RU2730941C1 - Method for differential diagnosis of peripheral lymph nodes affection in hodgkin's lymphomas and non-hodgkin's lymphomas using ultrasonic elastography - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method refers to medicine, namely to ultrasonic diagnostics, and can be used for differential diagnostics of peripheral lymph nodes affection in Hodgkin lymphoma (HL) and non-Hodgkin's lymphomas (NHL). Method comprises compression elastography, during which type of elastogram is determined: second type is characterized by inhomogeneity of the colour palette of colouring with shades of blue, green and red colours - elastographic features of heterogeneity of the lymph node with predominance of the rigid component along the periphery; third type is characterized by predominance of intense blue staining with inclusions of green colour shades - elastographic features of rigidly-non-uniform structure of lymph node in whole volume; fourth type is characterized by intensive blue staining of more than 90 % of lymph node volume - elastographic signs of rigid structure of lymph node. Further, shear wave is subjected to elastography, during which shear wave velocity is determined. If observing fourth type of elastogram and shear wave velocity 2.84 ± 0.79 m/s diagnose HL. If observing second or third type of elastogram and shear wave velocity of 2.47 ± 0.84 m/s NHL is diagnosed.

EFFECT: method provides differential diagnosis of peripheral lymph nodes affection in HL and NHL by detecting differences in elastic properties of altered peripheral lymph nodes.

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Description

The method relates to medicine and can be used to assess the elastic properties of altered peripheral lymph nodes in Hodgkin's lymphoma (HL) and non-Hodgkin's lymphomas (NHL) using ultrasound elastography for the differential diagnosis of these nosologies.

Malignant lymphomas are a heterogeneous group of malignant lymphoproliferative tumors that differ in morphological structure, biological properties, clinical manifestations, course and prognosis.

Modern diagnostics of lymphomas is a complex process that combines several research methods at once. Only this approach can provide accurate verification of the diagnosis, which serves as the basis for choosing the most effective treatment.

The "gold" standard in detecting the true causes of changes in lymph nodes is considered to be a biopsy of a tumor for the purpose of morphological assessment of its histogenesis and determination of the biological characteristics of the tumor [Kovaleva E.V., Danzanova T.Yu., Sinyukova G.T., Lepedatu P.I., Gudilina E.A. Kolyadina I.V., Zeynalova P.A., Semenova A.A. Multiparameter ultrasound diagnostics of altered lymph nodes in primary multiple malignant tumors, including breast cancer and lymphoma // Malignant tumors 2018; 8 (4): 37-44].

The disadvantage of this method is its invasive nature. In urgent oncohematological patients, invasive methods of obtaining tumor material may be impracticable due to the extremely high risk of lethal complications [AV Logachev, TT Kondratyeva, PA Zeynalova, DV Komov, TE Kochoyan. , Allakhverdieva G.F., Kashiya Sh.R. Accurate diagnosis of tumors of intrathoracic localization: the possibilities of an urgent cytological method // Bulletin of the Russian Oncological Center. N.N.Blokhin RAMS. 2017.Vol. 28.No. 1-2. S.86-88].

Modern capabilities of ultrasound diagnostics make a significant contribution to the issues of differential diagnosis of lymphoproliferative diseases. Today, ultrasound examination (ultrasound) is one of the main methods of visualization and assessment of lymph nodes. The advantages of ultrasound include: low cost, real-time examination and high resolution.

Differential diagnosis of HL and NHL with ultrasound of peripheral lymph nodes in the standard gray-scale B-mode is impossible due to the absence of pathognomonic signs between altered lymph nodes in these nosologies [Xin-Wu Cui, Jenssen C, Saftoiu A., Ignee A., Dietrich C.F. New ultrasound techniques for lymph node evaluation // World J Gastroenterol. 2013. V. 30. No. 19. P. 4850-4860]. Signs detected during the study of altered lymph nodes in the standard gray-scale B-mode, such as shape, contour, echo structure, give us insufficient information for a full differential diagnosis [Xin-Wu Cui, Jenssen C, Saftoiu A., Ignee A., Dietrich C .F. New ultrasound techniques for lymph node evaluation // World J Gastroenterol. 2013. V. 30. No. 19. P. 4850-4860]. The use of modern ultrasound technologies, such as elastography, allows a more detailed study of the structure, namely the elastic properties, of specifically altered lymph nodes. There are two types of elastography - compression and shear wave. Compression elastography is a method of qualitative assessment of stiffness using manual compression with further construction of color maps. Shear wave elastography is a method for quantifying the stiffness of the lymph nodes by using special amplified ultrasound pulses (groups of pulses), which cause secondary shear waves in the tissues, having a transverse direction with respect to the primary pulses. The speed of propagation of shear waves is directly proportional to the stiffness of the lymph node [Alymov Y. V., Sholokhov B. N., Podvyaznikov C.O., Mudunov A.M., Berdnikov S.N. New possibilities of ultrasound assessment of the state of the lymph nodes in the neck in cancer of the oral mucosa // Tumors of the head and neck. 2016.Vol. 6.No. 1. S. 33-38].

In the world literature, there are no studies devoted to the use of ultrasound elastography in the differential diagnosis of HL and NHL with lesions of peripheral lymph nodes. According to international sources, compression elastography and shear wave elastography were considered only as a tool in the diagnosis of metastatic and lymphoproliferative changes in lymph nodes with sensitivity, specificity and accuracy of 66.7-83.9%, 35.1-97.1% and 61.1 -84.5%, respectively [Lo W. C, Cheng PW, Wang CT, Liao LJ Real-time ultrasound elastography: an assessment of enlarged cervical lymph nodes. Eur. Radiol. 2013. No. 23. P. 2351-2357. Teng D. K., Wang H., Lin Y. Q., Sui G. Q., Guo F., Sun L. N. Value of ultrasound elastography in assessment of enlarged cervical lymph nodes. Asian Pac. J. Cancer Prev. 2012. No. 13.P. 2081-2085. Zhang Y., Lv Q., Yin Y., Xie M., Xiang F., Lu C, Yan T., Li W., Xu H., Huang Y. The value of ultrasound elastography in differential diagnosis of superficial lymph nodes ... Frontiers of Medicine in China. 2009. No. 3. P. 368-374. Choi Y.J., Lee J.H., Baek J.H. Ultrasound elastography for evaluation of cervical lymph nodes. Ultrasonography. 2015. No. 34. P. 157-164. Piscaglia F., Noise C, Dietrich C. F., Cosgrove D. O., Gilja O. H., Bachmann Nielsen M. et al. The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications. UltraschallMed. 2012. No. 33. P. 33-59.].

The objective of the invention is the differential diagnosis of altered lymph nodes in LH and NHL, taking into account their elastic properties.

Technical result:

The revealed differences in the elastic properties of the altered peripheral lymph nodes by the claimed method in HL and NHL contribute to the establishment of a preliminary diagnosis when biopsy is impossible.

The task is solved by performing compression elastography and shear wave elastography of altered peripheral lymph nodes in patients with HL and NHL. Compression elastography for altered lymph nodes in HL is characterized mainly by the fourth type of elastogram, and in NHL - the second and third types of elastograms; the shear wave velocity in the altered lymph nodes with HL is higher than with NHL: 2.84 ± 0.79 m / s and 2.47 ± 0.84 m / s, respectively.

The inventive method is illustrated in figures 1-4.

Figure 1. Gray-scale image of the altered left supraclavicular lymph node in standard B-mode.

Figure 2. Compression elastography of the altered left supraclavicular lymph node using eSie Touch technology.

Figure 3. Four-step classification of the qualitative assessment of elastograms obtained using compression elastography, proposed by Furukawa M.K. and co-authors in 2007.

Figure 4. Shear wave ultrasound elastography of the altered right supraclavicular lymph node using ARFI technology (Virtual Touch Quantification).

The inventive method is carried out as follows: the procedure is carried out in an ultrasound diagnostics room by an ultrasound diagnostics doctor using an ultrasound diagnostics apparatus equipped with specialized software for compression elastography and shear wave elastography with a linear high-frequency sensor. The study used a Siemens Acuson S2000 ultrasound machine equipped with ARFI (Virtual Touch Quantification - Shear Wave Elastography) and eSie Touch (Compression Elastography) technology.

At the first stage, the patients underwent ultrasound examination of peripheral lymph nodes in the B-mode with obtaining a gray-scale image of the altered superficial lymph node located at a distance of more than 2.0 cm from the vascular structures (Fig. 1).

At the second stage, the software for the compression elastography was activated. When this function is activated, the image on the screen is divided into two zones: a zone with a gray-scale image in B-mode and an elastogram zone, represented by superimposing a color compression image on a gray-scale B-mode. To obtain an elastogram of the altered lymph node for 5 seconds, light manual compression of the investigated structures was performed by the sensor until the moment when several consecutive static images containing a minimum amount of noise and artifacts were not displayed in the area of interest on the monitor screen. The hardness of the tissues on the screen was displayed in different colors - blue (characterizes hard tissue), green (moderately hard tissue) and red (soft tissue) (Fig. 2). The obtained elastograms were evaluated according to the four-stage classification of quality characteristics proposed by Furukawa M.K. et al. in 2007 [Furukawa M.K., Kubota A., Hanamura N., Furukawa M. Clinical application of real-time tissue elastography to head and neck cancer - evaluation of cervical lymph node metastasis with real-time tissue elastography. Nippon Jibiinkoka Gakkai Kaiho. 2007. Vol. 110.No.7. P. 503-505 (In Japanese)] (Fig. 3):

первый тип (мягкие) - характеризуется преобладанием зеленого окрашивания с включениями красного и синего цвета - эластографические признаки неоднородности лимфатического узла с преобладанием мягко-эластического компонента;

the first type (soft) - characterized by a predominance of green coloration with inclusions of red and blue - elastographic signs of lymph node heterogeneity with a predominance of a soft-elastic component;

второй тип (умеренно мягкие) - характеризуется неоднородностью цветовой палитры окрашивания оттенками синего, зеленого и красного цветов - эластографические признаки неоднородности лимфатического узла с преобладанием жесткого компонента по периферии;

the second type (moderately soft) - characterized by a heterogeneity of the color palette of staining with shades of blue, green and red - elastographic signs of heterogeneity of the lymph node with a predominance of a hard component along the periphery;

третий тип (умеренно жесткие) - характеризуется преобладанием интенсивного синего окрашивания с включениями зеленых оттенков цвета - эластографические признаки жестко-неоднородной структуры лимфатического узла во всем объеме;

the third type (moderately hard) - characterized by the predominance of intense blue coloration with inclusions of green shades of color - elastographic signs of a rigidly heterogeneous structure of the lymph node throughout the volume;

четвертый тип (жесткие) - характеризуется интенсивным синим окрашиванием более 90% объема лимфатического узла - эластографические признаки жесткой структуры лимфатического узла (наличие участка зеленого цвета может соответствовать сосудистой ножке лимфатического узла).

the fourth type (hard) - characterized by intense blue staining of more than 90% of the lymph node volume - elastographic signs of a rigid structure of the lymph node (the presence of a green area may correspond to the vascular pedicle of the lymph node).

According to the results of our study, it was revealed that during compression elastography for the altered lymph nodes in HL was characterized mainly by the fourth type of elastogram, and in NHL - the second and third types of elastograms.

At the third stage, shear wave elastography was performed using ARFI (Virtual Touch Quantification) technology. When this function is activated, the area of the altered lymph node is first determined to measure the shear wave velocity by overlaying a 0.7 × 0.5 cm window of interest on a standard gray-scale ultrasound image (Fig. 4). When measuring the shear wave velocity, the sensor was installed perpendicular to the area under study, the window of interest - in the area of the altered lymph node. The process of measuring the shear wave velocity was carried out in an automatic mode by sequentially pressing two buttons on the panel of the ultrasonic apparatus. At least 10 measurements are required to obtain a reliable average shear wave velocity.

In the course of the study, it was revealed that the shear wave velocity in the altered lymph nodes with HL is higher than with NHL, 2.84 ± 0.79 m / s and 2.47 ± 0.84 m / s, respectively.

In the period 2017-2018, 111 patients underwent ultrasound elastography of 195 altered lymph nodes. The preliminary diagnosis, established as a result of the performed elastography, coincided with the histological conclusion in 93.0% of cases.

Clinical examples

1. Patient K., 24 years old

Complaints: an uneven increase in the volume of the neck and induration in the supraclavicular region on the left.

Anamnesis: considers himself a patient for about two months, when she began to notice a seal in the left supraclavicular region with a further gradual uneven increase in neck volume. As planned, an ultrasound examination of the lymph nodes of the neck and supraclavicular regions was performed, during which enlarged lymph nodes with altered structure were revealed. A fine-needle aspiration biopsy was performed - lymphoproliferative disease was diagnosed without additional clarification. Sent to the N.N.Blokhin Oncology Research Center for further examination and further treatment.

At the first stage of diagnosis, the patient underwent ultrasound examination of peripheral lymph nodes using compression elastography and shear wave elastography. According to the results of the study: in the middle third of the neck on the left, several hypoechoic lymph nodes with sizes up to 2.1 × 1.3 cm, with increased blood flow are determined; in the left supraclavicular region, multiple hypoechoic lymph nodes up to 2.6 × 1.8 cm in size, heterogeneous structure, with increased blood flow are determined. Other groups of peripheral lymph nodes, such as submandibular, chin, cervical on the right, supraclavicular on the right, subclavian, axillary, inguinal, femoral, are not enlarged, the structure is not changed. According to elastography, the altered lymph nodes corresponded to type 4 elastogram, the shear wave velocity was 2.84 ± 0.79 m / s. A preliminary diagnosis of Hodgkin's lymphoma was established.

2. Patient A., 67 years old.

Complaints: general weakness, an increase in the volume of the cervical, axillary and inguinal lymph nodes.

Anamnesis: the patient considers himself ill for 2.5 months, when weakness appeared with little physical exertion and an increase in the size of the inguinal and axillary lymph nodes. I went to the doctor at the place of residence, during the examination, metastatic changes in the cervico-supraclavicular lymph nodes on both sides were suspected without an undetected primary focus. He was sent to the N.N.Blokhin National Medical Research Center of Oncology for further examination and further treatment.

At the first stage of diagnosis, the patient underwent ultrasound examination of peripheral lymph nodes using compression elastography and shear wave elastography. According to the results of the study: multiple altered lymph nodes are determined:

- in the chin area - up to 2.3 × 1.2 cm;

- in the submandibular areas: on the right - up to 2.2 × 1.1 cm, on the left - up to 2.2 × 1.0 cm,

- in the neck area: on the right - up to 3.1 × 1.3 cm, on the left - up to 1.8 × 0.5 cm,

- in the supraclavicular areas: on the right - up to 1.4 × 1.0 cm, on the left - 1.9 × 1.0 cm,

- in the subclavian areas: on the right - up to 2.5 × 1.0 cm, on the left - 1.3 × 1.0 cm;

- in the armpits: on the right - up to 5.3 × 1.9 cm, on the left - up to 3.7 × 2.0 cm,

- in the groin areas: on the right up to 4.4 × 3.1 cm, on the left up to 4.3 × 2.6 cm.

According to elastography, the altered lymph nodes corresponded to type 2–3 elastograms, the shear wave velocity was 2.47 ± 0.84 m / s. A preliminary diagnosis was made of non-Hodgkin's lymphoma of an unspecified type.

Claims (1)

A method for differential diagnosis of peripheral lymph node lesions in Hodgkin's lymphoma (HL) and non-Hodgkin's lymphomas (NHL) using ultrasound diagnostics, characterized in that the patient undergoes compression elastography, during which the type of elastogram is determined: the second type is characterized by the heterogeneity of the color palette of staining with shades of blue, green and red colors - elastographic signs of lymph node heterogeneity with a predominance of a rigid component along the periphery; the third type is characterized by the predominance of intense blue coloration with inclusions of green shades of color - elastographic signs of a rigidly heterogeneous structure of the lymph node throughout the volume; the fourth type is characterized by intense blue staining of more than 90% of the lymph node volume - elastographic signs of a rigid structure of the lymph node; thereafter, shear wave elastography is performed, during which the shear wave velocity is determined; when the fourth type of elastogram and the shear wave velocity of 2.84 ± 0.79 m / s are detected, LH is diagnosed, and when the second or third type of elastogram and the shear wave velocity is 2.47 ± 0.84 m / s, NHL is diagnosed.

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