Fine Needle Aspiration Biopsy of Follicular Thyroid Tumors

US-guided fine needle aspiration cytology is currently the best diagnostic tool for thyroid nodules. The aim of this research was to make a detailed and objective determination of the morphological characteristics of cells in cytological smears in an attempt to distinguish benign from malignant follicular tumors. The research included 62 patients with cytologically diagnosed follicular or oncocytic tumors, and 15 patients with nodular hyperplasia. Echographic findings were divided into three groups: isoechogenic, hypoechogenic and hyperechogenic nodules. We analyzed the cellularity of the smear, cohesion between follicular cells, acinar formations, bare nuclei, characteristics of the nucleus and the cytoplasm, and the presence of colloid. The statistical analysis of cytological parameters has indicated that none of the cytological parameters alone is discriminating enough between non-tumor and tumor changes, or benign and malignant follicular thyroid nodules. The analysis of age, sex, nodule size and ultrasound findings has not shown the correlation between any of these parameters with the malignant or benign follicular tumors. The cytological analysis of the smears for patients with follicular tumors, in combination with clinical data and other diagnostic methods, contributes to more precise diagnostics, but is not sufficient for the differentiation between benign and malignant follicular tumors

Granular Cell Tumor – Clinically Presented as Lymphadenopathy

Granular cell tumors are relatively uncommon benign lesions occurring in almost any part of the body. We report the cytological diagnosis of granular cell tumor in 25-year-old male patient who presented with an inguinal mass clinically suspected to be a lymphadenopathy. Fine needle aspiration revealed polygonal cells with abundant, granular cytoplasm and eccentrically located vesicular nuclei and inconspicuous nucleoli. The histopathological examination of the surgical excision confirmed the diagnosis. If resection is complete, local surgical excision is curative for benign granular cell tumors. Granular cell tumor has a characteristic cytological appearance, and fine-needle aspiration cytology has been suggested to be diagnostic modality of choice

Granular Cell Tumor – Clinically Presented as Lymphadenopathy

Granular cell tumors are relatively uncommon benign lesions occurring in almost any part of the body. We report the cytological diagnosis of granular cell tumor in 25-year-old male patient who presented with an inguinal mass clinically suspected to be a lymphadenopathy. Fine needle aspiration revealed polygonal cells with abundant, granular cytoplasm and eccentrically located vesicular nuclei and inconspicuous nucleoli. The histopathological examination of the surgical excision confirmed the diagnosis. If resection is complete, local surgical excision is curative for benign granular cell tumors. Granular cell tumor has a characteristic cytological appearance, and fine-needle aspiration cytology has been suggested to be diagnostic modality of choice

PAX8-PPARg Oncogene in Follicular Thyroid Tumors: RT-PCR and Immunohistochemical Analyses

US-guided fine needle aspiration cytology is currently the best diagnostic tool for thyroid nodules. However, it is not sensitive and specific enough for differentiating between benign and malignant follicular tumors. A potentially useful marker for this differentiation is the PAX8-PPARg rearrangement, identified in follicular thyroid carcinomas, but not in follicular adenomas or other types of thyroid tumors. The aim of this research was to determine the clinical significance of the PAX8-PPARg oncogene in diagnostics follicular thyroid tumors. The study included 62 patients with follicular or Hürthle cell tumors. Gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) from paraffin embedded tissues, and PCR products were checked using the agarose gel electrophoresis. The immunohistochemical analysis was performed on archive paraffin embedded tissues with the monoclonal PPARã antibody. The statistical analysis has indicated that neither the expression of PAX8-PPARg mRNA, nor the immunohystochemical analysis with the PPARg antibody correlate with the patohystological diagnosis. The oncogene PAX8-PPARg has not met the expectations as a reliable tumor marker for differentiation between benign and malignant thyroid tumors, which makes the only reliable histological criteria – capsular and vascular invasion

PAX8-PPARg Oncogene in Follicular Thyroid Tumors: RT-PCR and Immunohistochemical Analyses

US-guided fine needle aspiration cytology is currently the best diagnostic tool for thyroid nodules. However, it is not sensitive and specific enough for differentiating between benign and malignant follicular tumors. A potentially useful marker for this differentiation is the PAX8-PPARg rearrangement, identified in follicular thyroid carcinomas, but not in follicular adenomas or other types of thyroid tumors. The aim of this research was to determine the clinical significance of the PAX8-PPARg oncogene in diagnostics follicular thyroid tumors. The study included 62 patients with follicular or Hürthle cell tumors. Gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) from paraffin embedded tissues, and PCR products were checked using the agarose gel electrophoresis. The immunohistochemical analysis was performed on archive paraffin embedded tissues with the monoclonal PPARã antibody. The statistical analysis has indicated that neither the expression of PAX8-PPARg mRNA, nor the immunohystochemical analysis with the PPARg antibody correlate with the patohystological diagnosis. The oncogene PAX8-PPARg has not met the expectations as a reliable tumor marker for differentiation between benign and malignant thyroid tumors, which makes the only reliable histological criteria – capsular and vascular invasion

Razina leptina u serumu kod raka dojke

Leptin is a polypeptide which is mostly produced in white fat tissue and is an important proinflammatory, proangiogenic, proinvasive and mitotic factor. There is ever more evidence suggesting the key role of leptin in the occurrence of breast cancer. The aim of the study was to investigate serum leptin levels in patients with benign breast tumors, as well as in various breast cancer phenotypes, taking into account leptin levels connected to menopausal status and body mass index (BMI). The study included 97 patients having their breast tumor surgically removed. Serum leptin level was determined by ELISA method in all study patients. Study results showed that significantly more women, regardless of having malignant or benign tumors, were postmenopausal and had a significantly higher level of leptin compared to the premenopausal group. The highest level of leptin was recorded in the group of postmenopausal obese women compared to other postmenopausal women but also compared to premenopausal women. According to BMI alone, obese women had a significantly higher level of leptin regardless of the type of tumor. The most significant differences in leptin levels observed through BMI were found in the Luminal B1 group. In conclusion, serum leptin level was shown to be a good diagnostic parameter suggesting a higher possibility of breast cancer development.Leptin je polipeptid koji se uglavnom proizvodi u bijelom masnom tkivu te predstavlja važan proupalni, proangiogeni, proinvazivni i mitotički čimbenik. Sve je više dokaza koji ukazuju na ključnu ulogu leptina u nastanku tumora dojke. Istraživali smo serumsku razinu leptina u bolesnica s benignim tumorima dojke, kao i kod različitih fenotipova malignih tumora dojke te ovisnost razine leptina o reproduktivnom statusu i indeksu tjelesne mase (ITM). Istraživanje je obuhvatilo 97 bolesnica kojima je tumor uklonjen kirurškim zahvatom. Serumska koncentracija leptina utvrđena je metodom ELISA u svih bolesnica uključenih u istraživanje. Znatno više žena, bez obzira na to jesu li imale zloćudni ili dobroćudni tumor, bilo je u postmenopauzi te su imale značajno više razine leptina u usporedbi s premenopauzalnim skupinama. Najviša razina leptina utvrđena je kod pretilih žena u postmenopauzi u usporedbi s drugim ženama u postmenopauzi, ali i u usporedbi sa ženama u premenopauzi. Prema ITM, pretile ispitanice su imale značajno više razine leptina bez obzira na vrstu tumora. Najznačajnije razlike u razinama leptina, promatrane kroz ITM, utvrđene se u skupini Luminal B1. Razina leptina u serumu je dobar dijagnostički parametar koji govori u prilog većoj predispoziciji za nastanak karcinoma dojke

Neoadjuvant Chemotherapy Affects TFF3 Peptide Expression in Luminal B Subtype of Breast Cancer – A Pilot Study

Aim: Trefoil factor family 3 (TFF3) peptide is normally expressed by epithelial cells in breast ducts, but it is also associated with different pathological conditions, including breast cancer. It is considered a marker of poor prognosis and associated with increased resistance to chemotherapy. Data on the effect of chemotherapy on TFF3 peptide expression are scarce. The aim of this pilot study was to assess suitability of research on this topic for large-scale studies. Methods: Formalin-fixed, paraffin-embedded samples of core biopsies and of surgically removed tumors from patients with luminal B subtype of breast cancer were used for immunohistochemical analysis. Changes in TFF3 peptide and Ki-67 expression and microvessel density (MVD) values before and after chemotherapy were analyzed, as well as the association between TFF3 peptide expression and Ki-67 expression and MVD values. Results: Significant reduction in TFF3 and Ki 67 expression was observed after chemotherapy, while MVD values did not differ significantly before and after chemotherapy. The association of TFF3 peptide expression and Ki-67 expression and TFF3 peptide expression and MVD values was not significant before or after chemotherapy. Conclusion: The data obtained in this pilot study suggest that a large-scale study is justified, and it other breast cancer subtypes should be included. (Bijelić N, Abramović M, Rajc J, Rođak E, Marušić Z, Tolušić Levak M, Pauzar B, Belovari T. Neoadjuvant Chemotherapy Affects TFF3 Peptide Expression in Luminal B Subtype of Breast Cancer – A Pilot Study. SEEMEDJ 2020; 4(2); 20-27

Interobserver Variability in Cytologic Subclassification of Squamous Intraepithelial Lesions – The Bethesda System vs. World Health Organization Classification

The aim of the study was to compare interobserver variability for The Bethesda System (TBS) and World Health Organization (WHO) classification of cervical squamous intraepithelial lesions. A total of 1,000 conventional Papanicolaou smears (156 positive and 884 negative) were examined »blindly« by three cytologists and one cytotechnician. The degree of observer agreement was expressed by kappa statistics using a program for the calculation of interobserver variation and association »Agree« (Svanholm and Jergensen, 1989). Kappa (x) was determined for each cytologic diagnosis within a particular classification and total for either classification. The association with and separation from other diagnoses was determined for each cytologic diagnosis in the form of conditional probability (Pj). In WHO classification, the diagnoses of dysplasia media and dysplasia gravis showed poor reproducibility (x=0.114 and x= 0.259, respectively), the diagnosis of dysplasia levis good reproducibility (x=0.639), and the diagnosis of carcinoma in situ excellent reproducibility (x=0.762). WHO classification yielded pool x of 0.741. In TBS classification, the diagnosis of LSIL showed good, and HSIL excellent reproducibility (x=0.542 and x=0.763, respectively). TBS classification yielded pool x of 0.699. Dysplasia media (Pj=0.121) and dysplasia gravis (Pj=0.274) were found to be morphologically poorly defined, and carcinoma in situ (Pj=0.777) and dysplasia levis (Pj=0.651) well defined diagnoses. LSIL was morphologically moderately defined (Pj=0.587) and HSIL well defined (Pj=0.789) diagnosis. Accordingly, TBS does not substantially improve diagnostic reproducibility of the cytologic diagnoses of squamous intraepithelial lesions, while providing considerably less information to the clinician than the four-grade dysplasia/CIS terminology, thus eliminating the opportunity of choosing a different procedure for the diagnosis of dysplasia media, which is of utmost importance in the population of young nulliparae

Izražaj TFF gena i proteina u tumorima dojke

The objective of this study was to determine diff erential expression of TFF1, TFF2 and TFF3 genes and proteins in breast tumor subtypes. In addition, we investigated the correlation between TFF genes within tumor subgroups, and TFF genes with clinical and pathologic characteristics of the tumor. Study group included 122 patients with surgically removed breast tumors. Samples were investigated using qRT-PCR and immunohistochemistry. TFF1 and TFF3 genes and proteins were expressed in breast tumors, while the levels of TFF2 gene and protein expression were very low or undetectable. TFF1 was signifi cantly more expressed in benign tumors, while TFF3 was more expressed in malignant tumors. Gene and protein expression of both TFF1 and TFF3 was greater in lymph node-negative tumors, hormone positive tumors, tumors with moderate levels of Ki67 expression, and in grade II tumors. A strong positive correlation was found between TFF1 and TFF3 genes, and the expression of both negatively correlated with Ki67 and the level of tumor histologic diff erentiation. Our results suggest that TFF1 and TFF3, but not TFF2, may have a role in breast tumor pathogenesis and could be used in the assessment of tumor diff erentiation and malignancy.Cilj ovoga istraživanja bio je utvrditi razlike u izražaju gena i proteina TFF1, TFF2 i TFF3 u različitim vrstama tumora dojke te ispitati korelacije između gena TFF i vrsta tumora te gena TFF i kliničko-patoloških karakteristika tumora. U studiju su bile uključene 122 ispitanice kojima je kirurški odstranjen tumor dojke. Uzorci su obrađeni metodom qRT-PCR i metodom imunohistokemije. Geni i proteini TFF1 i TFF3 bili su izraženi u tumorima dojke, dok izražaj gena i proteina TFF2 nije otkriven u tumorskom tkivu. TFF1 je bio izraženiji kod dobroćudnih tumora, dok je TFF3 bio izraženiji kod zloćudnih tumora. TFF1 i TFF3 su bili izraženiji u hormonski ovisnim tumorima, tumorima bez metastaza u limfnim čvorovima, tumorima s umjereno visokim izražajem Ki67 i umjereno diferenciranim tumorima. Jaka pozitivna korelacija uočena je između gena TFF1 i TFF3, a oba su negativno korelirala s faktorom Ki67 i stupnjem diferenciranosti tumora. Dobiveni rezultati pokazuju kako bi TFF1 i TFF3 mogli imati ulogu u patogenezi tumora dojke te bi se potencijalno mogli rabiti za određivanje tumorskog statusa i procjenu malignosti tumora

Citodijagnostika folikularnih tumora štitnjače

US-guided fine needle aspiration cytology is currently the best diagnostic tool for thyroid nodules. The aim of this research was to make a detailed and objective determination of the morphological characteristics of cells in cytological smears in an attempt to distinguish benign from malignant follicular tumors. The research included 62 patients with cytologically diagnosed follicular or oncocytic tumors, and 15 patients with nodular hyperplasia. Echographic findings were divided into three groups: isoechogenic, hypoechogenic and hyperechogenic nodules. We analyzed the cellularity of the smear, cohesion between follicular cells, acinar formations, bare nuclei, characteristics of the nucleus and the cytoplasm, and the presence of colloid. The statistical analysis of cytological parameters has indicated that none of the cytological parameters alone is discriminating enough between non-tumor and tumor changes, or benign and malignant follicular thyroid nodules. The analysis of age, sex, nodule size and ultrasound findings has not shown the correlation between any of these parameters with the malignant or benign follicular tumors. The cytological analysis of the smears for patients with follicular tumors, in combination with clinical data and other diagnostic methods, contributes to more precise diagnostics, but is not sufficient for the differentiation between benign and malignant follicular tumors.Citološka punkcija pod kontrolom ultrazvuka je nedovoljno osjetljiva i specifična za razlikovanje benignih i malignih folikularnih tumora. Cilj istraživanja je bio utvrditi citomorfološke karakteristike stanica punktata histološki verificiranih folikularnih i onkocitnih tumora te odrediti vrijednost pojedinih citoloških parametara u diferencijaciji benignih i malignih tumora. U istraživanje je uključeno 62 ispitanika s citološkom dijagnozom folikularnog ili onkocitnog tumora te 15 ispitanika s čvorastom hiperplazijom. Ehografski, čvorovi su bili izoehogeni i hipoehogeni, a prema veličini su podijeljeni u skladu sa pT klasifikacijom SZO. Semikvantitativno je analizirana celularnost uzorka, kohezija me|u stanicama, morfologija nakupina, gole jezgre, karakteristike jezgre i citoplazme te koloid. Statisti~ki, ni jedan od citolo{kih parametara sam za sebe nije dovoljan diskriminirajući faktor između netumorskih i tumorskih promjena, kao ni između benignih i malignih folikularnih tumora štitnjače. Analizom dobi, spola, veličine čvora ni UZV nalaza nije dokazana povezanost bilo kojeg od ovih parametara s malignim ili benignim folikularnim tumorom. Citološka analiza punkata u kombinaciji sa kliničkim podacima i drugim dijagnostičkim metodama doprinosi preciznijoj dijagnostici, ali sama za sebe nije dostatna za diferencijaciju benignih i malignih folikularnih tumora