Myoepithelial Carcinoma Arising in a Salivary Duct Cyst of the Parotid Gland: Case Presentation.

Cystic lesions observed in parotid glands are relatively rare and comprise 2-5% of all parotid primaries. A salivary duct cyst (SDC) is a true cyst representing 10% of all salivary gland cysts. The risk of malignant transformation of SDC's epithelium is extremely rare. In the literature, only three cases of carcinoma ex SDC of the parotid gland are described. This report presents the first in the literature case of myoepithelial carcinoma (MECA) arising from a parotid SDC. A 75-year-old male patient was referred to the Department of Cranio-Maxillofacial Surgery of the Jagiellonian University in Cracow, Poland due to a cystic tumor arising from the right parotid gland. Superficial parotidectomy with facial nerve preservation was performed. Histological examination confirmed a rare case of MECA emerging from the SDC. The immunohistochemical profile of MECA ex SDC was presented. During 6 months of the follow-up, local recurrence or distant metastasis was not observed.

Molecular profiling of primary uveal melanoma: results of a Polish cohort.

There is no published data regarding the molecular alterations of Polish patients with primary uveal melanoma. We performed whole exome sequencing of 20 primary uveal melanomas (UMs), 10 metastasizing and 10 non-metastasizing cases to identify significant molecular alterations. We detected mutations and copy number variants in the BAP1 gene in 50% (10 cases) of the cases. GNA11 mutations were detected in 50% (10 cases) including nine p.Q209L and one p.R183C. GNAQ mutations gene were detected in 40% (8 cases) and all were p.Q209P. SF3B1, EIF1AX, PLCB4 , and PALB2 mutations were detected in one case each. Genetic aberrations of FBXW7 were detected in 55% of cases, with copy number loss of 10 and missense mutation in one. Gain or loss of copy number was observed in 60%, 60%, and 10% of cases in MYC, MLH1 , and CDKN2A genes, respectively. BAP1 and GNAQ tumor suppressor genes are more often mutated in UM with metastasis, while GNA11 mutations are more frequently detected in non-metastasizing tumors. MYC copy gain was present twice as frequently (80% versus 40%) in cases with versus those without metastases. BAP1 mutation correlated with worse overall survival; while GNA11 mutation and CDKN2A loss correlated with better and worse progression-free survival, respectively. We have confirmed BAP1 prognostic potential and documented frequent MYC amplification in metastasizing cases. Although GNA11 mutation and CDKN2A loss significantly correlated with progression-free survival in our study, our sample size is small. The prognostic significance of GNAQ/GNA11 mutation and CDKN2A loss would require further investigation.

Machine learning models demonstrate that clinicopathologic variables are comparable to gene expression prognostic signature in predicting survival in uveal melanoma.

PURPOSE: Since molecular assays are not accessible to all uveal melanoma patients, we aim to identify cost-effective prognostic tool in risk stratification using machine learning models based on routine histologic and clinical variables. EXPERIMENTAL DESIGN: We identified important prognostic parameters in a discovery cohort of 164 enucleated primary uveal melanomas from 164 patients without prior therapies. We then validated the prognostic prediction of top important parameters identified in the discovery cohort using 80 uveal melanomas from the Tumor Cancer Genome Atlas database with available gene expression prognostic signature (GEPS). The performance of three different survival analysis models (Cox proportional hazards (CPH), random survival forest (RSF), and survival gradient boosting (SGB)) was compared against GEPS using receiver operating curves (ROC). RESULTS: In all three selection methods, BAP1 status, nucleoli size, age, mitotic rate per 1 mm2, and ciliary body infiltration were identified as significant overall survival (OS) predictors; and BAP1 status, nucleoli size, largest basal tumor diameter, tumor-infiltrating lymphocyte density, and tumor-associated macrophage density were identified as significant progression-free survival (PFS) predictors. ROC plots for the median survival time point showed that significant parameters in SGB studied model can predict OS better than GEPS. For PFS, SGB model performed similarly to GEPS. The time-dependent area under the curve (AUC) showed SGB model performing better than GEPS in predicting OS and metastatic risk. CONCLUSIONS: Our study shows that routine histologic and clinical variables are adequate for patient risk stratification in comparison with not readily accessible GEPS.

Downregulation of Polo-like kinase-1 (PLK-1) expression is associated with poor clinical outcome in uveal melanoma patients.

INTRODUCTION: Uveal melanoma (UM) is the most common primary eye tumour in adults. Distant metastases are seen in 50% of cases regardless of treatment, which contributes to high mortality rates. Polo-like kinase-1 (PLK-1) is a protein regulator of mitotic entry and cytokinesis. Increased PLK-1 expression has been shown in different tumours, which makes its inhibition a potential treatment target. To date, no study has been published to discuss the prognostic role of PLK-1 expression in patients with uveal melanoma. MATERIAL AND METHODS: We assessed by immunohistochemistry PLK-1 expression in uveal melanoma cells collected in 158 patients treated by primary enucleation. We determined the correlation between PLK-1 levels evaluated by the immunoreactivity scale (IRS) method and detailed clinical as well as histological parameters. Additionally, we determined the association between PLK-1 expression levels and long-term prognosis. RESULTS: Elevated PLK-1 expression in tumour cells, defined as IRS > 2, was observed in 70% (111/158) of cases, whereas low expression or no expression was seen in the remaining 30% (47/158) of patients. There was a significant correlation between low PLK-1 expression and a higher clinical tumour stage (pT, p = 0.04) as well as a higher AJCC prognostic stage group (p = 0.037). We observed an inverse correlation between PLK-1 expression and tumour cell pigment content (p = 0.0019). There was no correlation between PLK-1 expression and other histological parameters such as mitotic rate or histological subtype. The Kaplan-Meier's analysis demonstrated that low PLK-1 expression was associated with significantly reduced overall survival (p = 0.0058). A similar trend, albeit not significant, was observed for disease-free survival (p = 0.088). CONCLUSIONS: Downregulated PLK-1 expression is a negative prognostic factor in uveal melanoma. It warrants further, multicentre research on prognostic role of PLK-1 expression and possibility of PLK-1 inhibition in uveal melanoma.

Clinical Significance of Nucleoli Cytomorphology Assessment in Patients With Uveal Melanoma.

AIM: To assess the prognostic significance of nucleolar morphological parameters in a large cohort of patients with uveal melanoma. PATIENTS AND METHODS: The presence, size and number of nucleoli of cancer cells were assessed in haematoxylin and eosin (HE)-stained slides of 164 formalin-fixed paraffin-embedded primary uveal melanoma tissue specimens. The results were correlated with clinicopathological features and patient survival. RESULTS: The presence of macronucleoli and multiple nucleoli significantly correlated with the epithelioid type of uveal melanoma, high mitotic rate, and marked pleomorphism. There was a positive correlation between the presence of macronucleoli as well as the number of nucleoli and the largest tumour basal diameter. The increased nucleolus count in tumour cells positively correlated with primary tumour (pT) staging. The presence of both prominent and multiple nucleoli was associated with significantly reduced overall and disease-free survival. CONCLUSION: Histological assessment of nucleolar morphology in routine HE staining would be a helpful low-cost method to obtain reliable prognostic information.

Vitamin D receptors (VDR), hydroxylases CYP27B1 and CYP24A1 and retinoid-related orphan receptors (ROR) level in human uveal tract and ocular melanoma with different melanization levels.

In recent years, a significant number of studies have investigated the preventive role of vitamin D in a number of different neoplasms. In this study, we analyze various components of the vitamin D signaling pathways in the human uveal tract and uveal melanoma, including analysis of the expression of vitamin D receptors (VDR), the activating and inactivating hydroxylases, respectively, CYP27B1 and CYP24A1, and the retinoic acid-related orphan receptors (ROR) α (RORα) and γ (RORγ) in these tissues. We further analyzed the expression of VDR, CYP27B1, CYP24A1, and ROR in relation to melanin levels, clinical stage and prognosis. Our study indicated that the uveal melanoma melanin level inversely correlated with VDR expression. We further showed that vitamin D is metabolized in uveal melanoma. This is significant because until now there has been no paper published, that would describe presence of VDR, hydroxylases CYP27B1 and CYP24A1, and RORα and RORγ in the human uveal tract and uveal melanomas. The outcomes of our research can contribute to the development of new diagnostic and therapeutic methods in uveal tract disorders, especially in uveal melanoma. The presented associations between vitamin D signaling elements and uveal melanoma in comparison to uveal tract encourage future clinical research with larger patients' population.

Clinical, Histopathological and Cytogenetic Prognosticators in Uveal Melanoma - A Comprehensive Review.

Uveal melanoma is the most prevalent primary intraocular cancer in adults. Although it accounts for only 5% of all melanomas, it is responsible for 13% of deaths due to this type of cancer. A wide variety of therapeutic options of primary tumor is available and progress in its management is noticeable. The fact still remains, however, that almost half of patients develop metastases which may be due to practically undetectable cancer spread present as early as at diagnosis of the primary focus. Metastatic disease is uniformly fatal despite systemic therapy. Prediction of metastasis is crucial for prognosis. It also allows targeting of emerging new therapeutic methods to the appropriate group of patients. The Authors reviewed literature concerning epidemiology and etiopathogenesis of uveal melanoma, and its clinical, histopathological and cytogenetic prognosticators.

[Malherbe's calcifying epithelioma (pilomatrixoma)--own experience]. / Nabloniak wapniejacy Malherbe'a (pilomatrixoma)--obserwacje wlasne.

PURPOSE: Malherbe's calcifying epithelioma is a rare hair matrix tumor. The objective is to present clinical cases and to analyze the variability of its image. MATERIAL AND METHODS: Among nearly 3500 patients with ocular tumors operated during the last 10 years in the Department of Ophthalmology and Ocular Oncology in Krakow we identified a group of 7 patients with histologically confirmed pilomatrixoma. A retrospective evaluation of their medical history was performed, paying particular attention to the co-existence of other diseases, form of growth and location of tumors, as well as treatment methods and their effectiveness. The results were compared with other clinical studies. RESULTS: Malherbe's calcifying epithelioma is characterized by clinical polymorphism and similarity to other much more frequent eyelid tumors. It usually has the form of a single, small, movable, slowly growing nodule covered by intact skin. In addition to the classic form described there are pediculated tumors, huge, fast-growing, perforating, as well as tumors in unusual locations and multiple lesions. CONCLUSIONS: The consequences of variation pilomatrixoma are clinical diagnostic errors. The one, sure and reliable criterion is a histopathology evaluation.

In vivo biocompatibility assessment of (PTFE-PVDF-PP) terpolymer-based membrane with potential application for glaucoma treatment.

The aim of the work was to evaluate the in vivo biological behaviour of polymeric membrane materials for glaucoma implants. The base material was biostable synthetic terpolymer (PTFE-PVDF-PP) with proved biocompability (PN-EN ISO 10993). The samples manufactured in the form a membrane were subjected to chemical and physical treatment to create an open pore system within the polymer matrix. As a porogenic phase biodegradable natrium alginate in a fibrous form was employed. The non-perforating deep sclerectomy technique was performed in a rabbit model. The clinical observations were made after 14 and 30 days. During the study clinical symptoms of a moderate degree were observed, and histopathological changes were typical for foreign body implantation. At the end stage of the study no significant difference in histopathological assessment was found between control and experimental group. Similarities observed in both groups and relatively mild histopathological changes in the tissue surrounding the implant indicate that the observed symptoms come from a deep scleral trauma caused by surgery, and not by the presence of the implant itself.

[Mesectodermal leiomyoma of the ciliary body--case report]. / Mezektodermalny miesniak gladkokomórkowy--opis przypadku.

PURPOSE: The aim of this report is to present a case of mesectodermal leiomyoma of the ciliary body. MATERIAL AND METHODS: In the left eye of the 15 years old female patient presenting 2 months history of deterioration of visual acuity a medium-pigmented, dome-shaped tumor at the inferotemporal side was detected. It measured 21.6 mm in base diameter 11.2 mm in thickness and was revealed with imaging techniques such as ultrasound, MRI and orbital radiography. Taking into consideration all clinical features, despite patients' young age, malignant melanoma of the ciliary body was suspected. Due to the size of the tumor and the impossibility of conducting conservative treatment the globe was eventually enucleated. RESULTS: The final diagnosis was established on the basis of histopathological microscopic examination and immunohistochemical stains. The co-expression of muscular (SMA, caldesmon, desmin), as well as neural markers (S-100 protein and synaptophysin), has been proved. CONCLUSIONS: Mesectodermal leiomyoma of the ciliary body is an extremely rare benign tumor, which originates from neural crests. It exhibits features of both muscular and neural differentiation.

[Ring melanoma]. / Czerniak okreziny blony naczyniowej galki ocznej.

PURPOSE: To describe five cases of ring melanoma. MATERIAL AND METHODS: There were 5 patients diagnosed with ring melanoma in Department of Ophthalmology and Ocular Oncology in Krakow between 2001-2007. The preliminary diagnosis was based on a clinical examination and ultrasound biomicroscopy and in 3 cases open biopsy was performed. RESULTS: Ring melanoma in 5 patients at the age between 48-73 were recognized. Four patients were using glaucoma medications. All patients were qualified for enucleation CONCLUSION: Ring melanoma is rare wariant of uveal melanoma. It often masquerades as unilateral glaucoma, and can be difficult to recognize.

[Uveal melanoma in patients with ocular or oculodermal melanocytosis]. / Czerniak blony naczyniowej u chorych z oczna lub oczno-skórna melanocytoza.

PURPOSE: To describe patients with ocular or oculodermal melanocytosis and uveal melanoma. MATERIAL AND METHODS: In Departament of Ophthalmology in Krakow 4 patients with ocular and 1 with oculodermal melanocytosis and uveal melanoma were diagnosed. RESULTS: In 4 patients with ocular melanocytosis and 1 with oculodermal melanocytosis the uveal melanoma was recognized and treated. Brachytherapy was used in 3 person, transcleral tumour resection in one case and in one enucleation was performed. During follow-up in two patients metastases to the liver were found. CONCLUSIONS: Patients with ocular and oculodermal melanocytosis should be regularly controled ophthalmoscopically for the occurrence of uveal melanoma.

Uveal melanoma in young patients.

INTRODUCTION: This study aimed to investigate the clinical profile of young patients with uveal melanoma treated in 1995-2002 in the Department of Ophthalmology, Jagiellonian University, Krakow, Poland. METHODS: Retrospective case-control series. RESULTS: Out of 800 patients with uveal melanoma treated between 1995 and 2002, there were 11 patients (1.4%) aged 20 or younger. The mean age of those patients was 17.9 (12-20, median 19) years. There were five men (45%) and six women (55%). In all cases, the tumor was unilateral. In five (45%) cases the tumor affected the right eye and in six (55%) cases the left eye. Eight (72%) patients were treated with local resection. Among these, eight patients, in two (18%) with iris or ciliary body melanoma we used adjuvant Ru-106 episcleral plaque brachytherapy (EPB). In two (18%) cases of choroidal melanoma, we performed I-125 EPB: one case ended with regression of the tumor, while the second did not respond to EPB and we had to enucleate the eye. In one (9%) case we performed enucleation as the primary treatment. The mean follow-up was 61.4 months, ranging 30-125 months. All those patients are still alive and no metastases were detected. CONCLUSIONS: Uveal melanoma is a rare malignancy in children and teenagers. In the present series, it occurred in the iris in more than 50% of cases.

Adenoma of the iris and ciliary body. Case report.

A case of rare tumor of the iris and ciliary body in a 24-year old woman is presented, which was diagnosed as adenoma of the nonpigmented ciliary body epithelium. The diagnosis was confirmed immunohistochemically.