Clinical and pathological aspects of condyloma acuminatum - review of literature and case presentation.

Condyloma acuminatum (CA) is a pathology caused by the human papillomavirus (HPV). It is manifested by the appearance of warts in the vulvar, pubic, and anorectal regions, but can occur in other areas. It is a common disease that can be prevented by using measures such as condoms or vaccine. Topical, local, pharmacological, surgical, and excisional therapy options are available for this pathology. Macroscopically, it appears as a vegetative tumor, with a single implantation base that branches towards the periphery, with a cauliflower appearance. CA is defined microscopically by acanthosis, parakeratosis, papillomatosis and koilocytosis. Immunohistochemical studies can detect the presence of various HPV strains or viral antigens and can emphasize certain specific characteristics; e.g., in the case presented in this study, we observed that the tumor had a fulminant evolution due to a strong vascular base identified with anti-cluster of differentiation (CD) 34 antibody, by the existence of epithelial cells with a high degree of cell proliferation, as evidenced by the anti-Ki67 antibody, the inactivation of the tumor suppressor gene and the appearance of immunolabeling for the anti-p53 antibody, by the strong immunoreactivity for p63 which reveals the existence of cells with dysplastic and neoplastic transformation potential, but also by detecting the immunolabeling for p16INK4a that is associated with the existence of HPV. Also, the tumor was immunoreactive for cytokeratin (CK) AE1∕AE3, partially immunoreactive for CK5∕6 in the basal layer and negative for CK7, which demonstrates the squamous epithelial origin of the described tumor. Subepithelial cells of the inflammatory system have been identified, such as macrophages immunolabeled with anti-CD68 antibody, T-lymphocytes immunolabeled with anti-CD3 antibody and rare B-lymphocytes immunolabeled with anti-CD20 antibody, which demonstrates the strong cellular response to remove the virus from the structure. Surgical and excisional treatment was helpful for the patient, because she was able to resume normal sexual activity and defecation, and on the other hand, microscopic studies showed the potential for malignant transformation of CA.

The influence of gestational diabetes mellitus (GDM) and gestational hypertension (GH) on placental morphological changes.

Gestational diabetes mellitus (GDM) and gestational hypertension (GH) are some of the most common medical conditions associated with pregnancy. These can be correlated with placental morphopathological changes and implicitly can influence good fetal development. The age and weight of the mother can be correlated directly proportionally with those of the fetus but also with histoarchitecture and placental vascularization. The placental appearance associated with GDM and GH reveals macroscopic features, such as calcifications, fibrin deposits and placental infarcts, but the most relevant pathological features are the microscopic ones, highlighted by the classical staining techniques: Hematoxylin-Eosin (HE), Periodic Acid-Schiff (PAS)-Hematoxylin and Masson's trichrome (MT), but also by immunohistochemical technique with the help of the anti-cluster of differentiation 34 (CD34) antibody that labeled the capital endothelium in the structure of the placental terminal villi and thus we were able to quantify the vascular density according to the associated medical pathology. The microscopic changes identified were represented by intravillous and extravillous fibrin depositions, massive placental infarctions caused by vascular suppression due to various causes, such as thrombosis, but also placental calcifications. All these macroscopic and microscopic morphopathological changes, together with the clinical data of the mother and the newborn, we have demonstrated that they are interconnected and that they can vary depending on the pathology, GH or GDM.

Evaluation of placental vascularization in thrombophilia and intrauterine growth restriction (IUGR).

The placenta is an essential organ in the proper development of pregnancy, and it can present a lot of structural and vascular lesions that can affect fetal development. One of the pathologies associated with pregnancy, which can change the placental structure is thrombophilia (TPh), and this can be correlated with an intrauterine growth restriction (IUGR) of the fetus. Maternal clinical aspects (age, weight) can be correlated with fetal ones (weight, gender), but also with the structural and vascular aspect of the placenta. The placental structure associated with TPh and IUGR shows macroscopic changes, such as fibrin deposition, calcifications and placental infarctions, but microscopic lesions are best highlighted by classical staining techniques: Hematoxylin-Eosin (HE), Masson's trichrome (MT) and Periodic Acid-Schiff (PAS)-Hematoxylin, but also by immunohistochemistry technique with the help of anti-cluster of differentiation 34 (CD34) antibody that could make it possible to quantify vascular density depending on the pathology. Microscopic changes were massive infarcts caused by vascular ischemia, intravenous and extravillous fibrin deposits, calcifications, and vascular thrombosis. All these clinical, morphological and morphopathological data are interconnected and may vary in the presence of TPh and IUGR.

Triple immunohistochemistry for assessing the inflammatory, vascular and progression of adenomyosis.

Adenomyosis is a benign pathology, common to both women at reproductive age as well as later during menopause. This condition is accompanied by a strong symptomatology, which has induced intense research on this topic. From a morphological point of view, it is represented by the existence of endometrial glands and, sometimes, of the periglandular stroma (endometriosis) in the structure of the myometrium, at a significant distance from the normal endometrium. Various inflammatory, vascular and mechanical factors accentuate the symptoms and evolution of this pathology. Our study included a total number of 32 patients, eight cases for each of the following histopathological subtypes: endometrium - proliferative phase, endometrium - secretory phase, myometrium with endometrial glands (adenomyosis), and myometrium with hyperplastic transformation of endometrial glands (hyperplastic adenomyosis), respectively. We have conducted clinical, morphological and morphopathological studies of the structures in question. Using the classical histological technique (Hematoxylin-Eosin), we identified the glandular structures; utilizing immunohistochemistry, we have labeled the endometrial epithelium with the anti-cytokeratin 7 (CK7) antibody and we analyzed the periglandular cell types of the immune system: T-lymphocytes using anti-cluster of differentiation (CD) 3 antibody, macrophages using anti-CD68 antibody, mast cells using anti-tryptase antibody, periglandular vascularization with the reaction using anti-CD34∕anti-CD31 antibodies, thus demonstrating their involvement in the development of adenomyosis. The interesting aspect of this study is the technique of simultaneously labeling of the inflammatory, vascular and epithelial elements.

Clinical, morphological and immunohistochemical survey in different types of endometriosis.

Endometriosis is a benign pathology, commonly found in women at reproductive age. It is represented by the ectopic presence of the endometrial glandular epithelium in several tissues and organs. This ectopically located tissue can display premalignant or even malignant changes under the influence of certain factors that affect cell structure, function and proliferation. Our study includes a total of 28 patients, with endometriosis of different localizations: ovarian or pelvic endometriosis, adenomyosis or endometriosis of the abdominal wall. We performed a clinical and statistical analysis upon the collected clinical and laboratory data, together with the results obtained by using classical histological and immunohistochemical (IHC) profiling. The classical staining revealed the existence of the ectopic glandular epithelium, while the IHC reactions obtained with the anti-cytokeratin (CK) 7∕anti-CK20, anti-estrogen receptor alpha (ERα)∕anti-progesterone receptor (PR) antibodies, ascertained that these tissues were of endometrial origin. The environmental, hormonal or inflammatory factors influence these areas, so that the ER∕PR scores may be modified, the cellular proliferation might be increased (Ki67+ marker), the anti-apoptotic B-cell lymphoma 2 (BCL2) protein expression and phosphatase and tensin homolog (PTEN) may also be modified. Moreover, tumor protein 53 (p53) was positive in cases with atypia, density of inflammatory cells clearly increased compared to the adjacent normal endometrium, respectively with cluster of differentiation (CD) 3+, CD20+, CD68+, CD79a+, and tryptase+ cells, all of which may influence the cellular structure, histological architecture of the surrounding microenvironment and cause premalignant or even malignant changes in endometriosis outbreaks.

Correlation of clinical and biological evidence - a dominant therapeutic element of succeeding in ectopic pregnancy.

Tubal pathology, smoking, pelvic inflammatory disease, miscarriage, medical or surgical abortion, usage of intrauterine devices (IUDs) for women with salpingitis latent injuries, older than 40 years, are risk factors for ectopic pregnancy. The objective of this study concerns the correlation of the clinical and biological evidence for the early diagnosis of the ectopic pregnancy and, as soon as possible, for the estimation for eventual risk of complications that may appear. The transvaginal ultrasound test, minimal increases in serum beta-human chorionic gonadotropin (ß-hCG) dynamics and blood counts are investigations of choice in achieving our objective. Overcoming ß-hCG critical level (>1198 IU÷mL), the decrease of platelets and changes in platelet constants announce the imminent risk of ectopic pregnancy rupture and the need to take a quick decision on the course of treatment.

Apert syndrome - clinical case.

Apert syndrome - acrocephalosyndactyly - is a rare autosomal dominant disorder representing 1:65 000 cases of living newborns. Characteristic malformations of the Apert syndrome are early craniostenosis, microviscerocranium and II-V finger syndactyly of hand and toes with proximal phalanx of the bilateral thumb "in delta". It is difficult to determine prenatal diagnosis in the second quarter, when examining the morphology of fetal signs; the dysmorphism signs appeared in the third pregnancy quarter. We present here the case of a newborn with Apert syndrome that was born prematurely in our Clinic after a monitored pregnancy, where there was issued a suspicion of cranio-facial dysmorphism, malposition and malformation of the feet and hands in the third quarter of prenatal pregnancy. The diagnosis of Apert syndrome was placed on clinical signs, laboratory and genetic tests. The clinical outcome of the baby in the maternity was favorable, the therapeutic management being established by a multidisciplinary team. Immediate complications were due to the case of prematurity: respiratory distress syndrome and the characteristics of the syndrome: micrognathia and naso-facial dysmorphism, syndactyly, bilateral foot metatarsus adductus.

Delayed interval delivery in twin pregnancy - case reports.

The implementation of assisted reproduction has increased the incidence of multiple pregnancies. Prenatal death of one fetus in the second trimester of twin pregnancy confronts the obstetrician with a difficult problem with regard to the management of pregnancy. The scarcity of the condition and the absence of the large-scale studies make it difficult to advise the parents on the prognosis and optimal management. The unavoidable birth or death of one premature neonate has led to the aim of delayed interval delivery for the other twin. We present in this report two cases of twin pregnancies with delayed-interval delivery and favorable outcomes for the surviving twins. The twin pregnancies conceived by in vitro fertilization (IVF) in HitMed Medical Center, Craiova, Romania. In the first case, one fetus dismiss in utero at 20 weeks of gestation. The second fetus was successfully delivered by Caesarean section, at 36 weeks. In the second case, the first fetus was delivered at 22 weeks. To save the surviving fetus, ligation of the umbilical cord at the cervical level was performed. The second fetus was delivered at 31 weeks by Caesarean section, in good conditions. We describe our management of the cases and the deliveries and the neonatal outcomes. In multiple gestation, prolongation of pregnancy after preterm dismiss in utero or even after delivery of one fetus is feasible in a closely monitored environment.

Pregnancy resulting from IMSI after testicular biopsy in a patient with obstructive azoospermia.

In this article, we report a case of pregnancy obtained in an infertile couple diagnosed with severe male factor infertility. The couple attended for fertility examination reporting a history of 10 years of infertility. The cause of infertility was obstructive azoospermia. The treatment consists of in vitro fertilization (IVF). The ovarian stimulation of female patient was done with antagonist protocol and after ovarian puncture was obtained nine oocytes. The urologist performed testicular sperm extraction (TESE). There were selected nine sperm cells by intra-cytoplasmic morphologically selected sperm injection (IMSI). For this purpose, we used an inverted microscope with high magnification equipped with ×60 air objectives with modulation contrast illumination. After intracytoplasmic sperm injection (ICSI) of sperm into the oocytes there were obtained six normal embryos from which three embryos were transferred into the uterus. A singleton pregnancy was achieved which was completed with birth of a healthy baby in time. This successful outcome shows that use of IMSI and ICSI procedures are really useful in selection of best spermatozoa obtained by TESE in treatment of obstructive azoospermia.

Borderline Brenner tumors associated with ovarian cyst - case presentation.

Borderline Brenner tumors represent quite a rare entity of ovarian tumors (about 2%) that develop from the surface ovarian epithelium. They are formed from papillary structures made of fibrovascular conjunctive axes covered by a transition epithelium, similar to the urinary bladder epithelium. According to the WHO classification, Brenner tumors present the following forms: benign, borderline and malignant. The benign ones are the most frequent, representing about 95%, the borderline represent about 5%, and the malignant ones less than 1%. We present the case of a 64-year patient who was diagnosed with right ovary cyst. The histopathological examination highlighted the presence of a borderline Brenner tumor at the same time with the cystic lesion, on the same ovary. The surgical treatment led to a complete cure of the patient, so that the yearly ultrasound reexamination did not trace the presence of any tumoral relapse.

Evaluation of the implantation site morphology in spontaneous abortion.

The aim of this study was the characterization of the implantation site through histological and immunohistochemical exams and the evaluation of the changes that appear in the pregnancies ended by spontaneous abortion compared to normal pregnancies ended by requested abortion. One hundred eight patients were divided in two groups: the study group that included 58 patients with spontaneous abortion and the control group that included 50 patients with requested abortion. There has been made uterine curettage in all the cases after a complete preoperative evaluation and the obtained product was sent for histopathological evaluation and immunohistochemical study using a VEGF antibody. Studying the histological sections, we noticed the vasculogenesis stages chronology and then according to the histological aspects of normal pregnancy we noticed the histological changes that occurred at the site of implantation in the cases with pathological pregnancies ended by miscarriage. Our results from this study seem to indicate a correlation between decidual vascular changes and the appearance of miscarriage. In pregnancies ended by miscarriage, we found delays in the trophoblast development according to the gestational age at which the event abortifacient happened. The study emphases the temporal differentiation of utero-placental angiogenesis comparing to villous vasculogenesis and angiogenesis in the first trimester miscarriage and normal pregnancy. At the control group, VEGF expression was positive in 88% of cases, while in the study group, pregnancies ended by spontaneous abortion, positive expression of VEGF was present in only 31% of cases. Our data suggest vascular disorders and are in concordance with other histological and ultrasound studies postulating the idea of a link between miscarriage and placental vascular bed pattern changes.

Thoracic endometriosis with a long delay in diagnosis.

This paper describes a case of thoracic endometriosis in 36-year-old woman with a long delay in diagnosis. At the admission in the hospital, the patient had a medical history of persistent dysmenorrhea since the age of 13, infertility and an episode of total right pneumothorax two months ago successfully resolved by minimum pleurotomy of the right hemitorax. She came with moderate pain on right hemithorax and dyspnea, which occurred on the first day of menstruation but she did not have any other respiratory symptoms such as hemoptysis, cough. Radiological imaging (chest radiography and computer tomography) at the time of admission confirmed recurrence of the right pneumothorax. She underwent surgical treatment of the right pneumothorax using a single-port video-assisted approach. Intraoperative macroscopic lesions were found catamenial pneumothorax characteristic diagnosis and biopsy material taken (parietal pleura) for histopathology. Immuno-histochemical tests confirmed the diagnosis of thoracic endometriosis. The gonadotropin-releasing hormone analogue was received by the patient early after surgery and there was no clinical or radiological recurrence at a four months follow-up.

Potential value of in situ cellular immune response in HPV subtype 16 and 18 positive cervical cancer.

UNLABELLED: There is no doubt that the association between infection of the cervical epithelium by carcinogenic Human Papilloma Virus (HPV), particularly types 16 and 18, and cervical cancer (CC) is responsible for the activation of the immune response (IR). Research on tumor infiltrating lymphocytes at the primary tumor site could give us important information on how the immune cells are fighting against cancer. AIM: The aims of our study were to assess HPV status and to evaluate the significance of in situ cellular IR in CC. MATERIALS AND METHODS: We performed a two-step retrospective analysis of IR in 18 CC: evaluation of HPV 16 and 18 infections by in situ hybridization and immune biomarkers (CD20, CD3, CD45) by immunohistochemistry. Immune cell profile, densities (assigned scores "0" if no inflammatory infiltrate, "1+" low, "2+" intense), tissue distribution and classical negative prognosis factors in relationship with survival and relapse were further assessed. RESULTS: We successfully demonstrated HPV 16 and/or 18 in all cases. We reported statistical significant correlations (p<0.005) between CD3, CD20, CD45 and survival (r=0.800), relapse (r=-0.892), clinical stage (r=-0.914), tumor size (r=-1) as well as the association between survival and CC subtype (r=0.548), FIGO stage (r=-0.914), tumor size (r=-0.800) and grading (r=0.61). CONCLUSIONS: The density of different immune cells is significantly involved in guiding prognosis of the CC in high-risk 16 and 18 HPV positive women; low cellular densities for CD3, CD20 and CD45 meaning limited immune response reflect negative disease outcomes promoting local relapse and decreased survival in such settings.

The role of immunohistochemistry in diagnosing a synchronous colon tumor.

Simultaneous presence of an epithelial and lymphoid tumor of the digestive tract is quite rarely met in literature. In this paper, we describe a case which presented such an association. Diagnosis was established by histological study, followed by immunohistochemistry. It is a synchronous colon tumor, associating a non-Hodgkin's lymphoma to a colon adenocarcinoma. The 57-year-old male patient has been clinically diagnosed with a tumor of the left abdominal quadrant and paraclinically (imaging and endoscopic) with colon neoplasm. Exploratory laparotomy revealed two tumors: one tumor of five centimeters in the sigmoid, with firm consistency, mobile on lower plans and the second tumor in the ceco-ascending colon, measuring about 7 cm, irregular, with firm consistency, mobile on lower plans, with lymph nodes extending to retroperitoneal space. The urinary bladder, kidneys, liver and stomach were of normal aspect. Subtotal colectomy was performed with latero-lateral ileo-sigmoid anastomosis. Microscopic examination revealed sigmoid tumor as G1 adenocarcinoma and cecal tumor as B-cell type lymphoma. Immunohistochemistry established the final diagnosis of cecal localization being a diffuse immunoblastic large B-cell non-Hodgkin's malignant lymphoma. The final diagnosis of this patient was actually a synchronous manifestation of a colon adenocarcinoma and non-Hodgkin's lymphoma. This association puts into question synchronous tumors etiopathogeny matter.

Prognostic biomarkers in endometrial adenocarcinoma.

Endometrial carcinoma is the most common malignancy in the female genital system and has increased in incidence during the past years. Our study was retrospective and included 79 patients with diagnosed endometrial adenocarcinoma. The parameters investigated in the study included clinical status, menopause, history of estrogen intake, obesity, histological results, transvaginal ultrasonography. We evaluated the status of the common clinicopathological features and immunohistochemical biomarkers of endometrial carcinoma. The main type of carcinoma was endometrial endometrioid carcinoma (68 cases), followed by serous carcinoma (seven cases). Immunohistochemical study performed included the following antibodies: cytokeratin, vimentin, ER, PR, PTEN, p53, ß-catenin, bcl-2, WT1 and Ki67. The immunohistochemical profile showed significant differences between the two subtypes. The majority of cases showed positivity for steroid hormones and the positivity correlated with the endometrioid subtype. We observed a correlation between p53 overexpression and specific histological alterations. A high percentage of Ki67 positivity tumors correlated with grade 3 tumors, as well as with a high percentage of p53 positivity. The study shows the importance of the use of biomarkers in the positive diagnosis and the guiding of therapeutic approach.