Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer.

BACKGROUND: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. PATIENTS AND METHODS: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin-eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). RESULTS: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. CONCLUSION: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.

Extracapsular tumor spread and the risk of local, axillary and supraclavicular recurrence in node-positive, premenopausal patients with breast cancer.

BACKGROUND: Extracapsular tumor spread (ECS) has been identified as a possible risk factor for breast cancer recurrence, but controversy exists regarding its role in decision making for regional radiotherapy. This study evaluates ECS as a predictor of local, axillary, and supraclavicular recurrence. PATIENTS AND METHODS: International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years. RESULTS: In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23-3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied. CONCLUSIONS: Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.

Factors predicting treatment responsiveness and prognosis in node-negative breast cancer. The International (Ludwig) Breast Cancer Study Group.

PURPOSE: An international trial (formerly Ludwig Trial V) has been conducted in 1,275 subjects to ascertain if perioperative chemotherapy is beneficial for node-negative breast cancer patients and to identify subgroups of patients who benefit from this therapy. PATIENTS AND METHODS: Node-negative breast cancer patients were randomized to receive either one cycle of perioperative chemotherapy or no adjuvant treatment. A detailed pathology review was conducted in 1,203 of the 1,275 patients enrolled. Stepwise Cox regression analysis was used to search for factors either predicting chemotherapeutic responsiveness and/or influencing disease-free survival (DFS). RESULTS: As expected, primary tumor size, grade, and the presence of peritumoral vascular invasion are the most important prognostic factors. Perioperative chemotherapy provides a DFS advantage at 5 years of median follow-up and such treatment is more effective for estrogen receptor-negative than for estrogen receptor-positive tumors, for histologic grade 2 and 3 than for grade 1 tumors, and for patients in whom no axillary lymph node metastases were found even after serial sectioning and review by the Central Pathology Laboratory. CONCLUSION: Hormone receptor status and tumor grade are important factors for predicting responsiveness to perioperative chemotherapy in node-negative breast cancer.

Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group.

PURPOSE: To evaluate the prognostic importance of immunocytochemically determined c-erbB-2 overexpression in the primary tumors of patients with breast cancer. PATIENTS AND METHODS: Primary tumors from 1,506 breast cancer patients (760 node-negative and 746 node-positive) who were treated in the International (Ludwig) Breast Cancer Study Group Trial V were studied. Node-negative patients were allocated randomly to either a single cycle of perioperative chemotherapy (PeCT) or no adjuvant treatment, and node-positive patients received either a prolonged chemotherapy (with tamoxifen for postmenopausal patients) or a single perioperative cycle. RESULTS: Tumors from 16% of the node-negative patients and 19% of the node-positive patients were found to be c-erbB-2-positive. In both groups c-erbB-2 positivity correlated with negative progesterone receptors (PR), negative estrogen receptors (ER), and high tumor grade. Lobular carcinomas were all negative, and, thus support the view that such tumors represent a defined subtype of breast carcinoma. The expression of c-erbB-2 was prognostically significant for node-positive but not for node-negative patients. However, in both subgroups, the prognostic significance was greater for patients who had received more adjuvant therapy. For node-positive patients, the effect of prolonged-duration therapy on disease-free survival (DFS) was greater for patients without c-erbB-2 overexpression (hazards ratio [HR], = 0.57; 95% confidence interval [CI], 0.46 to 0.72) than for those with c-erbB-2 overexpression (HR, 0.77; 95% CI, 0.51 to 1.16). Similarly, for node-negative patients, the effect of PeCT on DFS was greater for those without c-erbB-2 overexpression (HR, 0.82; 95% CI, 0.61 to 1.09) than for those with c-erbB-2 overexpression (HR, 1.22; 95% CI, 0.66 to 2.25). CONCLUSION: We conclude that tumors with overexpression of the c-erbB-2 oncogene are less responsive to cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant therapy regimens than those with a normal amount of gene product.

Prognostic importance of thymidylate synthase expression in early breast cancer.

PURPOSE: To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. PATIENTS AND METHODS: The level of TS expression was evaluated in 210 node-negative and 278 node-positive patients enrolled onto Trial V of the International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. RESULTS: High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44% of node-positive patients with low TS expression (P = .03). Forty-one percent of patients with node-positive high-TS-expressing tumors were alive after 10 years, compared with 49% of those with low TS expression (P = .06). The association between TS and disease-free survival (DFS) and overall survival (OS) was independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/ progestin receptor (PR) status, c-erb B-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P < .01 for DFS; P < .01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. CONCLUSION: In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy.

Cathepsin B immunohistochemical staining in tumor and endothelial cells is a new prognostic factor for survival in patients with brain tumors.

The cysteine endopeptidase, cathepsin (Cat) B, and its endogenous inhibitor, stefin A, were found relevant for cancer progression of many neoplasms, including human brain tumors. Histological sections of 100 primary brain tumors, 27 benign and 73 malignant, were stained immunohistochemically for Cat B and stefin A. The immunohistochemical staining of Cat B in tumor cells, endothelial cells, and macrophages was scored separately from 0-12. The score in tumor and endothelial cells was significantly higher in malignant tumors compared with benign tumors (P<0.000). A significant correlation between immunostaining of Cat B (scored together for tumor and endothelial cells) and clinical parameters, such as duration of symptoms, Karnofsky score, psycho-organic symptoms, and histological score was demonstrated. Univariate survival analysis indicated that total Cat B score above 8 was a significant predictor for shorter overall survival (P = 0.003). In glioblastoma multiforme, intense Cat B staining of endothelial cells was a significant predictor for shorter survival (P = 0.003). Stefin A immunostaining was weak and detected only in a few benign and some malignant tumors, suggesting that this inhibitor alone is not sufficient in balancing proteolytic activity of Cat B. We conclude that specific immunostaining of Cat B in tumor and endothelial cells can be used to predict the risk of death in patients with primary tumors of the central nervous system.

Comparative accumulation of 99mTc and 131I in thyroid nodules: case report.

Imaging was performed with both pertechnetate and 131I in 58 patients with thyroid nodules. Pertechnetate concentrated in all 12 follicular carcinomas, in two out of seven papillary carcinomas, and in some benign nodules that did not accumulate 131I in the 24-hr images.

Causes of microsatellite instability in colorectal tumors: implications for hereditary non-polyposis colorectal cancer screening.

Microsatellite instability (MSI) analysis was performed using a "reference panel" of microsatellite markers in 345 unselected primary colorectal cancers (CRC). Thirty-five (10%) tumors were classified as high MSI (MSI-H). We identified 6 (17%) MSI-H tumors with germline mutations in mismatch repair (MMR) genes (tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC) syndrome) and 29 (83%) MSI-H tumors without germline MMR mutations (sporadic MSI-H tumors). Hypermethylation of the hMLH1 promoter was found in 26/29 (90%) sporadic MSI-H tumors but only in 1/6 (17%) HNPCC tumors (P<.001). Somatic alterations were identified in both MMR genes in HNPCC tumors but mainly in the hMSH2 gene in sporadic MSI-H tumors. LOH at MMR loci was detected in 3/6 (50%) HNPCC tumors and in 4/26 (15%) informative sporadic MSI-H tumors. These results together indicate different mode of inactivation of MMR genes in sporadic MSI-H tumors versus MSI-H tumors in HNPCC patients. We therefore propose that MSI analysis of newly diagnosed primary CRC followed by methylation analysis of hMLH1 promoter in MSI-H tumors and mutational analysis of MMR genes in MSI-H tumors lacking hMLH1 promoter methylation might be an efficient molecular genetic approach for HNPCC screening.

Prognostic factors in follicular carcinoma of the thyroid--a multivariate survival analysis.

AIMS: Multivariate studies of the diagnosis, treatment and prognosis of patients with follicular carcinoma of the thyroid gland are relatively scarce. The aim of our multivariate analysis was to study the factors associated with survival of patients with follicular carcinoma in Slovenia, in an iodine-deficient region. METHODS: This retrospective study was carried out in a group of 154 patients (113 women, 41 men; median age 61 years) with follicular carcinoma of the thyroid treated at the Institute of Oncology in Ljubljana between 1972-1992. Data on patient gender, age, disease history, extent of disease, morphological characteristics, mode of therapy and survival were collected. Statistical correlations between possible prognostic factors and survival were analysed by univariate and Cox's multivariate analysis. RESULTS AND CONCLUSIONS: The 10-year survival of the 154 patients was 60%. Multivariate analysis showed that tumour differentiation, primary tumour size, vascular invasion, distant metastases, regional lymph-node metastases, histological tumour type and age were independent prognostic factors for survival. The best prognosis was found in patients with well-differentiated T1 or T2 tumours, without extensive vascular invasion, without distant or regional metastases and aged under 46 years. Patients with Hürthle-cell type carcinomas had better prognosis than those with the follicular type. The worst prognosis was found in patients with poorly differentiated T4 tumours, with extensive vascular invasion, with distant or regional metastases and aged over 60 years.

Immunohistochemical localization of group II phospholipase A2 in the tumours and mucosa of the colon and rectum.

BACKGROUND: Group II phospholipase A(2)(PLA(2)) is an enzyme important in malignant transformation and in the invasion process of malignant cells. The aim of the present study was to investigate the expression of group II PLA(2)in the cancers of the colorectum, peritumoural mucosa and in the mucosa distant from the tumour. METHODS: Resection specimens from 57 patients with colorectal carcinoma (caecum 10, ascending 10, transverse 10, sigmoid colon nine, and rectum 18) were analysed immunohistochemically. Histological slides from paraffin blocks were stained by the human monoclonal group II PLA(2)antibody ('Upstate Biotechnology', Lake Placid, NY 12946, USA. Antibody Class: IgG1k. Immunogen: HPC purifed human sperm phospholipase A(2)- 14 kDa enzyme) using the standard DAKO peroxidase-labelled streptavidin-biotin method by TechMate 500 stainer. Group II PLA(2)expression was evaluated semi-quantitatively according to the extensivity and intensivity of the positive cells. For statistical evaluation the Kruskal-Wallis one way analysis of variance on ranks and the Mann-Whitney rank sum tests were used. RESULTS: The highest expression of group II PLA(2)was found in the peritumoural mucosa (median 4.00), much lower in the mucosa distal from the tumour (median 0.70) and almost no activity in the tumour itself (median 0.00), all differences were statistically significant (all pairwise multiple comparison procedures - Dunn's Method P<0.05). The expression of group II PLA(2)was higher in the left colon and rectum than in the right colon (Mann-Whitney rank sum test P<0.05). CONCLUSIONS: Our results suggest that there is variation of the group II PLA(2)expression throughout the mucosa and tumours of the colorectum, which might reflect the progression of neoplastic process.

Effect of primary treatment on survival in anaplastic thyroid carcinoma.

AIMS: Anaplastic thyroid carcinoma (ATC) is a fatal disease despite combined treatment consisting of chemotherapy, radiotherapy and surgery. The optimal sequence of treatment modalities is not known. The purpose of our retrospective non-randomized study was to find out whether timing of the treatment modality had any influence on survival, and to find out if primary surgery prolongs survival in comparison to primary chemotherapy and/or radiotherapy. METHODS: From our database of 162 patients with ATC treated at the Institute of Oncology Ljubljana from 1972-98, 79 patients (26 men, 53 women; age: 40-86 years, mean age 65 years) were included in this retrospective study. The 83 patients with distant metastases on admission, with the survival shorter than one month or patients without any treatment were excluded. The 79 patients were classified into (1) primary surgery group (n=26) and (2) primary chemotherapy and/or radiotherapy group (n=53), including the 12 patients in whom surgery was performed after chemotherapy and/or radiotherapy. The survival of both groups was compared by log-rank test and group characteristics by ANOVA and(2 test using SPSS program. RESULTS: In comparison to the primary surgery group, the patients from the primary chemotherapy and/or radiotherapy group were older and had faster growing, and larger tumours, which were not confined to the thyroid, and more frequently had regional metastases. There was no difference in the survival of the two groups (P=0.17). Survival for longer than one year was observed in 25% of patients with primary surgery and in 21% of patients with primary chemotherapy and/or radiotherapy. The best results (50% survival at one year) were obtained in patients in whom the tumour was surgically removed after primary chemotherapy and radiotherapy. CONCLUSION: This study suggests that the timing of the treatment modalities has an impact on survival and that treatment should start with chemotherapy and/or radiotherapy, with surgery to follow if possible.)

Primary bone sarcoma with rhabdomyosarcomatous component.

We present three cases of primary bone sarcoma with rhabdomyosarcomatous component which in one case appeared in a pure form, i.e., as rhabdomyosarcoma; in the other two cases it presented as one of multiple components of the tumor. The first patient was a 70-year-old man with a tumor of the left femur involving surrounding soft tissue of the thigh. Histologically, this was a case of so-called dedifferentiated chondrosarcoma with pleomorphic rhabdomyosarcoma representing high grade malignant component. The second patient, a 31-year-old man, developed a tumor in the left tibia which was a rare, fibrosarcoma-like type of rhabdomyosarcoma. The third patient was a 43-year-old woman with a tumor in the left tenth rib which was shown to be osteo- and chondrosarcoma with a minor rhabdomyosarcomatous component and was classified as malignant mesenchymoma. All patients were treated by surgery and chemotherapy. The first two of them died of metastatic disease 3 months, and 3 years and 4 months following surgery, respectively. Light microscopical diagnosis of rhabdomyosarcoma of hematoxylin-eosin sections was confirmed immunohistochemically in each case using reactions to desmin, muscle specific actin and myoglobin, and ultrastructurally in two cases. Rhabdomyosarcomatous component in primary bone tumors appears to be rarely present but more cases may be diagnosed in the future, if immunohistochemical and ultrastructural examinations are to be employed.

Comparison of standardized immunohistochemical and biochemical assays for estrogen and progesterone receptors in breast carcinoma.

The purpose of this study was to determine estrogen receptor (ER) and progesterone receptor (PR) expression assessed by dextran-coated charcoal method (DCC) and standardized immunohistochemical method (IHC) in a prospective series of 557 primary breast carcinomas, to assess the concordance between the two assays, and to evaluate the association between hormone receptor expression and various clinicopathological parameters. For ER, results of both methods were in agreement in 73.6% of the cases (277 positive, 133 negative), 74 tumors (13.3%) where IHC+/DCC- and 73 (13.1%) were IHC-/DCC+. For PR, concordant results were observed in 72.7% of the cases (201 positive and 204 negative), 127 tumors (22.8%) were IHC+/DCC- and 25 (4.5%) were IHC-/DCC+. Irrespective of the method used, ER and PR positivity showed a strong negative association with tumor grade. ER+ tumors were significantly more common among older patients. With IHC, PR+ cases were more common among tumors of lobular and mucinous type and among node positive tumors. The only parameter that was related to the concordance rate of ER determination by the DCC and IHC method was the age of the patients, with agreement being significantly lower in the group of patients younger than 50 years. On the other hand, discordant PR determination was more often observed in tumors of lower grade, node positive tumors and in tumors of lobular and mucinous type.

Transfection of mammalian cells by the methods of receptor mediated gene transfer and particle bombardment.

The efficacy of currently developed methods for gene transfer into mammalian cells depends primarily on the transfection technique, and also on the type of targeted cells. Considering the importance of gene transfer in the creation of gene therapies, our study was aimed at the assessment of transfection capacity of receptor mediated gene transfer method (RMGT), and method of particle bombardment (helios gene gun system--HGG) in different normal and malignant mammalian cells ex vivo. In addition, the HGG was also assessed for its ability to transfect tumor cells of subcutaneous (s.c.) tumors in C57Bl/6 mice in vivo. Using RMGT an average ex vivo transfection rate of 35.7%, and 20.4% was achieved in malignant melanoma B-16, and human breast adenocarcinoma MCF7, respectively. However, in normal fibroblast L929 cells the transfection by RMGT succeeded only in 2.1% of the cells. On the other hand, the transfection efficacy of HGG was comparable in both malignant cell lines resulting in an average gene transfer to 9.6% of B-16 and 10.5% of MCF7 cells, while only 3.9% of normal fibroblasts were successfully transfected. Application of HGG for an in vivo gene transfer into s.c. B-16 melanoma tumors in C57Bl/6 mice resulted in a successful but limited transfection of the epithelium as well as of the superficially sited tumor cells. Taking into consideration both methods, RMGT is more appropriate for ex vivo transfection of cells, under the condition that target cells express a specific receptor for the molecule attached to the carrier. On the other hand, HGG is not complicated to use, no requirements for specific structures on target cells are necessary (potentially usable in different cells), and it has applicability in direct in vivo transfection processes.

Added value of blue dye in sentinel node biopsy for breast cancer.

Sentinel node biopsy in breast cancer is a new rapidly advancing minimal invasive procedure which enables nodal staging of clinically node negative breast cancer patients without performing complete axillary dissection. There are still controversies over the added value of Blue Dye when lymphoscintigraphy and gamma probe are used. In our series, 91 consecutive patients with invasive breast carcinoma were operated by a single surgeon, using lymphoscintigraphy, gamma probe and Blue Dye. The sentinel nodes (SLN) were histologically examined by HE and immunohistochemistry. Lymphoscintigraphy was succesful in 81 patients (89%). After the injection of Blue Dye, SLN could be identified in all 91 patients. Metastases in the SLN were present in 35 patients. We retrieved 128 SLN, of these 93 were hot and blue, 19 only hot and 16 only blue. The distribution of metastatic and nonmetastatic SLN between these three labeling groups was not different (P = 0.9361). We could not show any difference in the metastatic involvement of SLN in patients in whom preoperative lymphoscintigraphy could visualise the SLN preoperatively compared to those in whom it could not (P = 0.7315). False negativity calculated in our initial series of 36 patients was 0%. Our study showed added value of Blue Dye in detection of metastatic and nonmetastatic SLN.

Differential diagnosis of the pleomorphic aspiration biopsy sample of nonepithelial lesions.

The major problem confronting the cytopathologist in interpretation of the pleomorphic aspiration biopsy sample (ABS) of nonepithelial lesions is to provide a reasonable differential diagnosis, since the presence of cellular pleomorphism alone does not always denote malignancy. One must be fully cognizant of a vast number of pathologic processes to make a correct interpretation. Some indication of the extent of the problem and the potential diagnostic pitfalls are outlined in selection of nonneoplastic processes and benign and malignant tumors of mesenchymal origin presenting as pleomorphic ABSs.

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.

Secretory breast carcinoma in a man diagnosed by fine needle aspiration biopsy. A case report.

Preoperative aspiration biopsy of a breast tumor in a 20-year-old male resulted in a diagnosis of secretory breast carcinoma. The material obtained from aspiration biopsy was also used for electron microscopic, immunocytochemical and flow cytometric analysis. The characteristic light microscopic features were numerous large secretory vacuoles containing proteinaceous material, which was also seen in the background of the smear. Electron microscopy revealed numerous intracellular lumina and some intercellular ones filled with secretory material as well as membrane-bound vacuoles. Immunoreactivity was positive for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, alpha-lactalbumin and vimentin. Flow cytometric analysis showed the tumor to be diploid. The affected breast and tumor were resected, and the cytologic diagnosis was confirmed histopathologically. The cytomorphologic features of secretory breast carcinoma seem to be alike in men and women and are sufficiently characteristic to permit a definitive preoperative diagnosis from fine needle aspiration biopsy smears. The differential diagnosis with other tumors is discussed briefly.

Papillary thyroid carcinoma with exuberant nodular fasciitis-like stroma in a fine needle aspirate. A case report.

BACKGROUND: Papillary thyroid carcinoma (PTC) with exuberant nodular fasciitis-like stroma (PTC-ES) is a new morphologic variant of conventional PTC. It is characterized by extensive reactive stromal proliferation, which may occupy 60-80% of the tumor. CASE: A 42-year-old female developed a tender, left-sided thyroid mass. The fine needle aspiration biopsy specimen contained, besides diagnostic epithelial features of PTC, many cohesive tissue fragments of cellular stroma. CONCLUSION: A correct cytopathologic diagnosis of PTC-ES can be established if both epithelial and stromal components are present in needle aspirates.

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.