[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.

[Mature teratoma of the anterior mediastinum with a predominance of the pancreatic component and signs of focal nesidioblastosis]. / Zrelaya teratoma perednego sredosteniya s preobladaniem pankreaticheskogo komponenta i priznakami fokal'nogo nezidioblastoza.

A case of a mature anterior mediastinal teratoma with a predominance of the pancreatic component (80% of the tumor) and signs of nesidioblastosis in a 46-year-old woman is presented. During histological examination, all components of the pancreatic parenchyma were determined - acini with interlobular and intralobular ducts, endocrine cells and islets of Langerhans of various sizes and shapes, as well as islet-duct complexes scattered in the acinar tissue. In addition to pancreatic tissue, cartilage, bronchial respiratory epithelium, small intestine tissue, hair follicles, and sebaceous glands were found in the neoplasm. Immunohistochemical examination revealed signs of focal nesidioblastosis. In the islets, insulin-positive ß-cells (80.0% of the volume of the islets), as well as endocrine cells expressing glucagon and somatostatin (10.0% of the volume of the islets) were determined. By 2020, only 4 such cases have been published in the English-language literature.

[Neuroendocrine markers in parathyroid tumors]. / Neiroendokrinnye markery v opukholyakh okoloshchitovidnykh zhelez.

The parathyroid glands (PTGs) are a key regulator of calcium and phosphorus metabolism in the human body. In terms of their, morphological and immunophenotypic characteristics, PTGs are neuroendocrine organs, and their neoplasms are neuroendocrine tumors. These neoplasms include adenoma and cancer; in addition, glandular hyperplasia may develop, which is most characteristic of multiple endocrine neoplasia (MEN1, MEN2a, and MEN4) syndromes. The morphological characteristics of pathologically altered PTGs in MEN syndromes are variable. The analysis and generalization of knowledge about the features and expression of various immunohistochemical markers in PTG tissue in health and in diseases are useful in the practical work of not only pathologists, but also clinicians of various specialties.

[Differential diagnostic value of the expression of the transcription factor PDX-1 in neuroendocrine and non-neuroendocrine tumors of the pancreas and other organs]. / Differentsial'no-diagnosticheskoe znachenie ékspressii transkriptsionnogo faktora PDX-1 v neiroéndokrinnykh i neneiroéndokrinnykh opukholiakh podzheludochnoi zhelezy i drugikh organov.

An important role in the differentiation of tissues in different organs is played by transforming factors (TFs); pancreatic and duodenal homebox 1 (PDX-1) is one of the earliest factors for pancreatic cells. Many malignant tumors, including neuroendocrine tumors (NETs), are similar in structure, and therefore the actual problem of oncomorphology is to search for narrow-specific markers and TFs. AIM: to comparatively analyze and assess the value of the expression of the TF PDX-1 in NETs and non-NETs of different localization and histogenetic origin. MATERIAL AND METHODS: Anti-PDX-1 antibodies were used to study 528 tumors divided into 3 groups: Group 1 included 394 NETs, among them there were those of the pancreas (n=173), stomach (n=46), bowel (n=65), lung (n=40), thymus (n=8), kidney (n=6), Merkel's cell carcinomas (n=14), NETs of the breast (n=3), larynx (n=2), trachea (n=2), bladder (n=1), and metastatic NETs (n=34) of unknown primary site; Group 2 consisted of 16 tumors, of them there were paragangliomas (n=6), medullary thyroid cancers (MTC) (n=6) and adrenal pheochromocytomas (APCC) (n=4); Group 3 comprised 118 non-NETs, among them there were tumors of the pancreas (n=54), stomach (n=26), bowel (n=17), lung (n=11), breast (n=3), kidney (n=4), adrenal glands (n=2), and bladder (n=1). RESULTS: PDX-1 was positive in 75.1% (130/173) of pancreatic NETs, all insulinomas (50/50), gastrinomas (11/11), somatostatinomas (3/3), ACTH-producing tumors (2/2); PDX-1 was positive in the non-functioning pancreatic NETs, all PPomas (19/19), 76.1% (35/46) of NETs without the hormone detected, 50% (2/4) of calcitoninomas, and 21.1% (8/38) of silent glucagonomas. PDX-1 was positive in 32.4% (11/34) of carcinoids and 50% (6/12) of neuroendocrine carcinomas, all duodenal NETs (18/18), 90% (9/10) of rectal carcinoids and 30.8% (4/13) colonic carcinoids, 37.5% (3/8) of thymic/mediastinal carcinoids, 66.7% (4/6) of kidney carcinoids, and 37.5% (9/24) of metastatic NETs of unknown primary site. PDX-1 was negative in all carcinoids of the colon and sigmoid (0/5), ileum and jejunum (0/24), lung (0/40), trachea (0/2), larynx (0/2), Merkel's cell carcinoma (0/14), breast (0/3), bladder (0/1), as well as MTC (0/6), APCC (0/4), and paragangliomas (0/6). PDX-1-positive non-NETs included 81.8% (18/22) of adenocarcinomas (AC) and all serous cystic, mucinous cystic, intraductal and acinar cell tumors of the pancreas (4/4, 3/3, 2/2, and 3/3), 57.1% of AC (8/14) and 83.3% of signet ring cell carcinomas of the stomach (10/12), 56.2% AC of the bowel (9/17), bladder cancer (1/1). PDX-1 was negative in all anaplastic cancers (0/2) and solid pseudopapillary tumors of the pancreas (0/20), cancers of the lung (0/11), kidney (0/4), breast (0/3), and adrenal glands (0/2). CONCLUSION: The expression of PDX-1 is very specific for most digestive tract NETs and non-NETs. Pancreatic ductal and acinar cell tumors and gastric signet ring cell carcinomas are most commonly PDX-1-positive. Most tumors that do not originate from the digestive tract have a PDX-1 negative immunophenotype.

[Clinical and morphological characteristics of parathyroid carcinoma]. / Kliniko-morfologicheskaia kharakteristika raka okoloshchitovidnoi zhelezy.

Parathyroid carcinoma (PTC) is a rare malignant tumor with the clinical manifestation of hyperparathyroidism, reliable morphological signs of invasive growth, and poor clinical prognosis. The differential diagnosis of PTC due to the rarity of this pathology, not always explicit morphological criteria, and the lack of a certain immunohistochemical panel is complex and needs further clarification. The paper summarizes an update on the clinical and morphological characteristics of PTC.

[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.

[A case of IgG4-related sclerosing disease with lymphadenopathy and thymus involvement].

The paper describes a case of generalized lymphadenopathy clinically recognized as malignant lymphoma in a 59-year-old woman. Her death occurred from bilateral pneumonia. Autopsy also showed a tumor-like mass in the thymus. On histological examination, the lymph nodes, thymus, and spleen exhibited an intensive polyclonal IgG4+ plasma cell infiltration. Lymphoid plasma cell infiltration with increased count of IgG+ plasma cells, progressive sclerosis, and phlebitis obliterans were found in the pancreas and peripancreatic adipose tissue, liver, kidney, epicardium, thyroid, pituitary, skin, and other organs. The case was regarded as IgG4-related sclerosing disease manifesting itself as lymphadenopathy and thymus enlargement.

[Variants of gastric carcinomas according to immunohistochemical mucins and CD10 expressions].

Mucins and glycoprotein CD10 expression in 55 carcinomas of the stomach has been studied by immunohistochemistry. According to a profile of mucins and CD10 expression, 3 immunophenotypic variants of carcinoma were founded: gastric, intestinal and gastro-intestinal. Gastric and gastro-intestinal variants were more frequently than intestinal one. The correlation between the expression of investigated markers and histological type of carcinoma wasn't revealed The estimation of Ki-67 index has shown that the highest proliferative activity (>20%) in carcinomas with gastric phenotype has been found more often than in gastro-intestinal ones.

[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.

[A solid-pseudopapillary tumors of the pancreas].

The review presents an update of solid-pseudopapillary pancreatic tumors, a rare and inadequately studied type of tumors that are predominantly encountered in girls and young women. It discusses the problems in the diagnosis based on the histological and imunophenotypical uniqueness of these tumors, which allows them to be differentiated from other types of pancreatic tumors with a less favorable prognosis. The correct diagnosis of a solid-pseudopapillary tumor determines the management tactic that requires no radiation or chemotherapy in the vast majority.

[Ultrastructural and immunohistochemical features of thyroid cancer].

The morphofunctional diagnosis of different forms of thyroid cancer should be made by immunohistochemical and electron microscopic studies.

[Significance of the expression of nucleolar argyrophilic proteins and antigen Ki-67 in the evaluation of cell proliferative activity and in the prediction of minimal (T1) lung cancer].

S u m m a ry. - The subject of the study was 20 cases of non-small-cell lung carcinomas, up to 3 cm in diameter, conventionally designed as minimal lung cancers removed in patients operated on at the N. N. Blokhin Cancer Research Centre, Russian Academy of Medical Sciences in 1986 to 2001. According to survival rates after surgery, the patients were divided into two groups: 1) those who died within the first two years; 2) those who were followed up for 3-5 years. Histological, histochemical, and immunohistochemical studies were performed. The expression of argyrophylic nucleolar organizer site proteins (Ag-NOS-proteins) that characterized the rate of cell proliferation (the duration of a cellular cycle) and the expression of Ki-67 antigen, which reflected the fraction of growth (the number of proliferating cells), were revealed in the tumor cells. Minimal lung cancers were found to be a heterogeneous group of neoplasms showing differences in both the rate of cell proliferation and the count of proliferating cells. The cell proliferation rate is a determinant of the clinical course of minimal lung cancers. Group 1 tumors characterized by the superexpression of Ag-NOS-proteins and, accordingly, the higher cell proliferation rate and the moderate count of proliferating cells had a poor prognosis even in the presence of Stage IA whereas Group 2 tumors with a large quantity of proliferating cells, but with the less rate of cell proliferation were characterized by a much better prognosis. The rate of cell proliferation (expression of Ag-NOS-proteins) and the count of proliferating cells (the expression of Ki-67 antigen) should be simultaneously studied to have more complete information on the proliferative potential of tumor cells and on the prediction of the course of neoplasms.

[Gastric tumor of complex structure].

The paper describes a case of gastric tumor comprising moderately differentiated adenocarcinoma and atypical carcinoid with metastases of both types of tumor cells in the lymph nodes. Electron microscopic and immunohistochemical studies of primary gastric tumor and lymph nodal metastases confirmed the presence of both differentiation types within one space-occupying lesion: such as goblet (mucin-producing) and neuroendocrine cells. The differentiation varied in different fields of vision with a preponderance of low-grade ultrastructural differentiation cells. Thus, electron microscopic and immunohistochemical studies of tumors not only verify their diagnosis and make a histogenetic differential diagnosis of various neoplasms, but also define the degree of their maturation.

[Expression of type 1 and type 2 mucins in colonic epithelial tumors].

Expression of MUC-1 and MUC-2 was investigated with immunohistochemical staining (PAP-method) in 5 cases of adenomas and in 60 cases of colorectal adenocarcinomas. The expression of MUC-1 and MUC-2 can be useful for diagnosis and prognosis in patients with colorectal carcinoma.

[Liver cancer: immunohistochemical and electron microscopic study].

Primary liver tumors, including 7 low-grade hepatocellular carcinomas (HC), 12 average-grade HC (including 2 mixed tumors and 2 cholangiocellular carcinomas (ChC)), obtained from 23 patients, were histologically, immunohistochemically, and electron microscopically. Certain markers were immunohistochemically studied to identify HC and ChC and differentiate liver carcinoma from metastatic tumors of the same organ.

[Vascular endothelial growth factor in patients with prostate cancer and benign prostatic hyperplasia].

The authors examined 25 patients with prostate cancer (PC) and 36 patients with benign prostatic hyperplasia (BPH). In the group of patients with morphologically verified PC mean serum level of vascular endothelial growth factor (VEGF) was significantly higher than in patients with BPH (p < 0.05). The study demonstrated strong negative association between VEGF and prostate specific antigen (PSA) levels (r = 0.72, p < 0.05) in PC patients. There was no association between VEGF serum level and the stage or malignancy of PC (Gleason score). In benign prostatic glands moderate VEGF expression was observed only in basal cells, whereas in cases of PC all tumor cells displayed active VEGF expression; the difference was significant (p < 0.05). High serum VEGF levels and its active expression in patients with PC suggest an important role of angiogenic factors in the pathogenesis of this disease. The negative association between VEGF and PSA serum levels in PC indirectly confirms antiangiogenic activity of PSA, shown before.

[Askenazi (Hurtle) cell tumors of the thyroid].

Oncocytic adenomas have primarily follicular structure; trabeculas, solid areas, necrosis are rare. They may possess malignant potential as their malignant transformation occurs in 35% cases against 5% in adenomas of follicular cells. Oncocytic follicular carcinomas can be hardly distinguished from oncocytic adenomas. Tumors larger than 4-5 cm in diameter are considered to be malignant. Main difference with adenomas is invasion into the capsule surrounding thyroid or into the vessels. They can be well or poorly differentiated or anaplastic. Oncocytic papillary carcinoma and oncocytic medullary carcinoma are rare. The clinical course of oncocytic tumors is more aggressive than that of tumors from follicular cells. Of key importance in differential diagnosis is electron microscopy (EM) and immunohistochemistry with antimitochondrial antibodies. EM may be also useful in determination of the degree of oncocytic tumors maturation.

[Insullar cancer. Diagnosis and place in the structure of thyroid carcinoma].

15 cases of thyroid insullar carcinoma in patients aged from 10 to 65 years are described. It is shown that the tumor has aggressive histological signs and represents a prognostically important form of thyroid carcinoma.