Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Stereology and flow-cytometry of well-differentiated follicular neoplasms of the thyroid gland

  • 27 Accesses

  • 24 Citations


A retrospective analysis of surgically resected thyroid nodules by stereology and DNA flow cytometry was performed in 15 follicular adenomas and 15 well-differentiated follicular carcinomas. The criteria for diagnosis were based on the WHO classification of thyroid tumours. By area-weighted random sampling of the visual fields for light-microscopic stereology, any subjective selection bias was precluded, and each point within the embedded neoplastic tissue was given equal probability of being analyzed. 150–250 tumour cell nucleus (TCN) profiles were studied per case by a semiautomatic image analyzing system. Flow cytometric analyses included measurement of the DNA index, and the percentages of cells in S-phase and in G2/M-phase. Adenomas and carcinomas did not differ in stereological estimates related to TCN size. As examination of the stereological techniques by nested analysis of variance showed that this result cannot be ascribed to inaccurate methods, it follows that determination of TCN size is not a useful tool for the diagnosis of malignancy in well-differentiated thyroid tumours. Both groups included similar proportions of diploid and aneuploid neoplasms. In the carcinoma group the percentage of tumour cells in the G2/M-phase was more than twice as high than in the adenoma group (P<0.01). The ratio of short to long TCN profile axis was significantly smaller, and the coefficient of variation of TCN profile area was significantly higher in carcinomas than in adenomas. These findings are consistent with more unequiaxed TCN and higher anisokaryosis in the malignant tumours. Despite the significant differences, however, overlap of data from individual cases precludes the use of these estimates as diagnostic criteria. Pooling of the follicular tumours and dichotomizing the sample by the DNA-index showed that mean TCN profile area is increased and surface-to-volume ratio of TCN is decreased in aneuploid as compared to diploid tumours. This finding indicates that aneuploidy is associated with an increase of TCN size.

This is a preview of subscription content, log in to check access.


  1. Abramowitz M, Stegun IA (1964) Handbook of Mathematical Functions with Formulas, Graphs, and Mathematical Tables. Dover Publications, New York

  2. Beck HP (1980) Evaluation of flow cytometric data of human tumors. Correction procedures for background and cell aggregations. Cell Tissue Kinet 13:173–181

  3. Böcker (1984) Schilddrüse. In: Pathologie 3, ed. Remmele W, Springer, Berlin Heidelberg New York, pp 415–445

  4. Boon ME, Löwhagen T, Willems JS (1980) Planimetric studies on fine needle aspirates from follicular adenoma and follicular carcinoma of the thyroid. Acta Cytol 24:145–148

  5. Boon ME, Löwhagen T, Lopes Cardozo P, Blonk DI, Kurver PJH, Baak JPA (1982) Computation of preoperative diagnosis probability for follicular adenoma and carcinoma of the thyroid on aspiration smears. Anal Quant Cytol 4:1–5

  6. Chen KTK, Rosai J (1977) Follicular variant of thyroid papillary carcinoma: A clinicopathologic study of six cases. Am J Surg Pathol 1:123–130

  7. Cruz-Orive LM (1976) Particle size-shape distributions: the general spheroid problem. I. Mathematical model. J Microsc 107:235–253

  8. Cruz-Orive LM (1980) On the estimation of particle number. J Microsc 120:15–27

  9. Droese M (1979) Aspirationszytologie der Schilddüse. Schattauer, Stuttgart

  10. Droese M, Mentgen-Nothum V, Eins S, Klar R (1981) Morphometrische Dignitätsbeurteilung follikulärer Schilddrüsentumoren im Feinnadelpunktat. Verh Dtsch Ges Pathol 65:384

  11. Feichter GE, Kühn W, Czernobilsky B, Müller A, Heep J, Abel U, Haag D, Kaufmann M, Rummel HH, Kubli F, Goerttler K (1985) DNA flow cytometry of ovarian tumors with correlation to histopathology. Int J Gynecol Pathol 4:336–345

  12. Fossa SD, Thorud E, Shoaib MC, Pettersen EO (1982) DNA flow cytometry of cells obtained from old paraffin-embedded specimens. A comparison with results of scanning absorption cytometry. Pathol Res Pract 181:200–205

  13. Franzen G, Olofsson J, Risberg B, Klintenberg C, Nordenskjöld B (1986) DNA measurements on formalin-fixed, paraffin-embedded squamous cell carcinomas from different ENT-regions. Pathol Res Pract 181:230–235

  14. Georgii A (1977) Die epithelialen Tumoren der Schilddrüse. Verh Dtsch Ges Pathol 61:191–208

  15. Greenebaum E, Koss LG, Elequin F, Silver CE (1985) The diagnostic value of flow cytometric DNA measurements in follicular tumors of the thyroid gland. Cancer 56:2011–2018

  16. Haag D (1980) Flow microfluorimetric deoxyribonucleic acid (DNA) analysis supplementing routine histopathologic diagnosis of biopsy specimens. Lab Invest 42:85–90

  17. Haemmerli G (1970) Zytophotometrische und zytogenetische Untersuchungen an knotigen Veränderungen der menschlichen Schilddrüse. Schweiz Med Wochenschr 100:633–641

  18. Hazard JB, Kenyon R (1954) Atypical adenoma of the thyroid. Arch Pathol 58:554–563

  19. Hedinger C, Sobin LH (1974) Histological Typing of Thyroid Tumors. World Health Organization, Geneva

  20. Hedley DW, Friedlander ML, Taylor IW, Rugg CA, Musgrove EA (1983) Method for analysis of cellular DNA content of paraffin embedded pathological material using flow cytometry. J Histochem Cytochem 31:1333–1335

  21. Johannessen JV, Sobrinho-Simoes M, Lindmo T, Tangen KO (1982) The diagnostic value of flow cytometric DNA measurements in selected disorders of the human thyroid. Am J Clin Pathol 77:20–25

  22. Johannessen JV, Sobrinho-Simoes M (1983) Well differentiated thyroid tumors. Problems in diagnosis and understanding. Pathol Annu 18:255–285

  23. Johannessen JV, Sobrinho-Simoes M, Finseth I, Pilström L (1983) Ultrastructural morphometry of thyroid neoplasms. Am J Clin Pathol 79:166–171

  24. Kriete A, Romen W, Schäffer R, Harms H, Haucke M, Gerlach B, Aus HM, ter Meulen V (1983) Computer analysis of chromatin arrangement and nuclear texture in follicular thyroid tumors. Histochemistry 78:227–230

  25. Kriete A, Schäffer R, Harms H, Aus HM (1985) Computer-based cytophotometric classification of thyroid tumors in imprints. J Cancer Res Clin Oncol 109:252–256

  26. Lang W, Georgii A, Atay Z (1977) Differentialdiagnose zwischen atypischem Adenom und follikulärem Carcinom der Schilddrüse. Verh Dtsch Ges Pathol 61:275–279

  27. Lang W, Georgii A, Stauch G, Kienzle E (1980) The differentiation of atypical adenomas and encapsulated follicular carcinomas in the thyroid gland. Virchows Arch A [Path Anat Histol] 385:125–141

  28. Lang W, Choritz H, Hundeshagen H (1986) Risk factors in follicular thyroid carcinomas. A retrospective follow-up study covering a 14-year period with emphasis on morphological findings. Am J Surg Pathol 10:246–255

  29. Löwhagen T, Sprenger E (1974) Cytologic presentation of thyroid tumors in aspiration biopsy smear. A review of 60 cases. Acta Cytol 18:192–197

  30. Luck JB, Mumaw VR, Frable WJ (1982) Fine needle aspiration biopsy of the thyroid. Differential diagnosis by videoplan image analysis. Acta Cytol 26:793–796

  31. Mattfeldt T, Mall G (1983) Dipyridamole-induced capillary endothelial cell proliferation in the rat heart — a morphometric investigation. Cardiovasc Res 17:229–237

  32. Mattfeldt T, Mall G (1984) Estimation of length and surface of anisotropic capillaries. J Microsc 135:181–190

  33. Mattfeldt T, Möbius HJ, Mall G (1985a) Orthogonal triplet probes: an efficient method for unbiased estimation of length and surface of objects with unknown orientation in space. J Microsc 139:279–289

  34. Mattfeldt T, Neurohr W, Müller A, Klinga K (1985b) Morphometrische Korrelate des Steroidrezeptorengehaltes duktal-invasiver Mammakarzinome. Verh Dtsch Ges Pathol 69:350–355

  35. Mattfeldt T, Neurohr W, Müller K, Klinga K (1985c) Stereologic correlates of steroid receptor concentration in invasive ductal breast cancer. Anal Quant Cytol Histol 7:310–314

  36. Mikuz G, Hofstädter F, Schwarzlmüller B (1977) Feulgenzytophotometrische Untersuchungen an „falsch“ und „richtig positiven“ zytologischen Präparaten von Feinnadel-Schilddrüsenpunktaten. Verh Dtsch Ges Pathol 61:290–294

  37. Miles RE, Davy P (1976) Precise and general conditions for the validity of a comprehensive set of stereological fundamental formulae. J Microsc 107:211–226

  38. Möller P, Gross C, Feichter G, Mattfeldt T, Kaufmann M (1985) Vergleich von Bindungsmustern etablierter und neuer monoklonaler Antikörper, von Antiseren und Lektinen mit impulscytophotometrischen und morphometrischen Parametern und dem Hormonrezeptorstatus am Mammacarcinom. Verh Dtsch Ges Pathol 69:405–408

  39. Rabenhorst G (1974) The diagnostic value of the DNA content of fine needle biopsies of the thyroid gland. Virchows Arch B [Cell Pathol] 16:379–383

  40. Schröder S, Böcker W, Dralle H, Kortmann KB, Stern C (1984a) The encapsulated papillary carcinoma of the thyroid. A morphologic subtype of the papillary thyroid carcinoma. Cancer 54:90–93

  41. Schröder S, Pfannschmidt N, Dralle H, Arps H, Böcker W (1984b) The encapsulated follicular carcinoma of the thyroid. A clinicopathologic study of 35 cases. Virchows Arch A [Pathol Anat] 402:259–273

  42. Schuh D, Steidl R, Voß K (1980) Unterscheidung von follikulären Adenomen und Karzinomen in der Schilddrüsenfeinnadelbiopsie durch computergestützte zytomorphometrische Untersuchungen. Zentralbl Allg Pathol Pathol Anat 124:557–560

  43. Schuh D, Steidl R, Mende T, Schneider H, Reske W (1984) Ergebnisse der automatischen Mikroskopbildanalyse von Schilddrüsenfeinnadelbiopsien. Zentralbl Allg Pathol Pathol Anat 129:35–41

  44. Sprenger E, Löwhagen T, Vogt-Schaden M (1977) Differential diagnosis between follicular adenoma and follicular carcinoma of the thyroid by nuclear DNA determination. Acta Cytol 21:528–530

  45. Tasca C, Stefaneanu L (1977) Cytology and cytophotometry in thyroid diseases. Acta Histochem 60:261–272

  46. Tschahargane C, Goerttler K, Ehemann V, Haag D (1978) Application of flow-through DNA measurements in thyroid diseases. Pulse Cytophotometry 3:527–532

  47. Vickery AL (1983) Thyroid papillary carcinoma. Pathological and philosophical controversies. Am J Surg Pathol 7:797–807

  48. Weibel ER (1979) Stereological Methods. I. Practical Methods for Biological Morphometry. Academic Press, London

  49. Weibel ER (1980) Stereological Methods. II. Theoretical Foundations. Academic Press, London

Download references

Author information

Correspondence to Torsten Mattfeldt.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mattfeldt, T., Schürmann, G. & Feichter, G. Stereology and flow-cytometry of well-differentiated follicular neoplasms of the thyroid gland. Vichows Archiv A Pathol Anat 410, 433–441 (1987). https://doi.org/10.1007/BF00712763

Download citation

Key words

  • Flow cytometry
  • Follicular neoplasms
  • Microscopy
  • Morphometry
  • Stereology
  • Thyroid gland