Fine-needle Aspiration Biopsy Technique Research Articles

Mapping Thyroid Changes in Size and Position during Enlargement in Adult Mice with Hyperthyroidism.

The thyroid in Graves' disease undergoes a considerable divergence in size and position from the normal anatomy. However, knowledge of the pathological anatomy related to the change, which is required before planned surgical or local intervention, or diagnosis, is neglected. To investigate Graves' disease, we well-established a model of mice that successfully mimics all the signs presented in the clinic. Under a long-term immunization (35 weeks), the animals displayed a big heterogeneity in thyroid size, like the cases of natural occurrence. These thyroids in the model were sized into various phases and registered. A blend of the registered thyroids and the thyroid and tracheal cartilage landmarks led to the production of site-dependent incidence graphs of thyroid in the front view and on the section for each phase. The merger of the incidence graphs of all the phases resulted in thyroid phase-dependent topography. The depicted graphs illustrate the fine localization of the thyroid in various sizes and their dynamic changes during enlargement, which may facilitate currently used fine-needle aspiration biopsy and ultrasonography-guided biopsy techniques. Familiarity with the knowledge might avoid misclassifying an abnormality as normal, or vice versa, and be helpful for imaging diagnosis and local surgery therapy in Graves' disease.

Comparison of low-cost phantoms for ultrasound-guided fine-needle aspiration biopsy training.

Phantoms and simulators are widely accepted methods to gain valuable experience and confidence for inexperienced trainees prior to seeing their patient and for refining their skills. A phantom model that is durable, simple, and inexpensive to produce and use would be ideal to train practitioners in ultrasound-guided fine-needle aspiration biopsy (USFNA) technique. In this study, we systematically compared several low-cost phantom models including gelatin, extra firm tofu, canned cooked pork, ballistics gel, and chicken breast for their haptic properties, echogenicity, teaching utility, and overall performance based on a Likert scale (1-5; 5 = best). Nine cytopathologists and cytopathology fellows who perform FNA regularly evaluated these models and completed the survey. The gelatin phantom, with a gelatin to water ratio of 1:8 by weight, was found to be the best for USFNA practice and overall performance, followed by the 1:10 gelatin phantom. Tofu and chicken breast phantoms were also good low-cost alternatives that needed only a few minutes of total preparation time. Low-cost, homemade phantoms can serve as excellent alternatives to commercial phantoms for practicing and teaching USFNA.

Biopsy strategies for intermediate and high suspicion thyroid nodules with macrocalcifications

Objectives (1) To find strategies to improve diagnostic performance of ultrasound-guided biopsy of intermediate and high suspicion thyroid nodules with macrocalcifications. (2) To find malignancy rates of nodules with macrocalcification. Materials and methods From 2018 to 2022, fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) were retrospectively evaluated. Macrocalcifications were categorized into three types: intra-nodular, rim and entirely calcified. Diagnostic performance was compared between biopsy modes (FNAB vs. CNB) and FNAB techniques (to-and-fro vs. whirling). Multivariate logistic regression was performed to determine features associated with performance of FNAB. Malignancy rates were calculated according to macrocalcification types. Results A total of 114 procedures (87 FNAB and 27 CNB) in 89 nodules per 86 patients (mean age, 64 years; 76 women) were performed. Overall, CNB performed better than FNAB (unsatisfactory rate: 3.7% vs. 33.3%, p = .005). For macrocalcification thicker than 2 mm, whirling FNAB technique demonstrated a comparable unsatisfactory rate with statistical trends toward significance (to-and-fro: 69.2% vs. whirling: 27.8%, p = .055). The entirely calcified nodule was associated with poor performance of FNAB (adjusted odds ratio 4.46 [95% CI: 1.19–16.67], p = .027). Overall malignancy was 22.5%, higher in intra-nodular macrocalcification than rim and entirely calcified types (68.4% vs. 21.1% vs. 10.5%, p = .025). Conclusion For the entirely calcified type, CNB should be considered first to improve diagnosis. For other types, FNAB can be performed, and whirling technique may be an alternative technique in thicker macrocalcification. Malignancy in intermediate and high suspicion nodules with macrocalcification have non-negligible rates.

Оценка диссеминации увеальной меланомы по склеральному каналу при тонкоигольной аспирационной биопсии

Introduction. Fine needle aspiration biopsy (FNAB) of uveal melanoma (UM) is an invasive procedure. Many authors consider UM FNAB to be safe procedure, however extraocular extension of the tumor through the scleral tracts may occur. Current studies of scleral tracts after FNAB do not compare different biopsy techniques (cannula-assisted and without cannula) in terms of UM cells. Purpose. To assess morphology of scleral tracts for the presence of malignant cells when different biopsy techniques are approached. Material and methods. Forty-four scleral samples were analyzed after transvitreal FNAB performed in 22 enucleated eyes with UM. Cannula-assisted FNAB was performed in 22 cases. In the same eyes FNAB (n=22) was performed without cannula. Results. FNAB material was adequate for cytological examination in all cases. UM was confirmed in 22 eyes pathologically. UM cell implantation was detected in 5 scleral samples after FNAB without cannula. No signs of cell implantation were seen after cannula-assisted FNAB. The risk of scleral tract UM cell implantation was statistically lower in cannula-assisted FNAB technique (p=0.018, Pearson Chi-square test). Conclusions. UM FNAB performed directly through the sclera without cannula is associated with tumor cells implantation in scleral tract. Cannula-assisted FNAB significantly reduces the incidence of UM implantation in scleral tract. Key words: uveal melanoma, fine-needle aspiration biopsy, enucleation, morphology, ophthalmology.

A novel combined animal tissue model for freehand and ultrasound-guided fine needle aspiration biopsy and smear preparation techniques training.

A variety of models are used for fine needle aspiration biopsy (FNAB) and smear preparation techniques training: human, animal and silicon models or combined models. We present fresh animal tissues as models for freehand and ultrasound (US)-guided FNAB technique training, enabling an integrated approach from tumour detection to smear evaluation. We introduced a novel combined animal tissue model using dietary animal meat with covering skin as a substrate. Animal liver tissue of various sizes, representing tumour, was inserted into the various layers of the substrate (subcutaneous fat, muscle tissue, proximity of bone). Freehand and US-guided FNAB smear preparation, including fixation, was then performed and assessed. The use of a combined animal tissue model for 6 freehand and 3 US-guided FNAB sessions showed a statistically significant improvement in the US-guided FNAB retrieval of liver tissue (Fisher's exact test, p = .0216), in smear preparation technique reflected in a decrease in the number of too thick smears after freehand FNAB (Fisher's exact test, p = .0070), in the overall number of smears satisfactory for evaluation by US-guided FNAB (Fisher's exact test, p = .0206) and in the number of flawless smears obtained in the freehand FNAB training sessions (Fisher's exact test, p = .0020). A unique advantage of the presented model encompassing various layers of animal tissues with covering skin, offers an integrated approach for FNAB training from "tumour" detection, puncture precision, to smear preparation and cytological evaluation for a wider audience and does not compromise patient safety.

Extraskeletal myxoid chondrosarcoma: combining cytopathology with molecular testing to achieve diagnostic accuracy

Advances in the genetics of soft tissue neoplasia have allowed for the diagnostic recognition of specific tumor types from small biopsy specimens, including those procured using the fine needle aspiration (FNA) biopsy technique. Extraskeletal myxoid chondrosarcoma (EMC) is a malignant mesenchymal neoplasm characterized by NR4A3 and, less specifically, by EWSR1 gene rearrangements. A series of EMC cytologic specimens was examined to demonstrate the diagnostic value of incorporating fluorescence in situ hybridization (FISH) testing in cytologic cases of suspected EMC. A search was made of our cytopathology and surgical pathology databases for cases diagnosed as EMC. FNA biopsy cytology, exfoliative cytology, imprint cytology, and FISH analysis were performed and examined using standard techniques. A total of 16 cases of EMC were retrieved from 15 patients (male/female ratio, 2.8:1; mean age, 62 years). Of the 15 patients, 10 were new patients with primary tumors, 2 had locally recurrent tumors, and 4 had metastases. The sites included the extremities in 10 cases, the trunk in 4, serous effusion in 1, and a mediastinal lymph node in 1 case. The specific cytologic diagnoses were EMC (14 cases; 88%), suspicious for EMC (n = 1), and malignant cells (n = 1). All cases for which FISH testing was successfully used were specifically recognized as EMC. Aspirates and imprint smears consisted of uniformly rounded cells set in an opaque myxoid/chondromyxoid stroma (less abundant and more diaphanous in the effusion sample), sometimes arranged in short anastomosing cords. FNA of 1 case of an EMC cellular variant mimicked a malignant small rounded cell tumor. EMC can be added to the growing list of soft tissue neoplasms that are specifically recognizable using cytopathology, coupled with judicious application of ancillary molecular testing.

Тонкоигольная аспирационная биопсия внутриглазных образований

Purpose: To present our experience of fine needle aspiration biopsy (FNAB) of intraocular tumors. Material and methods: Within 3 years FNAB was performed in 154 eyes (154 patients) for prognostic (n= 121) and diagnostic purposes (n=33). The mean tumor thickness in group of diagnostic FNAB was 6.0 mm (range, 2.3-10.5 mm), in prognostic – 5.5 mm (range, 2.0-11.3 mm). Transscleral, transvitreal and transcorneal FNABs were performed using our new custom designed thin-wall 25 and 27G needles by our improved FNAB technique. All samples were analyzed cytologically.In cases of uveal melanoma (UM) genetic testing (GT) was performed to estimate prognosis. Cytogenetic and molecular-genetic tests on cells and remnant liquid were held in cases of UM. Results: Cytologycally informative materials was obtained in 136 of 154 (88%) FNAB samples. Diagnostic FNAB yield was revealed to be 97% (n=32): in 20 cases UM was detected, in 8 – metastases, in 3 – intraocular lymphoma and in 1 – subretinal hemorrhage. Prognostic FNAB revealed either spindle or round-shaped cells of UM in 104 of 121 cases (informative value – 86%). No signs of tumor growth within the scleral track were seen. In 2 cases vitreous hemorrhage was seen that required vitrectomy. The average follow-up period was 11 months (3 to 41 months). No severe complications were detected. Conclusion: Our FNAB improved technique allows to provide excellent tissue samples suitable for differential diagnosis and estimating prognostic with no severe complications.

Preoperative morphological diagnosis of axillary lymph nodes in a breast center consultation service: evaluation of fine-needle aspiration and core biopsy techniques.

Preoperative routine examination of axillary lymph nodes (ALN) in breast cancer patients is carried out physically and by ultrasound imaging; unsuspicious nodes will lead to a sentinel node (SN) procedure, suspicious ones require axillary dissection (AD). Pre-operative biopsy techniques like fine needle aspiration (FNA) or core biopsy (CB) may reduce the number of false "suspicious" cases and prevent overtreatment. We evaluated the effectiveness of both biopsy techniques. After physical and ultrasound examination 241 suspicious ALNs were found in 214 patients. Ultrasound-guided FNA and/or CB procedures were chosen randomly, resulting in 138 FNA and 86 CB. In 17 further events both FNA and CB were employed. The samples were examined in our Cytology lab or in the Pathology Department and the findings correlated with post-operative histological lymph node reports. Patients with histologically proven breast cancer underwent sentinel node biopsy, cytologically or histologically positive FNA/CB-findings prompted ALN dissection. Out of 155 FNA samples 34 were not representative (21.9%), 89 showed no tumor cells (57.4%), 30 showed positive tumor cells (19.4%), leaving two missing. All 103 CB showed representative material, positive in 62 (60.2%) and negative in 41 (39.8%) cases. Correlation with histological reports revealed a statistically non-significant advantage for CB over FNA regarding total accuracy (92.9% vs. 78.3%) and sensitivity (92% vs. 73.7%). Preoperative CB and alternative FNA are valuable complementary methods of predicting ALN involvement in breast cancer patients and may spare the patient unnecessary ALN dissection.

Teaching and learning FNA biopsy: An update for the modern audience

Teaching and learning FNA biopsy: An update for the modern audience

Fine-needle aspiration biopsy for suspected uveal metastases

ObjectiveOne indication of fine-needle aspiration biopsy (FNAB) is the diagnostic confirmatory of a clinical suspicion of uveal metastasis. We analyzed our experience in this clinical setting to assess the effectiveness of FNAB technique. DesignRetrospective study. Participants28 patients (28 eyes) underwent FNAB biopsy. MethodsAspirates were performed using 25-gauge needle and were classified into the following categories: positive, atypical, negative, or nondiagnostic. The electronic medical records provided all clinical data. Subsequent clinical course was considered as the diagnostic standard. ResultsSubsequent clinical course was metastatic tumour in 19 cases (68%) and nonmetastatic tumour in other 9 cases, considered as the diagnostic standard. Cytological interpretations for metastases were positive in 19 cases (68%), atypical in 2 cases (7%), negative in 4 cases (14%), and nondiagnostic in 3 cases (11%). The metastasis-positive cases included 9 adenocarcinoma, 3 uveal lymphoma, 3 small cell carcinomas, 3 non–small cell carcinomas, and 1 metastatic paraganglioma. Both of the atypical cases were suggestive for non-Hodgkin lymphoma. The 4 negative cases for metastases included 2 true negative cases, and 2 false negative aspirates that subsequently proved to be metastatic adenocarcinoma. The 3 nondiagnostic cases included 1 schwannoma, 1 low-grade uveal non-Hodgkin lymphoma, and 1 metastatic adenocarcinoma. The overall sensitivity for FNAB was 87.5%, with a specificity of 100%. ConclusionsFNAB of suspected uveal metastases is a reliable diagnostic technique.

04:03 PM Abstract No. 410 Comparative analysis before and after the utilization of an introducer needle technique for CT-guided fine-needle aspiration biopsy of lung nodules

04:03 PM Abstract No. 410 Comparative analysis before and after the utilization of an introducer needle technique for CT-guided fine-needle aspiration biopsy of lung nodules

Teaching FNA techniques and ultrasound guided FNA

Teaching FNA techniques and ultrasound guided FNA

Efficacy of an Intensive, Ultrasound-Guided Fine-Needle Aspiration Biopsy Training Workshop in Tanzania.

BackgroundFine-needle aspiration biopsy (FNAB) is a minimally invasive, cost-effective diagnostic tool that can be used in low-resource settings. However, adequacy and accuracy of FNAB is highly dependent on the skills of the operator and requires specialized training. Poor technique can preclude definitive diagnoses because of insufficient quality or quantity of FNAB samples. We evaluated the efficacy of an intensive training experience in Tanzania on improving ultrasound-guided FNAB techniques.MethodsA 2-day workshop offered didactic lectures, demonstrations, and hands-on practicum on fundamentals of ultrasound imaging and FNAB technique. A prospective interventional study design was used with pre- and postintervention surveys and assessments to measure the effect of the workshop on specific skills related to slide smearing and ultrasound-guidance among participants.ResultsTwenty-six pathologists and radiologists, including trainees in each specialty, participated in the workshop. Pre- and postworkshop assessments demonstrated that most participants improved significantly in nearly all technical skills for slide smearing and ultrasound-guided FNAB. After the workshop, most participants demonstrated substantial improvements in ability to prepare the ultrasound equipment, measure the lesion in three dimensions by ultrasound, target lesions in one pass using both parallel and perpendicular approaches, and prepare high-quality aspirate smears.ConclusionAn in-country 2-day workshop in Tanzania was efficacious in transferring basic skills in FNAB smear preparation and ultrasound-guided FNAB, resulting in skills enhancement among participating pathologists and radiologists. Although mastery of skills was not the goal of this short workshop, participants demonstrated proficiency in most technical elements after workshop completion, and the workshop generated interest among select participants to pursue additional intensive training in cytopathology.

Lymph node cytopathology: Essential ancillary studies as applied to lymphoproliferative neoplasms.

Ancillary testing is absolutely integral to the correct recognition and classification of lymphoid neoplasms as procured with the fine-needle aspiration (FNA) biopsy technique. In patients with a newly diagnosed lymphoid neoplasm, immunophenotyping with flow cytometry, immunohistochemistry, or both is a standard that is currently expected by oncologists before any form of therapy is initiated. This is often the case also for patients with recurrent/relapsed disease. The cellular material obtained with FNA is perfectly suited to meet this demand. That said, the exceptional complexity of modern-day lymphoma classification often precludes definitive subclassification in a subset of lymphomas for a variety of reasons with the FNA biopsy technique, even with the application of ancillary tests. These include a requirement for definitive knowledge of the nodal architecture (eg, Hodgkin lymphoma), of the histologic grade via the counting of cells per microscopic field (follicular lymphoma), and of molecular findings (often unobtainable because of limitations of cellularity). The application of molecular tests to lymph node aspirates continues to evolve but is still largely confined to specialized medical centers. The intent of this article is to briefly review the diagnostic approach and algorithm for handling lymph node aspirates at the authors' own laboratory. This article highlights what the authors and others consider to be essential ancillary tests and discusses their respective advantages and shortcomings. It lists limited and extended antibody panels and molecular tests that the authors have found helpful not only for correctly recognizing lymphoma with FNA cytopathology but also for subtyping lymphomas whenever possible.

Extra-pleuric coaxial system for CT-guided percutaneous fine-needle aspiration biopsy (FNAB) of small (≤20mm) lung nodules: a novel technique using multiplanar reconstruction (MPR) images.

The aim of the study is to present the diagnostic feasibility, usefulness, and safety of a novel technique for coaxial CT-guided fine-needle aspiration biopsy of small (≤20mm in diameter) lung nodules. A 18-gauge (G) (1.2×40mm) needle is inserted through the skin in the depth of the thoracic wall tissues remaining outside the pleura. Its positioning is planned and adjusted using multiplanar reconstruction (MPR) images along the 18-G guide needle axis tracing a reference outline extended from the needle tip to the target nodule. When the insertion of the 18-G extra-pleuric needle (EPN) proves to be precise, a 22-G Chiba needle is then passed through the outer 18-G EPN until it reaches the thoracic lesion for the sampling procedure. Patient population included 153 males and 94 females, with a mean age of 61.3±21.6years. Mean nodule diameter was 14.1±2.2mm. The lesion depth from pleural plane ranged from 0mm to 127mm. An average of 1.29 aspirates were performed per lesion. The most common complication was pneumothorax in 27 cases; there were no cases of PNX requiring chest tube insertion. Intrapulmonary bleeding along the needle track was observed in 32 patients. Exploiting the advantage of MPR images, our novel technique of extra-pleuric coaxial system with a 18-G EPN allows the operator to multiple samplings of small (≤20mm) target lesions in various locations with a thinner (22-G Chiba) needle, thus reducing the degree of pleural, parenchymal, or adjacent organs damage.

Role of fine needle aspiration biopsy cytology in the diagnosis of infections.

The role of fine needle aspiration biopsy (FNAB) cytology in diagnosing infections has expanded due to the increase in the number of immune compromised patients and the increasing role of FNAB in the developing world where infection is a major cause of illness. FNAB has become the first procedural test in cases where the clinical and imaging findings suggest an infectious lesion or where there is a differential diagnosis of infection or metastatic or primary tumor. This applies to FNAB of palpable or image directed or deep seated lesions accessed by EUS and EBUS. This article details a recommended approach and technique for FNAB of infectious lesions, and discusses the role of rapid on site evaluation and the application of ancillary testing including the rapidly expanding array of molecular tests based on FNAB material. The utility of recognizing suppurative and granulomatous infectious patterns in FNAB direct smears, and the specific cytomorphological features on routine Papanicolaou and Giemsa stains and on special stains of FNAB smears is described for a large number of bacterial, fungal, viral, parasitic, and protozoan infections. The role of cytopathologists is to now train cytopathologists in sufficient numbers to provide FNAB services, teach trainee cytopathologists and cytotechnologists, and to encourage our clinical colleagues to use FNAB in the diagnosis of infections and other lesions to the benefit of patients and the medical system. Diagn. Cytopathol. 2016;44:1024-1038. © 2016 Wiley Periodicals, Inc.

Fine-Needle Aspiration Biopsy in Orbital Lesions: A Retrospective Study of 225 Cases

To describe and analyze results from the fine-needle aspiration biopsy (FNAB) technique, used as a diagnostic tool, in patients with orbital lesions. Retrospective case series. setting: Institutional (Karolinska Hospital, Stockholm). 207 patients with 210 orbital lesions. 225 FNABs of the orbit. Successful diagnosis from FNAB. Of the 210 orbital lesions evaluated with FNAB, a successful cytologic diagnosis was achieved in 176 (84%). In more than half of the orbital lesions (54%), the FNAB diagnosis in addition to imaging appearance, clinical appearance, and clinical history provided sufficient information for treatment, and the patient did not require an incisional or excisional biopsy. Ninety-seven patients underwent additional excisional or incisional biopsy; FNAB diagnoses and the histopathologic diagnoses corresponded in 87% of the cases with an intraclass correlation coefficient of 0.84 (95% confidence interval [CI] 0.76-0.90). The difference was statistically significant between the ability to make a successful cytologic FNAB diagnosis in palpable lesions vs nonpalpable lesions (successful diagnosis in 90% [CI= 85%-95%] vs 75% [CI= 66%-84%];P<.01). Neither the orbital quadrant location, nor the radiologic appearance (diffuse vs encapsulated), nor size of the lesion affected the success of FNAB diagnoses (all P > .7). There was a complication in 6 cases (3%). All complications were temporary and none led to permanent damage. FNAB proved effective and exceedingly safe. With the current healthcare climate of minimally invasive surgery and cost control, FNAB should be considered as a valid alternative to open surgery in the evaluation and management of orbital lesions.

Epidermoid/Dermoid cysts mimicking odontogenic infections: review of literature

Introduction: Dermoid/Epidermoid cysts are rare pathologic lesions that may involve the floor of the mouth. Infection and inflammation of the cyst can produce a clinical picture very similar to the submandibular and submental abscesses with odontogenic origin. Dermoid/epidermoid cysts are on the floor of the mouth with submental or submandibular component can be mistaken for odontogenic infections. Methods: Four biopsy proven dermoid/epidermoid cysts operated in the Mashhad University of Medical Sciences, Ghaem hospital (2012-2013), were reviewed. Results: Four patients, including two classic cases and two infected dermoid/epidermoid cysts, were erroneously diagnosed as odontogenic infection. Discussion: The lesions located solely below mylohyoid muscle need to be removed through anextraoral approach but the lesions above the mylohyoid muscle or those that have both supra- and infra-mylohyoid components can be removed through an intraoral incision.Conclusion: Dermoid/epidermoid cysts should be considered in the differential diagnosis of submental/submandibular swellings. In the absence of an odontogenic cause of infection, fine-needle aspiration biopsy and appropriate imaging evaluation techniques with sonography, CT or MRI are mandatory for correct diagnosis and surgical treatment planning. The clinicians should be very cautious to differentiate odontogenic infections from infected dermoid/epidermoid cysts.

Seasonal fluctuations in the steady-state mRNA levels of suppressor of cytokine signaling-3 (SOCS-3) in the mammary gland of lactating and non-lactating ewes

Prolactin (PRL) is a hormone that plays a crucial role during pregnancy and lactation. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, which is an important pathway in signal transduction from PRL to target cells, can be modulated by various factors, including suppressor of cytokine signaling-3 (SOCS-3). PRL may increase and decrease SOCS-3 expression, and its actions are mostly dependent on additional factors such as the photoperiod. There is also evidence for a relationship between suckling and SOCS-3 expression in the mammary gland. The aim of this study was to examine the influence of seasonality and physiological status on SOCS-3 expression levels in ovine mammary glands. Mammary gland fragments were obtained from 18 Polish Longwool ewes, and the fine-needle aspiration biopsy technique was used on 4 groups of animals under specific physiological and photoperiodic conditions: non-lactating ewes during long days (LD; n=6), ewes on day 30 (n=6) or day 56 of lactation (n=6) and non-lactating ewes during short days (SD; n=6). SOCS-3 mRNA levels were measured by real-time PCR. The results of this study confirmed that SOCS-3 mRNA expression in sheep is dependent on the season and stage of lactation. The highest expression of the examined factors was noted in the mammary glands of non-lactating sheep during SD, and the lowest levels were observed in ewes on day 30 of lactation. The transcript levels observed in the tissues collected from non-lactating sheep during SD and LD were higher (74% and 41%, respectively) compared with the expression observed on day 30 of lactation. On day 56 of lactation, the SOCS-3 mRNA level was similar to that observed in the udders of non-lactating sheep during LD. These results indicate that SOCS-3 could play an integrating role between hormones and other factors that are involved in the physiological functions of the mammary gland.

Ultrasound and cytological diagnostics of thyroid - its proper application in case of coexisting disturbing clinical signs and symptoms, suggestive of active proliferative lesion

Ultrasound and cytological diagnostics of thyroid - its proper application in case of coexisting disturbing clinical signs and symptoms, suggestive of active proliferative lesion