Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

Because of advances in the understanding of histological and molecular characteristics in ovarian cancer, it is now possible to recognize the existence of five subtypes, which in turn has allowed a more refined therapeutic approach and better design of clinical trials. Each of these five subtypes has specific histological features and a particular biomarker expression, as well as mutations in different genes, some of which have prognostic and predictive value. CA125 and HE4 are examples of ovarian cancer biomarkers used in the diagnosis and follow-up of these malignancies. Currently, somatic or germinal mutations on BRCA1 and BRCA2 genes are the most important biomarkers in epithelial ovarian cancer having prognostic and predictive value. This article will review the histological and molecular characteristics of the five subtypes of ovarian cancer, describing the most important biomarkers and mutations that can guide in diagnosis, screening and tailored treatment strategy.

[Tissue reaction to breast prostheses. Periprosthetic capsular contracture]. / Reacción tisular a las prótesis mamarias. Contractura capsular periprotésica.

Silicone breast prostheses prompt the development of a fibrous casing or periprosthetic capsule. Capsular contracture, due to retraction of the fibrous tissue, is the most frequent and important complication of these implants. It produces varying degrees of hardening and, in advanced cases, deformity of the breast. It has been closely related to the type of surface of the implant (smooth or textured) and with the alignment of the collagen fibers, and it has been suggested that the formation of a continuous capsule, with collagen fibers aligned in parallel and circularly around the smooth prostheses, promotes the development of concentric contractile forces that pulling in unison give rise to contracture. With microporous textured prostheses a significantly lower incidence of capsular contracture has been shown in comparison with smooth prostheses. It is believed that tissue growth within the microporous structure gives rise to multidirectional contractile forces, with a tendency to neutralize one another when their effect is added over the implant. The capsule of these implants presents a base zone composed of multiple layers of collagen fibers aligned in parallel, which might contract. However, the adherence of the microporous textured prostheses might counteract the contractile forces.

A quantitative approach to the classification of hypospermatogenesis in testicular biopsies for infertility.

Absolute counts of germ cells were performed in 110 testicular biopsy specimens from 59 patients with either idiopathic infertility or varicocele and in a series of five autopsy specimens from age-matched controls. The tubular diameter, thickness of the tubular wall, and density of Leydig cells were measured. The following patterns were identified by germ-cell counts in the biopsy specimens: normal cell population, mild decrease in germ cells with normal ratio of cell types, advanced hypospermatogenesis with abnormal ratio of cell types, and Sertoli cell only. This sequence of progressive hypospermatogenesis was remarkably similar in both series. A separate category of maturation arrest was not recognized. Cell counts also correlated between right- and left-sided samples from the same patient in both series of biopsies. Reduction of tubular diameter, thickening of the tubular wall, and increase in Leydig cell density were often seen in severe stages of germ-cell impairment, although with an irregular distribution.

Anorectal atresia. An experimental model in the rat.

Aiming to assess the development of the anorectal sphincteric apparatus and whether it is influenced by the presence of an intestinal conduit through the muscular complex, we seek to develop an experimental model of anorectal atresia in foetuses of female pregnant rats, given orally the herbicide ethylenethiourea (ETU). Six 3-months-old, 300 g female Wistar rats were included in the study group (SG). The foetuses of another unexposed rat formed the control group (CG). In the SG 54, foetuses were alive, all had hypoplasia of the tail and 47 (87%) had no visible anal orifice. The 18 foetuses of the CG were normal. The histological study was performed at the level of the pubic symphysis. Type I anorectal atresia was defined when this section demonstrated an intestinal conduit and Type II when only a muscular cord was found, without any intestinal tube. This study was completed in 15 (32%) of the SG, 9 (60%) with anorectal atresia Type II and 6 (40%) with atresia Type I, and in 11 animals (61%) of the CG. The thickness of the sphincter muscle was larger in the CG (260.47+/-35.32 micro) than in the SG (208.98+/-55.01 micro), p<0.05, but this difference was due to the animals showing atresia Type II. To conclude: ETU had a teratogenic effect. The foetuses with atresia, particularly Type II, had a decreased development of the muscular complex. The presence of an intestinal conduit does not significantly influence the development of the muscular complex.

[Congenital segmental dilatation of the colon]. / Dilatación segmentaria congénita del colon.

Segmental dilatation of the colon is a rare congenital entity that cause chronic constipation in children. A new case is presented and another 9 former cases described in the literature are reviewed. We think that this entity may be diagnosed before the operation, if it is kept in mind. So, the barium enema and rectal biopsy are of paramount importance. The resection of the dilated ++ segment is the treatment of choice.

[Melanotic medulloblastoma. Ultrastructural and histochemical study of a case]. / Meduloblastoma melanótico. Estudio ultraestructural e inmunohistoquímico de un caso.

A electron microscopic and immunohistochemical study of a Melanotic medulloblastoma is reported. The cerebellar tumor was located in the vermis of a 6-year-old boy, dead 11 months after diagnosis. The tumor consisted of medulloblastoma-like areas with focal differentiation and pseudoepithelial structures pigmented with melanin. Electron microscopy showed melanosomes and tight junctions in pigmented areas. On immunohistochemistry, the cytoplasm of melanotic cells were positive to S-100 protein and the differentiated glial cells to GFAP. The tumor histogenesis, its relationship with other pigmented tumors of the CNS and their low frequency is commented on.

P-glycoprotein expression is increased in human secretory and gestational endometrium.

To determine the expression, distribution, and intracellular localization of the multi-drug resistance gene product P-glycoprotein (Pgp) in the human menstrual cycle and in early gestational endometrium, we retrospectively studied 36 endometrial samples utilizing 3 murine monoclonal antibodies (MAbs), MAb C219, MAb C494, and MAb JSB-1, which recognize spatially distinct cytoplasmic epitopes of Pgp. Formalin-fixed, paraffin-embedded endometrial samples obtained from 36 women of reproductive age with normal menstrual cycles were assigned morphologic menstrual dates: proliferative (N = 10), secretory (N = 19), menstrual (N = 1), and gestational endometrium (N = 6). The cellular localization, staining intensity, and percentage of Pgp immunoreactive cells varied with the phase of the menstrual cycle. Early proliferative endometria revealed no Pgp immunoreactivity for all three MAbs. Mid-proliferative endometria showed weak immunostaining in less than 15% of the glandular epithelia. Late proliferative endometria showed a strong apical paranuclear/Golgi staining pattern. Early secretory endometria showed strong luminal membranous, subnuclear vacuolar membranous, and supranuclear vacuolar membranous immunostaining to all 3 MAbs in greater than 80% of the glandular epithelia. Apical paranuclear/Golgi and membranous staining were present in nonvacuolated mid-secretory glands. Immunoreactivity diminished in the late secretory phase with mild to moderate staining in less than 35% of the endometrial glands. Menstrual endometria showed weak, focal staining. All gestational endometria showed marked cytoplasmic, membranous, and apical/Golgi immunostaining both in the hypersecretory (Arias-Stella) endometrial glands as well as in the decidua. In general, the intensity of MAb C494 immunostaining was weaker than that of MAb C219 or JSB-1. These results suggest the following: Pgp expression parallels that of nuclear progesterone receptor expression in the normal human endometrial cycle and early gestational endometrium; Pgp expression corresponds to rising plasma and tissue levels of progesterone as well as to morphologic changes in the endometrial glandular epithelium associated with the marked development of the secretory apparatus; Pgp expression is hormonally regulated and may be involved in uteroplacental transport of substrates important in the implantation process and in early embryo-endometrial interactions; and Pgp may be involved in the transport of progesterone across the uterine epithelium during pregnancy.

Cell counting and three-dimensional reconstruction to identify a cellular wave in human spermatogenesis.

OBJECTIVE: To collect quantitative and stereologic data on the main cell types represented in the seminiferous tubule in order to produce a three-dimensional representation of the morphologic events of normal cell production and maturation. STUDY DESIGN: Three-dimensional reconstruction and differential cell counting were performed on serial sections of normal testicular tissue from normal young men through image analysis and computer-based rendering. RESULTS: Peculiar periodicity in the total number of tubular cells considered along the sequence of serial sections was recognized. Also, consensual periodicity pertaining to each cell type was recognized. Adjacent high cellularity and low cellularity segments included a fairly constant mixture of cell types considered. CONCLUSION: A newly defined cellular wave, composed of regular alternations of high and low cellularity segments, was identified in the normal human seminiferous tubule.

Fusocellular gonadal stromal tumour of the testis with epithelial and myoid differentiation.

We describe an unusual fusocellular gonadal stromal tumour with a benign behaviour in the left testis from a 16-year-old man. The neoplasm consisted of a non-encapsulated proliferation of irregularly arranged, fusiform cell bundles in fibrous connective tissue. The tumour cells contained a slightly infolded nucleus, some dilated rough endoplasmic reticulum cisternae, abundant filament bundles which connected to subplasmalemmal electron-dense bodies, pinocytotic vesicles and a discontinuous basal lamina. The intercellular spaces were narrow and the tumour cells were joined by desmosomes. These cells were immunoreactive for muscle actin, alpha-actinin and vimentin. Focal immunostaining for collagen type IV was observed around the cells. No immunoreactivity for keratins, desmin S-100 protein or XIIIa factor was found. The findings suggest that the tumour arose from the peritubular myoid cells.

Ovarian endometriosis and clear cell carcinoma, leiomyomatosis peritonealis disseminata, and endometrial adenocarcinoma: an unusual, pathogenetically related association.

A 42 year-old female with a preoperative clinical diagnosis of ovarian cancer underwent laparotomy which revealed leiomyomatosis peritonealis disseminata (LPD) in the peritoneum and omentum and a left ovarian endometriotic cyst associated with a clear cell carcinoma. A grade 1, superfically invasive villoglandular endometrial endometrioid adenocarcinoma was also found. Microscopically, the endometriotic cyst wall contained an extensive peripheral band-like condensation of stromal cells. These cells were strongly positive for alpha inhibin and may have been the hormonal source responsible for the induction of the simultaneous LPD and endometrial adenocarcinoma. It is proposed that endometriosis is not only a precursor of clear cell carcinoma but, through secondary hormonal induction of the surrounding ovarian stroma, may also provide a hormonal stimulus for diverse proliferative processes.

[Giant axonal neuropathy. Presentation of 2 familial cases]. / Neuropatía axonal gigante. Aportación de dos nuevos casos familiares.

A review of 20 cases of giant axonal neuropathy (4 of them familial) described in the literature, and two new cases in brothers whose parents had no consanguinity is reported. A recessive autosomic pattern of inheritance is suggested. Curly hair, a typical phenotypic feature, was not initially present in our cases. This feature developed, however, later in the older brother. Clinical manifestations include an early predominantly motor polyneuropathy, subsequently involving the central nervous system. Clinical course is progressive and gait becomes impaired by the age of 10 to 13 years. Electrophysiologic studies show an axonal polyneuropathy with decreased evoked potential amplitude in motor and sensitive conduction speed. Diagnosis is achieved through a sural nerve biopsy showing an axonal thickening. Electron microscopy shows this to be related to a neurofibrillar accumulation.