April 2016

A 55 year old male with a sore throat

Ryan Okal MD, Jeffrey Vos MD, Jeffrey Stead MD, and Flavia Rosado MD

Overview

A 55-year-old male presented to his primary care physician with a sore throat. The physical exam revealed an ill-defined left tonsillar mass and bilateral cervical lymphadenopathy. He was sent to the emergency department (ED) for a suspected peritonsillar infection, and received antibiotics.  A CBC at that time revealed an elevated white blood cell count (14.8 K/uL) with absolute lymphocytosis (8.5 K/uL). The symptoms persisted, and the patient underwent a tonsillectomy to rule out malignancy. Subsequent imaging studies revealed improvement of the cervical lymphadenopathy.

Gross and Microscopic Description

The specimen consisted of a 4.5 x 4.0 x 1.5 cm oriented tonsil with pink-tan mucosa and a 1.0 cm ill-defined ulcerated lesion. The resection margins were inked, and representative sections were submitted.

Microscopic examination revealed a polymorphous lymphoid infiltrate centered around a well-delineated focus of necrosis (see images A and C). The infiltrate was composed of scattered large atypical cells with bilobed nuclei and prominent nucleoli in a background of variably-sized lymphocytes, immunoblasts, eosinophils, histiocytes, and plasma cells (see image B). Scattered apoptotic cells and numerous mitotic figures were noted. By immunohistochemistry, the large cells were positive for CD30, CD20, PAX5, CD45, OCT2, and fascin, and negative for CD15 and CD3. The large cells were also positive for Epstein-Barr virus encoded RNA (EBER) in situ hybridization studies (see image D). CD3 does not show any T-cell abnormalities. A B-cell gene rearrangement study was negative for clonality.

image-a.jpg
Image A: 10x
image-b.jpg
Image B: 40x
image-c.jpg
Image C: 4x
image-d.jpg
Image D: 10x

Diagnosis

What is the most likely diagnosis ?

Answer

Please select an answer above.

Discussion

Epstein-Barr Virus (EBV) infections are known to persist quiescent in B-cells after initial childhood exposure. In the setting of age-related, pathologic, or iatrogenic immunosuppression, a wide spectrum of B-cell lymphoproliferative disorders may develop in nodal and extranodal sites. These range from benign self-limited EBV-lymphadenitis to more aggressive types of B-cell lymphoma (choice B, EBV DLBCL). EBV-positive mucocutaneous ulcer is a newly-described entity that falls along this spectrum.

EBV-positive mucocutaneous ulcer presents as a firm, ulcerated single lesion within the oropharynx; however, cases have been described along the GI tract and skin.  Our case had characteristic histologic findings previously described - polymorphous infiltrate of small lymphocytes, eosinophils, plasma cells, histiocytes, and RS-like cells. Reported cases also describe plasmacytoid apoptotic cells, arterial infiltration with thrombosis, and lesional rimming by small lymphocytes, which were not apparent in this particular case.

The IHC and gene rearrangement studies are important in distinguishing mucocutaneous ulcer from other malignant processes such as CHL and DLBCL. The large, atypical RS-like cells are PAX-5-positive B-cells with co-expression of CD30 and variable co-expression of CD20, mimicking CHL. However, the positive CD45 and OCT-2 staining with a negative CD15 expression are helpful to distinguish EBV-mucocutaneous ulcer from CHL. Morphologically, EBV-mucocutaneous ulcer can be identical to polymorphous examples of EBV-DLBCL. In our case, the negative B-cell gene rearrangement study, along with the spontaneous clinical improvement, were not in keeping with the diagnosis of EBV-DLBCL. Of note, although clonality studies in EBV mucocutaneous ulcers are often negative, a case series of 26 mucocutaneous ulcers reported B-cell clonality in 7 cases (38.9%) and T-cell clonality in 6 cases (37.6%).

Mucocutaneous ulcer usually behaves as a benign process with spontaneous resolution; however, it may occasionally persist or evolve into lymphoma, warranting close clinical follow-up.

Reference

  1. Dojcinov, S. D., Venkataraman, G., Raffeld, M., Pittaluga, S., & Jaffe, E. S. (2010). EBV Positive Mucocutaneous Ulcer - A Study of 26 Cases Assocaited With Various Sources of Immunosuppression. American Journal of Surgical Pathology, 34(3), 405-417.
  2. Kjeldsberg, C. R., Perkins, S. L., et xiii alia (Eds.). (2010). Practical Diagnosis of Hematologic Disorders (5th ed., Vol. 1 and 2). Chicago, IL: ASCP Press.
  3. Swerdlow, S. H., Campo, E., Harris, N. L., Jaffe, E. S., Pileri, S. A., Stein, H., . . . Vardiman, J. W. (Eds.). (2008). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (4th ed.). Lyon: International Agency for Research on Cancer.