Root cause analysis of indeterminate diagnoses in serous fluids cytopathology

Our plain-English summary of Root cause analysis of indeterminate diagnoses in serous fluids cytopathology, by H.N. Gokozan, A. Harbhajanka, S. Lyden, et al (Diagnostic Cytopathology, 2021).

The study

• Authors: H.N. Gokozan, A. Harbhajanka, S. Lyden, C.W. Michael
• Journal: Diagnostic Cytopathology
• Published: 2021;49(5):633-639
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: The International System for Reporting Serous Fluid Cytopathology proposed five diagnostic categories: Nondiagnostic (ND), Negative for Malignancy (NFM), Atypia of Undetermined Significance (AUS), Suspicious for Malignancy (SFM) and Malignant (MAL) (Primary or Metastatic). The indeterminate (AUS/SFM) categories are challenging for management. The goal of this study is to reveal the root causes contributing to indeterminate diagnoses (ID).

Materials And Methods: We searched our archives between 1 January 2017 and 30 June 2019, and performed a root cause analysis (RCA) using the "5 whys" method to determine the contributing factors of ID.

Results: Nine hundred eleven specimens were evaluated and diagnosed: ND (9, 1%), NFM (667, 73.2%), AUS (51, 5.6%), SFM (27, 3%) and MAL (157, 17.2%). More than one factor contributed to 38/78 ID. Low volume (<50 cc), and low cellularity were identified in 31 and 51 cases, respectively. Three cases were simply deferred to concurrent biopsy. Eleven cases were called atypical, favor reactive mesothelium despite confirmatory IHC. Atypical lymphoid population was reported in seven cases. Cellblocks (CB) were low in cellularity despite volume >1000 mL in 13 cases. Two mesotheliomas were underdiagnosed as suspicious.

Conclusions: Low cellularity and low volume were the most common contributing factors, highlighting the importance of adequate sample collection. Adequate volume specimens with low cellularity may benefit from a close inspection and a second CB. Some IDs can be switched to NFM or MAL with careful consideration of clinical, radiologic findings and ancillary testing, and concurrent surgical pathology correlation when available.

© 2021 Wiley Periodicals LLC.

In plain English

This study, from University Hospitals Cleveland Medical Center, looked at why pathologists sometimes gave uncertain results on body-cavity fluid samples. Its uncertain categories were 'atypia of undetermined significance' and 'suspicious for malignancy'. It does not discuss asbestos. The authors reviewed 911 fluid samples received from 1 January 2017 to 30 June 2019. They examined the 78 uncertain cases (51 atypical, 27 suspicious) with a 'root cause analysis' that asks 'why' repeatedly. More than one cause was found in 38 of the 78. Too few abnormal cells was the most common cause (51 cases). Low fluid volume, under 50 cc, was found in 31 cases. In 13 cases, the processed cell block was poor in cells even though more than 1000 mL had been submitted. In 11 cases, stains showed the cells came from the cavity lining, yet they were still called atypical. On later review, two malignant mesotheliomas had been called only 'suspicious'. The authors concluded that low cellularity and low volume were the most common causes. They also concluded that malignant mesothelioma can be diagnosed from fluid cytology alone when set criteria are met.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective review of laboratory archives, with a root cause analysis using the '5 whys' method
• Who was studied: 911 serous fluid (effusion) specimens received by the cytopathology laboratory at University Hospitals Cleveland Medical Center/Case Western Reserve University between 1 January 2017 and 30 June 2019. Abdominal/pelvic washings and cyst extractions were excluded. 78 indeterminate cases (51 atypia of undetermined significance, 27 suspicious for malignancy) were analysed.
• Exposure: Not applicable. The study did not examine asbestos or any other exposure. It examined the causes of indeterminate cytology diagnoses.
• Main results:
  • Diagnoses of all 911 specimens: nondiagnostic 9 (1%), negative 667 (73.2%), atypical 51 (5.6%), suspicious 27 (3%), malignant 157 (17.2%)
  • More than one contributing factor was found in 38 of the 78 indeterminate cases
  • Low cellularity of the atypical cells was found in 51 of 78 indeterminate cases (65%): 29 of 51 atypical and 22 of 27 suspicious
  • Low specimen volume (less than 50 cc) was found in 31 of 78 indeterminate cases (40%): 23 of 51 atypical and 8 of 27 suspicious
  • 19 atypical cases carried a comment favoring reactive mesothelium. In 11 of these, stains highlighted mesothelial cells and epithelial markers were negative.
  • Cell blocks were low in cellularity despite adequate specimen volume in 13 cases
  • Atypical lymphoid populations were reported in four cases. The article states that three more were reported as suspicious for lymphoma.
  • Three cases (one malignant melanoma, one mesothelioma, one angiosarcoma) were worked up for the incorrect differential diagnosis. Three cases (one atypical, two suspicious) were deferred to concurrent biopsy.
  • On retrospective review, two malignant mesotheliomas had been under-called as suspicious for malignancy, suggesting malignant mesothelioma
  • Among the 78 indeterminate cases, a concurrent biopsy was positive for malignancy in 20 cases
  • Among the 78 indeterminate cases, a history of malignancy before the effusion was noted in 35
  • In 7 of the 78 indeterminate cases, the patients had neither a history of malignancy nor a malignant follow-up
• The authors' conclusion: The authors concluded that the most common causes of indeterminate diagnoses were low tumor cellularity and low specimen volume. They concluded that malignant mesotheliomas can be called on cytopathology findings alone when specified criteria for malignancy are recognized.
• Limitations the authors state:
  • Because the study was retrospective and not all procedure notes recorded how much fluid was collected, the authors could not fully identify why samples were low in volume

Topics

Medical terms in this study, explained in our Lexicon: Serous Fluid, Cytopathology, Biopsy, Mesothelium, Mesothelioma, Pathology.

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