Dr. Ralph H. Hruban
Dr. Günter Klöppel
Case 3 -
Mixed acinar-endocrine carcinoma (MAEC) of the pancreas
Drs. Toshio Morohoshi and Nobuyuki Ohike
1st Department of Pathology, Showa University
This 51-year-old female patient had a one-year history of a
large tumor in the tail of her pancreas and liver metastases. There was a markedly elevated elastase l
level (40,000ng/dl), while CEA and CA19-9 levels were normal. The patient died of hemorrhage from the
pancreatic tumor. The present tumor tissue is autopsy material.
Case 3 - Figure 2
A solid mass 22x15x13cm mass was seen in the tail of the
pancreas. The cut surface revealed whitish lobulated nodules with central cystic necrosis. Direct
invasion into the stomach wall and liver metastases were present.
The tumor is partly necrotic. The nodules are separated by
fibrous cords, and the neoplastic cells show a solid growth pattern, partially with acinar arrangement.
The neoplastic cells have round to oval nuclei and amphiphilic to eosinophilic cytoplasm. The chromatin
of the nuclei is somewhat coarse and the nucleus contains a prominent nucleolus. There are 2-3
The neoplasm has an acinar and an endocrine component. However, as these two components are difficult
to distinguish by light microscopy. .
Electron microscopy revealed
that the neoplastic cells contained zymogen-like granules with an average size of 433nm,
concentrated near the apical cell membrane.
The neoplastic cells label diffusely with antibodies
to trypsin. Approximately one third of the neoplastic cells express chromogranin A. Individual cells
stain for glucagon. Tissue from a liver metastasis shows similar staining features.
Mixed acinar-endocrine carcinoma (MAEC) of the pancreas (a
variant of acinar cell carcinoma).
The differential diagnosis includes pure acinar cell carcinomas, pancreatoblastomas, and endocrine tumors. Acinar cell carcinomas (ACCs) often
have scattered endocrine cells, and it appears that the only difference between ACCs and MAECs is the
number of endocrine cells. Pancreatoblastomas are composed of mixed acinar,
ductal and occasionally endocrine components. Typically they have characteristic "squamoid corpuscles",
which are not seen in MAECs and ACCs. Of the endocrine tumors, well
differentiated endocrine neoplasms with scattered (entrapped?) acinar cells, endocrine tumors with
oncocytic changes, and poorly differentiated endocrine tumors may come into question. In particular, the
differential diagnosis versus the latter two is difficult, because they show a comparatively aggressive
course similar to MAEC (or ACC). An extensive search for endocrine and exocrine markers is necessary for
the correct diagnosis of these tumors. MAEC tumors may be misdiagnosed as endocrine tumors.
According to the WHO classification, mixed exocrine-endocrine
carcinomas of the pancreas are malignant epithelial neoplasms. Among these neoplasms mixed
ductal-endocrine carcinoma (MDEC) and mixed acinar-endocrine carcinoma (MAEC) can be distinguished. In
MDEC an MAEC the exocrine and endocrine elements are intimately admixed in the primary tumor and in its
metastases, and the endocrine cell elements comprise at least one third to half of the tumor tissue.
Biologically, the behavior of these neoplasms is similar to ductal adenocarcinoma or acinar cell
carcinoma. However, if the endocrine component consists of a small cell carcinoma or poorly
differentiated endocrine tumor, the biological behavior may be affected by the endocrine component. As
ACCs often have scattered endocrine cells, MAEC appears to be only a variant of ACC thus named when
endocrine cells exceed 30% of the tumor. ACCs and MAECs share most clinicopathological features and,
therefore may form a single tumor entity.
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- Morohoshi T, Sagawa F, Mitsuya T (1990) Pancreatoblastoma with marked elevation of serum alpha-fetoprotein. An autopsy case report with immunocytochemical study. Virchows Arch A Pathol Anat Histopathol. 416:265-270.
- Klimstra DS, Rosai J, Heffess CS (1994) Mixed acinar-endocrine carcinomas of the pancreas. Am J Surg Pathol 18:765-778
- Ohike N, Kosmahl M, Kloppel G (2004) Mixed acinar-endocrine carcinoma of the pancreas. A clinicopathological study and comparison with acinar-cell carcinoma. Virchows Arch 445:231-235