Australian Society of Cytology

Case of the Month

September 2002 - Answer and Discussion

Right pleural fluid: MALIGNANT; adenocarcinoma, the staining profile favours a primary lung adenocarcinoma.


Immunohistochemistry for cytokeratin 7 showing strong diffuse cytoplasmic positivity.	Immunohistochemistry for CEA showing diffuse membrane positivity.


Immunohistochemistry for EMA shows diffuse cytoplasmic positivity without membrane accentuation.	Immunohistochemistry for thyroglobulin transcription factor one (ttf-1) shows strong nuclear positivity in almost 100% of tumour cells.

DISCUSSION

A diagnosis of malignant epithelial tumour is easy to make in this case. The common differential diagnosis is adenocarcinoma versus mesothelioma. The clinical information supplied is, as usual, inadequate. A positive or negative history of asbestos exposure should be mentioned, the radiological findings should be commented upon and any past history of malignancy is relevant.
The cytological features are well covered in the literature (see references1-4).
It is often surprising that a mucin stain is negative when there appears to be well defined cytoplasmic vacuolation on the smears and cell block. Possible explanations are that it represents glycogen, fat or hydropic degeneration which can occur when cells are floating in fluid. Immunohistochemistry can be useful in distinguishing between adenocarcinoma and mesothelioma. Glandular markers such as CEA, Ber-EP4, Leu M1, B72.3 can be positive in the former and mesothelial markers such as Calretanin and cytokeratin 5/6 are a positive in the latter. EMA will show diffuse cytoplasmic positivity in adenocarcinoma and a distinctive membranous positivity in a malignant mesothelioma (it is negative in benign mesothelial proliferations) (see reference 2-5).

Determining that the primary site of an adenocarcinoma can be problematic. Lung is obviously the most likely based on frequency and proximity. Using differential cytokeratin staining it should be positive for cytokeratin 7 and negative for cytokeratin 20. Nuclear positivity for Thyroid Transcription Factor-1 (TTF-1) in this setting is a very strong indication that lung is the primary site provided a primary thyroid carcinoma has been excluded (see reference 6 ).

REFERENCES

Stevens MW, Leong AS-Y, Fazzalari NL, Dowling KD, Henderson DW. Cytopathology of malignant mesothelioma: A stepwise logistic regression analysis. Diagnostic Cytopathology 1992;8:333-41.
Whitaker D, Shilkin KB, Sterrett GF: Cytological appearances of malignant mesothelioma. Malignant Mesothelioma. Hemisphere, New York, pp 167-182, 1992.
Whitaker D, Sterrett GF, Shilkin KB: Mesotheliomas. In Gray W, ed: Diagnostic Cytopathology. Churchill Livingstone, Edinburgh, 1995, p195-224.
Leong AS-Y,Stevens MW, Mukherjee TM. Malignant mesothelioma: cytologic diagnosis with histologic, immunohistochemical, and ultrastructural correlation. Seminars in Diagnostic Pathology 1992;9:141-50.
Kuhlmann L, Berghauser KH, Schaffer R. Distinction of mesothelioma from carcinoma in pleural effusions. An immunocytochemical study on routinely processed cytoblock preparations. Pathology, Research & Practice 1991;187:467-71.
Ordonez NG. Thyroid Transcription Factor-1 is a marker of lung and thyroid carcinomas. Advances in Anatomic Pathology 2000;7:123-7.