Classification of Cervical Precursor Lesions via Local Histogram and Cell Morphometric Features.

Cervical squamous intra-epithelial lesions (SIL) are precursor cancer lesions and their diagnosis is important because patients have a chance to be cured before cancer develops. In the diagnosis of the disease, pathologists decide by considering the cell distribution from the basal to the upper membrane. The idea, inspired by the pathologists' point of view, is based on the fact that cell amounts differ in the basal, central, and upper regions of tissue according to the level of Cervical Intraepithelial Neoplasia (CIN). Therefore, histogram information can be used for tissue classification so that the model can be explainable. In this study, two different classification schemes are proposed to show that the local histogram is a useful feature for the classification of cervical tissues. The first classifier is Kullback Leibler divergence-based, and the second one is the classification of the histogram by combining the embedding feature vector from morphometric features. These algorithms have been tested on a public dataset.The method we propose in the study achieved an accuracy performance of 78.69% in a data set where morphology-based methods were 69.07% and Convolutional Neural Network (CNN) patch-based algorithms were 75.77%. The proposed statistical features are robust for tackling real-life problems as they operate independently of the lesions manifold.

A whole-slide image grading benchmark and tissue classification for cervical cancer precursor lesions with inter-observer variability.

The cervical cancer developing from the precancerous lesions caused by the human papillomavirus (HPV) has been one of the preventable cancers with the help of periodic screening. Cervical intraepithelial neoplasia (CIN) and squamous intraepithelial lesion (SIL) are two types of grading conventions widely accepted by pathologists. On the other hand, inter-observer variability is an important issue for final diagnosis. In this paper, a whole-slide image grading benchmark for cervical cancer precursor lesions is created and the "Uterine Cervical Cancer Database" introduced in this article is the first publicly available cervical tissue microscopy image dataset. In addition, a morphological feature representing the angle between the basal membrane (BM) and the major axis of each nucleus in the tissue is proposed. The presence of papillae of the cervical epithelium and overlapping cell problems are also discussed. Besides that, the inter-observer variability is also evaluated by thorough comparisons among decisions of pathologists, as well as the final diagnosis.

The prognostic relationship between histopathological and immunohistochemical features of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed type.

Hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular and cholangiocarcinoma are the most common cancers of the liver. In this study, our first aim is to evaluate the relationship between prognosis and clinicopathological parameters. The second aim involves investigating the need for immunohistochemical staining and patterns of tumours to differentiate between them. Sixty-one cases were included in this study. For IHC, we used Hep par-1, CK7, CK19, CD56 and p53 staining, and the patterns of tumours were evaluated in haematoyxylin-eosin sections. No significant differences were found in Kaplan-Meier life analysis between the tumour types and OS and DFS values, but these values were greater in HCC than in ICC. There were no relationships between clinicopathologic parameters and OS and DFS. Although the multifocality, stage and grade of tumour were higher in HCC than in ICC, the perineural invasion and lymph node metastasis were more common in ICC than in HCC. The diagnosis was changed in 4 cases, from HCC to ICC in one case and to combined type in 3 cases after IHC. Pathologist should be alert to mixed patterns in terms of diagnosis and IHC, because it helps differential diagnosis in these cases.

Case for diagnosis. Atypical fibroxanthoma.

Atypical fibroxanthoma is a rare superficial fibrohistiocytic tumor. Clinically, it presents itself as a painless, solitary, ulcerated, and slow-growing nodule found mainly on sun-exposed areas - especially of the head and neck - of elderly individuals. The diagnosis is based on histopathological and immunohistochemical features. Immunohistochemical staining plays a critical role for the exclusion of differential diagnoses. Since atypical fibroxanthoma has an indolent clinical course, surgical excision is adequate for treatment. We present a case of atypical fibroxanthoma on the ear of a patient.

Case for diagnosis. Atypical fibroxanthoma

Abstract Atypical fibroxanthoma is a rare superficial fibrohistiocytic tumor. Clinically, it presents itself as a painless, solitary, ulcerated, and slow-growing nodule found mainly on sun-exposed areas - especially of the head and neck - of elderly individuals. The diagnosis is based on histopathological and immunohistochemical features. Immunohistochemical staining plays a critical role for the exclusion of differential diagnoses. Since atypical fibroxanthoma has an indolent clinical course, surgical excision is adequate for treatment. We present a case of atypical fibroxanthoma on the ear of a patient.

Second evaluation of the mesenteric tissue after ethanol fixation improved the total and metastatic number of lymph nodes in colorectal resections.

CONTEXT: There is a correlation between prognosis of the colorectal carcinomas and the number of retrieved and metastatic lymph nodes (LNs) from mesentery/mesorectal region. At least 12 LNs must be sampled for accurate evaluation of patients. A number of factors related to surgeon, pathologist, patient and disease could affect the total LN number. For maximizing LN yield, pathologist can use ancillary methods, as fat clearance and special solutions. AIMS: This study investigates the effect of second evaluation after ethanol fixation on total and metastatic LN number and assesses factors that influence the dissected LN number. MATERIALS AND METHODS: 177 colorectal resections were refixed with ethanol for a night, after standard LN sampling. Mesentery/mesorectal tissue was reevaluated for missed LNs. Results were statistically analyzed, P values <0.05 were considered significant. RESULTS: Mean LN number increased from 26 to 30 (median: 20 to 25, P < 0.001) after ethanol fixation. Fourteen cases had additional metastatic LNs after reevaluation of the fat tissue and 5 of them upstaged. 22.5% (44/177) of the patients had <12 LNs before ethanol fixation and this decreased to 14.3% (26/177) after ethanol fixation. Resection type and length, tumor localization, size and histologic degree, pT and neoadjuvant therapy (P < 0.001) had an impact on the LN number (P = 0.034 for histologic degree, P = 0.02 for pT, P < 0.001 for others). CONCLUSIONS: Carrying out a second evaluation with ethanol fixation increased total and metastatic LN number and could lead upstage of pN. Ethanol fixation is cost-effective, easy accessible and applicable method; it may improve accuracy of LN assessment and staging, which are important for patients' outcome.

Microcystic, elongated, and fragmented pattern of invasion in relation to histopathologic and clinical prognostic factors in endometrioid endometrial adenocarcinoma.

OBJECTIVE: To investigate the association of microcystic, elongated, and fragmented (MELF) pattern of invasion with prognostic factors in endometrioid endometrial adenocarcinoma (EEA). MATERIAL AND METHODS: Stained tissue sections from 83 cases of EEA operated by the same gynecologic oncologist were reviewed to identify cases showing MELF-type invasion in this retrospective study. The association of MELF pattern with age, tumor grade, depth of myometrial invasion, and presence of lymphovascular space invasion (LVSI) was analyzed. RESULTS: FIGO grade 2 and grade 1 tumors were evident in 53.0% and 38.6% of patients, respectively. Depth of myometrial invasion was <50% in 72.0% of patients, and LVSI was absent in 77.1%. MELF pattern was confirmed in 35 (42.2%) patients. Presence of MELF pattern was associated with significantly higher mean ± standard deviation age (62.9±6.9) years vs. 58.9±9.1 years, p=0.033), and found to be more likely in patients with high-grade tumor (FIGO grade III; 85.7% vs. 14.3%, p<0.001), deep (≥50%) myometrial invasion (78.3% vs. 21.7%, p<0.001), and presence of LVSI (94.7% vs. 5.3%, p<0.001) as compared with absence of MELF pattern. CONCLUSION: In conclusion, our findings revealed a high rate of MELF pattern among patients with EEA alongside the association of MELF pattern with poor prognostic factors such as high grade tumor, deep myometrial invasion, and LVSI.

What does the Data of 354,725 Patients from Turkey Tell Us About Cervical Smear Epithelial Cell Abnormalities? - The Epithelial Cell Abnormality Rate is Increasing - Quality Control Studies and Corrective Activity are Musts.

OBJECTIVE: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. MATERIAL AND METHOD: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. RESULTS: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells /Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. CONCLUSION: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.

Immunocytoexpression profile of ProExC in smears interpreted as ASC-US, ASC-H, and cervical intraepithelial lesion.

AIMS: We aimed to investigate the immunocytoexpression profiles of a novel assay ProEx C for topoisomerase II alpha (TOP2A) and minichromosome maintenance protein 2 (MCM2) in abnormal interpreted smears. SETTINGS AND DESIGN: Screening programs with Papanicolaou smear and high risk group human papilloma virus testing have yielded a dramatic reduction of cervical cancer incidence. However, both of these tests have limited specificity for the detection of clinically significant cervical high grade lesions. ProEx C for topoisomerase II alpha (TOP2A) and minichromosome maintenance protein 2 (MCM2) has been considered to have tight association with high grade intraepithelial lesions. MATERIALS AND METHODS: A total number of 54 SurePath cervical cytology specimens of patients previously interpreted as atypical squamous cells-undetermined significance (ASC-US), atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H), low grade squamous intraepithelial lesion (LSIL), and high grade squamous intraepithelial lesion (HSIL) were included in our study. RESULTS AND CONCLUSIONS: ProEx C was positive in 14 of HSILs (100%), 3 of 19 LSILs (16%), 2 of 4 ASC-Hs, and none of ASC-USs (0%). The ProEx C test showed very intense nuclear staining in all cytologically abnormal cells. Further studies are indicated to evaluate the diagnostic role of ProEx C.

Co-existence of BRAF V600E Gene Mutation in Tumor and Non-tumoral Surrounding Tissues in Colorectal Cancer.

BACKGROUND/AIM: The murine sarcoma viral (V-Raf) oncogene homolog B (BRAF) V600E mutation, which increases protein kinase activity in BRAF-mitogen-activated protein kinase kinase (MEK) - extracellular signal-regulated kinases (ERK) (mitogen-activated protein kinase (MAPK)) signaling, is found in 5-40% of all colorectal carcinoma cases. Proteins with this mutation are reported to be 130-fold more active, which results in induced proliferation, differentiation, cellular survival, and angiogenesis. The aim of the present study was to investigate tumor tissues, together with the surrounding non-tumoral tissues, for BRAF mutation presence, which may be an indicator for possible recurrence or prognosis as in the 'field carcinogenesis' model. MATERIALS AND METHODS: The BRAF V600E genotype of 152 colorectal adenocarcinoma paraffin-embedded specimens were determined by mutant-allele-specific amplification-polymerase chain reaction. RESULTS: According to our results, the presence of BRAF mutation increases risk of lymph node invasion by 1.55-fold [χ(2)=3.83, p=0.05, odds ratio (OR)=1.55, 95% confidence interval (CI)=1.00-2.42], histologically medium or high-grade tumor by 1.60-fold (χ(2)=4.34, p=0.030, OR=1.60, 95% CI=1.03-2.48), vascular invasion by 1.55-fold (χ(2)=3.55, p=0.05, OR=1.55, 95% CI=0.99-2.42), perineural invasion by 1.50-fold (χ(2)=3.16, p=0.07, OR=1.5, 95% CI=0.96-2.33) and the combination of these poor prognostic features by 1.54-fold (χ(2)=2.47, p=0.11, OR=1.54, 95% CI=0.93-2.53). We also found that females are more prone to having the mutation and that being female increases the risk of having this mutation by 1.54-fold (χ(2)=3.58, p=0.05, OR=1.54, 95% CI=0.97-2.44). CONCLUSION: BRAF V600E mutation in non-tumoral surrounding tissue in patients with colorectal cancer may be used as a valuable marker to foresee clinical outcome or a possible recurrence. To our knowledge, this was the first study to take into consideration the non-tumoral surrounding tissues in addition to the tumor tissue.

Patients with epithelial cell abnormality in PAP smears: correlation of results with follow-up smears and cervical biopsies.

OBJECTIVE: Cervical carcinoma has been included in the preventable diseases category ever since the use of cervical cytology in routine practice. The Pap test is an efficient screening test. We aimed to compare the cervical cytology diagnosis with biopsy and smear follow up results in our institution. MATERIAL AND METHOD: We aimed to compare the diagnosis of cytology material examined in our institution during the 2009-2012 period with their biopsy and smear follow ups. The diagnoses were compared with the follow up smears and/or cervical biopsies. RESULTS: 13610 Pap tests were examined during September 2009-July 2012. Among these cases, there were 370 atypical squamous cells of undetermined significance (ASCUS), 29 atypical squamous cells-high grade intraepithelial lesions cannot be excluded (ASC-H), 155 low grade squamous intraepithelial lesion (LSIL), 33 high grade squamous intraepithelial lesion (HSIL), and 5 atypical glandular cell (AGC) diagnoses. The ratio of atypical squamous cell (ASCUS and ASC-H) to squamous intraepithelial lesions was 2.12. Squamous intraepithelial lesion was verified in 47 of 91 ASCUS cases. Among patients who had a cervical biopsy, 52 of 64 LSIL cases and all of the 21 HSIL cases had biopsy-proven SIL. CONCLUSION: Atypical squamous cell (ASC) is the most common diagnosis in abnormal cervical cytology. As it is indefinite, ASC is used as a quality assurance parameter and the aim is to decrease its use. As the ratio of epithelial cell abnormality is variable in different populations, the ASC/SIL is a more definite variable to be used for quality assurance. The efficiency in clinical use of the cervical cytology screening test is determined by biopsy verification. Our epithelial cell abnormality, ASC/SIL ratio and cytology-histology correlation values were parallel to the literature, proving that the methods are used reliably at our institution.

Three-step approach versus see-and-treat approach in patients with cytological abnormalities.

The aim of this study was to compare the results of see-and-treat procedure with the classical three-step procedure in terms of initial cytology and LEEP reports. We searched the pathology charts of patients that had LEEP were searched retrospectively and then they were divided into 2 groups according to the presence or absence of a cervical biopsy before LEEP. There were 116 patients in the study. Of the patients with ASCUS/LSIL cytology and a positive cervical biopsy 48.4% had CIN 2-3 at LEEP, in contrast only 19% of the patients without a prior cervical biopsy had CIN 2-3 at LEEP (p=0.031); there was no statistically significant difference between the 2 procedures in patients with a HSIL and ASC-H smear result (p=0.726 and p=1.0 respectively). In conclusion patients with ASC-H and HSIL cytology see-and-treat approach seems more advantageous, avoids delay in treatment, noncompliance and risk of skipping lesions at biopsy.

Endocervical glandular involvement, multicentricity, and extent of the disease are features of high-grade cervical intraepithelial neoplasia.

This study aimed to evaluate the rate of endocervical glandular involvement, positive surgical margins, multicentricity, and disease extent between low-grade and high-grade cervical intraepithelial lesions after loop electrosurgical excision procedure (LEEP). Pathology medical records of patients who underwent LEEP were reviewed retrospectively. Patients with negative LEEP results were excluded. Loop electrosurgical excision procedure reports of patients with cervical intraepithelial neoplasia (CIN) 1, 2, and 3 were compared. There was no statistically significant difference between patients with CIN 1 (n=24), CIN 2 (n=27), and CIN 3 (n=64) when age and surgical margin positivity were considered. Endocervical glandular involvement, multicentricity, and disease extent were higher in patients with CIN 3 (P=.001, P=.002, and P=.001, respectively). In conclusion, we recommend that patients with endocervical glandular involvement, lesions involving more than two-thirds of the LEEP specimen, and multicentricity be followed up more closely.

Xanthomatous hyperplastic polyps of the stomach: clinicopathologic study of 5 patients with polypoid gastric lesions showing combined features of gastric xanthelasma and hyperplastic polyp.

Gastric xanthelasmas are uncommon benign lesions that are macroscopically well-demarcated yellow or yellow-white plaques and are microscopically formed by collections of foamy macrophages. Because gastric hyperplastic polyps may rarely be associated with xanthelasma, we aimed to report 5 cases of combined lesions showing features of gastric xanthelasma and hyperplastic polyps observed over the past 3 years at our institution among 4497 patients who underwent gastric endoscopy. The patients were 3 men and 2 women aged 45 to 78 years. The lesions were located in oxyntic mucosa, except one in the antrum, and measured 2 to 6 mm. Three patients showed associated chronic gastritis; none showed evidence of Helicobacter pylori infection. Combined lesions of hyperplastic polyp with xanthelasma appear to have an association with chronic gastritis, and the lipid accumulation may be the cause of hyperplasia in the overlying mucosa.

The Predictive and Prognostic Significance of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 Expression in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common fatal cancer and an important healthcare problem worldwide. There are many studies describing the prognostic and predictive effects of epidermal growth factor receptor 2 (c-erb-B2) and epidermal growth factor receptor 1 (EGFR), transmembrane tyrosine kinases that influence cell growth and proliferation in many tumors. OBJECTIVES: The current study aimed to investigate the expression levels of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 in hepatocellular carcinoma (HCC) and their correlation with other clinicopathologic features. PATIENTS AND METHODS: Fifty HCC cases were stained immunohistochemically with these markers. Correlations between the markers and clinicopathologic characteristics and survival rates were analyzed. RESULTS: No membranous c-erb-B2 staining was seen, whereas cytoplasmic positivity was present in 92% of HCC samples, membranous EGFR was observed in 40%, PI3K was found in all samples, and mTOR was seen in 30%, whereas reduced or absent PTEN expression was observed in 56% of samples and loss of p27 was seen in 92% of the cases. c-erb-B2 and mTOR overexpression, as well as reduced expression of p27, all correlated with multiple tumors (P = 0.041, P < 0.001, and P < 0.001, respectively). P27 loss, and mTOR and EGFR positivity were significantly correlated with AFP (P = 0.047, P = 0.004, and P = 0.008, respectively). Angiolymphatic invasion was more commonly seen in EGFR- and ERCC1-positive cases (P = 0.003 and P = 0.005). EGFR was also correlated with histological grade (P = 0.039). No significant correlations were found among PTEN , PI3K, and the clinicopathological parameters. Disease-free or overall survival rates showed significant differences among therapy modalities, AFP levels, angiolymphatic or lymph node invasions, and ERCC1 and p27 expression levels (P < 0.05). CONCLUSIONS: c-erb-B2, EGFR, mTOR, ERCC1 overexpression levels, and loss of p27 may play roles in hepatocarcinogenesis and may be significant predictors of aggressive tumor behavior. These markers were found to be correlated with certain clinicopathologic features, therapy modalities, and survival rates in the current study. These findings may help in planning new, targeted treatment strategies .

CDX2, COX2 and MUC2 expressions in Barrett's esophagus: can they be useful in determination of the dysplasia?

OBJECTIVE: The description of Barrett's esophagus which is a risk factor for esophageal adenocarcinoma has differences, and the need of goblet cells for diagnosis is controversial. However, the pathophysiology in the metaplasia seen in Barrett's esophagus is not totally understood and new methods are searched for the assessment of progression to dysplasia. We aimed to search the immunohistochemical expression of CDX2, COX2 and MUC2 in Barrett's esophagus to detect any early evidence of intestinal metaplasia or dysplasia. MATERIAL AND METHOD: The staining properties were examined in the intestinal metaplastic (goblet cell-containing columnar epithelium), columnar (non-goblet columnar epithelium), distant columnar (non-goblet columnar epithelium distant from intestinal metaplastic epithelium) and squamous epithelium in 59 pathologically diagnosed Barrett's esophagus, 22 of which having dysplasia. The results were compared statistically with Pearson and Fisher exact tests. RESULTS: The distribution of the staining of intestinal metaplastic, non-goblet columnar distant columnar, and squamous epithelium, respectively were as follows: for CDX2 76.3%, 23.7%, 1.7%, 0%; for COX-2 93.2%, 47.5%, 8%, 62.9%; for MUC2 93.2%, 11.9%, 4% and 0%. The expression of CDX2, COX2 and MUC2 in the intestinal metaplastic epithelium was higher than the expression in distant and non-goblet columnar epithelium. The expression of CDX2, COX2 and MUC2 in the foci of dysplasia decreased significantly (18.2%, 27.3%, 31.9%, and p=0.039, 0.0001, 0.0001, respectively). COX2 expression in squamous epithelium was also lower when the adjacent mucosa has dysplasia (p=0.014). CONCLUSION: The CDX2, COX2 and MUC2 expressions were seen in the intestinal epithelium having goblet cells. The use of the markers in the diagnosis is controversial but the difference in the Barrett esophagus-dysplasia sequence seems to be meaningful.

Female genital system tuberculosis: a retrospective clinicopathological study of 1,548 cases in Turkish women.

PURPOSE: The incidence of tuberculosis (TB) has increased worldwide in the past decade and it still remains an important global public health problem. METHOD: A retrospective clinicopathological study of 1,548 cases of female genital tuberculosis between 1940 and 2011 was conducted. RESULTS: The mean age of the cases was 29.49 years. Involvement of the endometrium was noted in 1,073, fallopian tubes in 164, cervix in 157, and 154 had multiple organ involvement. Clinically, 115 cases (7.4%) were diagnosed as having primary infertility and 12 cases (0.8%) as having secondary infertility. There was a coexistent carcinoma in 1.5% of the cases. Peritoneal tuberculosis in 21 cases and tuberculous lymphadenitis in 7 cases were seen as well. CONCLUSION: The clinicopathological criteria of female genital tuberculosis in the different organs are described, and special attention is paid to infertility associated with tuberculous lesion, and awareness of the fact that the disease is still with us is thus particularly important.

Xanthogranulomatous sialadenitis clinically mimicking a malignancy: case report and review of the literature.

BACKGROUND: Xanthogranulomatous tissue reaction is a well-documented process that is most common in kidney. There are other uncommon sites being documented as case reports in the literature. We would like to describe the clinicopathologic findings in a case of xanthogranulomatous sialadenitis that involved the parotid gland, which was clinically thought to be a tumoral mass, and compare it with the 4 previously reported cases. CASE REPORT: A 52-year-old man presented with a left parotid mass. Fine needle aspiration biopsy was consistent with Warthin's tumor. The mass lesion was excised. DISCUSSION: The lesion measured 2.5 × 1.5 × 1.5 cm. Microscopic examination revealed sheets of foamy macrophages centrally admixed with neutrophils, eosinophils, lymphocytes, plasma cells and scattered giant cells indicating a xanthogranulomatous reaction. As a conclusion xanthogranulomatous tissue reaction can mimic neoplasms.