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Morphometric Evaluation of Fine Needle Biopsy of Single Thyroid Nodules
Path. Res. Pract. 185, 722-725 (1989)
Morphometric Evaluation of Fine Needle Biopsy of Single Thyroid Nodules I. Sassi, F. Mangili, M. Sironi, M. Freschi and A. Cantaboni
Cattedra di Anatomia e Istologia Patologica, Universita'degli Studi, Istituto H S. Raffaele, Milan, Italy
SUMMARY Area, perimeter, maximum diameter and form factors of nuclei of FNABs of thyroid nodules were measured with a MOP Videoplan. 23 cases were selected from patients with a scintigraphically cold single thyroid nodule. The mean values of area, perimeter and maximum diameter were significantly different (p < 0.001) between the adenoma and carcinoma cases; no differences were found for the form factors. Altl]ough the analyses gave significant results, a certain amount ofoverlap ofthe benign and malignant populations was present; therefore the significance of the standard deviation, assumed to be an index ofvariability of the nuclear area, was evaluated and this parameter was found to discriminate the two populations. The standard deviation of the nuclear area measured in 14 cases diagnosed as suspicious gave 77% accuracy in discriminating benign from malignant cases.
Introduction Fine needle aspiration biopsy (FNAB) has proved to be of great value and is currently used with excellent results for the preoperative evaluation of thyroid nodules in several Institutions5 . FNAB, in fact, is regarded as the most accurate diagnostic tool for the diagnosis of thyroid malignancies; several studies have reported sensitivity values ranging from 57% to 98% and specificity in the range of 99%1,8. The efficiency of this test has been shown to be 93% in a study on 476 FNABs observed at our laboratory if the suspicious cases are included in the malignant ones. Nevertheless differentiating benign nodules from well differentiated carcinomas on cytological material obtained by FNAB is not always possible. The experience of the cytopathologist has proved to be pivotal for the diagnostic accuracy, which is however at its lowest in cases of follicolar carcinoma and Hurtle cell tumor 6,8-10. Furthermore a certain number of cases is reported as "suspicious" implying that no definite commitment can be taken on the biological· behaviour of the thyroid nodule, notwithstanding the adequacy of the material, the slides and the experience of the cytopathologist: 0344-0338/89/0185-0722$3.50/0
In order to overcome the difficulties involved in a subjective diagnosis, attempts were made to quantify the changes observed in malignant cells compared to normal or adenoma cells 2, 3,11. The aim of this study was to assess some parameters, such as shape and size of the nucleus of the aspirated and smeared thyroid cells by the morphometric technique and to evaluate whether these parameters are useful to discriminate benign from malignant nodules where a cytological diagnosis of "suspicious" was reported. Material and Methods From 1984 to 1987, 476 patients had thyroid FNAB in this Hospital; out of these, 23 cases were selected meeting the following criteria: single, scintigraphically hypocaptant nodule; subsequent surgery and histological examination confirming the cytological diagnosis; aspirations and smears performed by the same physician; good preservation of the material with at least 40 thyroid cells having well defined nuclear borders. Smears from each case were air-dried or fixed with Merckofix® and stained with Giemsa or Papanicolau respectively. Ten cases had a confirmed diagnosis of adenoma and 13 of carcinoma. © 1989 by Gustav Fischer Verlag, Stuttgart
Morphometry of Thyroid Nodules . 723 The slides used for the morphometric study were all stained with Papanicolau. For each case measurements were performed on the nuclei of 40 cells. No measurements were performed on the cytoplasm since it was difficult to define the cytoplasmic boundaries 2. Area, perimeter, maximum diameter and form factors (Form AR, Form PE, Form Ell) were computed by a MOP Videoplan morphometer, after outlining the nuclei, displayed on a TV screen, with a graphic tablet by an optic pen. A 100 x immersion objective was used according to Boon 3 ; the final total enlargement on the graphic tablet was approximately 1400. Measurements were performed twice at different times by two operators with different experience. The mean value, standard deviation and multiple variance T test were computed by the MOP Videoplan and were stored as reference values for benign and malignant cases respectively. Subsequently 14 cases diagnosed as cyrologically "suspicious" were submitted to morphometric analysis; only the mean value of the nuclear area and the standard deviation of the nuclear area were used to classify each case as benign or malignant, using the reference values previously procured.
Results The mean value of the nuclear area of the ten adenomas ranged from 31.18 to 67.34 square micron, with standard deviations ranging from 5.05 to 9.49; the mean nuclear area of all the adenomas was 50.55 square micron ± 6.55 (Table 1).
The mean area of the nuclei of the 13 carcinomas ranged from 62.79 to 122.57 square micron with standard deviations ranging from 13.22 to 32.91. The mean nuclear area of all carcinomas was 82.05 ± 20.28 (Table 1). Although the mean values of the nuclear area of the adenomas differed significantly (p < 0.001) from those of the carcinomas, this parameter alone was not helpful in distinguishing all benign from malignant cases since the values of the two groups partly overlapped. The standard deviation of the nuclear areas, assumed as an index of cellular pleomorphism4, allowed to discriminate benign from malignant cases (Fig. 1). The mean values of perimeter and the maximum diameter failed to give any better discrimination than area (Table 2); form factors were not significantly different in benign and malignant cases. The mean values of the nuclear area of the 13 cases classified as suspicious ranged from 48.7 to 169.1 square micron with standard deviation ranging from 6.9 to 27.2 (Table 3). By subdividing the cases according to the final histological diagnosis (Fig. 2) 4 cases of carcinoma and 3 cases of Hurtle cell tumors fell above the lower limit for malignant cases as previously determined. Three cases of adenoma fell below the higher limit for adenomas. Two cases of adenomas and one case of carcinoma fell between the 50
Table 1. Morphometric results obtained on smear from FNABs of 10 adenomas and 13 carcinomas Case Adenomas 1 2 3 4 5 6 7 8 9 10 Mean Carcinomas 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean
Projected nuclear area (mean) ~m2
± SD
41.61 44.00 31.18 45.32 67.34 45.25 45.64 61.84 56.08 67.27 50.55
6.2 5.2 5.0 6.2 7.4 5.0 5.6 8.4 9.5 6.9 6.5
97.08 66.69 122.00 64.86 73.53 86.61 79.28 90.12 85.95 87.41 69.46 62.79 80.37 82.05
13.4 19.8 32.9 13.2 25.9 14.7 20.9 20.4 19.0 20.9 21.5 18.2 22.7 20.4
40
SO 30
• • ,.,. •
20
10
•
•
J=====::::::;~================ 0 o ((J
00
O-l------,.-----r------,.------,
o
200
100
NUCLEAR AREA
Fig. 1. Scattergram showing mean nuclear area and S.D. of 10 cases of adenoma and 13 cases of carcinoma. -0 = Adenoma, • = carcinoma. Table 2. Morphometric results obtained on smears from FNABs of 10 adenomas and 13 carcinomas Perimeter (mean) ~m
Max diameter (mean) ~m
Adenomas (10 cases)
25.29 (SD = ± 4.03)
8.01 (SD = ± 1.43)
Carcinomas (13 cases)
33.36 (SD = ± 4.95)
10.51 (SD = ± 1.7)
724 . 1. Sassi et al. Table 3. Morphometric results obtained on smears from FNABs classified as suspicious Case
1 2 3 4
5
6 7 8 9 10 11 12 13 14
Projected ± SD nuclear area (mean) IJ.m 2
Histological diagnosis
75.4 54.5 59 83 81.8 74.9 86.4 66.9 72.7 66.7 48.7 169.1 95.0 81.9
Hurtle cell adenoma Follicular adenoma Follicular adenoma Hurtle cell adenoma Hurtle cell adenoma Papillary carcinoma Papillary carcinoma Follicular adenoma Follicular carcinoma Follicular carcinoma Follicular adenoma Papillary carcinoma Follicular adenoma Hurtle cell carcinoma
17.0 7.0 10.6 15.8 19.2 11.3 22.4 8.6 21.4 15.9 10.0 40.0 11.0 27.2
50
•
40
SD
30
• • •• • ••
20
10 0
a
a
0
100
200
NUCLEAR AREA
Fig. 2. Scattergram of nuclear area and S.D. of 13 cases classified as suspicious at FNAB, subdivided according to the final histological diagnosis. - 0 = Adenoma, • = carcinoma and Hurtle cell neoplasm.
lower limit of malignant cases and the higher limit of benign cases. Discussion Suspicious cases, as diagnosed on FNABs of single, cold nodules of the thyroid, by histology turn out to be malignant in approximately 25% of cases 10 . The fact that the remaining patients undergo unnecessary surgery has prompted studies meant to classify suspicious cases at FNAB in an objective manner. Flow cytometry showed unequivocal evidence of DNA aneuploidy in 68% of 17 undifferentiated thyroid carci-
nomas? Although results on flow cytometry of well differentiated cancers of the thyroid are not available at the moment, it is likely that aneuploidy will be even lower in better differentiated cancers and therefore its discriminating power can be assumed to be unsatisfactory. Morphometric studies gave contradictory results; the nuclear area was found to have a critical value of 90 square micron under which all cases were benign; 76% of cases with nuclear area beyond the critical value were malignant3 . Opposite conclusions were reached in a subsequent study, where morphometry was considered unable to improve results of subjective diagnosis on thyroid FNABsl. Our results showed that the nuclear area is the only partially useful parameter in diagnosing thyroid nodules. In fact 78.3 % of cases were correctly classified taking into account the nuclear area only; the remaining cases could not be classified since their nuclear areas had values falling where the areas ± SD or the range of benign and malignant cases overlapped. The overlapping disappeared taking into account also the standard deviation of the nuclear areas, thus by this parameter all cases were correctly classified. The standard deviation of each suspicious case allowed to classify 10 cases as benign or malignant, since its values fell definitely in the benign or the malignant range of the reference values. For all these cases the morphometric classification was confirmed to be correct by the histological diagnosis (Table 3), since Hurtle cell tumors, being erratic in their biological behaviour, must be managed as if they were malignant. Three cases fell in the range of the standard values between the lowest and the highest value of malignant and benign cases respectively. Two of these cases were diagnosed as benign and one as malignant by histology. At the moment morphometry does not appear to discriminate completely between benign and malignant cases on suspicious FNAB specimens, although it can help in correctly classifying 77% of suspicious cases. References 1 Akerman M, TennvallJ, Biorklund A, Martensson H, Moller T (1985) Sensitivity and specificity of fine needle aspiration cytology in the diagnosis of tumors of the thyroid gland. Acta Cytologica 29: 850-855 2 Bondeson L, Bondeson A, Lindholm K, Ljungberg 0, Tibblin S (1983) Morphometric studies on nuclei in smears of fine needle aspirates from oxyphilic tumors of the thyroid. Acta Cytologica 27:437-441 3 Boon ME, Lowhagen T, Willems J (1980) Planimetric studies on fine needle aspirates from follicular adenoma and follicular carcinoma of the thyroid. Acta Cytologica 24: 146-148 4 Brown LJR, Seeton NC (1985) Assessment of Dysplasia in colo'rectal adenomas: an observer variation and morphometric study. J Clin Pathol3S: 174-179 5 Gagneten CB, Roccatagliata G, Lowenstein A, Soto F, Soto R (1987) The role of fine needle aspiration biopsy cytology in the evaluation of the clinically solitary thyroid nodule. Acta Cytologica 31: 595-598
Morphometry of Thyroid Nodules . 725 6 Kini SR, Miller JM, Hamburger JI (1981) Problems in the cytologic diagnosis of the "cold" thyroid nodule in patients with lymphocytic thyroiditis. Acta Cytologica 25: 506-512 7 Klemi PJ, Joensuu H, Eerola E (1988) DNA Aneuploidy in anaplastic carcinoma of the thyroid gland. Am J Clin Path 89: 154-159 8 Luck JB, Mumaw VR, Frable WJ (1982) Fine needle aspiration biopsy of the thyroid. Differential diagnosis by videoplan image analysis. Acta Cytologica 26: 793-796
9 Rosen IB, Wallace C, Strawbridge HG, Walfish PG (1981) Reevaluation of needle aspiration cytology in detection of thyroid cancer. Surgery 90: 747-756 10 Silverman JF, West RL, Larking EW, Park HK, Finley JL, Swonson MS, Fore WW (1986) The role of fine needle aspiration biopsy in the rapid diagnosis and management of thyroid neoplasm. Cancer 57: 1164-1170 II Wright RG, Castles H, Mortimer RH (1987) Morphometric analysis of thyroid cell aspirates. J Clin Pathol 40: 443-445
Received July 5, 1989 . Accepted August 9, 1989
Key Words: Thyroid nodules - Fine needle biopsy - Adenoma - Thyroid carcinoma Dr. 1. Sassi, Cattedra di Anatomia e Istologia Patologica, Universita' degli Studi, Istituto H S. Raffaele, Via Olgettina 60, Milano, Italy
Morphometric Evaluation of Fine Needle Biopsy of Single Thyroid Nodules I. Sassi, F. Mangili, M. Sironi, M. Freschi and A. Cantaboni
Cattedra di Anatomia e Istologia Patologica, Universita'degli Studi, Istituto H S. Raffaele, Milan, Italy
SUMMARY Area, perimeter, maximum diameter and form factors of nuclei of FNABs of thyroid nodules were measured with a MOP Videoplan. 23 cases were selected from patients with a scintigraphically cold single thyroid nodule. The mean values of area, perimeter and maximum diameter were significantly different (p < 0.001) between the adenoma and carcinoma cases; no differences were found for the form factors. Altl]ough the analyses gave significant results, a certain amount ofoverlap ofthe benign and malignant populations was present; therefore the significance of the standard deviation, assumed to be an index ofvariability of the nuclear area, was evaluated and this parameter was found to discriminate the two populations. The standard deviation of the nuclear area measured in 14 cases diagnosed as suspicious gave 77% accuracy in discriminating benign from malignant cases.
Introduction Fine needle aspiration biopsy (FNAB) has proved to be of great value and is currently used with excellent results for the preoperative evaluation of thyroid nodules in several Institutions5 . FNAB, in fact, is regarded as the most accurate diagnostic tool for the diagnosis of thyroid malignancies; several studies have reported sensitivity values ranging from 57% to 98% and specificity in the range of 99%1,8. The efficiency of this test has been shown to be 93% in a study on 476 FNABs observed at our laboratory if the suspicious cases are included in the malignant ones. Nevertheless differentiating benign nodules from well differentiated carcinomas on cytological material obtained by FNAB is not always possible. The experience of the cytopathologist has proved to be pivotal for the diagnostic accuracy, which is however at its lowest in cases of follicolar carcinoma and Hurtle cell tumor 6,8-10. Furthermore a certain number of cases is reported as "suspicious" implying that no definite commitment can be taken on the biological· behaviour of the thyroid nodule, notwithstanding the adequacy of the material, the slides and the experience of the cytopathologist: 0344-0338/89/0185-0722$3.50/0
In order to overcome the difficulties involved in a subjective diagnosis, attempts were made to quantify the changes observed in malignant cells compared to normal or adenoma cells 2, 3,11. The aim of this study was to assess some parameters, such as shape and size of the nucleus of the aspirated and smeared thyroid cells by the morphometric technique and to evaluate whether these parameters are useful to discriminate benign from malignant nodules where a cytological diagnosis of "suspicious" was reported. Material and Methods From 1984 to 1987, 476 patients had thyroid FNAB in this Hospital; out of these, 23 cases were selected meeting the following criteria: single, scintigraphically hypocaptant nodule; subsequent surgery and histological examination confirming the cytological diagnosis; aspirations and smears performed by the same physician; good preservation of the material with at least 40 thyroid cells having well defined nuclear borders. Smears from each case were air-dried or fixed with Merckofix® and stained with Giemsa or Papanicolau respectively. Ten cases had a confirmed diagnosis of adenoma and 13 of carcinoma. © 1989 by Gustav Fischer Verlag, Stuttgart
Morphometry of Thyroid Nodules . 723 The slides used for the morphometric study were all stained with Papanicolau. For each case measurements were performed on the nuclei of 40 cells. No measurements were performed on the cytoplasm since it was difficult to define the cytoplasmic boundaries 2. Area, perimeter, maximum diameter and form factors (Form AR, Form PE, Form Ell) were computed by a MOP Videoplan morphometer, after outlining the nuclei, displayed on a TV screen, with a graphic tablet by an optic pen. A 100 x immersion objective was used according to Boon 3 ; the final total enlargement on the graphic tablet was approximately 1400. Measurements were performed twice at different times by two operators with different experience. The mean value, standard deviation and multiple variance T test were computed by the MOP Videoplan and were stored as reference values for benign and malignant cases respectively. Subsequently 14 cases diagnosed as cyrologically "suspicious" were submitted to morphometric analysis; only the mean value of the nuclear area and the standard deviation of the nuclear area were used to classify each case as benign or malignant, using the reference values previously procured.
Results The mean value of the nuclear area of the ten adenomas ranged from 31.18 to 67.34 square micron, with standard deviations ranging from 5.05 to 9.49; the mean nuclear area of all the adenomas was 50.55 square micron ± 6.55 (Table 1).
The mean area of the nuclei of the 13 carcinomas ranged from 62.79 to 122.57 square micron with standard deviations ranging from 13.22 to 32.91. The mean nuclear area of all carcinomas was 82.05 ± 20.28 (Table 1). Although the mean values of the nuclear area of the adenomas differed significantly (p < 0.001) from those of the carcinomas, this parameter alone was not helpful in distinguishing all benign from malignant cases since the values of the two groups partly overlapped. The standard deviation of the nuclear areas, assumed as an index of cellular pleomorphism4, allowed to discriminate benign from malignant cases (Fig. 1). The mean values of perimeter and the maximum diameter failed to give any better discrimination than area (Table 2); form factors were not significantly different in benign and malignant cases. The mean values of the nuclear area of the 13 cases classified as suspicious ranged from 48.7 to 169.1 square micron with standard deviation ranging from 6.9 to 27.2 (Table 3). By subdividing the cases according to the final histological diagnosis (Fig. 2) 4 cases of carcinoma and 3 cases of Hurtle cell tumors fell above the lower limit for malignant cases as previously determined. Three cases of adenoma fell below the higher limit for adenomas. Two cases of adenomas and one case of carcinoma fell between the 50
Table 1. Morphometric results obtained on smear from FNABs of 10 adenomas and 13 carcinomas Case Adenomas 1 2 3 4 5 6 7 8 9 10 Mean Carcinomas 1 2 3 4 5 6 7 8 9 10 11 12 13 Mean
Projected nuclear area (mean) ~m2
± SD
41.61 44.00 31.18 45.32 67.34 45.25 45.64 61.84 56.08 67.27 50.55
6.2 5.2 5.0 6.2 7.4 5.0 5.6 8.4 9.5 6.9 6.5
97.08 66.69 122.00 64.86 73.53 86.61 79.28 90.12 85.95 87.41 69.46 62.79 80.37 82.05
13.4 19.8 32.9 13.2 25.9 14.7 20.9 20.4 19.0 20.9 21.5 18.2 22.7 20.4
40
SO 30
• • ,.,. •
20
10
•
•
J=====::::::;~================ 0 o ((J
00
O-l------,.-----r------,.------,
o
200
100
NUCLEAR AREA
Fig. 1. Scattergram showing mean nuclear area and S.D. of 10 cases of adenoma and 13 cases of carcinoma. -0 = Adenoma, • = carcinoma. Table 2. Morphometric results obtained on smears from FNABs of 10 adenomas and 13 carcinomas Perimeter (mean) ~m
Max diameter (mean) ~m
Adenomas (10 cases)
25.29 (SD = ± 4.03)
8.01 (SD = ± 1.43)
Carcinomas (13 cases)
33.36 (SD = ± 4.95)
10.51 (SD = ± 1.7)
724 . 1. Sassi et al. Table 3. Morphometric results obtained on smears from FNABs classified as suspicious Case
1 2 3 4
5
6 7 8 9 10 11 12 13 14
Projected ± SD nuclear area (mean) IJ.m 2
Histological diagnosis
75.4 54.5 59 83 81.8 74.9 86.4 66.9 72.7 66.7 48.7 169.1 95.0 81.9
Hurtle cell adenoma Follicular adenoma Follicular adenoma Hurtle cell adenoma Hurtle cell adenoma Papillary carcinoma Papillary carcinoma Follicular adenoma Follicular carcinoma Follicular carcinoma Follicular adenoma Papillary carcinoma Follicular adenoma Hurtle cell carcinoma
17.0 7.0 10.6 15.8 19.2 11.3 22.4 8.6 21.4 15.9 10.0 40.0 11.0 27.2
50
•
40
SD
30
• • •• • ••
20
10 0
a
a
0
100
200
NUCLEAR AREA
Fig. 2. Scattergram of nuclear area and S.D. of 13 cases classified as suspicious at FNAB, subdivided according to the final histological diagnosis. - 0 = Adenoma, • = carcinoma and Hurtle cell neoplasm.
lower limit of malignant cases and the higher limit of benign cases. Discussion Suspicious cases, as diagnosed on FNABs of single, cold nodules of the thyroid, by histology turn out to be malignant in approximately 25% of cases 10 . The fact that the remaining patients undergo unnecessary surgery has prompted studies meant to classify suspicious cases at FNAB in an objective manner. Flow cytometry showed unequivocal evidence of DNA aneuploidy in 68% of 17 undifferentiated thyroid carci-
nomas? Although results on flow cytometry of well differentiated cancers of the thyroid are not available at the moment, it is likely that aneuploidy will be even lower in better differentiated cancers and therefore its discriminating power can be assumed to be unsatisfactory. Morphometric studies gave contradictory results; the nuclear area was found to have a critical value of 90 square micron under which all cases were benign; 76% of cases with nuclear area beyond the critical value were malignant3 . Opposite conclusions were reached in a subsequent study, where morphometry was considered unable to improve results of subjective diagnosis on thyroid FNABsl. Our results showed that the nuclear area is the only partially useful parameter in diagnosing thyroid nodules. In fact 78.3 % of cases were correctly classified taking into account the nuclear area only; the remaining cases could not be classified since their nuclear areas had values falling where the areas ± SD or the range of benign and malignant cases overlapped. The overlapping disappeared taking into account also the standard deviation of the nuclear areas, thus by this parameter all cases were correctly classified. The standard deviation of each suspicious case allowed to classify 10 cases as benign or malignant, since its values fell definitely in the benign or the malignant range of the reference values. For all these cases the morphometric classification was confirmed to be correct by the histological diagnosis (Table 3), since Hurtle cell tumors, being erratic in their biological behaviour, must be managed as if they were malignant. Three cases fell in the range of the standard values between the lowest and the highest value of malignant and benign cases respectively. Two of these cases were diagnosed as benign and one as malignant by histology. At the moment morphometry does not appear to discriminate completely between benign and malignant cases on suspicious FNAB specimens, although it can help in correctly classifying 77% of suspicious cases. References 1 Akerman M, TennvallJ, Biorklund A, Martensson H, Moller T (1985) Sensitivity and specificity of fine needle aspiration cytology in the diagnosis of tumors of the thyroid gland. Acta Cytologica 29: 850-855 2 Bondeson L, Bondeson A, Lindholm K, Ljungberg 0, Tibblin S (1983) Morphometric studies on nuclei in smears of fine needle aspirates from oxyphilic tumors of the thyroid. Acta Cytologica 27:437-441 3 Boon ME, Lowhagen T, Willems J (1980) Planimetric studies on fine needle aspirates from follicular adenoma and follicular carcinoma of the thyroid. Acta Cytologica 24: 146-148 4 Brown LJR, Seeton NC (1985) Assessment of Dysplasia in colo'rectal adenomas: an observer variation and morphometric study. J Clin Pathol3S: 174-179 5 Gagneten CB, Roccatagliata G, Lowenstein A, Soto F, Soto R (1987) The role of fine needle aspiration biopsy cytology in the evaluation of the clinically solitary thyroid nodule. Acta Cytologica 31: 595-598
Morphometry of Thyroid Nodules . 725 6 Kini SR, Miller JM, Hamburger JI (1981) Problems in the cytologic diagnosis of the "cold" thyroid nodule in patients with lymphocytic thyroiditis. Acta Cytologica 25: 506-512 7 Klemi PJ, Joensuu H, Eerola E (1988) DNA Aneuploidy in anaplastic carcinoma of the thyroid gland. Am J Clin Path 89: 154-159 8 Luck JB, Mumaw VR, Frable WJ (1982) Fine needle aspiration biopsy of the thyroid. Differential diagnosis by videoplan image analysis. Acta Cytologica 26: 793-796
9 Rosen IB, Wallace C, Strawbridge HG, Walfish PG (1981) Reevaluation of needle aspiration cytology in detection of thyroid cancer. Surgery 90: 747-756 10 Silverman JF, West RL, Larking EW, Park HK, Finley JL, Swonson MS, Fore WW (1986) The role of fine needle aspiration biopsy in the rapid diagnosis and management of thyroid neoplasm. Cancer 57: 1164-1170 II Wright RG, Castles H, Mortimer RH (1987) Morphometric analysis of thyroid cell aspirates. J Clin Pathol 40: 443-445
Received July 5, 1989 . Accepted August 9, 1989
Key Words: Thyroid nodules - Fine needle biopsy - Adenoma - Thyroid carcinoma Dr. 1. Sassi, Cattedra di Anatomia e Istologia Patologica, Universita' degli Studi, Istituto H S. Raffaele, Via Olgettina 60, Milano, Italy