Morphometric and immunohistochemical features of TTF-1 positive lung tumors: improvement of approaches to the diagnosis of unknown primary sites metastases

Authors

  • Oleksandra Poslavska State Institution “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine” V. Vernadskogo str., 9, Dnipro, Ukraine, 49044, Ukraine https://orcid.org/0000-0002-3133-8413
  • Igor Shponka State Institution “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine” V. Vernadskogo str., 9, Dnipro, Ukraine, 49044, Ukraine https://orcid.org/0000-0002-7561-6489

DOI:

https://doi.org/10.15587/2519-4798.2020.199841

Keywords:

TTF-1, СК7, Кі-67, карциноми легенів, ImageJ

Abstract

Verification of lung tumors in the practical activity of a pathomorphologist reached a completely different level due to the use of additional highly sensitive diagnostic methods (immunohistochemical (IHC) and cytogenetic studies). Thyroid transcription factor 1 (TTF-1) plays a key role in lung morphogenesis and is expressed in about 90 % of pulmonary small cell carcinomas. The positivity of TTF-1 in pulmonary and extrapulmonary neuroendocrine tumors is actively debated in the literature, therefore, the results of IHС on TTF-1 in metastases from an unknown source should be interpreted carefully and constantly improve differential diagnostic algorithms, expanding IHC panels with organ-specific markers, and focus on additional morphometric indicators research of nuclei of tumor cells.

The aim of the work is to investigate the complex of morphological, morphometric, and IHC characteristics of TTF-1 positive lung tumors to improve the diagnostic algorithms for metastases from an unknown primary source.

Materials and methods. A retrospective analysis of histological, morphometric and IHC characteristics of the biopsy material TTF-1 of positive lung carcinomas from 36 patients (10 women and 26 men) aged 29 to 81 years (mean 58.03±10.83 years) for the period 2015–2018, taken from the archive of the morphological department of the medical-diagnostic center of LLC “Pharmacies of the Medical Academy” (Ukraine, Dnipro).

Results. In the diagnosis of carcinomas of unknown primary localization with suspected lung origin, it is necessary to take into account morphological, morphometric and IHC features together, which is associated with the similarity of metastases of squamous cell carcinomas of the head and neck, mucinous adenocarcinomas of the gastrointestinal tract and neuroendocrine carcinomas from Merkel cells corresponding to the histological forms lung tumors, as well as insufficient sensitivity of the marker TTF-1.

Conclusions. Use of the minimum primary (Cytokeratin, Pan AE1 / AE3 (+) / Vimentin (- / +) / CD45 (-) / S100 (- / +)) and secondary (Ck 7 +, Ck 20 -, TTF-1 + ) IHC panels will prove that the phenotype of carcinoma of unknown primary site corresponds to the form of disseminated lung carcinoma, and additional markers Сk HMW, p63, Chromogranin A, Synaptofisin and / or CD56 together with morphometric indices of the nuclei will determine the histological form of lung carcinoma with justification for the use of appropriate therapy

Author Biographies

Oleksandra Poslavska, State Institution “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine” V. Vernadskogo str., 9, Dnipro, Ukraine, 49044

PhD, Associate Professor

Department of Pathological Anatomy and Forensic Medicine,

Igor Shponka, State Institution “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine” V. Vernadskogo str., 9, Dnipro, Ukraine, 49044

MD, Professor, First Vice-Rector

Department of Pathological Anatomy and Forensic Medicine

References

  1. Jagirdar, J. (2008). Application of Immunohistochemistry to the Diagnosis of Primary and Metastatic Carcinoma to the Lung. Archives of Pathology & Laboratory Medicine, 132, 384–396.
  2. Bobos, M., Hytiroglou, P., Kostopoulos, I., Karkavelas, G., Papadimitriou, C. S. (2006). Immunohistochemical Distinction Between Merkel Cell Carcinoma and Small Cell Carcinoma of the Lung. The American Journal of Dermatopathology, 28 (2), 99–104. doi: http://doi.org/10.1097/01.dad.0000183701.67366.c7
  3. Verset, L., Arvanitakis, M., Loi, P., Closset, J., Delhaye, M., Remmelink, M., Demetter, P. (2011). TTF-1 positive small cell cancers: Don’t think they’re always primary pulmonary! World Journal of Gastrointestinal Oncology, 3 (10), 144–147. doi: http://doi.org/10.4251/wjgo.v3.i10.144
  4. Travis, W. D. (2012). Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas. Modern Pathology, 25 (S1), S18–S30. doi: http://doi.org/10.1038/modpathol.2011.150
  5. Varadhachary, G. R., Raber, M. N. (2014). Cancer of Unknown Primary Site. New England Journal of Medicine, 371 (8), 757–765. doi: http://doi.org/10.1056/nejmra1303917
  6. Poslavskaya, O. V. (2016). Determination of linear dimensions and square surfaces areas of morphological objects on micrographs using ImageJ software. Morphologia, 10 (3), 377–381.
  7. Poslavska, O. V., Shponka, I. S., Gritsenko, P. O., Alekseenko, O. A. (2018). Morphometric analysis of pancytokeratin-negative neoplastic damages of the lymphatic nodes of the neck. Medical Perspectives, 23 (1), 30–37. doi: http://doi.org/10.26641/2307-0404.2018.1.124915
  8. Leech, S. N., Kolar, A. J. O., Barrett, P. D., Sinclair, S. A., Leonard, N. (2001). Merkel cell carcinoma can be distinguished from metastatic small cell carcinoma using antibodies to cytokeratin 20 and thyroid transcription factor 1. Journal of Clinical Pathology, 54 (9), 727–729. doi: http://doi.org/10.1136/jcp.54.9.727
  9. Kervarrec, T., Tallet, A., Miquelestorena-Standley, E., Houben, R., Schrama, D., Gambichler, T. et. al. (2019). Morphologic and immunophenotypical features distinguishing Merkel cell polyomavirus-positive and negative Merkel cell carcinoma. Modern Pathology, 32 (11), 1605–1616. doi: http://doi.org/10.1038/s41379-019-0288-7
  10. Ross, J. S., Wang, K., Gay, L., Otto, G. A., White, E., Iwanik, K. et. al. (2015). Comprehensive Genomic Profiling of Carcinoma of Unknown Primary Site. JAMA Oncology, 1 (1), 40–49. doi:10.1001/jamaoncol.2014.216

Published

2020-04-01

How to Cite

Poslavska, O., & Shponka, I. (2020). Morphometric and immunohistochemical features of TTF-1 positive lung tumors: improvement of approaches to the diagnosis of unknown primary sites metastases. ScienceRise: Medical Science, (2 (35), 29–34. https://doi.org/10.15587/2519-4798.2020.199841

Issue

Section

Medical Science