Difficulties of differential diagnosis of lymphomas using the example of a clinical case


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Abstract

Introduction. Pathologies of the lymphatic system are a large group of diseases, the differential diagnosis of which is difficult in all groups of patients, especially in children. The issue of differential diagnosis of lymphomas, in particular, using ultrasound diagnostic methods, has been little studied, which is why it is relevant for study. The authors of the work analyzed a clinical case in order to assess the difficulties of identifying and differential diagnosis of lymphomas; The objectives include the study of literary sources on the topic, compared with the results of the study in the clinical case under review. The study was conducted on the basis of the Collective Clinical Hospital No. 2 using a specific clinical case with a description. During the writing of the work, statistical data was assessed, a general description of the characteristics of lymphomas and their clinical manifestations was given; the importance of their differential diagnosis and its features in pediatric patients is assessed, and diagnostic options using instrumental and histological research methods are given. In conclusion, conclusions from the study are presented. Along with this, the authors point out the importance of further study of the issue, and also compare the research output with existing literature data.

Full Text

Relevance. Lymphomas in children are a relatively rare, but quite serious pathology, the incidence increases every year. In this regard, there is an increasing need for differential diagnosis of neoplasms with diseases such as acute bacterial and viral lymphadenitis, tuberculosis, infectious mononucleosis, anaplastic large cell lymphoma, Kawasaki disease, non-Hodgkin lymphomas, etc. The “golden” standard in studying the etiology of changes in lymph nodes is a biopsy of the neoplasm , instrumental research methods allow one to avoid invasive procedures, which significantly reduces the risk of complications, and are also the preferred diagnostic method. When diagnosing pathologies of lymph nodes, high-resolution echography is characterized by high sensitivity in comparison with clinical examination - 97% and 73%, respectively. At the same time, the specificity of ultrasound examination reaches 93% when combining echography with fine-needle puncture, which defines echography as an ideal visual tool for assessing adenopathy in the neck. Ultrasound is the most common and highly accurate method for examining lymph nodes, however, ultrasound differential diagnosis of lymphomas has not been studied enough, the issue is actively discussed, which makes its study relevant. Introduction. Hodgkin's lymphoma (B-cell lymphoma) is a malignancy affecting the lymph nodes and is characterized by the presence of atypical multinucleated Berezovsky-Reed-Sternberg cells and their precursors, mononuclear basophilic Hodgkin cells. A distinctive feature of HL in childhood is considered to be a tendency to extranodal location, as well as widespread lesions without clear localization, i.e. diffuse. Children with severe immunosuppression (infected with the Epstein-Barr virus, autoimmune diseases (rheumatoid arthritis, SLE), etc.) are especially at risk of developing the disease. Clinical manifestations of Hodgkin's lymphoma are not immediately detected, and complaints for the most part are not specific, but a separate concept is distinguished - lymphoproliferative symptom complex. It includes the following manifestations: enlarged lymph nodes (primarily cervical); general weakness, weight loss of more than 10% over several months, low-grade body temperature (symptoms of intoxication due to the production of cytokines by Hodgkin cells), prolonged cough, pain, itching. Cough is often caused by an increase in intrathoracic and mediastinal lymph nodes, manifested by signs of bronchial obstruction (without an inflammatory process) when assessing the function of external respiration. Lymphoblastic leukemia and metastasis of retinoblastoma to lymph nodes can give a similar clinical picture. According to the classification of the World Health Organization, there are 2 types of Hodgkin lymphomas: classical HL; nodular HL with lymphoid predominance. Nodular HL is much less common and is characterized by the formation of separate nodes without mixing with surrounding tissues. The “gold standard” for diagnosing Hodgkin lymphoma and establishing the appropriate diagnosis is immunohistochemical analysis of biopsy material, a general blood test, a biochemical blood test, as well as instrumental research methods. The final diagnosis is made only after confirming the presence of the above-mentioned histological picture by biopsy. [1] In 2021, in the Voronezh region, Hodgkin lymphoma was detected in 40 patients, however, it is not possible to establish the age range of patients due to the lack of specific statistics. The prevalence of various types of lymphoma in patients under 34 years of age is about 15.8%. HL in childhood is rare in children under 5 years of age, accounting for 40% of cases among all lymphomas; in the age group up to 12 years, boys are more often affected; in adolescents, the ratio of HL in boys and girls is approximately the same. The incidence of HL in children is 0.7-0.9 per 100,000 children (according to International registries). [2] The purpose of the work is to analyze a clinical case to assess the difficulties of identifying lymphomas in children and confirm scientific literature data on the issue under study. The objectives of the work are: search, study and systematization of information from literary sources; description of a clinical case; justification of the output data of the conducted research; processing of the received data. Materials and research methods. The study was carried out on the basis of the BUZ VO "VODKB No. 2" using methods of description, analysis, synthesis and induction. Research results. A promising option for differential diagnosis of various types of lymphomas, especially Hodgkin lymphoma, is the use of instrumental research methods. Ultrasound is a universal method for examining lymph nodes; its advantages include the availability and wide applicability of the method, its safety and high cost relative to other research methods. Contrast-enhanced ultrasound (CEUS) and color Doppler ultrasound (CDC) have become increasingly widespread, allowing detection of changes in the shape and structure of lymph nodes, as well as assessment of blood flow characteristics. CEUS allows you to determine not only quantitative, but also qualitative accumulation and distribution of contrast. In the presence of a malignant neoplasm, the pattern of distribution of the echo-contrast substance is a hyper-contrast, heterogeneous distribution, while in a benign course, polymorphic foci of a heterogeneous structure are often detected. In this case, it is preferable to use compression elastography, which has greater sensitivity and specificity. The use of these differential diagnostic methods can significantly reduce the invasiveness of a classic study with biopsy material sampling. [3] It is advisable to carry out ultrasound examination in B-mode using color dispersion and elastography, which increases the accuracy of differential diagnosis of lymphoproliferative processes and lymphadenitis. [4] For the differential diagnosis of lymphomas and malignant gliomas of the central nervous system, the effectiveness of using multiparametric MRI mapping and multislice computed tomography (MSCT) is discussed. Lymphomas have a hypointense signal in T1 and an isointense signal in T2 with clear homogeneous accumulation of contrast agent, vasogenic edema. [5] Differential diagnosis of pathologies of the lymphatic system in children is difficult. This is due to a significant limitation not only by the complexity of most methods in children, but also by direct contraindications associated with the age of the patients. For this reason, the first-line method in diagnosing diseases of any system, including the lymphatic system, is ultrasonography. Let us consider in more detail the differential ultrasound diagnosis of lymphomas. When the lymph nodes are enlarged, the echogram visualizes a hyperechoic thickening of the capsule in the area of the node's hilum. The difference between the lymphoproliferative process and the inflammatory process lies in the change in the lumen of the vessels entering the lymph node through its gate (in the first case, they are compressed by tumor cells). The cortical substance of the parenchyma of the altered lymph node differs slightly from the brain; diffuse heterogeneous hypoechogenicity is noted, sometimes there are areas of anechoicity; the shape of the lymph node, along with its dimensions, has been changed. In the CDC mode, the blood flow in the parenchyma is practically unchanged when the process is benign, while malignant neoplasms are characterized by a clear picture of increased blood flow intensity both in the center and in the capsule area. It should be noted that in non-Hodgkin lymphomas, the lesion mainly affects the axillary, retrosternal, paracardial and peripheral lymph nodes, the spread occurs to non-adjacent areas by specific “jumps”, while in Hodgkin lymphoma the involvement of adjacent groups of lymph nodes in the pathological process is typical. However, the information obtained from B-mode research is often sufficient only to differentiate diseases of inflammatory and non-inflammatory etiology, as well as to assume the presence of a lymphoproliferative process; in the case of lymphomas, the method may not be informative enough. For a more detailed study of the structure, it is preferable to perform elastography, which allows one to evaluate the elastic properties of lymph nodes. It should be noted that the color compression elastogram image is superimposed on the gray scale B-image. Thus, Hodgkin's lymphoma is manifested predominantly by blue staining, which indicates a significant rigidity of the lymph node structure, while non-Hodgkin's lymphomas are characterized by heterogeneous staining in shades of green, blue and red (the predominance of a rigid structure along the periphery, closer to the capsule), or intense blue staining with significant green inclusions (heterogeneous-hard structure of the entire parenchyma). [6]The next stage of the study is the study of a clinical case. Patient 15 years 8 months. She was admitted to the BUZ VO “VODKB No. 2” with complaints of an uneven increase in the volume of the neck and a thickening in the neck area in the supraclavicular region on the left. History: considers herself sick for about a month, when she independently felt a painless lump in the supraclavicular area on the left; There are no other complaints. Other groups of lymph nodes (submandibular, mental, supraclavicular on the right, subclavian, retrosternal, ulnar, femoral, inguinal) are not enlarged, the structure is not changed. She was routinely sent for an ultrasound examination of the neck area. During a polypositional differential examination, a hypoechoic conglomerate is visualized, closer to a round shape with fuzzy even contours, measuring 3.9x2.5 cm (bordered by a capsule). The echostructure is heterogeneous due to even more hypoechoicny inclusions, as well as areas of increased echogenicity (Fig. 1-4). Blood flow during CDK is not reliably determined. Conclusion: formation (more data on a malignant lesion) of the left supraclavicular region - lymphoma (?). Subsequently, the patient was referred for a fine-angle biopsy under ultrasound control to obtain the results of a histochemical study. The ultrasound picture did not quite correspond to the typical signs of malignant lymphomas, since the echostructure in this case is usually homogeneous, the hilum is clearly visible, and a distinct vascular pattern is determined. Conclusion. Despite the fact that the differential diagnosis of lymphomas is still insufficiently studied and significantly complicated, ultrasound is a highly effective method of preliminary diagnosis compared to other diagnostic methods. Adenopathy, in particular lymphoma, is a rather complex pathology that requires early differential diagnosis, especially in children. In this vein, ultrasound can be considered a fairly effective differential method. diagnosis of neoplasms with the following types of lymphopathies: Hodgkin and non-Hodgkin lymphomas, lymphadenitis, tuberculosis in the lymph nodes, necrotic melting of lymph node structures. For this purpose, B-mode, elastography, and color circulation are used. Ultrasound methods are low-traumatic, they can be combined with any type of procedure in order to increase the specificity of the study, especially with fine-angle biopsy in the diagnosis of lymphomas of various etiologies. Thus, ultrasound is a highly informative method, ideal for screening and differential diagnosis of lymph node pathologies. Further study of the topic will make it possible to more specifically define clear criteria and increase the efficiency of timely diagnosis.

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About the authors

Yaroslava Constantinovna Mikhailyuk

Voronezh State Medical University named after N.N. Burdenko

Email: lacerta.c8@gmail.com
ORCID iD: 0000-0002-6334-1449
SPIN-code: 7678-5370
Russian Federation, 10 Studencheskaya street, 394036 Voronezh, Russian Federation

Anastasia Sergeevna Ivanova

Voronezh State Medical University named after N.N. Burdenko

Author for correspondence.
Email: a.s.ivanova13@mail.ru
ORCID iD: 0000-0001-5643-4770
SPIN-code: 5117-0227
Scopus Author ID: 1133215

Assistant at the Department of Instrumental Diagnostics

Russian Federation, 10 Studencheskaya street, 394036 Voronezh, Russian Federation

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