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1. Clinical, histopathological and immunohistochemical features of brain metastases originating in colorectal cancer: a series of 27 consecutive cases

Viorel Scripcariu, Delia Gabriela Ciobanu Apostol, Gabriela Florenta Dumitrescu, Mihaela Dana Turliuc, Anca Sava

Introduction: Brain metastases (BMs) originating in colorectal cancer (CRC) have a significant importance for patients survival. Because in literature there are only isolated case reports and only few series published on this issue, we aimed to assess the incidence of BMs from CRC, to identify patient s characteristics and BMs clinical, histopathological (HP) and immunohistochemical (IHC) features, and to compare the data we obtained with those from literature. Patients, Materials and Methods: We present a retrospective study of 27 histologically confirmed cases of BMs from CRC among all 1040 patients who received metastasectomy in the Department of Neurosurgery, Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, in an eight-year period (January 2011 to December 2018). Patients characteristics (gender, age), primary tumor location, time from primary tumor surgery to BMs surgery and BMs features (number, location and HP characteristics) were investigated. Histochemical [Alcian Blue (AB) and Periodic Acid-Schiff (PAS)] staining and IHC stainings for cytokeratin (CK) 7, CK20, caudal-type homeobox 2 (CDX2) and human epidermal growth factor receptor 2 (HER2)/neu were performed on all available BMs specimens. Results: There were 27 consecutive patients with BMs from CRC, corresponding to 2.59% of all patients with BMs during the eight-year period we have studied, most of them being diagnosed and treated in 2016. Male:female ratio was 1.45. The mean age for all patients at diagnosis of the BMs was 62.25 years (range: 40-79 years). The origin of the primary cancer was mainly the colon (62.96% of all cases). Of all 27 patients, only two (7.4%) presented neurological symptoms without a diagnosis of CRC. BMs were identified in a period ranging from six months to 70 months after the initial diagnosis. The average time between diagnosis of the primary tumor and of the BMs was 25.92 months. At the moment of the diagnosis of BMs, 17 (62.96%) patients also had other systemic metastases. Most of the cases (55.55%) were situated in the supratentorial compartment. IHC stainings were negative for CK7 and positive for CK20 and CDX2 in all BMs from colonic adenocarcinomas (ADCs), a profile consistent with a non-neuronal and gastric origin. AB and PAS stainings revealed pools of extracellular mucin, especially in cases of mucinous ADC. Ki67 labeling index ranged between 90% and 100%. IHC staining with anti-HER2/neu antibody showed in 25 (96.15%) cases a strong and diffuse aberrant nuclear staining. Conclusions: BMs originating in CRC represent a rare pathology and have particular clinical and IHC features that could vary from one series to another series. In a few cases, BMs may be diagnosed in the absence of a known CRC diagnosis and in these situations, the correct diagnosis is of interest. However, a panel of antibodies can help in establishing a correct diagnosis. Our study was among the first to analyze the HER2/neu expression pattern in BMs from CRC and we found a strong aberrant nuclear expression of this molecular marker on IHC investigation. Related to the data published so far in the literature, it is possible that HER2/neu aberrant expression in the tumor nuclei of the BMs from our series may express the metastatic tumor cell phenotype that was previously subjected to cytostatics and radiation therapies. As such, we suggest that HER2/neu aberrant expression in BMs originating in CRC could represent a proof for the worst prognosis of these patients.

Corresponding author: Delia Gabriela Ciobanu Apostol, Assistant Professor, MD, PhD; e-mail: delia.ciobanu@umfiasi.ro; Dana Mihaela Turliuc, Associate Professor, MD, PhD; e-mail: turliuc_dana@yahoo.com

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2. Male breast involvement in chronic lymphocytic leukemia. A case report and review of the literature

Vasiliki Anagnostopoulou, Niki Mantha, Konstantinos Sapalidis, Eirini Tolparidou, Elisavet Georgiou, Triantafyllia Koletsa

Male breast lymphoma is a rare extranodal lymphoma occupying the mammary gland, and it could be either primary or secondary. A 78-year-old man presented an enlargement of the right breast. He had no medical history of interest. On physical examination, a unilateral, painless breast lump was found, with no skin changes or nipple discharge. There was no palpable lymphadenopathy. Routine laboratory tests revealed leukocytosis and lymphocytosis. Excisional biopsy of the breast lesion revealed mammary tissue infiltration by chronic lymphocytic leukemia (CLL) with plasmacytoid features and immunoglobulin G/kappa monotypic expression. To our knowledge, this is the first report of male breast involvement by CLL. Considering important the collection of clinicopathological data of all reported male breast lymphoma cases, a literature review is presented.

Corresponding author: Triantafyllia Koletsa, Assistant Professor of Pathology, MD, PhD; e-mail: tkoletsa@auth.gr

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3. Ectopic lamellar Pacinian corpuscle within the thymus. Atypical or abnormal location?

Ivan Varga, Matej Nosal, Pavel Babal

Lamellar (Pacinian) corpuscle is a cutaneous encapsulated sensory corpuscle, mainly functioning as a rapidly adapting low-threshold mechanoreceptor with characteristic onion skin-like appearance. Even though the Pacinian corpuscle is typically located in the skin, histomorphologically and confirmed by using immunohistochemical methods, we have identified it within the interstitium of the thymus of a newborn with congenital heart defect. To the best of our knowledge, this is the first such account ever to be published. The structure of the thymic Pacinian corpuscle was the same as the Pacinian corpuscle in the skin. The ectopic thymic Pacinian corpuscle can be hypothetically explained as the consequence of impaired migration of neural crest cells, since neural crest-derived cells play an important role in the development of the Pacinian corpuscle, as well as the thymus and heart. In general, the occurrence of ectopic Pacinian corpuscle in different organs is rare. In the scientific literature, there are reports of its sporadic presence in the pancreas, in the lymph nodes, inside the prostate and the urinary bladder wall. Our report presents the first described case of the Pacinian corpuscle in a heterotopic location in the thymus. Similar to other incidental findings of this anatomic structure, explanation of its ectopic development, as well as its local function remains only speculative.

Corresponding author: Ivan Varga, Professor, PhD; e-mail: ivan.varga@fmed.uniba.sk

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4. Cardiac axis evaluation as a screening method for detecting cardiac abnormalities in the first trimester of pregnancy

Florina Nela Osvar, Adrian Claudiu Ratiu, Florica Voita-Mekeres, Gheorghe Florin Voita, Mihaela Gabriela Bontea, Mariana Racovita, Gabriel Mihai Mekeres, Florian Dorel Bodog

Congenital cardiac abnormalities refer to especially anatomic malformations of the heart that normally occur during fetal heart development, before eight weeks after conception. Aim: The aim is to investigate the association between cardiac axis and congenital heart abnormalities for a potential underline clinical application of cardiac axis evaluation during detection by abnormalities at the time of first trimester ultrasound. It is known that aneuploids can be associated in almost half of cases with cardiac abnormalities, so the angle of the cardiac axis could be a potential indirect marker for the detection of aneuploids in the first trimester of pregnancy. Being easy to obtain, from the cross-section at the chest level with the visualization of the four chambers, does not require additional sections to those provided in the current guides, we aim to prove its usefulness in diagnosing aneuploids and congenital cardiac abnormalities along with the translucent nuchal flow, at the level of the venous duct and the presence of tricuspid regurgitation. Conclusions: Cardiac axis has a higher value for the detection of congenital cardiac abnormalities with respect to the nuchal translucency, tricuspid regurgitation and inverted A wave at the level of the venous duct.

Corresponding author: Florica Voita-Mekeres, Lecturer, PhD; e-mail: mekeres_florina@yahoo.com; Gheorghe Florin Voita, PhD Student; e-mail: voita_florin@yahoo.com

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5. Saccular function evolution related to cochlear implantation in hearing impaired children

Romica Sebastian Cozma, Maria Cristina Hera, Mihail Dan Cobzeanu, Raluca Olariu, Oana Roxana Bitere, Cristian Martu, Lucia Corina Dima-Cozma, Cristina Gena Dascalu, Madalina Gabriela Georgescu, Violeta Necula, Luminita Mihaela Radulescu

Vestibular sensorial input is essential for psychomotor development of the very small children. In consequence, possible vestibular impairment induced by cochlear implantation in deaf children could affect the balance and walking learning process. Some of cochlear implanted children can present congenital vestibular deficit. The anatomical and embryological relation between auditory and vestibular system explains why congenital neurosensorial hearing loss may associate vestibular impairment. The cochlear implant surgery presents a vestibular lesion risk. Bilateral vestibulopathy, as it appears in early childhood, has a poor prognosis for the psychomotor and cognitive development. Even probably rare, bilateral vestibulopathy induced by simultaneous bilateral cochlear implantation can delay the acquisition of motor skills. This pathology can be avoided by an appropriate surgical indication related to the vestibular preoperative status. This study reports the vestibular saccular functional modifications after the cochlear implantation in children. The cervical vestibular evoked myogenic potentials (cVEMPs) were performed in children before and after the cochlear implantation. Since previous studies report different vestibular impairment related to the portelectrode insertion approach, another objective of our study was to assess the saccular postoperative status depending of the insertion by cochleostomy (CO) or through the round window (RW). We performed cVEMPs for 80 patients (135 cochlear implanted ears) before and after cochlear implantation. We have detected preoperative saccular areflexia in 33 (24.4%) ears. In the group of 102 (75.6%) ears with preoperative normal saccular function, 72 (70.6%) ears preserved the cVEMP response after the surgery, while in 30 (29.4%) ears the cVEMP response was lost. Reporting our findings to the portelectrode insertion method, we found normal saccular function in 73.3% of the cochlear implanted ears by RW surgical approach and in 68.42% ears by CO approach. These results suggest that the RW portelectrode insertion is the recommended strategy in order to avoid the saccular vestibular impairment.

Corresponding author: Raluca Olariu, MD, PhD; e-mail: dr.olariu_raluca@yahoo.com; Mihail Dan Cobzeanu, Professor, MD, PhD; e-mail: cobzeanu_dan@yahoo.com

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6. A research on abortion: ethics, legislation and socio-medical outcomes. Case study: Romania

Andreea Mihaela Nita, Cristina Ilie Goga

This article presents a research study on abortion from a theoretical and empirical point of view. The theoretical part is based on the method of social documents analysis, and presents a complex perspective on abortion, highlighting items of medical, ethical, moral, religious, social, economic and legal elements. The empirical part presents the results of a sociological survey, based on the opinion survey method through the application of the enquiry technique, conducted in Romania, on a sample of 1260 women. The purpose of the survey is to identify Romanians perception on the decision to voluntary interrupt pregnancy, and to determine the core reasons in carrying out an abortion.

Corresponding author: Andreea Mihaela Nita, Senior Lecturer, PhD; e-mail: andreea_nita2005@yahoo.com; Cristina Ilie Goga, Assistant Professor, PhD; e-mails: cristin_il@yahoo.com, cristina_ilie.goga@ucv.ro

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7. Abdominal wall endometriosis versus desmoid tumor - a challenging differential diagnosis

Alexandru Carauleanu, Razvan Mihai Popovici, Claudia Florida Costea, Raluca Anamaria Mogos, Dragos Viorel Scripcariu, Irina Daniela Florea, Ali Cheaito, Adina Elena Tanase, Raluca Maria Haba, Mihaela Grigore

Aim: Abdominal wall endometriosis (AWE) in young women, with previous gynecological abdominal surgery, is the first condition considered by many practitioners when a tumor in the region of the scar appears. AWE seems to be caused by an iatrogenic transfer of endometrial cells at the level of the scar. The onset of the disease may be late in many cases. Despite the fact that the disease could be totally asymptomatic, there are certain risk factors that can be identified during the anamnesis, such as: heredity, menarche at the age of >14 years, menstrual cycle <27 days, delayed menopause, excessive alcohol and caffeine consumption. Suggestive signs include cyclic or continuous abdominal pain caused by a palpable abdominal wall mass with a maximum tenderness in the region of the surgical scar. The differential diagnosis is complex and rare entities like desmoid tumors (DTs) must be taken into consideration. Desmoid tumor, or the so-called aggressive fibromatosis (AF), is a rare fibroblastic proliferation. This tumor can develop in any muscular aponeurotic structure of the body and is considered benign but with a high recurrence rate. DTs can cause local infiltration, subsequently producing certain levels of deformity and potential obstruction of vital structures and organs. The differential diagnosis is challenging in this situations, the imagery exams are useful, especially in detecting the precise location of the tumor. The histological examination of the tumor can state the final and precise diagnosis.

Corresponding author: Claudia Florida Costea, Associate Professor, MD, PhD; e-mail: costea10@yahoo.com; Razvan Mihai Popovici, Assistant, MD, PhD; e-mail: razpopovici@yahoo.com

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8. Rare retroperitoneal conditions that mimic uterine myoma

Razvan Mihai Popovici, Alexandru Carauleanu, Claudia Florida Costea, Irina Daniela Florea, Dragos Viorel Scripcariu, Raluca Anamaria Mogos, Ali Cheaito, Adina Elena Tanase, Raluca Maria Haba, Mihaela Grigore

The most frequent tumoral condition of the uterus is represented by uterine myoma. The diagnosis, in most cases, is established by clinical examination and ultrasound scan. Nevertheless, there are rare cases, in which the surgical findings reveal a retroperitoneal tumor instead of a uterine myoma. These could be represented by schwannomas or Castleman disease. The schwannomas are rarely malignant and arise from the Schwann cells of nerve fibers. These tumors are frequently found at the level of the head, neck and mediastinum and rarely in the pelvis. Generally, schwannomas localized at retroperitoneal level are asymptomatic and with a very slow growth rate. The treatment consists in complete surgical resection. The recurrence rate is low and, generally, the prognosis is good. The Castleman disease is considered a rare entity, but it should be always taken into consideration when it comes to a differential diagnosis in a young patient who presents a retroperitoneal mass at imagery exams. The condition affects the lymphatic system and is characterized by a hyperplasia of the lymph nodes, sometimes associated with herpes virus infection. The clinical picture is often non-specific; the pain may be the only symptom. The imaging methods are not always conclusive for the final positive diagnosis and the histopathological examination is always necessary. Pelvic Castleman disease can be misdiagnosed as myoma or an adnexal tumor. In this article, we review the present knowledge regarding the pathogenesis, pathology and management of these rare retroperitoneal tumors. Both conditions, when located in pelvis must be taken into consideration in the differential diagnosis of uterine myomas, especially in the pedunculated form.

Corresponding author: Claudia Florida Costea, Associate Professor, MD, PhD; e-mail: costea10@yahoo.com; Alexandru Carauleanu, Senior Lecturer, MD, PhD; e-mail: acarauleanu@yahoo.com

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9. Severe traumatic brain injury (TBI) - a seven-year comparative study in a Department of Forensic Medicine

Razvan Stefan Tolescu, Marian Valentin Zorila, Mircea-Sebastian Serbanescu, Kamal Constantin Kamal, George Lucian Zorila, Ilie Dumitru, Charoula Florou, Laurentiu Mogoanta, Ion Alexandru Vaduva, Liliana Stanca, Roxana Eugenia Zavoi

Deaths caused by traumatic brain injury (TBI) increase in incidence every year worldwidely, mainly in developing countries. Thus, World Health Organization (WHO) estimates that in 2020, TBI will become the third main cause of death. In our study, we evaluated the deaths caused by TBI recorded within the Institute of Forensic Medicine of Craiova, Romania, between 2011 and 2017. Therefore, according to age, the cases were divided into two groups: people aged 0-18 years old (including 18 years old) and people aged over 18 years old (a total of 1005 cases, of which 971 were adults and 34 included in the age group 0-18 years old). In both groups, most patients were males from the rural area. In adults, falling was the main legal entity of the cases, followed by car accidents (which were the most common in children). In both groups, in car accidents, most of them were pedestrians and car occupants. Various aggressions (human, animal, self-injury) were found in 94 (9.68%) of the adult cases and in four (11.76%) cases of children. Another parameter under study was the blood alcohol concentration, being observed that most of the subjects with positive blood alcohol content died from car accidents. By evaluating the Glasgow Coma Scale (GCS) score as a prognostic factor, most of the subjects presented third and fourth degree coma at admission; still, 5.14% of the adult patients who deceased had GCS score 15 at admission, death occurring probably by developing some intracranial hematomas in time. Regarding the morphology of the lesions, most patients presented various forms of cranial fractures, 185 (19.05%) adults in association with extradural hemorrhages/hematomas, but also there were four cases with extradural hematomas without any cranial fractures. In children, there was highlighted a single case of extradural hemorrhage under the fracture line. Seventy-eight percent of the adults and 44.12% of children presented subdural hematomas associated with other meningo-cerebral lesions. Also, 83.63% of the adults and 97% of children presented brain contusions. In both groups, brain laceration was observed in approximately 50% of the cases.

Corresponding author: Mircea-Sebastian Serbanescu, Lecturer, MD, PhD; e-mail: mircea_serbanescu@yahoo.com; George Lucian Zorila, University Assistant, MD, PhD; e-mail: zorilalucian@gmail.com

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10. Genetic aspects in schizophrenia. Receptoral theories. Metabolic theories

Simona Corina Trifu, Anca Vladuti, Antonia Ioana Trifu

Ties between schizophrenia (SCZ) and genetics are undeniably significant issue prone to be discussed in the nowadays psychology. Recent research on this domain focuses more on specific genes and heredity (specifically monozygotic pairs of twins) for diagnosing SCZ, than on environmental influences. SCZ is considered a multifactorial disease, thought to convert from a merger of risk and biological genes and environmental factors that could alter and reshape the trajectory of brain development. On this regard, this review sums up recent and innovative methods of distinguishing schizophrenic features from other mental illnesses in patients, based on chromosomal and genes changes. The term reverse genetics is no longer up to date, being replaced with genome scanning and positional cloning. For many researchers, genome scanning is continuing the reverse of the sensible strategy for detecting various important biological disorders, which may start from the discovery of a protein or any other molecule involved in a biological process, being followed by its gene cloning. Genes being discovered in this manner could become candidate genes for the disease. However, genome scanning occurs through testing each chromosomal segment (or mitochondrial genome) for the counter transmission of the disease.

Corresponding author: Simona Corina Trifu, Lecturer, PhD; e-mail: simonatrifu@yahoo.com

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11. The sphenoethmoidal sinus and the modified anatomy of the related structures

Mugurel Constantin Rusu, Sorin Hostiuc, Andrei Gheorghe Marius Motoc, Carmen Aurelia Mogoanta, Julietta Cristina Sava, Mihai Sandulescu

The anterior extent of the sphenoidal sinus in the posterior ethmoid was less investigated. Our purpose was to study whether, or not, the occurrence of a sphenoethmoidal sinus (SES) relates to a sagitally-shortened ethmoid. A retrospective cone-beam computed tomography (CBCT) was performed on 36 patient files. In six patients were found SES extended anteriorly above the posterior third of the middle turbinate (MT). Two of these patients had bilateral SES with ethmoidal chambers included in the lateral and superior nasal walls and draining in the sphenoethmoidal recesses. The correlation between the nasion-to-concha sphenoidalis distance and the presence of SES was statistically significant (less than 40 mm in SES cases and more than 40 mm in non-SES cases). We also found: (i) superior turbinates (STs) with ethmoidal and sphenoidal insertions on one side and ethmoidal and maxillary insertions on the opposite side (the maxillary insertion of ST modifies surgical landmarks and was not previously reported), (ii) MT perforation and (iii) pterygoid recess of the maxillary sinus located beneath the pterygopalatine ganglion fossa. The SES thus shortens sagitally the lateral nasal wall but does not modify its morphology. The MT perforation, ST maxillary insertion and the pterygoid recess are rare anatomic variants not reported previously in our knowledge.

Corresponding author: Mugurel Constantin Rusu, Professor, MD, PhD, Dr. Hab.; e-mail: mugurel.rusu@umfcd.ro

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12. Spontaneous rupture of immature gastric teratoma with hemoperitoneum in a newborn with 3-year follow-up

Chul Kyu Roh, Min Jung Jung, Jiyoon Kim, Susie Chin, Ahrim Moon

Among the subtypes of germ cell tumors, teratomas are the most frequent in the pediatric population and commonly occur in the sacrococcygeal region and the gonads. Less than 1% of all teratoma are found in abdominal organs including the stomach, liver, and kidney. Gastric teratomas are very rare tumors predominantly found in infants. Moreover, an immature gastric teratoma is exceptionally rare. Here, we present a case of immature gastric teratoma with spontaneous rupture in a newborn who was preoperatively diagnosed with neuroblastoma. On the first day after birth, the neonate presented with progressive abdominal distension accompanying respiratory distress. A firm mass was detected during a physical examination of the abdomen. An emergency exploratory laparotomy revealed hemoperitoneum resulting from a rupture of the tumor located in the posterior wall of the gastric antrum. Complete resection of the tumor and gastroduodenostomy were performed. The pathology evaluation revealed a grade 3 immature gastric teratoma with no malignant components. The patient was treated with adjuvant chemotherapy to prevent recurrence, since the tumor was ruptured in the abdominal cavity and the level of alpha-fetoprotein was decreased but still remained high above the normal range after surgery. In conclusion, physicians should be aware of the existence of gastric teratoma as the differential diagnosis of a huge abdominal mass in infants, especially neonates. Complete surgical removal of the tumor and long-term follow-up has been adopted as the standard management for immature gastric teratoma, although there has been controversy with adjuvant chemotherapy.

Corresponding author: Min Jung Jung, MD; e-mail: mj@schmc.ac.kr

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13. Clear cell change in follicular adenoma of the thyroid. A diagnostic challenge

Jose-Fernando Val-Bernal, Maria Martino

Clear cells in thyroid neoplasms can take two main forms: balloon-shaped and signet-ring cells. Balloon-shaped cell change in follicular adenoma is rare. A review of the literature has revealed only 20 previously published cases. We report herein a new case in the right thyroid lobe of a 45-year-old man. The clinicopathological data of the 21 cases including our paper have revealed that the ages of the patients ranged from 22-70 years, with a mean of 41.6 years. There was a clear predominance in women (M:F, 1:6). The most frequent location was in either of both lobes (81.8%), rarely affecting the isthmus. One case was observed in an ectopic thyroid in the submandibular region. The size ranged from 0.7-5.5 cm (mean 2.9 cm). The type of surgical intervention where this data was reported it was lobectomy for 10 (55.5%) cases, thyroidectomy for six (33.3%) cases, and simple excision for two (11.1%) cases. In one patient, the lobectomy was accompanied by cervical lymph node dissection. No cases recurred or extended outside the thyroid. The main differential diagnoses include intrathyroidal clear cell tumor of parathyroid origin, clear cell carcinoma of follicular, oncocytic, papillary, medullary or undifferentiated (anaplastic) origin, paraganglioma, metastatic clear cell carcinoma, especially of renal origin, metastatic balloon cell melanoma, and clear large-cell lymphoma. A thyroid lesion showing clear cell change constitutes a diagnostic challenge in cytological and biopsy diagnosis. Careful observation of the routine techniques along with the aid of an adequate immunohistochemical panel is essential to reach a correct biopsy diagnosis.

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

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