Histopathology

In large neoplasms, extensive necrosis is typical and the preserved tissue is usually found in the tumour periphery under the fibrous capsule. This tissue exhibits a solid monomorphic pattern with variable sclerosis. More centrally there is a pseudopapillary pattern, and these components often gradually merge into each

Fig. 10.36 Solid pseudopapillary tumour. Solid area containing cholesterol crystals and foreign body giant cells.
Fig. 10.37 Solid pseudopapillary tumour. In this solid area, the uniform tumour cells are separated by vascular hyalinized stroma.

other. In both patterns, the uniform polyhedral cells are arranged around delicate, often hyalinized fibrovascular stalks with small vessels {1395}. Neoplastic cells that are arranged radially around the minute fibrovascular stalks may resemble 'ependymal' rosettes. Luminal spaces are consistently absent. In the solid parts, disseminated aggregates of neoplastic cells with foamy cytoplasm or cholesterol crystals surrounded by foreign body cells may be found. The spaces between the pseudopapillary structures are filled with red blood cells. The hyalinized connective tissue strands may contain foci of calcification and even ossification {1193}. The neoplastic cells have either eosino-philic or clear vacuolar cytoplasm. Occasionally they contain eosinophilic, diastase-resistant PAS-positive globules of varying size, which may also occur outside the cells. Glycogen or mucin cannot be detected. Grimelius positive cells may occur. The round to oval nuclei have finely dispersed chromatin and are often grooved or indented. Mitoses are usually rare, but in a few instances prominent mitotic activity is observed {1358}. In rare cases, there is also vessel invasion {2140}. The neoplastic tissue is usually well demarcated from the normal pancreas, although a fibrous capsule may be absent and invasion of tumour cell nests into the surrounding pancreatic tissue may occur {1193, 1358}.

Criteria of malignancy

Although criteria of malignancy have not yet been clearly established, it appears that unequivocal perineural invasion, angioinvasion, or deep invasion into the surrounding tissue indicate malignant behaviour, and such lesions should be classified as solid-pseudopapillary carcinoma. Nishihara et al. {1358} compared the histological features of three metasta-sizing and 19 nonmetastasizing solid-pseudopapillary neoplasms, and found that venous invasion, degree of nuclear atypia, mitotic count and prominence of necrobiotic cell nests (cells with pyknotic nuclei and eosinophilic cytoplasm) were associated with malignancy. However neoplasms in which the above-mentioned histological criteria of malignancy are not detected may also give rise to metastases. Consequently, benign appearing solid-pseudopapillary neoplasms must be classified as lesions of uncertain malignant potential.

Histochemistry and immunohistochemistry

The most consistently positive markers for solid-pseudopapillary neoplasms are alpha-1-antitrypsin, alpha-1-antichymo-trypsin, neuron specific enolase (NSE), vimentin and progesterone receptors {306, 945, 963, 1226}. The cellular reaction for alpha-1-antitrypsin and alpha-1-antichymotrypsin is always intense, but only involves small cell clusters or single cells, a finding that is characteristic of this neoplasm. Alpha-1-antitrypsin also stains the PAS-positive globules. Staining for NSE and vimentin, in contrast, is usually diffuse.

Inconsistent results have been reported for epithelial markers, synaptophysin, pancreatic enzymes, islet cell hormones and other antigens such as CEA or CA 19.9. Most authors report negative results for chromogranin A, CEA, CA 19.9 and AFP. A few neoplasms have been found to express S-100 {945, 1226, 1358}. Cytokeratin is detected in 30% {946} to 70% {963, 2195}, depending on the method of antigen retrieval applied.

Usually, the staining for keratin is focal and faint. The keratin profile (CK 7, 8, 18 and 19) is that of the ductal cell {740, 1844}. Positive immunoreactivity for trypsin, chymotrypsin, amylase and/or phospholipase A2 has been reported {166, 1072, 1192, 1226, 1844}, but has not been confirmed by most other authors {812, 945, 1282}. Similarly, focal positivity for glucagon, somatostatin and/or insulin has been described in some tumours {1226, 2021, 2147}, but was not detected in most other cases {1072, 1282, 1844}.

Ultrastructure

The neoplastic cells have round or markedly indented nuclei containing a small single nucleolus and a narrow rim of marginated heterochromatin. The cells show abundant cytoplasm, which is rich in mitochondria. Zymogen-like granules of variable sizes (500-3000 nm) are conspicuous, probably representing deposits of alpha-1-antitrypsin. The contents of these granules commonly dis integrate, forming multilamellated vesicles and lipid droplets {946, 1031, 1226, 2154}. Neurosecretory-like granules have been described in a few tumours {867, 880, 1684, 2119, 2147}. Intermediate cell junctions are rarely observed and micro-villi are lacking, but small intercellular spaces are frequent.

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