[About the first publication of I.M. Sechenov. (To the 195th anniversary of his birth)]. / O pervoi publikatsii I.M. Sechenova. (K 195-letiyu so dnya rozhdeniya).

Ivan Mikhailovich Sechenov is a Russian physiologist, a natural scientist, and the creator of the Russian physiological school. The classic work «Reflexes of the Brain¼, published in 1863, became revolutionary in its own way for medicine and society, since the reflex nature of conscious and unconscious activity was proved. Along with numerous well-known scientific works, there is an early student publication in the Moscow Medical Journal published by A. I. Polunin. It describes the medical history of a patient with a tumor who was unsuccessfully treated for a long time in accordance with the humoral theory of pathology. This publication makes it possible to understand why I. M. Sechenov became disillusioned with practical medicine, but found his vocation in the study of physiology. The article is devoted to the 195th anniversary of the birth of I. M. Sechenov.

[Modern view on the problem of diagnostics of renal angiomioadenomatous tumor].

INTRODUCTION: Angiomyoadenomatous tumor as a nosological entity is not included in the latest version of the International Histological Classification of Kidney Tumors (WHO, 2022) and is related to provisional entity. Currently, there is no consensus among researchers about the nosological affiliation of an angiomyoadenomatous tumor. AIM: To comparatively analyze the histological, immunophenotypic, ultrastructural and molecular parameters of renal angiomyoadenomatous tumor and clear cell papillary renal cell tumor. MATERIALS AND METHODS: The study was performed on surgical specimen from 5 and 10 patients with renal angiomyoadenomatous tumor and with clear cell papillary renal cell tumor, respectively. Immunohistochemical study was carried out on paraffin sections according to the standard protocol. Antibodies HMWCK, AE1/AE3, 7, E-Cadherin, EMA, PAX8 and 9 were chosen. To study tumor tissues on semi-thin and ultra-thin sections, an electron microscope Philips TECNAI 12 BioTwinD-265 was used. For in situ fluorescent diagnostic detection, defined centromere probes, LSI 13/21, LSI N25 /LSI ARSA, TelVysion telomeric probe and a two-color VHL/CEP3 probe were used. RESULTS: Angiomyoadenomatous tumor is characterized by a three-phase structure. In contrast to clear cell papillary renal cell tumor, angiomyoadenomatous tumors show complete membranous expression of CA9. CONCLUSION: Our results allow to state that angiomyoadenomatous tumor and clear cell papillary renal cell tumor are different neoplasms.

Panniculitis as a manifestation of metal-associated autoimmune/inflammatory syndrome induced by adjuvants: a case-based review.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is associated with a hyperergic response of the immune system. The spectrum of clinical changes in ASIA is extensive and difficult to diagnose. Panniculitis is a heterogeneous group of diseases characterized by lesions of the adipose tissue. Panniculitis may become one of the signs of ASIA progress.To describe the clinical signs and morphological changes in the subcutaneous fat as a manifestation of ASIA, developing after osteosynthesis with metal structures.In this case-based review, were searched for all articles published in PubMed and Scopus databases until March, 2021 using the following keywords "panniculitis", "erythema nodosum", "Weber-Christian Disease", "idiopathic lobular panniculitis", "Autoimmune/inflammatory syndrome induced by adjuvants", "Shoenfeld's syndrome", "metal allergy" "metal implants", "metal hypersensitivity" and reviewed them. Irrelevant items and duplicates were excluded.We report a case of an adult female patient presenting with a non-healing uninfected surgical wound following implantation of metal osteosynthesis construction and panniculitis developed after surgery. A comprehensive examination of the patient to check for ASIA was conducted. Considering the medical history of exposure to metals, tissue lesions, arthralgia, myalgia, low-grade fever, the disappearance of symptoms on the background of immunosuppressive therapy suggested the diagnosis of ASIA.Report affords clinicians and pathologists additional insight into the clinical and morphological picture of ASIA-associated panniculitis which, if remain unidentified, may cause severe complications. We recommend the removal of constructions with adjuvant activity in patients with suspected ASIA-associated manifestations.

[Differential diagnosis of IgG4-related disease]. / Differentsial'naya diagnostika IgG4-svyazannoi bolezni.

IgG4-related disease is a chronic autoimmune fibro-inflammatory disease characterized by the presence of lymphoplasmacytic infiltrate, storiform fibrosis, obliterating phlebitis, increased number of IgG4+ cells in tissue, and, in most cases, an elevated serum IgG4 level. This disease often affects the pancreas, salivary glands and lymph nodes, but can involve almost any tissue. Its etiology is still unclear, the central role in the pathogenesis belongs to B-lymphocytes, T2-helpers, interleukins 1-ß, 4, 5, 10, 13 and tumor growth factor 1-ß. The ambiguous clinical picture and frequent simultaneous involvement of several organs make it difficult to diagnose, so biopsy plays a leading role in making a diagnosis. The characteristic microscopic picture, the presence of certain populations of lymphocytes are key criteria in establishing the correct diagnosis.

[Evaluation of morphological activity of primary Sjogren's syndrome on bioptates of minor salivary glands]. / Otsenka morfologicheskoi aktivnosti bolezni Shegrena po bioptatam malykh slyunnykh zhelez.

BACKGROUND: The results of the morphological study of the minor salivary glands can be used to assess the activity of the primary Sjogren's syndrome and to decide on adequate therapy.The existing protocol of The Sjögren's International Clinical Collaborative Alliance (SICCA) prescribes the methodology for examining biopsy specimens for suspected Sjögren's disease, however, experts interpret data from the analysis of histological preparations differently. OBJECTIVE: To identify morphological forms of sialadenitis, as well as to determine the focus score in Russian patients based on the retrospective analysis of minor salivary glands biopsies of patients with primary Sjogren's syndrome. MATERIAL AND METHODS: Biopsies of minor salivary glands were studied in 92 patients with primary Sjogren's syndrome and 42 patients without rheumatic disease. RESULTS: Focal lymphocytic sialadenitis was detected in 69 patients with primary Sjogren's syndrome. The focus score in patients with primary Sjogren's syndrome was 7.32 (2.8-14.17). In patients without rheumatic diseases, this index was 0.48 (p<0.05). Patients with confluent lymphocytic foci need immunohistochemical examination and dynamic monitoring to exclude lymphoproliferative diseases. CONCLUSION: The index of morphological activity of sialadenitis in primary Sjogren's syndrome ranges from 2.8 to 14.17 and reflects the activity of the underlying disease.It should be taken into account in the diagnosis and prescription of adequate therapy. Further study of the correlations of morphological and clinical and laboratory parameters will lead to clarification of the criterion signs of the disease.

[Possibilities of multiphoton microscopy for the diagnosis of the vulvar lichen sclerosus]. / Vozmozhnosti mul'tifotonnoi mikroskopii dlya diagnostiki skleroticheskogo likhena vul'vy.

BACKGROUND: Vulvar lichen sclerosus (VLS) is a chronic and recurrent dermatosis of an inflammatory nature with severe focal atrophy of the skin. Connective tissue changes are polymorphic and are still not taken into account in histological diagnostics due to the difficulty of interpreting routine histological methods. In this work, we use multiphoton microscopy (MPM) as a new imaging technique that provides detailed information about the organization of collagen fibers in the dermis based on a non-linear second harmonic generation (SHG) process. OBJECTIVE: To determine the degree of connective tissue damage in lichen sclerosus using standard histological techniques and to reveal the diagnostic capabilities of multiphoton microscopy. MATERIAL AND METHODS: We studied 42 biopsies with a histopathological diagnosis of VLS and 10 biopsies of normal vulvar skin. Histological, histochemical and immunohistochemical evaluation was used in comparison with MPM data. Quantitative analysis included the determination of the thickness, length of collagen fibers and the average intensity of the SHG signal. RESULTS: A comprehensive study of the skin showed 4 groups of changes that can be regarded as the degree of the dermis damage: initial, mild, moderate, severe. The affected area at the initial and mild degree has subtle changes, however, it is reliably identified by quantitative analysis of the SHG signal. So, the initial degree is characterized by thin (1.3-1.8 µm) long (56-69 µm) collagen fibers, with a moderate degree, the fibers are thickened (3.4-4.3 µm) and fragmented (22-37 µm). The affected area in moderate and severe cases undergoes homogenization, which is associated with the deposition of extremely thin (0.6-0.9 µm) short (16-28 µm) collagen fibers and the expression of type V collagen. CONCLUSION: Multiphoton microscopy in the second harmonic generation mode is a reliable method for identifying collagen fibers in tissues. The study made it possible to identify 4 degrees of the dermis damage in vulvar lichen sclerosus.

[ANCA-associated small-vessel vasculitides]. / ANTsA-assotsiirovannye vaskulity.

ANCA-associated vasculitides refer to systemic small-vessel vasculitides. The paper shows the role of antineutrophil cytoplasmic antibodies in the development of immune inflammation of blood vessels and tissues. It considers the pathogenesis of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis and presents the clinical and morphological manifestations of the diseases.

[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.

[Assessment of histologic activity in colitis]. / Otsenka gistologicheskoi aktivnosti kolitov.

The histological activity of the bowel inflammation is an extremely important morphological criterion that is encountered in the diagnosis of colitis. However, the determining of its degree is subjective and still does not have a generally accepted principle of gradation. The article describes the most common scale-schemes for assessing the severity of colitis, that include the degree of microscopic changes. The results of the analysis of the of histological activity degree on the material of colonobioptates in colitis of various etiologies (467 patients) are presented. It has been shown that the Geboes scale of ulcerative colitis can be used to assess histological activity in all forms of colitis. The histological features of inflammation should be reflected in the pathological diagnosis and are essential for clinical decision making. This index allows for a comparative analysis of clinical, endoscopic and morphological parameters and better control of the patient's condition during the treatment.

[A new look at colonic mucosal structural rearrangement and the stages of chronic colitis]. / Novyi vzglyad na strukturnuyu perestroiku slizistoi obolochki tolstoi kishki i stadii khronicheskogo kolita pri vospalitel'nykh zabolevaniyakh kishechnika.

OBJECTIVE: To revise the existing criteria to improve the definition of chronic colitis stages in inflammatory bowel diseases (IBDs). MATERIAL AND METHODS: A total of 100 cases of IBDs (ulcerative colitis (n=70) and Crohn's disease (n=30) diagnosed in 2017 to 2019 were examined. Thirty patients with colitis were selected for a comparison group, who were assigned to an infective colitis group or a drug-induced colitis one at the final diagnosis. RESULTS: The sequence of chronic colitis stages was defined from Stage 1 (early changes) to Stage 3, which are characterized by progressive mucosal structural rearrangement. Mainly at Stage 3 that characterizes the final stage of structural rearrangement in the mucous membrane, where dysplastic changes (the onset of tumor transformation) are detected. CONCLUSION: For the diagnosis of chronic colitis in IBD, it is mandatory to detect mucosal structural rearrangement. Stages 1 and 2 are characterized by early structural changes in the mucous membrane, whereas the process becomes irreversible at Stage 3. The identification of colitis stages is of diagnostic and, undoubtedly, prognostic value.

[Pulmonary embolism and diffuse alveolar bleeding: combination options and therapy features].

The analysis of the mechanisms of the formation of a rare clinical combination of pulmonary embolism (PE) and diffuse alveolar hemorrhage (DAH), which are complications of systemic vasculitis associated with antibodies to the cytoplasm of neutrophils (primarily granulomatosis with polyangiitis), systemic lupus erythematosus and secondary antiphlogistic syndrome primary antiphospholipid syndrome and Goodpastures syndrome. Taking into account the chronological sequence of the occurrence of PE and DAH, 3 variants of the onset of these potentially fatal additions to the underlying disease were considered: the anticipatory DAH development of PE, delayed from DAH PE and joint (within 24 hours) formation of PE and DAH. A review of single descriptions of such a combination of complications of granulomatosis with polyangiitis is carried out, criteria are indicated, a working classification of severity is given and, taking this into account, a modern program of therapy for DAH as an independent event and in combination with PE.

[Severe spine lesion following alkaptonuria. Case report]. / Tyazheloe porazhenie pozvonochnika pri alkaptonurii. Opisanie klinicheskogo sluchaya.

Alkaptonuria is a rare autosomal recessive disease. In these patients, melanin-like compounds as the final products of impaired metabolism of homogentisic acid are deposited mainly in connective tissue, including cartilage tissue of intervertebral discs. Similar to other degenerative spine diseases, lumbar segment is often damaged. The authors report a 67-year-old patient with alkaptonuria. Compression of cauda equina by damaged cartilage masses of intervertebral discs and spine ligaments with deposits of ochronotic pigment is described. Previously diagnosed alkaptonuria in this patient was confirmed by surgical findings (black pigmentation) and histological data.

[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.

[Microscopic polyangiitis]. / Mikroskopicheskii poliangiit.

The paper describes an autopsy case of a 69-year-old woman with microscopic polyangiitis lasting about 1.5 months despite intensive treatment. She had generalized productive vasculitis, extracapillary productive glomerulonephritis, adult respiratory distress syndrome with focal pneumonia, isolated lung atelectasis, splenic infarction, and toe and finger gangrene. Morphological differences from those of granulomatosis with polyangiitis and Churg-Strauss syndrome are presented.

[Panniculitis in modern rheumatology].

AIM: To study clinical and laboratory features of panniculitis (Pn) in modern rheumatology. MATERIALS AND METHODS: The study included 690 patients with Pn (615 women and 75 men, average age 39.410.26) with the prevailing referral diagnosis of Erythema nodosum (59.2%), Pn (27.5%), Rheumatic disease Rd (9%), other diseases (4.4%),who had been on outpatient and/or inpatient treatment for 10 years. All patients were examined according to our diagnostic algorithm: general clinical, immunological and histological examinations, computed tomography of the chest organs, tuberculin tests. RESULTS: Pn with Rd was diagnosed in 140 patients (118 women and 22 men, average age 40.2114.87), average disease duration 31.06 [0.1; 541] months. In most cases (49%) patients had idiopathic lobular Pn which belongs to the group of systematic lesions of connective tissue (M35.6), as well as systemic lupus erythematosus and Behcet disease (13% each), rheumatoid arthritis (8%), dermatomyositis (6.4%), etc. Matching of the referral and final diagnoses was 35% in case of Rd. Among the examined patients prevailed those with a moderate (51.07%) degree of activity of the underlying disease. Within the study group Pn was represented by all forms, but mainly by nodular form (64.02%). Mesenteric form was characteristic only for idiopathic lobular Pn. The main features of Pn associated with Rd were identified. In modern clinical practice the type of Pn and the activity of the underlying disease determine the approaches to treatment.

[Idiopathic lobular panniculitis: clinical and morphological correlations]. / Idiopaticheskii lobuliarnyi pannikulit: kliniko-morfologicheskie korreliatsii.

Panniculitis is a heterogeneous group of diseases that are characterized by a subcutaneous adipose tissue (SAT) lesion and frequently occur with involvement of the musculoskeletal system and viscera in the process. This is a chronic multiple organ disease. The gold standard for its diagnosis is noted to be a morphological study. The paper presents the current classification of panniculitis. OBJECTIVE: To study the morphological features of idiopathic lobular panniculitis (ILP) in accordance with the nature of the course and clinical forms of the disease. SUBJECT AND METHODS: Biopsy specimens were studied in 62 patients with various clinical forms of ILP. Biopsy and surgical materials were investigated by light optical morphological methods. The results were statistically processed using a statistical analysis software Statistica Version 10 package for Windows ('StatSoft Inc.', USA). The differences were considered statistically significant at an error level of p<0.05. Methods, such as Pearson's c2 test (analysis of contingency tables), Student's t-test, Z-test for comparison of proportions, nonparametric tests, such as Mann-Whitney U-test, Kruskal-Wallis test, were used to assess the results. RESULTS: The nature of the morphological parameters of the disease corresponded to the course of ILP. The acute course of the disease was characterized by the predominance of liponecrosis and inflammation concurrent with productive-destructive vasculitis. In the chronic course, there was a preponderance of lymphohistiocytic infiltrate with gigantic macrophages (lipophages) and granuloma-like structures. The above morphological changes were characteristic of the phagocytic morphological stage of node formation. The fibroplastic stage of panniculitis was absent in this study. The morphological features of the disease were shown depending on the form of idiopathic lobular panniculitis, which may be of diagnostic value in the differential diagnosis of panniculitis. CONCLUSION: The pathologist must first of all pay attention to the preferential localization of pathological changes (in the SAT septa or slices), the presence or absence of vasculitis and the nature of the infiltrate. The skin in panniculitis is typically intact or has minimal changes following the pattern seen in reactive ones. Panniculitis shows an undulatory course, and therefore all signs of this disease are present in biopsy specimens; however, morphological signs of the acute inflammatory, lipophagic or fibroplastic stage of the disease predominate depending on the stage and activity of the process.

[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.

[Idiopatic Lobular Panniculitis as a common clinical problem].

AIM: To present clinical and laboratory characteristics of various forms of idiopatic lobular panniculitis (ILP) in modern rheumatology practice. MATERIALS AND METHODS: The study included 67 people (58 women and 9 men aged 20 to 76) with the referral diagnosis of "Erythema nodosa? Undifferentiated panniculitis?" in 76.2% of cases with a median disease duration of 78.91 [48; 540] months observed in the V.A. Nasonova Research Institute of Rheumatology. In 2007-2017 in addition to general clinical examination immunological, histological and immunohistochemical studies, computed tomography (CT) of the chest organs and tuberculin tests were performed. RESULTS: Analysis of clinical manifestations allowed to distinguish four forms of ILP: nodular (n=30), plaque (n=10), infiltrative (n=15) and mesentric (n=12). The minimum median duration of the disease was detected in plaque form (8 [5; 11.5] months), while the median duration in case of infitrative form was 8.25 times longer (66 [36; 102] months, p38 °C and a small number (up to 5) of drain nodes; infiltrative - fever >38 °C, ulceration of nodes with the expiration of oily mass and scarring; mesenteric - pain in the abdominal area, the number of nodes less than 5 and the abdominal cavity CT results (inflammation of the adiopose tissue of the intestinal mesentery, omentum, adipose tissue of the pre - and retroperitoneal areas). CONCLUSION: The forms and activity of the disease determine the approaches to treatment in modern clinical practice. There is an obvious need to expand knowledge about this pathology among doctors and conduct further research in order to timely diagnose and search for the most effective methods of ILP treatment.

[Autoimmune/inflammatory syndrome induced by adjuvants]. / Autoimmunnyi/vospalitel'nyi sindrom, assotsiirovannyi s ad''iuvantami.

The development of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is associated with the hyperergic reaction of the human immune system. The development of autoimmune inflammation is preceded by contact with internal or external trigger factors (adjuvants) of immune disorders. ASIA is associated with an individual genetic predisposition that is probably associated with the carriage of HLA-DRB1*01 or HLA-DRB4. The paper presents five possible options for the impact of adjuvants in the pathogenesis of autoimmune disorders. It gives diagnostic criteria for the syndrome, as well as its clinical, laboratory and morphological manifestations. Emphasis is laid on the importance of morphological changes in the diagnosis of autoimmune disorders. The spectrum of morphological changes in ASIA is extensive. The tissues show signs of immune inflammation, such as lymphohistiocytic infiltration, granulomatous inflammation, and scleroderma-like changes. The characteristic feature is the regression of clinical, laboratory, and morphological manifestations after adjuvant removal.

[Is scleromyxedema a skin problem or systemic pathological process?] / Skleromiksedema - dermatologicheskaia problema ili sistemnyi patologicheskii protsess?

Scleromyxedema is regarded as a rare cutaneous mucinosis from a group of lichen myxedematosus characterized by diffuse mucin deposition, sclerosis, and lichenoid eruptions in the absence of thyroid disease. The paper discusses the pathogenesis of the disease and histological changes in tissues. It underlines the need for using histochemical tests to identify acidic and neutral glycosaminoglycans and gives a differential diagnosis of this disease.