Background. Mutations in the SMARCA4 gene of the SWI/SNF chromatin remodeling complex occur in 10% of nonsmall cell lung cancer (NMRL). SMARCA4-deficient lung tumors are aggressive neoplasm with poor outcome. Morphological, immunohistochemical and clinical description of this tumor type is lacking.

The aim of the study was to investigate clinical and morphological characteristics and frequency of SMARCA4 expression loss in patients with lung tumors.

Material and methods. Specimens from a total 100 non-small cell lung cancer cases were immunohistochemically examined for expression of SMARCA4 and SMARCA2. EGFR, BRAF mutations and gene rearrangement of ALK or ROS1 were tested by immunohistochemical, PCR-based or FISH techniques among cases with loss of SMARCA4 expression.

Results. Loss of SMARCA4 expression was detected in 14 (14%) cases. Most of them are men — 93%. The average age was 63 years. In most cases (64%) SMARCA4-deficient tumors have been diagnosed as adenocarcinoma. The mutation was significantly associated with smoking history (p-value 0.009). Mutations in EGFR, BRAF genes and rearrangement of ALK or ROS1 in the SMARCA4-deficient tumor group have not been detected.

Conclusion.  SMARCA4-deficient tumors are subgroup of NMRL, prevalent in smoking men and diagnosed as lung adenocarcinoma without activating mutations.

The low incidence, nonspecific clinical picture and absence of pathognomonic symptoms of vulvar adenocarcinoma make primary diagnosis very difficult. It could take months from the appearance of first symptoms to the final diagnosis and the start of specific treatment.

There are limited options of standard treatment for this pathology. Therefore, attempts to use therapy that has proven itself in the other malignant tumors, based on molecular biological characteristics, are promising.

Overexpression of HER2, which plays an important role in the carcinogenesis processes, is often observed in cases of extramammary Paget’s disease. We report a case of extramammary Paget’s vulvar cancer treated with a combination of cytostatic and targeted anti-HER2 agents.

Triple-negative breast cancer (TNBC), while not the most frequent subtype, has a surprisingly aggressive course and low sensitivity to current antitumour drugs. Detection of predictive BRCA-mutation and administration of targeted therapy in the first lines of treatment of metastatic TNRML can significantly affect the life expectancy of patients. The clinical case of patient O. with BRCA-associated bilateral metachronous metastatic breast cancer demonstrates how important it is to implement a personalised approach in time. During the patient’s treatment, it was important to constantly compare the initial morphological profile of the tumour and the clinical course of the disease in order to suspect a discrepancy and to revise the surgical material. The administration of systemic drug therapy, taking into account the genetic and immunohistochemical features of the tumour, made it possible to achieve prolonged recurrence-free periods in two consecutive lines of treatment with preservation of the patient’s decent quality of life.

At the moment, the standard of treatment in the Russian Federation for late stages of well-differentiated thyroid cancer (hereinafter referred to as WDTC) with a recorded radioiodine-resistant tumor status is the sequential administration of multikinase inhibitors: Sorafenib, Lenvatinib. Treatment protocols for subsequent lines have not been developed. The purpose of this article is to review the main molecular genetic features of WDTC and present the clinical observation of a patient with metastatic radioiodine-resistant follicular varient of papillary thyroid cancer (hereinafter referred to as PTC), which has progressed after previous lines of therapy. The patient’s tumor biological material was submitted for next-generation sequencing (NGS), which allows detection of all classes of molecular changes for a large number of genes. Due to the discovery of an ALK mutation and the lack of registered standards for subsequent treatment, ALK inhibitors were prescribed. This attempt to individualize therapy was successful: a partial response was registered during therapy and a significant clinical improvement in the patient’s general condition was noted. Therapy with ALK inhibitors continues to this day (46 months as of October 2023) and has a favorable toxicity profile. Thus, we can conclude that when the basic standards for the treatment of metastatic well-differentiated thyroid cancer have been exhausted, there is an individual selection of targeted therapy depending on the molecular genetic characteristics of the tumor process. 

The indications for immunotherapy are expanding every year and the therapeutic algorithms for most types of solid tumors are steadily evolving towards the wider and earlier use of immune checkpoint inhibitors (ICI). However, everything has its price, and along with the treatment response, this class of drugs has brought a number of peculiar autoimmune complications associated with ICI and called immune-related adverse events (irAEs). Taking into account the peculiarities of the mechanism of action, the range of complications of this therapy is limited only by the list of structures and tissues of the human body. A special place is occupied by neurological adverse events due to their diversity, complexity of diagnosis requiring multidisciplinary approach, and relatively low prevalence.

The purpose of this work is to describe the peculiarities of the course and diagnosis of leukoencephalopathy on the background of skin melanoma treatment with the use of checkpoint inhibitors. A clinical case of a patient with melanoma IIC who developed retrograde amnesia and convulsive syndrome on the background of immunotherapy is presented. On the basis of clinical picture and examination data the diagnosis of «leukoencephalopathy» was established. Any organs and systems can be affected during the whole period of ICT treatment. Clinicians should keep in mind the possibility of leukoencephalopathy development after the start of this therapy.

Ovarian cancer is a serious problem in clinical oncology due to the frequent detection of the disease in late stages, as well as the extremely low effectiveness of treatment at the stage of development of resistance to platinum drugs. The use of immunotherapy in this setting is not a standard option, but several early phase trials of its potential effectiveness are described in the literature. This clinical case presents a successful experience with the use of immune checkpoint inhibitors in a pretreated patient with platinum-resistant metastatic ovarian cancer, which was accompanied by various immune-related adverse events.

Primary involvement of the pancreas in non-Hodgkin’s lymphoma is very rare. The symptoms of the tumor are nonspecific, and the results of instrumental diagnostics are often similar to pancreatic adenocarcinoma. Considering the fundamental differences in approaches to treatment and prognosis of these diseases, making an accurate diagnosis is only possible through morphological examination of tumor tissue samples. The difficulty of collecting a sufficient number of tissue samples, especially for immunohistochemical analysis, and the need for repeated tumor biopsies, in some cases lead to unnecessary surgical interventions.

The process of tumor differentiation is a central aspect of the histopathological classification of solid malignancies and is closely related to the biological behavior of the tumor (poorly differentiated tumors/dedifferentiated tumors are known to be more aggressive than more differentiated tumors). The mechanisms by which tumor cell differentiation is disrupted are poorly understood, but pathologists and molecular tumor biologists have introduced the concept of dedifferentiation to explain the phenotypic changes that occur in solid tumors. In this review, we discuss a case of detection of dedifferentiated cancer, where even with the help of molecular testing of a tumor sample, we were not completely able to unambiguously determine the original source of the process, which entailed difficulties in choosing treatment tactics. And the main question that we asked ourselves during the treatment process: should treatment be based on molecular markers identified in the tumor, or should treatment be carried out according to the recommendations for the treatment of tumors of an undetected primary location with empirically selected chemotherapy?

Desmoid tumor (DO) is a rare monoclonal connective tissue tumor arising from deep soft tissues, characterized by invasive growth and a tendency to local relapses and incapable of metastasis [1].

The purpose of presenting this clinical case is to assess the significance of timely diagnosis, the choice of an individually correct treatment method, tactics of further observation, therapy.

To achieve this goal, a number of literature sources were studied, a clinical case of surgical treatment of a desmoid tumor of the anterior abdominal wall was presented in our medical institution (Northwestern State Medical University named after I.I.Mechnikov, St. Petersburg).

The difficulty of the case was the significant size of the indolent tumor, insensitive to systemic therapy, in a young man, and therefore the decision on surgical treatment tactics was also ambiguous. In each clinical case, it is worth taking an individual approach to treatment tactics. When choosing observational tactics, strict outpatient monitoring and regular follow-up should be performed.