The assessment of the relationship between the vascularity of FIGO Type 4-7 leiomyomas and abnormal uterine bleeding.

The current study aimed to analyse and compare the vascularity of FIGO Type 4-7 leiomyoma specimens obtained from women with or without abnormal uterine bleeding (AUB). The records of 31 women who underwent myomectomy for FIGO Type 4-7 leiomyomas in a university hospital setting were analysed. Group I (n = 16) was composed of women that were symptomatic for AUB and group II (n = 15) consisted of asymptomatic cases. The myomectomy material(s) of each case were processed with CD34 staining and evaluated by Image J® software (Image J 1.52a, Wayne Rasband National Institutes of Health, Bethesda, MD). There was no statistically significant difference between the rates of vascular areas in the specimens of the two groups (p>.05). Although areas with large vessels were higher in group I compared to group II, the difference did not reach statistical significance (p>.05). AUB caused by FIGO Type 4-7 leiomyomas seems to be related to factors other than vascular density.Impact StatementWhat is already known on this subject? Uterine leiomyomas are the most common benign gynaecologic neoplasms with a prevalence of approximately 40% in women of reproductive age. They are most often asymptomatic but when symptomatic, abnormal uterine bleeding (AUB) is one of the most commonly observed symptoms. Although there are some hypothetical explanations, the exact pathogenesis underlying leiomyoma-associated AUB has not yet been elucidated. Almost a century ago, the vascular abnormalities of fibroids were hypothesised as one of the etiopathological factors correlated with clinical symptoms, such as AUB, and current data suggest that the vascular map of leiomyomas consists of an avascular core surrounded by a vascularised capsule. To our knowledge, there are no studies in the literature comparing the histopathological evaluation of the vascularity scores of FIGO Type 4-7 leiomyomas in symptomatic (with AUB) and asymptomatic (without AUB) women.What the results of this study add? The study revealed that there was no statistically significant difference between the vascularity scores of FIGO Type 4-7 leiomyomas excised from the symptomatic and asymptomatic women. Large vessel densities also did not statistically significantly differ between the two groups.What the implications are of these findings for clinical practice and/or further research? This study revealed that AUB caused by FIGO Type 4-7 leiomyomas was related to factors other than vascular density.

Do MCF7 cells cope with metformin treatment under energetic stress in low glucose conditions?

There is a growing body of evidence about metformin being effective in cancer therapy. Despite controversies about the ways of its effectiveness, several ongoing clinical trials are evaluating the drug when used as an adjuvant or a neo-adjuvant agent. We aimed to investigate metformin's effects on proliferation, metastasis, and hormone receptor expressions in breast cancer cell line MCF-7 incubated in two different glucose conditions. MCF-7 cells were incubated in high or low glucose media and treated with various doses of metformin. The cell viability was studied using MTT test. The Ki-67, estrogen and progesterone receptor expression were evaluated by ICC and galectin-3 expression was evaluated by ELISA or spectrophotometrically. The cell viability following consecutive metformin doses in either glucose condition for 24 and 48 h represented a significant decrease when compared to control. The proliferation detected in low glucose medium following metformin at doses < 20 mM was found significantly decreased when compared to high glucose medium at 48 h. In terms of galectin-3 levels, the increase in high glucose medium treated with metformin and the decrease in low glucose medium were found statistically significant when compared to control. Progesterone receptor staining demonstrated a significant increase in low glucose medium. Our findings represent better outcomes for cancer lines incubated in low glucose medium treated with metformin in terms of viability, receptor expression and metastatic activity, and highlight the potential benefit of metformin especially in restraining the cancer cell's ability to cope energetic stress in low glucose conditions.

Pro-Gastrin Releasing Peptide: A New Serum Marker for Endometrioid Adenocarcinoma.

BACKGROUND: Gastrin-releasing peptide (GRP) is thought to play a role in the metastatic process of various malignancies. The more stable precursor of GRP, pro-GRP (ProGRP), has been shown to be secreted by neuroendocrine tumors. This study was designed to assess the validity of ProGRP as a diagnostic marker in endometrioid adenocarcinomas (EAs) of the endometrium. METHODS: Thirty-seven patients with a diagnosis of EA, 23 patients with endometrial hyperplasia, and 32 age-matched controls with normal endometrial histology were recruited for this study. Serum ProGRP and cancer antigen 125 (CA125) values were compared between groups. RESULTS: Median serum ProGRP levels were significantly higher in the cancer group compared to corresponding levels in both the hyperplasia and control groups (p = 0.008 and p < 0.001 respectively; endometrial cancer: 27.5 pg/mL; hyperplasia: 16.1 pg/mL; controls: 12.9 pg/mL). Age and endometrial thickness were positively correlated with ProGRP levels (r = 0.322, p = 0.006 and r = 0.269, p = 0.023, respectively). Receiver Operating Characteristic curve analyses for EA revealed a threshold of 20.81 pg/mL, with a sensitivity of 60.7% and specificity of 81.4%, positive predictive value of 68% and negative predictive value of 76.1%. CONCLUSION: Significantly higher ProGRP levels were observed in patients with EA than in controls. Serum ProGRP has good diagnostic sensitivity and specificity for EA.

Diagnostic Value of S100p, IMP3, Maspin, and pVHL in the Differantial Diagnosis of Pancreatic Ductal Adenocarcinoma and Normal/chronic Pancreatitis in Fine Needle Aspiration Biopsy.

INTRODUCTION: Differentiation between pancreatic ductal adenocarcinoma (PDAC) from benign mimickers is a well-known problem in cytological materials. Recent studies incorporated biological markers into this question and some studies showed that expression of S100P, IMP3, and maspin as well as nonexpression of von Hippel-Lindau gene product (pVHL) were significantly correlated with PDAC. In this study, we aimed to investigate diagnostic value of maspin, IMP3, S100P, and pVHL immunostaining in fine needle aspiration biopsies (FNABs) of pancreatic lesions. MATERIALS AND METHOD: In all, 33 cases of FNAB cell blocks of PDAC and 34 cases of surgical non-neoplastic pancreas specimens which were retrieved from the archives slides from 2007 to 2011 were included in this study. All the cases were stained with maspin, IMP3, S100P, and pVHL. Expression patterns of markers were scored and compared with benign mimickers. Test performance of each antibody and possible antibody combinations were also evaluated. RESULTS: The study was composed of 33 PDAC and 34 control cases (8 chronic pancreatitis, 3 mucinous cystic neoplasm, and 23 nontumoral pancreatic tissue of PDAC). Diagnostic sensitivity for malignancy in S100P, IMP3, and maspin was 84.8%, 81.8%, and 87.5%, respectively. Specificity of these three markers was 100%. Sensitivity and specificity of pVHL for detecting nontumoral pancreatic tissue were 100% and 81.8%, respectively. When maspin, IMP3, and S100P expression were used together as triple test, sensitivity was 62.5% and specificity 100%. However, when any two of each three markers were evaluated (triple test/dual response), sensitivity reached 93.8% and specificity 100%. CONCLUSION: We observed that dual response in triple test (positive staining with two of these three markers) of maspin, IMP3, and S100P immunocytochemistry is very sensitive and specific in differential diagnosis of PDA and non-neoplastic pancreatic lesions. pVHL may have an additional role, when triple assessment is not satisfactory.

Fine needle aspiration biopsy features with histologic correlation in mediastinal hepatoid yolk sac tumor presenting with sternum metastasis: a case report.

BACKGROUND: The hepatoid variant of yolk sac tumor (H-YST) is an exceedingly rare and highly malignant neoplasm. We present and discuss our experience with cytologic and histopathologic features of a mediastinal H-YST presenting with sternum metastasis, which to the best of our knowledge has not been previously reported. CASE: A 38-year-old man presented with a large mass on the sternum. Computed tomography of the thorax showed a large anterior mediastinal mass with sternum metastsis and multiple lung metastases. Laboratory examination revealed elevated serum alpha-fetoprotein (60,000 IU/mL). No tumor was found in the other organ systems. A percutaneous fine needle aspiration biopsy and subsequent open surgical biopsy were performed on the sternum metastasis. Cytologically, the tumor was composed of monotonous, large, round to polygonal hepatoid cells forming solid sheets and trabeculae entrapped with endothelial cells resembling hepatocellular carcinoma. Histopathologic sections of tumor showed tumor cells with eosinophilic to clear cytoplasm arranged in a solid, trabecular growth pattern, with some acinar formations. Immunohistochemical study supported the hepatoid origin. CONCLUSION: Fine needle aspiration cytology, together with the characteristic clinical presentations and specific tumor markers, is crucial to the initial diagnosis of H-YST.

Risk of HSIL (CIN 2-3) on colposcopic biopsy is minimal in postmenopausal women with LSIL on cytology and a negative HRHPV test.

BACKGROUND: Current cervical cancer screening guidelines recommend a 1-year follow-up period for patients with a postmenopausal low-grade squamous intraepithelial lesion (LSIL) who are test negative for high-risk human papillomavirus (HrHPV). The aim of this study was to assess whether such patients had an increased immediate risk of high-grade squamous intraepithelial lesion. METHODS: We assessed 54 HrHPV-negative women with postmenopausal LSIL in the Department of Obstetrics and Gynecology of our hospital between 2012 and 2013. All patients underwent liquid-based cytology and reflex HrHPV testing (for human papillomavirus [HPV] types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). Colposcopic examination and guided biopsy were performed by the same gynecologist (MO). RESULTS: The average age of the patients was 53.1 ± 3.2 years. There were 33 patients (61%) with cervical intraepithelial neoplasia (CIN) grade 1 and 21 who were non-dysplastic. None of the patients was positive for CIN 2 or any other lesions. CONCLUSIONS: If the HPV test is negative, repeat cytology after 12 months is recommended by the American Society for Colposcopy and Cervical Pathology for cases of HrHPV-negative postmenopausal LSIL. We recommend reflex HPV testing as the best choice for patients who test positive for postmenopausal LSIL by Pap smear, in line with the literature. Diagn. Cytopathol. 2016;44:969-974. © 2016 Wiley Periodicals, Inc.

The role of cytopathology in diagnosing HPV induced oropharyngeal lesions.

HPV detection in fine needle aspirates from suspected head and neck metastasis may be useful in clinching the diagnosis of HPV related oral squamous cell carcinoma. Ascertaining the HPV status of a particular tumor on cytological specimens could be useful for prognostication as HPV-related tumors appear to have a better prognosis and clinical outcome. The various techniques of detection are reviewed.

Human papillomavirus genome detection by in situ hybridization in fine-needle aspirates of metastatic lesions from head and neck squamous cell carcinomas.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) often present with metastatic disease. The diagnosis of metastatic lesions usually is determined by fine-needle aspiration. Human papillomavirus (HPV) is now being considered as a causative agent in a subset of HNSCC. The objectives of this study were, first; to search for the presence of HPV DNA by in situ hybridization (ISH) in metastatic lesions from HNSCC using alcohol-fixed, archival, cytopathologic material; second, to characterize the cytologic features of HPV-positive metastatic lesions of HNSCC; and, third, to determine whether there is a correlation between the presence of HPV DNA and the origin of metastatic lesions. METHODS: The authors performed chromogenic ISH analysis for HPV DNA on fine-needle aspiration materials from metastatic lesions from 26 patients with HNSCC. Along with the ISH analysis, a detailed cytologic review was performed, and cytopathologic features were recorded. The HPV DNA status in metastatic lesion was correlated with cytopathologic features and primary tumor location. RESULTS: The integration of HPV DNA was visualized microscopically on tumor cell nuclei in 15% of aspirates. The anatomic locations of the study samples were as follows: 16 lymph node aspirates (11 cervical lymph nodes and 5 lymph nodes at other sites other), 5 tracheostomy sites, and 5 miscellaneous sites located on the head and neck area. Cytologic review revealed 13 keratinized and 13 nonkeratinized metastatic tumors. HPV DNA was detected in four metastatic sites (three lymph nodes and one tracheostomy site). All HPV DNA-positive tumors were of the nonkeratinizing type (P < 0.05; Fisher exact test). The origins of HPV-positive tumors included two laryngeal sites, one nasopharyngeal site, and one oral cavity site. CONCLUSIONS: The current findings showed that archival cytology slides can be used for HPV DNA detection with ISH. The results also showed that HPV DNA-containing HNSCC has distinctively nonkeratinizing cytologic features. The authors concluded that HPV DNA not only is involved in the initiation of tumoral processes but also plays an important role in the development of metastatic disease.

Mutational analysis of K-ras segregates ovarian serous carcinomas into two types: invasive MPSC (low-grade tumor) and conventional serous carcinoma (high-grade tumor).

We previously proposed a dualistic model for ovarian serous carcinogenesis. One pathway involves the stepwise development of invasive micropapillary serous carcinoma (MPSC) from serous borderline tumor (atypical proliferative serous tumor) to noninvasive and then invasive MPSC. The carcinomas that develop in this fashion are characterized by low-grade nuclei and frequent K-ras mutations. They generally pursue an indolent course. In the other pathway conventional serous carcinoma (CSC) develops from the ovarian surface epithelium without what appears to be intermediate stages. These tumors display high-grade nuclei, wild-type K-ras, and are very aggressive. Some of these CSCs display micropapillary architecture and simulate invasive MPSCs. This raises the possibility that these CSCs develop from an invasive MPSC. To address this question we reviewed 31 moderately and poorly differentiated CSCs and identified 7 with morphological features of invasive MPSC. These seven tumors exhibited micropapillary architecture in at least 25% of the tumor but contained high-grade nuclei. The 31 tumors were assessed for K-ras mutations using digital polymerase chain reaction-based analysis. Despite their micropapillary architecture, all 7 CSCs with micropapillary features contained wild-type K-ras as did the other 24 pure CSCs. The results indicate that CSCs with micropapillary features are not derived from invasive MPSCs. The molecular findings also support the view that ovarian serous carcinomas should be graded as low- and high-grade tumors.

Multinodular hydropic leiomyoma of the uterus with perinodular hydropic degeneration and extrauterine extension.

Multinodular hydropic leiomyoma (MHL) of the uterus is one of the rarest variants of uterine leiomyomas and can create some diagnostic problems. Only five cases have been reported previously. We describe an MHL with perinodular hydropic degeneration in a 48-year-old woman. Gross examination revealed a large and predominantly intramural, edematous multinodular uterine tumor and extrauterine, small grape-like nodules overlying the lateral surface of the uterine serosa. Histologically, the tumor was composed of extra-intrauterine benign, small smooth muscle nodules with perinodular hydropic degeneration, prominent intramural dissecting growth pattern, and satellite nodules closely resembling vascular invasion. Immunohistochemically, these cells stained for desmin, smooth muscle actin and vimentin. The patient had no evidence of disease for 18 months after hysterectomy. Multinodular hydropic leiomyoma is a clinically benign tumor and should not be confused with intravenous leiomyomatosis and some other unusual leiomyoma variants.