Roberto Lio

Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions.

Beclin 1 and LC3 autophagic genes are altered in several human cancer types. This study was designed to assess the expression of Beclin 1 and LC3 in cutaneous melanocytic lesions, in which they have not yet been investigated. In melanoma, we correlated their expression with conventional histopathologic prognostic factors. In 149 lesions, including benign nevi, dysplastic nevi, radial growth phase melanomas, vertical growth phase melanomas, and melanoma metastases, proteins were evaluated by immunohistochemistry, and, in representative cases of benign nevi, vertical growth phase melanomas and melanoma metastases were evaluated by Western blotting. In most lesions, messenger RNA level was also assessed by real-time reverse transcriptase polymerase chain reaction. Both genes were expressed in all the investigated conditions. Beclin 1 cytoplasmic protein and messenger RNA, as well as LC3 messenger RNA, significantly decreased with tumor progression (P < .05). The percentage of cases with high cytoplasmic expression of beclin 1 from 100% in benign nevi declined to 86.4% in dysplastic nevi, 54.5% in radial growth phase melanomas, 54.3% in vertical growth phase melanomas, and 26.7% in melanoma metastases. The lowest expression of LC3 II protein was observed in melanoma metastases (53.3% of cases) (P < .05); LC3 II protein overexpression was, however, found in several nonbenign lesions, with the highest percentage (45.5%) in radial growth phase melanomas. LC3 II protein expression was inversely correlated to thickness, ulceration, and mitotic rate. In a multivariate analysis, messenger RNAs for both genes discriminated between nonmalignant (benign and dysplastic nevi) and malignant (radial, vertical growth phase melanomas, and melanoma metastases) lesions. Our results, therefore, indicate that beclin 1 and LC3 II autophagic gene expression is altered also in melanocytic neoplasms.

Endocrine inactive pituitary carcinoma metastasizing to cervical lymph nodes: A case report

A 64-year-old woman experienced an episode of disorientation in relation to time, place, and people, as well as of visual defect and impaired balance. Physical examination showed a bitemporal hemianopsia and truncal ataxia. Computerized tomography of the skull revealed a sellar mass consistent with the diagnosis of pituitary adenoma. The patient progressively lost consciousness and died. At postmortem examination, a pituitary neoplasm with arachnoid metastases was present. Metastatic cervical lymph nodes were also detected. Histologic aspects of the primary tumor and of lymph node metastases were quite similar. Immunohistochemical investigation revealed the epithelial origin of the neoplasm and failed to disclose endocrine activity. At ultrastructural examination, the cells of the primary tumor and of the metastases lacked specific granules. These findings support the evidence of a primary metastasizing pituitary carcinoma.

Morphometric distinction of low- and high-grade dysplasias in gastric biopsies

Substantial agreement has previously been demonstrated between qualitative and morphometric grading of gastric dysplasia. In the present study, a further attempt is made to quantitatively define the dysplastic changes in relation to associated benign or malignant changes of gastric mucosa. In total, 232 cases were studied and were associated with benign peptic ulcer (89 cases), histologically proven gastric cancer (88 cases), and gastritis-associated mild, moderate, and severe dysplasias (55 cases). The analysis showed that one discriminant function consisting of seven morphometric features is sufficient to separate the regenerative and cancer-associated cases. The classification results obtained on the basis of this discriminant function in both training and testing sets are encouragingly similar, indicating that the classification is reliable. This was further confirmed by the results of the application of this rule in the mild, moderate, and severe dysplasia biopsies (the above-mentioned gastritis-associated cases) used in a previous study. The quantitative analysis permits two grades, instead of three, to be distinguished: low-grade and high-grade dysplasia.

Correlation between immunohistochemically determined oestrogen receptor content, using monoclonal antibodies, and qualitative and quantitative tissue features in ductal breast cancer

Previous studies have shown that oestrogen receptor content in breast cancer was correlated with qualitative and also, more strongly, with quantitative nuclear features in tissue sections. However, even with the better reproducible quantitative microscopical assessments, the variance in the correlation with oestrogen receptor was considerable. This might be due to the implicit problems of oestrogen receptor determination with the biochemical assay. Therefore, receptor content was studied using monoclonal antibodies in 50 consecutive invasive ductal breast cancers. Oestrogen receptor status was compared with qualitative features and with the mean and standard deviation of the nuclear area, morphometrically evaluated on immunostained and adjacent haematoxylin and eosin stained sections. In agreement with earlier observations, nearly all tumours with prominent elastosis were oestrogen receptor positive; but a minority of negative cases also showed elastosis. The correlation between the other qualitative features and receptor status was weak. A significant inverse correlation (P<0.001) existed between the receptor status and the mean and standard deviation of the nuclear area. Even with the highly reproducible morphometrical analysis, correlation between nuclear oestrogen receptor content and quantitative nuclear features was relatively weak. This might indicate that receptor status and nuclear morphometric features reflect different biological characteristics of breast cancers.

Bronchiolo-alveolar carcinoma: An analysis of survival predictors

Macroscopic and microscopic features of tumours have been analysed in 37 bronchiolo-alveolar carcinomas. Lymphocytes, Langerhans cells, collagen (mature and/or myofibroblastic), were quantitatively or semiquantitatively evaluated. Histology, stage, type of fibrosis, nuclear profile features (area and shape factors), amount and type of mucin secreted, number of mitoses, Langerhans cells, myofibroblasts and LeuM1+ cells were not related to survival. Gross morphology of the tumour and, to a lesser extent, lymphoid infiltrates (in particular UCHL1+ and L26+ peritumoral lymphoid cells) were the only variables significantly related to survival. Estimated survival functions were computed according to Coxs model: well demarcated tumours behaved significantly better than poorly demarcated tumours and even more so than diffuse or multiple mass. Lymphoid infiltrates were significantly more represented in and around well demarcated tumours: however, their survival predicting value was less than that of the gross type.

Distinction between diffuse cutaneous malignant follicular center cell lymphoma and lymphoid hyperplasia by computerized nuclear image analysis

The difficult differential diagnosis between the diffuse variants of cutaneous lymphoid hyperplasia (CLH; synonym: pseudolymphoma) and malignant follicular center cell lymphomas (FCCL) often requires a multidisciplinary approach. Eighteen CLH and 11 FCCL, diagnosed by conventional histology and immunophenotyping and subsequently examined with a polymerase chain reaction to show clonal immunoglobulin heavy-chain gene rearrangements, were subjected to a novel type of automated nuclear image analysis. Of all nuclear parameters tested in azure A-stained semithin sections, the mean nuclear profile area (TN) of lymphoid cells was the best criterion to distinguish between CLH and FCCL (p = 9 x 10 6). Additional distinctive features, in the order of decreasing significance, were the SD of TN; all chromatin textural parameters combined; and the light and the dark fractions of the central nuclear profile areas. Parameters related to the chromatin pattern were independent of nuclear profile size in FCCL, but not in CLH. Two lesions registered as CLH displayed the nuclear characteristics favoring this diagnosis, but showed B-cell monoclonality at the DNA level. In conclusion, computerized nuclear image analysis is a helpful additional diagnostic tool in the evaluation of diffuse CLH and cutaneous FCCL.

Juvenile ossifying fibroma of the orbit Case report and review of the literature

A case of juvenile ossifying fibroma (Jof) expanding the left side of the ethmoidal bone and partially invading the homolateral orbital cavity is presented. the patient was a seven-year-old boy who experienced painless progressive proptosis of the left eye and mild limitation of the ocular excursion in the upper-external direction of gaze. A review of the literature and a discussion of clinical, radiographic and histopathologic findings are reported to differentiate Jof from other fibro-osseous orbital lesions bordering on cranial cavities. the importance of thin (1.5 mm) computed tomographic scanning sections with cross-sectional multiplanar image reconstructions is stressed for determining the right surgical approach.

Epithelial Cyst of the Superior Oblique Muscle Trochlea

Abstract Most of the congenital orbital cysts are choristomas such as dermoid or epidermoid and only in a few cases they are epithelial. Clinically, they manifest as cystic movable formations mostly localized in the upper temporal quadrant of the orbit. We describe here the case of a 49-year-old man with an orbital cyst localized in the upper-nasal quadrant of the orbit and which was showing signs of a gradual enlargement and progression over the past weeks. Computed tomography revealed a cyst of 1.9 × 1.6 cm in size and located within the trochlea of the upper oblique muscle. The cyst was completely extirpated after orbitotomy performed by superciliary approach. Histopathology revealed a cyst with nonkeratinized cuboidal epithelium. Postoperative course was uneventful, without inflammation signs, and after 5 weeks excellent functional and aesthetic effects were achieved with no iatrogenic alteration of the ocular motility.