Immunohistochemical expression patterns of S100, synaptophysin, chromogranin A and neuron specific enolase in predicting malignant behaviour in paragangliomas.

PURPOSE: The purpose of this study was to evaluate the role of immunohistochemical markers in the prediction of malignancy in paragangliomas. METHODS: Our institute's patient records between 1990-2012 were retrieved in order to identify patients who were treated for paragangliomas. Size and location of the tumour, existence of concurrent metastatic disease, patient demographics and survival were recorded. Haematoxylin-eosin stained slides were reviewed and all tumours were stained specifically for neuron specific enolase (NSE), chromogranin, synaptophysin and S100 protein positivity. Positivity and expression patterns of the above markers were evaluated and compared between malignant and benign tumours. Malignant behaviour was defined when patient had concurrent or subsequent lymph node involvement, local recurrence and/or metastases. RESULTS: A total of 22 patients with a diagnosis of paraganglioma were treated in our institutes. Female to male ratio was 1.75: 1. The mean age was 43.5 and 51.6 years for women and men, respectively. In 5 patients the tumors had malignant clinical behavior. Their mean size was 3.65 cm for benign and 4.56 cm for malignant neoplasms. NSE expression was diffuse in 47.1% and 0% for benign and malignant tumors, respectively (p=0.10). S100 expression in the periphery of the tumour was typical in 88.2% and 0% for benign and malignant tumors, respectively (p<0.001). CONCLUSION: Immunohistochemical profile from the combination of NSE, synaptophysin chromogranin and S100 staining patterns can serve as a cheap and valuable tool for correctly distinguishing between malignant and benign paragangliomas with high diagnostic accuracy.

Survivin expression as an independent predictor of overall survival in pancreatic adenocarcinoma.

CONTEXT: Survivin is an antiapoptotic protein with a role in tumorigenesis and suggested prognostic value in several proliferative diseases. AIMS: This study aimed to examine the role of survivin as a prognostic marker in pancreatic adenocarcinoma (PDAC). SETTINGS AND DESIGN: Fifty-one specimens of PDAC were assessed for survivin expression by immunohistochemistry. SUBJECTS AND METHODS: Overall survival and 1-, 3-, and 5-year survival were retrieved retrospectively. STATISTICAL ANALYSIS USED: Bivariate analysis was conducted using Chi-square and Mann-Whitney U tests, while survival analysis was conducted using Kaplan-Meier statistics. RESULTS: Of the 51 assessed cases, 49% were positive for survivin. Survivin expression was significantly correlated 1-year survival and overall survival, particularly in bcl-2 positive cases. CONCLUSIONS: Survivin may be implicated in the bcl-2 and p53 pathways and therefore in the biology of PDAC. Its potential use as a survival predictor and therapeutic target represent a promising field.

Prognostic significance of EGFR and COX-2 expression in colorectal cancer and their association. A study in Greek population.

PURPOSE: Colon cancer is one of the most common malignancies. Various prognostic markers have been proposed and individualized treatment strategies have been adapted according to tumor molecular and genetic characteristics. The purpose of the present study was to retrospectively analyze a possible association between the expression of COX- 2 and EGFR and clinical and histopathological factors of patients undergoing colon surgery in a Greek population. METHODS: Data from our department's prospectively collected database were retrieved for a total of 100 consecutive colectomies that were performed in our department. We examined patient age, sex, tumor stage and location of the tumor. Histological data were also retrieved concerning major tumor diameter, histological grade and immunohistochemical expression of cyclooxygenase (COX)-2 and epithermal growth factor receptor (EGFR). RESULTS: There was no difference between tumors of different differentiation in the expression of EGFR (p=0.146), while there was statistically significant difference in the expression of COX-2 between these groups (p=0.001). There was no difference between these patients in the expression of EGFR (p=0.136), while a statistically significant difference was found in the expression of COX-2 between the same patient groups (p<0.005). CONCLUSION: These data are quite important in order to certify that colorectal cancer molecular and genetic diversity between different study populations is not a confounding factor in the application and clinical implementation of trending individualized decision making in oncological treatments.

Parecoxib's effects on anastomotic and abdominal wound healing: a randomized Controlled trial.

BACKGROUND: Current evidence regarding the effects of selective cyclooxygenase inhibitors on gastrointestinal anastomoses is controversial. An experimental randomized control study was conducted in our institution to histopathologically evaluate the consequences of parecoxib, on intestinal and abdominal wound healing. METHODS: Twenty-four adult Wistar rats underwent laparotomy, ascending colon transection, and hand-sewn anastomosis. They were randomized to receive either parecoxib (0.5 mg/kg twice daily) or 0.9% normal saline by intraperitoneal injection postoperatively. Animals were euthanatized either on the third or the seventh postoperative day. Semiquantitative methods were used to evaluate both intestinal and abdominal wounds for inflammatory cell composition, angiogenesis, fibroblasts, granular tissue, collagen deposition, epithelization, and presence of necrosis, exudate, and abscess formation. Results are presented as (parecoxib: median [IQR] versus control: median [IQR], P-value). RESULTS: No macroscopic anastomotic leakage or wound dehiscence was observed. Intestinal anastomoses in the parecoxib group, showed significantly decreased epithelization (2 [1] versus 3 [1], [P = 0.004]) and collagen deposition (2 [0] versus 3 [1], [P = 0.041]). No difference was observed in angiogenesis (3 [1] versus 2.5 [1], [P = 0.158]). Abdominal wall specimens appeared to demonstrate decreased epithelization (2 [2] versus 4 [0.5], [P = 0.0004]) in the treatment group. No difference between the two groups was identified regarding collagen deposition (2.5 [1] versus 2 [0.5], [P = 0.280]) and angiogenesis (2.5 [1] versus 2 [1], [P = 0.633]). Necrosis was significantly more present in the parecoxib group in both specimen types, (3.5 [1] versus 2.5 [1], [P = 0.017]) and (3 [1] versus 1 [0.5], [P < 0.0001]). CONCLUSIONS: The present study shows that despite the absence of clinical adverse effects, parecoxib can impair anastomotic and abdominal wound healing on a histopathological level.

Protective effects of N-acetylcystein and atorvastatin against renal and hepatic injury in a rat model of intestinal ischemia-reperfusion.

AIM OF THE STUDY: We sought to examine whether the separate and combined effect of N-acetylcystein (NAC) and atorvastatin prevented hepatic and renal tissue injury induced by intestinal ischemia-reperfusion (I/R). MATERIAL AND METHODS: 40 male Wistar rats were allocated into 5 experimental groups; Control (n=8): sham, I/R (n=8): rats underwent occlusion of superior mesenteric artery for 45min, Atorvastatin (n=8): rats received 10mg/kg atorvastatin, NAC (n=8): rats received 160mg/kg NAC, NAC&Atorvastatin (n=8): rats received both aforementioned agents. Administration of the agents was facilitated by oral gavage 24h before I/R. Serum levels of urea, creatinine, transaminases, IL-1ß, IL-6, TNF-α, ICAM-1, as well as liver and kidney histopathological examination were evaluated. RESULTS: Pretreatment with either NAC or Atorvastatin or their combination led to lower levels of transaminases and ICAM-1 (2.75±0.46, 2.88±0.84 and 1.5±0.76 respectively for NAC, Atorvastatin and I/R groups), while only their combination led to lower ratios of IL-1, IL-6 and TNF-α than I/R group (1.3±0.12 vs 1.94±0.54, 1.21±0.11 vs 2.12±0.96 and 1.33±0.11 vs 2.14±0.77, respectively). NAC was associated with enhanced renal tissue histology, while atorvastatin was found superior in protecting hepatic tissue degenaration. CONCLUSIONS: Both agents, seperately and combined, seem to exhibited tissue-specific protective activity against intestinal I/R induced injury.

The effects of antioxidants on a porcine model of liver hemorrhage.

PURPOSE: The aim of this study is to assess the efficacy of the combination of N-acetylcysteine (NAC) and deferoxamine (DFO) in the resuscitation from hemorrhagic shock in a porcine model of bleeding during hepatectomy. METHODS: Twenty-one pigs were divided randomly to three groups: Sham (S) group, n = 5; fluid (F) resuscitation group, n = 8; and fluid plus NAC plus DFO (NAC&DFO) resuscitation group, n = 8. The animals of groups F and NAC&DFO were subjected to left hepatectomy and controlled hemorrhage from the traumatic liver surface. Shock was established within 10 minutes and maintained for 30 minutes at mean arterial pressure (MAP) of 30 to 40 mm Hg. Resuscitation followed the shock period with crystalloids and colloids. Group NAC&DFO received additionally NAC and DFO in doses of 200 mg/kg and 65 mg/kg, respectively. The total time of the experiment was 6 hours. RESULTS: Animal weight, blood loss, excised liver mass, and MAP at the end of the shock period were comparable between experimental groups. Group NAC&DFO received significantly lower volume of both crystalloids and colloids (35% and 42% less, respectively) compared to group F. Hepatocellular proliferation (proliferating cell nuclear antigen) was higher in the antioxidant group. Apoptosis, measured by caspase-3, was restored to sham group levels when NAC and DFO were administered. CONCLUSIONS: Our experimental study showed that coadministration of NAC and DFO during liver hemorrhage can decrease the amounts of fluids needed for resuscitation. Moreover, the antioxidant combination restores the energy dependent apoptosis and proliferation of the hepatocytes.

Expression of Inflammatory and Regenerative Genes in a Model of Liver Ischemia/Reperfusion and Partial Hepatectomy.

PURPOSE/AIM: Hepatic ischemia/reperfusion (I/R) describes the paradox of additional tissue injury caused by reperfusion. The aim of this survey was to investigate the mRNA expression of genes exerting their inflammatory and regenerative reaction in a porcine model of I/R and extended hepatectomy. MATERIAL AND METHODS: Twelve pigs were used, weighing 30-35 kg in average, which were allocated in two groups: the I/R group with eight pigs and the sham-operated (control) one with four pigs. The I/R group underwent portacaval anastomosis and Pringle maneuver followed by extended hepatectomy. The hepatoduodenal ligament was occluded for 150 min and the liver remnant was reperfused for 24 hours. Blood samples were steadily received throughout the surgical procedure, where hepatic biopsies were taken for pathological evaluation. Animals were sacrificed in 24 hours after the onset of reperfusion. RESULTS: Between the two groups, statistically significant differences were noticed in serum values of AST, ALT, ALP, and total bilirubin in the early and late phase of reperfusion. The mRNA expression of iNOS, IL-1b, and TGF-a did not increase significantly in the I/R group. Conversely, the mRNA modification of IL-6, STAT-3, and E-selectin demonstrated significantly increased expression in I/R animals. CONCLUSIONS: In the present survey, a new I/R swine model was proposed and specific parameters were analyzed, revealing differences between the study groups.

Effect of gonadal steroid receptors alterations on the pathophysiology of pelvic organ prolapse and urinary incontinence.

BACKGROUND: The aim of this study was to investigate the contribution of the gonadal steroid receptors expression to the pathophysiological pathways of pelvic organ prolapse (POP) and urodynamic stress urinary incontinence (USUI) after menopause. METHODS: This was a prospective closely-matched controlled clinicopathological study. Immunohistochemistry for estrogen receptor isoform α (ER-α) and ß (ER-ß), as well as for progesterone receptor (PR), was performed on formaline-fixed and paraffin-embedded sections of specimens coming from the pubocervical fascia of postmenopausal women who were allocated into three groups: patients with synchronous POP and USUI (Group A), patients diagnosed with only POP (Group B), and patients without POP or USUI who underwent gynecological surgery for another benign indication (control group, Group C). RESULTS: There was no statistically significant difference among the three groups for age, parity, body mass index, or smoking. The expression of ER-α receptors was found significantly reduced among samples of Group B when compared with control group. Statistically significant reduction not only for ER-α, but for ER-ß, as well, was noticed among samples of Group A, compared to the other two groups. No remarkable differences concerning the density of PR receptors were observed among the three groups. CONCLUSIONS: Alterations of ER-α in the pubocervical fascia and around the urethra in postmenopausal women may play an important role in the pathophysiology of POP. In addition, the risk for developing USUI among POP patients seems to be strongly associated with the reduction of both estrogen receptors (ER-α and ER-ß) expression.

Diagnostic and Therapeutic Challenges of Intrahepatic Biliary Cystadenoma and Cystadenocarcinoma: A Report of 10 Cases and Review of the Literature.

The objective of this study was to present our experience with intrahepatic biliary cystadenomas and cystadenocarcinomas in 10 patients surgically managed in our department. Intrahepatic biliary cystadenomas and cystadenocarcinomas are rare cystic tumors that are often misdiagnosed preoperatively as simple cysts or hydatid cysts. They recur after incomplete resection and entail a risk of malignant transformation to cystadenocarcinoma. A retrospective review was conducted of patients with histologically confirmed intrahepatic biliary cystadenomas and cystadenocarcinomas between August 2004 and February 2013 who were surgically managed in our department. A total of 10 patients, 9 female and 1 male (mean age, 50 years), with cystic liver were reviewed. The size of the cysts ranged between 3.5 and 16 cm (mean, 10.6). Five patients had undergone previous interventions elsewhere and presented with recurrences. Liver resections included 6 hepatectomies, 2 bisegmentectomies, 1 extended right hepatectomy, and 1 enucleation due to the central position and the large size of the lesion. Pathology reports confirmed R0 resections in all cases. All patients were alive after a median follow-up of 6 years (range, 1-10 years), and no recurrence was detected. Intrahepatic biliary cystadenoma and cystadenocarcinoma should be considered in differential diagnosis in patients with liver cystic tumors. Because of the high recurrence rate and difficult accurate preoperative diagnosis, formal liver resection is mandatory. Enucleation with free margins is an option and is indicated where resection is impossible.

Comparative Effects of Ischemic Preconditioning and Iron Chelation in Hepatectomy.

PURPOSE/AIM: Major hepatectomies can result in severe ischemia/reperfusion (I/R) injury of the liver. The aim of this survey is to comparatively evaluate the effects of a surgical and a pharmacological hepatoprotective modality on the liver remnant in a porcine model of hepatectomy. MATERIAL AND METHODS: Twenty-one Landrace pigs were randomly divided into three groups: a control group (CON) (n = 7), an Ischemic Preconditioning (PRE) group (n = 7) and a Desferoxamine (DFX) treated one (n = 7). Animals were subjected to 120 min of liver ischemia with subsequent 75% hepatectomy followed by 24-hr reperfusion. In all animals, continuous intracranial pressure (ICP) monitoring was employed. Blood samples were collected at t0, t6, t12, and t24 hrs after reperfusion. Liver remnant specimens were excised for histological examination. RESULTS: In the PRE group, ICP was statistically lower at t6 time point compared to CON group and in comparison with t0. In addition, ICP was significantly lower at all-time points after reperfusion in the DFX group. Finally, with regard to DFX and PRE group correlation, ICP was significantly lower at t0, t12, and t24 time points after reperfusion in the DFX group. In the PRE group, NH3 levels were significantly lower at t12 after reperfusion compared to CON and DFX groups. Histological evaluation elucidated significantly less hepatocellular necrosis, apoptosis, and degeneration in the PRE and DFX groups correlated to CON group. CONCLUSIONS: Both hepatoprotective modalities including PRE and DFX administration are associated with lower ICP levels and correlated with attenuated liver remnant injury.

A case of postmenopausal androgen excess.

Ovarian steroid cell tumors are very rare but potentially life-threatening neoplasms. They represent less than 0.1% of all ovarian tumors, typically present in premenopausal women and frequently manifest with virilization. Signs of hyperandrogenism may appear in postmenopausal women due to tumorοus and non-tumorοus adrenal and ovarian causes as well due to the normal aging process. In any case, steroid cell tumor should be suspected in postmenopausal women who present with rapid progressive androgen excess symptoms. This report describes a case of a 67-year-old postmenopausal woman with signs of hyperandrogenism, where an ovarian steroid cell tumor was diagnosed and treated by laparoscopic bilateral salpingo-oophorectomy and synchronous hysterectomy.

Expression of gonadal steroid receptors in the ovaries of post-menopausal women with malignant or benign endometrial pathology: a pilot study.

This pilot study aimed to investigate the expression of estrogen (ER) and progesterone receptors (PR), as well as their subtypes [alpha (ERα), beta (ERß)], in the ovaries of postmenopausal women with benign or malignant endometrial pathology. Twenty postmenopausal women (age 66.2 ± 7.4 years) were included, diagnosed with benign (n = 10) or malignant [(serous/papillary (n = 4), endometrioid (n = 6)] endometrial lesions. Higher ERß and PR ovarian expressions were observed comparing women with endometrioid versus non-endometrioid endometrial carcinoma (p = 0.022 and p = 0.029, respectively). Age, age at menarche and presence of hypertension were negatively associated with ERs and PR expression. The expression of ERα and ERß was inversely correlated with menopausal age, which was not verified for PR. No significant association was observed between ERs or PR expression and benign or malignant endometrial pathology. Higher expression of ERß and PR in the postmenopausal ovary is associated with the presence of a less aggressive type of endometrial cancer, comparing women with endometrioid versus non-endometrioid lesions. The expression pattern of ovarian receptors did not differ regarding the development of benign or malignant endometrial lesions. Larger observational studies are necessary to confirm the significance of our findings.

Anal adenocarcinoma complicating chronic Crohn's disease.

INTRODUCTION: Colorectal adenocarcinoma and Crohn's disease are known to be associated entities. However, a carcinoma arising within a chronic perianal fistulous tract in a patient with Crohn's disease is a rare complication. PRESENTATION OF CASE: We present a case of a 40-year-old male patient with a long-standing perianal Crohn's disease who developed an anal mucinous adenocarcinoma within the fistulous tracts. DISCUSSION: Although, Crohn's disease and colorectal carcinoma association is well established, few cases have been reported where the cancer has originated within a perianal fistula. Constant mucosal regeneration occurring within a fistula seems to be the predominant pathogenetic mechanism, while immunosuppressants and anti-TNF agents may also contribute to the malignant transformation. Unfortunately, the lack of suspicion and the inadequate physical examination or colonoscopy due to exacerbation of the perianal symptoms could lead to delayed diagnosis; and thus, a poor prognosis. CONCLUSION: Albeit a rare complication, clinicians should maintain a high degree of vigilance about the possible development of adenocarcinoma in patients with long-standing perianal Crohn's disease. Thus, these patients should be kept under regular surveillance with examination under anaesthesia and biopsies or curettage of the tracts.

A 12-year experience at a tertiary hospital on patients with multiple primary malignant neoplasms.

PURPOSE: The incidence of multiple primary malignant neoplasms (MPMN) has dramatically increased. The purpose of this retrospective study was to present the 12-year experience at a University Hospital in patients with MPMN and to investigate the role of genetic factors in their pathogenesis. METHODS: The medical records of 7516 cancer patients, treated in our Institution from 2000 to 2012, were reviewed. Diagnosis of MPMN was based on the Warren and Gates' criteria. RESULTS: Among 7516 patients, 39 (0.5%) (10 men, mean age 70.0±6.98 years, and 29 women, mean age 64.7±8.24 years) presented with MPMN. Eighty-two percent of them developed 2 primary malignant neoplasms (PMNs), whereas 3 PMNs were developed in 7 patients. Breast cancer was the most common cancer type diagnosed among female patients (59%); 14 and 3 had 2 and 3 PMNs, respectively. Eight had a family history of breast cancer while in 3 genetic testing revealed mutations in BRCA1 and BRCA2 genes. The second most common type of malignancy was colorectal cancer (24%); 5 developed 2 PMNs, whereas 2 developed 3 PMNs. Five patients had a family history of colorectal cancer. Colon cancer was the most frequent neoplasm among male patients (50%; 3 developed 2 and 2 3 PMNs. In 2 patients the family history was positive for colorectal cancer. CONCLUSIONS: Although many factors may contribute to MPMN development, positive family history and inherent mutations significantly predispose to MPMN appearance. Thus, management of MPMN patients should be based on a detailed family history and genetic testing.

The effects of hemorrhagic shock secondary to hepatectomy in a swine model.

BACKGROUND: Ischemia-reperfusion injury caused by severe hemorrhagic shock and subsequent resuscitation leads to deterioration of hepatic homeostasis and possibly to liver failure. The present study focuses on determining whether there is a different biological response to hemorrhagic shock by different sources of hemorrhage, hepatic hemorrhage (HH) versus peripheral hemorrhage. METHODS: Twenty-one male swine (Sus scrofa domesticus) were randomly allocated in three groups as follows: sham group (S, n = 5), central venous hemorrhage group, (CVH) (n = 8), and HH group (n = 8). Hepatectomy of the left liver lobe was carried out in groups CVH and HH, and the animals were subjected to controlled bleeding from the internal jugular vein and the traumatic liver surface, respectively. After 10 min of hemorrhage, shock was maintained for 30 min at mean arterial pressure levels of 30 mm Hg-40 mm Hg and resuscitation was initiated with crystalloids and colloids. Hemodynamic parameters and fluid balance were monitored throughout the 6 h of total duration of the experiment. Blood samples were collected at 0-, 40-, and 360-min time points for transaminases, albumin, and interleukin-6 measurement. Hepatic tissue was harvested at the end of the experiment for oxidative marker and proliferation analysis. RESULTS: Although blood loss was comparable between the two groups, the amount of fluids needed for resuscitation was higher for the HH group. Inflammatory response, measured by interleukin-6, was found higher in HH group. Oxidative stress markers did not reveal statistically significant difference between the two groups. Liver hemorrhage decreased hepatocellular proliferation measured by proliferating cell nuclear antigen. CONCLUSIONS: Our study provides evidence that HH entails worse consequences for the hepatocytes than systemic hemorrhage. Higher needs for resuscitation fluids, decreased proliferation, and augmented inflammatory response when HH takes place are findings with possible clinical importance in liver surgery and trauma.

Uncommon benign lesions of the adrenal glands mimicking sinister pathologies: report of 8 cases.

PURPOSE: To present series of patients with large rare primary lesions of the adrenal glands that were operated in our department. The initial indication for surgery was decided based on their impressive similarity to other more sinister adrenal pathologies. METHODS: The clinical records of the department and histopathology reports, covering the 1986-2015 period were assessed. Rare adrenal pathologies that preoperatively were clinically mimicking other adrenal tumors were included. RESULTS: In total, 8 patients (age range 20-75 years) with rare tumors of the adrenal glands were found. Seven patients had a preoperative indication for adrenalectomy due to the possibility of malignancy. In one patient surgery was undertaken due to the possible diagnosis of adrenal hemorrhagic cyst. Among these patients 4 had a histopathologic diagnosis of hemangiomas, one of a lymphangiomatous cyst and 3 of myelolipomas. CONCLUSION: Rare benign tumors of the adrenal glands can present as very large lesions that can be either diagnosed incidentally or due to atypical symptoms. Though unusual, they should be considered in the differential diagnostic approach of adrenal lesions, because they share common clinical and radiological characteristics with more sinister and frequent lesions such as malignant tumors and also hematomas.

Loss of Raf-1 kinase inhibitor protein (RKIP) is strongly associated with high-grade tumor budding and correlates with an aggressive phenotype in pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human cancers and is known to inhibit Ras/Raf/MEK/ERK signaling. By suppressing the activation of the NFkB/SNAIL circuit, RKIP can regulate the induction of epithelial-mesenchymal transition (EMT). The aim of this study was to evaluate RKIP expression and to determine its association with clinicopathological features, including EMT in form of tumor budding in pancreatic ductal adenocarcinoma (PDAC). METHODS: Staining for RKIP was performed on a multipunch Tissue Microarray (TMA) of 114 well-characterized PDACs with clinico-pathological, follow-up and adjuvant therapy information. RKIP-expression was assessed separately in the main tumor body and in the tumor buds. Another 3 TMAs containing normal pancreatic tissue, precursor lesions (Pancreatic Intraepithelial Neoplasia, PanINs) and matched lymph node metastases were stained in parallel. Cut-off values were calculated by receiver operating characteristic (ROC) curve analysis. RESULTS: We found a significant progressive loss of RKIP expression between normal pancreatic ductal epithelia (average: 74%), precursor lesions (PanINs; average: 37%), PDAC (average 20%) and lymph node metastases (average 8%, p<0.0001). RKIP expression was significantly lower in tumor buds (average: 6%) compared to the main tumor body (average 20%; p<0.005). RKIP loss in the tumor body was marginally associated with advanced T-stage (p=0.0599) as well as high-grade peritumoral (p=0.0048) and intratumoral budding (p=0.0373). RKIP loss in the buds showed a clear association with advanced T stage (p=0.0089). CONCLUSIONS: The progressive loss of RKIP seems to play a major role in the neoplastic transformation of pancreas, correlates with aggressive features in PDAC and is associated with the presence of EMT in form of tumor budding.

Hofbauer cells morphology and density in placentas from normal and pathological gestations.

PURPOSE: In placentas from uncomplicated pregnancies, Hofbauer cells either disappear or become scanty after the fourth to fifth month of gestation. Immunohistochemistry though, reveals that a high percentage of stromal cells belong to Hofbauer cells. The aim of this study was to investigate the changes in morphology and density of Hofbauer cells in placentas from normal and pathological pregnancies. METHODS: Seventy placentas were examined: 16 specimens from normal term pregnancies, 10 from first trimester's miscarriages, 26 from cases diagnosed with chromosomal abnormality of the fetus, and placental tissue specimens complicated with intrauterine growth restriction (eight) or gestational diabetes mellitus (10). A histological study of hematoxylin-eosin (HE) sections was performed and immunohistochemical study was performed using the markers: CD 68, Lysozyme, A1 Antichymotrypsine, CK-7, vimentin, and Ki-67. RESULTS: In normal term pregnancies, HE study revealed Hofbauer cells in 37.5% of cases while immunohistochemistry revealed in 87.5% of cases. In first trimester's miscarriages and in cases with prenatal diagnosis of fetal chromosomal abnormalities, both basic and immunohistochemical study were positive for Hofbauer cells. In pregnancies complicated with intrauterine growth restriction or gestational diabetes mellitus, a positive immunoreaction was observed in 100 and 70% of cases, respectively. CONCLUSIONS: Hofbauer cells are present in placental villi during pregnancy, but with progressively reducing density. The most specific marker for their detection seems to be A1 Antichymotrypsine. It is remarkable that no mitotic activity of Hofbauer cells was noticed in our study, as the marker of cellular multiplication Ki-67 was negative in all examined specimens.

Hofbauer cells morphology and density in placentas from normal and pathological gestations / Morfologia e densidade das células de Hofbauer em placentas de gestações normais e patológicas

PURPOSE: In placentas from uncomplicated pregnancies, Hofbauer cells either disappear or become scanty after the fourth to fifth month of gestation. Immunohistochemistry though, reveals that a high percentage of stromal cells belong to Hofbauer cells. The aim of this study was to investigate the changes in morphology and density of Hofbauer cells in placentas from normal and pathological pregnancies. METHODS: Seventy placentas were examined: 16 specimens from normal term pregnancies, 10 from first trimester's miscarriages, 26 from cases diagnosed with chromosomal abnormality of the fetus, and placental tissue specimens complicated with intrauterine growth restriction (eight) or gestational diabetes mellitus (10). A histological study of hematoxylin-eosin (HE) sections was performed and immunohistochemical study was performed using the markers: CD 68, Lysozyme, A1 Antichymotrypsine, CK-7, vimentin, and Ki-67. RESULTS: In normal term pregnancies, HE study revealed Hofbauer cells in 37.5% of cases while immunohistochemistry revealed in 87.5% of cases. In first trimester's miscarriages and in cases with prenatal diagnosis of fetal chromosomal abnormalities, both basic and immunohistochemical study were positive for Hofbauer cells. In pregnancies complicated with intrauterine growth restriction or gestational diabetes mellitus, a positive immunoreaction was observed in 100 and 70% of cases, respectively. CONCLUSIONS: Hofbauer cells are present in placental villi during pregnancy, but with progressively reducing density. The most specific marker for their detection seems to be A1 Antichymotrypsine. It is remarkable that no mitotic activity of Hofbauer cells was noticed in our study, as the marker of cellular multiplication Ki-67 was negative in all examined specimens.

OBJETIVO: Em placentas de gestações sem complicações, as células de Hofbauer desaparecem ou se tornam raras após o quarto ou quinto mês de gestação. Entretanto, a imunohistoquímica revela que uma alta porcentagem de células estromais pertencem às células de Hofbauer. O objetivo do presente estudo foi investigar as alterações da morfologia e densidade das células de Hofbauer em placentas de gestações normais e patológicas. MÉTODOS: Foram examinadas 70 placentas: 16 provenientes de gestações normais a termo, 10 de abortos espontâneos no primeiro trimestre, 26 de casos diagnosticados como anormalidade cromossômica do feto, e amostras de tecido placentário com complicações causadas pela restrição de crescimento intrauterino (8) ou pelo diabetes mellitus gestacional (10). Cortes corados com hematoxilina-eosina (HE) foram submetidos a estudo histológico e imunohistoquímico utilizando-se os seguintes marcadores: CD 68, lisozima, antiquimotripsina A1, CK-7, vimentina, e Ki-67. RESULTADOS: Em gestações normais a termo, o estudo HE revelou células de Hofbauer em 37,5% dos casos, enquanto a imunohistoquímica as revelou em 87,5% dos casos. Em abortos do primeiro trimestre e em casos de diagnóstico prenatal de anormalidades cromossômicas fetais, tanto o estudo básico como o estudo imunohistoquímico foram positivos para células de Hofbauer. Em gestações complicadas pela restrição de crescimento intrauterino ou pelo diabetes mellitus gestacional, imunoreação positiva foi observada respectivamente em 100 e 70% dos casos. CONCLUSÕES: As células de Hofbauer estão presentes nos vilos placentários durante a gestação, embora com densidade progressivamente reduzida. O marcador mais específico para sua detecção parece ser a antiquimotripsina A1. Vale salientar que atividade mitótica de células de Hofbauer não foi detectada em nosso estudo, uma vez que o marcador de multiplicação celular Ki-67 foi negativo em todas as amostras examinadas.