The Impact of MGMT Promoter Methylation and Temozolomide Treatment in Serbian Patients with Primary Glioblastoma.

Background and objective: Despite recent advances in treatment, glioblastoma (GBM) remains the most lethal and aggressive brain tumor. A continuous search for a reliable molecular marker establishes the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter as a key prognostic factor in primary glioblastoma. The aim of our study was to screen Serbian patients with primary glioblastoma for an MGMT promoter hypermethylation and to evaluate its associations with overall survival (OS) and sensitivity to temozolomide (TMZ) treatment. Materials and methods: A cohort of 30 Serbian primary glioblastoma patients treated with radiation therapy and chemotherapy were analyzed for MGMT promoter methylation and correlated with clinical data. Results: MGMT methylation status was determined in 25 out of 30 primary glioblastomas by methylation-specific PCR (MSP). MGMT promoter hypermethylation was detected in 12 out of 25 patients (48%). The level of MGMT promoter methylation did not correlate with patients' gender (p = 0.409), age (p = 0.536), and OS (p = 0.394). Treatment with TMZ significantly prolonged the median survival of a patient (from 5 to 15 months; p < 0.001). Conclusions: Due to a small cohort of primary GBM patients, our study is not sufficient for definitive conclusions regarding the prognostic value of MGMT methylation for the Serbian population. Our preliminary data suggest a lack of association between MGMT promoter methylation and overall survival and a significant correlation of TMZ treatment with overall survival. Further population-based studies are needed to assess the prognostic value of the MGMT promoter methylation status for patients with primary glioblastoma.

Solitary Basaloid Follicular Hamartoma: A Report of Two Cases.

Basaloid follicular hamartoma (BFH) is rare benign follicular malformation that is often clinically misdiagnosed. Patients with BFH demonstrate a variety of clinical manifestations and associated abnormalities. BFH may be a familial, congenital, or acquired condition with localized or generalized distribution. Several clinical variants of generalized BFH are known, and they can be associated with a diverse spectrum of abnormalities. Herein, we report two cases of solitary BFH in pediatric patients, both documented dermoscopically.

Pembrolizumab-induced lichen planus in patients with metastatic melanoma: a report of two cases and prognostic implications of cutaneous immune-related adverse events.

Patients receiving immune checkpoint inhibitors (ICIs) commonly experience cutaneous immune-related adverse events (irAEs). We present two cases, a 51-year-old female and a 70-year-old male, that were undergoing treatment with pembrolizumab for metastatic melanoma and developed scaly, erythematous papules on their skin. Following skin biopsies, histological analysis confirmed the diagnosis of lichen planus. In the first patient, acitretin at a dosage of 25 mg/day was administered for 6 months, resulting in complete resolution of lichen lesions. Imaging scans showed no signs of melanoma. The second patient was treated with topical betamethasone dipropionate ointment for several weeks, which led to a favorable therapeutic response. During follow-up, a thoracic CT scan showed several micronodular lesions in the right lung, whereas brain and abdomen CT scans showed no signs of the disease. Lichen planus is not a commonly reported irAE in patients treated with ICIs. This report underscores the importance of conducting skin biopsies in patients receiving ICI therapy and highlights the potential prognostic importance of skin irAEs in patients with melanoma receiving such treatment.

A Comparison of MGMT Testing by MSP and qMSP in Paired Snap-Frozen and Formalin-Fixed Paraffin-Embedded Gliomas.

Comparative analysis of the conventional methylation-specific PCR (MSP) vs. the quantitative MSP (qMSP) assessment of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in 34 snap-frozen (SF) glioma samples was performed. The accuracy of the semi-quantitative MSP was compared with the corresponding qMSP semi-quantitative values using two semi-quantitative cut-off values (0-unmethylated and 1-weakly methylated) to discriminate methylated from unmethylated samples. In the case of the cut-off value 0, MSP test showed 80.0% sensitivity and 78.9% specificity compared to the reference qMSP analysis. However, when using the cut-off value 1, the diagnostic accuracy of the MSP test was significantly higher (85.7% sensitivity, 85.2% specificity). Fleiss' Kappa statistical analyses indicated moderate agreement (Fleiss' Kappa Coefficient = 0.509; 70.59% agreement) between MSP and qMSP semi-quantitative measurements of MGMT promoter methylation in glioma patients, justifying the conventional MSP use in diagnostics and confirming its high reliability. Further, we aimed to compare the validity of SF and formalin-fixed paraffin-embedded (FFPE) glioma samples for MGMT testing. Statistical analyses indicated moderate overall agreement of FFPE glioma samples and SF MSP semi-quantitative measurements (Fleiss' Kappa Coefficient = 0.516/0.509; 70.0% agreement) and emphasized their low reliability in the assessment of highly methylated MGMT promoter samples.

Intraventricular Neurocysticercosis: Comparative Analysis of Different Localizations. Clinical Course and Treatment. A Systematic Review.

Background Neurocysticercosis is significant due to its high prevalence and considerable morbidity and mortality. The intraventricular form of NCC is less common than parenchymal, may have a rapidly progressive course and it requires a corresponding therapeutic response. Despite the extensive literature dealing with NCC and intraventricular cystic lesions, no systematic reviews have addressed similar work related to the clinical course and treatment of the infestation. Our main objective was to analyze the clinical type of the disease and the management for each ventricle separately on the basis of case reports or series of patients with individual data on the course of the disease and its treatment. As a control group, we used data on signs&symptoms and treatment of patients from published series on intraventricular neurocysticercosis. Method We performed a search in the Medline database. Google Scholar was also randomly searched. We extracted the following data from the eligible case/series: age and gender, symptoms, clinical signs, diagnostic examinations and findings, localization, treatment, follow-up period, outcome, and publication year. All data are presented in the form of absolute and relative numbers. The frequency of signs and symptoms, treatment and outcomes of the observed groups were checked by the Chi-square test and Fisher's test. The hypothesis was tested with p <0.05 as statistical significance. Results We selected 160 cases of intraventricular neurocysticercosis (IVNCC) and divided them according to their localization into five categories. Hydrocephalus was recognized in 134 cases (83.4%). Patients with isolated IVNCCare are younger (P=.0264) and have a higher percentage of vesicular cysts (p <.00001). In mixed IVNCC, degenerative and multiple confluent cysts predominate (p = 0.00068). Individuals carrying fourth + third ventricular cysts (potentially obstructive form) are younger than individuals with lateral ventricles (potentially less obstructive forme) (p = .0083). The majority of patients had individual symptoms for a longer period before the acute onset of the disease (p <.00001). The predominant clinical manifestation is headache (88.7%); the proportion within the groups ranged from 100% to 75% without statistical significance (p.074214). The same was true for patients with symptoms of vomiting or nausea, who had a lower and roughly balanced percentage of 67.7% to 44.4% (p.34702). Altered level of consciousness (ranging from 21% to 60%) and focal neurological deficit (from 51.2% to 15%) are the only clinical category with statistical significance (p <0.001 and p.023948 ). Other signs and symptoms were less frequent and statistically irrelevant. Surgical resection of the parasite was the predominant type of treatment, varying from 55.5% to 87.5% (p- .02395); endoscopy (48.2%) and craniotomy (24.4%), each individually, showed statistical significance (.00001 and .000073, respectively). The difference was also relevant among patients who had CSF diversion performance with/without medical treatment (p-.002312. Postoperatively, 31.8% of patients received anthelmintics with/without anti-inflammatory or other drugs. Endoscopy, open surgery, and postoperative antiparasitic therapy showed statistical differences (p < 0.001). Favorable outcomes or regression of symptoms were recorded in 83.7%, mortality 7.5%. In the case series, the clinical signs&symptoms were as follows: headache-64%, nausea and vomiting 48.4%, focal neurological deficit 33.6% and altered level of consciousness 25%. Open surgery was the predominant form of intervention (craniotomy (57.6% or endoscopy 31.8%); with statistical significance between them (p< .00001). Conclusion. Ventricular neurocysticercosis is an alarming clinical condition. Hydrocephalus is the dominant diagnostic sign. Isolated IVNCC patients were recognized at a younger age than Mix.IVNCC individuals; poeple with cysts in the fourth and third ventricles (as a potentially more occlusive type of disease), presented their symptoms at a younger age than individuals with LVNCC. The majority of patients had long-term signs and symptoms before the acute onset of the disease. Headache, nausea& vomiting are the most common symptoms of infestation accompanied by altered sensorium and focal neurological deficits. Surgery is the best treatment option. A sudden increase in ICP due to cerebrospinal fluid obstruction with a successive cerebral hernia is the leading cause of fatal outcomes.

Unusual Clinical Presentation of Giant Extragenital Condyloma.

Dear editor, Condylomata accuminatum (CA) is a human papillomavirus (HPV) related sexually transmitted infection (STI), clinically characterized by solitary or even clustered dark red or pink lesions solely affecting the anogenital area (1). CA involving the extragenital, non-mucosal skin has been sporadically reported (2-4). Diagnosis of CA is usually straightforward when the lesions are located on the anogenital area. However, involvement of extragenital skin may pose a diagnostic challenge. Herein, we report a rare case of giant linear extragenital CA without coexisting genital lesions, diagnosed with a synergic intervention of dermatoscopy and clinics. A 70-year-old Caucasian man was referred to our department for an atypical asymptomatic seborrheic keratosis presenting as a linear verrucous plaque (20 × 2 cm) with few solitary reddish satellite papules on the abdomen (Figure 1, a). No similar lesions were present in both cutaneous and mucosal districts. Medical history was unremarkable, and the patient denied having recent sexual intercourse or any history of condylomas. Remarkably, the patient underwent a diet in the last 8 months that resulted in a loss of 30 kg. We employed dermatoscopy to further assess the lesions, highlighting a finger-like pattern on the main lesion (Figure 1, c), while satellite lesions presented a mosaic pattern (Figure 1, b). The clinical appearance and these dermatoscopic findings were suggestive of condyloma acuminatum (CA), but due to its extraordinary presentation we also performed an incisional biopsy. Histopathological examination reviled features compatible with the diagnosis of CA (Figure 1, d, e). To better characterized the HPV genotype (high-risk and low-risk HPV) a polymerase chain reaction (PCR) from lesional tissue sample was performed and found HPV type 6 positivity. The lesions were successfully removed by electrosurgery. Regular follow-up was scheduled. Sexually transmitted infections (STIs) were also screened, namely syphilis, gonorrhea, chlamydia trachomatis, and HIV status. In addition, laboratory tests and imaging examinations (radiography of the chest and ultrasound examination of the abdomen) revealed no pathological findings. CA involving the extragenital skin has been reported within intertriginous areas, including the inframammary fold, the groin, and the axillary vault, as well as mucosal surface such as intraoral and conjunctival mucosa (1-5). In most cases, extragenital CA coexisted with genital lesions. Staples et al. reported three obese patients with extragenital CA on the skin of the abdominal pannus (3). However, all of the patients had involvement of the inguinal folds, from where the CA had extended. Generally, CA is acquired by genital, oral, or anal sexual contact. Among the wide spectrum of HPV genotypes, types 6 and 11 are responsible of 90% of CA (1). Our paradigmatic case allows us reflect on the concept of transitory immune dysregulation due to a significant amount of weight loss, and the position of the lesions in particular seems to suggest that frictional triggers may disrupt the barrier integrity, leading to higher probability of infection. Dermoscopy is a noninvasive diagnostic tool with a significant role in the assessment of melanocytic and non-melanocytic skin tumors. Furthermore, the utility of dermatoscopy has expanded to the field of inflammatory and infectious skin disease, where dermoscopy enhances the differential diagnosis between them. Seborrheic keratosis, as the most common benign epithelial tumor, can occur anywhere in the skin excluding the palms, soles, and mucosa (6). In the anogenital area, seborrheic keratosis usually resembles CA. However, dermatoscopically, seborrheic keratosis can be immediately identified by the presence of milia-like cysts, comedo-like openings, fissures, finger-print structures, and sharply demarcated borders (6). In contrast, reports of CA dermoscopy suggested four different dermoscopic patterns: fingerlike, mosaic, knoblike, and the most commonly, an unspecific pattern (7). Our case showed that dermoscopy of extragenital CA presented a mosaic pattern in an early stage of CA, while fully developed lesions revealed a fingerlike pattern, as has previously been reported by Dong et al. (7), where two different stages of clinical development of CA exhibit distinctive dermoscopic patterns, which correlates with our case. We did not observe the typical dermoscopic features of seborrheic keratosis. CA arising in an extragenital area is very rare and perhaps also underestimated. Thus, dermatologists should be aware of this unusual presentation even in the absence of genital HPV involvement. Moreover, dermoscopy may facilitate CA recognition in a such uncommon location. To our knowledge, this is the first report of extragenital condyloma acuminatum documented dermoscopically.

Eruptive Nevi on the Palms and Soles with no Association with an Underlying Disease or Medications.

Eruptive melanocytic nevi are an unusual phenomenon characterized by sudden onset of multiple melanocytic nevi on previously unaffected skin. The majority of case reports have linked this condition with blistering skin disease or immunosuppression. There are only three reports of eruptive nevi developing on the palms and /or soles in healthy individuals. Herein we present the clinical and dermoscopic features of two cases of eruptive acral nevi that developed in healthy individuals in the absence of any recognizable underlying disease and review the current literature of eruptive nevi.

Long-lasting undetected neurocysticercosis.

Neurocysticercosis is the most common parasitic disease of the nervous system, nevertheless, it can remain undetected for a long period of time, especially if it occurs in non endemic areas and regions with low-endemicity. Inadequate diagnostic procedures and lack of clinician's dedication towards this health issue can lead to a missed diagnose. Herein, we present a case of a 51-year-old male, with a missed diagnosis of neurocysticercosis for more than two decades. A history of epilepsy had started twenty-one years earlier and was of unclear etiology. Recently, after neurological worsening and headaches, brain computed tomography and magnet resonance imaging was performed as well as Western blot immunoassay of serum and cerebrospinal fluid, surgery, and pathohistological examination of the extracted cysts. Neurocysticercosis was confirmed. Combined therapy that consisted of albendazole and prednisolone was administered for a period of four weeks. Also, antiepileptic therapy was continued. Both clinical status and brain imaging showed the apparent improvement in the patient's condition. Review of the literature was implemented in the discussion that deals with proper and adequate therapy option and outcome factors in neurocysticercosis patients. Over a long period of time, the majority of patients develop seizures as the most common symptom, which requires the administration of medications. Proper diagnostic procedures and adequate combination of surgery and conservative treatment areessential.

Morphological and morphometric characteristics of choroid plexus psammoma bodies during the human aging.

Psammoma bodies are one of many choroid plexus aging changes which origin is still enigma for the scientists. During our investigation psammoma bodies were studied on 30 postmortem brains by light microscopy. They stained red with HE, and were PAS and AB PAS positive. The largest number of lamellas were stained blue with Mallory's connective tissue stain, except peripheral and next to the center lamella which stained red. During the aging, psammoma bodies became larger and more irregular, which was followed with group area and perimeter, single psammoma body average area and average perimeter, average diameter and contour index increase. Psammoma bodies mearged in the second and the third age group and mearging process led to larger and more irregular structures formation. The results of this investigation suggest that psammoma bodies are more frequent in choroid plexus of healthy older people and during the aging they obtain larger dimensions, more irregular contours, which is the result of their mutual mearging.