and the recently described entity of mammary analogue secretory carcinoma (MASC) characterized by the translocation t(12; 15)(p13; q25) ETV6-NTRK3. Secondly, sclerosing polycystic adenosis was described in 1996 as possibly a salivary counterpart to benign fibrocystic disease of the breast, but recent molecular evidence of clonality suggests it is neoplastic in nature. Finally, new molecular developments in salivary duct carcinoma and molecular mechanisms responsible for high grade transformation and tumour progression in other neoplasms will be addressed.
    Diagnostic Histopathology. 09/2012; 18(9):388–396.
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    ABSTRACT: There are only 4 unequivocal cases of metastasizing middle ear carcinoid previously reported. To present a case of metastasizing middle ear carcinoid, to review previously reported cases, and to discuss the clinical nature of this tumor, which is similar to "orthotopic" carcinoids bearing definite metastatic potential. Case report. PATIENT, INTERVENTION, RESULTS: We present a 72-year-old woman who developed ipsilateral parotid gland and cervical lymph node metastases 8 and 11 months after surgical removal of a primary middle ear lesion. She subsequently required 2 revision procedures and radiotherapy for local recurrences. Her case was complicated by nonsurgically induced permanent facial nerve paralysis, the cause of which remains obscure. At the end of the 8-year follow-up, the patient was alive with locally, recurrent tumor eroding the cranial base and invading the posterior intracranial fossa but with no signs of metastases. Light microscopy and immunohistochemical analysis. Considering the reported high rate of recurrence and their consequent metastases, a middle ear carcinoid should be classified as a neuroendocrine low-grade carcinoma.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 08/2012; 33(8):1418-21. · 1.44 Impact Factor
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    ABSTRACT: Di Palma S, Simpson R H W, Marchiò C, Skálová A, Ungari M, Sandison A, Whitaker S, Parry S & Reis-Filho J S (2012) Histopathology Salivary duct carcinomas can be classified into luminal androgen receptor-positive, HER2 and basal-like phenotypes Aims:  The aim of this study was to devise a molecular classification for salivary duct carcinomas (SDCs) based on the similarities between SDCs and breast carcinomas and on characteristics of the microarray-based gene expression profiling-defined molecular subtypes of breast cancer. Methods and results:  Forty-two pure salivary duct carcinomas, 35 of which contained an in-situ component as defined by histological review and/or immunohistochemical analysis, were stained with antibodies for oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6. Based on these markers, tumours were classified into HER2, luminal androgen receptor-positive, basal-like, luminal and indeterminate phenotype. Analysis revealed that 16.7%, 69%, 4.8%, 9.5% and 0% were of HER2, luminal androgen receptor-positive, basal-like, indeterminate and luminal phenotype, respectively. The in-situ and invasive components displayed the same molecular subtype in all but one case. Conclusions:  Salivary duct carcinomas can be classified into molecular subgroups approximately equivalent to those in the breast. We also report on the existence of a subgroup of bona fide pure salivary duct carcinomas that have a 'basal-like' phenotype. Understanding the phenotypic complexity of SDCs may help to expedite the identification of novel therapeutic targets for these aggressive tumours.
    Histopathology 08/2012; · 2.86 Impact Factor
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    ABSTRACT: Mammary Analog Secretory Carcinoma (MASC) is a new entity of malignant salivary gland tumors that morphologically resembles mammary secretory carcinoma and carries the identical ETV6-NTRK3 fusion gene. We report our first case of MASC in Japan occurring in the parotid gland of a 37-year-old female patient with a t (12; 15) (p13; q25) translocation. Histologically, the tumor was composed of monomorphic cuboidal cells with low-grade vesicular nuclei and pale eosinophilic cytoplasm, and formed microcystic and tubular spaces with periodic acid-Schiff-positive secretion. Immunohistochemically, the tumor cells tested positive for cytokeratin, vimentin, and S-100 protein. MASC is a morphological mimicker of acinic cell carcinoma, but is a distinct neoplasm characterized by a specific chromosomal translocation. An accumulation of similar case studies is mandatory in order to clarify biological behaviors.
    Pathology International 02/2012; 62(2):149-52. · 1.72 Impact Factor

Publication Stats

971 Citations
229.67 Total Impact Points

Institutions

  • 1992–2014
    • Charles University in Prague
      • • Department of Pathology (3. LF)
      • • Lékařská fakulta v Plzni
      Praha, Praha, Czech Republic
  • 2002–2013
    • Fakultní nemocnice Plzeň
      Pilsen, Plzeňský, Czech Republic
  • 2002–2011
    • Faculty of Medicine in Pilsen
      Pilsen, Plzeňský, Czech Republic
  • 2005
    • University of Surrey
      Guilford, England, United Kingdom
  • 2004
    • University Hospital Olomouc
      Olmütz, Olomoucký, Czech Republic
  • 2001
    • Slovak Medical University in Bratislava
      Presburg, Bratislavský, Slovakia
  • 1999
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 1997–1998
    • University of Exeter
      Exeter, England, United Kingdom
  • 1992–1994
    • University of Helsinki
      • Department of Pathology
      Helsinki, Province of Southern Finland, Finland