Early detection of altered epithelium can help in controlling the further progression by timely intervention. Alterations in cellular adhesion are one of the hallmarks of cancer progression, which can be detected at the intracellular level using high-resolution electron microscopy. This study aimed to evaluate the role of electron microscopy in the establishment of ultrastructural markers for early detection of altered epithelium using tissues from 4-Nitroquinoline-1-Oxide (4NQO) induced rat tongue carcinogenesis. Our previous study using light microscopy displayed no histopathological alterations in 4NQO treated tissues until 40 days of treatment, while dysplasia, papilloma and carcinoma were detected at 80/120, 160 and 200 days, respectively. However, electron microscopy detected alterations such as detachment of desmosomes from cell membranes and their clustering in the cytoplasm, increased tonofilaments, keratohyaline granules and thickened corneum in 40 days treated corresponding tissues. These alterations are apparent with hyperkeratosis/hyperplasia but remained undetected using light microscopy. Further, in dysplasia, papilloma and carcinoma, gradual and significant loss of desmosomes, leading to the significant widening of intercellular spaces, was observed using iTEM software. These parameters may serve as indicators for progression of oral cancer. Our results highlight the importance of electron microscopy in the early detection of subcellular changes in the altered epithelium.

The appropriate supply of nutrients in pregnant cows has been associated with the optimal development of foetal tissues, performance of their progeny and their meat quality. The aim of this study was to evaluate supplementation effects of grazing cows in different stages of gestation on skeletal muscle development and performance of the progeny. Thereby, 27 Nellore cows were divided into three groups (n=9 for each group) and their progeny as follows: UNS, unsupplemented during gestation; MID, supplemented from 30 to 180 days of gestation; LATE, supplemented from 181 to 281 days of gestation. The percentage composition of the supplement provided for the matrices was the following: ground corn (26.25%), wheat bran (26.25%) and soya bean meal (47.5%). The supplement was formulated to contain 30% CP. Supplemented matrices received 150 kg of supplement (1 and 1.5 kg/day for cows in the MID and LATE groups, respectively). After birth, a biopsy was performed to obtain samples of skeletal muscle tissue from calves to determine number and size of muscle fibres and for messenger RNA (mRNA) expression analysis. The percentage composition of the supplement provided for the progeny was the following: ground corn grain (30%), wheat bran (30%), soya bean meal (35%) and molasses (5%). The supplement was formulated to contain 25% CP and offered in an amount of 6 g/kg BW. Performance of the progeny was monitored throughout the suckling period. Means were submitted to ANOVA and regression, and UNS, MID and LATE periods of supplementation were compared. Differences were considered at P<0.10. Birth weight, average daily gain and weaning weight of the offspring did not differ among treatments (P>0.10). Similarly, no differences were observed between calves for nutrient intake (P>0.10). However, greater subcutaneous fat thickness (P=0.006) was observed in the calves of LATE group. The ribeye area (P=0.077) was greater in calves born from supplemented compared with UNS cows. The supplementation of pregnant cows did not affect the muscle fibre size of their progeny (P=0.208). On the other hand, calves born from dams supplemented at mid-gestation had greater muscle fibre number (P=0.093) compared with calves from UNS group. Greater mRNA expression of peroxysome proliferator-activated receptor α (P=0.073) and fibroblast growth factor 2 (P=0.003) was observed in the calves born from MID cows. Although strategic supplementation did not affect the BW of offspring, it did cause changes in carcass traits, number of myofibres, and mRNA expression of a muscle hypertrophy and lipid oxidation markers in skeletal muscle of the offspring.

As the understanding of the nutritional regulation of muscle growth mechanisms in fish is fragmentary, the present study aimed to (1) characterise ontogenetic changes in muscle growth-related genes in parallel to changes in muscle cellularity; (2) determine whether an early decrease in dietary protein:energy ratio by fat addition affects the muscle growth mechanisms of rainbow trout (Oncorhynchus mykiss) alevins; and (3) determine whether this early feeding of a high-fat (HF) diet to alevins had a long-term effect on muscle growth processes in juveniles fed a commercial diet. Developmental regulation of hyperplasia and hypertrophy was evidenced at the molecular (expression of myogenic regulatory factors, proliferating cell nuclear antigen and myosin heavy chains (MHC)) and cellular (number and diameter of white muscle fibres) levels. An early decrease in dietary protein:energy ratio by fat addition stimulated the body growth of alevins but led to a fatty phenotype, with accumulation of lipids in the anterior part, and less caudal muscle when compared at similar body weights, due to a decrease in both the white muscle hyperplasia and maximum hypertrophy of white muscle fibres. These HF diet-induced cellular changes were preceded by a very rapid down-regulation of the expression of fast-MHC. The present study also demonstrated that early dietary composition had a long-term effect on the subsequent muscle growth processes of juveniles fed a commercial diet for 3 months. When compared at similar body weights, initially HF diet-fed juveniles indeed had a lower mean diameter of white muscle fibres, a smaller number of large white muscle fibres, and lower expression levels of MyoD1 and myogenin. These findings demonstrated the strong effect of early feed composition on the muscle growth mechanisms of trout alevins and juveniles.

The molecular basis and control of the biochemical and biophysical properties of skeletal muscle, regarded as muscle phenotype, are examined in terms of fibre number, fibre size and fibre types. A host of external factors or stimuli, such as ligand binding and contractile activity, are transduced in muscle into signalling pathways that lead to protein modifications and changes in gene expression which ultimately result in the establishment of the specified phenotype. In skeletal muscle, the key signalling cascades include the Ras-extracellular signal regulated kinase-mitogen activated protein kinase (Erk-MAPK), the phosphatidylinositol 3′-kinase (PI3K)-Akt1, p38 MAPK, and calcineurin pathways. The molecular effects of external factors on these pathways revealed complex interactions and functional overlap. A major challenge in the manipulation of muscle of farm animals lies in the identification of regulatory and target genes that could effect defined and desirable changes in muscle quality and quantity. To this end, recent advances in functional genomics that involve the use of micro-array technology and proteomics are increasingly breaking new ground in furthering our understanding of the molecular determinants of muscle phenotype.

A large number of studies in the last three decades have identified only a handful of biological features in the evolution of human premalignant breast lesions (PBL). They have shown that PBL have a positive growth balance, which may be driven/regulated by oestrogen receptor, erbB-2, and p53. There is marked genetic diversity in PBL, and use of newer technologies such as SAGE, DNA microarrays, and high-throughput proteomics will significantly improve our understanding of evolution of PBL over the next decade.

We analysed a large series of axillary lymph nodes, with and without metastases following radical mastectomy for breast cancer. We found left/right asymmetry in numbers of lymph nodes, and also asymmetry of lymph node dimensions, which could have been the caused by tumoral antigenic stimulation. The distribution of hyperplastic node patterns differed significantly.

The purpose of the present study was to evaluate the biological behaviour of the marginal epithelium, that proliferates and eventually covers laryngeal granulomas, and to reveal the applicability of the recently re-introduced Ljubljana classification when reporting reactive epithelial hyperplastic lesions.

A retrospective clinical and histomorphological analysis was performed on 149 laryngeal granuloma biopsies. Epithelial changes were classified according to the Ljubljana classification into normal epithelium; simple, abnormal, or atypical hyperplasia; and carinoma in situ. Atrophic epithelium, not evaluated separately in the Ljubljana classification, was additionally assessed. Simple hyperplasia was found in 98 cases (65.8 per cent), abnormal hyperplasia in seven (4.7 per cent), atrophic epithelium in 24 (16.1 per cent), and normal squamous epithelium in 20 (13.4 per cent). Atypical hyperplasia and carcinoma in situ were not observed.

The results of our study clearly showed that the proliferation of the covering epithelium mostly in the form of simple hyperplasia, is entirely reactive and therefore reversible. No epithelial hyperplastic lesions were found that were previously described to be associated with an increased risk of malignant alteration, namely atypical hyperplasia and carcinoma in situ. However, since an initial growth of an invasive malignant neoplasm might macroscopically imitate the appearance of laryngeal granuloma, a histological examination in all aetiological forms of laryngeal granulomas is required. By clearly discerning the benign nature of epithelial changes in laryngeal granulomas, the recently re-evaluated and further formulated Ljubljana classification may also influence the clinical handling of patients.

In 1923, Masson described a neoplastic process consisting of papillary hyperplasia of the endothelial cells, with a consequent obliteration of the vascular lumen, followed later by degenerative changes. Masson coined the term vegetant intravascular haemangioendothelioma, however, these days it is more commonly known as papillary endothelial hyperplasia (PEH), or by the pseudonym, Masson's tumour. Although relatively rare, there are numerous accounts of PEH in the literature, describing its predilection for the head and neck region. Our case report describes the finding of a PEH within the paranasal sinuses, a site not previously mentioned even in the largest of series found on literature search. We will then discuss the relevant histological features of the lesion, and its natural history.

Adenomatoid hyperplasia of palatal minor mucous glands is rare but significant because the clinical appearance mimics malignant disease. The typical history of a painless, indolent palatal swelling, together with the histological picture of benign glandular hyperplasia and hypertrophy, are illustrated in this report.