Cytomorphological features of metastatic squamous cell carcinoma in serous effusions

Our plain-English summary of Cytomorphological features of metastatic squamous cell carcinoma in serous effusions, by C.C. Huang, C.W. Michael (Cytopathology, 2014).

The study

• Authors: C.C. Huang, C.W. Michael
• Journal: Cytopathology
• Published: 2014;25(2):112-9
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: To study the cytomorphological features of squamous cell carcinoma (SCC) in serous effusions.

Methods: Conventional smears from 23 SCC were reviewed for the following features: cellularity, single cells, cell clusters, long cords, squamous pearls, cell-in-cell, 'windows', polygonal cells, anucleated cells, tadpole cells, fibre cells, third-type cells, refractile cytoplasmic ring, two-tone cytoplasm, cytoplasmic density, cytoplasmic vacuoles, signet ring cells, nuclear/cytoplasmic ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleolus, anaplastic cells and mitosis. Subsequently, we also reviewed 15 reactive mesothelium, 18 mesotheliomas and 24 adenocarcinomas for comparison.

Results: Most SCC smears comprised mixed populations of single cells and cell clusters. Keratinized squamous cells and squamous pearls were diagnostic for well-differentiated SCC. Squamous eddies, appreciated on the cell block sections appearing as two-dimensional cell clusters with a swirling pattern, were characteristic for SCC. Poorly differentiated/third-type cells with atypical cytoplasmic keratinization, manifest as two-tone cytoplasm with a well-defined border and occasionally a refractile central ring, were an important clue for the squamous origin of the cells. Features including cell-in-cell, cytoplasmic vacuolation, double or multinucleated cells, anaplastic cells and mitotic figures were present in various degrees, and were not of diagnostic value.

Conclusions: Certain cytological features are diagnostic for SCC, whereas other features of poorly differentiated SCC often overlap with those of reactive mesothelial cells, mesothelioma, metastatic adenocarcinoma or urothelial carcinoma in serous effusions. The combination of clinical history, appropriate immunohistochemical panel and cytomorphological features are important to ensure a correct diagnosis.

© 2013 John Wiley & Sons Ltd.

In plain English

This study did not examine asbestos exposure. It looked at how to recognise, under the microscope, squamous cell carcinoma (SCC) that had spread into fluid around the lungs, abdomen or heart, and how to tell it apart from malignant mesothelioma and other conditions. The authors searched University of Michigan pathology records from 1989 to 2011 and found 36 such cases among 18,626 fluid samples. Slides survived for 23 of them (17 pleural, five peritoneal, one pericardial). These were compared with slides from 15 reactive mesothelium, 18 malignant mesothelioma and 24 adenocarcinoma cases. Poorly differentiated 'third-type' cells were seen in all SCC cases and in none of the comparison cases. A refractile cytoplasmic ring was seen in more than half of SCC cases and in no controls. Cell windows and two-tone cytoplasm were seen in all mesotheliomas and in some SCC cases. On staining, WT1 was positive in none of 15 SCC cases and in all 18 mesotheliomas, and p63 the reverse (12 of 15 versus 0 of 18). The authors concluded that clinical history, a suitable staining panel and cell features together are needed for a correct diagnosis.

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 archived cytology slides from one pathology department (case series with a comparison group)
• Who was studied: 36 cases of metastatic squamous cell carcinoma in pleural, peritoneal or pericardial fluid, found among 18,626 serous fluids at the University of Michigan between 1989 and 2011. Smears were available for 23 cases (17 pleural, five peritoneal, one pericardial). The comparison group was 15 reactive mesothelium, 18 malignant mesothelioma and 24 adenocarcinoma cases.
• Exposure: Not an exposure study. Asbestos and fiber types are not mentioned. Malignant mesothelioma appears only as a comparison group for microscope features.
• Main results:
  • Among all 36 cases, primary lung SCC (15 cases) accounted for 42% of all the metastases and 50% of the pleural metastases.
  • Poorly differentiated 'third-type' cells were present in all 23 SCC specimens. They were absent in the reactive mesothelium, malignant mesothelioma and adenocarcinoma comparison cases.
  • Atypical keratinization of third-type cells, including refractile ring formation, was found in more than half of the SCC cases (13 of 23, 57%, in Table 2) and in none of the controls.
  • Keratinized polygonal cells, anucleated cells, tadpole cells and fibre cells were seen in 7, 2, 4 and 5 of the 23 SCC cases respectively. None were seen in controls.
  • Cell windows were seen in 8 of 23 SCC cases. In those cases they appeared as tight straight spaces rather than the biconvex spaces seen between mesothelial cells. Table 2 records cell windows in all 15 reactive mesothelium and all 18 mesothelioma cases.
  • Double or multiple nucleated cells, anaplastic cells and mitoses were uncommon in SCC and were not specific for SCC.
  • WT1 staining was positive in 0 of 15 SCC cases, 15 of 15 reactive mesothelium cases, 18 of 18 malignant mesotheliomas and 0 of 24 adenocarcinomas.
  • p63 staining was positive in 12 of 15 (80%) SCC cases, 0 of 15 reactive mesothelium cases, 0 of 18 malignant mesotheliomas and 3 of 24 (13%) adenocarcinomas.
• The authors' conclusion: The authors concluded that metastatic SCC is very rare in serous effusions and is usually not difficult to diagnose with clinical history and characteristic features. However, some features overlap with reactive mesothelium, mesothelioma, adenocarcinoma or urothelial carcinoma. In their view, clinical history, an appropriate immunohistochemical panel and cell features are together important for a correct diagnosis.
• Limitations the authors state:
  • Slides could be discarded after 10 years under regulatory guidelines, so only 23 of the 36 cases could be reviewed.
  • The authors could not assess how often patients with known SCC who developed an effusion had a malignant effusion, because the laboratory system did not store clinical information.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Squamous Cell Carcinoma, Mesothelium, Mesothelioma, Adenocarcinoma, Squamous Cell, Well-Differentiated, Cell Block, Reactive Mesothelial Cells.

Related studies

• Cytomorphologic features of metastatic urothelial carcinoma in serous effusions — C.C. Huang, A. Attele, et al. (2013)
• "Cannonballs" and psammoma bodies: unusual cytologic features of metastatic pulmonary small-cell carcinoma in a pleural effusion — A.B. Conway, M.K. Hart, et al. (2013)
• Small orangiophilic squamous-like cells: an underrecognized and useful morphological feature for the diagnosis of malignant mesothelioma in pleural effusion cytology — L. Chen, S.G. Caldero, et al. (2014)
• Pseudomesotheliomatous carcinoma due to pleural metastasis from renal pelvic cancer — Y. Katsuya, M. Fukusumi, et al. (2014)
• Calretinin. A selective marker of normal and neoplastic mesothelial cells in serous effusions — M.C. Barberis, M. Faleri, et al. (1997)
• Utility of HBME-1 immunostaining in serous effusions — V. Ascoli, C. Carnovale-Scalzo, et al. (1997)

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