Merkel Cell Carcinoma and Azzopardi Phenomenon

Abstract

To the Editor: Foci of strongly hematoxyphilic blood vessels appearing as the result of chromatin diffusion secondary to necrosis of neoplastic tissue are sometimes referred to as the Azzopardi phenomenon.1 This phenomenon was named after John G. Azzopardi, who had identified the basophilic granular material in the vessel wall as DNA, having examined cases of small cell carcinoma of the lung.2 Merkel cell carcinoma (MCC) is an aggressive primary neuroendocrine tumor of the skin that was described by Toker3 in 1972. The most important differential diagnosis of MCC is metastatic small cell carcinoma of the lung; it often requires combined assessment of the clinical features, light microscopy, and immunohistochemistry.4-6 A paper by Schmidt and coworkers7 that appeared in this journal in 1998 documented the presence of the Azzopardi phenomenon in MCC. Yet, most recently, Patterson and Wick,8 the authors of the new AFIP Atlas of Nonmelanocytic Tumors of the Skin, have stated that the Azzopardi phenomenon is never seen in primary neuroendocrine tumors of the skin, in particular MCC, suggesting that this histopathological feature may be used as a clue to metastatic small cell carcinoma of the lung. Besides the paper of Schmidt et al,7 the only other two articles mentioning the Azzopardi phenomenon in MCC that we were able to find in the literature are the paper by Sibley et al9 and the paper by Foschini and Eusebi.10 This controversy prompted us to review our cases of MCC to check whether the Azzopardi phenomenon is present in this cutaneous neoplasm. Among 83 cases of MCC retrieved from our files, the Azzopardi phenomenon was found in three tumors (Fig. 1). This frequency is somewhat lower than was seen in the series of Schmidt and colleagues, who identified DNA deposits in vessel walls in 7 of 76 studied cases of MCC. Interestingly, all seven of these cases were found among the so-called small cell variant. Although the morphological subdivision of MCC into intermediate, small cell, and trabecular subtypes is used, in our experience, this subclassification is arbitrary: a majority of our cases exhibited a combination of these three morphological patterns. Likewise, all three cases in which we detected the Azzopardi phenomenon manifested small cell areas, intermediate cell morphology, and trabecular arrangement of the neoplastic cells. It seems to us that the Azzopardi phenomenon is indeed a rare feature in MCC, but, taken alone, it cannot be used as a diagnostic criterion for distinguishing MCC from metastatic small cell carcinoma of the lung.FIGURE 1: The Azzopardi phenomenon in Merkel cell carcinoma of the skin: several vessels with dense DNA depositions in their walls.Marina Vazmitel, MD Academy of Postgraduate Education of Belarus Minsk, Republic of Belarus Michal Michal, MD Dmitry V. Kazakov, MD, PhD Sikl's Department of Pathology Charles University, Medical Faculty Hospital Pilsen, Czech Republic