RU2553378C1 - Differential diagnostic technique for high differentiated cancer in patients with nodular forms of thyroid diseases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: fine-needle aspiration of nodular thyroid growths is controlled by ultrasonic examination. A puncture needle containing an aspirate is washed twice in normal saline 1 ml, centrifuged; a supernatant is selected, and thyroglobulin is measured by enzyme immunoassay. If the thyroglobulin content is less than 272.5 ng/ml, the absence of high differentiated cancer is stated; the value falling within the range of 272.5-355.5 ng/ml shows a risk of high differentiated thyroid cancer; if the thyroid value is more than 355.5 ng/ml, high differentiated thyroid cancer is suspected.

EFFECT: invention provides the pre-operative differential diagnostics of high differentiated cancer in the patients suffering nodular forms of thyroid diseases, and also enables the further selection of an adequate method of treating.

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Description

The invention relates to medicine, namely to oncology, surgery, laboratory diagnostics, and can be used in the preoperative period to improve the differential diagnosis of highly differentiated cancer in patients with nodular forms of thyroid diseases to select an appropriate treatment method.

According to the WHO classification (1988), the following are the nodular forms of thyroid diseases: I. Nodular colloid goiter, to varying degrees, proliferating; II. Tumors: 1. Epithelial: a) benign; b) malignant; 2. Non-epithelial (benign and malignant) [1, 2]. Nodal forms of thyroid diseases are united by the presence of a “nodal formation” or “nodule” in the thyroid parenchyma. The term "nodular formation" or "node" means a focal formation of the thyroid gland, determined by palpation or using any visualization method, characterized by various morphological features [1, 2]. Due to the heterogeneity of the histostructure of nodular formations, difficulties arise in their differential diagnosis at the preoperative stage, which can lead to the wrong choice of treatment tactics. Oncomarkers are used for the differential diagnosis of cancer and benign diseases, including thyroglobulin [3, 4, 8].

Thyroglobulin is synthesized exclusively by thyroid cells (follicular A and B cells) of the thyroid gland and malignant tumors originating from follicular cells [3]. Highly differentiated malignant tumors actively produce thyroglobulin both in the thyroid gland and in its metastases in the lymph nodes [3]. However, the determination of thyroglobulin in blood serum does not have independent diagnostic value, since there are no differences in the level of its content in benign diseases and highly differentiated thyroid cancer [4].

However, an immunocytochemical study revealed that the expression of thyroglobulin increases directly in the tissue of a malignant thyroid tumor, in which case thyroglobulin can be considered a diagnostic indicator for highly differentiated thyroid cancer [5].

A known method for the study of thyroglobulin in flush with a puncture needle from the lymph nodes to detect metastases of thyroid cancer [6, 7]. However, this method is intended for the diagnosis of metastases only, and not for the differential diagnosis of highly differentiated cancer and benign nodular forms of thyroid diseases and does not contain indications of the diagnostic values of thyroglobulin.

A known method for the determination of thyroglobulin by enzyme-linked immunosorbent assay in blood serum [8]. The method [8] is characterized in that 1) the content of thyroglobulin is determined in the blood serum, and not directly in the tissue of the thyroid nodules; 2) based on this method, it is impossible to conduct differential diagnosis of highly differentiated cancer and benign nodal forms of thyroid diseases; 3) the indicated diagnostic indicators of thyroglobulin are relevant only for blood serum.

A known method for the study of thyroglobulin in the washout of an aspirate with a fine needle aspiration biopsy of nodular thyroid gland formation [9, 10]. The known method has the following disadvantages: 1) the methodology of the method is not disclosed; 2) only the average values of thyroglobulin in different clinical groups are indicated, but there are no diagnostic values of thyroglobulin necessary for the differential diagnosis of highly differentiated cancer and benign nodular forms of thyroid diseases. In the presented form, the known method [9, 10] cannot be used as a diagnostic method. This method is used as a prototype.

The objective of the invention is the creation of a method for the differential diagnosis of highly differentiated cancer in patients with nodular forms of thyroid disease to select an adequate treatment method.

The essence of the invention lies in the fact that in the method of differential diagnosis of highly differentiated cancer in patients with nodular forms of thyroid disease, including a fine-needle aspiration biopsy of nodules of the thyroid gland under the control of ultrasound, the puncture needle with the aspirate contained in it is washed twice with 1 ml of isotonic sodium solution chloride, then centrifuged, the supernatant is taken and thyroglobulin is determined by enzyme immunoassay, if the thyroglobulin content is less than 272.5 ng / ml - suggest the absence of highly differentiated thyroid cancer, in the range 272.5-355.5 ng / ml - the risk of highly differentiated thyroid cancer, higher than 355.5 ng / ml suggest highly differentiated thyroid cancer .

The proposed method was developed as a result of a study of thyroglobulin content in a cell aspirate obtained by fine-needle aspiration biopsy from nodules of the thyroid gland in 80 patients. Of these, 37 are patients with highly differentiated thyroid cancer and 43 are benign forms of nodular diseases (nodular colloid goiter, thyroid adenomas). Thyroglobulin was determined by enzyme-linked immunosorbent assay using an automated analyzer "Multiscan EX" (Finland) and a set of reagents for immunoenzymatic determination of thyroglobulin Thyroid IFA-TG (Russia, St. Petersburg). As a diagnostic threshold for highly differentiated thyroid cancer, a thyroglobulin level of more than 355.5 ng / ml has been established. The sensitivity of the method in the differential diagnosis of nodules of the thyroid gland was 64.9%, and the specificity was 95.3%. The area under the POC curve (AUC) was 0.85 ± 0.04, which, taking into account the expert scale for AUC values, refers to very good results [11]. The application of the proposed method in addition to standard research methods (ultrasound and cytological studies) allowed to increase the sensitivity in differential diagnosis from 64.9% to 86.5%, and specificity from 62.8% to 92.9%. The levels of thyroglobulin in the washout of the thyroid aspirate from the puncture needle for benign thyroid nodular diseases (single-multinodal colloid goiter, benign tumors) were found to be less than 272.5 ng / ml, the risk of highly differentiated thyroid cancer in the range of 272.5-355 , 5 ng / ml and highly differentiated thyroid cancer - above 355.5 ng / ml.

The proposed method is as follows: 1) perform a fine-needle aspiration biopsy of nodules of the thyroid gland under ultrasound control and receive a cell aspirate; 2) a puncture needle (21G) containing the obtained aspirate is washed twice with 1 ml of isotonic sodium chloride solution and the resulting mixture is placed in a special tube; 3) centrifuge and select the supernatant; 4) conduct an enzyme immunoassay; 5) analyze the results: if the value of thyroglobulin is less than 272.5 ng / ml - suggest the absence of highly differentiated cancer and the likelihood of benign thyroid disease, in the range 272.5-355.5 ng / ml - the risk of highly differentiated thyroid cancer, above 355, 5 ng / ml suggest highly differentiated thyroid cancer.

The application of the method may have important diagnostic value in case of an uncertain cytological diagnosis, which includes a "follicular tumor" of the thyroid gland. “Follicular tumor” means the possibility of cancer or adenoma of the thyroid gland without significant differences between these diseases, which can lead to the wrong choice of surgical treatment [12]. The true diagnosis is established only after postoperative histological examination of the removed drug based on the presence of tumor invasion of the capsule and blood vessels [12].

We give examples of practical implementation of the proposed method.

Example 1

Patient S., 53 years old (medical history No. 2808/11), was admitted to the clinic with complaints of the presence of nodular formation in the neck. An anamnesis of the disease for 9 months, when an examination by an endocrinologist revealed nodular formation of the thyroid gland. Rapid node growth over the past 3 months. Concomitant diseases: type 2 diabetes mellitus, hypertension. Upon receipt, the condition is satisfactory. The function of the thyroid gland is euthyroidism. On palpation, the thyroid gland is not enlarged, a nodular formation, rounded in shape, dense, with a diameter of up to 1.5 cm, is displaced during swallowing, is determined in the right lobe. Peripheral lymph nodes of the neck are not enlarged. Ultrasound of the thyroid gland: Right lobe 49 × 17 × 18 mm. In the upper pole of the right lobe is a hypoechoic node 16.8 × 10.8 mm with clear contours of a heterogeneous structure with peri-intranodular blood flow. Left lobe 50 × 17 × 18 mm without nodular formations. Conclusion of ultrasound: nodular formation of the thyroid gland. A fine-needle puncture aspiration biopsy was performed under ultrasound control with cytological examination and enzyme-linked immunosorbent assay for thyroglobulin content in the wash of aspirate from a puncture needle.

Cytological diagnosis: follicular tumor.

Thyroglobulin in the washout of the aspirate - 402.6 ng / ml.

Given the high level of thyroglobulin 402.6 ng / ml (<355.5 ng / ml), the data of ultrasound and cytological studies in patient C. established thyroid cancer T1N0MO. Patient S. is directed to surgical treatment. Surgical treatment, adequate from oncological positions, was performed - extrafascial thyroidectomy.

Postoperative histological diagnosis (No. 2218/11): follicular thyroid cancer.

This example indicates that based on the inclusion in the complex diagnosis of nodular thyroid formations, studies of the thyroglobulin content in the washout of thyroid aspirate, even with an uncertain cytological diagnosis, which is a “follicular tumor,” can more accurately diagnose the presence of thyroid cancer in the preoperative period and perform adequate volume of surgical treatment.

Example 2

Patient Sh., 57 years old (medical history No. 4666/10), was admitted to the clinic with complaints of the presence of nodular formation in the region of the right lobe of the thyroid gland. An anamnesis of the disease for 10 years, periodically observed by the endocrinologist, notes the gradual growth of the node. The function of the thyroid gland is euthyroidism. On palpation in the right lobe of the thyroid gland, a nodular formation of a round shape, normal density, with a diameter of up to 3 cm, is displaced during swallowing. Peripheral lymph nodes of the neck are not enlarged. Ultrasound of the thyroid gland: the entire right lobe is occupied by a hypoechoic node 25 × 13 × 19 mm with fuzzy contours, a rim, a homogeneous structure, with intranodular blood flow. The left lobe is not changed. Conclusion of ultrasound: nodular formation of the right lobe of the thyroid gland. A fine-needle puncture aspiration biopsy was performed under ultrasound control with cytological examination and enzyme-linked immunosorbent assay for thyroglobulin content in the wash of aspirate from a puncture needle.

Cytological diagnosis: follicular tumor.

Thyroglobulin in aspirate flush - 82.8 ng / ml.

Given the thyroglobulin level of 82.8 ng / ml (<272.5 ng / ml), the results of ultrasound and cytological studies in patient Sh. Suggest that there is no thyroid cancer and a benign disease, thyroid adenoma is most likely. Patient Sh. Is directed to surgical treatment. The removal of the right lobe of the thyroid gland - hemithyroidectomy.

Postoperative histological diagnosis (No. 4823/10): adenoma from Ashkenazi cells, nodular colloid goiter.

The indicated example shows that the study of thyroglobulin content in aspirate washout in the complex diagnosis of thyroid nodules even with an uncertain cytological diagnosis (“follicular tumor”) allows us to exclude thyroid cancer and suggest adenoma. In this connection, it became possible to perform organ-saving surgery (hemithyroidectomy) while preserving the left lobe of the thyroid gland.

Example 3

Patient G., 66 years old (medical history No. 8471/10), was admitted to the clinic with complaints of an enlarged thyroid gland. In 1986, a thyroid resection. Relapse after 8 years. The function of the thyroid gland is hypothyroidism. On palpation in the right lobe of the thyroid gland, a nodular formation is up to 2 cm in diameter, in the left - 1.5 cm. Nodules of soft-elastic consistency, displaced by swallowing. Peripheral lymph nodes are not enlarged. Ultrasound of the thyroid gland: in the left lobe - hypoechoic with a smooth contour nodular formation 23 × 22 mm with peri-intranodular blood flow. In the right lobe, the nodular formation is 15 × 11 mm isoechoic, with a fuzzy contour, intranodular blood flow. Conclusion of ultrasound: nodular formations of the thyroid gland.

A fine needle aspiration biopsy was performed under ultrasound control with cytological examination and enzyme-linked immunosorbent assay using thyroglobulin from a puncture needle.

Cytological diagnosis:

The node of the right lobe is a follicular tumor; the node of the left lobe is a colloidal goiter.

Thyroglobulin in the flush of aspirate from the node of the right lobe - 288.6 ng / ml.

Thyroglobulin in the washout of the aspirate from the node of the left lobe - 120.4 ng / ml.

Given the level of thyroglobulin 288.6 ng / ml (in the range of 272.5-355.5 ng / ml), ultrasound and cytological examination in patient G. suggest cancer of the right lobe of the thyroid gland and benign disease (colloid goiter) of the left lobe.

Patient Sh. Is directed to surgical treatment. Thyroidectomy was performed.

Postoperative histological diagnosis (No. 8728/10): papillary cancer of the right lobe of the thyroid gland, nodular macrofollicular goiter of the left lobe.

The indicated example shows that in complex diagnostics, the study of thyroglobulin content in the flush of aspirate from nodular formations contributes to a more accurate differential diagnosis for multinodular thyroid formations in the preoperative period and the choice of adequate surgical tactics.

The technical result of using the invention is to improve the differential diagnosis of highly differentiated cancer in patients with nodular forms of thyroid diseases in the preoperative period to select an appropriate treatment method.

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Claims (1)

A method for the differential diagnosis of highly differentiated cancer in patients with nodular forms of thyroid disease, including conducting a fine needle aspiration biopsy of nodular thyroid formations under ultrasound examination, characterized in that the puncture needle with the aspirate contained in it is washed twice with 1 ml of isotonic sodium chloride solution, then centrifuged supernatant is selected and thyroglobulin is determined by enzyme-linked immunosorbent assay, and if the content of ty rheoglobulin less than 272.5 ng / ml - suggest the absence of highly differentiated thyroid cancer, in the range of 272.5-355.5 ng / ml - the risk of highly differentiated thyroid cancer, above 355.5 ng / ml suggest highly differentiated thyroid cancer.