Histological comparison of in vitro and in vivo development of peripheral posterior capsule opacification in human donor tissue.

In order to study the mechanisms involved in the development of posterior capsule opacification (PCO) we compared in vivo developed PCO with PCO formed in tissue culture with focus on the periphery of the lens capsule to evaluate lens regeneration potential. We studied three human tissue groups: Cultured lens capsules after mock cataract surgery (n = 6, 30 days), lens capsules from donors that had previously undergone cataract surgery (IOL capsules) (n = 12) and intact lenses (n = 6). All samples were stained with Vimentin, alpha Smooth Muscle Actin, Picro Sirius Red (for collagen) and Paired box protein (Pax6). We found that cultured capsules and less developed IOL capsules consisted mainly of monolayers of mesenchymal cells, while more developed IOL capsules, contained lens epithelial cells (LECs), globular cells and lens fiber cells. Many IOL capsule samples expressed collagen I and III in areas where cells were in contact with the IOL. Pax6 had a similar dispersed distribution in less developed IOL capsules and cultured capsules, while more developed IOL capsules and intact lenses, concentrated Pax6 in LECs at the equatorial lens bow. The similarities between cultured capsules and less developed IOL capsules indicate that our in vitro developed PCO is comparable to early in vivo developed PCO. The similar morphology of more developed IOL capsules and intact lenses seems to indicate an attempt at lens regeneration.

Clinical and Ultrasound Characteristics of the Microcystic Elongated and Fragmented (MELF) Pattern in Endometrial Cancer According to the International Endometrial Tumor Analysis (IETA) criteria.

OBJECTIVES: To describe sonographic features of the microcystic elongated and fragmented (MELF) pattern of myometrial invasion (MI) using the International Endometrial Tumor Analysis (IETA) criteria; to assess the effect of the MELF pattern on preoperative ultrasound evaluation of MI; and to determine the relationship of the MELF pattern to more advanced stage (≥ IB) and lymph node metastases in women with endometrioid endometrial cancer. METHODS/MATERIALS: We included 850 women with endometrioid endometrial cancer from the prospective IETA 4 study. Ultrasound experts performed all ultrasound examinations, according to the IETA protocol. Reference pathologists assessed the presence or absence of the MELF pattern. Sonographic features and accuracy of ultrasound assessment of MI were compared in cases with the presence and the absence of the MELF pattern. The MELF pattern was correlated to more advanced stage (≥IB) and lymph node metastases. RESULTS: The MELF pattern was present in 197 (23.2%) women. On preoperative ultrasound imaging the endometrium was thicker (p = 0.031), more richly vascularized (p = 0.003) with the multiple multifocal vessel pattern (p < 0.001) and the assessment of adenomyosis was more often uncertain (p < 0.001). The presence or the absence of the MELF pattern did not affect the accuracy of the assessment of MI. The MELF pattern was associated with deep myometrial invasion (≥ 50%) (p < 0.001), cervical stromal invasion (p = 0.037), more advanced stage (≥ IB) (p < 0.001) and lymph node metastases (p = 0.011). CONCLUSIONS: Tumors with the MELF pattern were slightly larger, more richly vascularized with multiple multifocal vessels and assessment of adenomyosis was more uncertain on ultrasound imaging. The MELF pattern did not increase the risk of underestimating MI in preoperative ultrasound staging. Tumors with the MELF pattern were more than twice as likely to have more advanced stage (≥ IB) and lymph node metastases.

Absence of amyloid-beta in lenses of Alzheimer patients: a confocal Raman microspectroscopic study.

We have compared the protein profiles in plaques and tangles in the hippocampus of post-mortem Alzheimer brains and in opaque and clear regions in the deep cortex of eye lenses of the same donors. From the 7 Alzheimer donors studied, 1 had pronounced bilateral cortical lens opacities, 1 moderate and 5 only minor or no cortical opacities. We focused on beta-sheet levels, a hallmarking property of amyloid-beta, the major protein of plaques and tau protein, the major protein of tangles in Alzheimer brains. Confocal Raman microspectroscopy and imaging was used in combination with hierarchical cluster analysis. Plaques and tangles show high levels of beta-sheets with a beta-sheet to protein ratio of 1.67. This ratio is 1.12 in unaffected brain tissue surrounding the plaques and tangles. In the lenses this ratio is 1.17 independently of the presence or absence of opacities. This major difference in beta-sheet conformation between hippocampus and lens is supported by Congo red and immunostaining of amyloid-beta and tau which were positive for plaques and tangles in the hippocampus but fully negative for the lens irrespective of the presence or absence of opacities. In line with a previous study (Michael et al., 2013) we conclude that cortical lens opacities are not typical for Alzheimer patients and are not hallmarked by accumulation of amyloid-beta, and can thus not be considered as predictors or indicators of Alzheimer disease as claimed by Goldstein et al. (2003).

Validation of digital image slides for diagnosis in cervico-vaginal cytology.

OBJECTIVE: To test the diagnostic concordance between microscopic (MI) and digital (DG) observation of cervico-vaginal (CV) cytology in a validation study of the technique. METHODS: Five cytotechnologists (CT) reviewed 888 routine CV cytology cases from the Cervical Pathology Unit of our center over a 2-week period of time. The cases were first observed by MI and at the end of the day the cases were observed by DG. STATISTICAL ANALYSIS USED: Agreement calculated using the Kappa index. RESULTS: Most of the diagnoses corresponded to benign (64%) or inflammatory conditions (14%) and 24% corresponded to the intraepithelial lesion or malignancy (ILM) category. The overall kappa coefficient of concordance was strong (0.87). Among the different CTs it was almost perfect in two, strong in two and moderate in one. In 18 cases (10%) there were discrepancies between techniques in the category of ILM. In 10 (56%) cases there was an overdiagnosis in DG and in 8 (44%) an overdiagnosis in MI. Only in two cases, the diagnostic discrepancy exceeded one degree of difference between lesions, and they were ASCUS or AGUS for DG and CIN 2 for MI. CONCLUSIONS: In this validation test in which routine cases during a two-week period have been used, observing the cases with both techniques on the same day, we have obtained a strong degree of concordance. The discordances obtained have not been considered relevant.

Absence of beta-amyloid in cortical cataracts of donors with and without Alzheimer's disease.

Eye lenses from human donors with and without Alzheimer's disease (AD) were studied to evaluate the presence of amyloid in cortical cataract. We obtained 39 lenses from 21 postmortem donors with AD and 15 lenses from age-matched controls provided by the Banco de Ojos para Tratamientos de la Ceguera (Barcelona, Spain). For 17 donors, AD was clinically diagnosed by general physicians and for 4 donors the AD diagnosis was neuropathologically confirmed. Of the 21 donors with AD, 6 had pronounced bilateral cortical lens opacities and 15 only minor or no cortical opacities. As controls, 7 donors with pronounced cortical opacities and 8 donors with almost transparent lenses were selected. All lenses were photographed in a dark field stereomicroscope. Histological sections were analyzed using a standard and a more sensitive Congo red protocol, thioflavin staining and beta-amyloid immunohistochemistry. Brain tissue from two donors, one with cerebral amyloid angiopathy and another with advanced AD-related changes and one cornea with lattice dystrophy were used as positive controls for the staining techniques. Thioflavin, standard and modified Congo red staining were positive in the control brain tissues and in the dystrophic cornea. Beta-amyloid immunohistochemistry was positive in the brain tissues but not in the cornea sample. Lenses from control and AD donors were, without exception, negative after Congo red, thioflavin, and beta-amyloid immunohistochemical staining. The results of the positive control tissues correspond well with known observations in AD, amyloid angiopathy and corneas with lattice dystrophy. The absence of staining in AD and control lenses with the techniques employed lead us to conclude that there is no beta-amyloid in lenses from donors with AD or in control cortical cataracts. The inconsistency with previous studies of Goldstein et al. (2003) and Moncaster et al. (2010), both of which demonstrated positive Congo red, thioflavin, and beta-amyloid immunohistochemical staining in AD and Down syndrome lenses, is discussed.

[Isolated conjunctival sebaceous adenoma associated with acute endophtalmitis]. / Adenoma sebáceo conjuntival aislado asociado a endoftalmitis aguda.

Sebaceous adenoma of the conjunctiva is a very rare lesion of uncertain origin. It is usually associated with Muir-Torre syndrome in which neoplasms are also found in other parts of the body. We present the case of a 71-year-old man without a previous or family history of neoplasia, who presented with severe inflammation and an infection in his right eye associated with a tumor of the conjunctiva near the caruncle. The lesion was excised and histopathology revealed a sebaceous adenoma. Microsatellite instability was not observed immunohistochemically. He remains alive and well.

Orbital amyloid tumor associated with myasthenia gravis.

We present a case of a 53-year-old female with an 11 year history of myasthenia gravis (MG) with palpebral ptosis in the left eye which had become more marked over the previous year. Examination revealed a painless left orbital mass causing ptosis. The tumor was surgically removed and histopathology revealed deposits of a hyaline substance which when stained with Congo Red had an apple-green birefringence with polarized light, typical of amyloid. In the absence of amyloid deposits elsewhere in the body, amyloid tumor (AT) was diagnosed. No myelo- or lymphoproliferative syndromes, systemic involvement by amyloidosis or any autoimmune disease were found. The evolution and aesthetic results where satisfactory. Only two cases of orbital AT associated with MG have been described previously; however, in one of the cases, the symptoms of the AT had led to a false diagnosis of MG.

Developing indicators for quality assurance in cytopathology. Catalan Society of Cytopathology.

BACKGROUND: Quality control in cytology must be established through reliable and easily measurable indicators. METHODS: From the Catalan Society of Cytopathology a group of experts has been established to write a document with 13 indicators that cover the entire cytological process, based on its Cytopathology Quality Guide. It has been elaborated through guides and documents with scientific evidence and DELPHI methodology in order to reach a structured consensus on the opinions of a group of experts. RESULTS: Thirteen indicators, covering all the cytologic process are expressed in worksheets specifying all their characteristics. CONCLUSION: This document allows the control of all stages of the cytological process.

Assessment of ovarian vascularization in the polycystic ovary by three-dimensional power Doppler ultrasonography.

OBJECTIVE: To assess whether there are differences in ovarian echogenicity and vascularization as assessed by three-dimensional power Doppler angiography (3D-PDA) between women with polycystic ovaries (PCO) and women with normal ovaries (NO). METHODS: Eighty-three women were classified into two groups according to the 2003 Rotterdam consensus criteria. The NO group comprised women (n = 45) with regular menstrual cycles and proven fertility, whereas the PCO group comprised women (n = 38) with oligo-anovulation, clinical and/or biochemical features of hyperandrogenism, and polycystic ovary morphology at two-dimensional ultrasound. All women were evaluated by means of 3D-PDA. The parameters studied in both groups were follicle number per ovary (FNPO), ovarian volume (OV), mean gray value (MG) and three vascular indices: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). RESULTS: The PCO group showed a higher mean OV as well as FNPO. No differences in MG, VI, FI and VFI were found between the groups. CONCLUSIONS: 3D-PDA indices are not useful for discriminating between normal and polycystic ovaries.

Prevention of posterior capsule opacification through intracapsular hydrogen peroxide or distilled water treatment in human donor tissue.

In order to determine whether posterior capsule opacification after cataract surgery, could be delayed or inhibited through the application of hydrogen peroxide (H2O2) or distilled water (H2Od),we extracted lens capsules from 25 human donor eye globes. Samples were treated for 5 min with either 30 mM H2O2 or H2Od or used as controls, and cultured for one month, during which dark field and tilt illumination photos were taken. These were used to observe and quantify, time until cellular growth and confluence on the posterior capsule. After culture, histological sections were stained for H&E, α-SMA, Ki-67 and vimentin and evaluated. We prevented cellular growth in 50% of H2Od and 58% H2O2 of treated samples. The overall prevention of cell growth compared to cultured controls was significant for both treatments while there was no significant difference between them. In the cases where cellular growth was not prevented, both treatments significantly delay cellular growth. Until day 28 none of the treated samples of either type that had shown growth reached total confluence. All cultured controls reached total confluence before treated samples (median = day 11.5). Also, histologically, there was a clear morphological difference between cultured controls and treated samples.

[MELF pattern in myometrial infiltration in endometrioid adenocarcinoma of the endometrium. A retrospective study of 70 cases]. / Patrón MELF de infiltración miometrial en el adenocarcinoma endometrioide del endometrio. Revisión de 70 casos.

INTRODUCTION: Endometrioid adenocarcinoma of the endometrium (EAE) usually has a favorable prognosis. Recently, the MELF (microcystic, elongated and fragmented) pattern of myometrial infiltration has been described. It is associated with lymphovascular invasion and lymph node metastasis. Seventy cases of EAE were reviewed to identify the presence of MELF and its correlation with other prognostic factors. MATERIAL AND METHODS: Hysterectomies performed for EAE during a 5-year period were reviewed, searching for MELF pattern. Its presence was correlated with other variables such as histological grade, depth of myometrial infiltration, pelvic and/or aortic lymph node metastasis, peritoneal implants and evolution. RESULTS: In 17 (24%) cases MELF pattern was detected. It was more frequent in low grade tumors; it was present in four grade 3 cases. In 9 (53%) cases there was deep myometrial infiltration. Five cases had lymph node metastasis in the pelvis and three in the para-aortic region. One of the patients died, another presented a vulvar recurrence and another pulmonary metastasis. CONCLUSION: MELF pattern can be seen in high grade EAE and correlates with deep myometrial infiltration and pelvic lymph node metastasis. Its presence does not seem to influence survival.

Human lens capsule thickness as a function of age and location along the sagittal lens perimeter.

PURPOSE: To investigate the variation in the thickness of the human lens capsule along the lens perimeter, as well as its changes with age. METHODS: Altogether, 26 human donor lenses, aged 12 to 103 years, were histologically processed. Sagittal sections were stained for collagen with periodic acid-Schiff (PAS). Serial images of the lens border were taken with a photomicroscope and 25x objective. Capsular thickness was measured every 250 microm along the entire lens perimeter. RESULTS: All studied capsules were thicker anteriorly, continuously increasing with age from 11 to 15 microm in average at the anterior lens pole. Maximum thickness was located at the anterior midperiphery, increasing with age from 13.5 to 16 microm. In most cases, there was a local thinning at a pre-equatorial zone, recovering to approximately 7 microm at the equator. The latter value, as well as the minimal thickness at the posterior pole (mean 3.5 microm), did not change with age, whereas the average thickness at the posterior periphery decreased from 9 to 4 microm. CONCLUSIONS: The human lens capsule thickness is at its maximum at the anterior midperiphery, which appears to be located central to the zonular insertion. It increases with age, especially at the anterior pole, while the midperipheral zone stabilizes or slightly decreases after the seventh decade. The anterior zonular insertion is actually related to a local pre-equatorial thinning, which remains unchanged with age. There was no posterior peripheral thickening, except in a few younger patients, with a modest relative maximum roughly at the equator. From here, the posterior capsule becomes progressively thinner and also diminishes with age, except for the thinnest, but stable posterior pole.

[Pregnancy-Associated Breast Cancer: An analytical observational study]. / Cáncer de mama asociado al embarazo: estudio analítico observacional.

BACKGROUND AND OBJECTIVE: Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy and up to one year postpartum. PATIENTS AND METHOD: A retrospective, analytical, observational study comparing 56 cases of breast cancer and pregnancy (PABC) diagnosed 1976-2008 with 73 patients with breast cancer not associated with pregnancy (non-PABC) was performed. Demographic data, prognostic factors, treatment and survival were reviewed and compared. RESULTS: The prevalence of PABC in our center is 8.3/10,000. The highest frequency (62%) appeared during the postpartum period. The stages are higher in PABC, being 31.3% advanced (EIII and EIV) in PABC versus 13.3% in non-PABC (P < .05). Regarding prognostic factors, 27.3% in PABC had a tumoral grade 3 versus 15.8% of non-PABC. Among women with PABC, 33.3% had negative estrogen receptors, 48.7% negative progesterone receptors and 34.5% positive Her2Neu compared with 22.2, 24.1 and 31%, respectively of non-PABC patients. Finally, positive lymph nodes were found in 52.8% of PABC, versus 33.8% non-PABC (P < .05). Overall and disease-free survival rate at 5 years for PABC was 63.7 and 74.2%, respectively. CONCLUSIONS: The poorer survival observed is possibly due to the presence of adverse prognostic features such as lymph node metastases, negative hormone receptors, tumoral grade iii, as well as a delay in diagnosis with a higher rate of advanced stages.

Lymphohistiocytoid mesothelioma of the pleura: a case report with cytological findings.

Lymphohistiocytoid malignant mesothelioma is an infrequent variant of sarcomatoid mesothelioma representing approximately 0.5-3.3% of malignant mesotheliomas. It has been related to asbestos exposure. The tumor is characterized by a diffuse large histiocyte-like cells proliferation mixed with an inflammatory infiltrate of lymphocytes and plasma cells. Its cytological diagnosis is difficult. We present a case of a 67-year-old female with lymphohistiocytoid mesothelioma involving the left pleura. The cytological, histological, and immunohistochemical features are discussed.

Three-dimensional power Doppler ultrasound diagnosis and conservative treatment of ectopic pregnancy in a cesarean section scar.

OBJECTIVE: To describe three-dimensional ultrasonographic features of an ectopic pregnancy in a cesarean scar. DESIGN: Description of a case. SETTING: Case report of one patient. PATIENT(S): A 38-year-old women with three previous cesarean deliveries. INTERVENTION(S): Three-dimensional ultrasonography was performed for diagnosis and treatment. MAIN OUTCOME MEASURE(S): Local administration of methotrexate under ultrasonographic guidance. RESULT(S): Ultrasonographic study revealed a gestational sac in the anterior wall of the uterine isthmus with peritrophoblastic flow. It was treated conservatively and successfully with local methotrexate administration under ultrasonographic guidance. CONCLUSION(S): The early diagnosis of ectopic cesarean scar pregnancy allows the conservative treatment with local administration of methotrexate under ultrasonographic guidance.

Tumor size and lymph node status in multifocal breast cancer.

Tumor size correlates with lymph node metastasis in breast cancer. In multifocal lesions there is controversy about considering the summation of the largest diameter of each tumor. A total of 122 patients with multifocal breast cancer were compared in a retrospective study with 177 patients with unifocal tumors, correlating tumor size with lymph node metastasis. In multifocal tumors, two sizes were considered: the diameter of the largest tumor and the combined diameter of all lesions. Relationship was established by three different logistic models using variables such as age, number of lesions, histologic type, and grade. At a same size of the largest diameter of a unifocal or multifocal lesions and the combined diameter of a multifocal lesion, the latter shows less probability of nodal metastasis indicating that combined diameter is an overestimation of the lesion size. Our results indicate that in multifocal breast cancer, only the diameter of the largest tumor breast cancer has relationship with lymph node metastasis.

Borderline cystic tumors of the ovary: gray-scale and color Doppler sonographic findings.

PURPOSE: The aim of the study was to determine the value of gray-scale and color Doppler sonography in distinguishing borderline cystic tumors (BCTs) from benign cysts and malignant tumors of the ovary. METHODS: The gray-scale and color Doppler sonographic features of 383 ovarian lesions in 374 nonpregnant women were retrospectively studied. Sonography was performed transvaginally for all but 7 lesions, which were imaged suprapubically. All of the lesions were surgically resected via laparoscopy or laparotomy. RESULTS: The histopathologic diagnoses were 27 BCTs, 35 ovarian carcinomas, and 321 benign cysts. Sonography diagnosed 24 (89%) of 27 BCTs as malignant lesions. Patients with BCTs, were younger than those with ovarian cancer (p < 0.001). BCTs showed intracystic papillae in 17 cases (63%), diffuse internal echoes in 11 (41%), intracystic septa in 8 (30%), a heterogeneous echo pattern in 7 (26%), and a solid pattern in 4 (15%). BCTs showed blood flow in 24 cases (89%) and lower pulsatility and resistance indices (RI) compared with benign lesions (p < 0.001 for both). Multivariate analysis revealed intracystic papillae as the only independent predictor of BCTs (p < 0.001). CONCLUSIONS: When a cystic mass has papillae, this is the only abnormal finding detected by gray-scale transvaginal sonography, and color Doppler imaging shows low RI values within the mass, a BCT should be suspected.

Endometrial hyperplasia with secretory changes.

OBJECTIVE: Secretory changes in endometrial hyperplasia are uncommon. The aim of this study is to review the morphologic and clinical findings of 24 cases of endometrial hyperplasia with secretory changes. METHODS: In 24 patients diagnosed with endometrial hyperplasia with secretory changes during 6 years, clinical characteristics such as menopausal status and hormone treatment were correlated with morphological features. A matched age control group of 24 women with conventional endometrial hyperplasia was used to compare the hormonal effect. RESULTS: Nineteen patients were premenopausal. Nine women showed simple hyperplasia without atypia and 15 complex hyperplasia, 7 of them with atypia. Seventeen women were under hormonal treatment at the time of diagnosis, 10 of them with progestins. In 7 patients endometrial adenocarcinoma could be seen, 5 coexisting with endometrial hyperplasia with secretory changes and in 2 appearing after 1 and 4 months. In control group only 2 patients were undergoing progestin hormonal treatment. CONCLUSIONS: Secretory changes can be found in hyperplastic endometrium, particularly in premenopausal women under hormonal treatment with progestins, with the risk of misdiagnosis.

Correlación entre ploidia y fase S, y características morfológicas y receptores hormonales en el cáncer de mama: estudio de 402 casos / Correlation between ploidy and S phase faction and morphological characteristic and hormonal recepyor in breast cancer: study of 402 cases

Con la finalidad de establecer la relación entre ploidia, fase S y las características morfológicas del carcinoma de mama se estudiaron 402 muestras de material en fresco. No se encontro ninguna relación entre ploidia y fase S, y el status de los ganglios linfáticos y la edad de los pacientes. Las lesiones aneuploides resultaron de mayor tamaño que los tumores diploides y usualmente no expresaban receptores hormonales. Los carcinomas ductales infiltrantes (322/402) mostraron mayor porcentaje de lesiones aneuploides y una fase S más elevada en relación con el incremento del grado histológico, la formación de túbulos, el pleomorfismo nuclear y el índice mitótico. En el análisis multivariante, el plemorfismo nuclear y el tamaño tumoral constituyeron las únicas variables independientes y con valor de predicción para la aneuploidia. El patrón de ADN y la fase S constituyen variables que se correlacionan con los cambios morfológicos y así proporcionan información objetiva y reproducible