Tumor of the Nose - A Rare Manifestation of a Metastatic Lung Cancer.

Lung cancer most often metastasizes to the central nervous system, bone and liver. Although metastases to the skin are quite rare, it is estimated that they may be the first clinical manifestation of this disease in 0.7%-12% of cases. Metastases to the skin are caused by adenocarcinoma (about 30%), squamous cell carcinoma (30%) and undifferentiated carcinoma (40%). Nasal tip metastases are extremely rare. They can be confused with more common skin problems, including non-melanoma skin cancers, rhinophyma, inflammatory tumors or infectious diseases. We report two patients with a tumor on the nose, which proved to be the first sign of the metastatic lung cancer.

Immunohistochemical results and case report of an incidental finding of uterine polypoid adenomyoma after long-time therapy for metrorrhagia.

We present a 25-year-old female woman with a 9-year history of metrorrhagia, in whom a uterine polypoid adenomyoma (UPA) was incidentally detected. Intense nuclear staining in the uterine adenomyoma tissue showed an immunoreaction with BAF250a/ARID1A, Arginase-2 as well as 1LRH-2E1/NR5A2, suggesting a role of these proteins and transcriptional activity of their genes in uterine polypoid adenomyoma development. Neither Nidogen-2 nor SF-1/NR5A1 were expressed in UPA.

Ovarian adult-type granulosa cell tumor concomitant with simple endometrial hyperplasia: a case study with selected immunohistochemistry.

Ovarian adult-type granulosa cell tumors are often associated with endometrial hyperplasia or even uterine cancer. Herein, we present a case report of a 65-year-old female patient who had undergone curettage of the uterine cavity several times due to abnormal and irregular uterine bleeding. Owing to recurrent episodes of vaginal bleeding as well as ineffective pharmacological treatment of simple endometrial hyperplasia without atypia, the patient underwent a laparoscopically-assisted vaginal hysterectomy. Owing to an enlarged right ovary with bluish color, intra-operative pathological examination was immediately performed. Surprisingly, an ovarian adult-type granulosa cell tumor was diagnosed, and the surgery was extended to pelvic lymphadenectomy and omentectomy. Immunohistochemical staining with selected antibodies (Arginase 2, Nidogen 2, BAF250a/ARID1A, GPR30, SF-1/NR5A, and 1LRH-2E1/NR5A2) was also performed. In conclusion, in cases of recurrent vaginal bleeding concomitant with endometrial hyperplasia, the existence of rare ovarian tumors connected with extensive estrogenic stimulation must be taken into account. Immunostaining with selected antibodies (Arginase 2, Nidogen 2, ARID1A, or GPR30) may help elucidate the possible molecular mechanisms associated with the BAF250a/development of various ovarian/endometrial abnormalities.

Severe acute toxicity following gemcitabine administration: A report of four cases with cytidine deaminase polymorphisms evaluation.

Gemcitabine (GCB) is a pyrimidine antimetabolite widely used in various solid tumors as a single agent or as a component of multidrug regimens. In the majority of patients, GCB is well tolerated, however life-threatening complications occasionally occur. The current report presents four cases of severe acute toxicity, which included two that were fatal, following administration of GCB alone or in combination with cisplatin. Of the four cases, in one, a Naranjo Adverse Drug Reaction Probability Score was definite, in two, probable and in one possible. To determine the potential causes of these toxicities, polymorphic variants of cytidine deaminase, the primary enzyme involved in the hepatic metabolism of GCB, were assessed. The homogeneous c.435TT variant was detected in one patient and a heterozygotic c.435CT variant in two, one of whom additionally harbored a heterozygotic c.79AC variant.

Content-based analysis of Ki-67 stained meningioma specimens for automatic hot-spot selection.

BACKGROUND: Hot-spot based examination of immunohistochemically stained histological specimens is one of the most important procedures in pathomorphological practice. The development of image acquisition equipment and computational units allows for the automation of this process. Moreover, a lot of possible technical problems occur in everyday histological material, which increases the complexity of the problem. Thus, a full context-based analysis of histological specimens is also needed in the quantification of immunohistochemically stained specimens. One of the most important reactions is the Ki-67 proliferation marker in meningiomas, the most frequent intracranial tumour. The aim of our study is to propose a context-based analysis of Ki-67 stained specimens of meningiomas for automatic selection of hot-spots. METHODS: The proposed solution is based on textural analysis, mathematical morphology, feature ranking and classification, as well as on the proposed hot-spot gradual extinction algorithm to allow for the proper detection of a set of hot-spot fields. The designed whole slide image processing scheme eliminates such artifacts as hemorrhages, folds or stained vessels from the region of interest. To validate automatic results, a set of 104 meningioma specimens were selected and twenty hot-spots inside them were identified independently by two experts. The Spearman rho correlation coefficient was used to compare the results which were also analyzed with the help of a Bland-Altman plot. RESULTS: The results show that most of the cases (84) were automatically examined properly with two fields of view with a technical problem at the very most. Next, 13 had three such fields, and only seven specimens did not meet the requirement for the automatic examination. Generally, the Automatic System identifies hot-spot areas, especially their maximum points, better. Analysis of the results confirms the very high concordance between an automatic Ki-67 examination and the expert's results, with a Spearman rho higher than 0.95. CONCLUSION: The proposed hot-spot selection algorithm with an extended context-based analysis of whole slide images and hot-spot gradual extinction algorithm provides an efficient tool for simulation of a manual examination. The presented results have confirmed that the automatic examination of Ki-67 in meningiomas could be introduced in the near future.

Comparison of the manual, semiautomatic, and automatic selection and leveling of hot spots in whole slide images for Ki-67 quantification in meningiomas.

Background. This paper presents the study concerning hot-spot selection in the assessment of whole slide images of tissue sections collected from meningioma patients. The samples were immunohistochemically stained to determine the Ki-67/MIB-1 proliferation index used for prognosis and treatment planning. Objective. The observer performance was examined by comparing results of the proposed method of automatic hot-spot selection in whole slide images, results of traditional scoring under a microscope, and results of a pathologist's manual hot-spot selection. Methods. The results of scoring the Ki-67 index using optical scoring under a microscope, software for Ki-67 index quantification based on hot spots selected by two pathologists (resp., once and three times), and the same software but on hot spots selected by proposed automatic methods were compared using Kendall's tau-b statistics. Results. Results show intra- and interobserver agreement. The agreement between Ki-67 scoring with manual and automatic hot-spot selection is high, while agreement between Ki-67 index scoring results in whole slide images and traditional microscopic examination is lower. Conclusions. The agreement observed for the three scoring methods shows that automation of area selection is an effective tool in supporting physicians and in increasing the reliability of Ki-67 scoring in meningioma.

Elastography in pancreatic solid tumours diagnoses.

INTRODUCTION: Pancreatic solid tumour diagnoses remain a challenge for modern medicine. However, using endosonography together with elastography helps to examine the elasticity of tissues and therefore may allow definition of the nature of pancreatic tumours. AIM: To evaluate the usefulness of elastography with the strain ratio method and quantitative evaluation of pancreatic solid tumours. MATERIAL AND METHODS: A total of 54 patients with pancreatic solid tumours were treated with ultrasound endosonography with fine-needle aspiration biopsy. The control group contained 26 patients with normal pancreas. Pancreatic solid tumours and normal pancreas were analysed with elastography and elasticity evaluation of the interest area (A), reference (B), and the strain ratio factor (B/A). Postoperative histopathological or cytological examinations were the final diagnoses. Both postoperative and cytological diagnoses were compared with average elasticity parameters (A) and strain ratio factors (B/A). RESULTS: Average elasticity parameters (A) and the strain ratio factors (B/A) were: 0.025% (0.01-0.05%) for malignant process, and (B/A) 33.93 (18.23-75.45); (A) - 0.26% (0.14-0.35%), and (B/A) 5.35 (3.47-7.8) for inflammatory process; (A) 0.54% (0.35-0.82%), and (B/A) 1.79 (1.02-2.05) for normal pancreatic tissue. CONCLUSIONS: Malignant tumours have higher tightness factor compared to inflammatory tumours and normal pancreatic tissue. Elasticity parameters reach the highest levels in normal pancreatic tissue, lower in inflammatory tumours, and the lowest in malignant tumours.

Hot-spot selection and evaluation methods for whole slice images of meningiomas and oligodendrogliomas.

The paper presents a combined method for an automatic hot-spot areas selection based on penalty factor in the whole slide images to support the pathomorphological diagnostic procedure. The studied slides represent the meningiomas and oligodendrogliomas tumor on the basis of the Ki-67/MIB-1 immunohistochemical reaction. It allows determining the tumor proliferation index as well as gives an indication to the medical treatment and prognosis. The combined method based on mathematical morphology, thresholding, texture analysis and classification is proposed and verified. The presented algorithm includes building a specimen map, elimination of hemorrhages from them, two methods for detection of hot-spot fields with respect to an introduced penalty factor. Furthermore, we propose localization concordance measure to evaluation localization of hot spot selection by the algorithms in respect to the expert's results. Thus, the results of the influence of the penalty factor are presented and discussed. It was found that the best results are obtained for 0.2 value of them. They confirm effectiveness of applied approach.

Papillary tumor of the pineal region. Report of two cases and literature review.

Papillary tumor of the pineal region (PTPR) was introduced to the WHO classification in 2007. This rare tumor of little known natural history and unpredictable behavior was described in fewer than 100 cases. Its optimal treatment is not established yet. We report another two cases of PTPR in whom tumors were totally removed via supracerebellar infratentorial approach and both were treated with radiotherapy. In a 37-year-old man the operation was delayed 6 years after the first tumor diagnosis and subsequent shunt placement. He has no complaints 10 years after the onset of the disease. A 45-year-old woman has no complaints 24 months after surgery. Our experience and the data from literature indicate that a total tumor removal is the major prognostic factor.

Recurrent pyoderma gangrenosum precipitated by breast cancer: a case report and review of the literature.

INTRODUCTION: Pyoderma gangrenosum is a rare clinical entity of poorly understood pathogenesis, characterized by rapidly progressing skin necrosis. In around half of patients pyoderma gangrenosum is a manifestation of underlying systemic diseases, such as rheumatoid arthritis, inflammatory bowel disease or myeloproliferative disorders. There have been very few reports on the association of pyoderma gangrenosum with solid malignancies. CASE PRESENTATION: We report a case of a 68-year-old Caucasian woman in whom pyoderma gangrenosum first appeared around 30 years earlier, at the time of exacerbation of rheumatoid arthritis, and recurred as a manifestation of locally advanced breast cancer. The causative role of the neoplastic process was partly confirmed by the healing of the skin ulceration only following effective endocrine cancer therapy, whereas earlier attempts with standard anti-inflammatory therapy were unsuccessful. CONCLUSIONS: Pyoderma gangrenosum has a recurrent nature and may be reactivated by various causes within several years. Therefore, a prompt and thorough diagnosis accompanied by treatment of the underlying disease is necessary.

Resistance to first line platinum paclitaxel chemotherapy in serous epithelial ovarian cancer: the prediction value of ERCC1 and Tau expression.

In oncology, a rational approach to identify patients who are likely to benefit from therapy, already before initiation of treatment, is urgently required. Excision repair cross-complementation group 1 enzyme (ERCC1) has been proposed as a molecular predictor of clinical resistance to platinum-based chemotherapy. Other data suggest Tau protein expression as a predictor of clinical outcome in cancer patients treated with paclitaxel-based chemotherapy as low tau expression may render microtubules more vulnerable to paclitaxel. Therefore, the combination of ERCC1 and Tau may be a valuable predictor of sensitivity to platinum/paclitaxel treatment. The primary aim of the study was to investigate whether ERCC1 and Tau protein expression correlates with patient outcome in newly diagnosed epithelial ovarian cancer (EOC) patients. Formalin-fixed, paraffin-embedded tissue sections from 227 newly diagnosed EOC patients were used for immunohistochemical staining for ERCC1 and Tau proteins. All patients received standard first-line combination platinum and paclitaxel chemotherapy. The patients were divided in a training set of 84 patients and an independent validation cohort of 143 patients. Neither ERCC1 nor Tau expression was associated with clinical response or platinum resistance in both the training and validation sets. Patients with ERCC1-positive tumors had significantly shortened progression-free and overall survival compared to patients with ERCC1-negative tumors, p<0.00001 and p=0.0006. In multivariate analysis ERCC1 also proved as an independent predictor of PFS and OS with HR of 3.86 and 1.98, respectively but the data could not be confirmed in the validation set. Tau expression was not associated with PFS or OS in this study. ERCC1 and Tau might serve as biomarkers of DNA repair and for paclitaxel sensitivity but the present study could not validate ERCC1 or Tau protein expression in tumors as pre-treatment tools to predict sensitivity to first-line platinum/paclitaxel chemotherapy.

Skull base secretory meningioma. Value of histological and immunohistochemical findings for peritumoral brain edema formation.

Meningiomas are very common neurosurgical problem. Their histological appearance, different size and localization, adherence to vital neural and vascular structures or extensive peritumoral brain edema (PTBE), especially in deep seated tumors, may lead to severe, life-threatening complications. We report a case of tuberculum sellae meningioma (TSM). A 48-year old female presented with 7-month history of blurred vision and progressive visual impairment. Intracranial tumor was confirmed by magnetic resonance imaging (MRI). After ophtalmological and endocrinological evaluation, the patient underwent surgical removal of the tumor. She immediately recovered from her visual disturbances and no tumor recurrences were seen during follow-up. Pathological diagnosis showed a meningioma of the secretory subtype (MS). We discuss the role of immunohistochemical staining in the diagnosis and the role of different factors in the PTBE formation. Selection of surgical route to the TSM is discussed, as well. Review of the literature is presented.

Tau protein as a potential predictive marker in epithelial ovarian cancer patients treated with paclitaxel/platinum first-line chemotherapy.

BACKGROUND: The aim of the study was to evaluate predictive and prognostic significance of microtubule-associated protein Tau in epithelial ovarian cancer (EOC) patients treated with paclitaxel and platinum-based chemotherapy. METHODS: 74 patients with EOC (stage I-IV) who underwent cytoreductive surgery followed by standard paclitaxel/platinum chemotherapy were included in the retrospective analysis. Their formalin-fixed, paraffin-embedded tissue specimens were immunohistochemically stained for Tau protein, using semi-quantitative DAKO test. Tau expression was acknowledged as negative (0 and 1+) or positive (2+ and 3+). The correlation between Tau expression, progression free survival (PFS) and overall survival (OS) was evaluated. Statistical analysis included Kaplan-Meyer estimator, long rank test, Mann Whitney test and Cox proportional hazards model. RESULTS: 25.7% (19/74) and 74.3% (55/74) of the patients were classified as Tau-negative and Tau-positive, respectively. Median PFS was 28.7 months for Tau-negative group and 15.9 months for Tau-positive group (p = 0.0355). In the univariate analysis 3-year OS in Tau-negative and Tau-positive groups was 80.2% and 52.4%, respectively (p = 0.0198). Low expression of protein Tau was associated with better OS, whereas an advanced stage at diagnosis, suboptimal surgery, serous histological type and resistance to first line chemotherapy were each correlated with worse OS (p <0,05). In multivariate analysis only resistance to first line chemotherapy remained significant (HR 22.59; 95% CI, 8.71-58.55; p <0.0001). CONCLUSIONS: Negative tau protein seems to be both good prognostic factor and a predictor of response to paclitaxel/platinum-based chemotherapy in EOC patients.

Stewart-Treves syndrome angiosarcoma expresses phenotypes of both blood and lymphatic capillaries.

BACKGROUND: The development of angiosarcoma in oedematous tissue is referred to as Stewart-Treves syndrome (STS). This rare and fatal complication is associated with chronic post mastectomy lymphoedema and radiotherapy for breast cancer. Angiosarcoma spread is facilitated by the formation of blood vessels (angiogenesis) and lymph vessels (lymphangiogenesis). In the future antiangiogenic therapy may improve the poor outcome of current treatments. There was evidence that blocking the angiogenenesis would inhibit progression of angiosarcoma. It seems reasonable to hypothesize that blocking the lymphangiogenesis may yield similar results. Although angiosarcomas commonly derive from blood vessels, in case of STS angiosarcomas chronic lymphoedema may suggest its lymphatic origin. The goal of this study was to visualize interstitial space and lymphatics in the central and peripheral regions of STS angiosarcoma. METHODS: On tissue samples obtained from STS angiosarcoma we have performed: first colour stereoscopic lymphography to visualise the morphology of lymphatic vessels and extracellular spaces, second immunohistochemical staining specific for lymphatic vessels endothelium (LYVE-1) and blood endothelial cells (CD31, factor VIII) and prolymphangiogenic vascular endothelial growth factor (VEGF-C) for precise identification of lymphatic endothelia. STS angiosarcoma morphology was assessed by comparison of pictures obtained on lymphography, microscopy and confocal microscopy. RESULTS: STS angiosarcomas present heterogenous morphology with areas dominated by hemangiosarcoma and lymphangiosarcoma structures. STS angiosarcoma expressed phenotypes of both blood and lymphatic endothelia. LYVE-1 and VEGF-C is expressed by STS angiosarcoma and may be used to discriminate tumour differentiation. Morphology of lymphatic vessels and spaces in the tumour suggest absence of their normal lymphatic function. CONCLUSIONS: Our results confirmed both hemangio- and lymphangiogenic origin of STS angiosarcoma. Expression of VEGF-C makes STS angiosarcoma a good candidate for targeted antilymphangiogenic therapy. However, morphology of intratumoral lymphatics on colour lymphography suggested their impaired function, which can hamper drug distribution.

The role of Tau protein in resistance to paclitaxel.

Resistance to taxanes, related to limited efficacy of systemic therapy in cancer patients, is multifactorial. Among mechanisms of resistance to taxanes, those related to microtubule-associated proteins (MAP), including protein Tau, are of great importance. Protein Tau (50-64 kD) binds to beta-tubulin in the same place as paclitaxel. In preclinical studies, low expression of Tau in cancer cells was associated with increased sensitivity to paclitaxel. High expression of Tau protein in ER-positive breast cancers indicates resistance to taxane-containing chemotherapy and sensitivity to hormonal treatment. This article reviews current knowledge on predictive value of protein Tau in response to taxanes. Better understanding of its role may facilitate patients selection to this sort of treatment and lead to treatment optimization.

Accuracy of a remote quantitative image analysis in the whole slide images.

The rationale for choosing a remote quantitative method supporting a diagnostic decision requires some empirical studies and knowledge on scenarios including valid telepathology standards. The tumours of the central nervous system [CNS] are graded on the base of the morphological features and the Ki-67 labelling Index [Ki-67 LI]. Various methods have been applied for Ki-67 LI estimation. Recently we have introduced the Computerized Analysis of Medical Images [CAMI] software for an automated Ki-67 LI counting in the digital images. Aims of our study was to explore the accuracy and reliability of a remote assessment of Ki-67 LI with CAMI software applied to the whole slide images [WSI]. The WSI representing CNS tumours: 18 meningiomas and 10 oligodendrogliomas were stored on the server of the Warsaw University of Technology. The digital copies of entire glass slides were created automatically by the Aperio ScanScope CS with objective 20x or 40x. Aperio's Image Scope software provided functionality for a remote viewing of WSI. The Ki-67 LI assessment was carried on within 2 out of 20 selected fields of view (objective 40x) representing the highest labelling areas in each WSI. The Ki-67 LI counting was performed by 3 various methods: 1) the manual reading in the light microscope - LM, 2) the automated counting with CAMI software on the digital images - DI , and 3) the remote quantitation on the WSIs - as WSI method. The quality of WSIs and technical efficiency of the on-line system were analysed. The comparative statistical analysis was performed for the results obtained by 3 methods of Ki-67 LI counting. The preliminary analysis showed that in 18% of WSI the results of Ki-67 LI differed from those obtained in other 2 methods of counting when the quality of the glass slides was below the standard range. The results of our investigations indicate that the remote automated Ki-67 LI analysis performed with the CAMI algorithm on the whole slide images of meningiomas and oligodendrogliomas could be successfully used as an alternative method to the manual reading as well as to the digital images quantitation with CAMI software. According to our observation a need of a remote supervision/consultation and training for the effective use of remote quantitative analysis of WSI is necessary.

Computer system for cell counting in selected brain tumors at Ki-67 immunohistochemical staining.

OBJECTIVE: To present a computerized system for cell counting in histopathologic slides of meningioma and oligodendroglioma stained immunohistochemically against Ki-67 antigen and discuss the variability of tumor cell numbers in the field of view of analyzed neoplasms to standardize tumor cellularity. STUDY DESIGN: A computer program using an algorithm based on mathematical morphology was developed to perform quantitative evaluation of slides. That solution was combined with the Support Vector Machine used for classification of cell immunoreactivity. RESULTS: The mean number of cells in the analyzed field of view from patients with meningioma was 623. Of these, 95% were in the 386-781 cells range. In oligodendrogliomas the mean was 474 cells and all results were in the 204-736 range. The mean relative discrepancy between results of our system and human expert score was 8%. CONCLUSION: The proposed system appeared to be an efficient tool for supporting histopathologic diagnosis. The applied sequential thresholding simulated well the human process of cell recognition. Cellularity of the analyzed tumors did not show stability within the specimens from different patients. The results were also highly variable in different fields of view obtained from the same patient.

Salivary gland calculi - contemporary methods of imaging.

Sialolithiasis is the most common disorder of major salivary glands. The main site of salivary stones' formation is submandibular gland, followed by parotid and sublingual gland. The aim of this article was to present current diagnostic imaging modalities carried out in patients suspected with salivary stones on the basis of own material and review of literature.Current diagnostic imaging tools used in the imaging of salivary stones were described and illustrated in this paper. These are: conventional radiography, sialography, ultrasonography, computed tomography, magnetic resonance sialography and sialoendoscopy.Digital subtraction sialography and ultrasonography are the methods of choice in the imaging of salivary gland calculi. Although sialography is a very old diagnostic method, still it is the best diagnostic tool in the imaging of subtle anatomy of salivary gland duct system. Digital subtraction sialography can show the exact location of salivary stone and enables imaging of salivary ducts' pathology (e.g. stenoses), which is especially important when sialoendoscopy is planned. Sialography is also used as the treatment method, i.e. interventional sialography. Nonenhanced computed tomography is recommended when multiple and tiny salivary stones are suspected. Magnetic resonance imaging is the evolving alternative diagnostic method. In this diagnostic modality there is no need for salivary ducts' cannulation and administration of contrast material. Thus magnetic resonance sialography can also be carried out in the acute sialoadenitis. In the future, sialoendoscopy may become one of the main diagnostic and treatment procedures for salivary duct disorders, especially in salivary stone cases.

Chromophobe renal cell cancer--review of the literature and potential methods of treating metastatic disease.

Chromophobe renal cell carcinoma (ChRCC) is a subtype of renal cell carcinoma (RCC). ChRCC is diagnosed mainly in 6th decade of life. An incidence of ChRCC is similar in both men and woman. Eighty six percent of ChRCCs cases are diagnosed in stage 1 or 2. Prognosis of ChRCC is better than in other types of RCC. Five- and 10-year disease free survival (DFS) for ChRCC was 83.9% and 77.9%, respectively. Expression of immunohistological markers: cytokeratins (CK), vimentin, epithelial membrane antigen (EMA), CD10 could be potentially helpful in diagnosis of different subtypes of RCC. From all conventional RCC, CD 117 was detected (overexpression) in membrane of cells ChRCC.Overexpression of CD117 on cellular membranes of ChRCC could be a potential target for kinase inhibitors like: imatinib, dasatinib, nilotinib. The potential targets for other kinase inhibitors (sunitinib and sorafenib) in ChRCC seem to be VEGFR and PDGFR. On the basis for formulating research hypotheses which should be verified by prospective studies.