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1. Periocular basal cell carcinoma: demographic, clinical, histological and immunohistochemical evaluation of a series of 39 cases

Claudia Florida Costea, Mihaela Dana Turliuc, Anca Sava, Gabriela Dimitriu, Gabriela Florenta Dumitrescu, Cristina Danca, Andrei Ionut Cucu, Camelia Margareta Bogdanici, Irina Iuliana Costache, Catalin Mihai Buzduga, Manuela Ciocoiu, Daniela Maria Tanase, Raluca Alina Dragomir, Alexandru Carauleanu

Background: Basal cell carcinoma (BCC) is the most frequent malignant epithelial tumor of the periocular area. The clinical and histological classification of periocular basal cell carcinoma (pBCC) is essential in order to establish the risk of recurrence and to compare the results of the treatment. Until now, there is no unitary histological classification of pBCC. Aim: The aim of this study is to identify the demographic, clinical and histopathological characteristics of adult patients with pBCC, in order to obtain useful data for comparison in other investigations and to identify the histological origin of this eyelid tumor, as there are only hypothesis on this issue. Materials and Methods: A descriptive retrospective study was conducted on a series of 39 consecutive patients over the age of 20, who were surgically treated for pBCC in the 2nd Ophthalmology Clinic of the Prof. Dr. Nicolae Oblu Emergency Clinical Hospital from Iasi, Romania, over an 11-year period (July 2007-February 2018). The analyzed data were the following: date of resection, patient age at resection, gender, tumor location, histological subtype, and immunohistochemical (IHC) expression patterns of anti-cytokeratin (CK) antibodies (anti-CK AE1/AE3, anti-CK5/6, anti-CK7, anti-CK17, anti-CK19, anti-CK20) and anti-epithelial membrane antigen (EMA) antibody. Results: A total of 39 histopathologically diagnosed cases of pBCC were evaluated. The mean age at resection was of 66 years (range: 26-87 years). As for gender, 17 (43.6%) were male patients, with a mean age of 64.84 years (range: 26-78 years) and 22 (56.4%) were female patients, with a mean age of 66.68 years (range: 46-87 years). The pBCC occurred on the right side in 18 (46.2%) cases and on the left in 21 (53.8%) cases. Of all removed specimens, 24 (61.53%) involved the lower eyelid, seven (17.94%) the medial canthus, five (12.82%) the upper eyelid, and three (7.62%) lacked the specification of the site. The most common histological subtype was nodular, accounting for 26 (66.7%) cases. Adenoid BCC was identified in four (10.3%) cases, and morpheaform in one (2.6%) case. Squamous differentiation (basosquamous subtype) was identified in eight (20.5%) cases. The IHC profile of pBCC included: strong immunopositivity for CK AE1/AE3, and CK17 all histological subtypes, and CK5/6 positivity only in squamous differentiation areas. No immunopositivity was identified for CK19, CK20, and EMA IHC staining. Conclusions: Our retrospective study indicates that most of pBCCs developed particularly in elderly female patients and tumors were located in the lower eyelid with a left side and lower eyelid preferences. Most of our pBCC cases were histologically classified as nodular subtype, and morpheaform and basosquamous form affected mostly the lower eyelid. pBCC IHC profile showed a strong immunopositivity for CK17, thus suggesting that the origin of this cancer is in the follicular germinative cells. We can conclude that our results showed a demographic, clinical, histological, and IHC profile which seems to be representative for Central and Eastern European countries, maybe due to the same genetic predisposition and environmental factors.

Corresponding author: Mihaela Dana Turliuc, Associate Professor, MD, PhD; e-mail: turliuc_dana@yahoo.com; Anca Sava, Professor, MD, PhD; e-mail: dr.anca.sava.68@gmail.com

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2. Monophasic sarcomatoid eccrine porocarcinoma. Report of a case and literature review

Jose-Fernando Val-Bernal, Marta Mayorga, Maria Martino, Sergio Sanchez-Santolino

Sarcomatoid porocarcinoma (SP) is a rare subtype of porocarcinoma composed of both malignant epithelial and sarcoma-like components. To our knowledge, only eight cases of this neoplasm have been published, all of them biphasic. A 42-year-old man presented with a latero-cervical nodule that had been noted for about five months. Histopathological study revealed an infiltrative tumor within the dermis and hypodermis without connection to epidermis, whose diagnosis was monophasic sarcomatoid eccrine porocarcinoma (SEP). The study of nine cases de SP, including the present, revealed that the ages of the patients ranged from 42 to 89 years (mean 72.3 years). There was no clear difference in the incidence with respect to gender. The location of the tumor was most common in the head and neck, followed by lower extremity. The size ranged from 2.5 cm to 3.5 cm (mean 3 cm). At the time of diagnosis, six (66.7%) lesions were ulcerated. No case was clinically diagnosed. Residual poroma was present in six (66.7%) cases. Only one case showed apocrine differentiation. Mitoses and comedonecrosis were frequent. Of the cases published, only four had a follow-up of at least 16 months. One patient succumbed to the tumor. We report for the first time a case of monophasic SEP without epidermal connection. The patient presented a regional lymph node metastasis three months after excision. The main differential diagnosis includes primary dermal melanoma and other rare variants of cutaneous melanoma, primary cutaneous clear cell sarcoma, primary cutaneous synovial sarcoma, and cutaneous metastasis from visceral sarcomatoid carcinoma.

Corresponding author: Jose-Fernando Val-Bernal, Professor, MD, PhD; e-mail: fernando.val@unican.es

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3. Immunoexpression of MMP-8, MMP-9 and TIMP-2 in dilated cardiomyopathy

Radu Mitrut, Alex Emilian Stepan, Claudiu Margaritescu, Bianca Catalina Andreiana, Ana Maria Kesse, Cristiana Eugenia Simionescu, Constantin Militaru

Alteration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) expression has been studied for various cardiac diseases, including dilated cardiomyopathy (DCM), with the significance of surrogate markers of extracellular matrix (ECM) remodeling. In this study, we determined the MMP-8, MMP-9 and TIMP-2 immunoexpression in the heart of patients diagnosed with DCM in relation to a histological composite score (HCS). The study included 40 cases of heart fragments that were processed by the usual paraffin inclusion technique, followed by a semi-quantitative evaluation of histopathological parameters, which summed, allowed the establishment of a HCS. Subsequently, the cases were immunohistochemically processed for MMP-8, MMP-9 and TIMP-2, followed by the semi-quantitative evaluation of their expression intensity. MMP-8 was identified only in myocardiocytes, while MMP-9 and TIMP-2 were present in both myocardiocytes and stroma, but with different intensity. The increasing intensity of MMP-8 and TIMP-2 immunoreactions was significantly associated with low HCS. In case of MMP-9, the immunostaining intensity analysis in relation to the HCS level revealed insignificant differences, but we found an association of increased and moderate intensity with low HCS. The imbalance between TIMPs and MMPs disrupts the ECM architecture and contributes to the remodeling process in DCM, aspect that can be used in the development of new clinical therapies.

Corresponding author: Alex Emilian Stepan, Associate Professor, MD, PhD; e-mail: astepan76@yahoo.com

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4. Complex evaluation in patients with knee osteoarthritis

Magdalena Rodica Traistaru, Diana Kamal, Daniela Teodora Maria, Marian Valentin Zorila, Dragos Ovidiu Alexandru, Otilia Constantina Rogoveanu, Mirela Radu, Kamal Constantin Kamal

Knee osteoarthritis (KOA) is a very common, slowly progressive and incurable articular disease resulting in the breakdown of cartilage and bone in the joint, which causes significant discomfort, pain and disability, with a significant socio-economic impact. The aim of our observational study for patients with symptomatic KOA was to investigate the changes of C-terminal telopeptide of type II collagen (CTX-II) in serum pre and post a complex rehabilitation program and to establish the correlation between all studied parameters [clinical, functional, serum CTX-II (sCTX-II) and histological aspects obtained through arthroscopy]. During 2016-2017, we performed an observational study including 24 patients, between 59 and 76 years old, diagnosed with KOA. Studied patients were completely assessed before (T1) and four months after a complex rehabilitation program (T2). The measured parameters were stiffness, pain, and physical function and we used the Visual Analogue Scale (VAS) for pain, with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), sCTX-II value obtained by enzyme-linked immunosorbent assay (ELISA) test, histological assessment of knee cartilage after arthroscopy. In the histological assessment of our patients, we observed that the cells of the superficial areas were round and hypertrophic, the cartilage tissue had few proteoaminoglycans and glycosaminoglycans, with an airy aspect of the matrix and degenerate cells, numerically reduced. After positive diagnosis, the complete treatment, including the rehabilitation program, seems to be the ideal option for improving the CTX-II values, as well as the quality of life in KOA patients.

Corresponding author: Dragos Ovidiu Alexandru, Associate Professor, MD, PhD, MSc; e-mail: dragosado@yahoo.com; Diana Kamal, MD, PhD, MSc; e-mail: dianakamal84@gmail.com

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5. The role of interleukin-6 as an early predictor of sepsis in a murine sepsis model

Iudita Maria Badea, Razvan Azamfirei, Bianca Liana Grigorescu, Gergo Raduly, Adina Hutanu, Marius Petrisor, Alexandra Elena Lazar, Emoke Almasy, Raluca Stefania Fodor, Adrian Man, Janos Szederjesi, Simona Gurzu, Leonard Azamfirei, Anca Meda Georgescu

Aim: Evaluating the role of interleukin-6 (IL-6) as an early predictor of sepsis in a murine model. Materials and Methods: The study divided 26 Wistar rats into two experimental groups in which sepsis was induced through the intraperitoneal injection of different Escherichia coli cultures [Group 1: Extended-spectrum beta-lactamase (ESBL)-producing culture and Group 2: Standardized ATCC35218 culture] and a control group. IL-6 levels were determined at 5 and 24 hours post-inoculation and immunohistochemistry (IHC) was performed on tissue samples from the sacrificed animals. Results: Mean plasma IL-6 levels in Group 1 peaked at 5 hours [37.4 pg/mL; standard deviation (SD) = 2.4 pg/mL] and decreased at 24 hours (34 pg/mL; SD=3.2 pg/mL) after inoculation. IL-6 levels in Group 1 were elevated compared to Group 2, at 5 hours (33.7 pg/mL; SD=3.3 pg/mL; p=0.019) and non-significantly so at 24 hours (32.5 pg/mL; SD=2.4 pg/mL; p=0.233). The results did not show an increase over control levels at either 5 hours (37.6 pg/mL; SD=3.4 pg/mL) or 24 hours (40.8 pg/mL; SD=2.9 pg/mL) after inoculation. The IHC shows a varying degree of IL-6 expression across all organ types studied. No statistically significant correlations were found between the tissue level quantification of IL-6 and serum values at 24 hours in either group. Conclusions: For an early stage of infection/inflammation, serum levels of IL-6 are not correlated with tissue-level inflammation disproving a potential role of IL-6 as a very precocious diagnostic and predictor test. Accumulation of IL-6 in lung, kidney and spleen tissue can be observed from the beginning of inflammation.

Corresponding author: Bianca Liana Grigorescu, Lecturer, MD, PhD; e-mail: biancagrigorescu20@yahoo.com; Leonard Azamfirei, Professor, MD, PhD; e-mail: leonard.azamfirei@umftgm.ro

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6. Letter to the Editor. Vascular foam cell dots in thyroid angioma-like lesions: fine needle aspiration or contrast substance-related lesions?

Adriana Handra-Luca, Habib Mohamed Ben Romdhane

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Corresponding author: Adriana Handra-Luca, MD, PhD; e-mails: adriana.handra-luca@aphp.fr, adriana.handra-luca@hotmail.com, adriana.handra-luca@univ-paris13.fr

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7. Unroofed coronary sinus: update on diagnosis and treatment

Eliza-Elena Cinteza, Cristina Filip, Gabriela Duica, Georgiana Nicolae, Alin Marcel Nicolescu, Mihaela Balgradean

Unroofed coronary sinus (UCS) is among the rarest congenital heart malformations in pediatric practice. Often, they are associated with persistent left superior vena cava (PLSVC) draining into the left atrium, and in this situation, there is a double intracardiac shunt, right-to-left and left-to-right. They are asymptomatic in the majority of the cases. Each ordinary imagistic method (transthoracic echocardiography, contrast transesophageal echocardiography, angiography) can be helpful in finding the diagnosis, but enhanced computed tomography scan can give an irrefutable diagnosis. The surgical intervention may consist in the recreation of a roof for the coronary sinus, and anastomosis of the PLSVC to the right atrial appendage.

Corresponding author: Eliza-Elena Cinteza, Lecturer, MD, PhD; e-mail: elizacinteza@yahoo.com

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