Arkhiv patologii最新文献

This study analyzes the modern (2021) WHO classification of lung tumors and reviews publications in Russian and English from databases including PubMed, Google Scholar, ClinicalTrials.gov, eLibrary, and CyberLeninka. The aim of this review is to identify key changes in the 2021 WHO classification compared to the 2015 edition and assess their significance for the diagnosis and personalized treatment of non-small cell lung cancer. Special attention is given to the handling of small biopsy specimens, which requires an integrated approach involving morphological examination, immunohistochemistry, and molecular genetic testing.

The genes of mismatch repair system (MMR) are responsible for correcting errors in DNA replication. MMR defects (dMMR) lead to mutations in microsatellites - repetitive nucleotide base sequences - resulting in microsatellite instability (MSI). Determination of dMMR/MSI status in tumors is an important factor for the development of patient management tactics, as the dMMR/MSI phenotype serves as both a marker of favorable prognosis and a predictor of response to immunotherapy in tumors of many localizations. MMR status is assessed via immunohistochemistry (IHC) on histological material. However, in some cases heterogeneity of intratumoral MMR protein expression (MMR heterogeneity) becomes an obstacle to this. MMR heterogeneity (areas of weak/absent staining on the background of normal expression) is poorly studied, especially in gastric cancer, in contrast to colorectal cancer and endometrial cancer. The lack of a methodology for interpreting this phenomenon leads to significant difficulties in stratifying patients who are indicated for dMMR/MSI status determination. The article systematizes current data on MMR heterogeneity in gastric cancer and tumors of other localizations, discusses molecular mechanisms, clinical significance and recommendations to overcome diagnostic limitations.

Infertility is a significant medical problem associated with morphological and functional changes in the endometrium and ovarian diseases that can lead to endometrial dysfunction. In this regard, it remains extremely important to study the role of endometrial and ovarian pathology in the development of infertility.

Objective: Comparative analysis of endometrial receptivity in young women with endometrial and ovarian factors of infertility.

Material and methods: We conducted a retrospective study that included 195 patients of reproductive age. Group 1 included patients with endometrial infertility factor (n=97), Group 2 included patients with ovarian infertility factor (n=38), Group 3 included women with a combination of both infertility factors (n=35). The comparison group consisted of women with infertility associated with male factor who were examined before IVF procedure (n=25). For pathomorphologic and immunohistochemical studies, the endometrium was sampled by pipelle biopsy on the 19^th-22^nd day of the menstrual cycle during the expected implantation window period.

Results: Analysis of the results of the pathomorphologic study revealed different degrees of impaired development of pinopodes and delayed secretory transformation of the endometrium in patients of the three groups. Immunohistochemical study revealed a significant decrease in the expression level of estrogen receptors (ER) and increase in the expression of progesterone receptors (PR) in the glandular compartment in all studied groups compared to the comparison group, as well as a decrease in the expression level of ER in the stromal compartment of the endometrium in patients of groups 1 and 3.

Conclusion: One of the leading causes of implantation disorders in patients with endometrial and ovarian infertility factors is impaired maturation of pinopodes, delayed secretory transformation of the endometrium and displacement of the implantation window, as well as decreased expression of ER and increased expression of PR in glandular compartments in patients of the studied groups compared to the morphological control group, decreased expression of ER in the stromal compartment, in patients of groups 1 and 3.

Objective: To analyze the pathomorphological and immunohistochemical characteristics of the hearts of patients who died from COVID-19.

Material and methods: A comprehensive pathomorphologic study of the heart in 88 autopsies of patients who died from severe COVID-19 was performed. The presence of SARS-CoV-2 infection was confirmed by positive PCR tests in all cases. Immunohistochemical study was used to analyze the expression of viral nucleocapsid protein (NP), CD3, CD68, CD31, CD34, Willebrand factor (vWF) in cell populations and myocardial structures.

Results: In most cases, polymorphism of structural changes was observed, which was expressed in a combination of signs of chronic and acute myocardial damage. Numerous foci of interstitial and perivascular fibrosis and lipomatosis, irregular hypertrophy of cardiomyocytes, amyloid deposits were indicative of previous cardiovascular diseases. Acute and subacute pathological changes in myocardium included circulatory disorders (hyperemia, intraluminal megakaryocytes, microvascular thrombosis, interstitial edema), vascular damage, and alterative changes in cardiomyocytes. Lymphomacrophage infiltration was present in 45% of cases and was associated with immunohistochemical detection of NP in cardiomyocytes and vascular cells. Weak expression of CD31 and high expression of vWF in microvascular endothelium was found.

Conclusion: NP expression in cardiomyocytes, macrophages and endothelial cells of cardiac vessels indicates their direct infection with SARS-CoV-2 virus and possible long-term persistence of viral infection. It was found that in severe COVID-19 CD3- and CD68-positive cells are detected in the heart; endothelial dysfunction is observed, which is indicated by decreased expression of CD31 and high expression of vWF. The identified myocardial changes may influence the development of post-COVID cardiovascular complications.

TRPS1 (Tricho-rhino-phalangeal syndrome type 1) - a transcription factor of the GATA family, has recently emerged as a promising immunohistochemical marker for breast cancer. This review summarizes current data on the diagnostic, prognostic, and potential therapeutic relevance of TRPS1, as well as its molecular functions and expression patterns across different breast cancer subtypes. TRPS1 demonstrates high sensitivity, including in diagnostically challenging cases such as triple-negative and poorly differentiated carcinomas, where traditional markers (GATA3, mammaglobin) may be absent or weakly expressed. The advantages of TRPS1 in the differential diagnosis of metastatic lesions and its possible role in prognostic panels are highlighted. Methodological limitations of the using marker, standardization needs and future perspectives for clinical implementation are also discussed in article.

Objective: Study of morphometric and ultrastructural features of follicular adenomas of the thyroid gland.

Material and methods: The study was conducted on the surgical material of the thyroid glands of 11 patients with a preliminary cytological conclusion of "Follicular neoplasia" and a further histologically established diagnosis of "Follicular adenoma". Material - fragments obtained from morphologically verified nodes of follicular adenoma, fragments of tissue outside the nodular formation served as control samples. Light and transmission electron microscopy were used to study semi-thin and ultra-thin sections of the thyroid glands, respectively. Morphometric analysis and statistical processing were performed on semi-thin sections.

Results: In follicular adenoma, the formation of intracellular microfollicles and narrowing of the lumen of the follicles with hypertrophy of the tumor cells: a reliable increase in the area of cells and their nuclei (p≤0.01), the numerical density of mitochondria (p≤0.001), a decrease in the diameter of the follicles (p≤0.001) were noted. The common ultrastructural features of the studied follicular adenomas are heterogeneous changes in the synthetic apparatus against the background of a sharp increase in the number of mitochondria. A possible mechanism of morphological rearrangements of tumor cells in follicular adenoma is compensatory adaptation at the level of cellular energy systems in response to dysfunction of the synthetic apparatus of thyrocytes. In the studied follicular adenomas with classical microfollicular morphology, signs of other, rarer histological patterns were found in a number of cells or in individual follicles, in particular, signet ring cell and clear cell patterns.

Conclusion: The diversity of the detected morphological rearrangements reflects the stage-by-stage development of follicular adenomas. A number of ultrastructural features suggest that the rarer histological patterns described for follicular adenomas originate from the classical microfollicular pattern as a result of multidirectional transformation.

Objective: Clinical and morphologic analysis of pathologic changes of digestive system organs in COVID-19 patients according to autopsy data of 2021-2024.

Material and methods: A retrospective clinical and morphologic analysis of data from 69 autopsies of patients who underwent COVID-19 (confirmed by polymerase chain reaction test) and had symptoms of digestive system lesions, according to clinical data, was performed. The data of case histories, autopsies, pathologoanatomic diagnoses and causes of death of patients were studied. Microscopic studies of tissue samples of stomach, intestine, liver, pancreas were performed. Immunohistochemical study with antibodies CD3, CD45, CD68, spike- and nucleocapsid-protein SARS-CoV-2 was performed.

Results: According to autopsy data, pathologic changes of the stomach that first developed and pre-existing more than 3 months after SARS-CoV-2 infection were detected in 49 (71.01%) of 69 cases. Among them, chronic superficial gastritis was the most common with 17 (34.99%) observations and acute stress-induced gastric erosions and ulcers with 13 (26.53%). Small and large intestinal lesions were seen in 15 (30.61%) cases, among which intestinal adenocarcinomas predominated with 6 (40.00%), colonic diverticula and chronic lymphocytic colitis with 3 (20.00%) cases each. Liver pathology, new-onset and pre-existing, was present in 100.00% cases: muscadic liver 45 (65.22%), massive liver necrosis (7.25%), hepatic steatosis and steatohepatitis (26.09%), brown atrophy (8.70%). Pancreatic lesions, new-onset and pre-existing, were detected in 57 (82.60%) cases. Among them, sclerosis and lipomatosis were more frequently registered in type 2 diabetes mellitus - 46 (80.70%) observations, pancreonecrosis - 11 (19.30%).

Conclusions: Gastric, intestinal, liver, and pancreatic pathology in COVID-19 patients may be either first-onset or preexisting. The detected persistence of nucleocapsid and spike proteins of the virus in tissues may cause direct and autoimmune tissue damage, leading to the development of new and progressive chronic diseases of the digestive organs.

One of the key differences between ovarian borderline serous tumors and low-grade serous carcinoma is the pattern of extraovarian tumor spread. Therefore, accurate diagnostics of the peritoneal implant's histotype plays a crucial role in treatment and disease prognosis. Despite established histological criteria for differential diagnosis, the classification of implant type remains subjective, and the interobserver reproducibility among pathologists is still understudied.

Objective: To assess the level of reproducibility in implant type classification among pathologists for ovarian borderline serous tumors and low-grade serous carcinoma.

Material and methods: A series of 33 slides from resected omentum and peritoneum specimens obtained from 23 patients with ovarian borderline serous tumors and low-grade serous carcinoma were independently evaluated by three gynecologic pathologists and three oncopathologists with varying experience in gynecologic pathology to determine implant type. A consensus diagnosis was established by majority agreement among gynecologic pathologists.

Results: The consensus diagnosis classified 42.4% of cases as low-grade serous carcinoma metastases and 57.6% as non-invasive implants of borderline serous tumors. The Fleiss' kappa was 0.61, indicating substantial reproducibility among all pathologists, but Cohen's kappa varied significantly (0.348-0.817). Reproducibility was perfect between gynecologic pathologists and between them and the consensus diagnosis. However, reproducibility among general pathologists was only moderate, while their agreement with the consensus diagnosis ranged from minimal to substantial.

Conclusion: This study confirms significant diagnostic challenges in distinguishing non-invasive implants of borderline serous tumors from low-grade serous carcinoma metastases among pathologists, highlighting the need for developing and implementing standardized diagnostic algorithms.

Objective: To improve the stratification algorithm for aggressive B-cell lymphomas in children based on the analysis of genetic changes in the genes TP53, MYC, BCL2, BCL6 and the long arm of chromosome 11 (11q).

Material and methods: A comprehensive cytogenetic and molecular genetic analysis of tumor samples was carried out using NGS and FISH methods. Rearrangements of the MYC locus and the presence of translocations with different chromosomal partners were investigated, as well as the analysis of mutations and deletions of the TP53 gene. The presence of MYC, BCL2, BCL6 rearrangements and 11q aberrations was investigated as part of the algorithm.

Results: It has been shown that the classical translocation, t(8;14)(q24;q32) MYC::IGH, is detected in 77% of cases with typical Burkitt lymphoma histology. This translocation was not present in 23% of the samples. In a group of cases with classic histology of Burkitt lymphoma, where the t(8;14)(q24;q32) translocation was absent, rare genetic variations were identified - 11q gain/loss, and atypical FISH patterns indicative of complex genetic changes. TP53 mutations were detected in 26-30% of cases, localized mainly in the DNA-binding domain. A wide range of genetic changes has been identified, including monoallelic TP53 deletions and atypical FISH patterns that require attention and additional research.

Conclusion: An improved diagnostic algorithm based on the combined use of FISH and NGS methods makes it possible to increase the accuracy of identification of genetic subtypes of aggressive B-cell lymphomas in children. This helps to categorize the diagnosis based on the molecular and genetic characteristics of the tumor, paving the way for improved prognosis and treatment effectiveness.

Objective: To evaluate changes in gene expression activity during preoperative testing for tumor hormone sensitivity to aromatase inhibitors and tamoxifen in postmenopausal women with ESR+/HER2- breast cancer.

Material and methods: The study included 174 breast cancer patients. Pathological examination of FFPE core biopsy specimens, performed before the hormone response test, and surgical specimens were examined, as well as immunohistochemistry (Ki67, ER, PR, HER2/neu) and molecular genetic testing of an expression panel of 45 target genes using quantitative real-time PCR.

Results: The use of aromatase inhibitors in the preoperative hormone response test is accompanied by statistically significant changes in the mRNA expression of 37 genes in breast tumors, of which a decrease in the expression level was found for 35 genes (ESR1, PGR, AR, ERBB2, FGFR4, MKI67, MYBL2, CCNB1, AURKA, BIRC5, CCND1, CCNE1, CDKN2A, KIF14, PPP2R2A, PTTG1, TMEM45B, TPX2, ANLN, MMP11, CTSL2, EMSY, PAK1, BCL2, BAG1, PTEN, TYMS, EXO1, UBE2T, NAT1, SCGB2A2, GATA3, FOXA1, ZNF703, CD274/PD-L1), an increase - for two genes (SFRP1, KRT5). While the use of tamoxifen statistically significantly correlates with a decrease in the level of mRNA expression of 35 genes: ESR1, PGR, AR, EGFR, ERBB2, FGFR4, MKI67, MYBL2, CCNB1, AURKA, BIRC5, CCND1, CCNE1, CDKN2A, KIF14, PPP2R2A, PTTG1, TMEM45A, TMEM45B, TPX2, ANLN, MMP11, EMSY, PAK1, BCL2, BAG1, PTEN, TYMS, EXO1, UBE2T, NAT1, GATA3, FOXA1, ZNF703, CD274/PD-L1, and an increase in only one gene - MYC.

Conclusion: Comparative mRNA expression analysis confirms that a short preoperative course of aromatase inhibitors induces a more potent and uniform molecular response, characterized by profound suppression of proliferation and complete inhibition of estrogen-dependent signaling. Tamoxifen therapy is also effective but results in less pronounced suppression of key targets and, crucially, may be accompanied by early activation of the MYC oncogene, a potential marker for resistance development.