[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.

[Adenoma of the parathyroid gland in a young woman with chronic kidney disease: primary or tertiary hyperparathyroidism?]

Clinical observation of a young woman with chronic kidney disease IV stage and hyperparathyroidism is presented. Ultrasound and99mTc-sestamibi scintigraphy of the anterior surface of the neck visualized a tumor of the left upper parathyroid gland. In a histological examination of distant education was diagnosed a solid parathyroid adenoma. The difficulty of differential diagnosis between primary and secondary/tertiary hyperparathyroidism in chronic kidney disease is discussed.

[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.

[Impact of various wound dressings on wound bed neoangiogenesis in patients with different forms of diabetic foot syndrome]. / Vliianie razlichnykh sredstv zakrytiia ran na neoangiogenez ranevogo lozha u patsientov s razlichnymi formami sindroma diabeticheskoi stopy.

AIM: To investigate the impact of various wound dressings on wound bed neoangiogenesis in patients with different forms of diabetic foot syndrome (DFS). SUBJECTS AND METHODS: The clinical (local tissue oxygenation) and immunohistochemical (CD31) markers of foot soft tissue neoangiogenesis were evaluated in patients with DFS receiving negative pressure (NP) therapy and collagen-containing dressings (CCDs) versus standard treatment. 63 patients with neuropathic and neuroischemic (without critical ischemia) forms of DFS were examined after wound debridement. In the postoperative period, 21 patients received NP treatment, CCDs were applied to 21 patients, and 21 patients had standard treatment. RESULTS: During NP therapy, there was statistically significantly intensified local microhemodynamics, as evidenced by transcutaneous oximetry (p < 0.05); the remaining two groups showed no statistically significant differences in transcutaneous oxygen tension during the treatment. Immunohistochemical examination revealed a significant increase in the number of newly formed vessels, as shown by anti-CD31 antibody staining (p < 0.05), in patients who had NP therapy and CCDs (p < 0.05). CONCLUSION: Vacuum (NP) therapy versus standard therapy most effectively affects wound bed neoangiogenesis. This is reflected in the increased local tissue microhemodynamics, as confirmed by immunohistochemical examination.

[Comparative evaluation of the intensity of reparative processes in the lower extremity soft tissues of diabetic patients receiving local negative pressure wound treatment and standard wound care]. / Sravnitel'naya otsenka intensivnosti reparativnykh protsessov v myagkikh tkanyakh nizhnikh konechnostei u patsientov s sakharnym diabetom na fone primeneniya lokal'nogo otritsatel'nogo davleniya i standartnoi terapii.

AIM: To study the intensity of soft tissue repair in patients with diabetic foot syndrome (DFS) during local negative pressure wound treatment versus standard wound care. SUBJECTS AND METHODS: The investigators estimated the clinical (wound sizes, local tissue oxygenation), histological (light microscopy), and immunohistochemical (CD31, CD68, MMP-9, and TIMP-1) markers for reparative processes in patients with DFS during vacuum therapy versus standard wound care. Forty-two patients with the neuropathic and neuroischemic (without critical ischemia) forms of DFS were examined after debridement. In the perioperative period, 21 patients received negative pressure wound therapy and 21 had standard wound care. RESULTS: During vacuum therapy, the area and depth of wound defects decreased by 19.8±7.8 and 42.8±5.6%, respectively (p=0.002) (as compared to the baseline data). In the control group, these indicators were 17.0±19.4 and 16.6±21.6% (p=0.002). There was a significant intensification of local microhemodynamics according to transcutaneous oximetry readings in the negative pressure wound treatment group. After 9±2 days of treatment, histological examination of granulation tissue revealed a significant reduction in edema, cessation of inflammatory infiltration, and formation of mature granulation tissue in Group 1. Immunohistological examination indicated a more obvious increase in the count of macrophages (CD68 staining) and a significant increment in the number of newly formed vessels, as evidenced by anti-CD31 antibody staining. During the treatment, there was a decline of the expression of MMP-9 and an increase in that of TIMP-1, as compared to those in the control group. CONCLUSION: The findings are indicative of the enhanced intensity of reparative processes in patients with DFS during vacuum therapy versus standard wound care, resulting in more rapidly decreased wound sizes, increased local microhemodynamics, reduced inflammation, and accelerated wound transition from the inflammatory to the proliferative phase.

[CDC73 mutations in young patients with primary hyperparathyroidism: A description of two clinical cases]. / Mutatsii v gene CDC73 u molodykh patsientok s pervichnym giperparatireozom (opisanie dvukh klinicheskikh sluchaev).

The article describes two clinical cases of severe primary hyperparathyroidism (PHPT) caused by parathyroid carcinoma in young female patients who underwent molecular genetic testing to rule out the hereditary forms of PHPT. In both patients, heterozygous germline nonsense mutations of tumor suppressor gene CDC73 encoding parafibromin (p.R91X and p.Q166X) were identified using next-generation sequencing with Ion Torrent Personal Genome Machine (Thermo Fisher Scientific - Life Technologies, USA). It is the first description of CDC73 mutations in Russia, one of the mutations is described for the first time in the world. Identification of germline mutations in the CDC73 gene in patients with PHPT necessitates regular lifelong screening for other manifestations of hyperparathyroidism-jaw tumor syndrome (HPT-JT), PHPT recurrence due to parathyroid carcinoma as well, and identification of mutation carriers among first-degree relatives.

[Adrenocortical oncocytoma].

The paper characterizes adrenocortical oncocytoma, a rare adrenal tumor, accompanied by Cushing's syndrome and estrogen and androgen production and provides histological and immunohistochemical features. The authors describe their observation of a 33-year-old female woman. It is shown that estimation of the malignant potential of adrenocortical oncocytomas requires a special approach and must be done using the Lin-Weiss-Bisceglia criteria.

[Impact of the local application of collagen on the activity of reparative processes in the lower extremity soft tissue of patients with diabetic foot syndrome]. / Vliyanie mestnogo primeneniya kollagena na aktivnost' reparativnykh protsessov v myagkikh tkanyakh nizhnikh konechnostei u bol'nykh s sindromom diabeticheskoi stopy.

AIM: To estimate of the rate of reparative processes in the lower extremity (LE) soft tissues of patients with diabetic foot (DF) syndrome in the local application of collagen-containing dressings (CCD) versus standard medical therapy. MATERIAL AND METHODS: The clinical (sizes, tissue oxygenation), histological, and immunohistochemical markers of reparative processes in LE soft tissues were analyzed in patients with diabetes mellitus during the local application of collagen-containing wound dressings versus standard treatment. Forty-two patients with postrevascularization neuropathic and neuroischemic DF syndrome were examined after standard surgical wound treatment. In the perioperative period, 21 patients received local treatment using CCD and 21 patients had standard treatment. RESULTS: In the patients using CCD, the area and depth of wound defects could be decreased by 26.4±17.2 and 30.4±25.6%, respectively (p=0.002 vs baseline). In the control group, those were 17.0±19.4 and 16.6±21.6%, respectively (p=0.002). Percutaneous oximetry assessment indicated significantly higher local microhemodynamics in the local collagen treatment group (p<0.05). According to the data of histological examination of wound defect tissues, after 10-day treatment, Group 1 showed a 80% reduction in edema (p<0.05), a 90% disappearance of inflammatory infiltrates (p<0.05), and formation of mature granulation tissue (p<0.05). Immunohistochemical examination revealed a more pronounced rise in the count of macrophages in the derma (p<0.05). When CCD was applied, the level of matrix metalloproteinase tended to more markedly decrease as compared to that in the control group. CONCLUSION: The findings suggest that the activity of reparative processes in LE soft tissues is enhanced in diabetic patients receiving local collagen therapy versus those having standard treatment. This manifests itself as a decrease in both the area and depth of wounds, enhancement of local tissue perfusion, a reduction of inflammation and a rapider wound transfer from proliferation to the epithelialization phase, as supported by histological and immunohistochemical findings.

[Features of angenesis against the background of negative pressure wound therapy in patients with neuropathic and neuroischemic forms of diabetic foot ulcers].

The authors analyzed clinical (size, tissue oxygenation), histological (light microscopy) and immunohistochemical (CD68, MMP-9, TIMP-1) features of reparative processes of soft tissue of lower extremities in patients with diabetes mellitus against the background of vacuum therapy in comparison with standard local treatment. Patients (31 cases) with diabetic foot ulcers were followed-up after surgical d-bridement and before plastic closure of the wound. During perioperative period 13 patients obtained the negative pressure wound therapy (NPWT of 90-120 mmHg) and 18 patients had the standard care. Given results supported higher efficacy of NPWT as compared with standard local care. The therapy caused rapid reduction of wound and its depth, increased local microcirculation and reduced inflammation. These data were confirmed by the histological and immunohistochemical studies. The high efficacy of the method of local treatment could significantly reduce the time of wound preparation for the next step of surgical treatment.

[Histological and immunohistochemical characteristics of ACTH-secreting tumors].

The histological and immunohistochemical characteristics of pituitary (corticotropinomas) and nonpituitary adrenocorticotropic hormone (ACTH)-secreting neuroendocrine tumors (NET) were comparatively analyzed. The study included 46 corticotropinomas and 37 ectopic ACTH-secreting tumors. Removed NET tissue was investigated using routine histological and immunohistochemical techniques. A study of the morphofunctional characteristics of removed NETs yielded the following data: their ability to express ACTH, growth hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin in both in pituitary and nonpituitary NET tumors. Angiogenic markers (CD31 and VEGF) were found in equal frequency. The histological structure of all corticotropinomas suggested their benign origin while nonpituitary NETs had different morphological structures, malignancy and invasiveness grades, and metastatic properties. The highest cell proliferation potential (Ki-67) was discovered in NET in ectopic ACTH syndrome as compared to corticotropinomas.

[The clinical practice guidelines for primary hyperparathyroidism, short version].

Primary hyperparathyroidism (PHPT) is an endocrine disorder of parathyroid glands characterized by excessive secretion of parathyroid hormone (PTH) with an upper normal or elevated blood calcium level. Classical PHPT refers to a symptomatic, multi-system disorder, wich can lead to a significant decrease in the quality of life, disability of patients, and even an increased risk of premature death. Hypercalcemia and the catabolic effect of PTH on various cells are considered as the main pathogenetic mechanisms of the PHPT associated complications. In the last two decades, there has been an increase in the incidence of PHPT, mainly due to the mild forms of the disease, primarily due to the routine calcium screening in North America, Western Europe and, Asia. High prevalence of the disease, as well as the variety of clinical manifestations, cause the attention of different specialists - physicians, rheumatologists, urologists, nephrologists, cardiologists and other doctors. This review cover the main issues of Russian guidelines for the management of PHPT, approved in 2020, including laboratory and instrumental methods, differential diagnosis, surgical and conservative approach, short-term and long-term follow-up. This guidelines also include the recommendations for special groups of patients with hereditary forms of PHPT, parathyroid carcinoma, PHPT during pregnancy.

Comparative Analysis of Clinical, Hormonal and Morphological Studies in Patients with Neuroendocrine ACTH-Producing Tumours.

This paper highlights the problem of neuroendocrine tumours (NETs) with clinical symptoms of hypercorticism caused by hypersecretion of adrenocorticotropic hormone (ACTH) by tumour cells. In most cases (85%), the tumours were localized in the pituitary gland (Cushing's disease); 15% of the patients had an extrapituitary tumour that manifest as an ectopic ACTH secretion (EAS). Comparative analysis of clinical, hormonal, histological, and immunohistochemical characteristics of pituitary and extrapituitary ACTH-secreting NET was performed. It included 46 patients with CD and 38 ones exhibiting ectopic ACTH secretion (EAS). Results of the study suggest differences between CD and EAS in terms of the severity of clinical manifestations and duration of the disease. Hormonal studies showed that EAS unlike CD was associated with high plasma ACTH and cortisol levels, late-evening salivary cortisol and daily urinary free cortisol, the absence of a 60% or greater reduction of cortisol in the HDDST test, and the presence of a low (less than 2) ACTH gradient in response to desmopressin administration with catheterization of cavernous sinuses. The study of morphofunctional characteristics of the removed NET demonstrated the ability of both pituitary and extrapituitary NETs to express ACTH as well as GH, PRL, LH, and FSH. The angiogenic markers (CD31 and VEGF) were detected with equal frequency regardless of the NET localization. The histological structure of all corticotropinomas suggested their benign origin, but extrapituitary NETs were represented by different morphological types with varying malignancy, invasiveness, and metastatic properties. A higher cell proliferation potential (Ki-67) was documented for NET in patients presenting with an ectopic ACTH secretion compared to those having corticotropinomas.