Marija Auersperg

Anaplastic Thyroid Carcinoma in Fine Needle Aspirates

OBJECTIVE To analyze the diagnostic problems with fine needle aspiration biopsy in anaplastic thyroid carcinoma (ATC) and to describe the cytomorphologic characteristics in 113 cases. STUDY DESIGN A retrospective analysis of 113 fine needle aspirates and 67 surgical specimens from 113 patients with ATC admitted to the Institute of Oncology, Ljubljana, in 1972-1992. RESULTS In a series of 113 fine needle aspirates of ATC, 3 (2.7%) were inadequate, 3 (2.7%) suboptimal and 107 (94.7%) diagnostic of malignancy. On reexamination, 96/107 (89.7%) were diagnosed as ATC, 6 (5.6%) as differentiated thyroid carcinoma, and 5 (4.6%) as a malignant tumor not otherwise specified. As to the predominant cell population, fine needle aspirates showed three different cell patterns: (1) pleomorphic cell (43 cases), (2) round cell (33 cases), and (3) spindle cell pattern (7 cases). In the present retrospective analysis we identified three main reasons for inadequate or nonrepresentative fine needle aspiration biopsy sampling: (1) tumor regressive changes (necrosis, hemorrhage, leukocytic infiltration), (2) extensive tumor fibrosis, and (3) distinct differentiated and anaplastic patterns in the same tumor. CONCLUSIONS The major diagnostic problem with fine needle aspiration biopsy (FNAB) of ATC is related to sample quality. Cytomorphologic features of ATC are highly specific and easy to recognize. Due to the simple technique and high diagnostic accuracy, FNAB is the method of choice in patients with ATC.

The Role of Radioactive Iodine in the Treatment of Hürthle Cell Carcinoma of the Thyroid

It is generally believed that Hürthle cell thyroid carcinoma (HCTC) does not accumulate radioactive iodine (RAI). The aim of our retrospective study was to find out if, after thyroid surgery and RAI ablation of the thyroid remnant, the metastatic or recurrent HCTC accumulates RAI. We reviewed the charts of 48 patients with histopathologically verified HCTC, who were treated at the Institute of Oncology in Ljubljana, Slovenia, from 1972 to 2000. In 16 patients (11 women, five men; 47-77 years old), who had distant metastases at presentation (eight patients) or recurrence (eight patients), whole-body RAI scanning was performed after the withdrawal of thyroid hormone replacement. Whenever RAI uptake was confirmed, the therapy with 5.6 GBq of RAI was performed. In 11 of 16 patients, the uptake (range 0.1-12%) of RAI was confirmed. Altogether, 46 therapeutic applications of RAI were given. We conclude that whole-body scanning with RAI should be performed in HCTC. RAI may be effective in the treatment of HCTC.

Neoadjuvant chemotherapy in 29 patients with locally advanced follicular or Hürthle cell thyroid carcinoma: a phase 2 study.

BACKGROUND It is believed that chemotherapy (ChT) is ineffective in follicular thyroid carcinoma (FTC) and Hürthle cell thyroid carcinoma (HCTC). The aim of our retrospective study was to find out whether neodjuvant ChT before thyroid surgery had any effect on the size of primary tumor in patients with FTC or HCTC. METHODS The study included 29 patients (20 women, 9 men; mean age: 60.8 years) with FTC or HCTC who had T3 or T4 tumor and were treated with neoadjuvant ChT from 1979 to 2004. A mean tumor diameter was 9.3 cm. Extrathyroid growth of tumor was present in 15 patients. Regional and distant metastases were detected in 6 and 12 patients, respectively. With respect to the site of metastatic spread, the lung was involved in eight patients and the skeleton in five. ChT consisted of vinblastine in 19 cases, vinblastine with adriamycin in 5 cases, or other ChT regimens in 5 cases. RESULTS Altogether, 67 cycles of ChT were given and tumor size decreased by >50% in 13 patients (=45%). ChT was effective in patients with FTC and HCTC in 47% and 43%, respectively. In the patients with and without distant metastases, the primary tumor size decreased by >50% in 17% and 65% (p=0.02), respectively. R0, R1, and R2 resection was performed in 15, 10, and 4 cases, respectively. Histopathology revealed that ChT (i.e., wide areas of tumor necrosis) was effective in seven patients (24%). The 5- and 10-year cause-specific survivals of the patients were 77% and 47%, while the 5- and 10-year disease-free intervals were 57% and 46%, respectively. Six patients are alive (median survival: 162 months), four of them have no evidence of disease, six patients died of other causes (median survival: 101 months), while 17 patients died of FTC or HCTC (median survival: 72 months). Among them, 16 died of distant metastases, while only one succumbed to locoregional recurrence and distant metastases. CONCLUSIONS ChT before surgical procedure may be effective in order to decrease the tumor size in FTC or HCTC in 45% of patients.

Effect of vinblastine on cell membrane fluidity in vinblastine-sensitive and -resistant HeLa cells

The electron paramagnetic resonance method (EPR) was used to study the effects of vinblastine (VLB) on cell membrane fluidity in wild-type HeLa cells (HeLa K) and its subclone, which is resistant to several drugs (HeLa CA). HeLa CA cells, obtained by treatment of HeLa K with CDDP, were found to be more resistant to VLB than to CDDP. The experimentally observed EPR spectra were correlated with the calculated spectra obtained by computer simulation. The results indicate that the cell membrane of HeLa K and HeLa CA cells is heterogeneous and can be described with at least three types of coexisting domains with different fluidity characteristics. The two more fluid domains of HeLa CA cells were found to be more fluid than in HeLa K cells. The fluidity of the less fluid domain remained unchanged but its portion in the membrane was increased. VLB treatment did not affect the membrane fluidity of HeLa CA cells significantly. On the other hand, 1 h of treatment of HeLa K cells with 1 ng/ml VLB did not change the fluidity characteristics of membrane domains but decreased the portion of the less fluid domains. This was also reflected in an average increase of the entire membrane fluidity. The observed changes were detected at VLB concentrations which were far below the cytotoxic level.

Marginal vacuoles in fine-needle aspirates of follicular thyroid carcinoma.

Marginal vacuoles (MV) found in Giemsa‐stained fine‐needle aspirates of the thyroid gland have been observed in toxic and also in non‐toxic goiters. The aim of our retrospective study was to disclose the incidence and diagnostic significance of MV in 46 smears from 43 patients with primary and/or metastatic follicular thyroid carcinoma (FTC). Typical MV, MV‐like structures, or both were found in 14 of 36 specimens (39%) of the primary tumor and in four of seven specimens (57%) obtained from metastases of FTC. No association between the appearance of MV/MV‐like structures and degree of tumor differentiation was demonstrated. On the other hand, MV or/and MV‐like structures were more frequently (69%) documented in hyperthyroid patients (P < 0.05). Accordingly, our study demonstrated relatively frequent appearance of MV or MV‐like structures in FTC independent of tumor differentiation. Their appearance, however, seems to be associated with hyperthyroidism. Diagn Cytopathol 1996;15:93–97.

Neoadjuvant Chemotherapy in 16 Patients with Locally Advanced Papillary Thyroid Carcinoma

BACKGROUND It is believed that chemotherapy (ChT) is ineffective in papillary thyroid carcinoma (PTC). The aim of our retrospective chart review was to find out if neoadjuvant ChT before thyroid surgery had any effect on the size of primary tumors in patients with PTC. METHODS The study included 16 patients (13 women, 3 men; median age 63.5 years) with PTC, who were treated with neoadjuvant ChT from 1988 to 2005. Poorly differentiated PTC, classical PTC, a follicular variant of PTC, and a Hürthle cell variant of PTC were diagnosed in 5, 5, 3, and 3 cases, respectively. The mean tumor diameter was 9.67 cm. Seven patients had a pT4 tumor. Regional and distant metastases were detected in 10 and 7 patients, respectively. ChT consisted of vinblastine in 11 cases, vinblastine with adriamycin in 2 cases, and other schedules in 3 cases. Four patients were also treated with preoperative external irradiation. RESULTS Altogether, 40 cycles of ChT were given. After ChT, the tumor size decreased in all 16 patients: by >50% in 7 (44%) patients and by <50% in 9 patients. R0, R1, and R2 resection was performed in 2, 10, and 4 cases, respectively. The median survival time of our patients was 88 months. Six patients are still alive; two died of causes not related to carcinoma, while eight patients died of PTC. CONCLUSIONS Neoadjuvant ChT before thyroid surgery may be effective in patients with locally advanced PTC. After neoadjuvant ChT, in 44% of patients, the tumor size decreased by >50%.

Effects of vinblastine on cell membrane fluidity and the growth of SA-1 tumor in mice

Cell membranes can be targets of some anti-cancer drugs. Therefore, the purpose of this study was to determine whether vinblastine (VLB) can also affect the tumor cell membrane. On the in vivo SA-1 tumor model, alteration of cell membrane fluidity (measured by electron paramagnetic resonance, EPR), cytotoxicity and morphological changes of the SA-1 tumor cells after VLB treatment were studied. The cytotoxic effect of VLB was biphasic, with an initial fast increase in cytotoxicity followed by a plateau. The surviving cells had increased membrane fluidity and were morphologically changed. The dose-response curve of VLB on membrane fluidity was also biphasic with an initial fast increase in membrane fluidity followed by a plateau. Since dose-response curves of VLB cytotoxicity and its effect on membrane fluidity were similar, there was a high correlation between both effects. The effect of VLB on membrane fluidity was the most pronounced at 24 h and 48 h after treatment. The results of this study indicate that VLB affects cell membrane by increasing the membrane fluidity of SA-1 tumor cells in vivo in a dose-and time-dependent manner. Therefore, this finding may be beneficially implemented also in priming cells for other cytotoxic drugs and for appropriate timing of drug sequence in combined schedules.

Prognosing the Survival Time of Patients with Anaplastic Thyroid Carcinoma using Machine Learning

Anaplastic thyroid carcinoma is a rare but very aggressive tumor. Many factors that might influence the survival of patients have been suggested. The aim of this study was to determine which of the factors, known at the time of admission to the hospital, might predict survival of the patients with anaplastic thyroid carcinoma. Our aim was also to assess the relative importance of the factors and to identify potentially useful decision and regression trees generated by machine learning algorithms. Our study included 126 patients with anaplastic thyroid carcinoma treated at the Institute of Oncology Ljubljana from 1972 to 1992. In this chapter, we compare the machine learning approach with previous statistical evaluations of the problem (univariate and multivariate analysis) and show that it can provide a more thorough analysis and improve the understanding of the data.

Effects of vinblastine on blood flow of solid tumours in mice

The aim of our study was to determine the effects of low doses of Vinblastine (VLB) on tumor growth and time course of blood flow changes in solid tumors of mice. Two murine tumors were used in the study; EAT carcinoma and SA-1 fibrosarcoma, syngeneic to CBA and A/J mice, respectively. Mice were treated with intraperitoneal injection of 2 different VLB doses when the tumors reached 6 mm in diameter. Antitumor effectiveness was determined by tumor growth delay assay. Tumor blood perfusion changes were assessed by means of Laser Doppler flowmetry. The antitumor effectiveness of both doses in SA-1 tumors was minimal, resulting in 2.0 days tumor growth delay. The antitumor effectiveness in EAT tumor was also minimal, but dose dependent; the lower dose induced 1.1 tumor growth delay, while the higher dose resulted in 2.1 tumor growth delay. This higher dose of 50 μg VLB produced statistically significant and highly reproducible decrease in blood flow. The maximum effect was reached 1.5 hours after the treatment. The lower doses did not significantly affected tumor blood perfusion. Our data demonstrate that VLB at the dose that minimally affect tumor growth, have a significant effect on tumor blood perfusion.