Comparison of nuclear DNA content in primary and metastatic papillary thyroid carcinoma.

Nuclear DNA values were determined in 40 primary papillary thyroid carcinomas, as well as in 52 corresponding local recurrences and metastases were observed either at the time of diagnosis or up to 20 years later. The patient population consisted of 34 survivors and 6 nonsurvivors. In survivors, both the primary tumors and their recurrences and metastases exhibited a majority of cells with DNA values within the normal diploid region, whereas nonsurvivors showed increased and scattered DNA values. In all cases, the primary tumors and the corresponding recurrences and metastases showed similar DNA distribution patterns even if many years had passed between the detection of the primary tumor and the metastases. The results indicate that in papillary thyroid carcinomas, the DNA distribution patterns in the primary tumor and the corresponding recurrences or metastases are generally similar throughout the entire period of disease.

Prognostic impact of nuclear DNA content in medullary thyroid carcinoma; a retrospective pilot study.

The prognostic significance of DNA content in medullary thyroid carcinoma was studied retrospectively in 16 patients. Five patients died within 3 years of medullary thyroid carcinoma and 11 patients survived for at least 10 years. Clinical data and tumour morphology were studied. DNA measurements on tumour cells in histologic sections were performed with slide cytophotometric technique. The tumours of the survivors had in all but two cases a DNA content comparable to that of normal cells, whereas the tumours of the non-survivors and two of the survivors had higher DNA content. The results indicate that DNA measurements in medullary thyroid carcinoma might be of use in addition to clinical and morphologic data and that further studies are warranted.

Biologic considerations and operative strategy in papillary thyroid carcinoma: arguments against the routine performance of total thyroidectomy.

Reasons cited for the routine performance of total thyroidectomy in patients with papillary thyroid carcinoma include: fear of multicentric neoplastic foci causing local recurrence and death; risk of anaplastic transformation of unresected multifocal microscopic carcinoma; toxicity of high-dose radioactive iodine to ablate normal thyroid remnants; and lack of reliable criteria for grading malignancy and identifying patients at high risk. However, autopsy studies have detected microscopic foci of papillary thyroid cancer as incidental findings in up to 24% of patients dead of other diseases. The prevalence of anaplastic transformation of papillary thyroid carcinoma as determined from reports in the literature is less than 1%. A retrospective investigation of 90 patients with papillary thyroid carcinoma derived from the Swedish National Cancer Registry showed no complications from radioiodine ablation of postoperative thyroid remnants in 45 patients. Retrospective analysis of the DNA content of tumors at the time of the initial operation showed a significant difference between a group of 10 patients who died of recurrent and metastatic papillary thyroid carcinoma and a group of 16 patients alive at least 10 years after operation despite distant metastases or recurrent cancer in the thyroid bed and/or cervical lymph nodes. The risk of permanent hypoparathyroidism is higher in patients after total thyroidectomy without apparent improvement in survival rates when compared with less extensive resections. Therefore it is proposed that the criteria for total thyroidectomy in patients with papillary thyroid carcinoma be limited to: tumors that clinically involve both lobes of the thyroid gland, extracapsular spread of cancer requiring enbloc resection, and reoperations where scarring prevents accurate delineation of the extent of the tumor. By differentiating patients at high risk for death from papillary thyroid carcinoma from patients at low risk, the measurement of DNA content may decrease the need for routine total thyroidectomy.

Oncocytic renal tubular adenoma (so-called oncocytoma) in seventeen-year-old girl.

Renal tubular neoplasms (adenomas or adenocarcinomas) are rare in children or young adults. Herein, we report an oncocytic renal tubular adenoma (so-called oncocytoma) that was found in a seventeen-year-old girl. Preoperative evaluation included aspiration of this tumor, and we suggest that preoperative aspiration is an important procedure in the diagnosis and management of suspected renal tumors in children and young adults.

Comparison of transrectal prostate digital aspiration and ultrasound-guided core biopsies in 99 men.

We compared digital transrectal needle aspiration and transrectal core prostate biopsies obtained with ultrasound guidance in 99 men. Both procedures were effective in identifying prostate cancer; complete sensitivity was 94 percent for aspiration and 90 percent for core biopsy. Aspiration confirmed 87 percent of 38 known cancers and 94 percent of 81 cancers overall, compared with 82 percent and 90 percent with core biopsies. The greatest number of cancers was found when both procedures were considered (95% of known and 98% of all cancers). Grading of both specimens was performed but was not equivalent. Unsatisfactory or inconclusive results by either procedure often obtained when cancer was present. We suggest digital transrectal needle aspiration as a first means of identifying most palpable prostate lesions. Transrectal core biopsies guided by ultrasonography should be used when suspicion of cancer cannot be confirmed by aspiration and when there is no palpable lesion (but clinical suspicion of cancer).

Squamous metaplasia in hormonally treated prostatic cancer. Significance during follow-up.

A prospective study of 59 hormonally treated prostatic cancer cases was undertaken during follow-up with sequential transrectal palpation and fine-needle aspiration. At initiation of therapy patients' ages ranged from forty-eight to eighty-two years (median, 68 years). The usual follow-up interval was 6 +/- 3 months, and follow-up periods ranged from six months to one hundred twenty months (median 48 months). The cytologic findings were categorized under four cytologic response types and palpation findings under five response grades. Four different degrees of squamous metaplasia (1+, 2+, 3+, 4+) were observed in smears, depending on semiquantitative determination of squamous metaplastic cells in relation to the total amount of benign and malignant epithelial cells in the smear. There were 341 follow-up observations in which both transrectal fine-needle aspiration cytology and palpation were done. In 306 of these, cytologic findings were found to be adequate. Comparison of squamous metaplasia with cytologic response types revealed a highly significant difference between the benign state and recurrence/frank malignancy. This was also true when frequency of squamous metaplasia was compared with palpatory response grades. It was found that squamous metaplasia can be a valuable adjunct to other cytomorphologic changes such as shrinkage of tumor cell size and decrease in size of nucleoli or its disappearance, in determining response to hormonal therapy.

Improved early detection of recurrence in prostatic carcinoma following hormonal therapy. Combined use of palpation and fine needle aspiration cytology.

Fifty-nine hormonally treated prostatic carcinoma patients were prospectively followed by rectal examination and fine needle aspiration cytology at six-month intervals for periods ranging from six to one hundred twenty months (median follow-up 48 mos). The cytologic findings and clinical impressions were divided into four or five categories, respectively, ranging from benign to clearly malignant. Cytologic material and clinical descriptions suitable for evaluation were available for 306 follow-up examinations. Of these, 209 were cytologically benign (including 191 without and 18 with clinical evidence of malignancy). The remaining 97 examinations showed cytologic evidence of malignancy of which 50 were clinically apparent (51.5%). While the correlation of clinical and cytologic findings was good (91.4%) in cases with no evidence of disease activity, our findings indicate that many recurrences which are occult to clinical examination may be detected by cytologic examination.

Determination of false negative rate in fine-needle aspiration of prostate. Study of sequential aspirations in 30 untreated carcinoma patients.

Despite several studies comparing the diagnostic accuracy of core needle biopsy and fine-needle aspiration (FNA) in the diagnosis of prostatic adenocarcinoma, no clear picture of the false negative rate for FNA is available. We studied 101 follow-up FNA evaluations in 30 patients with untreated well-differentiated carcinoma. The patients were followed for a median of two years and seven months and had from two to seven FNA follow-up evaluations (median = 2.5 evaluations per patient). If three inadequate evaluations are omitted, the combined rate of positive plus suspicious FNA biopsies was 92.9 percent (88.8% plus 4.1%, respectively). The residual false negative rate was 7.1 percent. The clinical features and follow-up data are described. A semiquantitative definition of "suspicious for malignancy" is suggested. We conclude that in experienced hands. FNA is a highly efficacious method for the diagnosis of prostatic adenocarcinoma.

Co-existent anaplastic and well differentiated thyroid carcinomas: a nuclear DNA study.

Clonal transformation of well differentiated follicular or papillary carcinomas has been suggested as a mechanism by which anaplastic carcinomas of the thyroid might arise. Of 126 cases of anaplastic (giant cell) carcinomas, 17 (13.5%) contained histologically well differentiated tumour foci within or adjacent to the high grade malignant anaplastic tumour. Cytophotometric DNA analysis after Feulgen staining was performed on 11 cases in order to evaluate ploidy of the anaplastic and the well differentiated tumour cells. The majority of these co-existent carcinomas (9/11) were papillary. All 11 anaplastic carcinomas demonstrated an aneuploid DNA pattern which correlated with a poor clinical outcome (7 of 11 died of disease in less than 6 months). In contrast six co-existent papillary and one co-existent follicular tumours were diploid. These data show that the co-existence of anaplastic and well differentiated carcinoma occurs only rarely and when it occurs only one third of the well differentiated tumours contain aneuploid tumour cells. This suggests that in the majority of cases of anaplastic thyroid carcinoma the malignant cells arise de novo rather than through clonal transformation of well differentiated carcinomas.

Nuclear DNA measurements in follicular thyroid adenomas.

The nuclear DNA content was measured retrospectively in histologically confirmed follicular adenomas in 20 patients, and prospectively in 25 patients. In the retrospective group two of the adenomas, and in the prospective group three of the adenomas were classified as atypical due to high cellularity and nuclear atypia, but with no sign of micro-invasive growth. In the group of patients studied retrospectively, the two patients with atypical adenoma had an aneuploid DNA pattern. One of these died 11 years after diagnosis with generalized disease. The other patient in this group with an aneuploid atypical adenoma is alive, as are all the remaining 18 patients with diploid adenomas. In the prospective group there were five aneuploid tumours. The atypical adenomas were aneuploid in two cases and polyploid in one case. No patient in the prospective group has shown any evidence of recurrence so far. Although DNA measurements are of value in distinguishing between low and high malignant potential in invasive tumors, the prognostic information if no invasion is found is uncertain. The importance of examining an adequate number of tissue blocks from the capsular region is emphasized.

Fine-needle biopsy cytology and DNA analysis. Their place in the evaluation and treatment of patients with thyroid neoplasms.

Fine-needle aspiration allows sampling of tissues without surgical biopsy. This technique provides accuracy, speed, patient acceptance, and individual cells for the study of neoplasia. When this procedure is combined with DNA analysis, it is possible to obtain preoperatively additional diagnostic and prognostic information superior to that obtained by clinical and morphologic methods alone. This information is of utmost importance when planning appropriate treatment.

Nuclear DNA content in anaplastic giant-cell thyroid carcinoma.

The nuclear DNA content was measured in 36 cases of anaplastic giant-cell thyroid carcinoma registered at Radiumhemmet, Karolinska Hospital, Sweden, between November 1973 and December 1985. The DNA content was measured in morphologically identified single tumor cells by image cytometry. Either fine needle aspirate material or histologic sections from primary tumors, recurrences, or metastases were studied. All tumors were aneuploid. Aneuploidy decreased in four of seven tumors studied sequentially. Analysis of the nuclear DNA content did not provide additional prognostic information and did not explain why occasional patients enjoy longer survival than expected.

Mucin production by pleomorphic adenomas of the parotid gland: a cytologic spectrum.

Mucinous salivary gland aspirations represent a special differential diagnostic problem. Considerations include pleomorphic adenoma, Warthin's tumor, chronic obstructive sialadenitis, and low-grade mucoepidermoid carcinoma. We herein discuss three cases that illustrate a spectrum of mucin production by pleomorphic adenomas. The literature is reviewed, and the possible distinction of pleomorphic adenoma from low-grade mucoepidermoid carcinoma is considered.

Smearing techniques for the concentration of particles from fine needle aspiration biopsy.

Fine needle aspiration biopsy of palpable masses yields a variety of specimens. Some are fluid, whereas others are semisolid; some contain numerous particles, whereas others contain no identifiable particulate fragments. Not surprisingly, no single smearing technique can reasonably be expected to provide good results with such a variety of specimens. This article describes a family of techniques, of which one or more are applicable to virtually any fine needle aspiration biopsy specimen. The techniques described and illustrated include the two-step, one-step, absorption, and watch-glass techniques.

Basal-cell adenoma of the salivary gland: a benign adenoma that cytologically mimics adenoid cystic carcinoma.

We describe the fine-needle aspiration cytology of two cases of basal-cell adenoma (BCA) of the parotid gland. Both consisted of groups of small uniform cells with scant cytoplasm and occasional single cells. Small amounts of metachromatic stroma were present in smears from one case. The cytologic and histologic similarities between (BCA) and the solid type of adenoid cystic carcinoma are emphasized. Unequivocal distinction between these two entities may not be possible by cytologic criteria alone.

Fine needle aspiration cytology of tubular adenoma of the breast. A report of two cases.

During the routine practice of fine needle aspiration of the breast, two tubular adenomas were encountered. The patients were 46 and 69 years of age. In one case the appearances indicated a benign epithelial proliferative lesion, while in the other, epithelial atypia necessitated surgical excision. The differential diagnoses included other benign epithelial proliferative lesions and carcinoma. To avoid inappropriate surgery, the cytomorphologic spectrum of benign epithelial proliferative lesions, including tubular adenoma, must be recognized.

Planimetric studies on fine needle aspirates from follicular adenoma and follicular carcinoma of the thyroid.

A planimetric study was performed on fine needle aspiration biopsy smears from 21 follicular thyroid adenomas, 13 follicular thyroid carcinomas and 7 nontoxic goiters. The nuclear and the cytoplasmic projected areas were measured in each smear on 50 cells with intact nuclei. The nuclear-cytoplasmic area was calculated. Significant differences in mean nuclear area were found between benign and malignant follicular neoplasms and between neoplastic cells and cells from nontoxic goiter. Planimetry of cells aspirated from follicular neoplasms permitted differentiation between carcinomas and adenomas with a high degree of statistical probability.

The cytology of a giant-cell, osteoclastoma-like malignant thyroid neoplasms. A case report.

The cytologic findings on aspirated material in a rare giant-cell, "osteoclastoma-like," malignant neoplasm of the thyroid are reported.

Differential diagnosis between follicular adenoma and follicular carcinoma of the thyroid by nuclear DNA determination.

Distinction between follicular adenomas and follicular carcinomas of the thyroid using fine needle aspiration cytology presents a problem. We investigated whether Feulgen photometric nucear DNA determination could offer additional, usable information for differential diagnosis. Since both diploid carcinomas and polyploid, widely scattered adenomas and nodular colloid goiter are seen, we found that nuclear DNA determinations proved useful in differential diagnosis only for occasional special cases.

3H-thymidine incorporation into mammary carcinoma cells obtained by needle aspiration before and during endocrine therapy.

3H-thymidine autoradiography was used to evaluate DNA-synthesis in carcinoma cells obtained by fine-needle aspiration biopsy from mammary carcinomas. Needle aspirates were analyzed before and after oophorectomy, and before and during treatment with oestrogen or anti-oestrogen (tamoxifen). Tumor regression occurred in 18 patients-in one of four following oophorectomy, in 15 of 38 treated with tamoxifen and in two of three given oestrogen. Seven tumors remained stationary for long periods-up to a year. In 20 cases there was tumor progression. Regression of tumors was preceded by a decrease in the fraction of 3H-thymidine-labeled cells (s-phase cells). The tumors that remained stationary or progressed retained significant levels of 3H-thymidine incorporation. This study thus showed that 3H-thymidine autoradiography can give an early estimate of tumour response to endocrine therapy. Considerable differences were found between the carcinomas in regard to proportions of S-phase cells. Further insight into this parameter may be useful for planning chemotherapy with S-phase specific agents.

PIP: Variations in DNA synthesis as measured by tritiated-thymidine autoradiography in mammary carcinoma before and during endocrine therapy were studied in patients treated for inoperable or locally recurrent mammary carcinoma. Tumor cells were collected by aspiration biopsy and immediately expelled into the incubating solution. Cell viability was assessed by staining unfixed cells with trypan blue and fixed cells with orecin. To assess viability tritiated-uridine incorporation was used in some experiments. The same cells were identified by each method. Bilateral oophorectomy was done in 4 patients. In the 1 case in which regression followed, a 5-fold decrease in DNA-synthesis was noted 1 week after oophorectomy but at 2 weeks no cells incoporated thymidine. In the 3 patients with tumor progression the fraction of labeled cells was unchanged. For antiestrogen therapy, Tamoxifen (Nolvadex) was used. Serial needle aspirates were collected from 38 patients who received 20 mg of Tamoxifen twice daily. Complete remission followed in 7, incomplete remission in 8, stationary disease in 7, and progression in 16. DNA synthesis fell to very low values after 1-3 weeks and remained low in the 7 cases with complete regression. Tumors showing partial regression showed diminished fractions of 5-phase cells (tritiated-thymidine-labeled cells) after 1-5 weeks. In 1 instance at 72 weeks the S-phase fraction of cells was higher than initial value. Tumor value remained stationary for 40 weeks and then increased. Antiestrogen therapy was stopped at 82 weeks. In those with progressive tumor growth there was high DNA synthesis. Between 20-30% of the cells were replicating DNA. None showed decrease in the fraction of S-phase cells, and 1 showed increase. For estrogen therapy, estradiol valepianate was given im every 2 weeks. Of the 3 patients who received estrogen therapy, 2 of the tumors responded and the DNA-synthesis rapidly decreased until none was measurable after 4 weeks. S-phase values prior to endocrine therapy showed no correlation with the therapeutic response. Tumors that responded showed a decrease in the proportion of S-phase cells during the first 3 weeks. In tumors responding to encocrine therapy the decrease in tritiated-thymidine incorporation was rapid and preceded reduction in tumor size. Data suggest that 2 aspirates should be studied before therapy and repeated after 2-4 weeks in order to include the minimal proportion of S-phase cells. The patients accepted the needle biopsies well. There were no growths of carcinoma at the puncture sites. About 5 weeks must elapse before tumor response can be assessed. Determining hormone receptors in surgically removed carcinoma specimens gives much more rapid indications as to possible response to endocrine therapy.