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Image of the Week
Edited and moderated by Stacey Mills, MD, Pathology Network's Image of the Week Blog is a forum for the discussion of interesting and often diagnostically challenging pathology images.
Wednesday, February 13, 2013
A 70-year-old woman with a uterine cervical mass.
A 70-year-old woman was noted on physical exam to have a uterine cervical mass.  A cervical conization was performed and several images from the resultant specimen are shown below. 
There is a prominent lymphoplasmacytic background highly evocative of a lymphoproliferative process.  Embedded within the inflammatory background are ill-formed nests and cords of larger cells with variable eosinophilic cytoplasm.  The nuclei in the latter cells are considerably enlarged, but nuclear chromatin is uniform from cell to cell.  Cell borders are indistinct and the larger nuclei appear to float in a syncytium of cytoplasm.  Mitotic figures, including atypical forms are easily found in this cell population.
What is your diagnosis?
Several immunohistochemical stains were performed and are shown below.
CD45 (LCA) (above) strongly stains the prominent background lymphoid infiltrate, but the larger cells are negative.
The larger cells were strongly positive for cytokeratin as seen above.
The cytokeratin positive cells also strongly and diffusely expressed p16 seen above.

In-situ hybridization for human papillomavirus was not performed but would be expected to be strongly positive. 
This is an example of a lymphocyte-rich variant of cervical squamous cell carcinoma that has also been referred to as lymphoepithelioma-like carcinoma because of its strong resemblance to nasopharygeal lymphoepithelioma.  The latter tumor, of course, is causally related to Epstein-Barr virus whereas the current tumor is undoubtedly due to human papillomavirus.   Tumor site overides histologic appearance with regard to causation.  Some earlier studies utilizing PCR instead of in-situ hybridization purported to show that EBV was present in a substantial number of these tumors.  However, this almost certainly represents false positivity due to EBV-containing lymphocytes common in the general population.  In contrast high-risk HPV is easily demonstrated by in-situ hybridization in these tumors.
The main reason for recognizing this histologically distinct variant is to avoid confusing this process with a lymphoma. The advent of type-specific immunohistochemical markers makes short work of this distinction provided the proper stains are ordered.  If an epithelial marker such as cytokeratin, p63 or EMA is not employed, the large numbers of adjacent lymphocytes can give a false sense of positivity in the epithelial cells on CD45 staining.  Tumors with this histologic appearance occur at a wide variety of anatomic sites where the above differential also occurs.
Whether cervical lymphoepithelioma-like carcinoma has clinically distinctive features is not entirely clear.  Some studies have suggested that stage for stage these tumors have less frequent lymph node metastases and better overall prognosis when compared to conventional squamous carcinoma of the cervix.  Other studies have also shown that all types of cervical carcinoma with a prominent inflammatory infiltrate tend to have a better overall prognosis.
Dr. amit kumar said:
Sir, The first image as mentioned gives the impression of a lymphoproliferative process but the clinching point is Cytokeratin stain. Thanks for highlighting a potential diagnostic pitfall Dr.Amit Kumar MD(Path)
Dr. JAIME A. MEJIA said:
The fact that lymphocytes can be the source of a false positive EBV probe caught my attention. Thanks Dr. Mills.
About the Author

Stacey E. Mills, MD
Stacey E. Mills, MD, a graduate of University of Virginia (UVA) and the UVA Medical Center, has authored nearly 230 articles, 20+ books, atlases and monographs—including the renowned Sternberg's Diagnostic Surgical Pathology. He has been a practicing Professor and Staff Pathologist at UVA for 30+ years and is Director of Surgical Pathology and Cytopathology. His clinical specialty is general surgical pathology with emphasis on neoplasms and neoplasm-like lesions. Dr. Mills is also Editor-in-Chief of The American Journal of Surgical Pathology.