[Neurofibromatosis type 1 associated with pheochromocytoma: a case report with a brief review of the literature].

We presented the clinical case of neurofibromatosis type 1 (NF-1) associated with pheochromocytoma (PHEO) in a man under 40 years old without family history. The diagnosis of NF-1 was established based on 4 signs of the disease (multiple café au lait macules, scoliotic changes in posture, the presence of multiple neurofibromas, Lisch nodules). The diagnosis of PHEO was determined by a significant increase of free metanephrin/normethanephrin levels in daily urine, a malignant CT phenotype of the right adrenal tumor, and confirmed by pathomorphological study. Genetic tests revealed a new mutation in one of the alleles of NF1 gene, a deletion of a 566 bp gene fragment, including exon 19 with a size of 73 bp. This mutation leads to splicing of exons 18 and 20, frameshift, and termination of protein synthesis. A study of the level of transcription of the genes associated with PHEO (RET, TMEM127, MAX, FGFR, MET, MERTK, BRAF, NGFR, Pi3, AKT, MTOR, KRAS, MAPK) was conducted, a statistically significant decrease in the level of transcription of the KRAS and BRAF genes and increase in the level of transcription of the TMEM127 gene in comparison with control samples have been detected. This case demonstrates the need for timely recognition of NF-1 for further appropriate patient's follow up and show the effectiveness of a multidisciplinary approach to the diagnosis and treatment of NF-1-associated catecholamine-secreting tumors.

[Solid pseudopapillary tumors of the pancreas: clinical and morphological characteristics, specific features of their immunophenotype, and diagnostic problems].

OBJECTIVE: To analyze 60 cases of solid pseudopapillary tumors (SPTs) of the pancreas, to reveal their most characteristic clinical and morphological features, and to study their possible histogenesis. MATERIAL AND METHODS: Sixty cases of SPTs of the pancreas underwent clinical, morphological, and immunohistochemical (IHC) examinations; a comparison group consisted of 86 pancreatic tumors of other histogenesis. RESULTS: It has been shown for the first time that SPTs are characterized by the nuclear expression of claudin 3 and the cytoplasmic expression of claudin 7. It has been also ascertained that the aberrant perinuclear (dot-like) expression of CD99 is a unique feature of these tumors. CONCLUSION: SPTs of the pancreas are distinguished by a diversity of clinical manifestations and morphological features, but have a unique immunophenotype, which can differentiate them from other types of pancreatic tumors.

[Challenges and opportunities for endoscopic ultrasound in the preoperative diagnosis of topical insulin the pancreas].

Insulinoma in most cases is monohormonal orthoendocrine tumor. This fact limits its searching area by a pancreas. However the insulinoma's clinical picture can be caused by other pathology. Therefore the main task of visual the tumor but also to use all the possibilities of each method for defining type of surgery and avoiding such errors and complications, as pancreatorrhage, damage of bile or pancreatic duct, necrosis of duodenal wall, etc. On the basis of our own experience of endoscopic ultrasound for 61 patients with 66 insulinomas, we have allocated the basic variants of insulinoma ultrasound pictures: hypoechoic, heteroechoic, isoechoic tumor, and also foci without a trustworthy contour. On the basis of the analysis of our own errors we have essentially added the technique, having used multiplane pancreas scanning and biplane tumor scanning. Important points in EUS algorithm are also the following items: detecting tumor relationship to pancreatic surface, distance from the tumor to the ducts, gastrointestinal wall and vessels--for definition of possibility of the tumor enucleation; careful scanning of pancreas even after detecting one tumor--for an exception of multiple tumors, especially at MEN-I; careful scanning of a contour of the gland for an exception of parapancreatic insulinomas; estimation of vascularization not only of the detected tumor and suspicious foci, but also of all the gland--for detection of hypervascularized isoechoic tumors; revealing and the description of focal changes, especially more homoechogeneous in comparison with surrounding parenchyma-- for selection patients for examination by other methods; scanning of zones of possible metastasis. Examination of patients with organic hyperinsulinism demands combined application of two or more techniques. Use of all modern possibilities of endosonography can put this technique on one of the first places in the diagnosis of insulinomas.

Serum angiogenic factors in patients with neuroendocrine tumors of abdominal organs.

The initial (before treatment) levels of VEGF, endostatin, and tumor necrosis factor-beta (TNF-beta) were measured in the sera of 20 patients with malignant and benign neuroendocrine tumors of the abdominal organs and 25 healthy controls. The initial levels of VEGF, endostatin, and TNF-beta in the total group of patients with neuroendocrine tumors of abdominal organs did not differ from the control. A significant difference was detected between the mean serum concentrations of endostatin in patients with benign and malignant neuroendocrine tumors: 64.1+/-14.7 and 107.8+/-14.1 ng/ml, respectively (p=0.043). The content of VEGF, endostatin, and TNF-beta did not correlate with patients' gender and age. A direct correlation between endostatin, TNF-beta concentrations and maximum size of the primary tumor was detected in patients with malignant neuroendocrine tumors. Direct correlations between the initial levels of VEGF and endostatin and an inverse correlation between VEGF and TNF-beta concentrations were detected in patients with benign neuroendocrine tumors. Relapse-free survival was significantly lower in patients with serum endostatin concentration >100 ng/ml and TNF-beta<30 pg/ml.

Cancer and soluble FAS.

A test system developed by the authors was used to measure serum concentrations of soluble Fas in patients with malignant and benign tumors of different location and morphology. Relationships between soluble Fas levels and the main clinical and morphological characteristics of cancer were evaluated. It is proven that the concentrations and incidence of detection of soluble Fas in the sera of patients with tumors are significantly higher than in normal subjects. No appreciable differences in the concentrations of soluble Fas were detected in malignant and benign tumors of the mammary gland, bones, ovaries, and adrenals. In thyroid cancer, soluble Fas levels were higher than in benign and hyperplastic processes in this organ. High level of soluble Fas is associated with late stages of the disease (ovarian cancer, cancer of the corpus uteri, adrenocortical and colorectal cancer) and with poor differentiation of the tumor (ovarian cancer and cancer of the corpus uteri), with local metastases (colorectal and adrenocortical cancer), and with tumor invasion into the myometrial tissue, intestinal wall, and adjacent tissues (cancer of the corpus uteri and colorectal cancer). A significantly high level of soluble Fas was detected in colorectal and adrenocortical cancer in the presence of at least 2 local metastases. Soluble Fas levels depended on tumor histogenesis in malignant and benign ovarian tumors. High concentration of soluble Fas was detected in large tumors in patients with ovarian cancer, cancer of the corpus uteri, colorectal cancer, thyroid cancer and adenoma, and in adrenocortical cancer. Initially high levels of soluble Fas are characteristic of patients whose tumors are little sensitive to nonadjuvant radiotherapy. The overall 5-year survival of patients with low levels of soluble Fas is better in osteosarcoma, cancer of the corpus uteri, ovarian and adrenocortical cancer.

Clinical and biochemical aspects of the carcinoid syndrome in neuroendocrine tumors of the abdominal and retroperitoneal organs and its impact for the disease prognosis.

Overall and relapse-free survival of 238 patients with neuroendocrine tumors of the abdominal and retroperitoneal organs was evaluated with consideration for the presence of the carcinoid syndrome. The incidence of the carcinoid syndrome was 15.6%. The presence of the carcinoid syndrome was inessential for survival and relapse prognosis in patients with neuroendocrine tumors of the abdominal and retroperitoneal organs. A trend to the development of earlier relapses was noted in patients with this syndrome. Diarrhea was found to be a prognostically unfavorable factor. The time of the carcinoid syndrome development was prognostically significant in patients with malignant neuroendocrine tumors. The mean secretion of epinephrine, norepinephrine, and dopamine with daily urine was significantly higher in patients with the carcinoid syndrome. A significant positive correlation between urinary excretion of catecholamines was detected (r=0.53; p<0.05).

Vascular endothelium growth factor in the sera of patients with adrenal tumors.

Serum levels of vascular endothelium growth factor were measured in 43 patients with adrenal tumors and 25 healthy subjects. The mean blood levels of the factor in patients with adrenal tumors significantly surpassed the control. No correlations between the level of vascular endothelium growth factor, patients age and sex were detected. The levels of this factor were maximum in patients with adrenocortical cancer, but its mean level differed negligibly from that in other morphological variants of tumors. The level of vascular endothelium growth factor tended to increase with increasing the stage of adrenocortical cancer. A direct correlation was revealed between the level of vascular endothelium growth factor and tumor size in adrenocortical cancer and aldosterone-producing adenoma. Presumably, vascular endothelium growth factor is involved into mechanisms of growth, invasion, and metastatic growth of adrenocortical cancer.

[Adrenal gland surgery].

The authors of the article analyze more than 30-year experience of surgical treatment of adrenal gland diseases, offering a detailed description of clinical and morphological features of the main nosological forms such as Itsenko-Cushing disease and syndrome, primary hyperaldosteronism, pheochromocytoma, incidentaloma, and malignant adrenal tumors. The paper contains basic diagnostic criteria, indications to operative treatment, and extents of surgery for each of the diseases considered, as well as comparative analysis of peculiarities of conventional ("open"), and endoscopic adrenal gland surgeries. The article demonstrates significance of various immunohistochemical markers in differentiation between malignant and benign adrenal tumors.

Serum interleukin-6 in patients with adrenal tumors.

The mean blood content of interleukin-6 in patients with adrenal tumors was much higher than in healthy donors. No correlations were revealed between interleukin-6 level, patients sex and age, stage and duration of the disease. Interleukin-6 concentration was maximum in patients with adrenocortical cancer. A negative correlation was found between interleukin-6 level and blood cortisol concentration in patients with cortisol-producing adenoma. In patients with aldosterone-producing adenoma, interleukin-6 level tended to correlate negatively with plasma renin activity.

Plasma content of soluble fas antigen in patients with adrenal tumors and tumor-like pathologies.

We compared plasma content of soluble Fas antigen (sFas) in 59 patients with tumors and tumor-like pathologies of the adrenal cortex and medulla and 60 healthy donors (control). The incidence and content of sFas in the plasma from patients with adrenal tumors was significantly higher than in healthy donors. A direct correlation was found between sFas content and patient's age. The maximum sFas concentrations were found in patients with pheochromocytoma and aldosterone-producing adenoma. In patients with adrenocortical cancer plasma content of sFas was lower than in patients with tumors of other morphological types. Plasma sFas content in patients with adrenocortical cancer directly correlated with the size of tumors. Our results suggest that sFas plays a role in the pathogenesis of primary adrenal tumors.

Soluble Fas antigen in the serum of patients with colon cancer.

Serum concentration of soluble Fas antigen (sFas) was measured in 60 normal subjects and 33 patients with colon cancer. The incidence of sFas detection and its serum content were higher in patients with colon cancer compared to normal subjects. No relationships between the incidence and level of sFas and patient's sex, age, duration and stage of the disease were found. Serum content of sFas tended to increase in patients with metastases to regional lymph nodes, liver, and lungs. The role of sFas as a marker predicting clinical course and outcome of colon cancer is discussed.

Soluble Fas antigen (sFAS) in the serum from patients with adrenal tumors.

Serum content of soluble Fas antigen was measured by enzyme immunoassay in 60 healthy donors, 31 patients with adrenal tumors, and 16 patients with diffuse-and-nodular hyperplasia of the adrenal cortex accompanying primary aldosteronism and Cushing's disease. sFas was more often detected in the serum from patients with tumors of the adrenal cortex and medulla and diffuse-and-nodular hyperplasia of the adrenal cortex and its content varied in a wider range in patients compared to healthy donors. No correlations were found between the incidence of sFas, its content, sex, and age of healthy donors and patients. The highest content of sFas was found in patients with pheochromocytoma and primary aldosteronism. sFas probably plays a role in the pathogenesis of adrenal tumors and hyperplasia.