A comparison of the effects of ifosfamide vs. mafosfamide treatment on intracellular glutathione levels and immunological functions of immunocompetent lymphocyte subsets

OBJECTIVE: To compare the sensitivity and potentials of flow and image cytometry in assessing DNA content. STUDY DESIGN: The study was performed on 152 tumors (oral cavity, uterine cervix, bladder, colorectum, breast). Flow cytometry was carried out on cell suspensions from frozen samples, and the results were expressed as the DNA index. Image cytometry was performed on Feulgen-stained sections, and the results were expressed as the rate of cells exceeding 2.5c or 5c. For colorectal and breast cancers, DNA content by image cytometry was also measured on imprints and was expressed as the DNA index or rate of cells exceeding 2.5c and 5c. RESULTS: Among flow cytometric diploid tumors, image cytometric analysis performed on histologic sections showed about 80% diploid tumors from the uterine cervix and breast cancers. The frequency decreased to 36% for oral cavity cancers. Generally satisfactory concordance was observed when flow cytometric aneuploid tumors were analyzed. A highly significant correlation was observed between DNA indices observed by flow and image cytometry on imprints. CONCLUSION: Image cytometry appears more sensitive than flow cytometry in detecting small, aneuploid clones, but its main limitation is the low power in resolving near-diploid cell populations. The results on imprints indicate that image cytometry is a potential alternative approach for small tumor samples.     

Combined analysis of flow cytometry and morphometry of ovarian granulosa cell tumor

BACKGROUND: It is difficult to determine the prognosis of granulosa cell tumors (GCT) at the time of diagnosis. METHODS: The nuclear DNA content of 17 patients with ovarian GCT was investigated by flow cytometry using paraffin-embedded tissue. Nuclear area (NA), nuclear perimeter (NP), and nuclear shape factor (NSF) were measured by an image analyzer using hematoxylin- and-eosin-stained sections. RESULTS: The follow-up period of the patients ranged from 2 months to 11 years. Thirteen tumors were diploid or near diploid, whereas one was tetraploid, and three were aneuploid. Two tumors had varying degrees of DNA content heterogeneity. Crude survival of the patients with an euploid tumor (13 diploid, 1 tetraploid) was more favorable than that of the patients with an aneuploid tumor. Patients with S-phase fraction (SPF) greater than 10% or DNA content heterogeneity experienced disease recurrence or metastasis. A significant difference was observed in NA and NP between those with and without metastasis. CONCLUSIONS: Our results indicate that DNA aneuploidy, large SPF, DNA content heterogeneity, and large NA and NP are adverse prognostic factors in GCT. Thus, flow cytometric and morphometric measurement may provide a rapid and valuable method to predict the biologic behavior of GCT.     

Improvement in cumulative response rates following implementation of a financial incentive

We present our experience in the treatment of growth hormone (GH)-producing pituitary adenomas using irradiation alone. Between 1983 and 1991, 21 patients suffering from GH-secreting pituitary adenomas were treated with radiotherapy alone. Two bilateral opposing coaxial fields were used in 10 patients and in the remaining 11 a third frontovertex field was added. Treatment was given in 1.8-2 Gy daily fractions and total dose ranged between 45 and 54 Gy. Treatment was given using a cobalt unit. Four patients treated with somatostatin prior to and 14 patients treated after the end of radiotherapy experienced symptom relief for 6-28 weeks. The 5-year actuarial rate of disease control was 72%. Five out of six failed patients had macroadenomas. Hypopituitarism was observed in 5/21 (24%) patients. Whereas RT alone is effective in the treatment of microadenomas, this is not true for large infiltrative macroadenomas.     

Neuro-ophthalmological alternations in patients with pituitary adenomas and intrasellar arachnoidocele

INTRODUCTION, MATERIAL AND METHODS: We studied 103 patients with hypophyseal tumors aged between 15 and 74, with a marked predominance of females. Results. Of these, 49 patients were diagnosed as having macroadenomas (47.5%), 27 with microadenomas (26.2%), 25 with arachnoidoceles (24.3%) and two with craniopharyngiomas (1.9%). Of the total there were 78.9% functioning tumors of which the commonest was prolactinoma. CONCLUSIONS: Kinetic and static perimetry complement each other as diagnostic methods to obtain information about damage to the visual pathway caused by these tumors.     

DNA analysis in hepatoblastoma by flow and image cytometry

BACKGROUND: In several types of tumors, including hepatocellular carcinoma, prognosis could be correlated with DNA ploidy. Few studies have been performed on hepatoblastoma with contradictory results. METHODS: Twenty-nine cases of nonpretreated hepatoblastoma were studied with flow cytometry and image cytometry for DNA index and proliferation index using paraffin-embedded tissue. RESULTS: Twenty-three (79.9%) tumors were diploid, and 6 (20.7%) were aneuploid (hyperdiploid). Patients with diploid tumors were younger than those with aneuploid tumors. With regard to stage, diploid tumors were almost equally distributed among stages (tumor, lymph node metastases, distant metastases), whereas aneuploid tumors tended to occur in higher stages (tumor, lymph node metastases, distant metastases). Diploid tumors had clearly a better prognosis than aneuploid tumors, although the difference was not statistically significant (flow cytometry, P = 0.06; image cytometry, P = 0.16). A more favorable prognosis was also noted for hepatoblastomas with low-proliferation index (< or = 7%), but the difference from tumors with high-proliferation index (> 7%) again was not statistically significant (P = 0.16). CONCLUSIONS: Although no statistically significant differences in prognosis between hepatoblastomas with diploid and aneuploid DNA content, respectively, were found, there is a clear tendency that diploid hepatoblastomas behave more favorably. The same is true for hepatoblastomas with low-proliferation index.     

Reassessment of the role of radiation therapy in the treatment of endocrine-inactive pituitary macroadenomas

OBJECTIVE: This prospective clinical trial was undertaken to assess the rate of tumor recurrence in patients with endocrine-inactive pituitary macroadenomas who underwent gross total surgical resection of their tumors and did not receive adjuvant radiotherapy. METHODS: Between December 1987 and July 1994, 45 patients with endocrine-inactive pituitary macroadenomas underwent transsphenoidal surgery. In 38 (84%) of these patients, gross total surgical resection was achieved and was confirmed by postoperative magnetic resonance imaging (n = 37) or computed tomography (n = 1). After receiving counseling from the neurosurgeon concerning the risks and benefits of radiation therapy, 32 of the 38 patients elected not to receive adjuvant radiotherapy. Patients were followed through March 1998 with radiographic imaging obtained every 6 months for the first 2 years, annually for postoperative Years 3 and 4, and then every 2 to 3 years thereafter. The study end point was defined as radiographic tumor recurrence or patient death. RESULTS: The mean follow-up duration for the study group was 5.5 years. During that time, 2 of 32 (6%) patients developed recurrence, at 18 and 24 months, respectively, after initial surgery. Both were successfully treated using radiation therapy, with one requiring additional surgery. Three additional patients died as a result of unrelated causes 9, 12, and 49 months, respectively, after initial surgery. Immunocytochemical analysis revealed 66% of the tumors to be weak gonadotroph cell adenomas, 22% to be null cell adenomas, 9% to be silent prolactinomas, and 3% to be silent corticotroph cell adenomas. CONCLUSION: This study demonstrates a 6% 5-year recurrence rate in patients with endocrine-inactive pituitary macroadenomas treated using gross total surgical resection alone. Reserving radiation therapy for the infrequent patient with recurrence and sparing the majority of patients the associated risks inherent in its use seems reasonable.     

Triple arthrodesis with lateral column lengthening for treatment of severe planovalgus deformity

The occurrence of abnormal nuclear DNA content in major salivary gland adenomas is not well known and its correlation with tumor recurrence has not been documented previously. From 1987 to 1991, 119 consecutive major salivary gland adenomas were operated on at Turku University Central Hospital. These tumors were analyzed by flow cytometry and 100 (84%) were found to be diploid, 12 (10%) near-diploid and 7 (6%) aneuploid with DNA indexes > 1.15. The mean proliferation rate measured as a percentage of cells in the S-phase fraction was 2.5 +/- 1.6%. The histological slides were then blindly reclassified according to current World Health Organization classification. As a result histological classification was changed in 3 tumors: malignant cells were found in 2 aneuploid tumors and 1 diploid neoplasm. Preoperative cytological fine-needle aspiration biopsy had been considered as possibly malignant in 2 of these cases. Among all case material 10 specimens were recurrent tumors; although the tendency to recur depended on the extent and adequacy of the surgery performed, multiple recurrences were associated with non-diploid tumors.     

Determination of DNA content in salivary gland tumors

BACKGROUND: DNA content determination is a useful tool in the characterization of different malignant tumors. AIM: To measure DNA content in cells of salivary gland tumors as adjunct to histological diagnosis, correlating morphologic and biological features of these tumors. MATERIAL AND METHODS: From the archives of the Pathology service of a general hospital, 21 salivary gland tumors, 15 pleomorphic adenomas, 3 mucoepidermoid carcinomas and 3 cystic adenoid carcinomas were selected. DNA content was determined in the histological samples using a flow cytometric DNA analysis. RESULTS: All pleomorphic adenomas had a normal or diploid DNA content. Fifty percent of malignant tumors had an aneuploid DNA content (1 mucoepidermoid carcinoma and 2 cystic adenoid carcinomas). CONCLUSIONS: DNA determination may help in the histological diagnosis of salivary gland tumors. The presence of aneuploidy suggests malignity.     

Transsphenoidal microsurgery of pituitary macroadenomas with long-term follow-up results

The authors have reported on 108 patients with pituitary macroadenomas (measuring 2 cm in at least one diameter) who underwent 117 transsphenoidal operations and five craniotomies, and were followed for periods ranging from 6 months to 14 years. Vision improved in 90% of the patients. Gross total tumor removal with no evidence of residual tumor tissue demonstrable on the postoperative computerized tomography scan was accomplished in 41% of cases. However, gross total tumor removal is not synonymous with complete tumor removal. Endocrine cure was possible in 25% of prolactin-secreting and 20% of growth hormone-secreting adenomas. The incidence of recurrence was 12%, with the majority occurring from 4 to 8 years postoperatively. Both the tumors with suprasellar extension of more than 2 cm and the hard fibrotic tumors had a higher recurrence rate. Postoperative administration of radiation therapy has been associated with a significantly lower recurrence rate than when this therapy was withheld. Transsphenoidal surgery of pituitary macroadenomas confined to the extra-arachnoid space is associated with a relatively small number of complications. The operative technique used in this series is described.     

Clinical experience in Hurthle cell tumors

In the period 1987-1997 6 patients with Hürthle cell carcinomas and 4 patients with Hürthle cell adenomas underwent primary surgical treatment (8.1% of all thyroid carcinomas). The diagnosis of Hürthle cell tumor was based on the presence of more then 75% Hürthle cells and the malignity on capsular or/and vascular invasion. All the patients with Hürthle cell cancer underwent total thyroidectomy, in three cases with Hürthle cell adenoma thyroid lobectomy was performed and in one case total thyroidectomy. Follow-up time ranged from 1 to 8 years after surgery (mean 4.5 years). There was no death and no recurrence. The Authors have studied the nuclear DNA content in Hürthle cell tumors: 3 adenomas were euploid and 1 was aneuploid, 4 carcinomas were aneuploid and 2 were euploid. The results in Authors' study of the DNA content and nuclear DNA ploidy are not uniformly consistent enough to allow a distinction between benign and malignant neoplasms and to evaluate the prognosis, but the number of patients and the follow up are still too limited.     

P53 protein expression and DNA ploidy in common epithelial tumors of the ovary

OBJECTIVE: To investigate p53 protein expression and DNA content in imprints from surgical biopsies of common epithelial tumors of the ovary. STUDY DESIGN: The study was based on 60 cases of epithelial tumors of the ovary (15 benign, 3 border-line and 42 malignant). For the demonstration of p53 protein, immunocytochemical staining with the avidin-extravidin technique was performed using monoclonal antibody p53 DO-7. DNA content was measured by image cytometry after Feulgen staining. RESULTS: There was a strong correlation between p53 expression and aneuploidy, with the difference between diploid and aneuploid tumors statistically significant (P < .001). A correlation was found between DNA ploidy, histologic grade and clinical stage (P < .001 and P < .05), respectively. There was no correlation between DNA ploidy and histologic type (P = .89). No correlation was observed between p53 protein expression and grade or clinical stage of the tumors. Nevertheless, a correlation of p53 expression between early (I, II) and advanced stages (III, IV) (P < .05) was observed. All benign and borderline tumors were diploid and did not express p53 protein. CONCLUSION: The results of the present study and the data in the literature stress the value of p53 expression and DNA ploidy in assessing the malignant potential of common epithelial ovarian cancers. However, the clinical application of these data requires further study.     

Unusual approaches to hypophyseal adenomas

For pituitary adenomas surgery, rhinoseptal transsphenoidal approach is used in 98 to 99% of the cases. Although this approach is fitting for microadenomas and the majority of macroadenomas, some of them develop extensions in the nasal fossas, the posterior cranial fossa, the suprasellar region, or into the cavernous sinus and will require other approaches. For the superior routes, the frontopterional approach gives good control of the suprasellar region, the anterior and middle base of the skull. The tumor dissection is performed inside the concavity of the chiasm and between the internal carotid artery and the optic nerve (optico-carotid approach). The frontopterional approach is used for superolateral extensions, especially in the lateral fissure. The bifrontal basal inter hemispheric approach, through a medial frontal bone flap tangential to the base, gives a good route to the suprasellar region and behind the dorsum, and also for tumors extended in the third ventricle in case of prefixed chiasm. For the inferior routes, the participation of ENT or craniofacial surgeons is a great help. The transfacial or transethmoidal approach performs a hollowing of the nasal fossas and gives a large interorbital tunnel adapted for tumors extended in the rhinopharynx and the ethmoid. The Le Fort I maxillary osteotomy offers also a large approach for adenomas extending in the rhinopharynx. The transcavernous approach from Dolenc, for adenomas progressing in the cavernous sinus requires a long and difficult procedure. The progression of some adenomas in many directions may require a combined approach in one or two procedures.     

Evidence of clonal divergence in colorectal carcinoma

BACKGROUND: The aim of this study was to investigate the generation of DNA ploidy diversity in different stages of colorectal carcinoma development. METHODS: DNA flow cytometry was performed on tissue samples from 20 colorectal adenomas, 38 colorectal carcinomas, 30 lymph node metastases, and 70 hematogenous metastases. RESULTS: DNA aneuploidy was detected in 30% of the adenomas, 82% of the primary colorectal tumors, 57% of the lymph node metastases, 92% of the liver metastases, and 100% of the other distant hematogenous metastases. Multiple DNA tumor stemlines were found in 10%, 39%, 29%, 24%, and 40%, respectively. Sixty-two percent of the DNA tumor stemlines detected in the lymph node or liver metastases were also present in the primary tumors. In primary carcinomas and lymph node metastases, the DNA index distribution had a bimodal shape with a minimum at the 1.2-1.4 region. In the hematogenous metastases, a higher percentage of hypertetraploid stemlines was found. CONCLUSIONS: The emergence of DNA aneuploidy as well as clonal divergence seems to take place during the transition from adenoma to carcinoma. The DNA aneuploid stemlines formed during this phase remain relatively stable over time, although ongoing clonal evolution at distant metastatic tumor sites cannot be completely ruled out.     

Prognostic significance of DNA flow cytometric analysis in patients with nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor among Southern Chinese. Previously, the authors described the prognostic significance of a serum antibody assay to a recombinant Epstein-Barr virus Bam HI-Z replication activator protein (ZEBRA) in NPC patients with long term follow-up. In this study, the authors further reported the use of DNA flow cytometry (DNA-FCM) as an additional technique for determining the prognosis of NPC patients in the same series. METHODS: One hundred and forty-three archival biopsies from 110 NPC patients were deparaffinized and subjected to DNA-FCM analysis. DNA ploidy state and various proliferative indices (PI) of the tumors were correlated with patient survival and frequency of recurrence. RESULTS: Among the biopsies analyzed, 119 were histologically positive NPC and 24 were negative. Fifty-one tumor biopsies that fulfilled the guideline criteria of the DNA Cytometry Consensus Conference were correlated with the clinical manifestations of the patients. Among them, 43 tumors (84%) were DNA diploid and 8 (16%) were aneuploid. Two PI, S-phase fraction (SPF) and proliferation fraction (PF), appear to be potentially useful prognostic indicators. For example, PF in patients who developed locoregional recurrence (15.1%) and distant recurrence (16.4%) after radiation therapy both were significantly higher than PF in patients who were in complete remission (8.2%) (P = 0.0005 and P = 0.004, respectively). Significant differences in SPF between patients with distant recurrence (10.6%) and those in remission (5.7%) also was found (P = 0.005). Using Kaplan-Meier analysis, patients with high PF, high SPF, and aneuploid tumors had significantly poorer 12-year survival rates (35%, 26%, and 28%, respectively) than those patients with low PF, low SPF, and diploid tumors (77%, 67%, and 59%, respectively) (P < 0.0009, P < 0.004, and P < 0.01, respectively). CONCLUSIONS: Determination of tumor PI and DNA ploidy state by DNA-FCM at diagnosis of NPC can be potentially useful in selecting a poor prognostic subgroup of NPC patients. These parameters may enable oncologists to plan for more stringent treatment strategies such as hyperfractionated and accelerated radiation therapy or concomitant chemoradiotherapy for these patients.     

Transsphenoidal microsurgical therapy of prolactinomas: initial outcomes and long-term results

OBJECTIVE: Prolactinomas are frequently treated primarily with dopamine agonists; however, these agents have disadvantages and require life-long therapy. We therefore reassessed transsphenoidal microsurgery as an alternative therapy. METHODS: We reviewed the data for 121 female patients treated surgically for prolactinomas between 1976 and 1979 (Group 1) and 98 patients treated between 1988 and 1992 (Group 2). RESULTS: Of 219 women, 92% with preoperative prolactin (PRL) values of < or = 100 ng/ml and 91% with intrasellar microadenomas experienced initial remission; 80 to 88% of patients with intrasellar macroadenomas or macroadenomas showing moderate suprasellar extension or focal sphenoid sinus invasion experienced remission. Women with PRL values of > 200 ng/ml and those with larger and more invasive adenomas experienced poorer outcomes (37-41% remission). Lower preoperative PRL values and adenoma stage were the best predictors of initial surgical outcomes. At the most recent evaluations, 89% of women who experienced initial remission continued to experience clinical remission; 85% exhibited normal PRL values, and 5% demonstrated mild, asymptomatic, recurrent hyperprolactinemia (PRL values of < 34 ng/ml). In Group 1, 84% of patients continued to experience remission (82% with normal PRL values) after a median follow-up period of 15.6 years. In Group 2, 97% of patients continued to experience remission (88% with normal PRL values) after a median follow-up period of 3.2 years. Lower postoperative PRL values were the best predictors of long-term remission. CONCLUSION: Transsphenoidal microsurgery is an effective alternative to long-term medical therapy for selected patients with prolactinomas. Successful outcomes and long-term remission were achieved in patients with microadenomas and noninvasive macroadenomas.     

Nuclear DNA ploidy pattern and tissue levels of dihydroxyphenylalanine and catecholamines in pheochromocytoma

Flow-cytometric analysis of nuclear DNA and measurements of tissue levels of dihydroxyphenylalanine (dopa) and catecholamines were performed using fresh samples of tissue taken from 17 patients with pheochromocytoma. Nine (53%) tumors had a diploid pattern of DNA, and 8 (47%) had an aneuploid pattern. The tissue concentrations of dopa, dopamine, norepinephrine, and epinephrine did not differ significantly between pheochromocytomas with a diploid and those with an anoeuploid pattern. These results suggest that there is no correlation between nuclear DNA ploidy and tissue levels of dopa and catecholamines in pheochromocytomas.     

Specific K-ras2 mutations in human sporadic colorectal adenomas are associated with DNA near-diploid aneuploidy and inhibition of proliferation

Recent studies indicate that p21ras proteins mediate their multiple cell functions through interactions with multiple effectors and that the number of new effectors is growing. We recently reported that K-ras2 mutations in human colorectal adenomas were associated with chromosome instability and proliferation changes. In the present study, we extend these previous observations. Hereditary and multiple (n > or = 5) adenomas and adenomas with early cancer were excluded. Dysplasia was moderate in 91 cases and high in 25, and the median adenoma size was 1.5 cm. K-ras2 spectrum analysis was done by sequence-specific oligonucleotide hybridization using nuclear suspensions provided by analysis and sorting of multiparameter flow cytometry. In particular, tissue inflammatory cells were separated for DNA diploid tumors, whereas DNA aneuploid epithelial subclones were analyzed separately. K-ras2 mutations and DNA aneuploidy were both detected in 29 of 116 (25%) cases. DNA aneuploid index was in the near-diploid region in the majority of cases. DNA aneuploidy was strongly associated with G-->C/T transversions. An association was also found between low S-phase values and G-->A transitions. These findings were confirmed using multivariate logistic regression analysis to account for the effects of size, dysplasia, site, type, age, and sex. These data suggest that specific K-ras2 mutations in a subgroup of human sporadic colorectal adenomas play a role in chromosome instability and, contrary to expectations, are associated with inhibition of proliferation.     

Detection of false DNA aneuploidy and false DNA multiploidy in flow cytometric DNA analysis

Although false DNA aneuploid peaks have previously been described in normal tissue, criteria for distinguishing them from 'true' near-diploid peaks have not been established. Normal thyroid (n = 4) and kidney (n = 1) tissue were allowed to autolyze over a fixed period of time and DNA content was analyzed by flow cytometry (FCM). Autolysis was associated with the development of distinct separate G0/G1 peaks which had low DNA indices (1.09-1.18) and showed decreased forward light scatter (FSC) when compared to fresh tissue. Using DNA content and FSC measurements similar false DNA aneuploid peaks were identified in 29/94 surgical specimens. These cases included both benign and malignant lesions from thyroid (n = 63) with the remaining 31 neoplastic cases being from breast (16), lymphoma (8), sarcoma (4), lung (2) and uterine (1) tissue. In addition, false DNA multiploidy was identified. None of these cases showed histological evidence of necrosis. In a parallel comparison study using image cytometry (ICM) on the thyroid nodules, the presence of false DNA aneuploidy was supported. Investigators should routinely employ quality control criteria to identify possible cases of false DNA aneuploidy when measuring DNA content using FCM.     

The accuracy of CT and MR evaluation of the sella turcica for detection of adrenocorticotropic hormone-secreting adenomas in Cushing disease

PURPOSE: To document the accuracy of CT and MR of the sella turcica for detecting adrenocorticotropic hormone-secreting adenomas in Cushing disease. METHODS: The radiologic findings of the sella turcica prior to transsphenoidal surgery are reviewed in 141 patients who had biochemical evidence of pituitary-dependent Cushing disease. Axial thin-collimation CT scans with sagittal and coronal reformations before and after contrast enhancement were obtained in 125 patients. Seventy-eight patients had MR examinations with a 1.5-T superconducting magnet. In 11 of the patients gadolinium-enhanced MR scans were also obtained. The preoperative interpretation of the imaging studies was correlated with the surgical findings and patients follow-up. RESULTS: The sella turcica was enlarged in 43 cases (30%). In 125 patients reformatted or direct coronal thin-collimation CT scans were available. Seventy-eight of the patients had MR. In the 12 patients with pituitary macroadenomas, the accuracy of CT (n = 10) and MR (n = 10) in respect to detection of the lesion was 100%. Of the 98 microadenomas assessed by CT, 47 (48%) were directly depicted as distinct hypodense lesions. In only 31 of 73 cases (42%), however, could CT predict the precise anatomic location and extent of the lesions. Only patients in whom the hypercortisolism was corrected by later surgery were considered for the correlation analysis. Of the 52 microadenomas assessed by MR, 28 (53%) were directly depicted as distinct lesions of reduced signal intensity on T1-weighted images, and in only 21 of 41 cases (52%) did MR show good correlation to the surgical findings. Some degree of partially empty sella was found in 22% of the patients. CONCLUSIONS: Although both the sensitivity and the diagnostic accuracy of imaging methods of the sella turcica have been considerably improved in comparison with previous reports, they still provide only a minor contribution to the diagnosis and differential diagnosis of Cushing syndrome.     

Dye leakage of four root end filling materials: effects of blood contamination

OBJECTIVES: A measurement of cell DNA content would be highly useful in determining the malignant nature of thyroid tumours in cases without distinctive features such as metastases, capsule invasion or emboli. Abnormal cell ploidy can be recognized with flow cytometry, but it is not known whether such results have diagnostic value. We therefore compared--in a double blind prospective study--the results of flow cytometry and pathologic diagnosis in fresh tumoural and non-tumoural thyroid cells. METHODS: Fifty unselected cold thyroid nodules were obtained from 50 consecutive patients (40 women, 10 men; age 18-80 years; mean 46) who underwent surgery within a 6 month period. Surrounding non-tumoural tissue was also obtained in 46 of them. Cell ploidy and the percentage of cells in each cell phase was determined with flow cytometry for both tumoural and nontumoural tissues. Two pathologists, unaware of the flow cytometric results, independently established the histologic diagnosis according to the WHO classification. RESULTS: The pathologic diagnosis was carcinoma in 7 cases (papillary carcinoma 6, vesicular carcinoma 1) and benign adenomas in 43 (29 macrovesicular, 11 microvesicular, 3 oncocytal). All the non-tumoural tissue samples were diploid. All 7 carcinomas were diploid and 10 of the 43 benign adenomas were aneuploid (4 near-diploid, 3 hyperploid, 1 near-tetraploid, 2 multiploid). The mean proliferation index was increased in 5 diploid tumours. CONCLUSION: These findings confirm that cell ploidy measured by flow cytometry is of no diagnostic value in the thyroid gland. It was also revealed that aneuploidy in adenomas may be related to tissue rearrangements of undetermined prognostic significance.