ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Vol. 66 No. 1, January-March 2025

1. Gestational trophoblastic diseases - literature review and atypical case reports

Anca-Maria Istrate-Ofiteru, Sidonia Catalina Vrabie, George-Lucian Zorila, Marian Valentin Zorila, Razvan Grigoras Capitanescu, Elena Iuliana Anamaria Berbecaru, Ilona Mihaela Liliac, Larisa Iovan, Bianca Catalina Andreiana, Valentin-Octavian Mateescu, Cristina Jana Busuioc, Dominic-Gabriel Iliescu, Marius Cristian Marinas

Gestational trophoblastic disease (GTD) arises from the abnormal development of trophoblastic tissue and encompasses a wide range of benign and malignant conditions. There is evidence that malignant transformation can occur in atypical areas of the placenta. A complete diagnosis of GTD involves assessing the signs and symptoms, with the most common being vaginal bleeding and pelvic-abdominal pain, alongside laboratory data and variations in human chorionic gonadotropin (hCG) levels. Imaging exploration, both local and distant, is critical for assessing tumor areas, utilizing various techniques such as ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT. Furthermore, a detailed histopathological analysis is essential, which includes classical examination with Hematoxylin-Eosin (HE) staining to highlight the presence of abnormal villi or transformed trophoblasts. Immunohistochemical staining with antibodies like anti-cytokeratin 7 (CK7) marks tumor cells with trophoblastic origin, while anti-p57 is present in incomplete hydatidiform moles (HMs) and absent in complete HMs (CHMs). The tumor proliferation index, obtained by calculating the density of tumor cells undergoing division and immunolabeled with the anti-Ki67 antibody, along with the invasion into the myometrial structure among myocytes immunolabeled with anti-alpha-smooth muscle actin (alpha-SMA) antibody, helps establish a definitive diagnosis and classify GTD. Diagnosis remains a challenge even among expert gynecologists and pathologists. This study has gathered data from literature and analyzed the evolution of a series of atypical cases and the management strategies related to the diagnosis and therapeutic opportunities of GTD.

Corresponding author: Razvan Grigoras Capitanescu, Lecturer, MD, PhD; e-mail: razvan.capitanescu@gmail.com; Marian Valentin Zorila, Lecturer, MD, PhD; e-mail: zorilavaly@yahoo.com.au

Abstract   Open Paper   Download PDF

2. Pancreatic neuroendocrine tumors - going beyond surgery. Literature review and experience of a tertiary center

Rucsandra-Ilinca Diculescu, Madalina Stan-Ilie, Christopher Jesse Vlad Pavel, Oana-Mihaela Plotogea, Gabriel Constantinescu, Vasile Sandru, Doina Istratescu, Valeriu Bogdan Popa, Valentin Enache, Sandica Nicoleta Bucurica, Catalina Poiana

Background: Surgery is the standard therapy for pancreatic neuroendocrine tumors (pNETs), but since post-resection fistulae and other surgery related complications are common, new minimal invasive approaches are emerging. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising tool for pNETs, with a good safety profile and favorable results. Patients, Materials and Methods: This is a single-center, retrospective case series including all patients with functional (F) and non-functional (NF) pNETs treated with EUS-RFA in the Department of Gastroenterology, Emergency Clinical Hospital of Bucharest, Romania, between March 2023 and March 2024 and followed for a mean period of 11.6 months. Technical success, clinical, sonographic and radiological response, adverse events (AEs) rate and severity were assessed. Case series: A total of five out of nine EUS-RFA were performed for pNETs, with a majority of NF-pNETs. In this pNET group, the mean size of the lesions was 13 mm. Technical success was achieved in 100% of patients and persistent clinical remission of hypoglycemia in the insulinoma case was attained. In the NF-pNET subgroup, two patients were successfully radiologically treated with complete disappearance of the lesions, one lesion showed cystic transformation, and one had modest size reduction at follow-up imagery. One procedure-related early AE occurred: mild abdominal pain with quick resolution. No major complications, nor death were reported. Conclusions: Reports from this literature review and small case series suggest that EUS-RFA can be effective in both F- and NF-pNETs, offering the best combination of real-time imaging guidance and minimal invasiveness with no severe AEs and short hospital stay.

Corresponding author: Madalina Stan-Ilie, Associate Professor, MD, PhD; e-mail: drmadalina@gmail.com

Abstract   Open Paper   Download PDF

3. Endometrioid adenofibroma of ovary - a literature review

Laurentiu Augustus Barbu, Liviu Vasile, Tiberiu Stefanita Tenea-Cojan, Gabriel Florin Razvan Mogos, Valeriu Surlin, Ionica Daniel Vilcea, Liliana Cercelaru, Stelian Stefanita Mogoanta, Nicolae-Dragos Margaritescu

Background/Objectives: Ovarian neoplasms are the third most common gynecological cancer and carry a poorer prognosis than breast cancer. Endometrioid borderline ovarian tumors (EBOTs) are intermediate epithelial lesions, histologically showing glandular patterns with mild to moderate atypia and no stromal invasion. Study selection for review: A comprehensive electronic search was conducted on PubMed to identify risk factors and etiological determinants associated with ovarian endometrioid adenofibroma (EA). Case presentation: A 27-year-old woman with a left ovarian cyst underwent a laparoscopic procedure to remove the adnexa after imaging showed a 6 cm mass. Surgery was successful, and she was discharged without complications. Conclusions: This study highlights the diagnostic challenges of EBOTs, the essential role of immunohistochemistry, and the need for careful surgical and fertility-preserving strategies. It also draws attention to possible risks linked to fertility treatments. Fertility preservation is crucial in young patients, favoring uterine and ovarian conservation. In early-stage, small, non-invasive tumors, laparoscopy is the preferred approach. EAs are uncommon benign ovarian tumors, accounting for approximately 1% of epithelial neoplasms, and are predominantly unilateral.

Corresponding author: Liviu Vasile, Lecturer, MD, PhD; e-mail: vliviu777@yahoo.com; Ionica Daniel Vilcea, Professor, MD, PhD; e-mail: ionica.vilcea@umfcv.ro

Abstract   Open Paper   Download PDF

4. Exploring the role of inflammation in age-related macular degeneration: new insights and implications for future therapies

Paul-Gabriel Borodi, Mark Slevin

The retina consists of one of the body s most delicate organs, being sensitive to various metabolic disturbances, vascular abnormalities and inflammatory processes. Age-related macular degeneration (AMD) impacts millions of people worldwide and represents a notable cause of blindness. Chronic inflammation, implicated in several degenerative diseases including Parkinson s and Alzheimer s diseases, as well as atherosclerosis, has been linked to AMD. Both histopathological and genetic investigations have underscored the immune system s role in AMD progression. The objective of this literature review was to summarize the actual knowledge, identify research gaps and to serve as a basis for future studies regarding the correlations between inflammation and AMD. We conducted a thorough search of the primary databases (Web of Science, Cochrane Library, PubMed/MEDLINE), using keywords such as age-related macular degeneration, inflammation, neurodegeneration, and C-reactive protein. We included systematic reviews and meta-analyses that offer the most relevant results in this research area. We also included the results from recent studies that have not yet been widely approached. Our strategy also consisted of looking for relevant articles in the reference list.

Corresponding author: Paul-Gabriel Borodi, MD; e-mail: borodi.paul@yahoo.com

Abstract   Open Paper   Download PDF

5. COVID-19 - multisystem disease

Roberta Andreea Cercel, Florin Ionut Buibas, Mircea-Sebastian Serbanescu, Adina Andreea Mirea, Florentina Dumitrescu, Ionica Pirici, Oana Badea-Voiculescu, Laurentiu Mogoanta, Mihai-Marius Botezat

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), caused a global public health crisis, with a significant impact on multiple body systems. This virus, a member of the Coronaviridae family, shows approximately 80% genomic similarity to SARS-CoV and approximately 50% genomic similarity to Middle East respiratory syndrome coronavirus (MERS-CoV). The spike (S) protein plays an essential role in the pathogenesis of the virus, as it facilitates its entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. In addition to the respiratory system damage, SARS-CoV-2 infection causes a variety of gastrointestinal (GI), neurological, cardiovascular (CV), ocular, renal, etc. clinical manifestations. Neurological complications, such as anosmia, ague, headache, encephalitis and cerebrovascular events, were frequently observed, being attributed to both direct viral invasion and a very strong systemic inflammatory response. GI symptoms such as diarrhea, nausea and vomiting are common and may occur independently of respiratory symptoms, and the presence of viral ribonucleic acid (RNA) detected in fecal samples suggests possible fecal-oral transmission. The CV system is affected by myocardial damage, inflammation and coagulation disorders, with an increased risk of thromboembolic events. At the ocular level, the virus was identified in ocular secretions, and conjunctivitis, uveitis and episcleritis were observed in about 11% of patients. Renal involvement, manifested by acute kidney injury, was detected in 0.5-7% of cases. In conclusion, SARS-CoV-2 infection is not limited to respiratory tract involvement but also has significant systemic implications.

Corresponding author: Florin Ionut Buibas, MD, PhD Student; e-mail: flaviancalui@yahoo.com

Abstract   Open Paper   Download PDF

6. Biomarkers in schizophrenia - past, present and future

Violeta Mancas, Dana Galieta Minca, Simona Corina Trifu

Schizophrenia is a complex and debilitating neuropsychiatric syndrome. Although research into the etiology of this pathology has advanced considerably, consistent results are still awaited. The discovery of biomarkers that could underlie diagnosis and treatment could revolutionize the management of this pathology, and approaching biomarkers from an evolutionary perspective, along with the multitude of existing and future studies, can provide important information. The complexity of this multifactorial pathology requires its approach from an integrated and multidisciplinary perspective, which considers research on neurodevelopment, genetics, imaging and, last but not least, neurobiological research. The present material aims to bring to light a series of recent research, as well as the approach to this pathology from an evolutionary perspective of neurodevelopment, in the hope that it will constitute an attractive point of view that could imagine new ways of approaching this pathology.

Corresponding author: Dana Galieta Minca, Professor, PhD; e-mail: dana.minca@umfcd.ro

Abstract   Open Paper   Download PDF

7. Hematomyelia after epidural anesthesia: a rare complication with putative multifactorial and occult etiology

Gabriela-Camelia Rosu, Ionica Pirici, Andrei Osman, Larisa Iovan, Ilona Mihaela Liliac, Cristina Jana Busuioc, Valentin-Octavian Mateescu, Roberta Andreea Cercel, Florina Carmen Popescu, Mihai-Marius Botezat

Subarachnoid hemorrhage (SAH) and spinal hematomas are considered serious but rare complications of spinal pathology. They occur after spinal anesthesia, especially in patients with risk factors such as autoimmune diseases, blood coagulation pathology, anticoagulant treatment, vascular malformations, intramedullary or spinal cord tumors, or can be multifactorial. Usually, anticoagulant therapy represents an additional factor regarding spinal SAH (SSAH) or spinal hematomas. None of the direct oral anticoagulants has a higher chance of producing a spinal hemorrhage. The diagnosis can be established based on the clinical picture of SSAH or myelopathy syndrome, completed with magnetic resonance imaging (MRI). In this study, we present the latest data from the literature regarding SSAH and hematomas and compare them with the data of a 77-year-old man with a history of atrial fibrillation, on oral anticoagulant treatment, who developed a SSAH and spinal hematoma after elective surgery for an inguinal hernia.

Corresponding author: Ionica Pirici, MD, PhD; e-mail: ionica.pirici@umfcv.ro; Ilona Mihaela Liliac, MD, PhD; e-mail: ilona.mihaela.liliac@gmail.com

Abstract   Open Paper   Download PDF

8. The effect of physical exercises on TNF-alpha, IL-6, and IL-8 cytokines expression and NK cells in cancer

Ligia Rusu, Tatiana Andreea Mihai, Ramona Adriana Schenker, Mihnea Ion Marin, Michael Schenker, Costin Teodor Streba, Dan Ionut Gheonea, Denisa Piele

The main process in developing cancer is carcinogenesis, which means that proliferation of the cells is developed and is based on interplay between intrinsic and extrinsic processes. Many researchers consider that cytokines produced during muscle contractions (i.e., myokines) could influence cancer cells. Myokines, produced by muscles during physical activity, may have anti-inflammatory and antitumor effects by directly influencing the tumor microenvironment and the immune system. These signaling molecules have the potential to modulate tumor cell growth and viability, suggesting that exercise may contribute to cancer prevention and control through complex biochemical mechanisms. The aim of this review was to analyze the effects of physical exercise on cytokines and implicitly its influence on the cancer cells, by performing in-depth documentation leading to a synthesis, for analysis of the possible contribution of physical exercises as therapeutic potential. The search for articles was also extended to databases. Multiple studies have shown that exercise can inhibit the development of tumor cells and so apoptosis may be induced for various malignant cells and much more short-term and long-term training interventions suggest that training volume may influence the inhibition of cancer cells. Still, the specific impact of training modalities, volumes, as well as intensities on serum collected from individuals undergoing exercise programs - and its subsequent effects on cancer cells - remains unclear.

Corresponding author: Tatiana Andreea Mihai; e-mail: andreea.ana.mihai@gmail.com

Abstract   Open Paper   Download PDF

9. The role of CDX2, MUC5AC, and p53 in the evaluation of the progression of serrated lesions toward colorectal carcinoma

Sergiu Marian Cazacu, Sevastita Iordache, Vlad Florin Iovanescu, Liliana Streba, Carmen Daniela Neagoe, Cristina Jana Busuioc, Dan Cartu, Mirela Marinela Florescu

Background: Serrated colorectal lesions represent a potential precursor of 15-30% of colorectal carcinoma, although the exact mechanisms are not fully understood. The serrated pathway of colorectal carcinogenesis may be correlated with gastric-type metaplasia of the colon and modified expression of caudal type homeobox 2 (CDX2) and local mucins (MUCs). Patients, Materials and Methods: We performed a retrospective study of patients with resected polyps during 2014-2021. The prevalence of serrated lesions, risk factors associated with malignant polyps, and the role of gastric-type metaplasia associated with serrated pathway of carcinogenesis (CDX2, MUC5AC) and of p53 immunostaining in serrated lesions with dysplasia and carcinoma were assessed. Results: Five hundred twenty two (522) patients had 1199 polyps removed. We noted a 12.8% prevalence of sessile serrated adenoma/polyps (SSA/P) and traditional serrated adenomas (TSA); 17.4% had hyperplastic polyps. The malignancy rate of resected polyps was higher in tubulovillous adenoma (TVA) and villous adenoma (12.3-20%) than in SSA/P (8.3%) and TSA (4.8%). In TSA, no significant associations between malignancy and age, gender, size, location, or endoscopic appearance were noted. In SSA/P, malignant polyps were much larger, especially for the right side lesions, but the macroscopic type was not correlated with malignancy risk. Immunohistochemistry (IHC) was performed in 26 polyps with dysplasia or carcinoma; all cases had CDX2 immunostaining in the tumor cell s nucleus, with an average percentage of 96.5%. MUC5AC immunostaining was identified in the tumor cells cytoplasm, with an average percentage of 31.81%; the intensity reaction was variable (average score 4.5). The percentage, intensity, and score for CDX2 IHC were similar for TSA and TVA and were lower for SSA/P with low-grade dysplasia (LGD), while for SSA/P with high-grade dysplasia (HGD) or carcinoma in situ (CIS), the percentage, intensity, and score were similar to TSA and TVA. p53 immunostaining was also positive in all cases, with an average percentage of 50.95% in the tumor cells nucleus. p53 and MUC5AC had increased percentage, intensity, and scores from LGD to HGD in SSA/P and decreased mean percentage, intensity, and scores in TSA and TVA. Conclusions: The risk of malignancy in serrated lesions seems lower than in conventional adenomas, however, sessile serrated lesions can be involved in the appearance of interval cancers because of flat and pale macroscopic aspects. Gastric-type intestinal metaplasia may be associated with the serrated pathway, but more studies are needed to clarify mechanisms associated with serrated carcinogenesis.

Corresponding author: Vlad Florin Iovanescu, MD, PhD; e-mail: iovanescu_vlad@yahoo.com; Carmen Daniela Neagoe, MD, PhD; e-mail: dananeagoe2014@gmail.com

Abstract   Open Paper   Download PDF

10. Contralateral breast cancer in patients carrying mutations in the BRCA1/2 gene

Sorana-Caterina Anton, Setalia Popa, Carmen Rodica Anton, Emil Anton, Delia Nicolaiciuc, Ovidiu-Sebastian Nicolaiciuc, Mihai Danciu, Sadiye-Ioana Scripcariu, Dragos Valentin Crauciuc, Mihaela Grigore

Aim: This study aim was to offer a better view of breast cancer (BC) in Romanian patients and to identify the most frequent BRCA1/2 germline mutations in a cohort of Romanian patients with contralateral BC (CBC). This is one of the first comprehensive studies to determine the contribution of BRCA1/2 germline mutations to CBC development in the Romanian population. Patients, Materials and Methods: This is a prospective study and included 281 patients with BC. We established the histological type and immunohistochemical profile for these breast tumors. We identified mutations in the BRCA1/2 oncogenes in those patients diagnosed with CBC. We investigated correlations between the BRCA1/BRCA2 genes mutation and the increased risk of collateral BC. Results: The most common histological type observed was ductal carcinoma. Our study group of tumors was classified into the following BC subtypes: 84.69% triple-negative BC, 9.60% Luminal A, 3.55% human epidermal growth factor receptor 2 (HER2)-positive and 2.13% Luminal B. Forty-one cases were diagnosed with collateral BC. For these 41 cases, genetic testing was performed for the BRCA1 and BRCA2 genes and we obtained seven cases with negative results and 34 cases with positive results for mutations in the BRCA1 gene, describing the following types of mutations: c.3067.C>T (24 cases - 70.6%), c.5266dupC (four cases - 11.8%), c.4035delA (six cases - 17.6%).Conclusions: This study offered a better view of BC in Romanian patients and identified the most frequent BRCA1/2 germline mutations in a cohort of Romanian patients with CBC. Also, these results demonstrate that BRCA1 gene mutations increase the risk for CBC development.

Corresponding author: Emil Anton, Associate Professor, MD, PhD; e-mail: emil.anton@yahoo.com; Delia Nicolaiciuc, Assistant, MD, PhD; e-mail: delianicolaiciuc@yahoo.com

Abstract   Open Paper   Download PDF

11. Regional retinal vulnerability in multiple sclerosis: integrating OCT, MRI, and clinical data for enhanced diagnosis and automated monitoring

Sorina-Elena Abdul-Salam, Ruxandra-Madalina Florescu, Alin-Stefan Stefanescu-Dima, Andrei-Theodor Balasoiu, Valeria-Carmen Albu, Ioana-Andreea Gheonea, Veronica Sfredel, Dragos-Ovidiu Alexandru, Mircea-Sebastian Serbanescu

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, often affecting the visual pathways. Optical coherence tomography (OCT) has emerged as a valuable, non-invasive imaging tool for assessing neuroaxonal damage in MS. This study investigates retinal neurodegeneration in MS patients, focusing on ganglion cell layer and inner plexiform layer (GCL+IPL) thinning, macular volume (MV), and retinal nerve fiber layer (RNFL) alterations, and their correlation with clinical and magnetic resonance imaging (MRI) parameters. A total of 43 MS patients and 38 healthy controls underwent three OCT investigations over three years, measuring GCL+IPL thickness, MV, and RNFL parameters. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS), and MRI data were available, with parameters such as lesion volume, whole brain volume, and white matter percentage analyzed. Statistical comparisons included t-tests, analysis of variance (ANOVA), and Pearson s correlation to evaluate OCT changes and their associations with clinical and MRI findings. MS patients exhibited significant GCL+IPL thinning, with quadrant analysis revealing regional disparities. Macular thickness showed no significant global differences; however, outer quadrant thinning was observed. RNFL analysis confirmed significant temporal quadrant thinning, further supporting its selective vulnerability in MS. Over three years, no significant longitudinal changes were detected in any OCT parameters (p>0.05). MRI lesion volume correlated strongly with EDSS (Pearson, r=0.61) and moderately with GCL+IPL thickness (Pearson, r=0.42), while a weaker correlation was found with temporal RNFL thickness. These findings reinforce OCT as an essential biomarker for MS-related neurodegeneration, particularly through GCL+IPL and temporal RNFL thinning. While macular changes were minimal, the observed selective temporal quadrant vulnerability aligns with previous research linking retinal alterations to trans-synaptic degeneration and optic radiation damage. The lack of significant longitudinal OCT progression over three years suggests that retinal atrophy may require longer monitoring periods to detect meaningful disease progression or to enable automated diagnosis. OCT is a reliable tool for detecting subclinical neurodegeneration in MS, particularly through temporal RNFL and GCL+IPL thinning. The moderate correlation between MRI lesion volume and retinal changes supports the integration of OCT with MRI for multimodal disease monitoring. The application of artificial intelligence (AI)-driven OCT analysis holds promise for enhanced MS diagnosis and automated progression monitoring. Future research should focus on long-term longitudinal studies, AI-assisted OCT diagnostics, and multimodal imaging approaches to optimize personalized MS management.

Corresponding author: Ruxandra-Madalina Florescu, MD, PhD Student; e-mail: ruxandra.florescu3@gmail.com

Abstract   Open Paper   Download PDF

12. Fibroepithelial lesions: assessing the risk of malignant phyllodes tumors in the breast

Alexandru Carauleanu, Cristina David, Simona Juliette Mogos, Gabriel Costachescu, Iustina Petra Solomon-Condriuc, Andrei Ionut Cucu, Gabriel Valentin Tanase, Claudia Florida Costea, Demetra Gabriela Socolov, Dragos Viorel Scripcariu, Florin Dumitru Petrariu, Adina Elena Tanase, Daniela Maria Tanase

Purpose: Phyllodes tumors (PTs) of the breast are rare fibroepithelial tumors (FETs), accounting for approximately 0.5% of all breast tumors. The diagnostic interpretation of borderline fibroepithelial lesions often requires further investigations. Patients, Materials and Methods: We used statistical analysis to evaluate the different surgical approaches, risk factors and prognosis during a five-year period, from January 2019 to December 2024, of women who underwent conservative surgeries for benign, borderline tumors and malignant breast tumors. Results: We examined a total of 481 breast tumors, with benign, borderline and reserved final diagnosis to paraffin, and discovered 35 FETs, corresponding to phyllodes-type tumors. Studies of enlarged PTs, which are often malignant on final paraffin results, are controversial regarding further postoperative treatment, because they require chemotherapy that is as aggressive as for soft tissue sarcomas, and also hormone therapy that has not shown long-term survival benefit yet. In order to improve the quality of life, survival rate, and disease management, the surgical team needs to be up to date with the latest protocols of management of the disease. Discussions: Management of breast tumors includes ultrasound examination, digital or three-dimensional (3D) mammography and magnetic resonance imaging (MRI) evaluation, while surgical management is consistent with core needle biopsy procedures and surgical excision known as tumorectomy, followed in certain cases by an enlarged sectorectomy. Conclusions: Aggressive surgery is sometimes necessary to achieve oncological safety margins and prevent subsequent disease recurrence.

Corresponding author: Claudia Florida Costea, Professor, MD, PhD; e-mail: costea10@yahoo.com; Adina Elena Tanase, Assistant Professor, MD, PhD; e-mail: adinnatanase@gmail.com

Abstract   Open Paper   Download PDF

13. Deep endometriosis. Clinical, histopathological and confocal microscopy correlations in intestinal sites

Elena Iuliana Anamaria Berbecaru, George-Lucian Zorila, Anca-Maria Istrate-Ofiteru, Daniel Pirici, Andreas Donoiu, Oana-Iulia Cretu, Gabriela-Camelia Rosu, Elvira Bratila, Dumitra Miron, Valentin-Octavian Mateescu, Cristina Elena Negroiu, Suzana Danoiu, Dominic-Gabriel Iliescu, Robertina-Iulia Tudorascu

Intestinal endometriosis (IE), a chronic condition affecting a notable percentage of women with endometriosis (estimates varying from roughly 4% to 37%) and can impact any part of the intestine, but it most frequently involves the rectum and sigmoid colon. This is a retrospective study that included 178 women diagnosed with this condition that were investigated taking into consideration the symptoms, diagnostic approaches, surgical treatments, and detailed features of the intestinal wall, including the behavior and quantity of interstitial cells of Cajal (ICC) correlated with the symptomatology experienced. We were able to highlight the most common symptoms such as pelvic pain and bowel disorders. The rectum was identified as the most commonly affected intestinal segment. Transvaginal ultrasound can be valuable in assessing IE, improving preoperative diagnosis and treatment strategies. Laparoscopic surgery remains the definitive diagnostic method, allowing direct visualization and excision of lesions. Surgical technique selections are complex and require careful consideration tailored to each patient. A reduction in ICC numbers may disrupt gut motility, emphasizing their importance in maintaining normal intestinal function, a factor particularly relevant in endometriosis where disruption of ICC networks can contribute to gastrointestinal dysfunction.

Corresponding author: Anca-Maria Istrate-Ofiteru, Lecturer, MD, PhD; e-mail: ancaofiteru92@yahoo.com; Dominic-Gabriel Iliescu, Professor, MD, PhD; e-mail: dominic.iliescu@yahoo.com

Abstract   Open Paper   Download PDF

14. Tumor microenvironment in squamous cell lung cancer - histological and immunohistochemical study

Ovidiu-Lucian Cimpeanu, Andrei Osman, Alina-Maria Georgescu, Elena Cristina Andrei, Bogdan Oprea, Valentin-Octavian Mateescu, Larisa Patru, Carmen Aurelia Mogoanta, Ionut Tanase, Adriana Mihaela Ciocalteu, Dan Iovanescu, Ilona Mihaela Liliac, Mihai Olteanu, Costin Teodor Streba

Globally, lung cancer is the primary cause of cancer-related mortality. Squamous cell carcinoma (SCC) of the lung, a subtype of non-small cell lung cancer (NSCLC), accounts for a significant portion of new cases and is primarily associated with smoking and environmental pollutants. This study investigates the histopathological and immunohistochemical (IHC) characteristics of the tumor microenvironment (TME) in SCC using tissue samples from 19 patients who underwent surgery for lung cancer. IHC markers, including cluster of differentiation (CD)68, CD3 and CD34 were used to assess various components of the TME, including immune cell infiltration, and angiogenesis. The results revealed significant presence of macrophages, T-lymphocytes, and myofibroblasts, as well as increased vascularization in the tumor stroma. These findings highlight the complex interaction between tumor cells and the surrounding stroma, contributing to tumor progression. Understanding these mechanisms is crucial for improving early diagnosis and therapeutic strategies for SCC.

Corresponding author: Ilona Mihaela Liliac, MD, PhD; e-mail: ilona.mihaela.liliac@gmail.com; Elena Cristina Andrei, MD, PhD; e-mail: andreicristina2201@gmail.com

Abstract   Open Paper   Download PDF

15. Ex vivo use of probe-based confocal laser endomicroscopy in lung cancer visualization: an ex vivo pilot study

Andreea-Georgiana Gheorghe, Liliana Streba, Alin Dragos Demetrian, Mircea-Sebastian Serbanescu, Daniel Pirici, Costin Teodor Streba

Lung neoplasia is the main cause of cancer death worldwide, with increasing incidence and an apparent stagnation in the decrease of morbidity. Early lung cancer (LC) diagnosis requires precise pathology and precise surgical intervention at the appropriate time. Current guidelines provide an outline for cancer management, involving multiple imaging methods as well as tissue-collection techniques; however, probe-based confocal laser endomicroscopy (pCLE), although being introduced several years ago, remains an experimental diagnostic method. Based on direct tissue observation that can occur during normal bronchoscopy, with the possibility of combining multiple imaging techniques in a single-step intervention, it however holds great promise. We included 18 consecutive patients diagnosed with LC over a period of six months who underwent curative surgery. After obtaining written consent and ethical approval, we used pCLE on ex vivo tissue samples that were later sent to pathology for confirmation. We then compared pCLE findings with the final pathology diagnosis. We included 12 males, median age in the study group being 64 years. We found 10 adenocarcinomas, four small cell lung carcinomas and four squamous cell carcinomas. The pCLE investigation provided key differentiating aspects between normal lung parenchyma, the structure of elastin fiber distribution and the shape and cellular content of alveoli, as opposed to the anarchic organization of the tumoral tissue. In conclusion, we presented here some of the first descriptive findings of lung tissue in pCLE imaging, thus contributing to the standardization of the technique for diagnostic purposes.

Corresponding author: Liliana Streba, MD, PhD; e-mail: liliana.streba@umfcv.ro; Alin Dragos Demetrian, MD, PhD; e-mail: alin.demetrian@umfcv.ro

Abstract   Open Paper   Download PDF

16. The outcomes of partial nephrectomy - considerations that contribute to positive surgical margins

Alexandru Iordache, Nicoleta Alina Mares, Niculae Iordache, Mihaela Gabriela Berdan, Mara Mardare, Alina Ioana Puscasu, Bogdan Florin Geavlete, Dragos Adrian Georgescu, Razvan-Cosmin Petca, Viorel Jinga, Octav Ginghina, Alexandru Blidaru

The diagnosis in the early stages of renal tumors, as well as the oncological outcomes equivalent to extensive nephrectomies, have increased interest in partial nephrectomy (PN), which is the preferred method for treating renal cell carcinoma less than 7 cm. The literature confirms that PN offers oncological outcomes equivalent to radical nephrectomy, especially in early stages. This is a prospective study, conducted in a single university center over a period of three years, aimed to evaluate the surgical and oncological outcomes regarding positive safety margins after PN performed using laparoscopic and open approaches. Following the analysis of the causes and consequences of incomplete tumor resection, the obtained results align with data from the literature. We found that specimens from laparoscopic surgery were approximately twice as likely to have positive surgical margins compared to tumors resected using the open approach, meaning that these patients require more intense follow-up both clinically and imaging. According to current published studies, positive safety margins are not predictors for disease recurrence rate, progression-free survival, or overall survival.

Corresponding author: Niculae Iordache, Professor, MD, PhD; e-mail: niculae.iordache@umfcd.ro; Octav Ginghina, Associate Professor, MD, PhD; e-mail: octavginghina@gmail.com

Abstract   Open Paper   Download PDF

17. Immunoprofile of some surface and cytoplasmic peripheral cell adhesion molecules in oral squamous cell carcinoma

Ionut-Octavian Ilie, Adrian Camen, Daniela Dumitrescu, Maria-Cristina Munteanu, Marius Matei, Mircea-Sebastian Serbanescu, Claudiu Margaritescu

Despite the recent advances in diagnosis and treatment, oral squamous cell carcinoma (OSCC) continues to have a low overall survival rate (around 50%), being a tumor with high locoregional aggressiveness and high risk of lymph node (LN) dissemination. Such behavior can also be explained by the alteration of the expression of adhesion molecules, allowing tumor cells to invade surrounding tissues and make them capable of metastasizing. In this regard, we initiated a study on the immunohistochemical expression of Integrin alphavbeta6, CD44 and Ezrin in OSCCs. A number of 39 such tumors with various locations in the oral cavity were investigated by enzymatic immunohistochemistry together with several samples of oral mucosa and oral dysplastic lesions. Using integrated optical density (IOD) as a method to quantify, we observed that the reactivity of these three markers decreased in the progression of dysplastic lesions and in the transition from well to moderately and poorly differentiated tumors. Also, in both conditions we noticed a shift of pattern reactivity from the continuous membrane to discontinuous membrane and cytoplasmic one, even to a nuclear pattern. In addition, the reactivity of the three markers was more evident in the invasion front and especially in these tumors with discohesive growth patterns. All this suggests the involvement of these adhesion molecules in the processes of transformation and malignant progression of OSCCs. It also explains their possible involvement in locoregional aggressiveness and LN dissemination.

Corresponding author: Daniela Dumitrescu, Assistant Professor, MD, PhD; e-mail: daniela.dumitrescu@gmail.com; Marius Matei, Associate Professor, MD, PhD; e-mail: mariusmatei44@yahoo.com

Abstract   Open Paper   Download PDF

18. Causes of death in the Emergency Department: a retrospective monocentric study

Adrian Iosif Moldoveanu, Radu Gheorghe Dan, Emil Florin Hut, Dan Iliescu, Laurentiu Vasile Sima, Bianca Moldoveanu, Catalina Oana Bazavan, Ovidiu Alexandru Mederle, Flavia Zara

The Emergency Department (ED) serves as a critical entry point for patients with life-threatening conditions, yet mortality within this setting remains a significant clinical and epidemiological concern. This retrospective monocentric study investigates the primary causes of death in the ED of Emergency Municipal Hospital, Timisoara, Romania, over a five-year period (2019-2023). A total of 63 cases were analyzed, integrating clinical data at the time of presentation with post-mortem pathological findings to ensure diagnostic accuracy. Results indicate that irreversible cardiac arrest (ICA) constituted the predominant cause of mortality, with non-shockable rhythms accounting for 88.88% of cases - asystole (80.35%) and pulseless electrical activity (19.65%) - while shockable rhythms (ventricular fibrillation and pulseless ventricular tachycardia) were observed in only 11.12% of cases. Among non-cardiac etiologies, septic shock (31.74%) and respiratory failure (17.46%) were the most prevalent contributors. These findings highlight the need for improved diagnostic methodologies, optimized resuscitation strategies, and enhanced resource allocation within emergency settings. This study underscores the necessity for systematic mortality documentation, evidence-based intervention protocols, and targeted management strategies to mitigate preventable deaths in the ED. The integration of clinical and autopsy-based data offers valuable insights into pathophysiological mechanisms contributing to ED mortality and provides a foundation for future research aimed at improving emergency medical outcomes.

Corresponding author: Radu Gheorghe Dan, Lecturer, MD, PhD; e-mail: radu.dan@umft.ro

Abstract   Open Paper   Download PDF

19. Pathology assessment of inflammatory bowel disease - prospective study from two referral centers

Christopher Jesse Vlad Pavel, Gabriel Constantinescu, Valentin Enache, Gabriel Becheanu, Madalina Stan-Ilie, Vasile Sandru, Oana-Mihaela Plotogea, Alexandru Constantinescu, Dan Ionut Gheonea, Bogdan Silviu Ungureanu, Horia-Dan Liscu, Mihai Mircea Diculescu, Alex Emilian Stepan

We aimed to perform a comprehensive prospective histological analysis in a cohort of 40 inflammatory bowel disease (IBD) patients, both prior to and during biological therapy. The main objective was to establish the impact of histological activity in assessing treatment response and therapy guidance. Biopsy samples were assessed in two different stages of the disease course - before introduction of biological therapy and during follow-up (6-12 months later). Clinical, biochemical and endoscopic parameters were simultaneously gathered. By univariate analysis, presence of lymphoid aggregates, mucin depletion and ulcerations had a strong association with treatment response. IBD diagnosis >5 years and previous biological therapy were the most susceptible to treatment non-response. Nancy Index (NI) >1 is highly accurate, sensitive and specific in defining treatment responders. In addition to NI, high histological burden (mucin depletion, lymphoid aggregates and ulcerations) seems to predict treatment response in biological therapy-treated patients. Instead of a stringent histological remission goal, histological improvement of individual parameters might be a more reasonable goal, avoiding the risk of overtreatment. Further research is needed to assess histological burden in patients with endoscopic remission in order to stratify low- vs. high-risk relapsers and to avoid under- or over-treatment.

Corresponding author: Mihai Mircea Diculescu, Professor, MD, PhD; e-mail: mmdiculescu@yahoo.com

Abstract   Open Paper   Download PDF

20. Hip osteoarthritis - histopathological aspects

Anton Tiberiu Paraliov, Razvan Marius Vicas, Rodica Dirnu, Natalia Guta, Lucretiu Radu, Laurentiu Mogoanta, Laura-Corina Nicolescu

Osteoarthritis is a complex, degenerative disease that can affect all the anatomical structures of the synovial joints. Most frequently, the joints of the hand, hip, and knee are affected, especially in the elderly patients. In our study, we evaluated 27 femoral heads, examining the histopathological changes that occurred in the articular cartilage, subchondral bone, and perisynovial soft tissues. At the level of the articular cartilage, there were observed a reduction in thickness, deformation of the articular surface, degradation of the cartilaginous matrix, the occurrence of fissures or fractures in the cartilaginous piece, a reduction in the number of chondrocytes, and changes in their morphology. In the subchondral bone, a rarefaction of the bone trabeculae and a reduction in their thickness were observed, along with an increase in the size of the alveolar cavities. These changes were accompanied by the formation of cystic cavities, non-homogeneous hypertrophy of the subchondral bone plate as a response to the reduction in thickness and change of the articular cartilage structure, or the reduction in the thickness of the subchondral bone plate. The trabecular bone exhibited an atrophic endosteum, absence of bone remodeling processes, cracks or even fractures in the trabecular bone. Likewise, we observed rare ectopic osteogenesis processes, either endochondral or desmal ones, forming osteophytes. The synovium and perisynovial connective tissue contained immune cells, vascular endothelial cells, fibroblasts, adipocytes, and other mesenchymal-derived stromal cells. The immunohistochemical study highlighted the presence of T-lymphocytes, B-lymphocytes, and macrophages, cells capable of synthesizing and releasing matrix metalloproteinases that are involved in the degradation of the articular cartilage. Exploration of cell proliferative capacity using the proliferating cell nuclear antigen (PCNA) showed that, in the articular cartilage, there are few cells (chondrocytes) capable of proliferation, while in the synovium there are numerous young fibroblasts capable of mitotic division.

Corresponding author: Lucretiu Radu, Associate Professor, MD, PhD; e-mail: lucretiu.radu@google.com; Laurentiu Mogoanta, Professor, MD, PhD; e-mail: laurentiu_mogoanta@yahoo.com

Abstract   Open Paper   Download PDF

21. Influence of the patient s demographic profile and tumor characteristics on reconstructive techniques in lip cancers

Ana Catalina Tantu, Marius Eugen Ciurea, Vasilica Mihaela Dumitrache, Alina Paunescu, Marilena Monica Tantu, Constantin Ciucurel, Elena Ioana Iconaru, Daniel Corneliu Diaconescu, Georgeta Ionescu, George Mihail Man, Sorina Octavia Hontaru, Consuela Dicu, George Popescu

With an incidence of approximately 30% of all oral cavity neoplasms, lip cancer significantly impacts the patient quality of life (QoL). The frequent localization is in the lower lip, predominantly affecting men aged between 60-70 years old. The surgical treatment aims at aesthetic and functional reconstruction of the lip. The present study aims at defining a demographic profile of patients with lip cancer and at establishing correlations between tumor characteristics and reconstruction methods. The analysis of the group of 26 patients showed that the lip cancer patient was predominantly female, urban, with a mean age of 73.27+/-11.17 years old, with squamous cell carcinoma of the lower lip, mean diameter of 1.52 cm and mean depth of 0.72 cm. The tumor characteristics revealed a guide of the decision on the method of lip reconstruction, considering the correlations between a variety of factors, including the size of the affected area, etiology and location of the formation, integration of the flap into the relaxed skin tension lines, the patient general condition, and the degree of cooperation. Regardless of the reconstructive method chosen, the aim is to preserve the functions of the lip in mastication, speech and definition of facial expression. Complex cases require extensive reconstructive interventions involving combinations of various types of flaps. Multidisciplinary management of these patients leads to improved QoL and prevention of recurrences.

Corresponding author: Marilena Monica Tantu, Professor, PhD; e-mail: marilena.tantu@upb.ro; Sorina Octavia Hontaru, Lecturer, PhD; e-mail: sorina.hontaru@upb.ro

Abstract   Open Paper   Download PDF

22. A rare case of diffuse large B-cell lymphoma of the frontal sinus and rapid review of literature

Raluca Morar, Norberth-Istvan Varga, Ioana Delia Horhat, Ion Cristian Mot, Flavia Zara, Raluca Maria Closca, Cristian Andrei Sarau, Oana Silvana Sarau, Dan Costachescu, Nicolae Constantin Balica

Introduction: Primary lymphoma of the paranasal sinuses, especially involving the frontal sinus, is exceedingly rare. Extranodal non-Hodgkin lymphoma (NHL) located in the head and neck frequently poses diagnostic challenges because its nonspecific symptoms can be mistaken for benign issues such as rhinosinusitis. Aim: This case report seeks to emphasize the challenges in diagnosis, the aggressive characteristics, and the effective treatment of an uncommon manifestation of diffuse large B-cell lymphoma (DLBCL) primarily affecting the frontal and ethmoid sinuses. Case presentation: We present a case of a 62-year-old male who initially presented with symptoms suggestive of acute rhinosinusitis complicated by periorbital cellulitis. Diagnostic workup included physical examination, laboratory investigations, computed tomography (CT) imaging, magnetic resonance imaging (MRI), histopathological (HP) analysis of biopsy specimens, immunohistochemical staining, and positron emission tomography (PET)-CT. The patient presented with right frontal headache, periorbital edema, palpebral ptosis, and posterior rhinorrhea. Initial CT revealed mucosal thickening, lytic changes, and a mass partially invading the right orbit. Following surgical excision, histopathology confirmed DLBCL with positivity for cluster of differentiation (CD)20, CD79a, B-cell lymphoma (Bcl)-6, and Bcl-2, and a Ki-67 proliferation index of 90%. Subsequent MRI revealed a hypointense mass extending into surrounding structures. Staging CT confirmed stage IVB disease. The patient received six cycles of Rituximab-Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone (R-CHOP) chemotherapy and radiotherapy for the frontal sinus. At the 6-month and 12-month follow-up CT scans, there was no evidence of metabolically active disease on PET-CT (Deauville score 1). During the 2-year follow-up, the patient remained in complete remission. Conclusions: This case underscores the importance of considering malignancy in cases of atypical sinusitis and the crucial role of HP examination of biopsy specimens. This case also highlights the importance of considering malignancy in cases of atypical sinusitis.

Corresponding author: Cristian Andrei Sarau, MD, PhD; e-mail: csarau@umft.ro

Abstract   Open Paper   Download PDF

23. Primary cardiac lymphoma: autopsy case report and literature review

Vladimir Tancos, Peter Bohus, Lucia Frohlichova, Alzbeta Blicharova, Dorota Sopkova

Primary cardiac lymphoma (PCL), defined as extranodal non-Hodgkin s lymphoma involving exclusively the heart and/or pericardium, is a neoplasm with an extremely low incidence, a high degree of malignancy, and a poor prognosis. It comprises 0.5% of all extranodal lymphomas and 1-2% of all primary cardiac tumors, while the most commonly reported subtype is diffuse large B-cell lymphoma (DLBCL). The tumor is more common in immunocompromised patients compared with those who are immunocompetent. Modern imaging methods now allow for earlier detection of these tumors, despite their variable clinical manifestation, which is often a cause of misdiagnosis. We present an autopsy case of undiagnosed PCL in an immunocompetent 72-year-old man, where postmortem examination revealed massive tumor infiltration of the right-sided heart chambers extending to the left ventricle. Histological analysis showed microscopic tumor infiltration within the left atrium as well. A diagnosis of DLBCL of non-germinal subtype was made based on immunohistochemistry.

Corresponding author: Dorota Sopkova, Deputy Head for Education, MD, PhD, MBA; e-mail: d.sopkova@gmail.com

Abstract   Open Paper   Download PDF

24. Incidental Walthard cell nests in the intestine. Report of two cases and review of the literature

Jose-Fernando Val-Bernal, Marta-Maria Mayorga, Horacio Requena-Cabello, Ramiro-Raphael Gutierrez-Vasquez, Sofia Del Carmen, Juan Garcia-Cardo

Walthard cell nest (WCN) is a rare incidental finding in the intestine including the vermiform appendix and the mesocolon. This article describes a case of WNCs in the vermiform appendix and the mesocolon. The location in the mesocolon is reported for the first time. A review of the seven published intestinal cases including our report is presented. The lesion is seen in children, adults, and both sexes. The number of present cell nests varied between one and three per case. The diagnosis rests on histopathological examination. A potential source for histopathological diagnostic error includes a NET. The coexistence of WCNs with an appendicular neuroendocrine tumor (NET) may complicate the diagnosis. WCNs show the immunohistochemical profile of urothelial differentiation. To establish a diagnosis of WCN the absence of significant atypia, significant mitotic activity, atypical mitoses, necrosis, desmoplastic stroma, and tissue invasion must be confirmed. The lesion is a benign proliferation and once the appendectomy or colectomy has been performed, no further treatment is required.

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

Abstract   Open Paper   Download PDF
Download cover
Download contents

Journal archive