Novel RET mutations in macedonian patients with medullary thyroid carcinoma: genotype-phenotype correlations.

Medullary thyroid carcinomas (MTCs) are rare neoplasms comprising 2-10% of all thyroid malignnancies. More than 75% are sporadic tumors and the remainder is familial and MEN2 related. Both sporadic and syndromic MTCs frequently show mutations in the RET proto-oncogene. It has been noted that some MTC cases present an indolent, and some an aggressive clinical course. Ki-67 expression is generally low, with documented exceptions, whereas high expression of Bcl-2 has been reported in majority of the cases. Some studies have shown that Ki-67 and Bcl-2 expressions have prognostic value, as well as RET mutational status. We analyzed 20 unrelated MTC cases for Ki-67, Bcl-2 expression and RET mutations and tested their intercorrelations, correlations to the morphologic features and stage of the tumors, as well as their influence on survival. In 13 of the 20 analyzed cases we found 23 sequence changes distributed in exons 8, 10-13 and 16. There were 11 different missense mutations, single nucleotide deletion with frameshift, and 8 different synonymous mutations. Only 4 of the sequence changes have been previously published. Twelve patients (60%) had tumors expressing one or more missense mutations or single nucleotide deletion and 7 of them (35%) had at least one damaging or possibly damaging RET mutation. Most of the tumors had low Ki-67 expression (mean 6.48% of cells) and high Bcl-2 expression (mean 68.3%). Significantly better survival was observed in cases with low Ki-67 (< 6.5%; p < 0.05), high Bcl-2 expression (> 68.3%; p < 0.01) and younger age at diagnosis (< 51 years; p < 0.05).

Synchronous occurrence of ileal stromal tumor (GIST) and colonic adenocarcinoma: a case report.

INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract. There is an increasing number of literature reports on synchronous occurrence of gastrointestinal stromal tumors and another malignancy of distinct etiology and evolution. The most reported cases include gastric synchronous occurrence of gastrointestinal stromal tumors and adenocarcinoma and gastric gastrointestinal stromal tumors and colonic adenocarcinoma. CASE REPORT: We present a case of a 77-old female, with synchronous cecal moderately differentiated adenocarcinoma in Stage IIA according to the TNM classification and ileal spindle cell type GIST with low malignant potential, positive for c-Kit, CD34, vimentin, Actin, and negative for S100. CONCLUSION: The synchronous occurrence of small bowel gastrointestinal stromal tumors and other primary gastrointestinal malignancies has been rarely reported. There is a need of further investigations to identify the relationship between gastrointestinal stromal tumors and colorectal cancers.

Dilemmas concerning the diffuse axonal injury as a clinicopathological entity in forensic medical practice.

Dilemmas and discussions concerning the diffuse axonal injury (DAI) and still existing in forensic medical practice are as it follows: 1. Whether the occurrence of DAI can indicate the type of traumatic event that has caused the head trauma, 2. Whether the presence of axonal damage in cases of hypoxia, ischaemia and other pathological conditions casts a shadow on the post-mortem pathological diagnosis of DAI and totally negates it, or there are certain clues in the findings that can point to the aetiology of the axonal damage. This paper discusses our findings based on neuropathological examination of 60 forensic cases of closed head injury. The neuropathological examination included: a macroscopic examination of the coronal sections and a microscopic examination involving an immunohistochemical method with antibody against ß-amyloid precursor protein. Our findings indicate that DAI, as a clinicopathological entity, is undoubtedly an acceleration-deceleration injury, predominant in road traffic accidents as it is classically outlined, and cases of falling from a considerable height. Our findings point to a certain difference between the features of traumatic and ischaemic axonal damage. In this paper we also investigate the correlation between pathological grades of DAI and the impairment of the brain function before death.

Histological features, Ki-67 and Bcl-2 immunohistochemical expression and their correlation with the aggressiveness of pheochromocytomas.

Pheochromocytomas and paragangliomas are rare neoplasms. Approximately 10% may present malignant behaviour. There are no reliable morphological signs of malignancy, except for the presence of metastasis. We performed morphological and immunohistochemical analysis on 15 pheochromocytomas and 5 paragangliomas aiming to find correlations between the morphological features of the tumours, immunohistochemical expressions of Ki-67 and Bcl-2, and the biological behaviour of the tumours. According to the biological behaviour of the tumors, the patients were divided into an indolent disease group (ID), and an aggressive disease group (AD). The morphological analysis included the PASS core parameters, greatest tumour diameter and weight, as well as age and gender of the patients, survival and disease-free periods after operation. According to histomorphological parameters, tumours were divided into tumours with "benign-like" morphology and tumours with "malignant-like" appearance. The disease course was neither correlated to the PASS score, nor to the individual parameters comprising it. The rest of the morphological parameters and the immunohistochemical expressions of Ki-67 and Bcl-2 were not able to predict the disease course, although we found significantly higher Ki-67 expression in paragangliomas in comparison to pheochromocytomas (p<0.01). Some of the PASS parameters (vascular invasion and presence of atypical mitoses) were positively correlated to the tumour weight (R=0.75; p<0.01, and R=0.56; p<0.05, respectively). The disease course was in positive correlation to the tumour weight, presence of vascular invasion and atypical mitoses; however there were no statistically significant differences regarding those parameters between the ID and AD groups (p>0.05).

The advantages of the application of amnion membrane in the treatment of burns.

A crucial and important factor for successful treatment of burns is the early covering of the burned area with skin substitutes. The covering of the burn requires material that restores the epidermal function and integrates itself into the process of healing. Biological dressings are the golden standard for the temporary covering of burns. All biological skin substitutes are susceptible to early graft reaction and the only exception is the amnion membrane. The importance of the amnion membrane as a biological dressing for burns amounts to: a barrier to bacterial colonization, hastens the epithelisation, and control of water loss. Amnioplasty is a method of application of amnion membrane on the recipient site. In this comparative study, 60 patients with dermal and sub-dermal burns were included. Research was made on an examination group of 30 patients with burns where the method of amnioplasty was applied, and for this amnion membrane conserved in 76% alcohol was used. The control group was made up of 30 patients with burns treated conventionally, and standard methods for the local treatment of burns were applied: exposition, occlusive dressing and initial excision with skin grafting. Pathohistological and microbiological analyses of the bioptical material were made. The degree of the burns was determined through a pathohistological analysis of the bioptical material taken the third day, and in some of the subjects where re-epithelialization was determined on the seventh day, the further re-epithelialization was observed clinically. Pathohistological examination enabled discrimination between bacterial colonization and the invasive bacterial infection. Furthermore, the type of bacterial colonization and infection was determined, which was confirmed with microbiological analysis. The analysis of the results from the microbiological and pathohistological researches of the bioptical material according to the bacterial colonization and infection showed that, although between the examined and the control group there was no statistically important difference, the value of p = 0.067 is close to the statistically important value of p < 0.05. The results of the pathohistological examination of the bioptical material taken the seventh day and analysed according to the re-epithelialization showed that there was a significant difference between the two groups of p < 0.035. It should be mentioned that, although according to the microbiological examinations of the bioptical material a statistically significant difference was not achieved, clinical significance was achieved. The obtained significance of p < 0.035 compared to the re-epithelialization in both groups approved the application of the method of amnioplasty. The histological analysis of the bioptical material not only determines the degree of the burns specifically, but facilitates the choice of method for further treatment, observes the speed of the re-epithelialization and plays an important part in the correct diagnosis and the early start of the specific therapy, important in preventing sepsis. The application of amnion membrane as a biological dressing speeds the re-epithelialization and prevents invasive bacterial infection. Pathohistological examination of the burns is recommended to be established as a standard method in clinical practice.