Use Of IC In Cytology

Question 1

What is IC used for?

Answer 1

IC is not necessarily conclusive but it can be helpful to clinicians who are faced with a difficult case and in cases that require imaging and invasive procedures where IC can assist in narrowing the search for the primary.

Question 2

What are the benefits of IC?

Answer 2

Can help clinicians who are faced with a difficult case.

Can assist in cases that require imaging and invasive procedures where IC can assist in narrowing the search for the primary (will give info on origin of tumour cells).

Time as well as money can be saved if IC is utilised properly.

Question 3

What is antibody for carcinoembryonic antigen (CEA) used for?

Answer 3

Antigen for CEA is very popular on panels to define adenocarcinoma.

The sensitivity varies from 90-50%.

Specificity in excluding mesothelial origin is usually more than 90% as long as monoclonal CEA antibodies are used.

Question 4

What is Calretinin a marker for?

Answer 4

Calretinin is the single best marker for mesothelial differentiation.

Calretinin found 100% staining in mesothelial cases compared to only focal staining if 23% of lung adenocarcinomas.

Question 5

What is TTF1 a marker for?

Answer 5

Thyroid transcription factor 1 (TTF1) is positive (nuclear staining) in up to 70-89% of primary lung adenocarcinomas.

In lung small cell carcinoma TTF1 is not helpful because most small cell carcinomas are TTF1 positive independent of organ site.

Question 6

What is COX-2 a marker for?

Answer 6

Colorectal cancers are COX-2 positive.

Question 7

What are CD7 and CK20 markers for?

Answer 7

Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are used to determine the origins of adenocarcinomas.

CK7+ve and CK20-ve - lung, female genital tract, breast, pancreas, upper GIT.

CK7-ve and CK20+ve - Lower GIT carcinomas.

Question 8

What is BER EP4 a marker for?

Answer 8

When cytology appears glandular but CEA is negative you need to make sure that the malignant cells are epithelial.

Use BER-EP4 which tends to be positive in carcinoma and negative in mesothelioma.

Question 9

What markers are helpful for identifying pancreatic carcinoma?

Answer 9

CA 19-9 and CEA tend to be helpful in metastatic pancreatic carcinoma. Both tend to be positive on these cases.

Question 10

What is WT-1 a useful marker for?

Answer 10

WT-1 is very useful for diagnosing serous carcinoma of the ovary. It shows positive expression in these cases.

Question 11

What marker may be used to help identify ovarian carcinoma?

Answer 11

CA125 although it tends to be seen with low specificity and sensitivity.

Question 12

What is Oestrogen Receptor (ER) a good marker for?

Answer 12

Breast cancer and most types of female tract cancer are oestrogen receptor positive.

Question 13

What marker might you used to identify prostate cancer?

Answer 13

Prostate Specific Antigen (PSA).

Question 14

What are the most common samples that require IC in the cyto lab?

Answer 14

Effusions. These may be pleural, pericardial or ascites (from the peritoneal cavity).

Question 15

If adenocarcinoma of unknown origin is found in a pleural effusion what is its most likely origin in each sex?

Answer 15

In adult make it is most likely of lung origin.

In adult women the most likely origin is breast with lung a close second.

Similar differential diagnosis is given for pericardial effusion.

Question 16

What is the most common cause of ascites with adenocarcinoma of unknown origin in each sex?

Answer 16

Likely to be ovarian in women and of GI origin in men.

Question 17

Is it possible to differentiate between stomach, pancreatic and ovarian cancers using ICC?

Answer 17

No.

Question 18

What are some limitations of ICC?

Answer 18

ICC cannot be used to distinguish on situ vs. reactive vs. inflammatory lesions, only cancers.

It is not possible to distinguish stomach, pancreatic and ovarian carcinomas using ICC.

Question 19

What might ICC be replaced by in the future?

Answer 19

Proteomic profiling. Better used on non formalin fixed material and is especially applicable to cytology preparations.

IC staining for selected panels may be replaced by proteomics profiling methods in future with each type of cancer having its own unique proteomics profile.

Question 20

What factors should be considered when choosing antibodies for use on IC?

Answer 20

It is recommended that predetermined panels are avoided. They will stop you truly thinking about what antibodies are required for a particular case and may be a waste of materials.

Decisions should be based on the cytological differential diagnosis, consideration of the quantity of material to test and patient clinical information.

1) . Clinical history should be examined (sex, age, site, previous history).
2) . Review previous cytology/histology material (compare morphology with previous sample).
3) . Look at cytological characteristics on cytological preparations (tight differential diagnosis).
4) . Select and run a panel.
5) . If the first panel does not contribute then widen the differential diagnosis (select additional IC stains, obtain more material, advise histological sampling).