Acinar Cell Tumors and Neoplasms

Acinar Cell Tumors and Related Neoplasms

• Acinar cell carcinoma can occur in both adults and children.
• Non-specific symptoms such as nausea, vomiting, and abdominal pain are typical.
• Jaundice is rare.
• About 15% of patients exhibit subcutaneous fat necrosis, eosinophilia, and arthralgia due to lipase secretion by the tumor.
• This clinical syndrome is more common with metastatic disease.
• Grossly appears as a well-defined fleshy mass, around 11 cm, potentially with hemorrhage, cystic degeneration, and necrosis.
• Growth patterns can be solid, trabecular, glandular, or papillary, and may mimic normal acinar structure.
• Intraductal growth may indicate a less aggressive form.
• Stroma is typically not prominent.
• Nuclei are round to oval with mild pleomorphism and single prominent nucleoli.
• Variable mitotic activity is observed
• Cytoplasm is abundant, eosinophilic, and granular.
• PAS-positive, diastase-resistant cytoplasmic zymogen granules may or may not be present.
• Immunoreactivity for trypsin, chymotrypsin, lipase, and amylase is typical, along with BCL10.
• BCL10 is homologous to carboxyl ester hydrolase, an enzyme produced by pancreatic acinar cells.
• Alpha-fetoprotein may be produced, leading to elevated serum levels.
• Mutations in the APC/ -catenin pathway are present in about 20% of tumors.
• Mutations in KRAS, SMAD4, and TP53 are rare, differing from pancreatic ductal adenocarcinoma.
• Overall prognosis is poor, with a 5-year survival rate of approximately 25%.
• Metastases occur in about half of cases at diagnosis, commonly to regional lymph nodes and the liver.
• Acinar cell cystadenoma is a rare, benign lesion consisting of unicystic or multicystic structures lined by well-differentiated acinar cells, usually not connected to the pancreatic ductal system.
• Acinar cell cystadenocarcinoma is the malignant counterpart, with larger, multilocular cystic tumors, greater atypia, and potential for invasion and metastasis, mimicking serous cystadenoma grossly

Mixed Acinar Neoplasms

• A minor endocrine component is found in one-third to one-half of acinar cell carcinomas.
• If over 25% of cells show neuroendocrine differentiation, it is designated as mixed acinar-neuroendocrine carcinoma (NEC).
• Mixed acinar-ductal carcinomas also occur, requiring at least 25% ductal component.
• Mixed acinar-neuroendocrine-ductal carcinoma rarely occurs.
• Acinar differentiation markers are present in about two-thirds of pancreatic tumors resembling pancreatic endocrine neoplasms, without prognostic significance.
• Acinar cell nodule, focal acinar transformation, acinar cell hyperplasia, or eosinophilic degeneration are variations that mimic neoplasm but have no known preneoplastic potential.

Pancreatoblastoma

• Most common pancreatic neoplasm in childhood, accounting for 25% of tumors in the first 10 years of life, but can occur in adults.
• Slight male predominance.
• Isolated cases reported with Beckwith-Wiedemann syndrome and familial adenomatous polyposis.
• Overall survival is approximately 50%.
• The mean tumor size is 10 cm, and partial encapsulation is typical.
• Very cellular tumors with a lobular appearance, composed of solid sheets and acini of uniform cells.
• Squamoid nests or corpuscles are a constant finding.
• Tumor cells within these corpuscles often have optically clear nuclei due to biotin accumulation.
• The stroma may be abundant and occasionally hypercellular, sometimes with heterologous cartilage or bone.
• Neuroendocrine, ductal, and/or primitive small round blue cell components may be present.
• Shows acinar (pancreatic enzymes), endocrine (synaptophysin and chromogranin), and ductal (CK7 and CK19) differentiation
• AFP may be produced, aligning with its primitive nature.
• Squamoid corpuscles are CK8/CK18/CK19/EMA positive and CK7 negative.
• Nuclear translocation of -catenin occurs due to mutations in the -catenin (CTNNB1) or APC gene.
• Majority of cases show loss of heterozygosity on chromosome 11p, similar to Wilms tumor and hepatoblastoma.
• Pancreatoblastoma is considered the infantile counterpart of acinar cell carcinoma.
• Not all pancreatic tumors in childhood are pancreatoblastoma; solid pseudopapillary tumors, endocrine tumors, lymphoma, and metastatic tumors also occur.

Solid-Pseudopapillary Tumor

• Also known as SPPT
• Preferred term for tumors previously called papillary and solid epithelial neoplasm, papillary-cystic neoplasm, or cystic-solid papillary carcinoma.
• Most (>90%) cases are found in young women, typically presenting with abdominal pain.
• A significant minority are found incidentally on imaging.
• Tumors are usually large and solitary.
• Multicentricity is rare.
• Appearance ranges from solid to almost entirely cystic with areas of hemorrhage and necrosis.
• Most cases have a well-developed capsule, but some are infiltrative into adjacent pancreas
• Invasion of adjacent organs is very rare.
• A few cases arise from the ovary, retroperitoneum, or GI tract, sometimes in the context of ectopic pancreas.
• Very cellular, resembling pancreatic endocrine neoplasm
• May have solid and cystic components, with pseudopapillae covered by epithelial cells.
• Cells around pseudopapillae are discohesive, with hyalinized fibrovascular cores.
• Cystic degeneration, cholesterol crystals, and foamy histiocytes are also present.
• Small vessels may be surrounded by a mucoid or myxoid material.
• Nuclei are ovoid and folded, with indistinct nucleoli and longitudinal grooves.
• Mitoses are few.
• Hyaline globules may be present within the cytoplasm.
• Clear cells can be prominent, with variants including pleomorphic and oncocytic types.
• Only focal, faint reactivity for keratin.
• Synaptophysin and CD56 can be focally or diffusely positive.
• Chromogranin is characteristically negative.
• Tumor cells may stain with claudin 5 (membranous), claudin 2 (cytoplasmic), galectin 3, progesterone receptor, estrogen receptor beta, CD10, CD99 (dot-like), and a-antitrypsin.
• Pancreatic enzymes are typically absent.
• E-cadherin shows membrane loss and aberrant nuclear localization of -catenin.
• Aberrant nuclear location of Beta-catenin is the most helpful diagnostic marker
• CD117 expression is found in about half of cases but is not associated with mutations of KIT, so its presence is not an indication for Gleevec therapy.
• DOG1 reactivity has also been reported.
• FLI-1 expression has been described as well, but SPPT do not contain the EWS/FLI-1 translocation.
• Histogenesis remains elusive.
• Progesterone receptors have been detected, leading to the hypothesis that SPPT could be derived from genital ridge/ovarian anlage-related stem cells attached to the pancreatic tissue during early embryogenesis.
• Pancreatic SPPTs are different from ordinary ductal adenocarcinomas and almost always exhibit -catenin (CTNNB1) gene mutations.
• Translocation der(17)t(13;17)(q14;p11) has been detected in a case.
• Abnormalities have also been reported within chromosomes 11q, 13q, 17q, 1q, and 8q.
• Treatment is surgical, and the overall prognosis is excellent.
• Approximately 10%-15% of cases result in local recurrence and/or metastases, usually in the liver or peritoneum.
• SPPT should be regarded as a neoplasm of low malignant potential.
• Larger tumor size, invasion into muscular vessels and/or adjacent structures, and histologic features such as diffuse growth pattern, extensive necrosis, and high mitotic rate have been correlated with aggressive behavior.
• Cases with an undifferentiated component and a very aggressive clinical course have been seen rarely.

Tumor Markers Summary

• Acinar cell carcinomas express trypsin, chymotrypsin, lipase, and amylase.
• Acinar cell carcinomas are BCL10 positive.
• Alpha-Fetoprotein (AFP) may be produced in some cases of acinar cell carcinomas (and in pancreatoblastoma).
• Mixed Acinar-Neuroendocrine Carcinoma is Chromogranin and/or Islet Cell Hormones positive in the neuroendocrine component.
• Pancreatoblastoma expresses pancreatic enzymes and synaptophysin and chromogranin and CK7 and CK19.
• Pancreatoblastoma may produce AFP.
• CK8, CK18, CK19, and EMA are positive in pancreatoblastoma squamoid corpuscles.
• CK7 is negative in pancreatoblastoma squamoid corpuscles.
• Solid-Pseudopapillary Tumors (SPPT) have only focal, faint Keratin reactivity.
• Solid-Pseudopapillary Tumors (SPPT) are Synaptophysin and CD56 focally or diffusely positive.
• Solid-Pseudopapillary Tumors (SPPT) are Chromogranin Characteristically negative.
• Solid-Pseudopapillary Tumors (SPPT) Claudin 5 has membranous staining.
• Solid-Pseudopapillary Tumors (SPPT) Claudin 2 has cytoplasmic staining and are Galectin 3, Progesterone Receptor, Estrogen Receptor Beta, CD10, CD99 and Alpha-1-Antitrypsin positive.
• Solid-Pseudopapillary Tumors (SPPT) lacks Pancreatic enzyme expression and E-cadherin and Beta-catenin shows aberrant nuclear localization.
• Solid-Pseudopapillary Tumors (SPPT) D0G1 and FLI-1 are positive.
• APC/β-catenin pathway shows mutations in about 20% of acinar cell carcinoma tumors, distinguishing them from pancreatic ductal adenocarcinoma.
• KRAS, SMAD4, and TP53 mutations are rare in acinar cell carcinomas, another distinction from pancreatic ductal adenocarcinoma.
• β-catenin (CTNNB1) or APC gene mutations in pancreatoblastoma lead to nuclear translocation of β-catenin. Loss of heterozygosity (LOH) on chromosome 11p is seen in most pancreatoblastoma cases, similar to Wilms tumor and hepatoblastoma.
• Β-catenin (CTNNB1) gene mutations are almost always present in SPPTs, resulting in membrane loss and aberrant nuclear localization of β-catenin.
• Translocation der(17)t(13;17)(q14;p11) has been detected in one case of SPPT.
• Chromosomes 11q, 13q, 17q, 1q, and 8q abnormalities have been reported in SPPT.
• Acinar cell carcinomas are characterized by pancreatic enzyme expression.
• Mixed acinar-neuroendocrine carcinomas express both acinar and neuroendocrine markers.
• Pancreatoblastoma displays acinar, endocrine, and ductal differentiation.
• SPPT has a unique immunohistochemical profile with hallmark beta-catenin nuclear localization and lacks pancreatic enzyme expression.
• The distinct mutation profiles help distinguish Acinar cell carcinoma vs. Pancreatic Ductal Adenocarcinoma
• Pancreatoblastoma are characterized by B-catenin mutations and 11p LOH SPPT almost always show B-catenin mutations