Mobilized peripheral blood (MPB) CD34+ cells were cultured to CD41+/CD34+ megakaryoblasts. Cells were sorted to obtain a pure megakaryoblast population that was reprogramed by a hOKSM self-silencing polycistronic vector using lentiviral delivery. The generated induced pluripotent stem cell (iPSC) lines were tested for silencing of the reprogramming construct by flow cytometry. Pluripotency of MML-6838-Cl2 iPSC line was confirmed by expression of associated markers and by in vivo spontaneous differentiation towards the 3 germ layers. The genomic integrity of iPSC line was shown by karyotyping. The MML-6838-Cl2 iPSC is, to our knowledge, the first to be generated from megakaryoblasts.

Gougerot and Carteaud confluent and reticulated papillomatosis (CARP) is an uncommon dermatosis characterized by hyperpigmented scaly macules or papillomatous papules coalescing into confluent patches or plaques centrally with a reticular pattern peripherally. We report a 28-year-old woman presenting at 16 weeks of gestation with an itchy rash that was biopsied and turned out to be consistent with CARP. Options for treatment were discussed but the woman refused to take any systemic therapy and used only moisturizers throughout her pregnancy. The rash subsided spontaneously after delivery.

Cutaneous melanoma is a highly aggressive tumor developing from melanocytes, its incidence is increasing, and prognosis in advanced stages is daunting. New therapies have been approved during the recent years with unprecedented results, including inhibitors of MAPK/ERK pathway and immune checkpoint blockade (anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) as ipilimumab, anti-programmed cell death protein 1 (PD-L1) as pembrolizumab and anti-programmed cell death protein 1 ligand (PD-L1), among many others). The aim of this paper is to review currently available metastatic melanoma therapies focusing mainly on new therapies that have demonstrated effectiveness, after several decades of little progress in the treatment of this disease.

Mesonephric adenocarcinoma is a rare variant of cervical adenocarcinoma. We present a case of mesonephric adenocarcinoma of endocervix with cervical and vaginal lobular mesonephric hyperplasia in a 57-year-old woman. Vaginal bleeding persisting for 12 months was the only symptom. Histopathologic findings and characteristic immunophenotype are crucial for the diagnosis. The tumor was composed of papillary formation with a central fi brovascular stroma, villoglandular and densely compact tubular structures containing intraluminal eosinophilic secretion, and coated with one or more rows of cylindrical atypical epithelial cells. There were 30 pathologic mitotic shapes found per 10 HPF. The tumor invaded nearly full-thickness of cervical stroma with positive lymphovascular space invasion and clear margins. The case demonstrated characteristic cytokeratin 7, vimentin and epithelial membrane antigen positivity and high Ki-67 proliferation index (60%). Estrogen receptors, progesterone receptors and carcinoembryonic antigen were negative. Intratubular lumen secretion was periodic acid-Schiff positive with periodic acid-Schiff negative carcinoma cells. Diff erential diagnoses include adenoma malignum, well-diff erentiated villoglandular adenocarcinoma, endometrioid adenocarcinoma, serous adenocarcinoma, mesonephric adenocarcinoma with a sarcomatous component, clear-cell carcinoma and mesonephric hyperplasia. Radical hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy was performed. Three years after the surgery, the patient remains well. There has not been any evidence of local or distant recurrence. There are no specific recommendations for the treatment of this rare disease. It remains uncertain whether surgical approach is sufficient or the treatment should include additional radio/chemotherapy.

A rare case of parasitic myoma mimicking an adnexal mass in a previously hysterectomized, postmenopausal woman is presented. Two years after vaginal hysterectomy (due to myomas), an asymptomatic right adnexal tumor was noted during regular annual follow up. Ultrasound demonstrated a large 4-5 cm solid mass in the right adnexa, while ovarian cancer biomarkers (CA 125 and HE4) were negative. Intraoperatively, another 3 cm large solid tumor located above the vaginal cuff was discovered. Both pelvic tumors were excised by laparoscopic surgery. The masses were confirmed by histopathology to be leiomyomas.

In patients with prostate cancer (PCa), prostate enlargement may give rise to lower urinary tract symptoms (LUTS); many patients suffer from moderate-to-severe symptoms. We compare the efficacy of degarelix and goserelin plus bicalutamide in improving LUTS in PCa patients.

Teratomas are tumors derived from germ cells, most frequently arising in the gonads. The aim of this study was to determine the number of ovarian teratomas diagnosed in the routine biopsy material at Ljudevit Jurak Clinical Department of Pathology, Sestre milosrdnice University Hospital Center during a 5-year period, as well as their clinical, gross and microscopic characteristics. Teratomas accounted for 48.6% (n=166) of primary ovarian tumors. The patient mean age was 34.74±12.37 years. Difference in the incidence of teratoma between the left and right ovary was not significant; bilateral teratoma was found in 13 patients. Teratomas were detected by ultrasonography in 115 (69.27%) cases and the rest were found during surgery performed for other indications. Most teratomas (n=161; 96.9%) were mature and cystic (dermoid cysts). Mature and solid teratomas were diagnosed in 5 (3.01%), ovarian struma in 2 (1.8%) cases and strumal carcinoid in 1 (1.2%) case. Mature cystic teratomas contained sebaceous material in 123 (76.8%) cases, and a total of 16 teeth were found; 157 (94.5%) teratomas measured <10 cm in largest diameter. Microscopically, mature cystic teratomas most frequently contained ectodermal (skin with appendages, mature glia and nerve ganglia) and mesodermal (fi brous, fat tissue, cartilage and bone) tissues. Frequently found tissues of endodermal origin were respiratory and intestinal epithelia. Small foci of thyroid tissue were found in 20 (12%) teratomas. Chronic granulomatous foreign body reaction in the wall of mature cystic teratomas was found in 11 (6.8%) tumors.

We report a 23-year-old woman, with three recent exertional syncopes. Transthoracic (TTE) and transesophageal (TEE) echocardiography found a large heterogeneous mass (38 x 35 mm) arising from the posterior mitral annulus, protruding in systole through the left ventricular outflow tract (LVOT). Heart MRI confirmed the echocardiography findings, suggesting a cardiac myxoma. Cardiac surgery accomplished the complete resection of the lesion, confirming a mass arising from the posterior mitral annulus and preserving mitral anatomy and function. Pathology was positive for a myxoma. Uneventful evolution allowed the discharge of the patient at the fifth postoperative day. Control TTE discarded any complication.

Benign multicystic peritoneal mesothelioma is an uncommon lesion arising from the peritoneal mesothelium. It is asymptomatic or presents with unspecific symptoms. Imaging techniques may reveal it, however the final diagnosis can only be made by histopathology. Surgery is the only effective treatment considering its high recurrence rate. We report a 19 years old male with Crohn’s disease. Due to persistent abdominal pain, an abdominal magnetic resonance imaging was performed, showing a complex cystic mass in the lower abdomen. The patient underwent surgery and the lesion was completely resected. The pathological study reported a benign multicystic peritoneal mesothelioma.

Pleural metastases mimic malignant mesothelioma result from rare tumours. The most common tumour that metastase to pleura is primary bronchogenic adenocarcinoma. Other primary lung tumours rarely matastase to pleura. Although lung is the most common site for renal cell carcinoma (RCC) metastases, pleural effusion and pleural matestases resulting pseudomesothelioma is very rare. Herein we report two cases of pseudomesothelioma resulting from small cell carcinoma and RCC.

Primary benign tumors of trachea are rare. Of them, tracheal leiomyoma, constitutes only 1% of all benign lower respiratory tract tumors. Here, we present a case of tracheal leiomyoma who has been receiving high doses of inhaled corticosteroids and bronchodilators for a year with a misdiagnosis of asthma. As the symptoms did not resolve with an overtreatment, she has been undergone radiologic study to find a possible alternative diagnosis. The chest roentgenogram revealed an opacity in the upper mediastinum. In computed tomography, a lesion has been detected in proximal trachea, arising from the posterior wall and protruding through the lumen and almost obliterating the air column. Rigid bronchoscopy has been performed under general anesthesia due to a high risk of bleeding and the endobronchial lesion, freely moving with respiration, has been removed and cryotherapy was applied to the base of the lesion. Receiving the histopathological diagnosis of leiomyoma, the patient is now on 12th month of the follow-up without any recurrence.

To establish the direct costs of diagnosing lung cancer in hospitalized patients.

Vesical tumors of infancy are of a low incidence and isolated clinical cases exist, and therefore there are no protocols regarding treatment and monitoring. In addition, the histological criteria used until now are the ones in the WHO 2004 guidelines.

Recent advances in microfluidic approaches have enabled the efficient isolation and detailed molecular characterization of circulating tumor cells (CTCs) in the peripheral blood of patients with cancer. Single-cell molecular analyses of CTCs reveal a tremendous degree of intracellular heterogeneity in CTC populations, reflective of heterogeneity across different patients as well as the underlying heterogeneity of tumors within each individual patient. These studies have enabled the identification of heterogeneous drug resistance mechanisms that can coexist in treatment refractory tumors. CTC analyses also enable serial noninvasive monitoring in patients and can capture the emergence of tumor heterogeneity over time, whether due to tumor evolution through genetic instability or through cellular plasticity. The presence and extent of intratumoral heterogeneity as revealed through the study of CTCs have important clinical implications for understanding and predicting the development of treatment resistance in a variety of solid tumors and for formulating appropriate therapeutic strategies in the effective treatment of cancer.

Blood vessel epicardial substance (BVES) is a tight junction-associated protein that regulates epithelial-mesenchymal states and is underexpressed in epithelial malignancy. However, the functional impact of BVES loss on tumourigenesis is unknown. Here we define the in vivo role of BVES in colitis-associated cancer (CAC), its cellular function and its relevance to patients with IBD.

In recent years, new drugs have been designed for treating advanced cutaneous malignant melanoma, in particular the metastases. They afford modest benefits despite the fact they are commonly heralded as breakthroughs in the lay press and by some medical opinion leaders. Unfortunately, the use of inflated descriptors of the drug efficacy leads to misunderstandings among the clinicians in charge of patients. Currently, vemurafenib, ipilimumab, pembrolizumab and nivolumab have demonstrated their relative activity in the control of advanced malignant melanoma. The results expected from surrogate markers of efficacy are magnified and idealized regarding the expectations from many patients. The recent therapeutic advance improves the median overall survival for a few months. Some combined treatments could possibly boost the current beneficial effects.

Anaplastic thyroid cancer is a rare and fatal malignancy, associated with significant local tumour and often treatment related morbidity. We report our experience in treating this cancer over a 20-year period.

We synthesized a new family of six 4(3H)quinazolinimines based on the reaction between (E)-N-(2-cyanophenyl)benzimidoyl chloride and substituted anilines reaching the formation of their corresponding C2, N3-substituted quinazoliniminium chlorides. This method provides novel, direct and flexible access to diverse substituted 4(3H)quinazolinimines. New compounds obtained following the proposed synthesis were fully characterized and, including the thirteen 4(3H)quinazolinimines synthesized by this method and previously reported by us, were used to study its cytotoxic effect on neoplastic cell lines. The mechanism involved in cell toxicity was also studied. Results showed that these compounds were highly cytotoxic, in particular on Human Promyelocytic Leukemia cells (HL60) and Chronic Myelogenous Leukemia cells (K562) when compared with conventional antineoplastic drugs such as etoposide and cisplatin. The mechanism associated to cytotoxic effect was mainly apoptosis, which not was decreased by antioxidant addition, thereby suggesting that the compounds exert apoptotic death through a mechanism unrelated with oxidative stress.

Previous reports highlighted the potential interest of cetuximab alone or in combination with chemotherapy in locally advanced or metastatic cutaneous squamous cell carcinomas (cSCC) care.

Pituitary metastasis occur in 1-5 % of patients with cancer. We report the discovery of a unique pituitary metastasis of breast cancer. A 67 years old woman was treated in 2003 for local adenocarcinoma. After bone metastatic relapse in 2008, the patient developed diplopia and diabetes insipidus. An MRI revealed a histologically proven metastatic pituitary nodule. Further explorations revealed failure of multiple endocrine axes. Pituitary metastases are relatively rare, but are probably under-diagnosed in the presence of advanced cancers with impaired general condition. This diagnosis should be considered in the context of cancer patients, with a recent history of diabetes insipidus, especially if the latter is associated with other neurological signs (ophthalmoplegia, cephallagia).