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AIM: To investigate the incidence of KIT immunohostochemical staining in (GI) stromal tumors (GISTs), and to analyze the clinical manifestations of the tumors and prognostic indicators. METHODS: We retrospectively analyzed 50 cases of previously diagnosed GISTs. Tissue samples were assessed with KIT (CD117 antigen), CD34, SMA, desmin, S-100, NSE, PCNA, Ki-67, and BCL-2 for immunohistochemical study and pathological characteristics were analyzed for prognostic factors. RESULTS: Fifteen tumors (30%) were negative in KIT staining. A significant association was observed between gender (male patients: 14/15) and KIT-negative staining (P = 0.003). The patients’s mean age was 56.6 years. Tumors developed in stomach (n = 8), small intestine (n = 5), large intestine (n = 1) and oesophagus (n = 1). The mean tumor size was 5.72 cm. The mitotic count ranged from 0-29/50 HPF (mean: 3.4) and 73% of tumors showed no necrosis. The majority of the tumors (67%) had dual or epithelioid differentiation. Tumors were classified as very low or low risk (n = 7), intermediate risk (n = 5), and high risk (n = 3) groups. Twelve (80%) patients were alive without evidence of residual tumor for an average period of 40.25 mo (12-82 mo); three patients developed metastatic disease to the liver and eventually died within 2-12 mo (median survival: 8.6 mo). CONCLUSION: A small subgroup of GISTs fulfils the clinical and morphological criteria of these tumors, and lacks KIT expression. These tumors predominantly developed in the stomach, being dual or epithelioid in morphology, which are classified as low risk tumors and presented a better survival status than KIT-positive tumors. The ability to diagnose GISTs still depends on immunohistochemical staining but the research should extend in gene mutations. (c) 2007 The WJG Press. All rights reserved.

The majority of ovarian masses in childhood and adolescence are non-epithelial in origin, with a predominance of germ cell tumors, while epithelial neoplasms comprise a small proportion of the total (approximately 15-20%). Mucinous cystadenomas in particular are only sporadically reported in this age group. We present a case of an ovarian mucinous cystadenoma with extended calcification in a premenarchal 11-year-old girl. Pediatric mucinous cystadenomas of the ovary may on rare occasions display extended calcification. Careful evaluation of the remaining pathological features of the tumor is needed in order to avoid misinterpreting this relatively non-specific finding as a feature of malignancy.

Uterine leiomyomas are extremely rare neoplasms in the pediatric and adolescent population. We report a case of a giant uterine leiomyoma measuring 30 cm in the largest diameter in a 16-year-old girl. To our knowledge this is the largest leiomyoma reported thus far in women under the age of 20 years. The patient was admitted to our hospital for the investigation of menstrual disorders, vaginal bleeding and progressive abdominal enlargement. Preoperative diagnosis was ovarian malignancy. Myomectomy was performed. Histopathologic study of the tumor showed an otherwise typical leiomyoma, both grossly and microscopically, with extensive hydropic and myxomatous degeneration and areas of prominent vessels, suggesting an angiomatous neoplasm. Leiomyomas in teenagers often exhibit histological features favoring the diagnosis of malignancy, and should be evaluated with extreme caution. The management of leiomyomas in these young patients should be conservative for the preservation of fertility.

Vascular lesions comprise benign and malignant neoplasms as well as non-neoplastic conditions that may be located in various sites but only rarely in the pelvis or the retroperitoneum. In our study we describe five diverse and unusual cases of vascular lesions of the pelvis, retroperitoneum and colon in female patients: a case of retroperitoneal angiosarcoma, pelvic hemangioendothelioma, pelvic angiomyxoma, retroperitoneal lymphangioleiomyomatosis and a case of diffuse cavernous hemangiomatosis of the colon, with emphasis on their clinicopathological features and differential diagnosis. The recent literature on the subject is also briefly reviewed.

To study the histopathological features of mesenchymal tumors of the uterine corpus with heterologous and hematopoietic components, and review their histogenesis and differential diagnosis from other neoplastic and non-neoplastic lesions.Ten cases of mesenchymal tumors of the uterine corpus, massively infiltrated by hematopoioetic cells, or composed of other benign heterologous elements (adipose tissue in the present cases) were retrieved from the archival files of our laboratory and studied histopathologically. Immunohistochemistry was applied in selected cases.Six of our studied cases were diagnosed as leiomyomas, two as lipoleiomyomas, one as a symplastic lipoleiomyoma, and one as an endometrial stromal tumor. The leiomyomas were massively infiltrated by lymphocytes (5 cases) or eosinophils (one case). Immunohistochemical study of the leiomyomas with massive lymphocytic infiltration revealed the presence of a predominantly B-cell population within the infiltrate, which was polyclonal in nature. The endometrial stromal tumor was severely infiltrated by histiocytes, and was positive for vimentin, CD10, PgR and negative for actin, desmin, ER and caldesmon.The presence of hematopoietic or heterologous elements within an otherwise bland uterine leiomyoma or endometrial stromal tumor may give rise to diagnostic difficulties. Regularity of the tumor margins, low mitotic activity and absence of nuclear atypia or necrosis should be established for the exclusion of a malignancy. In the presence of massive lymphocytic infiltration of a leiomyoma the clonality of the infiltrate may aid in differentiating it from a malignant lymphoma. The pathogenesis and clinical significance of these rare neoplasms remain to be clarified.

To investigate the primary site and the pathological features of secondary intestinal tumors in females, with emphasis on their differential diagnosis from primary neoplasms of the intestines.Seven cases of secondary intestinal tumors in females were retrieved from the archival files of our laboratory. The relative clinical data were also reviewed. Inmmunohistochemistry was performed in cases with diagnostic difficulties.The primary site of the tumor was defined as follows: the ovary (ovarian adenocarcinoma) in five cases (71.4%), the skin (cutaneous malignant melanoma) in one case (14.28%) and the uterine corpus (mixed mullerian tumor) in one case (14.28%). In two cases the primary site was not determined initially, but the investigation showed that the primary tumor was ovarian in origin. In five cases the existence of a primary tumor was already known. Immunohistochemistry was applied in three cases for confirmation of the suspected primary tumor by histological examination.Histological diagnosis of secondary intestinal tumors may be extremely difficult, especially when the primary site is not previously known, and because of the tendency of certain secondary tumors to mimic, both grossly and microscopically, the primary ones. Immunohistochemistry is extremely helpful in resolving these diagnostic difficulties.

Aim: The aim of the study is to further investigate the clinicopathological features of solitary necrotic nodules. Material and methods: Twenty-three archived cases of solitary necrotic nodule of the liver, which were preoperatively misdiagnosed as liver metastases were studied. The pathological findings were correlated with the clinical data of the patients. Results: The nodules were solitary in 20 cases and multiple (2) in three cases, and measured from 0.5-1.5 cm in diameter. Twenty-one cases were located in the right lobe of the liver (91.6%) and two in the left lobe (8.69%). Twenty nodules were found in the subcapsular region (86.95%), while three nodules were located within the hepatic parenchyma (13.04%). More then half of our cases (12) were accompanied by extended calcification. Granulomatous tissue resembling "burnt-out" parasitic granulomas was found in three cases. Conclusions: Solitary necrotic nodules of the liver often mimic malignancy in abdominal imaging. Thus, permanent histopathology of the operative specimen remains the only accurate method of diagnosis. Their pathogenesis is most likely variable, and most reported cases are linked either to a parasitic or a vascular origin. Despite the designation of these lesions as "solitary" they may occasionally be multiple. In addition to the standard histological criteria of solitary necrotic nodules, the relatively small size (15 mm or less) and the frequent presence of calcifications seem to further characterize this enigmatic entity. Solitary necrotic nodule should be included in the differential diagnosis of small liver lesions with extensive necrosis. © Humana Press Inc. 2007.

Growth hormone-releasing hormone (GHRH) stimulates the production and release of growth hormone in the pituitary and induces cell proliferation in a variety of peripheral tissues and tumors. These extrapituitary effects of GHRH are in many cases mediated by a splice variant of GHRH receptor designated SV1 that differs from the pituitary GHRH receptor in a small portion of its amino-terminal region. While SV1 has been detected in several primary tumors and many cancer cell lines its expression in normal tissues remains unclear. In this study we report the results of an immunohistochemical analysis for SV1 and GHRH expression in normal mouse tissues. For the detection of SV1 immunoreactivity we used a polyclonal antiserum against segments 1-25 of the SV1 receptor protein. Mouse heart, colon, lungs, small intestine, stomach and kidneys exhibited increased SV1 immunoreactivity. These tissues were also positive for GHRH expression, however, tissues such as the endometrium were positive only for GHRH and not for SV1 expression. On the contrary, testis were positive for SV1 and not for GHRH expression. These results indicate that SV1 may play a role in normal physiology. © 2006 Elsevier B.V. All rights reserved.

Breast cancer is the leading cause of death from cancer in women. The metastatic involvement of the breast from nonmammary neoplasms is a relatively rare condition. Female patients are affected five to six times more frequently than male patients. We present seven patients with metastasis in the breast from extramammary tumors. Females seemed to be more frequently affected (6 women and 1 man) and included a wide range of ages (17-70 years old). All female patients had suspicious-looking abnormalities (B1-RADS 4) or lesions highly suspicious of malignancy (BI-RADS 5) in the mammography, without a confirmative fine needle aspiration cytology. The primary malignancies were equally distributed between non-hematological (1 renal adenocarcinoma, 1 melanoma, 1 leiomyosarcoma) and hematological (1 non-Hodgkin's, 2 Hodgkin's lymphomas and 1 leukemia). Treatment is therefore modified, taking into consideration the treatment and prognosis of the primary disease.

The development of ectopic decidua is generally considered as a physiologic phenomenon of pregnancy, even though it has been occasionally noted in non-pregnant women. We present three cases of ectopic decidua located in the greater omentum and discuss the histopathologic characteristics, as well as the problems encountered in the differential diagnosis from metastatic lesions. Decidual transformation of the omentum could simulate, both grossly and microscopically, malignant neoplastic lesions such as malignant deciduoid mesothelioma, metastatic mucin-producing adenocarcinoma or even metastatic squamous carcinoma. The application of immunohistochemistry is essential for the establishment of the diagnosis, especially in the presence of deceptively atypical vacuolated cells resembling carcinoma cells. Ectopic decidua does not require any therapeutic intervention because it usually regresses postpartum without any complications.

Gonadoblastoma is a rare tumor occurring almost exclusively in phenotypic females with intersex disorders and dysgenetic gonads. We report a case of gonadoblastoma in an 18-year old female who was admitted to our hospital for the investigation of primary amenorrhea. The patient underwent bilateral gonadectomy. A histopathologic study revealed streak gonads with extended calcification and bilateral gonadoblastoma. We describe the histopathologic features of gonadoblastoma and the pattern of its potential malignant transformation. Difficulties in the histological diagnosis of this rare tumor are also discussed. The need for early prophylactic removal of dysgenetic gonads, especially in patients that carry the Y chromosome, is emphasized.

During the last 15-year period in our laboratory, 14 cases of malignant change of endometriosis were diagnosed in women 37-70 years of age. Seven cases were adenocarcinomas, one case was an adenosarcoma and six cases presented the morphology of endometrial stromal sarcoma. Eleven cases developed in various sites of the genital system (5/11 in the ovaries, 3/11 in the uterus 2/11 in the vagina, 1/11 in the tubal wall) and three cases in extragenital sites (1/3 in the omentum, 1/3 in the pelvis, 1/3 in the colon). Immunohistochemical investigation for the expression of cytokeratines, vimentin, hormonal receptors, E-cadherin, desmine and smooth muscle actin was performed by a streptavidin-biotin method. The immunopathology profile and follow-up results after therapy are presented.

Six cases of extraovarian cystic tumors of mullerian type are reported. Patient age ranged from 27-71 years. Tumor diameters were 5-11 cm and were located in the mesentery (4/6) and retroperitoneum (2/6). Four tumors were of mucinous type (1/4 of borderline malignancy) and two of serous type. These tumors clinically and histopathologically mimic other primary tumors of the peritoneum. The problems of differential diagnosis are discussed.

Primary fallopian tube cancer is the rarest of all gynecologic cancers, presenting as benign pelvic disease or more often as ovarian cancer and almost all cases are diagnosed at operation or autopsy. Primary adenocarcinoma is the most common histological type of primary tube cancer which has traditionally been managed and treated in the same manner as epithelial ovarian cancer. However, unlike ovarian cancer, fallopian tube cancer is not routinely suspected and treatment may be delayed and also seems to have a worst prognosis than ovarian cancer. We present a retrospective study involving 12 patients with primary fallopian tube cancer treated in our department. The clinicopathologic characteristics and treatment are reviewed.

Primary tumors of the appendix are rare and most of them are unrecognized preoperatively, presenting as appendicits, pelvic masses or with no typical abdominal pain. Two cases of mucinous tumors of the appendix presenting as primary ovarian tumors are described. It is important for the gynecologist-oncologist to include mucinous tumors of the appendix into the differential diagnosis of any case of mucinous ovarian tumor and peritoneal pseudomyxoma, especially when these tumors are associated with extraovarian disease.

Resection of the irradiated gut in women with cervical cancer is complicated by high morbidity and mortality mainly due to accidental injuries to the adjacent intrapelvic structures. To eliminate these injuries a new method is proposed.Six patients between 41 and 56 years old who had received radiation therapy for cervical cancer were operated on for post-radiation injury of the terminal ileum. All patients underwent partial resection of the irradiated small bowel plus right colectomy. The surgical technique was undertaken so as to leave parts of the small bowel (20 to 45 cm) adherent to the adjacent organs when complete resection was judged precarious.All patients had an uneventful recovery with 6 to 14 days hospitalization. No complications related to the remaining intrabdominal parts of the gut were observed. All patients died of the primary disease over 1 to 5 years postoperatively.The method is safe, simple and eliminates injuries to the adjacent structures.

The aim of this study was to investigate the clinicopathological features of nine unusual vascular tumors of the female genital tract and to investigate the problems in the differential diagnosis from other genital lesions.In a review of 15,000 specimens of the female genital system examined in our Laboratory during the last decade, nine cases of vascular tumors were found.A capillary hemangioma of the endometrium, one capillary and one cavernous hemangioma of the cervix, six vulva lesions (one capillary, and one cavernous hemangioma and four angiokeratomas) and one hemangiosarcoma of the mons pubis in a 76-year-old patient were diagnosed.The differential diagnosis of the vascular tumors must be made mainly from endometriotic lesions and melanomas. Immunohistochemistry (S-100, CD31, CD34, CKS, EMA) aid in the diagnosis. Local excision is adequate for the benign vascular lesions.

The clinicopathological findings of three cases of endometrial adenocarcinoma arising in uteri with developmental anomalies are described.

Segmental liver grafts with a calculated ideal liver weight (CILW) less than 40% may be associated with portal flow-related injuries and primary dysfunction. This study evaluated the effect of mesocaval shunts on the survival of grafts with a CILW less than 20%. Sixteen pigs underwent orthotopic transplantation of segmental liver grafts with a CILW less than 20%. In eight animals (study group), transplantation was combined with a mesocaval shunt, and eight animals served as controls without a mesocaval shunt. Liver function, systemic hemodynamics, portal vein pressure, intracranial pressure, and cerebral perfusion pressure were assessed postoperatively. The controls showed a rapid impairment of liver function reflected by a significant elevation in aspartate aminotransferase, international normalized ratio, bilirubin, and intracranial pressure and a decrease in cerebral perfusion pressure compared with the study group (P

Epidermoid carcinoma (PSCC) of the endometrium is a rare form of endometrial cancer that constitutes about 0.1% of all malignant epithelial tumors of the uterus. The diagnosis of PSCC is based on strict criteria and is made in the absence of a glandular component of the tumor. Squamous cell carcinoma of the endometrium should enter the differential diagnosis in postmenopausal patients in the presence of atypical squamous cells in the uterine curettage, while the cervical biopsies are negative for malignancy. The presence of HPV should be investigated as well, so that its pathogenetic relation is clarified. While no significant relation was found to p-53, C-NEU and EGFR expression this investigation must be continued because. HPV may interact with tumor suppressor genes.

From January 1993 to December 1998, nine patients with serous papillary endometrial carcinoma (SPEC) were diagnosed and treated at the 2nd Department of Obstetrics and Gynecology, Areteion University Hospital. The incidence of SPEC in our Clinic was 6.77%. The mean age of patients was 65.5 years (range 54-82 years). All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and epiploectomy. Abdominal and para-aortic lymph node sampling was performed in all cases and peritoneal washings were examined cytologically. Histological sections of the specimens, stained with haematoxylin-eosin, were retrieved from the Laboratory of Pathology and re-evaluated by two pathologists. All cases conformed to the diagnostic criteria for SPEC. Immunohistochemical studies were performed in paraffin blocks retrieved from the files, by a streptavidin-viotin method for the detection of vimentin (ENZO monoclonal ab), secretory component (DAKO polyclonal ab), CEA (DAKO monoclonal ab), EMA (DAKO monoclonal ab). The hormonal receptor status, assessed by appropriate positive and negative controls, was studied as well. The presence of mucin and glycogen was studied by histochemical reaction, PAS, PAS diastase and mucicarmine. Serous papillary carcinoma is an unusual but distinct type of endometrical adenocarcinoma, a non-hormonal dependent tumor, with aggressive biologic behavior. Its recognition is mandatory for a correct therapeutic approach.

In aortic reconstruction, intestinal and muscular ischaemia in the lower limbs occurs during cross-clamping of the aorta. After restoration of blood flow, reactive oxygen intermediates may lead to systemic injury to local or remote organs. In this study we investigated the usefulness of a shunt and vitamin E administration against the oxidant load generated in ischaemia-reperfusion phases.In three groups of pigs (n=16) aortic reconstruction was simulated. In Group A (n=5) clamping of the infrarenal aorta was performed for 2 hours. In Group B (n=6), during aortic cross-clamping, a shunt was used to give flow to the inferior mesenteric and internal iliac arteries. In Group C (n=5) vitamin E was administered before aortic cross-clamping. In all groups we evaluated sigmoid histology after reperfusion, while the oxidant load was estimated by measuring superoxide dismutase (SOD) activity in blood samples from portal and jugular vein.Histology of the sigmoid revealed increased postischaemic injuries in Group A, while the protective effect of shunt and vitamin E was apparent in Group B and C, respectively. SOD activity was minimized in Group C.Vitamin E protected the sigmoid from postischaemic injury and is responsible for the decreased levels of SOD activity.

The expression of lactoferrin (LF), ceruloplasmin (CP) and secretory component (SC) in various thyroid diseases was investigated using an immunohistochemical method. LF is an iron-binding protein overexpressed in certain human adenocarcinomas. CP is implicated in carcinogenesis and SC is part of the local immune defense system. Sections of 15 follicular adenomas, 5 follicular carcinomas (FC), 16 papillary carcinomas (PC), 15 goitres and 2 cases of lymphocytic thyroiditis were re-examined and investigated immunohistologically by a streptavidin-biotin method. A positive immunostain reaction for CP and LF was observed in all cases of PC and FC. A positive immunostain reaction for SC was observed in 13/16 cases of PC and 4/5 cases of FC. A negative immunostain reaction for CP, LF and SC was observed in medullary cancers, in follicular adenomas and in the cases with goitre. We conclude that the immunostain expression of LF, CP and SC is a valuable diagnostic aid in the differential diagnosis between benign and malignant thyroid tumors. The expression of SC indicates the presence of a local immunodefensive system.

The expression of lactoferrin (LF), ceruloplasmin (CP) and secretory component (SC) in various thyroid diseases was investigated using an immunohistochemical method. LF is an iron-binding protein overexpressed in certain human adenocarcinomas. CP is implicated in carcinogenesis and SC is part of the local immune defense system. Sections of 15 follicular adenomas, 5 follicular carcinomas (FC), 16 papillary carcinomas (PC), 15 goitres and 2 cases of lymphocytic thyroiditis were re-examined and investigated immunohistologically by a streptavidin-biotin method. A positive immunostain reaction for CP and LF was observed in all cases of PC and FC. A positive immunostain reaction for SC was observed in 13/16 cases of PC and 4/5 cases of FC. A negative immunostain reaction for CP, LF and SC was observed in medullary cancers, in follicular adenomas and in the cases with goitre. We conclude that the immunostain expression of LF, CP and SC is a valuable diagnostic aid in the differential diagnosis between benign and malignant thyroid tumors. The expression of SC indicates the presence of a local immunodefensive system.

The aim of the study is to further investigate the clinicopathological features of solitary necrotic nodules. Twenty-three archived cases of solitary necrotic nodule of the liver, which were preoperatively misdiagnosed as liver metastases were studied. The pathological findings were correlated with the clinical data of the patients. The nodules were solitary in 20 cases and multiple (2) in three cases, and measured from 0.5–1.5 cm in diameter. Twenty-one cases were located in the right lobe of the liver (91.6%) and two in the left lobe (8.69%). Twenty nodules were found in the subcapsular region (86.95%), while three nodules were located within the hepatic parenchyma (13.04%). More then half of our cases (12) were accompanied by extended calcification. Granulomatous tissue resembling “burnt-out” parasitic granulomas was found in three cases. Solitary necrotic nodules of the liver often mimic malignancy in abdominal imaging. Thus, permanent histopathology of the operative specimen remains the only accurate method of diagnosis. Their pathogenesis is most likely variable, and most reported cases are linked either to a parasitic or a vascular origin. Despite the designation of these lesions as “solitary” they may occasionally be multiple. In addition to the standard histological criteria of solitary necrotic nodules, the relatively small size (15 mm or less) and the frequent presence of calcifications seem to further characterize this enigmatic entity. Solitary necrotic nodule should be included in the differential diagnosis of small liver lesions with extensive necrosis.

e13556 Background: The mammalian target of rapamycin (m-TOR) kinase plays a central role in coordinating cell growth in response to mitogens, amino acid and energy sufficiency. The pathway leading to mTOR activation by these factors, is important for the regulation of protein synthesis and cell survival with implications in carcinogenesis. For these reasons, mTOR is currently under investigation as a potential target for anti-cancer therapy. The aim of this study was to determine the phospho-mTOR (p-mTOR) kinase expression in breast cancer tissues and the relationships with clinicopathological parameters of the breast tumors. Methods: We investigated the status of p-mTOR, in 140 breast carcinomas by immunohistochemistry. Western blot analysis was performed to verify the expression levels of p-mTOR. The relationship of protein expression with clinicopathological data and the correlations of protein expression levels were explored. Multiple logistic regression analyses with stepwise method was used in order to find independent factors associated wth p-mTOR. Results: 47.1% of the patients were p-mTOR positive. In univariate analyses a greater proportion of p-mTOR positive patients was found in those having progesterone receptors, in those hving higher grades of differentiation. When multiple analysis was conducted the only factor that was independently associated with p-mTOR kinase was the tumors grade of differentiation adjusted for age. Subjects with moderate grade of differentiation had greater likelihood for being p-mTOR positive compared to those with low grade of differentiation with odds ratio equal to 3.869 (95% CI: 1.35-11.04, p=0.012). Conclusions: The kinase p-mTOR was found in the neoplastic cells of almost half of the patients were enrolled. Overexpression of p-mTOR was correlated with well-to-moderately differentiated tumors (p

The clinical picture with the pathology findings of 89 atheromatic plaques which were removed following endarterectomy of the internal carotid artery, for the purpose of determining the clinical significance of the haemorrhagic atheromatic plaque were correlated. Intraplaque haemorrhage was determined in 44 of the 57 plaques (72.2%) of symptomatic patients while in the asymptomatic patients haemorrhage was noted in 12 of the 32 plaques (37.5%) p0.001. The extent of haemorrhage was25% of the plaque thickness in 21 of 44 symptomatic plaques (47.72%) and in the asymptomatic plaques in 3 out of 12 (25%) p0.05. The incidence of ulceration of the intima, with or without the presence of thrombus, was more frequent in the haemorrhagic plaques (68.42%) as compared with the non-haemorrhagic (31.57%), without any significant difference between the symptomatic and asymptomatic plaques. Communication of haemorrhage with the lumen was observed in 8 of 24 plaques (33.33%), 7 of which (29.16%) were symptomatic. The presence of haemorrhage in the atheromatic plaque of the internal carotid artery does not seem to play any direct role in the pathogenesis of the symptoms but, nevertheless, it constitutes a significant indication of instability of the atheromatic plaque.