[Morphological features of IgG4-related lesions at various sites]. / Morfologicheskie osobennosti IgG4-sviazannykh porazhenii razlichnykh lokalizatsii.

OBJECTIVE: To determine the morphological features of IgG4-related lesions and to improve pathomorphological criteria for diagnosing various clinical variants of IgG4-related disease. MATERIAL AND METHODS: Biopsy and surgical materials from 100 patients with tumor-like lesions at various sites (63 cases of IgG4-related lesion and 37 cases of non-IgG4-related inflammatory processes) were studied. Histological and immunohistochemical studies were conducted to determine the absolute counts of CD138+ cells, IgG+ and IgG4+ in the inflammatory infiltrates, as well as IgG4/IgG and IgG4/CD138 cell ratios. RESULTS: When IgG4-related disease manifested, pancreatic, lacrimal, and salivary gland lesions prevailed. Brisk lymphoplasmacytic infiltration is characteristic for tissue damage in the eye, salivary glands, thyroid, pancreas, and skin. The formation of moiré fibrosis was specific to damages to the pancreas, liver and bile ducts, and eye tissues. Obliterative phlebitis is most often observed in pancreatic and salivary gland lesions. According to international criteria, the frequency of achieving the required level of IgG4+ plasma cells in each organ was high in lesions of the pancreas, bile ducts, and lymph nodes and that was low in lesions of the salivary and lacrimal glands and skin. The IgG4+/CD138+ and IgG4+/IgG+ cell ratios exceeded 40% in all cases. CONCLUSION: The morphologic diagnosis of IgG4-related disease is based on the detection of lymphoplasmacytic infiltration, moiré fibrosis, and obliterative phlebitis, as well as on the calculation of the absolute number of IgG4+ plasma cells in the inflammatory infiltrate and on the determination of IgG4+/IgG+ and IgG4+/CD138+ cell ratios. The number of IgG4+ plasma cells depends on the location of the lesion and on the phase of the process.

Comparative Analysis of Blood Plasma Proteome in Patients with Renal Cell Carcinoma.

Comparative mass spectrometric analysis of protein composition was carried out in 36 blood plasma specimens from patients with renal cell carcinoma and 20 specimens from donors. Analysis of protein composition of plasma specimens devoid of the major protein fractions showed a 20-50% higher level of protein identifications in patient' specimens. Specimens of the control and experimental series were similar by protein composition, 70-80% identifications in experimental and control series coinciding. High similarity of biological processes with participation of the proteins identified in both series was observed. The greater part of proteins in both series were located extracellularly and were exosomal (specimens from renal cancer patients) or vesicular (specimens from healthy volunteers).

Soluble Ligand of the Immune Checkpoint Receptor (sPD-L1) in Blood Serum of Patients with Renal Cell Carcinoma.

The content of the soluble ligand of the immune checkpoint receptor (sPD-L1) was determined in the blood serum of 106 patients with renal cell carcinoma and 11 patients with benign kidney tumors by direct ELISA (Human sPD-L1 Platinum ELISA; Affimetrix, eBioscience). The control group included 19 healthy men and 18 women. Serum level of sPD-L1 significantly surpassed the control values in both patients with primary renal cancer (p<0.0001) and in patients examined during disease progression (p<0.05). In patients with benign kidney tumors, the level of this marker was significantly higher than in the control (p<0.05), but lower than in patients with renal cell carcinoma. The sPD-L1 level significantly increased with disease stage (p<0.001); it was higher in the presence of metastases in regional lymph nodes irrespective of their number (N1 or N2) than in the absence of metastases (N0); it was also increased in patients with distant metastases (M1) and patients with grade III-IV tumors in comparison with grade III-IV tumors (p<0.05). The highest sPD-L1 levels were recorded in patients with tumor size corresponding to T2 and T3 and decreased in patients with T4 tumors. Thus, sPD-L1 level in patients with renal cell carcinoma correlated with tumor grade and metastasizing and can be considered as a promising marker in monitoring of the effect of anti-PD1/PD-L1 therapy.

[Mitochondrial disorders in multiple sclerosis]. / Mitokhondrial'nye narusheniia pri rasseiannom skleroze.

AIM: To determine the mitochondrial dysfunction in multiple sclerosis (MS). MATERIAL AND METHODS: Fourteen adult patients with MS and 23 healthy people were examined. Cytochemical analysis of lymphocytes in peripheral blood was carried out. The activity of the mitochondrial enzymes involved in metabolism of carbohydrates (lactate dehydrogenase, LDH), amino acids (glutamate dehydrogenase, GDH), fatty acids (alpha-glycerophosphate, α-GPDH) and II complex of the mitochondrial respiratory chain (succinate dehydrogenase, LDH), and the level of lactate in the blood were measured. RESULTS AND CONCLUSION: The activity of α-GPDH was reduced in 62.5% patients and increased in 37.5%. GDH activity in all patients was lowered. LDH activity was reduced in 71.4% patients and compensatory increased in 28.6%. In 66.7% patients, LDH activity was reduced and in 33.3% compensatory increased. Increased blood lactate was observed in 33.3% patients before meal and 44.4% after carbohydrate loading. After carbohydrate loading, in 33.3% patients lactate levels in the blood increased and in 11.1% increased above normal values. Therefore, the enzyme activity have decreased in most patients that suggests the decompensation of mitochondrial function. The results indicate the advisability of administering the energotrophic drugs carnicetin and coenzyme Q10 (idebenone) in patients with MS.

[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.

[A case of cutaneous protothecosis]. / Nablyudenie prototekoza kozhi.

The paper describes a case of a rare opportunistic infection, such as skin lesion caused by achlorophyllic unicellular algae of the genus Prototheca. It provides a detailed pathologic description of the foci of cutaneous protothecosis, such as pandermal inflammatory infiltrate, granulomas, pseudoepitheliomatous hyperplasia, and intraepidermal abscesses. Criteria for pathogen detection in histological sections are given.

[The growth factor of endothelium of vessels and its receptors type I and II in blood serum in patients with kidney cancer: clinical morphological correlations.]

The progress in treatment of kidney cancer is related to application of anti-angiogenic medications. Therefore, investigation and searching for new molecular markers characterizing its angiogenic activity is actual still. The purpose of study is to compare VEGF, VEGFR1 and VEGFR2 in blood serum of healthy people, patients with cancer and benign tumors of kidney and to analyze their relationship with main clinical morphological characteristics of neoplasms. The study sampling consisted of 94 patients with cancer and 10 patients with benign tumors of kidney. The control group included 80 individuals. The concentration of analyzed proteins was determined using QuantikineТ (R&D Systems, USA), a reagents' kit for direct immune enzyme analysis. The content of VEGF, VEGFR1 and VEGFR2 in blood serum of patients with cancer of kidney was reliably higher than in control group. The level of VEGF also was increased in patients with benign tumors. Under threshold level of VEGF of 365 pg/ml the diagnostic sensitivity of detection of primary cancer of kidney amounted to 67% and specificity - 70%. The stage of disease and T and N indices were correlated only with VEGFR1 level. The relationship between level of markers and histological structure and degree of differentiation of cancer of kidney was not established. Therefore, VEGF and its receptors have a limited diagnostic value under cancer of kidney but they can be applied for monitoring and prognosis of efficiency of anti-angiogenic therapy.

[Gastric cancer concurrent with IgG4-related disease: A clinical case and a review of literature]. / Sochetanie raka zheludka s IgG4-svyazannoi bolezn'yu (klinicheskoe nablyudenie i obzor literatury).

The paper presents the data available in the literature on IgG4-related disease (IgG4-RD) concurrent with malignancies at different sites, as well as possible common pathogenetic mechanisms of their development and morphological diagnostic criteria for IgG4-RD. The authors give their own observation of gastric signet ring cell carcinoma concurrent with morphologically verified IgG4-RD.

[Kaposi's sarcoma in the grafted lung]. / Sarkoma Kaposhi v transplantirovannykh legkikh.

The paper provides a clinical note. A 45-year-old patient suffered from severe primary emphysema and underwent bilateral lung transplantation. A year after surgery, exercise dyspnea again appeared in the patient. Lung computed tomography revealed multiple rounded soft tissue masses; thoracoscopic biopsy and further histological examination proved the development of Kaposi's sarcoma in the patient. The tumor disappeared completely following corrected immunosuppressive therapy. After 22 months of transplantation, the patient died from gastrointestinal bleeding. This case is of interest due to that Kaposi's sarcoma develops extremely rarely in the allogeneic lung after its transplantation.

[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.

[The morphological parameters of cell regeneration in gastric carcinomas and their prognostic value].

OBJECTIVE: To make an integrated assessment of the proliferative activity of gastric cancer (GC) (Ki-67 and mitotic index - MI) and the degree of tumor cell apoptosis (apoptotic index - AI), by calculating the cell regeneration coefficient (CRC) in relation to the histological variant and functional immunophenotype (IPT) of a tumor and to determine if there is a possible association of the above indicators with adjusted 4-year relapse-free survival rates. SUBJECTS AND METHODS: Surgical specimens obtained from 55 patients with CC were examined. The tumors were divided into histological variants in accordance with the International histological classification criteria (WHO, 2010) and into IPT by a set of the produced mucins MUC1, MUC2, MUC5AC, MUC6, and the glycoprotein CD10. MI and AI were estimated from the number of mitoses and apoptotic bodies in the 5-microm-thick hematoxylin- and eosin-stained tumor histological sections; Ki-67 was determined by scoring the number of its immunopositive nuclei per 1000 counted tumor cells at x1000 magnification. RESULTS: The values of Ki-67, MI, AI, and CRC in GC were found to be significantly related to the tumor histological variant and IPT; and MI, AI and CRC were also associated with adjusted 4-year relapse-free survival rates. The Ki-67 index in the gastric carcinomas is of no prognostic value, which is most likely to be attributable to the inadequacy of this indicator for the estimation of the biological potential of tumors growing in the tissues with constantly regenerative cell populations, which is peculiar to the epithelium of the gastric mucosa, particularly to that of the necks of the glands, which most GCs are histogenetically related to. CONCLUSION: Thus, the values of MI, AI, and CRC are best used as additional prognostic factors in patients with GC. At the same time, the prognostic value of Ki-67 in GC has been overestimated, as shown by the authors' data.

[Incidental renal cell carcinoma: clinical and morphological features].

This article is devoted to the evaluation of features of incidental, or asymptomatic renal cell carcinoma (RCC). The study included 268 patients with RCC aged 25 to 92 years who underwent examination and treatment in the urological clinic MRSRCI for the last 5 years. 163 (60.8%) patients had incidental renal tumors (Group 1), 105 (39.2%)--symptomatic renal tumors (Group 2). In incidental renal tumors, tumor nodule was smaller compared with symptomatic RCC--5,74 +/- 3.0 vs 6.4 +/- 3.6 cm. Stage I and II disease was diagnosed in 130 (79.7%) patients in Group 1 and only in 69 (65.7%) patients in Group 2 (P < 0.05). No significant differences in the distribution of the degree of nuclear atypia according Fuhrman nuclear grade were identified. The organ preservation surgery were performed more frequently in incidental RCC than in symptomatic RCC, in 47 (28.9%) and 21 (20%) cases, respectively; in addition, regional and distant metastases were diagnosed less frequently. With this in mind, it should be suggested that incidental tumors have a better prognosis than tumors with clinical manifestations.

[Comparative clinical and morphological characteristics of incidental and symptomatic renal cell carcinoma].

Over the last two decades, marked increase in detection of incidental or asymptomatic renal cell carcinoma (RCC) in developed countries was observed. The study included 268 patients aged from 25 to 92 years with RCC, which underwent evaluation and treatment in urology clinic MRSRCI for the past 5 years. There were no significant differences in the frequency of histological types of RCC between incidental and symptomatic tumors. Among incidental neoplasms with clear- cell structure, tumor with small size--up to 4 cm (T1a stage) and moderate to high degree of differentiation (G 1-2 according Fuhrman) were predominant. Papillary variant of RCC was detected at a higher stage of the disease and characterized by a high degree of nuclear atypia, which indicates its high malignant potential. Chromophobe RCC was usually diagnosed at T3 stage. The average age of men and women with chromophobe RCC was 46.5 +/- 6.8 years; there were no age difference in patients with symptomatic and incidental RCC. Among the benign tumors of the kidneys, angiomyolipoma was most commonly diagnosed--in 13 (53.8%) cases. Thus, incidental tumors have a better prognosis than symptomatic 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.

Comparative analysis of cells with combined apoptosis and proliferation markers in thyroid tissue specimens from patients with cancer, adenoma, and autoimmune diseases.

Combined phenotypes of cells with membrane and intracellular expression of apoptosis and proliferation regulation markers (p53, bcl-2, CD95, CD95L, Ki-67) were studied by flow cytometry of cell suspension from thyroid tissue specimens from patients with autoimmune diseases, adenoma, and thyroid cancer. The incidence of cell groups with phenotypes p53/Ki-67, p53/CD95, bcl-2/Ki-67, bcl-2/CD95, CD95/Ki-67, p53/CD95L, CD95/CD95L, and bcl-2/CD95L was evaluated and the density of receptor distribution on/in each cell group are presented. Patients with autoimmune diseases had high incidence of cells with phenotypes p53/Ki-67, p53/CD95, bcl-2/Ki-67, bcl-2/CD95, CD95/Ki-67, p53/CD95L, CD95/CD95L, and bcl-2/CD95L; cells with the bcl-2/CD95 phenotype were the most incident. Patients with thyroid adenoma had high levels of cells with p53/CD95L phenotype, while patients with thyroid cancer had significantly lower levels of p53 expression in the p53/CD95L cell group. The density of CD95L receptors on CD95/CD95L-positive cells was 4-7-fold higher in patients with thyroid tumors; the density of CD95L receptors on CD95/CD95L cells was maximum in thyroid adenoma and minimum in thyroid cancer. These data indicate differences in the expression of apoptosis and proliferation markers in thyroid adenoma, cancer, and autoimmune diseases. Analysis of the expression of these markers in the above diseases can be useful for differential diagnosis.

[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.

[Angiomyolipoma of the secondary contracted kidney in a renal graft recipient].

The special feature of the presented case is a combination of various pathological processes which developed in the recipient's kidney after renal transplantation, such as chronic glomerulonephritis progressing to nephrosclerosis; benign tumor to angiomyolipoma, xantogranulomatosis, and thesaurismosis which develop after massive infusion therapy.