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Der Nuklearmediziner 2019; 42(03): 194-205
DOI: 10.1055/a-0916-6604
Benigne Schilddrüsenknoten – Update 2019
© Georg Thieme Verlag KG Stuttgart · New York

Morphologische Diagnostik und genetische Alterationen von Schilddrüsentumoren mit Follikelzelldifferenzierung

Morphological diagnosis and genetic alterations of thyroid tumours with follicular cell differentiation
Kurt Werner Schmid
1   Institut für Pathologie, Universitätsklinikum Essen, Universität Duisburg-Essen
,
Ken Herrmann
2   Klinik für Nuklearmedizin, Universitätsklinikum Essen, Universität Duisburg-Essen
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Publikationsdatum:
03. September 2019 (online)

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Zusammenfassung

Die morphologische Diagnostik von Schilddrüsentumoren dient in erster Linie dem klinischen Management. Die Feinnadelbiopsie (FNB) soll eine Entscheidungshilfe für oder gegen eine Operation sein; der intraoperative Gefrierschnitt soll das Operationsausmaß mitbestimmen und Zweitoperationen vermeiden helfen. Die beiden letztgenannten Methoden haben aber beträchtliche Limitationen, sodass in vielen Fällen die morphologische Dignitätsbestimmung erst in der endgültigen Paraffinhistologie gelingt, wobei für die exakte Diagnosefindung auch der Einsatz der Immunhistochemie und zunehmend molekularpathologischer Analysen zur Verfügung stehen.

Die klassische Unterteilung der Schilddrüsentumoren in benigne und maligne wurde nach der 2017 veröffentlichen WHO-Klassifikation um die Gruppe der Neoplasien mit unsicherem/(extrem) geringem Malignitätspotenzial erweitert. Durch die Etablierung der „nicht invasiven follikulären Neoplasie mit PTC-äquivalenten Kernmerkmalen (NIFTP)“ wird erstmalig aufgrund des erwiesenen indolenten biologischen Verhaltens eine Subgruppe von nach bisherigen Diagnosekriterien als gekapselte follikuläre Variante des papillären Karzinoms (FV-PTC) klassifizierte Tumoren nicht mehr als Krebs bezeichnet, wodurch den betroffenen Patienten sowohl eine Übertherapie als auch die psychologische Belastung durch die Krebsdiagnose erspart wird.

Der in der Pathologie erhobene Befund von Schilddrüsenneoplasien beruht zwischenzeitlich auf einer Reihe durchaus subtiler morphologischer und/oder molekularpathologischer Kriterien. Dieser Befund ist aber der entscheidende Parameter des weiteren Managements der betroffenen Patienten/Patientinnen, was auch maßgeblich die Nuklearmedizin betrifft. Darüber hinaus bietet die Nuklearmedizin äußerst vielversprechende neue diagnostische und auch therapeutische Ansätze zur Behandlung des Schilddrüsenkarzinoms.

Abstract

The morphological diagnosis of thyroid tumours determines primarily the clinical management of the respective patients. The fine needle biopsy (FNB) should be a decision-making tool for or against surgery; the intraoperative frozen section is intended to help determine the extent of surgery and to help prevent second surgeries. However, the latter two methods have considerable limitations. Thus in many cases the final diagnosis has to be made on paraffin histology. Immunohistochemistry and increasingly molecular pathological analyzes are available for exact diagnosis.

According to the in 2017 published WHO classification, the traditional classification of thyroid tumours into benign and malignant tumours has been expanded by the introduction of the group of neoplasms with uncertain/(extremely) low malignant potential. Due to the establishment of „non-invasive follicular neoplasia with papillary-like nuclear features (NIFTP)“ a subgroup of encapsulated follicular variant papillary carcinoma (FV-PTC) with proven indolent biological behavior is no longer referred to as cancer thus avoiding overtreatment as well as the psychological burden of cancer diagnosis.

The pathological diagnosis of thyroid tumours is based on a variety of quite subtle morphological and/or molecular pathological criteria, representing the decisive parameter for the further management of patients, which also applies to nuclear medicine. In addition, nuclear medicine offers highly promising new diagnostic and therapeutic approaches to both diagnosis and therapy of thyroid carcinoma.

Schlüsselwörter

Schilddrüsenneoplasie - Morphologische Diagnose - Molekularpathologie - NIFTP - Übertherapie

Keywords

Thyroid neoplasia - morphological diagnosis - molecular pathology - NIFTP - overtreatment
 

  • Literatur

  • 1 Lloyd R, Osamura RY, Klöppel G. et al. (eds.) WHO Classification of Tumours of Endocrine Organs. Tumours of the thyroid gland. . 4th Edition. Lyon: IARC; 2017: 65-143
    Google Scholar
  • 2 Histological classification of thyroid and parathyroid tumours. In: DeLellis RA, Lloyd RV, Heitz PU. et al. (eds.) World Health Organization Classification of Tumours. Pathology & Genetics. Tumours of Endocrine Organs. . 3rd Edition. Lyon: IARC; 2004: 49-123
    Google Scholar
  • 3 Schmid KW, Reiners C. Wann ist die Feinnadelbiopsie der Schilddrüse am effektivsten?. Pathologe 2001; 32: 169-172
    PubMedGoogle Scholar
  • 4 Ting S, Synoracki S, Bockisch A. et al. Die klinische Bedeutung der Schilddrüsenzytologie. Pathologe 2015; 36: 543-552
    CrossrefPubMedGoogle Scholar
  • 5 Tötsch M, Schmid KW. Auswirkungen für die Beurteilung der Feinnadelbiopsie (FNB) der Schilddrüse nach der Einführung der NIFTP. Onkologe 2019; 07: 590-595
    PubMedGoogle Scholar
  • 6 Schmid KW, Sheu-Grabellus SY. Schilddrüse. In: Amann K, Kain R, Klöppel G. Pathologie. Urogenitale und Endokrine Organe, Gelenke und Skelett. Berlin Heidelberg: Springer-Verlag; 2016
    Google Scholar
  • 7 Dralle H, Musholt TJ, Schabram J. et al. German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors. Langenbecks Arch Surg 2013; 398: 347-375
    CrossrefPubMedGoogle Scholar
  • 8 Brierley JD, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours. 8th Edition. Hoboken: Wiley Blackwell; 2016: 51-54
    Google Scholar
  • 9 Schmid KW, Synoracki S, Dralle H. et al. Proposal for an extended pTNM classification of thyroid carcinoma: Commentary on deficits of the 8th edition of the TNM classification. Pathologe 2018; 39: 49-56
    CrossrefPubMedGoogle Scholar
  • 10 Haugen BR, Alexander EK, Bible KC. et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016; 26: 1-133
    CrossrefPubMedGoogle Scholar
  • 11 Kirchner J, Schaarschmidt BM, Sawicki LM. et al. Evaluation of Practical Interpretation Hurdles in 68Ga-PSMA PET/CT in 55 Patients: Physiological Tracer Distribution and Incidental Tracer Uptake. Clin Nucl Med 2017; 42: e322-e327
    CrossrefPubMedGoogle Scholar
  • 12 Verma P, Malhotra G, Agrawal R. et al. Evidence of Prostate-Specific Membrane Antigen Expression in Metastatic Differentiated Thyroid Cancer Using 68Ga-PSMA-HBED-CC PET/CT. Clin Nucl Med 2018; 43: e265-e268
    CrossrefPubMedGoogle Scholar
  • 13 Giesel FL, Kratochwil C, Lindner T. et al. 68Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers. J Nucl Med 2019; 60: 386-392
    CrossrefPubMedGoogle Scholar
  • 14 Herrmann K, Schottelius M, Lapa C. et al. First-in-Human Experience of CXCR4-Directed Endoradiotherapy with 177Lu- and 90Y-Labeled Pentixather in Advanced-Stage Multiple Myeloma with Extensive Intra- and Extramedullary Disease. J Nucl Med 2016; 57: 248-251
    CrossrefPubMedGoogle Scholar
  • 15 Heitkötter B, Steinestel K, Trautmann M. et al. Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid. Oncotarget 2018; 9: 9867-9874
    CrossrefPubMedGoogle Scholar
  • 16 Damle NA, Bal C, Singh TP. et al. Anaplastic thyroid carcinoma on 68 Ga-PSMA PET/CT: opening new frontiers. Eur J Nucl Med Mol Imaging 2018; 45: 667-668
    CrossrefPubMedGoogle Scholar
  • 17 Kratochwil C, Flechsig P, Lindner T. et al. 68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer. J Nucl Med 2019; 60: 801-805
    CrossrefPubMedGoogle Scholar
  • 18 Loktev A, Lindner T, Burger EM. et al. Development of novel FAP-targeted radiotracers with improved tumor retention. J Nucl Med 2019; DOI: 10.2967/jnumed.118.224469.
    CrossrefPubMedGoogle Scholar
  • 19 Nikiforov YE, Seethala RR, Tallini G. et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: A paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol 2016; 2: 1023-1029
    CrossrefPubMedGoogle Scholar
  • 20 Nikiforov YE, Baloch ZW, Hodak SP. et al. Change in diagnostic criteria for noninvasive follicular thyroid neoplasm with papillary-like nuclear features. JAMA Oncol 2018; 4: 1125-1126
    CrossrefPubMedGoogle Scholar
  • 21 Evans HL. Follicular neoplasms of the thyroid. A study of 44 cases followed for a minimum of 10 years, with emphasis on differential diagnosis. Cancer 1984; 54: 535-540
    CrossrefPubMedGoogle Scholar
  • 22 Evans HL. Encapsulated papillary neoplasms of the thyroid. A study of 14 cases followed for a minimum of 10 years. Am J Surg Pathol 1987; 11: 592-597
    CrossrefPubMedGoogle Scholar
  • 23 Moreno A, Rodriguez JM, Sola J. et al. Encapsulated papillary neoplasm of the thyroid: retrospective clinicopathological study with long term follow up. Eur J Surg 1996; 162: 177-180
    PubMedGoogle Scholar
  • 24 Schröder S, Böcker W, Dralle H. et al. The encapsulated papillary carcinoma of the thyroid. A morphologic subtype of the papillary thyroid carcinoma. Cancer 1984; 54: 90-93
    CrossrefPubMedGoogle Scholar
  • 25 Schmid KW. Warum muss ein Schilddrüsentumor als Karzinom klassifiziert werden, wenn er sich biologisch nicht wie Krebs verhält? Die „nicht-invasive follikuläre Neoplasie mit PTC-äquivalenten Kernmerkmalen (NIFTP)“ als Vorbild. Onkologe 2019; DOI: doi.org/10.1007/s00761-019-0548-7.
    CrossrefPubMedGoogle Scholar
  • 26 Theurer S, Dralle H, Führer-Sakel D. et al. Morphologic diagnostic criteria of noninvasive follicular neoplasia with papillary-like nuclear features (NIFTP) : A diagnostic challenge for the patient's benefit. Pathologe 2019; 40: 220-226
    CrossrefPubMedGoogle Scholar
  • 27 Xu B, Farhat N, Barletta JA. et al. Should subcentimeter non-invasive encapsulated, follicular variant of papillary thyroid carcinoma be included in the noninvasive follicular thyroid neoplasm with papillary-like nuclear features category?. Endocrine 2018; 59: 143-150
    CrossrefPubMedGoogle Scholar
  • 28 Shafique K, LiVolsi VA, Montone K. et al. Papillary thyroid microcarcinoma: Reclassification to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): a retrospective clinicopathologic study. Endocr Pathol 2018; 29: 339-345
    CrossrefPubMedGoogle Scholar
  • 29 Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell 2014; 159: 676-690
    CrossrefPubMedGoogle Scholar
  • 30 Jin A, Xu J, Wang Y. The role of TERT promoter mutations in postoperative and preoperative diagnosis and prognosis in thyroid cancer. Medicine (Baltimore) 2018; 97: e11548
    PubMedGoogle Scholar
  • 31 Melo M, da Rocha AG, Vinagre J. et al. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab 2014; 99: E754-765
    CrossrefPubMedGoogle Scholar
  • 32 Bullock M, Ren Y, O'Neill C. et al. TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas. Clin Endocrinol (Oxf) 2016; 85: 283-290
    CrossrefPubMedGoogle Scholar
  • 33 Melo M, da Rocha AG, Vinagre J. et al. Coexistence of TERT promoter and BRAF mutations in papillary thyroid carcinoma: added value in patient prognosis?. J Clin Oncol 2015; 33: 667-668
    CrossrefPubMedGoogle Scholar
  • 34 Xing M, Liu R, Liu X. et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol 2014; 32: 2718-2726
    CrossrefPubMedGoogle Scholar
  • 35 Führer D, Musholt T, Schmid KW. Molecular Pathogenesis of Thyroid Nodules: Relevance for Clinical Care. Laryngorhinootologie 2017; 96: 590-596
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 36 Rosai J, DeLellis RA, Carcangiu ML. et al. AFIP Atlas of Tumor Pathology. 4th Series, Fascicle 21. Tumors of the thyroid and parathyroid glands. Silver Spring, Maryland: American Registry of Pathology; 2014
    Google Scholar
  • 37 Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet 2013; 381: 1058-1069
    CrossrefPubMedGoogle Scholar
  • 38 Zhang Y, Yu J, Lee C. et al. Genomic binding and regulation of gene expression by the thyroid carcinoma-associated PAX8-PPARG fusion protein. Oncotarget 2015; 6: 40418-40432
    CrossrefPubMedGoogle Scholar
  • 39 Liu R, Xing M. TERT promoter mutations in thyroid cancer. Endocr Relat Cancer 2016; 23: R143-155
    CrossrefPubMedGoogle Scholar
  • 40 Máximo V, Botelho T, Capela J. et al. Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid. Br J Cancer 2005; 92: 1892-1898
    CrossrefPubMedGoogle Scholar
  • 41 Ganly I, Ricarte FilhoJ, Eng S. et al. Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid malignancy. J Clin Endocrinol Metab 2013; 98: E962-972
    CrossrefPubMedGoogle Scholar
  • 42 Nikiforova MN, Lynch RA, Biddinger PW. et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab 2003; 88: 2318-2326
    CrossrefPubMedGoogle Scholar
  • 43 Sahin M, Allard BL, Yates M. et al. PPARgamma staining as a surrogate for PAX8/PPARgamma fusion oncogene expression in follicular neoplasms: clinicopathological correlation and histopathological diagnostic value. J Clin Endocrinol Metab 2005; 90: 463-468
    CrossrefPubMedGoogle Scholar
  • 44 Volante M, Collini P, Nikiforov YE. et al. Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 2007; 31: 1256-1264
    CrossrefPubMedGoogle Scholar
  • 45 Dettmer MS, Schmitt A, Komminoth P. et al. Poorly differentiated thyroid carcinoma: An underdiagnosed entity. Pathologe 2019; 40: 227-234
    CrossrefPubMedGoogle Scholar
  • 46 Volante M, Landolfi S, Chiusa L. et al. Poorly differentiated carcinomas of the thyroid with trabecular, insular, and solid patterns: a clinocopathological study of 183 patients. Cancer 2004; 100: 950-957
    CrossrefPubMedGoogle Scholar
  • 47 Decaussin M, Bernard MH, Adeleine P. et al. Thyroid carcinomas with distant metastases: a review of 111 cases with emphasis on the prognostic significance of an insular component. Am J Surg Pathol 2002; 26: 1007-1015
    CrossrefPubMedGoogle Scholar
  • 48 Landa I, Ibrahimpasic T, Boucai L. et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest 2016; 126: 1052-1066
    CrossrefPubMedGoogle Scholar
  • 49 Landa I, Ganly I, Chan TA. et al. Frequent somatic TERT promoter mutations in thyroid cancer: higher prevalence in advanced forms of the disease. J Clin Endocrinol Metab 2013; 98: E1562-1566
    CrossrefPubMedGoogle Scholar
  • 50 Liu X, Bishop J, Shan Y. et al. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer 2013; 20: 603-610
    CrossrefPubMedGoogle Scholar
  • 51 Latteyer S, Tiedje V, König K. et al. Targeted next-generation sequencing for TP53, RAS, BRAF, ALK and NF1 mutations in anaplastic thyroid cancer. Endocrine 2016; 54: 733-741
    CrossrefPubMedGoogle Scholar
  • 52 Kunstman JW, Juhlin CC, Goh G. et al. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet 2015; 24: 2318-2312
    CrossrefPubMedGoogle Scholar
  • 53 Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg 2014; 140: 317-322
    CrossrefPubMedGoogle Scholar
  • 54 Robert Koch Institut. Krebs in Deutschland. 2017 https://www.krebsdaten.de/Krebs/DE/Content/Publikationen/Krebs_in_Deutschland/kid_2017/kid_2017_c73_schilddruese.pdf?__blob=publicationFile
    PubMedGoogle Scholar
  • 55 Hung YP, Barletta JA. A user's guide to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Histopathology 2018; 72: 53-69
    CrossrefPubMedGoogle Scholar
  • 56 Koperek O, Scheuba C, Cherenko M. et al. Desmoplasia in medullary thyroid carcinoma: a reliable indicator of metastatic potential. Histopathology 2008; 52: 623-630
    CrossrefPubMedGoogle Scholar
  • 57 Machens A, Schmid KW, Dralle H. Advances in the Diagnosis and Surgical Management of Medullary Thyroid Carcinomas. In: Shifrin AL. Treatment and Management of Endocrinopathies, Chapter 3. Amsterdam: Elsevier; 2019
    Google Scholar
  • 58 Schmid KW. Histopathology of C Cells and Medullary Thyroid Carcinoma. Recent Results Cancer Res 2015; 204: 41-60
    PubMedGoogle Scholar
  • 59 Vuong HG, Altibi AM, Duong UN. et al. Role of molecular markers to predict distant metastasis in papillary thyroid carcinoma: Promising value of TERT promoter mutations and insignificant role of BRAF mutations-a meta-analysis. Tumour Biol 2017; 39: 1010428317713913
    CrossrefPubMedGoogle Scholar
  • 60 Yip L, Nikiforova MN, Yoo JY. et al. Tumor genotype determines phenotype and disease-related outcomes in thyroid cancer: a study of 1510 patients. Ann Surg 2015; 262: 519-525 ; discussion 524-525
    CrossrefPubMedGoogle Scholar
  • 61 Tiedje V, Ting S, Herold T. et al. NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma. Oncotarget 2017; 8: 42613-42620
    CrossrefPubMedGoogle Scholar
  • 62 Schmid KW, Führer D. Rolle der Molekularpathologie beim Schilddrüsenkarzinom. Tumordiagnostik, Zytologie und Zielgerichtete Therapie. Onkologe 2015; DOI: doi.org/10.1007/s00761-014-2858-0.
    CrossrefPubMedGoogle Scholar