Difficulties in diagnostics of lung tumours in biopsies: an interpathologist concordance study evaluating the international diagnostic guidelines

Abstract

AimsAccurate and reliable diagnosis is essential for lung cancer treatment. The study aim was to investigate interpathologist diagnostic concordance for pulmonary tumours according to WHO diagnostic criteria.MethodsFifty-two unselected lung and bronchial biopsies were diagnosed by a thoracic pathologist based on a broad spectrum of immunohistochemical (IHC) stainings, molecular data and clinical/radiological information. Slides stained with H&E, thyroid transcription factor-1 (TTF-1) clone SPT24 and p40 were scanned and provided digitally to 20 pathologists unaware of reference diagnoses. The pathologists independently diagnosed the cases and stated if further diagnostic markers were deemed necessary.ResultsIn 31 (60%) of the cases, ≥80% of the pathologists agreed with each other and with the reference diagnosis. Lower agreement was seen in non-small cell neuroendocrine tumours and in squamous cell carcinoma with diffuse TTF-1 positivity. Agreement with the reference diagnosis ranged from 26 to 45 (50%–87%) for the individual pathologists. The pathologists requested additional IHC staining in 15–44 (29%–85%) of the 52 cases. In nearly half (17 of 36) of the malignant cases, one or more pathologist advocated for a different final diagnosis than the reference without need of additional IHC markers, potentially leading to different clinical treatment.ConclusionsInterpathologist diagnostic agreement is moderate for small unselected bronchial and lung biopsies based on a minimal panel of markers. Neuroendocrine morphology is sometimes missed and TTF-1 clone SPT24 should be interpreted with caution. Our results suggest an intensified education need for thoracic pathologists and a more generous use of diagnostic IHC markers.

Real-World Diagnostic Accuracy and Use of Immunohistochemical Markers in Lung Cancer Diagnostics

“…The results support a good overall diagnostic accuracy for lung cancer subtypes for small specimens. However, we can confirm our previous findings that neuroendocrine morphology is sometimes missed, and that TTF-1 clone SPT24 occasionally causes diagnostic problems [ 6 ]. Problems relating to TTF-1 clone SPT24 were seen in the Stockholm cohort, while in the Lund cohort, clone 8G7G3/1 was used for histological specimens and clone SPT24 was only used for cytology (due to weaker staining in CytoLyt ® /PreservCyt ® -fixed Cellient™-cell blocks).…”

“…Given the limited specificity of neuroendocrine markers [ 34 ], routine inclusion of such markers is not recommended in NSCC cases [ 7 ]. However, both our present and previous study [ 6 ] support a need to improve diagnostics, especially of LCNEC.…”

“…In a previous study, we found a moderate interobserver concordance among 20 pathologists for the diagnosis of non-selective lung and bronchial biopsies based on morphology, thyroid transcription factor-1 (TTF-1), and p40 [ 6 ] (the recommended panel for NSCC without distinct features [ 7 , 8 ]). Similar results have been shown in a study on tissue microarrays with a panel of four IHC markers [ 9 ].…”

“…The main conclusions from our study [ 6 ] were that the suboptimal specificity of TTF-1 clone SPT24 may cause diagnostic problems, that neuroendocrine morphology is sometimes missed, and that overuse (as well as occasional underuse) of IHC staining occurs. However, it was not possible in the same study to evaluate real-world diagnostic accuracy when any IHC marker could be ordered.…”

Radiomics in Lung Metastases: A Systematic Review

“…Lung biopsy is the diagnostic gold standard to distinguish between primitive lung tumors or LM, but it is an invasive technique that may not be performed in all cases, cannot be repeated indefinitely, and may be burdened by more or less serious complications. Another inherent downside to conventional biopsy is the fact that, even if guided by imaging, it can provide information solely related to the specific tumor specimen from which cells are sampled, only allowing a limited assessment of tumor heterogeneity with no ability to interrogate the whole tumor structure [ 10 , 11 , 12 , 13 , 14 ].…”