Diagnosis and treatment of thyroid cancer in adult patients - Recommendations of Polish Scientific Societies and the National Oncological Strategy. 2022 Update [Diagnostyka i leczenie raka tarczycy u chorych doroslych - Rekomendacje Polskich Towarzystw Naukowych oraz Narodowej Strategii Onkologicznej. Aktualizacja na rok 2022].

The guidelines Thyroid Cancer 2022 are prepared based on previous Polish recommendations updated in 2018. They consider international guidelines - American Thyroid Association (ATA) 2015 and National Comprehensive Cancer Network (NCCN); however, they are adapted according to the ADAPTE process. The strength of the recommendations and the quality of the scientific evidence are assessed according to the GRADE system and the ATA 2015 and NCCN recommendations. The core of the changes made in the Polish recommendations is the inclusion of international guidelines and the results of those scientific studies that have already proven themselves prospectively. These extensions allow de-escalation of the therapeutic management in low-risk thyroid carcinoma, i.e., enabling active surveillance in papillary microcarcinoma to be chosen alternatively to minimally invasive techniques after agreeing on such management with the patient. Further extensions allow the use of thyroid lobectomy with the isthmus (hemithyroidectomy) in low-risk cancer up to 2 cm in diameter, modification of the indications for postoperative radioiodine treatment toward personalized approach, and clarification of the criteria used during postoperative L-thyroxine treatment. At the same time, the criteria for the preoperative differential diagnosis of nodular goiter in terms of ultrasonography and fine-needle aspiration biopsy have been clarified, and the rules for the histopathological examination of postoperative thyroid material have been updated. New, updated rules for monitoring patients after treatment are also presented. The updated recommendations focus on ensuring the best possible quality of life after thyroid cancer treatment while maintaining the good efficacy of this treatment.

Occurrence of Arrhythmias in Women with Thyroid Cancer Receiving Suppressive Doses of Levothyroxine.

Aim of the study: To assess the occurrence of cardiac arrhythmias caused by high doses of levothyroxine in patients with thyroid cancer with subclinical hyperthyroidism. Materials and Methods: This prospective study included 98 women divided into three groups according to plasma thyroid stimulating hormone (TSH) concentration: <0.1 µU/mL, 0.1-0.39 µU/mL, or 0.4-4.0 µU/mL (control group). All participants underwent laboratory tests and an electrocardiography (ECG) Holter test to assess their heart rate and the occurrence of arrhythmias. Statistical analysis assessed differences between groups in all clinical parameters and factors influencing the occurrence of arrhythmias. Results: There were no differences between groups in the maximum, average, or minimum heart rate or in the incidence of the studied cardiac arrhythmias. Heart rate in women with a TSH concentration of <0.1 µU/mL depended on age and the presence of arterial hypertension, and heart rate in women with a TSH concentration of 0.4-4.0 µU/mL depended on free triiodothyronine concentration and the presence of arterial hypertension; no relationship was identified for women with a TSH concentration of 0.1-0.39 µU/mL. One-way logistic regression analysis did not identify any factors influencing the occurrence of arrhythmias. Conclusions: While maintaining normal free triiodothyronine levels, the use of suppressive doses of levothyroxine after thyroidectomy for differentiated thyroid cancer does not induce clinically significant arrhythmias or affect average heart rate. None of the studied clinical parameters influenced the risk of arrhythmia.

Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer.

Intra-tumor heterogeneity (ITH) results from the coexistence of genetically distinct cancer cell (sub)populations, their phenotypic plasticity, and the presence of heterotypic components of the tumor microenvironment (TME). Here we addressed the potential association between phenotypic ITH revealed by mass spectrometry imaging (MSI) and the prognosis of breast cancer. Tissue specimens resected from 59 patients treated radically due to the locally advanced HER2-positive invasive ductal carcinoma were included in the study. After the on-tissue trypsin digestion of cellular proteins, peptide maps of all cancer regions (about 380,000 spectra in total) were segmented by an unsupervised approach to reveal their intrinsic heterogeneity. A high degree of similarity between spectra was observed, which indicated the relative homogeneity of cancer regions. However, when the number and diversity of the detected clusters of spectra were analyzed, differences between patient groups were observed. It is noteworthy that a higher degree of heterogeneity was found in tumors from patients who remained disease-free during a 5-year follow-up (n = 38) compared to tumors from patients with progressive disease (distant metastases detected during the follow-up, n = 21). Interestingly, such differences were not observed between patients with a different status of regional lymph nodes, cancer grade, or expression of estrogen receptor at the time of the primary treatment. Subsequently, spectral components with different abundance in cancer regions were detected in patients with different outcomes, and their hypothetical identity was established by assignment to measured masses of tryptic peptides identified in corresponding tissue lysates. Such differentiating components were associated with proteins involved in immune regulation and hemostasis. Further, a positive correlation between the level of tumor-infiltrating lymphocytes and heterogeneity revealed by MSI was observed. We postulate that a higher heterogeneity of tumors with a better prognosis could reflect the presence of heterotypic components including infiltrating immune cells, that facilitated the response to treatment.

Artificial Intelligence Improves the Accuracy in Histologic Classification of Breast Lesions.

OBJECTIVES: This study evaluated the usefulness of artificial intelligence (AI) algorithms as tools in improving the accuracy of histologic classification of breast tissue. METHODS: Overall, 100 microscopic photographs (test A) and 152 regions of interest in whole-slide images (test B) of breast tissue were classified into 4 classes: normal, benign, carcinoma in situ (CIS), and invasive carcinoma. The accuracy of 4 pathologists and 3 pathology residents were evaluated without and with the assistance of algorithms. RESULTS: In test A, algorithm A had accuracy of 0.87, with the lowest accuracy in the benign class (0.72). The observers had average accuracy of 0.80, and most clinically relevant discordances occurred in distinguishing benign from CIS (7.1% of classifications). With the assistance of algorithm A, the observers significantly increased their average accuracy to 0.88. In test B, algorithm B had accuracy of 0.49, with the lowest accuracy in the CIS class (0.06). The observers had average accuracy of 0.86, and most clinically relevant discordances occurred in distinguishing benign from CIS (6.3% of classifications). With the assistance of algorithm B, the observers maintained their average accuracy. CONCLUSIONS: AI tools can increase the classification accuracy of pathologists in the setting of breast lesions.

Spectroscopic identification of benign (follicular adenoma) and cancerous lesions (follicular thyroid carcinoma) in thyroid tissues.

Thyroid follicular nodules are quite common in the population, however only a small proportion is malignant. Thyroid cancer differs from adenoma by features of cellular atypia, angioinvasiveness and possibility of metastasis via blood vessels mainly in the lungs and bones. Pathomorphological examination of the postoperative material plays a significant role in the diagnosis of cystic thyroid lesions. De facto, there is no possibility to determine with certainty whether the lesion is benign or malignant before surgery, therefore new methods are being sought to meet clinical needs. The study aimed to investigate if Fourier-transform infrared spectroscopy (FTIR) spectroscopy and Raman spectroscopy combined with multidimensional analysis can be a useful tool in distinguishing between thyroid adenomas and carcinomas. The obtained results indicate quantitative and qualitative alterations within proteins and fats derived from patients' tissues samples. Raman spectroscopy additionally shows significant changes in the amount of tissue collagen due to the pathogenic process. In the spectra of the second FTIR derivative, shifts of vibrations corresponding to the ß-sheet and α-helix structure are observed towards the lower rates of wave numbers in the case of neoplastic tissues. Using the leave-one-out cross-validation, sensitivity and specificity calculated with Principal Component Analysis-Linear Discriminant Analysis (PCA-LDA) clearly shows the possibility to distinguish between pathologically changed and normal thyroid tissue as well as differentiate follicular thyroid adenoma (FTA) from widely invasive follicular thyroid carcinoma (WI-FTC) tissues.

Spectroscopic analysis of normal and neoplastic (WI-FTC) thyroid tissue.

Thyroid cancer holds the first place of the malignant tumors of the endocrine system. One of the less common thyroid cancers is follicular thyroid carcinoma (FTC), which is very difficult to diagnose because it gives the same image as adenoma, which is benign. Certainty of the diagnosis is gained only when FTC gives metastases. Therefore, it was decided to compare normal and neoplastic (FTC) thyroid tissues with Fourier Transform Infrared (FTIR) spectroscopy. The obtained FTIR spectra and Principal Component Analysis (PCA) allowed us to conclude that there are differences in the FTIR spectrum between normal tissues and those affected by cancer. In addition, the results indicate that there is a decrease in the number of functional groups that build cellular and tissue structures in tumoral tissues. The shifts of wave numbers corresponding to the protein and lipid function group vibrations, as well as the calculated second derivative of the FTIR spectra showed the structural changes in neoplastic tissues. Moreover, the deconvolution of the amide I massif indicates that in cancerous tissues the prevailing secondary structure is ß-sheet structure, while in normal tissues it is α-helix. The obtained results allow us to conclude that infrared spectroscopy, in addition to providing information on the composition of tested samples, can be an excellent diagnostic tool contributing to understanding the FTC substrate.

Clinical importance of follicular lesion of undetermined significance (diagnostic category III according to Bethesda System) diagnosed from Fine-Needle Aspiration Biopsy.

INTRODUCTION: Follicular Lesion of Undetermined Significance (FLUS) belongs to the most controversial category of the Bethesda System. The aim of the study was to specify the risk of malignancy in patients with FLUS diagnosis in the material from the Institute of Oncology in Gliwice. This is the first Polish study specifying the risk of malignant neoplasm presence when Fine-Needle Aspiration Biopsy (FNAB) results in a report of diagnostic category III (DC III). MATERIAL AND METHODS: Three hundred and ninety-five primary DC III diagnoses from FNABs of the thyroid gland performed from 2010 to 2015 were analysed. Correspondence of DC III with diagnoses from repeated FNABs and histopathology reports was evaluated. RESULTS: From 395 DC III patients, 27 were treated surgically for clinical indications, receiving six diagnoses of cancer. Repeat FNAB was performed in 180 cases, and primary diagnosis was confirmed in 41 cases. In the second FNAB there was one diagnosis of "Papillary Thyroid Carcinoma" and one "Suspicious for Papillary Thyroid Carcinoma". From eight patients treated surgically in these series prior cytological cancer diagnosis was confirmed in two cases. Forty-six patients were subjected to third and subsequent FNABs; in one case the diagnosis was "Suspicious for Malignancy". In the analysed material the risk of cancer in patients with FLUS is 2.78%. Taking into account all 56 subsequent FNABs in which the primary diagnosis was confirmed, the risk decreases to 2.43%. CONCLUSIONS: The diagnosis of FLUS in the absence of clinical indications is not a basis for surgical treatment.

Suspicious for follicular neoplasm or follicular neoplasm? The dilemma of a pathologist and a surgeon.

INTRODUCTION: Cytological material obtained from Fine Needle Aspiration Biopsy (FNAB) does not permit us to distinguish between follicular carcinomas, adenomas, and hyperplastic nodules. The limitations of the method are: lack of possibility to assess the presence of tumour capsule, eventual capsular invasion, and angioinvasion. An unequivocal conclusion of whether what we have to deal with is a neoplastic or benign lesion is possible only after histopathological examination. The aim of the study was to confirm justification for using the term "Suspicious for Follicular Neoplasm" (SFN) in cytological diagnostics of thyroid carcinoma. MATERIAL AND METHODS: Three hundred and fifty-two primary SFN FNAB diagnoses (diagnostic category IV [DC IV] - according to Bethesda System) obtained from 2010 to 2015 in the Institute of Oncology in Gliwice were analysed, and their correlation with histopathological diagnoses was verified. RESULTS: In the Institute of Oncology in Gliwice, 352 primary SFN diagnoses (diagnostic category IV [DC IV] - according to Bethesda System) were established. Surgical treatment was undertaken after first FNAB in six cases, giving confirmation of a neoplasm in five cases, one of which was a follicular carcinoma. Second FNAB performed in 90 patients confirmed DC IV diagnosis in 53 cases. Third FNAB concerned 26 patients, providing another 14 diagnoses of DC IV. 26 out of 352 patients were subjected to surgery, and then histopathological examination confirmed a neoplasm in 19 cases (which comprises 73%), five of which were carcinomas. CONCLUSIONS: High positive predictive value PPV = 73% of SFN diagnosis justifies undertaking surgical treatment in any case of this diagnosis.