In our laboratory, CD56+/CD45− neuroendocrine malignancies are only rarely detected in solid tissue specimens, with only 12 cases seen in approximately 2000 specimens (0.6%) over five and three quarter years. However, this figure is probably an underestimate, because the anti-CD56–PE/anti-CD3–FITC/anti-CD45–PC5 combination was not used in studies where the number of retrieved cells was limited—for example, small biopsy specimens.
Take home messages
- Anti-CD56 antibodies should be included in flow cytometric studies of solid tissue specimens wherever possible
- Recognition of the CD56+/CD45− immunophenotype can help avoid the potential misclassification of such specimens as natural killer cell malignancies, especially if autofluorescence/non-specific staining is misinterpreted as weak CD45 expression
- The CD56+/CD45− immunophenotype is a useful rapid indicator for the presence of neuroendocrine malignancies, thus leading to the appropriate immunohistochemical studies necessary to facilitate their correct diagnosis
Anti-CD56 antibodies have been reported to be of value in the identification of neuroendocrine malignancies by immunohistochemical studies.4,5
Our cases illustrate that anti-CD56 antibodies can also be used in flow cytometric studies to identify these malignancies, with the added advantage that the concurrent use of anti-CD45 and anti-CD56 antibodies in three (or more) colour fluorochrome antibody panels also enables demonstration of the non-leucocyte lineage (negative CD45 expression)8
of these malignancies.
Three of the 12 CD56+/CD45− malignancies were Merkel cell carcinomas, sometimes referred to as primary neuroendocrine carcinomas of the skin.5
These uncommon malignancies exhibit the following immunohistochemical characteristics: staining for keratin 20 (approximately 90% of cases), chromogranin A (approximately 33% of cases), CD57 (approximately 15% of cases), and synaptophysin in a minority of cases.5
Our study demonstrates the usefulness of the CD56+/CD45− immunophenotype in raising the possibility of Merkel cell carcinoma, although this immunophenotype is not specific for this particular neuroendocrine malignancy.
“Our study demonstrates the usefulness of the CD56+/CD45− immunophenotype in raising the possibility of Merkel cell carcinoma”
The detection of CD56 and CD57 expression on neuroectodermal malignancies by flow cytometry has been reported previously,6
but the expression of CD45 in these cases was not mentioned, probably because only two colour flow cytometric studies were performed. However, because neuroectodermal malignancies are not routinely sent to our department for flow cytometric studies, we were unable to determine whether these malignancies would also demonstrate the CD56+/CD45− immunophenotype. Furthermore, because we do not routinely test for CD57 expression, we are unable to comment on whether the 12 neuroendocrine malignancies in our series would have also expressed CD57.
Our study highlights the usefulness and importance of including anti-CD56 antibodies in flow cytometric studies of solid tissue specimens wherever possible. Furthermore, the recognition of this CD56+/CD45− immunophenotype is important to avoid the potential misclassification of such specimens as NK cell malignancies, especially if autofluorescence/non-specific staining is misinterpreted as weak CD45 expression.
In conclusion, we report that flow cytometric detection of the CD56+/CD45− immunophenotype is a useful rapid indicator for the presence of neuroendocrine malignancies, thus leading to the appropriate immunohistochemical studies necessary to facilitate their correct diagnosis.