Relationships between body composition analysis measures in Greek women and US white women.

We investigated the regional changes in body composition relative to age, in healthy Caucasian women living in the Mediterranean area. Body composition of total and subtotal body was measured, and fat mass (FM) ratios along with FM and lean mass (LM) indices were calculated in 330 women aged 20-85 years, using DXA. Data were compared with the NHANES reference database. Peak bone mineral density and bone mineral content of total body were 1.149 g/cm(2) and 2,209 g and were achieved between ages 41 and 50. Peak %FM of total body, FM index (FMI; FM/height(2)), FM of trunk to legs, and FM of trunk to limbs were 41.5%, 13.69 kg/m(2), 1.623, and 1.14, respectively. Peak %FM and FMI were achieved between 61 and 70 years. Unlike US counterparts, in our series, both FM ratios showed a propensity for women to accrue fat in the trunk following the android pattern of fat distribution. Peak LM index for total body (LMI; LM/height(2)) and limbs (ASMMI; appendicular skeletal muscle mass/height(2)) was 18.08 kg/m(2) and 7.33 kg/m(2), respectively, and was achieved between 61 and 70 years. For Greeks, the ASMMI was greater from 55 years onwards. Greek women have increasing bone mass in early adulthood followed by significant decline during fifties and onwards. Compared with US white women, Greek women have significantly greater truncal fat for all ages, implying a greater risk of obesity-associated diseases. Middle-aged and older Greek women have greater appendicular skeletal muscle mass, which may eliminate the overall risk of sarcopenic obesity.

[Colorectal carcinogenesis]. / La carcinogenèse colorectale.

Colorectal adenocarcinomas were long thought to be an homogeneous entity, in which traditional adenomas of the colon were the best-recognized and most common precursor lesions. Current morphological and molecular data suggest an alternative pathway of colorectal carcinogenesis involving "serrated neoplasia". This pathway seems to be responsible for approximately 10% to 15% of sporadic colorectal adenocarcinomas. These serrated lesions, that may progress to cancer, show relatively distinct histopathological molecular and epigenetic features not commonly seen in traditional adenomas. Key characteristics of the serrated neoplasia pathway include BRAF gene mutations, excess CpG island methylation, and subsequent microsatellite instability. A major challenge for pathologists is to identify these new potential precursor lesions, in order to enable early diagnosis and treatment.

Expression of Syndecan-1 in Chronic Liver Diseases: Correlation With Hepatic Fibrosis.

BACKGROUND/AIM: The mechanisms underlying the contribution of the heparan sulfate proteoglycan syndecan-1 to liver tissue injury and to crucial biological processes, such as fibrogenesis, remain to be elucidated. Therefore, we investigated the immunohistochemical expression of syndecan-1 in chronic liver diseases (CLDs) and its probable role in hepatic fibrosis. MATERIALS AND METHODS: Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections of biopsy material obtained from 128 patients diagnosed with CLDs. The correlation between syndecan-1 expression and the stage of fibrosis was investigated. RESULTS: According to the severity of fibrosis, cases were categorized into three groups: early fibrosis; intermediate fibrosis; advanced fibrosis. Syndecan-1 expression was significantly enhanced in advanced fibrosis compared to early (p<0.012) and intermediate (p<0.003) fibrosis. CONCLUSION: In CLDs, syndecan-1 immunohisto-chemical overexpression was found to be positively correlated with the severity of fibrosis, suggesting its probable role in hepatic fibrogenesis.

Osteonecrosis of the tibial plateau: magnetic resonance imaging appearances with quantitation of lesion size and evidence of a pathogenesis of meniscal injury.

PURPOSE: To determine the magnetic resonance (MR) imaging appearances of osteonecrosis of the tibial plateau and perform quantitative analysis of the extent of the necrotic area. MATERIALS AND METHODS: Twenty-eight patients (34 knees) with osteonecrosis were retrospectively evaluated using MR imaging and other modalities where available. A computerized image analysis program that allowed quantification of the lesion size was used to obtain measurements of the extent of involvement, which were then incorporated into each stage of the disease. RESULTS: The MR imaging findings of osteonecrosis of the tibial plateau included subchondral regions of abnormal signal intensity (n = 28), a double-line sign (n = 11), and fractures (n = 9). Meniscal tears and cartilage abnormalities were disclosed in the affected knee compartment with an equal frequency (n = 17). The size of the necrotic lesion varied among different stages of the disease as follows: 6.8% to 15.7% (stage I); 6.5% to 59.3% (stage II); 23.5% to 61.3% (stage III); and 34.3% to 75% (stage IV). The extent of involvement was greater in stage II than that in stage I (P < 0.001) and in stage IV than that in stage III (P < 0.05), whereas the extent of involvement in stage III was not significantly greater than that in stage II (P > 0.05). CONCLUSIONS: The MR imaging characteristics of osteonecrosis of the tibial plateau are variable. The association of osteonecrosis at this site with meniscal tears and cartilage abnormalities has important implications for pathogenesis of the disease as it relates to physical stress. Quantification of the lesion size provides precise information for optimal staging of the disease.

Synchronous presentation of GISTs and other primary neoplasms: a single center experience.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms of the digestive tract and may occasionally arise within the abdomen without gastrointestinal tract connection. GISTs have recently attracted widespread interest because of the development of effective targeted molecular agents against it. While synchronous occurrence of a GIST with a tumor of different histogenesis was thought to be very rare, it is now apparent that they are more common than previously believed. PATIENTS AND METHODS: We report our experience with GISTs and also six cases of GIST coexisting with other primary neoplasms. Using immunohistochemistry and mutational analysis, a possible correlation was investigated. A review of the literature was also conducted. RESULTS: There were no significant differences in the immumohistochemical and molecular profile between single GISTs and GISTs coexisting with other tumors, nor was there any mutational correlation between GISTs and the coexistent tumors of different histogenesis regarding KIT and PDGFRA genes. CONCLUSION: Further molecular biology studies are required in order to investigate thoroughly the simultaneous development of tumors with different histotypes.

Primary squamous cell carcinoma of the ovary. Review of the literature.

PURPOSE: Primary squamous cell carcinoma (SCC) of the ovary is rare. Most cases arise from a cystic teratoma or less frequently from Brenner tumor or endometriosis. We reviewed 36 cases of primary ovarian SCC reported in the literature including a case diagnosed and treated in our institution. METHODS: Data was collected by using the key-words "primary squamous cell carcinoma" and "ovary" on Google Scholar and PubMed in April 2018. All reviewed cases were analyzed according to diagnosis, surgical approach, adjuvant therapy and outcome. RESULTS: To date 23 articles presenting 36 cases of primary ovarian SCC are reported. Nine patients had stage I, 8 stage II, 11 stage III and 5 stage IV disease, whereas 3 patients had in situ carcinoma. All patients underwent surgery (mainly hysterectomy with bilateral salpingo-oophorectomy). Adjuvant therapy was reported in 24 patients, 15 of which received chemotherapy, 6 radiotherapy and 3 a combination of both. Chemotherapy regimens were similar to the ones used in ovarian carcinoma (more often platinum plus paclitaxel). Follow-up period was in general short and survival varied between 9 days and 14 years, depending on the stage at diagnosis. CONCLUSIONS: Primary ovarian SCC is a rare entity with poor prognosis, compared to serous carcinoma. Treatment is usually extrapolated from classical ovarian carcinoma algorithms, including surgical management combined with adjuvant chemotherapy with or without radiotherapy. Further investigations are needed to define optimal treatment, such as chemotherapy regimens and the role of radiotherapy and lymph node dissection.

Association of low Syndecan-1 expression with adverse histopathological parameters in gastric carcinomas.

PURPOSE: Since syndecan-1 is an adhesion molecule involved in tumor invasion and metastasis, we evaluated the relationship between syndecan-1 expression and histopathological features of gastric carcinomas. METHODS: Syndecan-1 expression was evaluated in 104 gastric carcinomas using immunohistochemistry. RESULTS: High, moderate and low syndecan-1 expression in carcinoma cells was observed in 17/104, 25/104 and 62/104 cases, respectively. High, moderate and low syndecan-1 expression in stromal cells was observed in 5/104, 22/104 and 77/104 cases, respectively. Low epithelial syndecan-1 expression was significantly associated with increased depth of invasion (p=0.034) and lymph vessel invasion (p=0.035). Low stromal syndecan-1 expression was significantly associated with histologic type (intestinal vs diffuse/mixed; p=0.04), increased histologic grade (p=0.04) and large tumor size (p=0.026). CONCLUSION: Low levels of tumor and stromal syndecan- 1 expression were associated with adverse histopathological parameters in gastric carcinoma. This suggests that syndecan-1 expression may be helpful for assessing the aggressiveness of gastric carcinomas.

Prognostic impact of lymphangiogenesis and lymphatic invasion (CD105 expression) in small cell lung carcinoma.

BACKGROUND: Lymphangiogenesis, an essential process in the metastasis of malignant tumors, has not been thoroughly studied. The possibility of using it to define subsets of patients with different prognosis in cancer could be of vital clinical importance. MATERIALS AND METHODS: Fifty patients (5 women, 45 men; mean age, 64.47 years) with SCLC were retrospectively studied. Tumor specimens were stained for CD105, and intratumoral lymphatic microvessel density (ILMVD) and lymphatic invasion were determined. RESULTS: Twenty-five patients were diagnosed with limited and 25 with extensive SCLC. All patients received chemotherapy and 32.7% radiation therapy. A direct association between ILMVD (CD105 expression) and lymphatic invasion was observed (p<0.046). CD105 expression was significantly associated with the stage of the disease (p=0.004) and the presence of metastasis (p=0.05). CONCLUSION: CD105 expression and lymphatic invasion correlated significantly with the clinical parameters and patient outcome, therefore, constituting an important prognostic role in SCLC.

Immunohistochemical expression patterns of neural and neuroendocrine markers, the neural growth factor receptors and the beta-tubulin II and IV isotypes in human thymus.

Increasing evidence suggests that neuroimmune networks play key roles in the thymic histophysiology and pathology. Prompted by this, we analyzed by immunohistochemistry the distribution of human thymic cells expressing major neural and neuroendocrine markers and neural growth factor (NGF) receptors in combination with the expression patterns of various cytokeratins. Additionally, since some beta-tubulin isotypes are preferentially expressed in neuronal cells, the immunotopographical distribution of thymic cells expressing beta-tubulin II, III and IV was analyzed. Thymic epithelial cells (TECs) expressed protein gene product 9.5 (PGP 9.5), chromogranin A (CHRA), synaptophysin (SYN), neuron-specific enolase (NSE), tyrosine hydroxylase (TH), CD56, CD57, neurofilaments (NF) (140-160 kDa), NGF receptors (TrKA and p75), beta-tubulin II and IV isotypes and cytokeratin 7, 8, 10, 13, 14, 18 and 19. PGP 9.5 was preferentially expressed in cortical TEC whereas SYN, CHRA, NSE, TH and NF 140-160 kDa were preferentially expressed in medullary TECs and Hassal corpuscles. Variable levels of expression of beta-tubulin II and IV were observed in all TEC subtypes whereas beta-tubulin III was undetectable in TECs. Subcapsular and cortical TECs display higher expression of beta-tubulin IV and lower expression of beta-tubulin II in comparison to those observed in medullary TEC and Hassal corpuscles. The diversity of the immunotopographical distibution and the expression of neural and neuroendocrine markers, the NGF receptors TrKA and p75, and the beta-tubulin II and IV isotypes in the distinct subtypes of TEC may reflect the diversity of their biological functions and/or their different stages of differentiation. The present results provide further immunohistological evidence that numerous neural and neuroendocrine factors may be required for the development and function of the human thymic microenvironment.

Immunohistochemical expression of cell-cycle proteins in gastric precancerous lesions.

BACKGROUND: The early indicator for the subject predisposed to gastric cancer is abnormal proliferation of gastric epithelial cells, such as atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia, which have been considered as precancerous lesions of gastric cancer. To determine whether p53 protein, cyclins D1, and D3, and p27(kip1) play a role in the carcinogenesis pathway of gastric cancer, we performed an immunohistochemical study of their expression in gastric precancerous lesions. METHODS: A total of 1 45 endoscopic gastric biopsy specimens of AG, IM, and gastric dysplasia were studied. These molecular markers were localized by immunohistochemistry. RESULTS: P53 was expressed in 15% of cases with gastric dysplasia and not in the pre-dysplastic stages of the gastric mucosa. All cases were concerning high-grade dysplasia. Cyclin D1 protein was almost undetectable in the precancerous lesions of gastric cancer. Cyclin D3 protein overexpression was seen in 10% of biopsies with IM, and 50% of biopsies with gastric dysplasia. High expression of p27(kip1) protein was demonstrated in all cases of chronic gastritis. As atrophy, IM, and dysplasia develop, expression of p27(kip1) protein is suppressed. In total, 15% of dysplastic cases showed no expression of p27(kip1) protein. CONCLUSIONS: (i) P53 mutation must be a late event during the development of gastric cancer. (ii) Cyclin D1 protein overexpression may not play a role in the progression from normal to neoplastic gastric mucosa, while overexpression of cyclin D3 is an earlier event during gastric carcinogenesis, and its role must be further evaluated. (iii) Reduced expression of p27(kip1) is a rather early event in gastric tumorigenesis, before dysplastic changes occur.

Differential expression of dysadherin in papillary thyroid carcinoma and microcarcinoma: correlation with E-cadherin.

Dysadherin is a novel glycoprotein, with an anti-cell-cell adhesion function. The aim of the present study was to examine the expression of dysadherin in thyroid papillary microcarcinoma (PMC), to associate it with the expression of E-cadherin and to investigate whether there are differences with papillary carcinoma (PC). A statistically significant difference in dysadherin and E-cadherin expression between PC and PMC and a negative correlation between E-cadherin and dysadherin expression regardless of tumor size were noted. Based on these findings it is hypothesized that retained cell-cell adhesion, through maintenance of the E-cadherin adhesion system, in PMC prevents neoplastic cells from dissociating easily from each other and metastasizing. Increased dysadherin expression is possibly one of the post-transcriptional mechanisms responsible for E-cadherin downregulation in thyroid papillary neoplasia.

Osteochondromas: review of the clinical, radiological and pathological features.

Osteochondroma is the most common benign bone tumor and usually occurs in the metaphyseal region of the long bones. This tumor takes the form of a cartilage-capped bony outgrowth on the surface of the bone. The vast majority (85%) of osteochondromas present as solitary, nonhereditary lesions. Approximately 15% of osteochondromas occur as multiple lesions in the context of hereditary multiple osteochondromas (HMOs), a disorder that is inherited in an autosomal dominant manner. Most lesions appear in children and adolescents as painless, slow-growing masses. However, depending on the location of the osteochondroma, significant symptoms may occur as a result of complications such as fracture, bony deformity, mechanical joint problems and vascular or neurologic compromise. Malignant transformation of osteochondromas can occur later in adulthood but rarely metastasize. The treatment of choice for osteochondroma is surgical unless the skeleton is still immature. Pathogenetic analysis showed that HMOs are caused by mutations in either of two genes: exostosis (multiple)-1 (EXT1), which is located on chromosome 8q24.11-q24.13 or exostosis (multiple)-2 (EXT2), which is located on chromosome 11p11-12. Recently, biallelic inactivation of the EXT1 locus was described in nonhereditary osteochondromas. The EXT1 and EXT2 proteins function in the biosynthesis of heparin sulfate proteoglycans (HSPGs) which are multifunctional proteins involved in several growth signaling pathways in the normal epiphyseal growth plate. Reduced EXT1 or EXT2 expression in osteochondromas is associated with disordered cellular distribution of HSPGs, resulting in defective endochondral ossification which is likely to be involved in the formation of osteochondromas. Here the clinical, radiological, pathological and pathogenetic features and the treatment modalities of osteochondroma are reviewed.

Alterations of p53 and Rb Pathways Are Associated with High Proliferation in Bladder Urothelial Carcinomas.

BACKGROUND/AIM: Since most cancers are associated with alterations of the p53 and Rb pathways, the expression of p53, p21, Rb, p16, p27, cyclin D1, cyclin A, cyclin B1 and Ki67 proteins were analyzed in bladder urothelial carcinomas (BUC). MATERIALS AND METHODS: One hundred twenty-two cases of BUC were studied by immunohistochemistry. RESULTS: The pathways p53/p21 and Rb/p16/cyclin D1 exhibited alterations in 81/115 and 63/84 cases, respectively. Alterations of the p53/p21 and Rb/p16/cyclin D1 pathways were positively correlated with high cyclin A expression. High expression of p53, Ki67, cyclin A and cyclin B1 was inversely correlated with the papillary morphology of the tumor and positively with tumor grade and T-stage. CONCLUSION: The results showed that a) alterations of the p53 and Rb pathways are associated with high proliferation of tumor cells in BUC and b) high expression of cell-cycle proteins is associated with adverse histopathological parameters of these tumors.

Expression of bcl2 family proteins and active caspase 3 in classical Hodgkin's lymphomas.

The expression of various bcl2 family proteins has been reported in Hodgkin and Reed-Sternberg cells, but the proteins bad, bid, and bim have not been analyzed in classical Hodgkin's lymphomas (HLs). This study aimed to investigate the expression of the proteins bcl2, bcl-xl, mcl1, bax, bak, bad, bid, bim, and active caspase 3, and the TUNEL (terminal deoxynucleotidyl transferase-mediated in situ labeling) index to gain further insight into the apoptosis profile of classical HLs. A high expression of the proteins bcl2, bcl-xl, mcl1, bax, bak, bad, bid, and bim in HRS cells was found in 27 of 101 (27%), 95 of 101 (94%), 27 of 97 (29%), 73 of 95 (77%), 37 of 102 (36%), 85 of 94 (90%), 19 of 109 (17%), and 43 of 91 (47%) cases, respectively. The high expression of bcl-xl, bax, and bad in HRS cells in most classical HLs indicates that these proteins may play predominant roles in the regulation of apoptosis in classical HLs. Active caspase 3-positive and TUNEL-positive Reed-Sternberg cells were detected in 47 of 70 (67%; range, 0%-12%) and 60 of 71 (85%; range, 0%-19%) cases, respectively. Significant positive correlations were found between bax/bcl2 (P = .002), bad/bcl2 (P = .020), bad/bcl-xl (P = .003), and bim/mcl1 (P = .036). Based on these findings, it could be hypothesized that the antiapoptotic proteins bcl2, bcl-xl, and mcl1 may counteract the expression of the proapoptotic proteins bax, bad, and bim, thereby contributing to the survival of Reed-Sternberg cells.

Alterations of the p53, Rb and p27 tumor suppressor pathways in diffuse large B-cell lymphomas.

Diffuse large B-cell lymphomas (DLBCL) display defects in cell cycle and apoptosis regulation. Therefore, the immunohistochemical expression patterns of the proteins p14, p21, Hdm2 and cyclin D2 were analyzed in relation to the previously reported expression of other major cell cycle proteins (p53, Rb, p16, p27, Ki-67 and cyclins A, B1, D2, D3 and E), apoptosis-associated proteins (bcl2, bcl-xl, bax, bak, bad and bid) and the B-cell differentiation immunophenotypes. Expression of the proteins p14, p21, Hdm2 and cyclin D2 was observed in 62/71 (87%), 22/76 (29%), 35/74 (47%) and 11/77 (14%) cases, respectively. Immunohistochemical alterations of the p53 (p53-Hdm2-p21-p14), Rb (Rb-p16-cyclin D [D2 or D3]) and p27 (p27-cyclin E) pathways were found in 56/77 (73%), 53/79 (67%) and 54/79 (68%) cases, respectively. Concomitant alterations of the p53-Rb, p53-p27 and Rb-p27 pathways were found in 40/77 (52%), 38/77 (50%) and 36/79 (46%) cases, respectively. Three concomitant alterations of the p53-Rb-p27 pathways were found in 28/79 (35%) cases. The main findings of the present study were the following: alterations of the p27 pathway were associated with higher expression of Ki-67 (p = 0.023); concomitant alterations of the p53Rb pathways and the p53-p27 pathways were associated with higher expression of cyclin A (p = 0.015 and p = 0.021, respectively) and concomitant alterations of the p53, Rb and p27 pathways were associated with higher expression of cyclin A (p = 0.013). Since cyclin A supports DNA replication, centrosome duplication and mitosis, these findings indicate that concomitant alterations of the p53, Rb and p27 pathways in DLBCL may have cooperative effects resulting in increased neoplastic cell proliferation. This might explain, at least partially, the association between concurrent aberrations of the p53, Rb and p27 pathways and aggressive clinical behavior in DLBCL.

Prognostic significance of HER-2, p53 and Bcl-2 in patients with epithelial ovarian cancer.

BACKGROUND: Several oncogenes and onco-suppressor genes have been implicated in epithelial ovarian carcinogenesis, but their clinical significance is not clear and conflicting data have been found in various studies. PATIENTS AND METHODS: The immunohistochemical expression of HER-2, p53 and Bcl-2 proteins was investigated in a cohort of 95 patients with advanced epithelial ovarian cancer (stages IIc-IV). These patients participated in a phase III randomized clinical trial and were treated either with paclitaxel/carboplatin, orpaclitaxel/carboplatin alternating with paclitaxel/cisplatin. RESULTS: Positive immunostaining for HER-2, p53 and Bcl-2 proteins was found in 18%, 70.5% and 69.5% of the cases, respectively. In multivariate analysis, older patients (< 63 vs. > or = 63 years, p < 0.001), worse grade (I-II vs. III, p = 0.04) and p53 expression (negative vs. positive, p = 0.002) were significant prognostic factors independently associated with survival. CONCLUSION: p53 status along with age and grade appear to be independent prognostic factors for survival in patients with epithelial ovarian cancer.

Early gastric carcinoma with oncocytic features and extensive metastases.

We present the case of a 63-year-old Caucasian woman with early gastric adenocarcinoma, suffering from extensive metastases at the time of initial presentation. Microscopic examination of the gastrectomy specimen revealed an invasive adenocarcinoma with oncocytic features. Interestingly, despite the fact that the carcinoma was pT1, it also was found to be N2, stage IV. The biologic behavior of oncocytic adenocarcinoma of the stomach is still unclear. We would like to present this case, so that its clinicopathological characteristics can be added to the few cases already published.

Orbital metastasis from verrucous carcinoma of the oral cavity: case report and review of the literature.

A rare case of metastatic verrucous carcinoma (VC) of the oral cavity is presented. The patient was referred to the Ophthalmology Department due to diplopia. The patient reported history of diagnosis of verrucous squamous carcinoma in the oral cavity occuring 6 years earlier that although excised presented several recurrences. The lesion metastasized to local lymph nodes and after being characterized as inoperable the patient underwent thirty-seven sessions of radiation therapy. Two months after completion of radiation therapy, the patient underwent an orbital CT scan that revealed a mass with morphological features consistent with secondary involvement of the orbit from the known VC. Although treated with chemotherapy, the patient died 5 months later. No other case of this entity, which usually presents as a slow-growing lesion enlarging with direct extension rather than frank invasion, metastasizing to the orbit has been reported in relevant literature.

A new concept of melanocytic neoplasia pathogenesis based on the phenotype of common acquired nevi.

Common melanocytic nevi are ubiquitous lesions which in some cases constitute a risk factor for the development of melanoma. To date, despite long term research there are no known molecular hallmarks for nevus development. We have observed that common acquired nevi excised from the same individual share remarkable similarity in their microscopic appearance and in the immunohistochemical expression of E-cadherin. Based on these observations, we hypothesize that all melanocytes are genetically similar in the same individual and changes predisposing to neoplasia are a global melanocytic event characteristic for each person and propose a microgenomics/proteomics approach to test this hypothesis.

Mitochondrial Membrane Dynamics and Inherited Optic Neuropathies.

Inherited optic neuropathies are a genetically diverse group of disorders mainly characterized by visual loss and optic atrophy. Since the first recognition of Leber's hereditary optic neuropathy, several genetic defects altering primary mitochondrial respiration have been proposed to contribute to the development of syndromic and non-syndromic optic neuropathies. Moreover, the genomics and imaging revolution in the past decade has increased diagnostic efficiency and accuracy, allowing recognition of a link between mitochondrial dynamics machinery and a broad range of inherited neurodegenerative diseases involving the optic nerve. Mutations of novel genes modifying mainly the balance between mitochondrial fusion and fission have been shown to lead to overlapping clinical phenotypes ranging from isolated optic atrophy to severe, sometimes lethal multisystem disorders, and are reviewed herein. Given the particular vulnerability of retinal ganglion cells to mitochondrial dysfunction, the accessibility of the eye as a part of the central nervous system and improvements in technical imaging concerning assessment of the retinal nerve fiber layer, optic nerve evaluation becomes critical - even in asymptomatic patients - for correct diagnosis, understanding and early treatment of these complex and enigmatic clinical entities.