A Case of Common Variable Immunodeficiency with CREBP Gene Mutation without Rubinstein Taybi Syndrome Features.

Hypogammaglobulinemias, based on inborn errors of immunity, are primary immunodeficiencies (PIDs) that can also be diagnosed for the first time in adulthood. Common variable immunodeficiency (CVID) is a multifactorial disease often symptomatic due to antibody deficiency. In addition, some PIDs are classified into the category of immunodeficiencies with syndromic features due to their accompanying clinical findings unrelated to immunity. In this article, a patient with CVID who was diagnosed in adulthood and who was revealed to have a mutation specific to Rubinstein-Taybi syndrome and clinical features reminiscent of this syndrome only after molecular tests was presented.

MiR-25 and KLF4 relationship has early prognostic significance in the development of cervical cancer.

Cervical squamous cell carcinoma (SCC) is one of the common cancer types among women. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in the formation and development of many cancer types by regulating expression of their targets. While many studies have investigated the relationship between miRNAs and cervical cancer, no robust miRNA biomarkers have been defined yet for diagnosis of cervical lesions. In this study, we performed a statistical meta-analysis to identify miRNAs and a class compassion analysis to evaluate mRNAs with the power to discriminate between normal, intraepithelial lesions and invasive cancer samples. Differentially expressed (DE) mRNAs were compared with the targets of meta-miRNAs. After bioinfomatics analysis and qRT-PCR validations with cytology samples and FFPE tissues, we defined miR-25 and its target KLF4 (Kruppel-like factor 4) as candidate biomarkers for in vitro studies. Our results showed that miR-25 expression was significantly higher in precancerous lesions and invasive carcinoma while presenting consistent expression patterns in both cytological and FFPE tissue samples. In line with this, its direct target KLF4 expression decreased in precancerous lesions in cytological samples and also in the invasive cancer group in FFPE tissues. Furthermore, in vitro studies showed that mir-25 inhibition decreased proliferation and motility of HeLa cells and promoted an increase in the protein level of KLF4. We conclude that inhibition of miR-25 may upregulate KLF4 expression and regulate cell proliferation and motility in cervical cancer.

Atypical glandular cells in Papanicolaou test: Which is more important in the detection of malignancy, architectural or nuclear features?

OBJECTIVE: Atypical glandular cells (AGCs) in Pap (Papanicolaou) smears are uncommon but may represent various benign and malignant lesions. The aim of this study was to evaluate the AGC incidence in Pap smears, analyse the relationship between AGC and malignancy, and reveal the importance of architectural and nuclear features observed cytologically in malignancies. METHODS: Patients diagnosed with AGC on the basis of cervicovaginal cytology between May 2011 and July 2018 were included in this study. All slides were retrospectively reviewed and subclassified according to the Bethesda 2001 classification system. The cytomorphological features observed in the smears were recorded. Cytohistological correlations were evaluated, and the significant clinicopathological findings for malignancy were determined. RESULTS: Of 87 536 Pap smears, 195 (0.22%) had AGC results and 156 had tissue follow-up. Among the 156 smears with AGC, 80 (51.3%) were diagnosed as AGC-NOS (atypical glandular cells, not otherwise specified) and 76 (48.7%) as AGC-FN (atypical glandular cells, favour neoplastic). Follow-up biopsies revealed benign pathologies in 49 cases (31.4%) and malignant pathologies in 107 (68.6%). The rate of malignancy observed in AGC-FN cases (89.5%) was higher than the rate of malignancy in AGC-NOS cases (48.8%). Among the cytomorphological features, nuclear irregularity, presence of macronucleoli, feathering, loss of polarity, papillary pattern, and three-dimensional formation were found to be significant indicators of malignancy. CONCLUSION: As AGC in Pap smear was associated with a clinically significant diagnosis in 68.6% of the cases in our study, we suggest that all patients with AGC should undergo further clinical assessment.

Lung Biopsy Findings of Patients Who Have Undergone a Liver and Kidney Transplant.

OBJECTIVES: Our objective was to analyze the incidence of pulmonary disorders in solid-organ transplant recipients and report on outcomes in these patients. MATERIALS AND METHODS: Seventy liver and kidney transplant patients, who underwent lung biopsy because of pulmonary symptoms between January 2000 and December 2015, were enrolled in the study. We examined and evaluated histopathologic findings of these patients based on clinical data recorded in patients' files. RESULTS: Patients' mean age was 44.5 ± 16.4 years. Of 70 patients, 25 underwent liver transplant and 45 patients underwent kidney transplant. Forty-six patients received organs from living donors and 24 from deceased donors. Biopsy results of all patients included nonspecific findings (28), organized pneumonia (2), tuberculosis (6), fungal infections (11), tumors (5), amyloidosis (1), diffuse alveolar damage (4), mixed bacterial infection (1), and bronchopneumonia (12). Forty-two patients (60%) died within 54.1 ± 53.3 months after transplant and 24.6 ± 41.9 months after lung biopsy. Autopsies were performed on 14 patients. The causes of fatal lung diseases included fungal infections (8), malignant tumors (4), amyloidosis (1), diffuse alveolar damage (4), and mixed bacterial infection (1). Aspergillosis was the most frequently implicated lung infection, occurring in 54.5% of patients with fungal infections. CONCLUSIONS: Pulmonary diseases remain an important cause of morbidity and mortality in solid-organ transplant recipients. Fungal infection, especially aspergillosis, was the leading cause of early death in these patients.

Clinical Use of Tumor Markers for the Detection and Prognosis of Bladder Carcinoma: A Comparison of CD44, Cytokeratin 20 and Survivin.

PURPOSE: To investigate the role of CD44, cytokeratin 20 (CK20) and survivin for the detection and prognosis of patients with urothelial carcinoma of the bladder. MATERIALS AND METHODS: The study included 82 patients who underwent transurethral resection of bladder tumors between 2009 and 2014. The patient and tumor characteristics with relevance to age, tumor size and focality, grade and stage, recurrence and progression were noted. Patients with carcinoma in situ, those who had at more than 3 sites of lesions and greater than 3 cm tumors were excluded. All cases were ex-smokers. All histological samples stained with hematoxylin and eosin were re-evaluated according to the 2004 World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification system and immunohistochemically stained for CD44, CK20 and survivin. RESULTS: The study group comprised 57 (69.5%) males and 25 (30.5%) females with a mean age of 60 years (range, 26-87 years). All were newly-diagnosed patients with bladder tumors. Immunohistochemical evaluation revealed that there was a statistically significant correlation between the grade and stage of the tumor with CK20 and survivin positivity (P < .05). As the grade and stage increased CD44 immunoreactivity significantly decreased (P = .002, P = .0001, respectively). However, relationship of protein expressions with recurrence and progression remained insignificant (P > .05). CONCLUSION: In cases of bladder urothelial carcinoma positivity for CD44, CK20, and survivin has significant relation with the tumor grade and stage while no significant relationship was determined in terms of recurrence and progression .

Metachronous Occurrence of Granular Cell Tumor in Breast Skin and Scalp: Diagnostic Challenging Differentiating Benign from Malignant and a Literature Review.

Granular cell tumor (GCT) is a Schwann cell related benign neoplasm of soft tissue. GCT is an uncommon entity that occurs in a wide variety of body sites, but it is generally presented in the skin, oral cavity, superficial soft tissue, and respiratory and digestive tracts. Most of the GCTs are benign but clinically and radiologically these may mimic malignancy. Histopathological diagnosis is gold standard for establishing the true nature of the lesion. GCT is most commonly solitary but in about 10% of cases can be multifocal, usually involving various skin and soft tissue sites versus involving various internal sites. Therefore, these can involve skin and soft tissue or submucosa and viscera. GCT is usually benign; however, local recurrence is common due to incomplete removal. Malignant cases are rarely reported in 1-2% of cases. In this study, we report clinical and histopathological findings of a 36-year-old woman with metachronous GCT in breast and scalp. The clinical features raise the question of whether these are metachronous benign GCTs or whether this is establishment of malignant behavior. The aim of this report is to present the histopathological and clinical features of GCT and the diagnostic challenge of differentiating benign from malignant GCT.

A single-center retrospective clinicopathologic study of endomyocardial biopsies after heart transplant at Baskent University Hospital in Ankara, 1993-2014.

OBJECTIVES: The purpose of this study was to investigate the frequency and prognostic importance of acute cellular rejection after heart transplant. MATERIALS AND METHODS: All 84 heart transplant patients at our center from January 1993 to January 2014, including all 576 endomyocardial biopsies, were evaluated with retrospective review of clinical records and endomyocardial biopsies. Routine and clinically indicated endomyocardial biopsies after heart transplant were graded for acute cellular rejection (2005 International Society for Heart and Lung Transplantation Working Formulation). Survival analysis was performed using Kaplan-Meier method. RESULTS: There were 61 male (73%) and 23 female recipients. Median age at heart transplant was 29 years (range, 1-62 y). Posttransplant early mortality rate was 17.9% (15 patients). In the other 69 patients, 23 patients died and 46 patients (66.7%) were alive at mean 69.3 ± 7.2 months after heart transplant. Mean follow-up was 35.4 ± 29.8 months (range, 0.07-117.5 mo). Mean 8.4 ± 4.2 endomyocardial biopsies (range, 1-19 biopsies) were performed per patient. Median first biopsy time was 7 days (range, 1-78 d). The frequency of posttransplant acute cellular rejection was 63.8% (44 of 69 patients) by histopathology; 86% patients experienced the first episode of acute cellular rejection within 6 months after transplant. There were 18 patients with acute cellular rejection ≥ grade 2R on ≥ 1 endomyocardial biopsy in 44 patients with acute cellular rejection. No significant difference was observed between survival rates of patients with grade 1R or ≥ grade 2R acute cellular rejection, or between survival rates of patients with or without diagnosis of any grade of acute cellular rejection. Acute cellular rejection was not related to any prognostic risk factor. CONCLUSIONS: Acute cellular rejection had no negative effect on heart recipient long-term survival, but it was a frequent complication after heart transplant, especially within the first 6 months.

The effect of extracorporeal shock wave lithotripsy on distribution of interstitial cells of Cajal in rabbit renal pelvis and proximal ureter.

BACKGROUND/AIM: An experimental study was performed to evaluate the effect of extracorporeal shock wave lithotripsy (ESWL) on the distribution of interstitial cells of Cajal (ICC) in rabbit renal pelvis and proximal ureter. MATERIALS AND METHODS: Six New Zealand rabbits were included. Right kidneys were exposed to a total of 3000 shock waves (14 kV) by using an electrohydraulic-type ESWL device. Right sides were allocated as the ESWL group (EG, n = 6) and left sides as the control group (CG, n = 6). Tissues were harvested on day 7. Tissues were examined histopathologically for the presence of edema, inflammation, congestion, hemorrhage, fibrosis, and vascularization. Mast cell tryptase and CD 117 (c-kit) staining was performed for ICC distribution. RESULTS: Although increased tissue edema in renal pelvises and increased inflammation in ureters were observed in EG, no statistical difference was detected between groups (P > 0.05). In CG, positive CD117 staining was detected in 2 renal pelvises and ureters. None of the EG samples showed CD117 staining and no statistical difference was detected between groups (P > 0.05). CONCLUSION: Rabbit does not appear to be a good model for investigating ICCs. ESWL may cause histopathological alterations in the renal pelvis and ureter. Since it has not been statistically proven, reduced contractility of the ureter after ESWL may not be attributed to altered distribution of ICCs in the renal pelvis and ureter.