Analysis of Clinical and Histopathological Findings in Microscopic Colitis.

OBJECTIVE: Microscopic colitis is a chronic inflammatory disorder characterized by a triad of chronic diarrhea, endoscopy without significant abnormality, and distinct histopathological features. Histopathologically, microscopic colitis is divided into 3 subtypes; collagenous colitis, lymphocytic colitis, incomplete microscopic colitis. The main purpose of this study was to analyze the detailed clinicopathological parameters of microscopic colitis cases in the Turkish population. MATERIAL AND METHOD: The clinicopathological parameters were evaluated in 53 microscopic colitis cases (37 collagenous colitis, 7 lymphocytic colitis, 9 incomplete microscopic colitis) diagnosed between 2010 and 2019. RESULTS: All cases had lymphoplasmacytosis. The presence of ≥20 eosinophils/high power field in the lamina propria was remarkable in 75.7%, 57.1%, and 11.1% of collagenous colitis, lymphocytic colitis, and incomplete microscopic colitis cases, respectively. One of the striking findings was the presence of concomitant Celiac disease in 29% of the lymphocytic colitis cases. In terms of drug use, proton pump inhibitors and nonsteroidal anti-inflammatory drugs were the most commonly used drugs. CONCLUSION: The mean age in our series is lower than the literature and a distinct male predominance was observed in lymphocytic colitis and incomplete microscopic colitis, contrary to the literature. These suggest that susceptibility to microscopic colitis may differ between ethnic groups. The presence of overt lymphoplasmacytosis, eosinophilic infiltration and epithelial damage are the microscopic features which should alert the pathologist for the diagnosis of complete microscopic colitis. Given that microscopic colitis is a common treatable cause of chronic diarrhea, awareness of the aforementioned histopathological features is of utmost importance for accurate diagnosis and not to miss incomplete cases.

Clinicopathological analysis of invasive cribriform carcinoma of the breast, with review of the literature.

Invasive cribriform carcinoma (ICC) is a rare type of a primary breast carcinoma. It is subdivided into two groups as pure and mixed types. There are limited studies comparing the pure and mixed ICC at present. We aim to investigate the clinicopathological, radiological, prognostic features, and survival outcomes of two types with reviewing the published literature. 16 pure ICC and 26 mixed ICC cases were evaluated. The population consisted of 41 female and 1 male patients. The only male patient was a pure ICC case. The median age was for pure and mixed type, 46.5 and 54 years, respectively. All ICCs were ER positive. All ICCs except one mixed ICC, were positive for PR. Only one mixed ICC was accepted HER2 positive (3+). Pure ICCs showed more favorable features than mixed ICCs such as lesser axillary lymph node involvement, lower grade, and proliferation index. Twenty-five patients had one of the following imaging methods; ultrasonography (US), mammography (MG), and magnetic resonance imaging (MRI). Irregular shape, hypoechogenicity, and spiculated margins were the most common US findings. Similarly, irregular shape+spiculated margin is the most common MG findings. The median follow-up time for pure and mixed ICC was 88 and 56.5 months, respectively. One mixed ICC case developed bone metastasis. One death occurred in each group. Reasons of death were unknown. The 5-year OS for both ICC groups was 100%. 10-year OS for pure and mixed ICCs was 100% and 90%, respectively. 5-year DFS was 100% for pure ICC, and 94% for mixed ICC.

The Histopathological Parameters Affecting Biochemical Recurrence in Radical Prostatectomies.

OBJECTIVE: To determine the relationship between biochemical recurrence and other histopathological factors in prostate cancer. STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Pathology and Urology Departments, Izmir Ataturk Training and Research Hospital, between 2001 - 2013. METHODOLOGY: 117 cases diagnosed with prostatic adenocarcinoma and treated by radical prostatectomy were reviewed retrospectively for histopathological features; whereas, other prognostic findings were noted. PSA levels and many other histopathological parameters were assessed in order to put forth their effect on biochemical recurrence. RESULTS: PSA level (p<0.001), tumor volume (p<0.001), Gleason score (p<0.001), extraprostatic extension (p<0.001), perineural invasion (p<0.001), ganglion involvement (p=0.040), vascular invasion (p<0.001), positive surgical margins (p<0.001), presence of tertiary pattern (p=0.004) and the involvement of the seminal vesicles (p<0.001) were found to be statistically related to the pathological stage. Age, perineural invasion, high grade tertiary pattern, intraluminal mucin, collagenous micronodules and foamy cytoplasmic changes were unrelated to recurrence. CONCLUSION: Histopathological features can be helpful in predicting prognosis in prostatic adenocarcinomas. However some of the histopathological factors such as intraluminal mucin and foamy cytoplasmic changes may not reflect high recurrence.

DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease.

BACKGROUND: Chronic hepatitis B infection is characterized by hepatic immune and inflammatory response with considerable variation in the rates of progression to cirrhosis. Genetic variants and environmental cues influence predisposition to the development of chronic liver disease; however, it remains unknown if aberrant DNA methylation is associated with fibrosis progression in chronic hepatitis B. RESULTS: To identify epigenetic marks associated with inflammatory and fibrotic processes of the hepatitis B-induced chronic liver disease, we carried out hepatic genome-wide methylation profiling using Illumina Infinium BeadArrays comparing mild and severe fibrotic disease in a discovery cohort of 29 patients. We obtained 310 differentially methylated regions and selected four loci comprising three genes from the top differentially methylated regions: hypermethylation of HOXA2 and HDAC4 along with hypomethylation of PPP1R18 were significantly linked to severe fibrosis. We replicated the prominent methylation marks in an independent cohort of 102 patients by bisulfite modification and pyrosequencing. The timing and causal relationship of epigenetic modifications with disease severity was further investigated using a cohort of patients with serial biopsies. CONCLUSIONS: Our findings suggest a linkage of widespread epigenetic dysregulation with disease progression in chronic hepatitis B infection. CpG methylation at novel genes sheds light on new molecular pathways, which can be potentially exploited as a biomarker or targeted to attenuate inflammation and fibrosis.

How to approach phyllodes tumors of the breast?

OBJECTIVE: Phyllodes tumor of the breast is a rare fibroepithelial breast tumor that comprise 0.3-0.9% of primary breast neoplasms. In this study, we aimed to present clinicopathologic symptoms of our patients along with their treatment modality. MATERIAL AND METHODS: Clinicopathologic properties and treatment modality of 20 phyllodes tumor patients who underwent surgery between January 2008 and January 2013 were retrospectively evaluated. RESULTS: Median patient age was 47 years (22-75). Fine-needle aspiration biopsy was applied to 19 patients. Biopsy results were reported as suspicious in four, malignant in three, benign in 11, and as non-diagnostic in one patient. Final histopathology reports revealed two benign, one malignant and one borderline tumor out of the four patients with suspicious findings on fine needle aspiration biopsy; all patients with malignant cytology had malignancy. There were two borderline and nine benign lesions within the benign biopsy group. Sixteen patients underwent segmental mastectomy, four patients underwent mastectomy with/without axillary dissection. The median tumor size was 6 (1-13) cm. Histopathologically, 11 (55%) tumors were benign, 5 (25%) were borderline, and 4 (20%) were malignant. Two of the four patients with malignancy underwent radiotherapy and chemotherapy, and one patient only received chemotherapy as adjuvant treatment. CONCLUSION: Phyllodes tumors are rare, mix-type breast tumors. Due to high rates of local recurrence and potential for malignancy, preoperative diagnosis and accurate management are important.

Coexistence of gastrointestinal stromal tumors (GISTs) and pheochromocytoma in three cases of neurofibromatosis type 1 (NF1) with a review of the literature.

It is well known that neurofibromatosis type 1 (NF1) is uncommonly associated with pheochromocytoma development and also, to a larger extent, with gastrointestinal stromal tumors (GISTs). We herein document three cases with the rare condition of NF1 coexisting with GIST and pheochromocytoma, while one of them also has a composite tumor and another has papillary thyroid carcinoma.

Primary mucinous cystadenocarcinoma of the breast with amplification of the HER2 gene confirmed by FISH - case report and review of the literature.

Fifty five-years-old woman was presented to the general surgery upon the palpation of a mass in her left breast. In the excisional biopsy performed, partially cystic tumor of 2 × 1 cm with solid areas was macroscopically observed. After through microscopic examination, the patient was diagnosed as invasive mucinous cystadenocarcinoma and the tumor was found to be ER- and PR-negative and C-erbB2 (2+). In the fluorescent in situ hybridization, HER2/neu gene amplification was observed. Here, we present the clinical, cytological, morphological and immunohistochemical features of a very rare type of breast carcinoma, mucinous cystadenocarcinoma of the breast, with the review of the relevant literature.

Predictive and prognostic factors in locally advanced breast cancer: effect of intratumoral FOXP3+ Tregs.

This study aimed to investigate the prognostic and predictive effect of FOXP3+ Tregs together with clinicopathologic factors in locally advanced breast cancer (LABC) patients. The medical records of 101 LABC patients who received neoadjuvant chemotherapy (NAC) between 2005 and 2012 were evaluated retrospectively. The density of intratumoral FOXP3+ lymphocytes in paraffin-embedded tissues was assessed by immunohistochemical analyses in appropriate cases. The relationship with clinicopathologic features, prognosis and chemotherapy response was investigated. HR(-) and HER2(+) tumors tended to have higher pre-chemotherapy Tregs than HR(+) tumors, and significantly higher pathologic complete response (PCR) rates were observed in these patients. Treg decline after NAC was associated with better pathological response rates. Lower intratumoral infiltration of FOXP3+ Tregs after NAC (<3.4/HPF) was significantly associated with higher PCR rates for breast, and close to the significance limit for total (or both for breast and axillary) PCR rates (PCR for breast: 25 vs. 2.9 % for low vs. high Treg, p = 0.001; PCR for breast + axillary tissue: 13.9 vs. 0 %, p = 0.05). Despite better PCR rates, patients with high intratumoral Treg infiltrates (≥11.5/HPF) before chemotherapy had significantly shorter overall survival than patients with low Treg infiltrates (<11.5/HPF). Cox multivariate regression analyses demonstrated that the density of Treg infiltration before chemotherapy was the strongest predictor for survival. This study established the predictive and prognostic effect of intratumoral FOXP3+ Tregs in LABC patients. To predict clinical outcome, evaluation of FOXP3+ Tregs in tumoral tissues before and after NAC should be considered for these high-risk patients.

Epithelioid schwannoma of soft tissue: unusual morphological variant causing a diagnostic dilemma.

Epithelioid variant of peripheral nerve sheath tumors is a rare but, at the same time, a well-known entity especially in the malignant counterpart. However, peculiar epithelioid morphology in soft tissue schwannomas is unusual and has been defined recently. These tumors may cause diagnostic errors owing to their increased cellularity and epithelioid morphology. Typical histologic features of classic schwannoma such as Antoni A and B areas, Verocay bodies, and hyalinized vessels are either absent or only present in focal areas. Furthermore, strong and diffuse S-100 protein expression is seen in both benign and malignant counterparts of epithelioid schwannoma. The findings that are suggestive of the benign nature of the lesion are long-term clinical history, small size, superficial localization, encapsulation, bland morphology, lack of mitosis and necrosis, and a benign clinical course after complete excision. Pathologists should be aware of the epithelioid variant of schwannoma to avoid false diagnosis of malignancy. We hereby report 3 cases of unusual benign epithelioid schwannoma of the soft tissue with special regard to problems in differential diagnosis.

Malakoplakia of the prostate diagnosed by elevated PSA level and transrectal prostate biopsy.

Malakoplakia is an inflammation which is thought to develop secondary to chronic Escherichia coli infections. Although often seen in the genitourinary tract, it can also be seen in colon, stomach, lung, liver, bone, uterus, and skin. In this case report, we present prostatic malakoplakia diagnosed by elevated prostate-specific antigen level and transrectal prostate biopsy.

MIB-1 counting methods in meningiomas and agreement among pathologists.

OBJECTIVE: To evaluate the correlation of MIB-1 labeling index (LI) obtained by 2 counting methods with histologic grade and investigate interobserver variability between these methods. STUDY DESIGN: A total of 65 meningiomas were analyzed for proliferation with 2 counting methods by 2 pathologists using MIB-1 antibody. In the first method, the most densely staining areas were counted (HL method). In the second method, randomly selected areas were counted (RS method). RESULTS: MIB-1 values correlated well with histologic grade in both methods. As expected, the tumors with recurrence had significantly higher LIs than the nonrecurrent tumors in each method. However, there was a statistically significant difference in the mean MIB-1 values of between the HL and RS methods. When MIB-1 LI was compared between 2 pathologists, perfect agreement in the HL method and substantial agreement in the RS method were achieved. CONCLUSION: Our results showed that values of MIB LIs differ with different counting methods. Nonetheless, both methods showed good correlation with World Health Organization grades. Therefore standardization of 1 counting method is of great importance for determining a reliable and specific cutoff value in assessing the risk of recurrence in meningiomas.