Solid Tumors and Tumor-like Lesions of the Pancreas
Moderators: Ralph H. Hruban and Günter Klöppel
Section 3 -
Less Common Solid Tumors of the Pancreas
Toshio Morohoshi and Nobuyuki Ohike
Although the majority of solid tumors of the pancreas are ductal adenocarcinomas, various types of
less common solid pancreatic tumors are often found in surgical pathology practice and in the rapidly
developing field of imaging techniques. It may be practical to summarize the common and less common
solid mass-forming pancreatic lesions in a list as below. Here we would like to present the
histopathological features of some of the less common tumors, including acinar cell carcinoma,
pancreatoblastoma, solid-pseudopapillary neoplasm, non-epithelial tumors, secondary tumors, and solid
variants of cystic tumors.
Solid Neoplasms and Lesions of the Pancreas
- Ductal adenocarcinoma and its variants
- Other less common neoplasms
- Acinar cell carcinoma and its variants
- Solid-pseudopapillary neoplasm
- Endocrine neoplasms
- Non-epithelial tumors
- Secondary tumors
Solid Variants of Primarily Cystic Neoplasms
- Solid variant of serous cystic neoplasm
- Intraductal papillary-tubular tumor (a variant of
intraductal papillary-mucinous neoplasm)
Acinar Cell Carcinoma and its Variants
- Acinar cell carcinoma (ACC)
This neoplasm may show several histological patterns, such as an acinar, solid, glandular, or
trabecular pattern, but most common are acinar and/or solid structures. The former consist of
well-developed acini having small lumina with basally oriented nuclei, and the latter are characterized
by sheets or cords of cells separated by delicate fibrovascular stroma. This neoplasm usually shows
expansive growth and forms nodes that are well demarcated from the surrounding pancreatic tissues, often
with pseudocystic changes at the center. The diagnosis is based on immunohistochemical staining for
pancreatic acinar cell markers such as trypsin (most reliable) and ultrastructural examination, which
reveals zymogen granules.
- Mixed acinar-endocrine carcinoma (MAEC)
MAEC is a variant of ACC that is so named when endocrine cells comprise at least 30% of the tumor.
Endocrine differentiation is determined by immunohistochemical labeling using antisera to synaptophysin,
chromogranin A, and pancreatic hormones., In MAECs the endocrine cells are either scattered among the
exocrine cells or form islet-like clusters of neoplastic cells with relatively sparse granular
Pancreatoblastomas are composed predominantly of various epithelial components, which mainly consist
of cells in acinar arrangement next to solid or sheet-like cell populations and squamoid corpuscles.
Ductular structures may also be seen, but well-formed ductules with tall columnar lining cells containing
mucin are uncommon. Endocrine components are also often found. The stroma may be hypercellular and
include neoplastic bone and cartilage.
The non-cohesive neoplastic cells are cuboidal to polygonal and have eosinophilic, somewhat granular
cytoplasm, similar to endocrine cells. In well-preserved areas, solid growth and pseudopapillary or
pseudorosette patterns with delicate microvasculature are seen. In the degenerated and cystic areas,
which are probably exposed to various ischemic and regressive changes, cytoplasmic vacuolization of tumor
cells, aggregates of foamy cells, hemorrhage, calcification, and cholesterol clefts are usually
recognized. At the periphery, tumor tissue intermingled with adjacent normal pancreatic tissue is seen.
The pseudopapillary pattern with hyalinized or myxoid fibrovascular stroma, one of the hallmarks of this
tumor, results from dyscohesion of tumor cells. Electron microscopically, zymogen- and endocrine-like
granules and apoptotic bodies are often detected in tumor cells. These neoplasms label with antibodies
to CD10 and show an abnormal nuclear pattern of labeling for beta-catenin.
A review of reported cases reveals various rare primary non-epithelial tumors of the pancreas. It may
be difficult to distinguish some sarcomas histologically from undifferentiated (anaplastic) carcinoma of
- Mesenchymal tumors
Benign or low-risk: neurofibroma, schwannoma, neuroma, leiomyoma, solitary
fibrous tumor (SFT), GIST, granular cell tumor, benign fibrous histiocytoma, hemangioma,
hemangioblastoma, lymphangioma, paraganglioma, angiomyolipoma and sugar tumor.
High-risk: leimyosarcoma, GIST, MFH, fibrosarcoma, sclerosing epithelioid
fibrosarcoma, liposarcoma, SFT, MPNST, PNET, malignant hemangiopericytoma, angiosarcopma,
- Malignant lymphoma
Primary pancreatic lymphomas are usually of B phenotype, including low-grade MALT lymphoma, follicular
lymphoma, and large B-cell lymphoma.
Secondary involvement of the pancreas by a malignant tumor is due to metastasis from a distant site
such as lung, breast, or prostate, to systemic spread of lymphoma/leukemia, or to invasion from an
adjacent organ, such as the stomach, liver, or retroperitoneum. It is difficult to distinguish
pancreatic adenocarcinoma from metastatic adenocarcinoma showing a solitary mass and involvement of the
pancreatic duct epithelium. Renal cell carcinoma is notorious for delayed metastasis and its difficult
differential diagnosis from several tumors with clear cell appearance (see next paragraph).
Solid Variants of Cystic Tumors
Solid Variant of Serous Cystadenoma
Serous cystadenomas usually have a microcystic spongy or an oligolocular gross appearance, but on
occasion the cystic spaces are absent in some areas or in the entire neoplasm. Histologically, the
neoplastic cells are similar to those of conventional serous cystadenoma and are polygonal to cuboidal
with clear to pale cytoplasm. However, they lack a cystic arrangement with nests resembling small ducts
or acinar structures, sheets, and a trabecular pattern separated by fibrovascular stroma.
Immunohistochemically, the tumor cells are positive for cytokeratins 7, 8, 18 and 19 and CA19-9. The
differential diagnosis includes clear-cell "sugar" tumor, clear cell adenocarcinoma, clear cell endocrine
tumor, hemangioblastoma, and metastatic renal cell carcinoma.
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