[IgG4-related ophthalmopathy]. / IgG4-svyazannaya oftal'mopatiya.

IgG4-related disease is a chronic inflammatory fibrosing disease of unknown etiology, characterized by the presence of volumetric lesions that can clinically simulate malignant tumors, a pronounced IgG4-positive lymphoplasmacytic infiltrate, and an increase in the level of IgG4 in the blood serum. A special form of the disease is IgG4-related ophthalmopathy, which requires differential diagnosis with inflammatory pseudotumor, lymphoma and granulomatous polyangiitis. 7 clinical cases of IgG4-related ophthalmopathy are presented. It has been shown that follicle-like structures with the structure of a lymph node are formed in the tissues of the orbit. Along with a large number of cells in the inflammatory infiltrate expressing CD138, IgG and IgG4, there are CD8+ and CD68+ cells. IgG4-related ophthalmopathy is a rare manifestation of IgG4-related disease. Its morphogenesis involves not only IgG, IgG4 and CD138 positive plasma cells, which are diagnostic. CD8 and CD68- positive cells are involved too. They persisted in large quantity in the lymphohistiocytic infiltrate. The study of the lymphocyte population can help in revealing the pathogenesis and morphogenesis of this rare disease.

[The morphological characteristics and immunophenotype of renal cell carcinomas with eosinophilic cytoplasm]. / Morfologicheskaia kharakteristika i immunofenotip pochechno-kletochnykh kartsinom s éozinofil'noi tsitoplazmoi.

Eosinophilic cellular renal cell carcinomas embrace a wide range of histological types described in the 2016 WHO International Classification of Kidney Tumors. A variety of histological manifestations associated with the features of tumor morphogenesis in this group poses difficulties in differential diagnosis. AIM: to investigate the morphological and immunophenotypic features of rare types of renal cell carcinomas with eosinophilic cytoplasm. SUBJECTS AND METHODS: An investigation was conducted using a surgical material from 294 patients with a kidney tumor. An immunohistochemical (IHC) study was performed on paraffin sections according to the standard protocol using a wide panel of antibodies. RESULTS: Based on a morphological analysis and IHC study, the tumors were divided into 3 groups: 1) 127 (43%) oncocytic tumors that expressed classical IHC markers for oncocytoma and chromophobe renal cell carcinoma; 2) 50 (17%) oncocytic tumors that did not correspond to the immunophenotypes of oncocytoma and chromophobe renal cell carcinoma; and 3) 117 (40%) eosinophilic cellular nononcocytic renal tumors. CONCLUSION: With the advent of the current differential diagnostic criteria, the classification of renal cell carcinomas continues to expand. To date, a hybrid oncocytic/chromophobic tumor, eosinophilic solid and cystic renal cell carcinoma, and follicular kidney cancer should be regarded as new nosological entities.

[Morphological and immunohistochemical characteristics of the molecular subtypes of urothelial carcinomas]. / Morfologicheskaia i immunogistokhimicheskaia kharakteristika molekuliarnykh podtipov urotelial'nykh kartsinom.

The molecular subtypes of urothelial carcinoma in each classification scheme have characteristic immunohistochemical features. At the same time, the results of conducted studies often demonstrate a discrepancy between the genomic profile of urothelial carcinoma and its immunophenotype, which complicates the immunohistochemical verification of the molecular subtypes of these tumors. OBJECTIVE: To compare the morphological and immunophenotypic characteristics of the molecular subtypes of urothelial carcinoma. MATERIAL AND METHODS: Surgical specimens from 196 patients diagnosed with urothelial carcinoma of the renal pelvis and bladder were investigated. Paraffin-embedded sections were immunohistochemically examined using the standard protocol. Antibodies against CK5/6, CK17, Rb1 (Dako), CK14, CK18, CK20, Cyclin D1, Cyclin E1, Cyclin A, Cyclin B, Chromogranin, E-Cadherin, P-Cadherin, p16, Uroplakin II, TUBB2B, Vimentin, ZEB-2 ('Novocastra'), CD44, GATA-3, and Uroplakin III ('Cell Marque') were used. RESULTS: Out of 68 (35%) superficial papillary urothelial carcinomas, 24 (12%) tumors constituted Molecular Class I and 12 (6%) and 32 (16%) ones did Molecular Classes II and III, respectively. Of the 128 (65%) muscle-invasive urothelial carcinomas, 57 (29%) tumors were referred to as the luminal-papillary molecular subtype, and 24 (12%) and 14 (7%) were as the luminal-infiltrated and luminal molecular subtypes, respectively. The basal squamous molecular subtype was verified in 31 (16%) neoplasms and the neuronal phenotype was detected in 2 (1%) cases. CONCLUSION: Most pT1 tissues correspond to Molecular Class II. In the muscle-invasive urothelial carcinoma group, the neoplasms with a luminal phenotype predominate over the tumors with basal and neuronal phenotypes.

[Markers of stem cells and their prognostic values for urothelial carcinomas of the urinary tract].

The fundamental question about the origin of cancer stem cells of urothelial carcinomas with luminal remains open. So far, no convincing evidence has been found to determine whether these events occur in a single cell, presumably basal, or are realized in different precursor cells of the urothelium. The potential of a number of potential stem markers as cancer stem cells in urothelial carcinomas and their prognostic significance are currently being investigated. AIM: Our aim was to carry out a comparative analysis of the expression of stem markers in the molecular subtypes of urothelial carcinomas, including ALDH1A1, CXCR4, CD24, CD82, CD105, CD133, NANOG, OCT4 and SOX-2. In addition, the relationship between the pattern of expression and the pathological features of the tumor was determined. PATIENTS AND METHODS: Surgical specimens from 196 patients with a diagnosis of urothelial carcinoma of the renal pelvis and bladder were studied. Immunohistochemical study was performed on paraffin sections using the standard protocol. Antibodies against ALDH1A1, CD82, CD133, CXCR4, NANOG, OCT4, SOX2 ("Abcam"), CD24, CD105 ("Invitrogen"), CD31, CD34 ("Novocastra") were used. RESULTS: The stem cell markers used in the study were expressed in all molecular subtypes of urothelial carcinoma and there were no differences in frequency and intensity of expression between different phenotypes. However, the frequency and intensity of expression of the markers correlated with the tumor stage and the grade of cellular anaplasia. CONCLUSION: Our results confirm that cancer stem cells with basal phenotype are not an exclusive subpopulation in urothelial tumors. Other progenitor cells with the immunophenotype of intermediate and/or umbrella cells can serve as cancer stem cells. These features of the expression in cancer stem cell markers will allow to develop new approaches to the treatment of urothelial carcinomas.

[Comparative morphological characteristics and immunophenotype of urothelial carcinomas of the renal pelvis and bladder]. / Sravnitel'naia morfologicheskaia kharakteristika i immunofenotip urotelial'nykh kartsinom pochechnoi lokhanki i mochevogo puzyria.

Urothelial carcinoma is one of the most frequently diagnosed malignant tumors of the bladder and upper urinary tract, which ranks seventh in the pattern of cancer. Urothelial carcinoma of the renal pelvis is less common; but has a more aggressive clinical course and a worse prognosis than that of the bladder. This is due to the clinical and morphological features of this form of cancer, which, unlike bladder cancer, have not been studied enough. OBJECTIVE: To comparatively analyze the morphological and immunophenotypic parameters of urothelial carcinomas of the renal pelvis and bladder. SUBJECT AND METHODS: Surgical specimens from 196 patients diagnosed with urothelial carcinoma of the renal pelvis and bladder were investigated. Paraffin sections were immunohistochemically examined using the standard protocol. Antibodies against CK5/6, CD138, CDX2 ('Dako'), CK7, CK14, CK20, CEA, CD10, CD117, EMA, E-Cadherin, HMWCK, p63, Uroplakin III, Vimentin ('Novocastra'), CD44, GATA-3, MUC1, MUC2, and MUC-5AC ('Cell Marque') were used. RESULTS: Most tumors (n=147 (75%)) were invasive. Of them, 65 (33%) cases had a histological structure of conventional urothelial cancer; and 3 (1.5%) had paradoxical differentiation. Divergent tumor zones were verified in 66 (34%) neoplasms; 4 (2%) cases showed an inverted growth pattern. Pseudosarcomatous stroma reaction in the invasion zones was verified in 9 (5%) cases. The tumor stage corresponded to pT2-pT4 in 128 (65%) tumors. CONCLUSION: Urothelial carcinomas of the renal pelvis and bladder show a broad spectrum of histological variants. The findings support that, unlike urothelial carcinomas of the bladder, the majority of primary urothelial carcinomas of the renal pelvis are high-grade and highly invasive.