Metastatic lung carcinoma in thyroid aspirates: A case series and literature review illustrating diagnostic challenges

Cytopathology. 2022 Nov;33(6):696-706. doi: 10.1111/cyt.13164. Epub 2022 Jul 26.

Abstract

Background: Papillary thyroid carcinoma (PTC) is the most common primary malignant thyroid neoplasm and malignant diagnosis in thyroid aspirates. Metastatic adenocarcinoma of the lung is an under-recognised mimicker which overlaps cytomorphologically and immunocytochemically with PTC. This case series reviews thyroid aspirates of metastatic lung carcinomas, aiming to address the similarities and methods of differentiating this entity from PTC.

Methods: Thyroid aspirates of metastatic lung carcinomas were obtained by a computerised search. Clinico-cytological features and ancillary test results were reviewed. A literature review was performed for published cases of metastatic lung carcinomas in thyroid aspirates.

Results: A total of 14 cases were found, including nine adenocarcinomas, three TTF1-positive non-small cell lung carcinomas (NSCLCs), one small cell carcinoma and one squamous cell carcinoma. The adenocarcinomas and TTF1-positive NSCLCs displayed PTC-like features including papillae/papillary-like fronds (n = 6/12, 50%), nuclear grooves (n = 5/12, 41.7%) and inclusions (n = 1/12, 8.3%), chromatin clearing (n = 3/12, 25%), calcifications (n = 3/12, 25%) and multinucleated giant cells (n = 2/12, 16.7%). Useful distinguishing features observed were prominent nucleoli, coarse chromatin, mitosis, and necrosis. TTF-1 immunocytochemistry was positive in most cases (n = 5/6, 83.3%), while PAX8 and thyroglobulin were consistently negative. EGFR exon 19 deletion was detected on cell block preparation in a single case, corresponding to its lung primary. The literature search yielded 84 cases of metastatic malignancies, with lung carcinomas comprising of 3.6%-33.3% in case series of metastatic malignancies.

Conclusion: Metastatic adenocarcinoma of lung and PTC share significant cytomorphological and immunocytochemical similarities. A high degree of caution, meticulous clinico-cytological assessment and prudent use of ancillary techniques is necessary to avoid potential misdiagnosis.

Keywords: cytology; fine needle aspiration; metastasis; thyroid.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma* / diagnosis
  • Adenocarcinoma* / pathology
  • Biomarkers, Tumor
  • Carcinoma* / pathology
  • Carcinoma, Papillary* / pathology
  • Chromatin
  • ErbB Receptors
  • Humans
  • Lung / pathology
  • Lung Neoplasms* / pathology
  • Thyroglobulin
  • Thyroid Cancer, Papillary / diagnosis
  • Thyroid Neoplasms* / pathology

Substances

  • Biomarkers, Tumor
  • Chromatin
  • Thyroglobulin
  • ErbB Receptors