Clinical History
A 63-year-old man with a history of mixed hyperlipidemia and gallstones underwent cholecystectomy for recurrent episodes of pancreatitis. A follow-up computed tomography (CT) scan revealed an interval increase in the size of an ill-defined, mass-like lesion in the pancreatic head with peripheral enhancement and central necrosis, concerning for malignancy (Figure 1). Endoscopic ultrasound with fine needle aspiration documented a solid/cystic mass and acinar cells on cytology. He underwent pancreaticoduodenectomy.
Macroscopic Description
Grossly, the resection specimen was remarkable for a 10 cm, well-circumscribed, tumor in the head of the pancreas, which had yellow and pink cut surfaces and areas of hemorrhage (Figure 2).
Histologic/Cytologic Features
Microscopic pictures of the tumor are shown in Figures 3-6. Sections revealed a highly cellular tumor with a delicate vascular network, scant intervening stroma, and foci of tumor necrosis. Neoplastic cells exhibited a prominent acinar pattern of growth with basally located nuclei. Some acini showed minute lumina. Individual tumor cells had moderate amounts of granular eosinophilic cytoplasm and uniform nuclei. Some neoplastic cells exhibited prominent nucleoli. There were scattered mitotic figures but no cellular pleomorphism. Tumor cells were immunoreactive for pancytokeratin AE1/AE3. Rare cells showed weak reactivity for synaptophysin. They were negative for chromogranin and nuclear β-catenin.
[line]
Please select your diagnosis in the poll, then see the answer and the discussion in the links below.
[line]
Loading ...
[line]
Click Here To See The Answer Answer: Acinar cell carcinoma
[line]
Click Here To See The Discussion Final diagnosis: Acinar cell carcinoma Educational Objectives and Discussion: Educational Objectives Discussion Acinar cell carcinoma (ACC) accounts for about 1-2 % of adult pancreatic neoplasms. The average age of adult patients is approximately 60 years. Some patients develop lipase hypersecretion and associated paraneoplastic syndrome. These tumors are generally well-circumscribed, at least partially encapsulated, solid, and large (average diameter 8-10 cm) with a homogenous pink to tan cut surface. They can arise in any part of the pancreas and are more common in the head region. Microscopically, these tumors are typically denselycellular with minimal stroma. They may have different architectural patterns, solid and acinar patterns being the most prevalent. Less common patterns include a glandular and trabecular pattern. Individual tumor cells have striking eosinophilic cytoplasm, uniform nuclei, and a characteristic large central nucleolus. The mitotic rate is variable, ranging from 5 to 20 (mean 14) per 10 high power fields. Vascular invasion within the capsule of the neoplasm is common. The eosinophilic cytoplasm reflects the presence of cytoplasmic zymogen granules. However, in some cases, the cytoplasmic granularity is not well developed, and special stains are required to document their presence. A cystic variant of ACC has been described as typically large, circumscribed tumors with cysts lined by single or multiple layers of neoplastic acinar cells. In these cystic lesions, there are areas of solid nests of acinar cells, areas of necrosis, and mitotic figures, which support a malignant process. The finding of granular Periodic Acid-Schiff (PAS)/diastase positivity in the apical cytoplasm may be enough to confirm a diagnosis of acinar cell carcinoma (Figure 7). The butyrate esterase stain detects the presence of enzymatically active lipase in the neoplastic cells and is highly specific for acinar differentiation. Trypsin (Figure 8), chymotrypsin, and BCL10 (clone 331.1) (Figure 9) antibodies are the most sensitive, and simultaneous use of any two of them allows the detection of nearly 100% of acinar cell carcinomas. Of these, BCL10 is the most sensitive and specific. They have a favorable prognosis compared to the more common pancreatic ductal adenocarcinoma. (1-4) Molecular studies have shown frequent mutations in ID3, ARID1A, APC, and CDKN2A tumor suppressor genes in ACC (5-7). TP53 mutation or deletion has been identified in 12-24% of ACC (5,6). About 23% of ACC harbor gene fusion involving BRAF and RAF1 with the most common fusions being SND1-BRAF and HERPUD1-BRAF (5). These tumors are more sensitive to MEK inhibitors. In addition, microsatellite instability has been found in 8-14% of ACC (8,9). Differential diagnosis: Well-differentiated pancreatic neuroendocrine tumor, previously called islet cell tumors/islet cell carcinomas, are the pancreatic counterparts of APUDomas (Amine Precursor Uptake and Decarboxylation tumors) or carcinoids. They can be functional or non-functional (more common), are composed of monotonous cells with typical coarse nuclear chromatin, and express general markers of neuroendocrine differentiation (diffuse/intense synaptophysin and usually also chromogranin staining). They are the most important differential diagnosis of acinar cell carcinoma. Similarities between the two include a solid, acinar, or glandular architecture, relatively minimal stroma, and nuclear uniformity. Features favoring the diagnosis of well-differentiated pancreatic neuroendocrine tumor include hyalinized or amyloid-like stroma between nests of neoplastic cells (indicative of insulinoma), trabecular or gyriform growth patterns (particularly when arranged in single cell-thick cords), central nuclear localization, a coarsely clumped “salt and pepper” chromatin pattern, paler cytoplasm with less granularity and diffuse rather than focal positivity for synaptophysin and chromogranin. (1,10) Mixed acinar-neuroendocrine carcinomas are malignant epithelial neoplasms with both acinar and neuroendocrine differentiation. They are defined as having > 30% of each line of differentiation by immunohistochemistry. They are best regarded as a subtype of acinar cell carcinoma because they share its clinical behavior and genomic features. (1,10) Mixed acinar-ductal carcinomas are malignant epithelial neoplasms with both acinar and ductal differentiation. They are defined as having > 30% of each line by immunohistochemistry. These tumors may present with extensive extracellular colloid-like pools of mucin or nests of columnar or signet ring cells with cytoplasmic mucin or individual gland pattern of infiltration with an associated desmoplastic stromal response. Ductal differentiation is based on immunohistochemical reactivity for glycoproteins such as CEA (using monoclonal antibodies), CA19-9, or B72.3. Treatment is like that of ACC. (1,11) Pancreatoblastomas are malignant epithelial neoplasms of the pancreas, principally affecting children in the first decade of life. However, it can rarely occur in adults. These are very cellular tumors and typically have more prominent lobules separated by cellular stromal bands. They are predominantly composed of solid sheets and acini of uniform cells with characteristic squamoid nests or corpuscles. Lesser amounts of a neuroendocrine component, ductal component, and/or primitive round blue cell component may be seen. Though acinar differentiation is the most common and predominant pattern in most cases, careful microscopic examination and additional sampling may help reveal ductal and/or neuroendocrine components as well as squamoid nests and cellular stromal bands. The age of the patient helps suggest the right diagnosis as pancreatoblastoma. (1) Solid pseudopapillary neoplasm (SPN) are low grade malignant pancreatic tumors composed of poorly cohesive epithelial cells forming solid and pseudopapillary structures that lack a specific line of pancreatic epithelial differentiation. SPN displaying a predominantly solid growth pattern without foamy cells or eosinophilic globules could be confused with ACC. However, SPN never exhibits true lumen formation, so the presence of an acinar or glandular pattern would References: [line] Case contributed by: Pragya Jain, MD Saryn Doucette, MD Department of Pathology and Laboratory Medicine Conflict of Interest: NO
exclude this entity. In contrast to ACC, SPN does not label with specific acinar markers (trypsin and chymotrypsin) and consistently shows diffuse nuclear β-catenin staining. (1,12)
Medical College of Wisconsin