Rossella Occhini

Spleen Depletion in Neonatal Sepsis and Chorioamnionitis

Neonatal sepsis and chorioamnionitis induce morphologic modifications and shrinkage of the thymus. We show fetal and neonatal morphologic modifications of the spleen in the same autopsy subjects as previously used to describe thymus shrinkage, including 10 preterm or full-term neonates who died of proven sepsis within 48 hours after birth and 20 fetuses spontaneously aborted because of extensive ascending chorioamnionitis. Control subjects included 10 fetuses from induced termination of pregnancy and 10 neonates who died suddenly during the perinatal period without evidence of chorioamnionitis. Spleen cell populations were studied by means of immunohistochemical analysis. Neonatal sepsis occurred with severe spleen depletion, involving both B and T lymphocytes (P < .001). Fetuses with chorioamnionitis also showed spleen cell depletion. These observations, to our knowledge not described before, indicate that preterm and term neonates show an inflammatory reaction similar to that of adult patients and that severe chorioamnionitis is associated with a nonspecific inflammatory response comparable to that of sepsis.

Nestin Expression in Adult and Developing Human Kidney

Nestin is considered a marker of neurogenic and myogenic precursor cells. Its arrangement is regulated by cyclin-dependent kinase 5 (CDK5), which is expressed in murine podocytes. We investigated nestin expression in human adult and fetal kidney as well as CDK5 presence in adult human podocytes. Confocal microscopy demonstrated that adult glomeruli display nestin immunoreactivity in vimentin-expressing cells with the podocyte morphology and not in cells bearing the endothelial marker CD31. Glomerular nestin-positive cells were CDK5 immunoreactive as well. Western blotting of the intermediate filament-enriched cytoskeletal fraction and coimmunoprecipitation of nestin with anti-CDK5 antibodies confirmed these results. Nestin was also detected in developing glomeruli within immature podocytes and a few other cells. Confocal microscopy of experiments conducted with antibodies against nestin and endothelial markers demonstrated that endothelial cells belonging to capillaries invading the lower cleft of S-shaped bodies and the immature glomeruli were nestin immunoreactive. Similar experiments carried out with antibodies raised against nestin and α-smooth muscle actin showed that the first mesangial cells that populate the developing glomeruli expressed nestin. In conclusion, nestin is expressed in the human kidney from the first steps of glomerulogenesis within podocytes, mesangial, and endothelial cells. This expression, restricted to podocytes in mature glomeruli, appears associated with CDK5.

Epidermal Growth Factor Receptor 1 Expression Is Upregulated in Undifferentiated Thyroid Carcinomas in Humans

BACKGROUND Epidermal growth factor receptor 1 (EGFR1) signaling is involved in human cancer cell progression and is responsible for aggressive biological behavior and poor clinical outcome in several human malignancies. Activation of the EGFR1 pathway has been proposed, among others, as being involved in the progression of thyroid cancer toward a thyroid-stimulating hormone (TSH)-independent phenotype. We have previously observed that undifferentiated thyroid carcinoma cells are hyper-sensitive to EGF signaling of downstream intracellular pathways, and this correlated both with the loss of TSH-dependency and increase in EGF-dependent proliferation and migration. Thus, we hypothesized that the upregulation of EGFR1 protein expression may be enhanced in parallel with transition toward a poorly differentiated phenotype in human thyroid carcinomas. METHODS The expression of EGFR1 was evaluated, by immunohistochemistry, in a series of 49 human thyroid carcinomas at different degrees of tumor differentiation. RESULTS The expression of EGFR1 protein was significantly upregulated in poorly differentiated and anaplastic thyroid carcinomas, whereas it was absent or faint in normal thyroid gland tissue and in differentiated thyroid papillary carcinomas. Of note, selected thyroid tumors characterized by a mixed population of differentiated and undifferentiated tumor cells, likely progressing from well to poorly differentiated and anaplastic phenotypes, exhibited EGFR1-negative differentiated fields together with EGFR1-positive poorly differentiated and anaplastic areas. CONCLUSIONS Upregulation of EGFR1 expression may be a molecular marker of dedifferentiation in thyroid epithelial carcinomas, likely being responsible for the activation of EGF signaling observed in tumor cells and favoring progression toward an angiogenic, poorly differentiated, TSH-independent phenotype.

Inflammatory myofibroblastic tumor of the orbit.

The authors describe an unusual case of orbital inflammatory myofibroblastic tumor (IMT) in a 17-year-old patient who presented with a painful exophthalmos of the left eye. After complete surgical excision, the mass was diagnosed as an IMT based on morphological and immunohistochemical features. No tumor recurrence was evident during 28-month follow-up. The authors discuss histopathological and immunohistochemical characteristics and review the literature of orbital IMT.

Histologic chorioamnionitis: different histologic features at different gestational ages

Abstract Objective: The aim of this study was to investigate the rate of the different histological chorioamnionitis (HCA) grade in relation to the gestational age in term and preterm delivery. Methods: Three hundred and ninety-two women with singleton pregnancy with spontaneous onset of labor either prematurely or at term, with histologic diagnosis of HCA, were enrolled. Placentas were classified as: deciduitis and/or histologic chorioamnionitis within the membranes (HCA1); amnionitis or inflammation of the chorionic plate without funisitis (HCA2); and histologic chorioamnionitis with funisitis (HCA3). Microbiological culture was performed on both placental and fetal membrane samples. Results: HCA1 was more frequent in women delivering at term than in preterm (p < 0.001). HCA2 was more represented in women delivering between 32 and 36 weeks (p < 0.001) and HCA3 occurred more frequently in those delivering within 32 weeks (p < 0.001). The positive bacterial culture was higher (p = 0.008) in presence of HCA3 in comparison with HCA1 and HCA2. Conclusions: This study showed a significantly different distribution of HCA grades in relation to gestational age at delivery. HCA may represent the expression of different subtending etiologies and may also reflect specific immune competence of gestational tissues at different gestational ages, strengthening as pregnancy advances.

Expression of Placental Neurotrophin-3 (NT-3) in Physiological Pregnancy, Preeclampsia and Chorioamnionitis

Neurotrophic factors are a group of proteins that act as paracrine and autocrine growth factors. They are involved in the regulation of morphogenesis and development of several tissues. The present study aims to evaluate, for the first time, the expression of Neurotrophin-3 in the human placenta during normal pregnancy and in preeclampsia and chorioamnionitis. Neurotrophin-3 mRNA, assessed by RT-PCR analysis in six term placentas, were observed in all the specimens examined. Neurotrophin-3 protein expression and tissue distribution was evaluated by immunohistochemistry in placenta samples from uncomplicated first trimester (n = 5) and term (n = 5) pregnancies as well as in specimens from preeclampsia (n = 5) and chorioamnionitis (n = 5). In first trimester specimens, strong immunoreactivity was present in villous stromal cells, in the cyto- and syncytiotrophoblast, in decidua cells and in endometrial glands. Third trimester specimens showed prominent immunostaining in cyto- and syncytiotrophoblast cells, in decidua cells and in the amniotic membranes. Villous stromal cells were weakly stained. Similar protein localization was observed in placentas with preeclampsia and chorioamnionitis. In the latter, however, positive villous stromal cells increased in number and in staining intensity when compared with controls and preeclampsia (p < 0.001). The roles of Neurotrophin-3 in pregnancy are presently unknown. A regulatory function on placenta and foetal brain development and maternal inflammatory response may be hypothesized.

Histopathology of explanted AlphaCor due to keratoprosthesis extrusion

AlphaCor keratoprosthesis (KPro) is a new‐concept poly (2‐hydroxyethyl methacrylate) one‐piece KPro that makes possible a two‐step implantation technique easy to perform with a short learning curve. In literature an 18% incidence of AlphaCor removal due to melting complications is reported. The histopathology of corneal tissue removed during a re‐operation while bearing an AlphaCor KPro has previously been described in the literature only in one report. Herein, the first histological features of an AlphaCor–corneal complex explanted because of KPro extrusion is described. The histopathology of the AlphaCor–corneal complex is characterized by mild inflammation in the corneal tissues, limited to the region surrounding the anteriorized and extruded part of the KPro. It is not possible to fully understand the mechanisms that trigger the device extrusion. One possible explanation could be a dislocation of the prosthesis in the corneal pocket due to the untied fixation stitch. Another explanation could be a foreign body reaction induced by KPro.

Orbital teratoma masquerading as lymphangioma

Orbital teratoma in a newborn produces rapid and unilateral proptosis, which, combined with poor eyelid closure, may lead to corneal exposure and vision loss. Early surgical excision of the mass is recommended to preserve visual function. We report a case of an orbital teratoma masquerading as a lymphangioma in 6-month-old girl. The lesion was entirely excised using a transconjunctival approach with good cosmetic and functional results.

Orbital metastasis associated with primary breast carcinoma in a man detected during peribulbar anesthesia for cataract surgery

Purpose A case of orbital infiltration by breast carcinoma in a male patient causing mild enophthalmos and subcutaneous mass detected accidentally during peribulbar anesthesia for cataract surgery is discussed. Methods The authors report a case of a 65-year-old man who came to the Ophthalmology Department for cataract surgery. During the presurgery peribulbar injection, a hard palpable mass located under the inferior left eyelid was noted, together with mild enophthalmos. A historical clinical screening revealed that 5 years previously the patient had undergone a right radical mastectomy to treat a ductal carcinoma of the breast. Results The patient underwent an incisional biopsy of the orbital mass that confirmed the clinical hypothesis of a metastasis. Discussion This case highlights the importance of the collection and screening of detailed clinical information on the patient before every ophthalmic operation including cataract surgery. The occurrence of progressive enophthalmos can represent an unusual symptom of orbital metastasis, commonly presenting with proptosis and diplopia.

Pediatric focally pigmented choroidal melanoma: Imaging with pathological correlation

We report a 9-year-old-boy with no predisposing factors who presented with left eye leukocoria from a complete retinal detachment at ophthalmoscopy. Imaging showed an intraocular dome-shaped mass of low to moderate internal reflectivity at ultrasound, low T2-weighted signal intensity, lack of T1-weighted high signal intensity, and subtle gadolinium-enhancement at magnetic resonance imaging, and lack of calcifications at computed tomography. Due to the rapid extensive intraocular growth, the affected eye was enucleated. Pathologic examination showed a choroidal melanoma with only focal pigmentation. Despite its very rare incidence in the pediatric population, choroidal melanoma should be included in the differential diagnosis of leukocoria.