Clinicopathological features and evaluation of microsatellite stability of colorectal carcinoma with cribriform comedo pattern.

BACKGROUND: Cribriform comedo-type adenocarcinoma (CCA) was a colon cancer subtype defined in the 2009 World Health Organization (WHO) classification. In the 2018 classification, it was a colon cancer subtype included in the adenocarcinoma, Not otherwise specified (NOS) group. A few studies have reported that colon cancers with a cribriform pattern have worse overall survival, and most of them are microsatellite stable (MSS). In this study, we evaluated CCAs based on their clinicopathologic features and microsatellite stability. We aimed to answer whether these tumors could be defined as a distinct morphologic subtype with prognostic significance. MATERIALS AND METHODS: Pathology reports and specimens from 449 patients with colorectal adenocarcinoma (CRA) were re-evaluated. All subtypes were determined. To evaluate MSS status, the CCA cases were immunohistochemically stained with anti-MLH1, MSH2, MSH6, and PMS2 antibodies. RESULTS: CCA was present in 40.5% of cases. These cases were found to have higher rates of lymph node metastasis, lymphovascular-perineural invasion, metastasis, and advanced stage ( P < 0.05). Also, 2.7% of CCA cases were microsatellite instable (MSI). However, no statistically significant result was found regarding overall survival and progression-free survival of CCA cases with MSI. CONCLUSION: According to the findings, CRAs with comedo cribriform patterns are tumors with more aggressive features. It can be said that these tumors have a specific molecular feature related to MSS. Because this feature is important for planning adjuvant chemotherapy, it may be useful to identify cases, particularly with a cribriform comedo pattern >90%. However, because no significant difference in survival rates was found, CCAs may not need to be defined as distinct subtypes.

Diagnosis of Immunoglobulin G4-related disease in a child with ligneous conjunctivitis: a novel mutation in plasminogen gene and plasminogen activator inhibitor-1 polymorphism.

OBJECTIVES: Ligneous conjunctivitis (LC) is a chronic conjunctivitis characterized by recurrent, firm, fibrin-rich, woody pseudomembranes on the palpebral conjunctiva. It is an ultrarare autosomal recessive disease associated with congenital plasminogen (PLG) deficiency due to mutations in the PLG gene (6q26). Immunoglobulin G4-related disease (IgG4-RD) is an idiopathic, systemic fibroinflammatory disease characterized by elevated serum IgG4 concentration and tissue infiltration of IgG4-positive plasma cells leading to organ enlargement, fibrosis and damage. CASE REPORT: A 7-year-old girl with LC was hospitalized for recurrent pancreatitis and diagnosed as IgG4-RD. PLG activity level was 15% (normal range 55-145%). Co-segregation analysis indicated that the patient was homozygous for the c. NG_016200.1(NM_000301.5):c.1465 T>C mutation in PLG gene. c. NG_016200.1(NM_000301.5):c.1465 T>C PLG variant was found to be heterozygous by NGS analysis in both parents. She also had plasminogen activator inhibitor - 1 (PAI-1) NG_013213.1(NM_000602.5):c.-816A>G (4G/4G) homozygous polymorphism and a heterozygote NG_001333.2 (NM_002769.5):c.292_293insC mutation in the serine protease 1 (PRSS-1) gene. However, heterozygous PRSS-1NG_001333.2 (NM_002769.5):c.292_293insC variant was found in the mother of the patient. All detected variants are currently considered as a variant of uncertain (or unknown) significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG) classification. Oral steroid, oral azathioprine, topical fresh frozen plasma, topical heparin, topical steroid and topical cyclosporine were given. After 3 years of follow-up, IgG4-RD is under partial remission and no pseudomembranes. CONCLUSION: She is the second case had both LC and IgG4-RD. We identified a NG_016200.1(NM_000301.5):c.1465 T>C novel homozygous mutation in PLG gene and a PAI-1 NG_016200.1(NM_000301.5):c.1465 T>C (4G/4G) homozygous polymorphism, which has been reported as a risk factor for thrombotic events.

Intradural Spinal Arachnoid Cysts in Children: A Collective Experience of 2 Centers.

BACKGROUND: Pediatric intradural spinal arachnoid cysts are rare and can cause spinal cord or nerve root compression. Spinal arachnoid cysts can cause pain, motor/sensory neurological impairments, gait disturbances, spasticity, and bladder problems depending on their location. This study discusses the clinical aspects, management, surgical nuances, and postoperative clinical outcomes of symptomatic congenital intradural spinal arachnoid cysts, which are rarely seen in the pediatric population. METHODS: Our study involves a retrospective evaluation of 8 pediatric patients who underwent surgery for spinal intradural arachnoid cysts at the Department of Neurosurgery, Kocaeli University School of Medicine, and the Department of Neurosurgery, Selros University School of Medicine. The demographic data of all patients, preoperative/postoperative clinical findings, surgical procedures, surgical complications, and radiological imaging were evaluated. RESULTS: The average age of the patients was 8.7 uated. surgicrange:1-17).The female to male ratio was 4:4. The most common complaint was weakness in the lower extremities (87.5%). Urinary problems (50%) and sensory disturbances (50%) were less frequently observed. All patients had dorsal localization of the cysts. Cyst excision was performed in 7 out of 8 patients, and cyst fenestration was performed in 1 patient. Postoperatively, 7 patients showed complete symptom resolution, while one patient had partial improvement. CONCLUSIONS: The success of surgical treatment depends on cyst location, neural tissue compression, and duration of symptoms. Complete removal or fenestration is determined by cyst location and accessibility. Intracystic shunts may be used in certain cases. Timely diagnosis and surgical intervention are crucial for improving neurological function in these rare cases.

Radiation-induced Desmoid Tumor Development in the Radiotherapy Field in a Child With Pineoblastoma: A Case Report.

Although treatment-related secondary malignancies are rare, they are important problems after the treatment of childhood malignant diseases. Irradiation-induced sarcomas are the development of sarcoma different from the primary tumor after a latent period of ≥3 years or more in the radiotherapy field. Desmoid tumor is extremely rare as irradiation-induced tumor. A 7.5-year-old girl was referred to our hospital after a subtotal mass excision for a solid lesion with a cystic component located in the pineal gland. Pathologic examination revealed pineoblastoma. After surgery, craniospinal radiotherapy, and chemotherapy consisting of vincristine, cisplatin, and etoposide were performed. Painless swelling in the left parieto-occipital region ~75 months after the end of the treatment developed in the patient. A mass was detected in the intracranial but extra-axial region by radiologic imaging methods. Due to the total removal of the mass and the absence of a tumor in the surgical margins, she was followed up without additional treatment. The pathologic diagnosis was a desmoid tumor. She was followed up disease free for ~7 years after the primary tumor and ~7 months after the secondary tumor. Treatment-related desmoid tumor development after treatment for a central nervous system tumor in a child is extremely rare.

Classification of high-grade endometrium carcinomas using molecular and immunohistochemical methods.

OBJECTIVES: As a result of the integration of molecular changes into the histological classification of cancers, which increases diagnostic repeatability, the differences between the groups become more prominent and targeted therapies gain significance. The most comprehensive molecular study regarding endometrial carcinomas (EC) is The Cancer Genome Atlas (TCGA) project. According to TCGA, endometrial carcinomas are classified into four molecular prognostic subgroups: copy-number-low/p53-wild-type (p53wt), DNA polymerase epsilon (POLE)-mutated/ultramutated (POLEmt), microsatellite-instability/hypermutated (MSI), and copy-number-high/p53-mutated (p53mt). In this study, we aim to apply the molecular classification to our high-grade endometrial cancer patients, and particularly, to identify our overtreated patients. MATERIAL AND METHODS: Ninety-seven patients diagnosed with high-grade EC in Selcuk University, Faculty of Medicine between 2009-2018 were retrospectively evaluated and classified into four subgroups. Primary outcomes of overall and progression-free survival were evaluated for clinical, pathological, and molecular features. Further, all molecular groups were divided into endometroid and non-endometrioid groups, and disease-free survival (DFS) and overall survival (OS) were investigated across groups. RESULTS: According to molecular classification, 23 patients (23.7%) were assigned to the MSI group, 21 (21.6%) to the POLEmt group, 40 (41.2%) to the p53mt group, and 13 (13.4%) to the p53wt group. Patients' DFS (p = 0.001) and OS rates (p = 0.001) were significantly different according to their molecular classification. The results of our analyses determined that, in the molecular classification of high-grade ECs, the p53mt group had the poorest prognosis and the POLEmt group had the best prognosis. Tumor size, myometrial invasion, lymphovascular space invasion (LVSI), lymph node metastasis, cervical invasion, ovarian invasion and stage showed statistically significant differences based on molecular classification (p < 0.05). CONCLUSIONS: The use of molecular classification in the clinical practice will allow more accurate prognostic prediction and more appropriate treatment planning, particularly as high-grade ECs constitute a heterogenous group with poor prognosis.

Can Dynamic Susceptibility Contrast Perfusion Imaging be Utilized to Detect Isocitrate Dehydrogenase Gene Mutation in Gliomas?

AIM: To explore the ability of dynamic susceptibility contrast perfusion imaging (DSC-PI) to detect isocitrate dehydrogenase (IDH) gene mutation in gliomas. MATERIAL AND METHODS: Preoperative DSC-PI data on histopathologically proven gliomas obtained between January 2015 and December 2019 were reviewed retrospectively. All magnetic resonance imaging (MRI) examinations were performed using a 1.5-T scanner. The maximum relative cerebral blood volume (rCBVmax), percentage signal recovery (PSR), and normalized PSR of tumor cores were calculated. Differences in these values between IDH-mutant and wild-type gliomas were compared, and receiver operating characteristic curves were generated. RESULTS: The patients (32 females, 47 males) were aged 21-76 years (mean 50.7 ± 15 years). The rCBVmax and all PSR values differed significantly between patients with IDH-mutant and those with wild-type tumors (p < 0.01 for all comparisons). CONCLUSION: The rCBVmax and PSR values obtained by DSC-PI may facilitate noninvasive detection of the IDH mutation status of gliomas. PSR provided more reliable values for differentiation of IDH-mutant gliomas from wild-type gliomas.

Clinical Features, Treatment and Outcome of Childhood Glial Tumors.

AIM: To evaluate the clinical features, treatment approaches, and outcomes of glial tumors in children. MATERIAL AND METHODS: Files (2006 to 2020) of children diagnosed with glial tumors and followed-up were reviewed retrospectively. Information regarding demographic and clinical characteristics, treatment approaches, and outcomes were retrieved from the patients? files. RESULTS: Of the total of 180 pediatric patients diagnosed with brain tumors, 73 (40.6%) had glial tumors. The children with astrocytoma were in the age range of 2?18 years (median age: 8.7 years), while the ages of children with ependymoma ranged from three months to 10 years (median age: 3 years). This difference was statistically significant (p < 0.0001). The male to female ratio was 1.6. The most common symptoms or signs were headaches (n=34, 46.6%), abnormal gait or coordination (n=22, 30.2%), vomiting (n=21, 28.8%), and cranial nerve palsies (n=20, 27.4%). The pathological diagnoses were astrocytomas (n=53, 72.6%), oligodendroglial tumors (n=2, 2.7%), ependymoma (n=15, 20.7%), and other glial tumors (n=3, 4.1%). The most common tumor location was supratentorial (n=42, 57.5%), while midline glioma was detected in seven patients. The 5-year overall survival (OS) rate of all glial tumors, astrocytoma, and ependymoma was 42%, 40%, and 55%, respectively. The 5-year OS rate of the tumor Grade I, II, III, and IV was 77.2%, 45%, 32%, and 0%, respectively (p < 0.0001). The 5-year OS rate of supratentorial, infratentorial, and spinal tumors was 25.6%, 63.6%, and 50%, respectively (p=0.021). In Cox regression analysis, it was found that the tumor resection and grade had an effect on the tumor prognosis. CONCLUSION: Treatment results are not satisfactory in high-grade astrocytomas. There is a need for new treatment approaches that would take cognizance of molecular features and adopt multidisciplinary approaches.

Precise discrimination between meningiomas and schwannomas using time-to-signal intensity curves and percentage signal recoveries obtained from dynamic susceptibility perfusion imaging.

BACKGROUND AND PURPOSE: Meningiomas and schwannomas are common extra-axial brain tumors. Discrimination is challenging in some locations when characteristic imaging features are absent. This study investigated the accuracy of percentage signal recoveries obtained from dynamic susceptibility contrast perfusion imaging (DSC-PI) in discriminating meningiomas and schwannomas. MATERIAL AND METHODS: Retrospective database research was conducted. Sixty nine meningioma and 15 schwannoma having DSC-PI between January 2016 and February 2020 were included. Time to signal intensity curves (TSIC) were analyzed and grouped as T1-dominant leakage, T2*-dominant leakage and return to baseline. Relative cerebral blood volume (rCBV), relative mean transit time (rMTT), percentage signal recovery 1 (PSR 1) and PSR 2 values were calculated. The differences between the groups were investigated. Receiver operating characteristic curves were operated. RESULTS: rCBV, rMTT, PSR 1 and PSR 2 values were statistically different between meningiomas and schwannomas. PSR 2 provided the best discrimination. With the cut off value of 1.08 for PSR 2, meningiomas and schwannomas were differentiated with 95.7% sensitivity and 93.3% specificity. TSICs were also different between two groups. Most of meningiomas showed T2*-dominant leakage (78.2%), whereas most of shwannomas showed T1-dominant leakage (93.3%). CONCLUSION: DSC-PI is a useful imaging tool for non-invasive discrimination of meningiomas and schwannomas. Particularly, percentage signal recoveries discriminates meningiomas and schwannomas with high sensitivity and specificity.

Pediatric Calvarial Tumors: 10 Years of Clinical Experience and Differences From the Literature.

ABSTRACT: Very few studies have focused exclusively on pediatric calvarial tumors. These studies have primarily addressed the similarities of the cases with those reported in the literature, as opposed to their distinctive features. In contrast, the present study is the most detailed study conducted in the last 10 years that includes only pediatric calvarial tumors and highlights their differences according to the literature. A total of 31 patients with pediatric calvarial tumor surgically treated in our center between 2010 and 2020 were included in the study. The patients' files were analyzed retrospectively and 17 different preoperative, intraoperative, and postoperative parameters were determined and compared with previous studies. Except for the tumors causing lytic or sclerotic lesions, there was at least one distinguishing aspect of our series in all parameters. Despite the many distinctive features, the consensus in the treatment of calvarial tumors is to perform complete resection of the tumor and, if possible, remove some of the adjacent healthy bone. Considering the age factor, however, closure of the resulting bone defects with cranioplasty to address issues of cosmesis and intracranial pressure is yet another aspect of pediatric calvarial tumors, because pediatric cranioplasty has its own specific complications. Using intraoperative neuronavigation and performing tumor resection alone without additional craniectomy are also methods the authors use to prevent major bone defects.

Histopathological and Clinical Features as Prognostic Factors of Atypical Meningiomas.

AIM: To analyze the correlation of clinicopathologic prognostic parameters with atypical meningiomas (AMs) and recurrence development as well as progression-free survival (PFS). MATERIAL AND METHODS: The neuropathology archive and hospital records of 75 patients with AM who underwent surgery in our institution between 2010 and 2019 were retrospectively reviewed. The pathological revision was performed according to the 2016 World Health Organization (WHO) criteria. Other clinicopathological parameters, such as age, gender, tumor location, preoperative tumor size, degree of resection, Psammoma body, nuclear atypia, main histological pattern, Ki67 labeling index (LI), radiotherapy, and dura and bone invasion, were also analyzed. Statistically, univariate and multivariate analyses were assessed to determine their potential impact on recurrence-related prognostic factors. RESULTS: Recurrence occurred in 20 patients. The mean PFS and follow-up time were 38.9 and 44.8 months, respectively. In univariate analysis, clinical and pathological features such as age of ?55 years, female sex, skull base tumor location, larger preoperative tumor size, increased mitotic count, small cells, hypercellularity, sheeting, necrosis, and dura and bone invasion were remarkable in patients with recurrence, but were not statistically significant. In multivariate analysis, increased mitotic activity and brain invasion either considered alone or combined were significantly associated with PFS. Nuclear atypia was also not associated with both tumor recurrence and PFS. However, clinical features did not significantly influence the PFS. CONCLUSION: This study found that recurrence could not be predicted by the presence of any of the clinicopathological features of AMs. We believe that molecular variables determined through routine neuropathological analysis will be needed in the future.

Corpus Callosum Lipomas in Children.

AIM: To determine the clinical and radiographical aspects of six patients diagnosed with pericallosal lipomas (PCL). MATERIAL AND METHODS: A retrospective analysis of patients who presented to the neurosurgery outpatient clinics of Selcuk Faculty of Medicine between 2009 and 2019, revealed that six patients were diagnosed with PCL. The clinical and magnetic resonance imaging (MRI) data were obtained by reviewing patients? records. RESULTS: A total of six patients (two girls and four boys), with a mean age of 53.8 months (38?72 months), were included in this study. They were followed up for a mean period of 36.5 months (32?41 months). PCL were detected on MRIs, which were obtained to investigate headache in two patients, epilepsy in one patient, frontal dermal sinus tract and left frontal epidermoid tumor in one patient, and subcutaneous lipoma associated with PCL in one patient. Five patients displayed tubulonodular lipomas and one patient displayed curvilinear lipomas. Agenesis or dysgenesis of the corpus callosum (CC) was observed in four (66%) patients. Two patients received surgical treatment for cosmetic skin problem. CONCLUSION: Because of the benign course of PCL, i.e. no growth or very slow growth, and close proximity to the surrounding neurovascular structures, surgical removal should be considered only in symptomatic PCL. Furthermore, other malformations and anomalies may accompany PCL.

Intraventricular microcystic meningioma in a child: a case report.

BACKGROUND: Microcystic meningiomas are extra axial masses that are extremely rare in the pediatric population. Intraventricular meningiomas are also rarely seen. CASE PRESENTATION: This case reports an 18-year-old boy who had an intraventricular mass on magnetic resonance imaging at the age of 12 years and had shown growth at a 6-year follow-up after subtotal resection. The mass was removed by total resection and pathological examination indicated microcystic meningioma. CONCLUSION: The present case is the first pediatric intraventricular microcystic meningioma in the literature. We believe that this unique case presented with its radiological, pathological and clinical features will contribute to the literature.

A case of recalcitrant acute generalized exanthematous pustulosis with Sjogren's syndrome: Successfully treated with low-dose cyclosporine.

Acute generalized exanthematous pustulosis (AGEP) is a reaction attributed mainly to drugs. Hydroxychloroquine is a rare cause of AGEP especially used in rheumatology and dermatology. Systemic corticosteroids are the first-line treatment agents in AGEP. But cyclosporine can be a good choice for patients resistant to systemic corticosteroid treatment in AGEP.

Aggressive treatment for urothelial cancer-complete urinary tract extirpation: Operative feasibility in two cases.

Bladder cancer (BC), the most common malignancy of the urinary tract, accounts for 90-95% of all urothelial carcinomas (UCs), while upper urinary tract UC (UUTUC) accounts for only 5-10%. Radical nephroureterectomy with excision of bladder cuff, and radical cystectomy with pelvic lymph node dissection and a urinary diversion (UD) are the gold standard treatments for UUTUC and muscle-invasive bladder cancer (MIBC), respectively. These two treatments can be performed simultaneously when a bilateral or unilateral UUTUC is present with a MIBC, and are called complete urinary tract extirpation (CUTE) and hemi-CUTE, respectively. This complex surgery can help the patient by avoiding multi-staged surgeries, repeated anesthesia, and delay in completion of treatment. Herein, we report the first cases of a hemi-CUTE and CUTE in our department and share our experience with this aggressive and complex surgical treatment.

Small Cell Lung Carcinoma Metastasis to Atypical Meningioma: Importance of Perfusion Magnetic Resonance Imaging Graphics in Differential Diagnosis.

We described the imaging findings of small cell lung carcinoma metastasis to atypical meningioma and the importance of magnetic resonance imaging perfusion graphics at the differential diagnosis. To be able to determine subtypes of meningiomas and differentiate whether they are malignant or benign may provide a preoperative idea to determine prognosis and surgical procedure.

Discrimination of cancerous and healthy colon tissues: A new laser-based method.

BACKGROUND: Femtosecond (fs) Laser Ionisation Mass Spectrometry (fs-LIMS) on colon tissues are described and investigated using ionization/fragmentation processes in details to present a new application in this study. Linear Time of Flight (L-TOF) mass analyzer was utilized to investigate paraffin-embedded human tissue in this study. The effect of fs laser intensity on the spectral characteristics was investigated and interpreted due to mass spectra obtained using 800 nm wavelength with 90 fs pulses at 1 kHz repetition rate. OBJECTIVES: Mass spectra of tissues were recorded from L-TOF system and then analyzed by performing a statistical approach called Principal Component Analysis (PCA). The fs-LIMS method applied is proposed as a new and pioneering technology to analyze tissues using L-TOF system, as a human free fast and reliable intra-operative cancer diagnosis method for guiding surgeon to clean the edges of cancerous tissues to be applied during the surgical operation, for pathological examinations. Fs-LIMS provides some unique diagnosis opportunities to investigate biochemical characteristics of cancerous tissues leading to obtain sensitive, fast, and reliable results. The analysis of tissue is based on distribution of molecular ion (m/z) peaks in low mass region (

Evaluation of Toll-Like Receptor Expression with Clinicopathologic Variables in Endometrium Cancer.

OBJECTIVES: Clinical evidence supports the association of toll-like receptor (TLR) with abnormal cell proliferation and cancer. In this study, we investigated the expression of TLRs 2, 4, 5, and 6 in healthy endometrium and endometrium cancer to study the relationship of these receptors' expression with carcinogenesis. METHODS: Patients who had undergone a hysterectomy owing to endometrium cancer (group 1, 66 patients), endometrial hyperplasia (group 2, 14 patients), and other reasons besides endometrium cancer (group 3, 20 patients as controls) were included. The cases in the first group were classified by histological type of the cancer, stage, grade, and size of the tumor. In all the cases, expressions of TLRs 2, 4, 5, and 6 were assessed, and the relationship of these receptors with clinicopathologic signs was analyzed. For immunohistochemical staining, nuclear and cytoplasmic stainings were considered positive. A Chi-squared test was used to assess the correlation of the groups. A p<0.05 was considered significant. RESULTS: The mean ages of patients in groups 1, 2, and 3 were 59.8 (range 33-83), 48.3 (range 40-59), and 53.4 (range 38-84) years, respectively. All types of TLRs were highly expressed in both types of endometrium cancer (groups 1 and 2). TLR expression was observed with a ratio of 87.9% in group 1, 100% in group 2, and 35% in group 3. There was a statistically significant association of TLR 2 among the three groups (p=0.000). TLR 6 expression in both group 1 and group 2 was significantly higher than that in the control group (p=0.000, p=0.000, respectively). In addition, TLR 6 was higher in cases with late-stage cancer (p=0.033). Regarding tumor grade and the size of the tumor, no association was found between TLR 2 and TLR 6. CONCLUSION: TLR 2 and TLR 6 were significantly more expressed in cases with endometrium cancer and endometrial hyperplasia. In addition, the presence of TLR 6 may indicate the presence of late-stage endometrial cancer.

The relation between Ring Box-1 protein overexpression and tumor grade and stage in bladder urothelial cell carcinoma.

BACKGROUND: Ring Box Protein-1 (RBX-1), a component of SCF E3 ubiquitin ligases, has a crucial role in bladder urothelial cell carcinoma (UCC) carcinogenesis and progression. OBJECTIVES: In the present study, it is aimed to determine the expression of RBX-1 protein in bladder UCC and the association between tumor grade, stage and RBX-1 expression. METHODS: Ninety UCC samples and 20 samples containing foci of normal bladder urothelium were recruited and analyzed immunohistochemically in terms of RBX-1 expression. Immuno-reactivity scoring system (IRS) was used to determine RBX-1 expression levels. RESULTS: RBX-1 overexpression was associated with high tumor grade (p= 0.001) and advanced stage (p= 0.001). pT1 tumors showed higher RBX-1 expression than pTa tumors. pT2 tumors showed not only higher expression than pTa tumors but also higher expression than the total of pTa and pT1 groups combined. There was no statistically significant relation between RBX-1 expression and patient gender (p= 0.116) or age (p= 0.191). CONCLUSIONS: In bladder UCC, RBX-1 overexpression is associated with high tumor grade and advanced stage and represents biological potential of invasiveness and aggressive disease. Results of the present study have to be supported with further studies to reveal clinical and therapeutic implications of RBX-1 overexpression in bladder UCC.