Chorea revealing systemic lupus erythematosus in a 13-year old boy: A case report and short review of the literature.

Among the neurological manifestations of systemic lupus erythematosus (SLE), chorea is rare, presenting in less than 7% of the pediatric SLE patients. It can appear early in the onset of SLE, be the first or even the sole clinical feature of the illness and has strongly been associated with the presence of antiphospholipid antibodies. We report on the case of a 13-year old boy, admitted with acute onset chorea and finally diagnosed with SLE. Subsequently, we present a short review of the literature on the epidemiology, suggested pathogenesis, clinical presentation and treatment of this rare presentation of SLE.

Wegener granulomatosis masquerading as pneumonia.

We report a case of an elderly patient with a limited form of Wegener granulomatosis, which simulated the clinical and imaging features of organizing pneumonia. Here we call attention to this atypical case presentation that eloquently illustrates the many faces of Wegener granulomatosis.

Prognostic significance of thymidine phosphorylase in superficial bladder carcinoma.

OBJECTIVE: We investigated the expression of thymidine phosphorylase (TP) in bladder carcinomas and assessed its prognostic significance in superficial bladder cancer samples. PATIENTS AND METHODS: We studied 142 primary bladder cancer samples immunohistochemically for nuclear thymidine phosphorylase (TPN), cytoplasmic (TPC) and stromal (TPSTR) expression. We correlated them with standard clinicopathological features (grade, stage, concurrent in situ, multiplicity, primary or recurrent status), as well with recurrence and progression. We examined also the relationship between TP and tumor microvessel density. RESULTS: The level of all types of TP correlated well with stage, while grade correlated well only with TPSTR and the presence of carcinoma in situ only with TPN. Patients with low levels of TPN had a longer tumor free interval, during a 38.6 months mean follow up time. Regarding the association between TP count and microvessel density we found the strongest association with TPSTR (p=0.003), a borderline statistical significance with TPC (p=0.049) and no relationship with TPN (p=0.072). CONCLUSIONS: We suggest that the assessment of TPN might be useful for predicting recurrence in superficial bladder cancer. We propose also that TP may stimulate angiogenesis.

Isolated torsion of the fallopian tube: a case report and review of the literature.

INTRODUCTION: Isolated torsion of the fallopian tube is a very rare condition. It occurs without ipsilateral ovarian involvement associated with pregnancy, haemosalpinx, hydrosalpinx, ovarian or paraovarian cysts and other adnexal alterations or even with an otherwise normal fallopian tube. We document a case of isolated torsion of the right fallopian tube associated with hydrosalpinx. CASE: The patient was a 39-year-old female, para 2, gravida 4, who was presented with acute pelvic pain, nausea and vomiting. Her medical history included an appendectomy and right hydrosalpinx diagnosed five months before admission by hysterosalpingography because of investigation for secondary infertility. The urinary pregnancy test was negative. Pelvic ultrasonography showed a dilated folded right tubular structure measuring 7.8 x 2.7 cm with thickened echogenic walls and mucosal folds protruding into the lumen; the ovaries and uterus were unremarkable. No free fluid in the cul-de-sac was noted. Preoperatively, a diagnosis of twisted right fallopian tube was suspected and an exploratory laparotomy confirmed the diagnosis of isolated torsion of the oviduct. The ipsilateral ovary appeared normal, but the fallopian tube was gangrenous and right salpingectomy was performed. The patient became pregnant three months after surgery. CONCLUSION: Isolated torsion of the fallopian tube should be considered in the differential diagnosis of patients with acute abdomen and previous medical history of hydrosalpinx.

Primary ovarian carcinosarcoma: a case report and review of the literature.

Primary ovarian carcinosarcoma is characterized by an admixture of malignant epithelial and stromal elements. This neoplasm is extremely rare with fewer than 400 cases reported in the English literature. Its histogenesis, clinical features and optimal treatment remain unclear because of the rarity of primary ovarian carcinosarcoma. This study focuses on the clinical, pathological, immunohistochemical features and survival of a 73-year-old patient with primary ovarian carcinocarcoma. The patient was treated with surgery followed by combined chemotherapy with carboplatin and taxol and assigned to FIGO Stage IIIc. She died from the disease 17 months after surgery. In conclusion, ovarian carcinosarcoma is a very aggressive tumor, especially when it is diagnosed at advanced stage.

Prognostic significance of angiogenesis in superficial bladder cancer.

OBJECTIVE: To assess the prognostic significance of angiogenesis parameters such as microvessel density (MVD) and vascular endothelial growth factor (VEGF) in superficial bladder cancer. PATIENTS AND METHODS: We studied 127 superficial bladder cancer samples immunohistochemically for the above factors. We compared them with standard clinicopathological features (grade, stage, concurrent in situ, multifocality, primary or recurrent status) as well as with p53 expression, recurrence and progression to muscle infiltrating disease. RESULTS: During a 36 months median follow up of 109 patients with superficial primary tumors (min. 3, max. 69 months), 80 of them recurred (73.4%), while 8 patients (7.3%) progressed to muscle invading disease. A significant correlation was noted between MVD and VEGF in all 127 samples (p = 0.019). No association was noted between MVD or VEGF with the other clinicopathological features, recurrence or progression. Although progression free survival rates of categorized microvessel density (up to and higher than median value) differed significantly only in grade 3 patients, no independent prognostic significance could be attributed to MVD. No correlation was observed between MVD or VEGF with p53 protein. CONCLUSIONS: Based on our data we suggest that VEGF is not useful for predicting recurrence or progression in superficial bladder cancer. Microvessel density determination may help to predict progression of grade 3 patients to muscle invasive disease but not as an independent prognostic factor.

Expression patterns of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27(Kip1) in urothelial carcinoma: correlation with other cell-cycle-related proteins (Rb, p53, Ki-67 and PCNA) and clinicopathological features.

INTRODUCTION: The expression pattern of cyclins D1 and E, as well as cyclin-dependent kinase inhibitors p21(Wa1/Cip1) and p27(Kip1) and their relationship to tumour behaviour and patients' prognosis was examined in 142 urothelial cell carcinomas. The expression of these proteins was also analyzed along with other cell-cycle-related proteins such as: p53, pRb and the proliferation-associated indices Ki-67 and proliferating cell nuclear antigen (PCNA). PATIENTS AND METHODS: These molecule markers were localized immunochemically using the monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10), and anti-p27 (1B4) in 142 patients with urothelial cell carcinoma. RESULTS: Focal positivity (<10% of tumour cells) or the absence of cyclin D1 immunostaining was observed in 105/142 (73.9%) of the tumours. Cyclin D1 expression was correlated with tumour grade and stage as well as with the existence of in situ component. In addition, cyclin D1 expression was positively correlated with p21(Waf1/Cip1) and p27(Kip1) and inversely with the Ki-67 score. Focal positivity (<20% of tumour cells) or the absence of cyclin E immunoreactivity was observed in 105/142 (73.9%) in all cases. Cyclin E expression was correlated with tumour stage. A positive relationship between cyclin E expression and the two associated proliferating indices Ki-67 and PCNA, as well as with p53 and p27(Kip1) proteins expression was noted. Absence or focal positivity (<5% of tumour cells) of p21(Waf1/Cip1) was detected in 88/142 (62%) of the carcinomas. p21(Waf1/Cip1) expression was correlated with tumour grade and stage. A positive relationship of its expression cyclin D1, cyclin E, p27 and pRb expression was observed. Absence or focal immunostaining (<20% of tumour cells) of p27 protein was detected in 55/141 (39%) in all cases. p27(Kip1) expression was correlated with tumour grade as well as with cyclins D1 and E. The prognostic significance of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1), p27(Kip1) in determining the risk of recurrence and progression with both univariate (log rank test) and multivariate (Cox regression) methods of analysis showed no statistically significance differences. CONCLUSION: These findings suggest that the level of the cell cycle regulators studied does not seem to have a clinical value in terms of predicting the risk of early recurrence and progression. In addition the interrelationship probably means their contribution to the regulation of cell growth through different pathways in bladder carcinogenesis.

Mucinous cystadenoma of the ovary with functioning stroma and virilization in pregnancy: a case report and review of the literature.

Virilization caused by ovarian tumors with functioning stroma during pregnancy is extremely rare and has been reported in many ovarian tumors. In mucinous cystadenomas with maternal virilization during pregnancy the stromal cells responsible for the hormone secretion resemble lutein or Leydig cells and have been referred to as luteinized stromal cells. We present a case of a 30-year-old, gravida 2, para 1, woman who presented at approximately the 38th week of pregnancy with features of virilization. At the same time, a cesarean section was performed because of fetal distress and a male weighing 3,030 g without any gross abnormalities was delivered. A large tumor of the right ovary was detected and a right salpingo-oophorectomy was performed. Histopathologically, the tumor proved to be a benign mucinous cystadenoma. Masses typically resembling lutein stromal cells or Leydig cells of the testes or ovarian hilus were found in the wall of the cyst below the mucinous epithelium. No crystalloids of Reinke were identified. The stromal component of the tumor was characterized as functioning stroma with luteinized stromal cells. The glandular mucinous epithelium showed focal positivity for human chorionic gonadotrophin. The cytoplasm of the luteinized stromal cells reacted strongly and diffusely with antiserum for vimentin. Also, the cytoplasm of the luteinized stromal cells showed focal intense positivity for synaptophysin, and focal mild positivity for human chorionic gonadotrophin. Staining results for oestrogen and progesterone receptors were negative. In conclusion, we present an unusual case of clinical virilization during pregnancy associated with an ovarian mucinous cystadenoma with functioning stroma. The virilizing manifestations disappeared after removal of the ovarian neoplasm, supporting the perception that the functioning ovarian stroma was responsible for the androgen production.

Prenatal diagnosis of congenital cystic adenomatoid lung malformation: case report and review of the literature.

Congenital cystic adenomatoid malformation of the fetal lung is an extremely rare developmental abnormality characterized by excessive overgrowth of the terminal respiratory bronchioles at the expense of the saccular spaces. We present a case of a 33-year-old, gravida 2, para 1, woman with congenital cystic adenomatoid lung malformation-type II diagnosed by ultrasound at the 20th week of gestation. On the right side of the chest an area with a maximum diameter of 18.5 mm and with small cystic lesions was recognized. The maximum diameter of the cysts was 0.5 cm. There were no other fetal abnormalities. The pregnancy was terminated and the postmortem examination confirmed the ultrasonographic findings. The cysts had the appearance of bronchiolus-like structures and were lined with cuboidal and columar epithelium. Distended alveoli were present, while the airways were normal in structure. No other congenital anomalies were found. In conclusion, in this study we describe the ultrasonographic and pathologic findings of an unusual case of congenital cystic adenomatoid malformation of the fetal lung.

Glycoprotein CD44 expression in normal, hyperplasic and neoplastic endometrium. An immunohistochemical study including correlations with p53, steroid receptor status and proliferative indices (PCNA, MIB1).

PURPOSE OF INVESTIGATION: We have studied by immunohistochemistry the presence and localization of CD44, estrogen and progesterone receptors, p53 and proliferative associated indices (MIB1, PCNA) in archival endometrial tissue, in order to determine their diagnostic and prognostic value as well as the possible correlations between them. METHODS: We examined 186 samples of endometrial tissue (100 endometrial carcinomas of endometrioid type, 40 cases of hyperplasia and 46 of normal endometrium). Patient records were examined for FIGO stage, grade, and depth of myometrial invasion, histology, and lympho-vascular space invasion. RESULTS: Strong membranous immunostaining (> 10% of neoplastic cells) was observed in 45% of the carcinomas. A statistically significant correlation was found in the expression of protein in stromal cells, when compared with epithelial cells (p < 0.0001). Immunohistochemical expression of CD44 was significantly lower in cancer cases than in normal endometrium, mainly in the secretory phase (p < 0.0001). CD44 positive cases by immunohistochemistry failed to show any statistical correlation with tumor grade or with vessel invasion. The expression of the protein was lower in FIGO Stage II compared with Stage I (p = 0.03). A positive relation of CD44 expression with progesterone receptor status (p = 0.02) was detected. CD44 expression was also positively associated with the proliferation associated with the proliferative index MIB1 (p = 0.001). CONCLUSION: CD44 is closely related to the secretory phase of the normal menstrual cycle and its expression is decreased in hyperplasia (simple or complex with or without atypia) and in cancer cases. These observations suggest that decreased CD44 expression might be functionally involved in the multiple mechanisms of the development and progression of endometrial lesions.

Primary postpartum haemorrhage due to a large submucosal nonpedunculated uterine leiomyoma: a case report and review of the literature.

The complications of leiomyomas during pregnancy are very rare and can be divided into those occurring during pregnancy, at delivery and in puerperium. We present an unusual complication of large submucosal nonpedunculated uterine leiomyoma in puerperium. The patient was a 32-year-old woman, gravida 2, para 1, who was admitted to our department from a private maternity clinic with a considerable drop in haemoglobin 23 hours after delivery of a healthy boy. The placenta had easily and spontaneously delivered. On admission to our department her haemoglobin was 6.3 g/dl. Pelvic examination disclosed the presence of fresh blood clots in the vaginal vault. A circular firm structure, 12 by 12 cm, was noted within the external cervical os. This mass was immovable. Total abdominal hysterectomy without salpingo-oophorectomy was immediately performed and the patient's postoperative course was uneventful. In conclusion, in this patient the uterine leiomyoma obstructed the cervical os and prevented the passage of lochia resulting in haematometra, uterine atony and subsequent serious uterine haemorrhage. In such cases ostetricians and gynaecologists should proceed immediately with surgical intervention to avoid a life-threatening situation.

Extramedullary hematopoiesis in the uterine isthmus: a case report and review of the literature.

Extramedullary hematopoiesis (EH) is the ectopic production of myeloid, erythroid and megakaryocytic elements. In postfetal life it usually occurs in conditions with hyperactive, depleted or infiltrated marrow; it is extremely rare in the genital tract. We report a case of EH in the uterine isthmus (UI) which was found incidentally in a 40-year-old patient who presented with a right ovarian cyst and a history of a right modified radical mastectomy for infiltrating invasive lobular carcinoma one year earlier. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Microscopic examination of UI revealed foci of hematopoiesis, consisting of white blood cell precursors confirmed by positive chloroacetate-esterase staining. Bone marrow biospy showed diffuse infiltration secondary to breast cancer. Further work-up, including a bone scan, showed multiple metastases suggesting that the high degree of bone marrow infiltration by neoplasmatic cells had stimulated the EH. In conclusion, the unusual finding of EH in UI heralded widespread infiltration of bone marrow.

Immunohistochemical expression of Retinoblastoma gene product in normal, hyperplastic and malignant endometrium. Correlation with p53 protein expression, c-erbB-2, hormone receptors' status and proliferative activity.

Alterations of the retinoblastoma (Rb) gene have been described in several human neoplasms and recently, it has been suggested that these alterations may play a role in the development of endometrial carcinomas. Paraffin sections from 31 cases of normal endometrium (16 proliferative, 15 secretory), 35 hyperplastic lesions and 89 endometrial carcinomas were investigated immunohistochemically for Rb protein (pRb) expression. The results were compared with p53 and c-erbB-2 protein expression, estrogen (ER) and progesterone (PR) receptors' status and with clinicopathological prognostic factors. pRb was expressed in normal, hyperplastic and neoplastic epithelium. Proliferative endometrium showed more intense and extensive pRb staining than secretory endometrium. pRb reactivity was heterogeneous in the hyperplastic endometrial cells. Lack or focal (< 10% of endometrial cells) pRb immunostaining was noted in 56.2% and 27% of carcinomas, respectively. In the remaining cases (16.8%) pRb staining was heterogeneous or diffuse. The absence or presence of pRb expression was independent of grade and stage. In normal proliferative and secretory endometrium, pRb expression was correlated with PR (p = 0.006 and p = 0.001, respectively), PCNA (p = 0.04 and p = 0.01, respectively) and MIB1 (p = 0.02 and p<0.0001, respectively) expression. In hyperplasias, pRb was related to PR (p = 0.016) and MIB1 (p < 0.0001) expression. In carcinomas, a relationship of pRb expression with p53 (p = 0.0015), ER (p = 0.0002), PR (p = 0.0004) and PCNA (p = 0.013) status was detected. We suggest that the absence or presence of pRb expression does not seem to be associated with the progression of endometrioid carcinoma. In addition, pRb seems to be normally regulated in relation to the proliferative growth fraction of the tumours.

Primary small-cell carcinoma of the endometrium: clinicopathological study of a case and review of the literature.

BACKGROUND: Small-cell carcinomas are almost always primary in the lungs and are highly malignant. These tumors may also occur in the female genital tract. However, primary small-cell carcinoma of the endometrium is extremely rare with very few cases reported in the English literature. This tumor may exhibit evidence of neuroendocrine differentiation and has a high propensity for systemic spread and poor prognosis. CASE: A 55-year-old postmenopausal woman with primary small-cell carcinoma of the endometrium, FIGO stage Ib, underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and sampling node biopsies of the parametrial spaces, followed by adjuvant combined chemotherapy. CONCLUSION: A case of small-cell carcinoma of the endometrium, is reported and its clinical, histological and immunohistochemical features are discussed.

Sclerosing stromal tumor of the ovary: a case report and review of the literature.

Sclerosing stromal ovarian tumor is an extremely rare neoplasm occurring predominantly in the second and third decades of life. It presents most often with non-specific symptoms. We describe a new case occurring in a young woman presenting with infertility and irregular menses. Ultrasound examination showed a left heterogenous ovarian mass without focal calcifications. Histological features included a pseudolobular pattern with focal areas of sclerosis, prominent vascularity and a two-cell population of spindled and polygonal cells. Immunohistochemical analysis for actin, vimentin, laminin, vascular epidermal growth factor (VEGF), oestrogen and progesterone receptors using formalin-fixed and paraffin-embedded materials showed predominant positivity for a-smooth muscle actin and consistent positivity for laminin and vimentin. The epidermal VEGF demonstrated rich tumor vascularity. Oestrogen and progesterone receptors were not expressed. suggesting hormonally independent development. Menstrual cycle disturbances, however, were corrected following extirpation of the tumor, indicating some endocrine involvement. In addition, the patient became pregnant ten months after the operation. The differential diagnosis is discussed.

Low expression of p27 protein combined with altered p53 and Rb/p16 expression status is associated with increased expression of cyclin A and cyclin B1 in diffuse large B-cell lymphomas.

The expression of the cyclin-dependent kinase inhibitor (CDKI) p27 protein was investigated in relation to (1) the expression of the cell cycle regulators p53, Rb and p16 and (2) the proliferation profile as determined by the expression of Ki67, cyclin A, and cyclin B1 in 80 cases of de novo diffuse large B-cell lymphomas (DLBCL). P27 expression was low/null in large tumor cells in 58/80 cases and intermediate/high in 22/80 cases. Increased expression of p53 protein was observed in 39/80 cases. Decreased expression of Rb and p16 proteins was mutually exclusive and was observed in 5/80 and 14/80 cases, respectively. The analysis of the p27 expression status (low/null versus intermediate/high) with respect to the p53 and/or Rb/p16 expression status showed that low/null p27 expression was significantly correlated with increased p53 expression (P =.018) and showed a strong trend for correlation with concurrent increased p53 expression and decreased Rb or p16 expression (P =.050). These findings suggest a tendency for concurrent alterations of the cell cycle regulators p27, p53, and Rb or p16 in DLBCL, which might result in impaired tumor growth control. Indeed, the analysis of the combined p27/p53/Rb/p16 expression status with respect to the proliferation profile showed that (1) three alterations in the combined p27/p53/Rb/p16 status (i.e., low/null P27 expression, increased expression of p53, and decreased expression of Rb or p16) were significantly correlated with increased expression of cyclin B1 (P =.005) and (2) two or three alterations were significantly correlated with increased expression of cyclin A (P =.014). These findings suggest combined impairment of a complex cell-cycle control network involving the CDK inhibitor p27, the P53 pathway, and the Rb1 pathway, which exerts a cooperative effect resulting in enhanced tumor cell proliferation.

Bilateral papillary renal cell carcinoma.

Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific.

Immunohistochemical localization of metallothionein in endometrial lesions.

Metallothioneins (MTs) are a group of ubiquitous low-molecular-weight proteins essential for the protection of cells against heavy metal ion toxicity. The immunohistochemical expression of MT was studied by immunohistochemistry using a monoclonal antibody (E9) against a conserved epitope of I and II isoforms in a series of 89 endometrial carcinomas, 34 cases of hyperplasia, and 32 samples of normal endometrium. In secretory phase endometrium, extensive MT expression was detected in most cases (92.4%). In contrast, MT immunoreactivity was confined to small foci in 22.2% of proliferative phase cases. The MT values in normal endometrium were inversely correlated with oestrogen receptor (ER) content (p<0.0001), progesterone receptor (PgR) content and with PCNA (p<0.0001) and MIB1 (p=0.001) scores. In hyperplastic lesions, MT expression was detected only in 3.3% of cases, while in the group of carcinomas it was observed in 23.1%. A statistically significant difference of MT expression was observed between carcinomas and simple hyperplasias (p=0.03). In carcinomas, MT expression was positively correlated with grade (p=0.0065), MIB1 (p=0.022), and p53 (p=0.006) expression, and inversely with PgR (p=0.03). A trend of inverse correlation between MT and ER receptor was also detected (p=0.07). These data suggest that MT expression seems to be under hormonal control in normal endometrium; that it may modify p53 expression; and that it could be used as an additional biological marker indicating aggressive behaviour in endometrial lesions.

Association of mast cells with fibrosis and fatty infiltration in the minor salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: To determine the distribution and density of mast cells in the minor salivary glands of patients with primary Sjögren's syndrome (pSS) and of normal controls. METHODS: Minor salivary gland biopsies were obtained from 19 patients with pSS, 9 with systemic lupus erythematosus, one each with rheumatoid arthritis, sarcoidosis, and Hodgkin's disease, and from 10 individuals who had subjective xerostomia with normal salivary gland biopsies. Biopsy specimens were evaluated for the degree of inflammation according to Tarpley's classification. Sections were analysed for staining with Toluidine blue and with the mast cell specific marker c-kit. The data obtained were correlated with the histological findings of fatty infiltration, fibrosis and lymphocytic infiltration. RESULTS: There was a significant correlation between the number of mast cells identified and the degrees of fibrosis and fatty infiltrates. There was no correlation between the intensity of lymphoid infiltration and the number of mast cells. c-kit staining showed a high correlation when compared to Toluidine blue staining. CONCLUSION: Mast cells in the minor salivary glands of patients with pSS are strongly associated with fibrosis and cell acid infiltration. However, there is no correlation with parameters of disease activity such as lymphoid infiltration.

Distribution of CD1a-positive Langerhans cells and lymphocyte subsets in transitional cell carcinoma of the urinary bladder. An immunohistological study on frozen sections.

The distribution of CD1a-positive Langerhans cells, CD4-positive T-helper cells, and CD8-positive T-suppressor cells in 36 patients with transitional cell carcinoma of the urinary bladder was studied immunohistochemically on frozen sections. Multiple tissue specimens from the tumour, the adjacent mucosa, and random bladder wall biopsies were examined. Langerhans cells were mainly interspersed among the tumour cells, whereas T-helper cells were present in aggregates in the stroma. T-suppressor cells were present both in aggregates in the stroma and among the tumour cells. There was a marginal relationship between the density of Langerhans cells and the density of T-helper/inducer cells and a good relationship with CD8-positive cells. There was no statistically significant difference in the population density of Langerhans cells associated with the various clinicopathological variables, including growth pattern, histological grade and stage, or patient's age and sex. On the contrary, a statistically significant difference was found in the CD1a/CD4 ratio among specimens of different grades. These results show that CD1a cell populations correlate with T-cell populations in bladder cancer, suggesting that Langerhans cells take part in the immune response carried out by T lymphocytes, their task being apparently antigen presentation.