To the Editor.—We read with interest the article “The Azzopardi Phenomenon” by Pritt and Cooper1 published in the Archives of Pathology & Laboratory Medicine. To our knowledge, we here report the first case of Burkitt lymphoma (BL) with this phenomenon.
An 8-year-old boy presented with a 3-month history of a painless mass over the right submandibular area. During this period, the mass progressed in size without other associated symptoms. Physical examination revealed a 5 × 4-cm node, but there was no hepatosplenomegaly or other lymphadenopathy. Laboratory data were within normal limits, including blood counts and biochemistry. Simple excision was performed. Tumor staging workup revealed a stage I BL. He received chemotherapy and was free from tumor for 6 years on last visit. Pathologically, the lymph node showed diffuse, monotonous infiltration of blue neoplastic cells with a prominent “starry-sky” pattern (Figure, a). The medium-sized tumor cells possessed round nuclei with clumped chromatin and multiple prominent basophilic nucleoli. Mitotic figures and apoptotic bodies were numerous. There were sheets of tumor necrosis with adjacent infiltrates of foamy histiocytes. Necrosis occupied 50% to 65% of the tumor areas and contained many blood vessels outlined by the deposition of basophilic material in the walls, imparting the Azzopardi effect (Figure, b). Immunohistochemically, the tumor cells expressed CD20 (Figure, c), CD10, and Bcl-6 but were negative for CD3, Bcl-2, terminal deoxynucleotidyl transferase, cytokeratin, and S100 protein. In situ hybridization for Epstein-Barr virus was also negative. Nearly 100% of the tumor cells were positive for Ki-67 (Figure, d). The results were consistent with BL.
The Azzopardi effect has been observed in 32% of lung small cell carcinoma cases2 and now serves as a criterion for the differentiation of small cell carcinoma from non–small cell carcinoma in lung pathology.2,3 The pathogenesis of this effect is intriguing. Azzopardi noted a strong association of this effect with tumor necrosis and attributed the DNA deposition to the liberation of nucleic acids in large amount from degenerating tumor tissue.2 To clarify the relationship of the Azzopardi effect with tumor necrosis in BL, we retrospectively reviewed an additional 56 cases of BL in archival file and evaluated the frequency and area of tumor necrosis. Azzopardi effect was not found in any case. However, 28 cases (50%) showed tumor necrosis with areas ranging from 5% to 70%. The previous findings suggest that the Azzopardi effect is a much rarer event for BL than for lung small cell carcinoma, and tumor necrosis is likely a sine qua non but not a sufficient element for its formation. Other factors, such as pH, permeability and solubility in the niche (vessel wall), endothelial cell function, and tumor type may also play a role. In this regard, Azzopardi has proposed that the intensity of the DNA deposition may reflect a balance between the rate of formation and the rate of removal.2
Azzopardi phenomenon has been noted in diffuse large cell lymphoma.4 However, in BL, a highly proliferative and frequently necrotic lymphoma, to our knowledge this phenomenon has never been reported previously. Our case expands the spectrum of tumors with Azzopardi phenomenon, which may lead to diagnostic problems with other blue cell neoplasms.
The authors have no relevant financial interest in the products or companies described in this article.