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The Azzopardi phenomenon.

To the Editor.--Although the Azzopardi phenomenon is well known to surgical pathologists, it is surprising that the article by Pritt and Cooper (1) in the September 2003 issue of Archives of Pathology & Laboratory Medicine was the first publication to describe this phenomenon since John G. Azzopardi found this change in 32 (32%) of 100 cases of small cell carcinoma (SCC) of lung and correctly identified the basophilic material as DNA in 1959. (2)

Medulloblastoma is a malignant embryonal tumor of the cerebellum, accounting for 14% of all pediatric central nervous system tumors, (3) and it is one of the so-called malignant small blue cell tumors bearing histological similarity to SCC. This tumor also can occur in adults, mainly in the age group of 21 to 40 years. (4) Although it rarely occurs beyond the fifth decade of life, medulloblastoma in an elderly person may be histologically indistinguishable from metastatic SCC to the cerebellum, particularly in frozen sections. (5)

We investigated the Azzopardi phenomenon in medulloblastomas/ primitive neuroectodermal tumors (PNETs). The phenomenon is encountered occasionally in diagnostic neuro-oncology practice but has not been studied previously in central nervous system tumors.

A total of 102 cases of medulloblastoma (n = 77)/supratentorial PNETs (n = 25) that were diagnosed during a period of 8.5 years (January 1997 to June 2005) were retrieved from the anatomic pathology files of Texas Children's Hospital (Houston, Tex). All the hematoxylin-eosin-stained sections for each case were histologically reviewed by two pathologists (H.T. and M.B.B.) to identify the Azzopardi phenomenon, excluding mimickers, especially crush artifact of tumor cells around the blood vessels.

The mean patient age at surgery was 5.9 years (range, 9 weeks to 18 years). Of these, 4 cases (3.9%) were found to show the Azzopardi phenomenon (3 medulloblastomas and 1 ependymoblastoma). None of these patients had been previously treated. Microscopically, all 4 cases showed diffuse cellular sheets of undifferentiated malignant tumor cells with scant cytoplasm and frequent mitotic figures, as well as large areas of geographic necrosis. Within and around the necrotic areas there were occasional vessels highlighted by the deposition of deeply basophilic, granular debris (Figure 1; hematoxylin-eosin, original magnification x400). These vessels were mostly of either capillary or venule type. In one case of medulloblastoma there were a few vessels with this change in the uninvolved molecular layer of cerebellum adjacent to the tumor necrosis (Figure 2; hematoxylin-eosin, original magnification x400).

We agree with Azzopardi's conclusion that "this phenomenon of DNA in the vessel wall is presumably the result of liberation of nucleic acids in large amounts from degenerating neoplastic cells," (2) given that this change was found to be confined to vessels adjacent to the large areas of tumor necrosis in all of our cases. However, the vast majority of medulloblastoma/ PNET cases, even those with moderate to large areas of tumor necrosis, did not show this phenomenon. The striking difference in the prevalence of the Azzopardi phenomenon between these morphologically similar tumors (4% in medulloblastoma/ PNET vs 32% in SCC of lung) is unexpected, and it may be related in part to the different biology of these tumors.


Department of Pathology

The Methodist Hospital

Houston, TX 77030




Department of Pathology

Baylor College of Medicine

Texas Children's Hospital

Houston, TX 77030

(1.) Pritt BS, Cooper K. The Azzopardi phenomenon. Arch Pathol Lab Med. 2003;127:1231.

(2.) Azzopardi JG. Oat-cell carcinoma of the bronchus. J Pathol Bacteriol. 1959;78:513-519.

(3.) Central Brain Tumor Registry of the United States (CBTRUS). Available at: Accessed September 20, 2006.

(4.) Giangaspero F, Bigner SH, Kleihues P, Pietsch T, Trojanowski JQ. Medulloblastoma.In: Kleihues P, Cavenee WK, eds. Pathology and Genetics of Tumours of the Nervous System. Lyon, France: IARC Press; 2000:129-137. World Health Organization Classification of Tumours.

(5.) Ramsay DA, Bonnin J, MacDonald DR, Assis L. Medulloblastomas in late middle age and the elderly: report of 2 cases. Clin Neuropathol. 1995;14:337-342.

The authors have no relevant financial interest in the products or companies described in this article.
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Article Details
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Author:Takei, Hidehiro; Adesina, Adekunle M.; Bhattacharjee, Meenakshi B.
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Letter to the editor
Geographic Code:1USA
Date:Apr 1, 2007
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