CytoPage Quiz – 2024 June – NUS Pathweb

CytoPage Quiz 2024 June

Question: Atypical cells in ascitic fluid

A 72 year old man presents with recurrent ascites. The cytology shows singly scattered atypical cells with vacuolated cytoplasm and some nuclear pleomorphism and prominent nucleoli, with an absence of prominent cellular aggregates. There was insufficient cellularity to perform a cell block for further ancillary tests.

Do you favour these cells to be:

A) Mesothelial origin
B) Metastatic carcinoma
C) Histiocytes

And how would you have called it, in the absence of a cell block?

Quiz written by Dr Benjamin Farah, Singapore General Hospital

Answer

A. Mesothelial cells

The lesional cells are of mesothelial origin, as indicated by their retention of skirting and windowing, their ovoid nuclei and dense cytoplasm and the lack of a clear cut second lesional population. In the absence of a cell block for further workup, the most prudent interpretation would be to suggest the presence of atypia and recommend clinical correlation and the option of biopsy for further workup.
Subsequent peritoneal biopsy performed showed the presence of atypical sheets of mesothelial cells infiltrating into fibroadipose tissue. Immunohistochemical staining confirmed mesothelial nature, as well as BAP1 loss (no loss of p16 with FISH). Findings were thus best in keeping with malignant epithelioid mesothelioma.

This case highlights a situation where mesothelioma may not present as a cellular yield of crowded three-dimensional groups, but as singly dispersed cells with more subtle atypia. Thus, diagnosis would be more reliant on cytomorphology of individual cells. Some tips for recognising the differences:

REACTIVE	MALIGNANT
Moderately cellular	Hypercellular
Monolayered sheets	2D and 3D clusters
Small cell groups	Large cell groups
Mild variation in cell size	Marked variation in cell size
Giant/multinucleated cells often absent	Giant/multinucleated cells present
No prominent cytoplasmic blebs/microvilli	Cytoplasmic blebs/microvilli prominent
Mild nuclear atypia	Pleomorphism, irregular nuclear contours, large nucleoli

If a cell block is available, the following stains could be attempted depending on cellularity:

Markers of mesothelial lineage:

Calretinin, CK5/6, WT-1, D2-40, EMA (membranous)

Markers of epithelial/adenocarcinoma lineage:

mCEA, MOC-31, Ber-EP4, Claudin-4, EMA (cytoplasmic)
Specific markers of specific adenocarcinoma types (ie TTF1, PAX8, etc).

Markers of malignancy:

BAP1 (loss of nuclear staining), MTAP (loss of cytoplasmic staining)

CDKN2A/p16 deletion can be detected by FISH which would support mesothelioma.

The following algorithm may also be of help: