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WHO Classification of Tumours
Acinar cell carcinoma
Pancreas


Histopathology

Histopathology
Acinar cell carcinomas are highly cellular, with a high neoplastic-cell-to-stroma ratio. These neoplasms are composed of large circumscribed nodules of neoplastic cells separated by hypocellular fibrous bands

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Hoorens A, Lemoine NR, McLellan E, Morohoshi T, Kamisawa T, Heitz PU, Stamm B, Rüschoff J, Wiedenmann B, Klöppel G (1993)
Pancreatic acinar cell carcinoma. An analysis of cell lineage markers, p53 expression, and Ki-ras mutation.
Am J Pathol 143: 685-98




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Klimstra DS, Heffess CS, Oertel JE, Rosai J (1992)
Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases.
Am J Surg Pathol 16: 815-37



. The desmoplastic stroma characteristic of ductal adenocarcinomas is generally absent. Tumour necrosis may occur and is generally infarct-like in appearance. Numerous small vessels surround the nests of neoplastic cells.

Architectural patterns
Of the several architectural patterns described

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Klimstra DS, Heffess CS, Oertel JE, Rosai J (1992)
Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases.
Am J Surg Pathol 16: 815-37



, the most characteristic is the acinar pattern, with neoplastic cells arranged in small acinar units; there are numerous small lumina within each island of cells, producing a cribriform appearance. In some instances, the lumina are more dilated, resulting in the glandular pattern, although individual glandular units, each surrounded by stroma, are not commonly encountered. A number of the microglandular carcinomas previously reported as “microadenocarcinoma” were more recently shown to have been acinar cell carcinomas
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Lonardo F, Cubilla AL, Klimstra DS (1996)
Microadenocarcinoma of the pancreas--morphologic pattern or pathologic entity? A reevaluation of the original series.
Am J Surg Pathol 20: 1385-93



. The second most common pattern is the solid pattern: solid nests of neoplastic cells lacking luminal formations separated by small vessels. Within these nests, cellular polarization is generally not evident, but there may be an accentuation of polarization at the interface with the vessels, resulting in basal nuclear localization in these regions and a palisading of nuclei along the microvasculature. In rare instances, a trabecular arrangement of neoplastic cells may be present, with exceptional cases also showing a gyriform appearance
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Klimstra DS, Heffess CS, Oertel JE, Rosai J (1992)
Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases.
Am J Surg Pathol 16: 815-37



. Recently, intraductal and papillary variants of acinar cell carcinoma have been reported
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Basturk O, Zamboni G, Klimstra DS, Capelli P, Andea A, Kamel NS, Adsay NV (2007)
Intraductal and papillary variants of acinar cell carcinomas: a new addition to the challenging differential diagnosis of intraductal neoplasms.
Am J Surg Pathol 31: 363-70




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Fabre A, Sauvanet A, Flejou JF, Belghiti J, Palazzo L, Ruszniewski P, Ruzniewski P, Degott C, Terris B (2001)
Intraductal acinar cell carcinoma of the pancreas.
Virchows Arch 438: 312-5




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Toll AD, Mitchell D, Yeo CJ, Hruban RH, Witkiewicz AK (2009)
Acinar Cell Carcinoma With a Prominent Intraductal Growth Pattern: Case Report With Review of the Literature.
Int J Surg Pathol :



. These neoplasms are composed of polypoid growths of neoplastic cells histologically similar to conventional acinar cell carcinoma projecting into dilated ducts, some of which retain a layer of normal ductal epithelium surrounding the carcinomatous polyp. In rare cases, true papillae may be found, with fibrovascular cores lined by neoplastic cells with acinar differentiation. Most such cases have areas with conventional histological features elsewhere in the neoplasm.

High magnification
At high magnification, the neoplastic cells of acinar cell carcinoma contain minimal to moderate amounts of cytoplasm that may be more abundant in cells lining lumina. The cytoplasm varies from amphophilic to eosinophilic and is characteristically finely granular, reflecting the presence of zymogen granules (although only minimal cytoplasmic granularity may be detectable in many cases). The nuclei are generally round to oval and relatively uniform, with marked nuclear pleomorphism being exceptional 1
Klimstra DS, Adsay NV (2001). Acinar cell carcinoma of the pancreas. A case associated with the lipase hypersecretion syndrome. Pathol Case Rev 6: 121-126.


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Peng HQ, Darwin P, Papadimitriou JC, Drachenberg CB (2006)
Liver metastases of pancreatic acinar cell carcinoma with marked nuclear atypia and pleomorphism diagnosed by EUS FNA cytology: a case report with emphasis on FNA cytological findings.
Cytojournal 3: 29



. A single, prominent, central nucleolus is characteristic but not invariably present. The mitotic rate ranges from 0 to more than 50 per 10 high power fields (mean, 14 per 10 high power fields). Zymogen granules are weakly positive with PAS staining, and resistant to diastase. Mucin production is generally not detectable with mucicarmine or Alcian blue stains and, if present, is limited to the luminal membrane in acinar or glandular formations. Owing to the scarcity of zymogen granules in many examples of acinar cell carcinoma, histochemical stains are relatively insensitive for documenting acinar differentiation, and very focal staining may be difficult to interpret.

Cytopathology
Fine-needle aspirates are usually highly cellular

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Ishihara A, Sanda T, Takanari H, Yatani R, Liu PI (1989)
Elastase-1-secreting acinar cell carcinoma of the pancreas. A cytologic, electron microscopic and histochemical study.
Acta Cytol 33: 157-63




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Labate AM, Klimstra DL, Zakowski MF (1997)
Comparative cytologic features of pancreatic acinar cell carcinoma and islet cell tumor.
Diagn Cytopathol 16: 112-6




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Samuel LH, Frierson HF (1996)
Fine needle aspiration cytology of acinar cell carcinoma of the pancreas: a report of two cases.
Acta Cytol 40: 585-91




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Stelow EB, Bardales RH, Shami VM, Woon C, Presley A, Mallery S, Lai R, Stanley MW (2006)
Cytology of pancreatic acinar cell carcinoma.
Diagn Cytopathol 34: 367-72




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Villanueva RR, Nguyen-Ho P, Nguyen GK (1994)
Needle aspiration cytology of acinar-cell carcinoma of the pancreas: report of a case with diagnostic pitfalls and unusual ultrastructural findings.
Diagn Cytopathol 10: 362-4



. The neoplastic cells are arranged in irregular solid sheets, small glandular clusters, and individually. The cytological appearance of acinar cell carcinoma closely mimics that of pancreatic neuroendocrine neoplasm, although smears from the latter are more likely to contain uniform plasmacytoid cells and speckled chromatin. Coarsely clumped chromatin and prominent nucleoli are typical of acinar cell carcinoma. Immunohistochemistry may be used on cytological specimens to confirm acinar differentiation
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Labate AM, Klimstra DL, Zakowski MF (1997)
Comparative cytologic features of pancreatic acinar cell carcinoma and islet cell tumor.
Diagn Cytopathol 16: 112-6



.

Ultrastructure
Exocrine secretory features are consistently found, with abundant rough endoplasmic reticulum arranged in parallel arrays and relatively abundant mitochondria

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di Sant'Agnese PA (1991)
Acinar cell carcinoma of the pancreas.
Ultrastruct Pathol 15: 573-7




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Hassan MO, Gogate PA (1993)
Malignant mixed exocrine-endocrine tumor of the pancreas with unusual intracytoplasmic inclusions.
Ultrastruct Pathol 17: 483-93




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Klimstra DS, Heffess CS, Oertel JE, Rosai J (1992)
Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases.
Am J Surg Pathol 16: 815-37




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Tucker JA, Shelburne JD, Benning TL, Yacoub L, Federman M (1994)
Filamentous inclusions in acinar cell carcinoma of the pancreas.
Ultrastruct Pathol 18: 279-86



. Most acinar cell carcinomas contain electron-dense zymogen granules ranging in size from 125 to 1000 nm. A second granule type, the irregular fibrillary granule, is detected ultrastructurally in many cases
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Chong JM, Fukayama M, Shiozawa Y, Hayashi Y, Funata N, Takizawa T, Koike M (1996)
Fibrillary inclusions in neoplastic and fetal acinar cells of the pancreas.
Virchows Arch 428: 261-6




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Klimstra DS, Heffess CS, Oertel JE, Rosai J (1992)
Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases.
Am J Surg Pathol 16: 815-37




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Klimstra DS, Rosai J, Heffess CS (1994)
Mixed acinar-endocrine carcinomas of the pancreas.
Am J Surg Pathol 18: 765-78




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Pasquinelli G, Preda P, Martinelli GN, Galassi A, Santini D, Venza E (1995)
Filamentous inclusions in nonneoplastic and neoplastic pancreas: an ultrastructural and immunogold labeling study.
Ultrastruct Pathol 19: 495-500



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Histological variants
Acinar cell cystadenocarcinoma
Acinar cell cystadenocarcinomas are rare, grossly cystic neoplasms with acinar differentiation

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Cantrell BB, Cubilla AL, Erlandson RA, Fortner J, Fitzgerald PJ (1981)
Acinar cell cystadenocarcinoma of human pancreas.
Cancer 47: 410-6




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Colombo P, Arizzi C, Roncalli M (2004)
Acinar cell cystadenocarcinoma of the pancreas: report of rare case and review of the literature.
Hum Pathol 35: 1568-71




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Hoorens A, Lemoine NR, McLellan E, Morohoshi T, Kamisawa T, Heitz PU, Stamm B, Rüschoff J, Wiedenmann B, Klöppel G (1993)
Pancreatic acinar cell carcinoma. An analysis of cell lineage markers, p53 expression, and Ki-ras mutation.
Am J Pathol 143: 685-98




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JACKSON SH, VARLEY H (1952)
Carcinoma of the pancreas associated with fat-necrosis.
Lancet 2: 962-7




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Stamm B, Burger H, Hollinger A (1987)
Acinar cell cystadenocarcinoma of the pancreas.
Cancer 60: 2542-7



. Most cases are large tumours (mean, 24 cm) with variably sized cysts that are often < 1 cm in diameter. The cysts are lined by layers of neoplastic cells with acinar morphology that immunolabel for pancreatic exocrine enzymes. The clinical behaviour of these neoplasms is not different from that of conventional acinar cell carcinoma.

Mixed acinar carcinomas
Rare neoplasms have shown a substantial (> 30%) proportion of more than one cell type. These “mixed acinar carcinomas” have been designated, depending upon the cell types identified, as “mixed acinar-neuroendocrine carcinoma”, “mixed acinar-ductal carcinoma”, or “mixed acinarneuroendocrine- ductal carcinoma”

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Hruban RH, Pitman MB, and Klimstra DS
Tumors of the Pancreas. Armed Forces Institute of Pathology
Washington, DC 2007




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Labate AM, Klimstra DL, Zakowski MF (1997)
Comparative cytologic features of pancreatic acinar cell carcinoma and islet cell tumor.
Diagn Cytopathol 16: 112-6




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Nojima T, Kojima T, Kato H, Sato T, Koito K, Nagashima K (1992)
Alpha-fetoprotein-producing acinar cell carcinoma of the pancreas.
Hum Pathol 23: 828-30




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Ohike N, Kosmahl M, Klöppel G (2004)
Mixed acinar-endocrine carcinoma of the pancreas. A clinicopathological study and comparison with acinar-cell carcinoma.
Virchows Arch 445: 231-5




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Villanueva RR, Nguyen-Ho P, Nguyen GK (1994)
Needle aspiration cytology of acinar-cell carcinoma of the pancreas: report of a case with diagnostic pitfalls and unusual ultrastructural findings.
Diagn Cytopathol 10: 362-4



. These mixed acinar carcinomas are described in greater detail in Ductal adenocarcinoma variants and mixed neoplasms.

Differential diagnosis
Other pancreatic neoplasms with a solid, cellular appearance should be considered in the differential diagnosis with acinar cell carcinoma. These include pancreatic neuroendocrine tumours (NETs), pancreatoblastoma, and solidpseudopapillary neoplasm

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Klimstra DS (2007)
Nonductal neoplasms of the pancreas.
Mod Pathol 20 Suppl 1: S94-112




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Klimstra DS, Pitman MB, Hruban RH (2009)
An algorithmic approach to the diagnosis of pancreatic neoplasms.
Arch Pathol Lab Med 133: 454-64



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Pancreatic neuroendocrine tumours (NETs).
These neoplasms are commonly confused with acinar cell carcinomas because they share certain architectural patterns (nesting, trabecular) and cytological features (uniform nuclei eosinophilic to amphophilic cytoplasm) and because acinar cell carcinomas may have focal or (in the case of mixed acinarneuroendocrine carcinomas) widespread labelling for chromogranin and synaptophysin. Features that favour a diagnosis of acinar cell carcinoma include single prominent nucleoli, granular eosinophilic cytoplasm, basal nuclear polarization, abundant acinar formations, absolutely no fibrotic stroma within neoplastic nodules, an elevated mitotic rate, and limited labelling for neuroendocrine markers

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Hruban RH, Pitman MB, and Klimstra DS
Tumors of the Pancreas. Armed Forces Institute of Pathology
Washington, DC 2007



. If the diagnosis of acinar cell carcinoma is considered, immunohistochemical labelling for trypsin and chymotrypsin are usually sufficient to establish the diagnosis, although it should be noted that scattered trypsin-expressing cells can be found in pancreatic NETs
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Yantiss RK, Woda BA, Fanger GR, Kalos M, Whalen GF, Tada H, Andersen DK, Rock KL, Dresser K (2005)
KOC (K homology domain containing protein overexpressed in cancer): a novel molecular marker that distinguishes between benign and malignant lesions of the pancreas.
Am J Surg Pathol 29: 188-95



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Pancreatoblastomas.
Pancreatoblastomas share with acinar cell carcinomas the consistent presence of acinar differentiation, both at the histological and immunohistochemical levels

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Sipos B, Klöppel G (2005)
[Acinar cell carcinomas and pancreatoblastomas: related but not the same].
Pathologe 26: 37-40



. Pancreatoblastomas most commonly affect children < 10 years of age, although cases in adulthood have been reported
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Klimstra DS, Wenig BM, Adair CF, Heffess CS (1995)
Pancreatoblastoma. A clinicopathologic study and review of the literature.
Am J Surg Pathol 19: 1371-89



. The characteristic feature of pancreatoblastoma is the squamoid nests. Squamoid nests are circumscribed islands of larger, spindled cells that may show keratinization. There is also more pronounced lobulation in pancreatoblastomas, and the stromal bands separating the lobules are hypercellular.

Solid-pseudopapillary neoplasms.
These neoplasms typically affect young females and are composed of uniform, poorly cohesive polygonal cells arranged in solid sheets and degenerative pseudopapillae supplied by an abundant network of small delicate vessels

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Klimstra DS, Wenig BM, Heffess CS (2000)
Solid-pseudopapillary tumor of the pancreas: a typically cystic carcinoma of low malignant potential.
Semin Diagn Pathol 17: 66-80



. True glands or acini are not present. Solid-pseudopapillary neoplasms usually contain aggregates of large eosinophilic hyaline globules, foamy histiocytes and cholesterol clefts. The mitotic rate is usually very low. Immunohistochemically, solidpseudopapillary neoplasms do not express trypsin, chymotrypsin, lipase, or chromogranin, although synaptophysin and CD56 (NCAM1) may be positive. Solid-pseudopapillary neoplasms will also express vimentin, CD10, α-1-antitrypsin, and β-catenin (nuclear)
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Abraham SC, Klimstra DS, Wilentz RE, Yeo CJ, Conlon K, Brennan M, Cameron JL, Wu TT, Hruban RH (2002)
Solid-pseudopapillary tumors of the pancreas are genetically distinct from pancreatic ductal adenocarcinomas and almost always harbor beta-catenin mutations.
Am J Pathol 160: 1361-9




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Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



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Diagnostic algorithms for tumours of the pancreas


Acinar pattern
Acinar pattern
 Solid pattern
Solid pattern
Acinar cell cystadenocarcinoma
Acinar cell cystadenocarcinoma
Mixed acinar-ductal carcinoma
Mixed acinar-ductal carcinoma