her2 status in premalignant dysplastic gastric lesions

Abstract is not required for Editorialis not required for Editorial (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 6 No. 8, August 2015. ISSN – [0976-3198] Int J Case Rep Images 2015;6(8):530–533. www.ijcasereportsandimages.com Barresi et al. 530 CASE REPORT OPEN ACCESS HER2 status in premalignant dysplastic gastric lesions Valeria Barresi, Antonio Ieni, Giovanni Tuccari The epidermal growth factor receptor family is constituted by four members with similar structures: HER1/erbB1, HER2/erbB2, HER3/erbB3 and HER4/ erbB4. These receptors play an important role in the processes of proliferation and differentiation of normal cells [1]. The binding of the ligand to these receptors causes the creation of homodimers and heterodimers as well as the activation of downstream signaling pathways [1]. Hence, any aberrations in their structure or function can cause transformation of normal cells to malignant cells with consequent tumor development and progression [1]. However, on the basis of results from an international randomized controlled trial (ToGA), the patients with advanced gastric adenocarcinoma (GC) positive for HER2 over-expression could be eligible for a target treatment with trastuzumab [2]. A significant reduction in the risk of mortality was appreciable when trastuzumab was added to the chemotherapy regimen [2]. There is general agreement with regard to a higher HER2 positivity in gastroesophageal junction cancer (24–35%) compared with GC (9.5–21%) [3]. The rate of HER2 immunoreactivity seemed to be vary variable in relation to the different neoplastic histotype of the stomach [4]. Generally, all studies have reported a prevalence of HER2 amplification in advanced GC of Valeria Barresi1, Antonio Ieni1, Giovanni Tuccari1 Affiliations: 1Azienda Ospedaliera Universitaria "Gaetano Martino" and Department of Human Pathology "Gaetano Barresi", Section of Anatomic Pathology, University of Messina, Messina 98123, Italy. Corresponding Author: Giovanni Tuccari, MD, Full Professor of Pathology Department of Human Pathology, "Gaetano Barresi" University of Messina, A.O.U. "Policlinico G. Martino" Pad. D, Via Consolare Valeria, 98125 – MESSINA (Italy); Ph: +39-90-2212539; Fax:+39-90-2928150 E-mail: [email protected] Received: 16 June 2015 Published: 01 August 2015 EdiTO iAlS OPEN A CE S intestinal type (81.6–91%) in comparison with diffuse or mixed ones (4–7.9%) [4]. In addition, a progressive increase in HER2 overexpression has been appreciated moving from the poorly cohesive WHO histotype to mitochondrion-rich adenocarcinomas (MRC), tubular adenocarcinomas and hepatoid carcinomas (HAS), these latter representing the top rate of HER2 positivity, characterized by an extremely poor prognosis [4]. Furthermore, HER2 overexpression was also significantly associated with a high grade, advanced stage and high Ki67-LI value, becoming thus an additional morphological parameter able to affect the mortality of patients with GC [5]. Finally, some investigations have been recently reported regarding the concordance of HER status in primary gastric cancer and corresponding lymph nodes or distant metastases, with either positive or negative conversion in HER2 overexpression [6, 7]. Generally speaking, chronic atrophic gastritis and intestinal metaplasia of the stomach have been regarded to as pre-neoplastic lesions, even if data from literature points towards the existence of other pathways, in which intestinal metaplasia may not play a role, as described by Japanese authors [8]. However, the true precancerous gastric lesion should be considered dysplasia, which includes cellular and structural atypia, also codified under the term intraepithelial neoplasia (IEN), a pathological condition that lies between atrophic gastritis and GC [9]. It is well known, that IEN may develop in the gastric or intestinal metaplastic epithelium and it can be categorized into four categories: indefinite for intraepithelial neoplasia, low-grade intraepithelial neoplasia (LG-IEN), high-grade intraepithelial neoplasia (HG-IEN) and suspicious for invasive cancer [10]. The IEN histological distinction as low or high-grade depends on the severity of architectural and cytological atypia. In LG-IEN, the mucosal structure is only faintly modified maintaining tubular differentiation with the proliferative zone limited to the outward portion, whereas HG-IEN exhibits increasing distortion of the mucosal architecture, resulting in crowded possibly irregular glands with obvious cellular atypia and proliferative activity distributed throughout the lesion [10]. High-grade intraepithelial neoplasia i

CD34 and CD105 Microvessels in Resected Bone Specimen May Implicate Wound Healing in MRONJ

Clinical treatment outcome of MRONJ (medication-related osteonecrosis of the jaw) surgery despite radical osseous removal and primary closure healing still shows differences in terms of outcome and disease recurrence. The study aims to assess the rate of angiogenesis of MRONJ lesions in order to understand the impact of angiogenesis and neoangiogenesis status on MRONJ surgical treatment outcome. This is the first study correlating microvessel density with prognosis in MRONJ surgically-treated patients. The immunohistochemical expression of CD34 and CD105 in MRONJ specimens obtained from surgically-treated patients was evaluated. The most vascularized areas detected by CD34 and CD105 were selected and the microvessel density value of the samples was registered. Samples were retrospectively divided according to the clinical outcome of MRONJ surgical treatment, dividing patients into two groups, “healed” and “not healed”. Statistical analysis was performed to assess if neovessels could influence treatment outcome in patients undergoing radical surgery. In the examined cohort, this value was highly predictive of better treatment outcome after radical surgery of MRONJ. Understanding of angiogenesis-dependent factors deserves further attention as a future target for MRONJ prevention and therapies

An Updated Review of Cribriform Carcinomas with Emphasis on Histopathological Diagnosis and Prognostic Significance

Cribriform is a histopathological term used to describe a neoplastic epithelial proliferation in the form of large nests perforated by many quite rounded different-sized spaces. This growth pattern may be seen in carcinomas arising in different organs, and shows important prognostic implications. Therefore, recent data in literature suggest that cribriform carcinoma is a histologically and clinically distinctive type of tumour that should be separated from other similar tumour types. In this article, the pathology of cribriform adenocarcinoma of the prostate, lung, breast, stomach, colon, thyroid, and skin is discussed with particular reference to morphologic and immunohistochemical features, differential diagnosis, and clinical behaviour

Age as a risk factor in the occurrence of pneumothorax after transthoracic fine needle biopsy: Our experience

AbstractTransthoracic needle biopsy (TTNB) of the lung is a well-established technique for diagnosing many thoracic lesions, and is an important alternative to more invasive surgical procedures. Complications of TTNB include pneumothorax, hemoptysis, hemothorax, infection, and air embolism, with the most common complication as pneumothorax. From June 2011 to June 2014 we performed a prospective study of 188 patients who underwent TTNB with CT guidance at University Hospital of Salerno, Italy. Pneumothorax occurred in 14 of 188 biopsies (7.45%). With the respect of age of patients pneumothorax occurred more frequently in patients aged 60–70 years, while it was less frequent in younger (<60 years) and older patients (>70 years). In conclusion, data of our prospective study documented that CT-guided TTNB is a safe and reliable procedure in elderly patients with suspected chest malignancy and is well tolerated

Pleural diffuse mesothelial lesions: A challenge for pathologists

Malignant mesothelioma (MM) is a highly aggressive tumor deriving from the mesothelial cells normally lining the body cavities.  Histologically, MM is classified in three major histopathological patterns, such as epithelioid, sarcomatoid and mixed type. It is well known that the diagnosis of MM can be very challenging, especially in small bioptic fragments or cytological specimens. The most common diagnostic pitfalls involve the distinction between primary epithelioid MM and metastatic adenocarcinoma as well as that between reactive epithelial/fibrous benign proliferations and MM. Recently, a pathologist’s panel suggested new practical strategies and recommendations for the MM diagnosis, regarding the interpretation of histo-cytological features and the composition of appropriate immunohistochemical algorithm. Finally, according to the updated international guidelines, morphological data require a careful clinico-pathological correlation to achieve an accurate diagnosis of pleural lesions

Corneal Structural Changes in Nonneoplastic and Neoplastic Monoclonal Gammopathies

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Immunohistochemical evidence of Aquaporin 1 (AQP1) in Fluoroedenite-induced mesotheliomas: a preliminary report

Malignant pleural mesothelioma (MPM) is a malignant tumour of the serosal membranes lining the pleural cavity, which has been linked with the occupational exposure to asbestos fibres; however, it rarely occurs in individuals not exposed to these fibres. In this regard, fluoroedenite (FE) fibres have been linked to increased mortality from pleural mesothelioma in Biancavilla, a town of eastern Sicily (Italy). These fibres are similar in size and morphology to amphibolic asbestos fibres and have been used as a building material for road paving and buildings in the town of Biancavilla and countries nearby. The aim of the present study was to investigate the immunohistochemical expression of Aquaporin 1 (AQP1) in a cohort of patients affected by MPM; taking into consideration its suggested independent prognostic role in asbestos related MPM, the possible correlation with clinicopathological parameters and patients outcomes was also evaluated

HER2 status in advanced gastric cancer: the dark side of the moon

The present study evaluated HER2 status between primary gastric and paired metastatic disease to lymph nodes, collecting 62 formalin-fixed paraffin-embedded representative tissue blocks as well as synchronous metastatic lymph nodes by immunohistochemistry and FISH. The discordant HER2 pooled rate, regardless either negative or positive conversion, was 9.26% in primary gastric carcinoma and corresponding nodal metastasis. Moreover, a high level concordance in HER2 expression between primary carcinoma and synchronous metastatic lymph nodes was achieved in 90.74% of cases. In our opinion, the observed event of discordant HER2 status should be ascribed to intra-tumor heterogeneity. In any case, the shift from positive to negative HER2 expression suggests that Trastuzumab could be the targeted treatment choice, while the opposite shift should be evaluated by a simultaneous HER2 determination in both primary and metastatic lymph nodes

Occult hepatitis B virus infection predicts non-alcoholic steatohepatitis in severely obese individuals from Italy

Obesity is associated with\ua0non-alcoholic fatty liver (NAFL), which may progress towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B virus infection (OBI) may contribute to hepatic damage in patients with\ua0chronic liver disease\ua0of different aetiologies (eg\ua0HCV, alcohol). However, information on the prevalence and clinical impact of OBI in obese individuals is lacking. The aims of this study were to investigate NASH prevalence and risk factors in obese people who underwent bariatric surgery

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study)

Simple Summary There is a lack of literature on the role of molecular classification in patients with morphological low-risk EC. We aimed to evaluate the incidence and prognostic role of p53 mutations in this specific subgroup of patients. Our findings show that 4.9% of low-risk EC are p53abn; the OR for the recurrence of p53abn versus p53wt patients was 5.23-CI 95% 0.98-27.95, p = 0.053. No difference in OS was observed between the two groups. Recurrences were mostly local and occur two years after diagnosis. Our data might serve as a valuable tool for clinicians' everyday practice, but larger prospective studies are urgently needed.Abstract No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis