Clinical History
A 58-year-old woman with no significant past medical history developed left abdominal pain. An abdominal MRI showed an irregular enhancing 4.5 x 4.0 cm pancreatic tail mass that was inseparable from vessels in the splenic hilum. Endoscopic ultrasound-guided fine-needle aspiration showed rare malignant cells, favoring adenocarcinoma. The patient subsequently underwent neoadjuvant therapy with Gemcitabine/Abraxane followed by a distal pancreatectomy, splenectomy, partial omentectomy and removal of surrounding lymph nodes.
Histologic/Cytologic Features
Figures 1-4 are representative photomicrographs of the tumor. The histologic examination revealed a small component of invasive ductal adenocarcinoma involving pancreatic parenchyma. Malignant glands were admixed with prominent nests of cells with cribriform/microcystic architecture containing intermingled epidermoid cells, mucin secreting cells, and intermediate/clear cells (the latter features resemble mucoepidermoid carcinoma of the salivary gland). The proportion of different cell types and microcystic architecture varied in different areas. Focal high grade pancreatic intraepithelial neoplasia (formerly PanIN-3) and pancreatic atrophy were also noted.
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Please Select Your Diagnosis in the Poll, Then See the Answer and the Discussion in the Links Below
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Click Here To See The Answer Answer: Pancreatic adenosquamous carcinoma with mucoepidermoid carcinoma-like features
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Click Here To See The Discussion Final diagnosis: Pancreatic adenosquamous carcinoma with mucoepidermoid carcinoma-like features Educational Objectives and Discussion: Educational Objectives 1. Review the clinicopathologic features of pancreatic adenosquamous carcinoma with mucoepidermoid carcinoma-like features Discussion The current tumor demonstrated that tumor cells were positive for pan-cytokeratin. p40, p63, and CK5 highlighted epidermoid tumor cells. CDX2 and CK20 highlighted luminal cells and mucin-producing cells. Synaptophysin, chromogranin, and CD56 stains were negative. Intracytoplasmic and luminal mucinous secretions were highlighted by mucicarmine stain (Figures 5-7). Molecular study showed mutations in KRAS, CDKN2A, SF3B1, and TP53 genes. Pancreatic mucoepidermoid carcinoma (PAN-MEC, more appropriately termed as pancreatic adenosquamous carcinoma with mucoepidermoid carcinoma-like features) has been proposed as one of the histologic subtypes of pancreatic adenosquamous carcinoma because of their Similar to salivary gland MECs, three intermingled cell types, including mucin-producing cells, epidermoid cells, and intermediate cells, are usually present in varying proportions in PAN-MEC. Mucin-producing cells (mucocytes) produce mucin (and are positive for mucin stains such as mucicarmine). These cells may have a vacuolated, columnar, or goblet cell-like appearance (Figure 8). Mucocytes often form the lining of microcysts or duct-like structures. Epidermoid cells are polygonal and squamoid in appearance with dense eosinophilic cytoplasm, which can be highlighted by immunohistochemical stains such as p40, p63, or CK5/6. Epidermoid cells commonly have nested, or sheet-like growth pattern and are often located at the periphery of the nests or cribriform/microcystic structures. While intercellular bridges may be found, keratin pearl formation, overt keratinization, or dyskeratosis is not typically seen. Intermediate cells are less differentiated, and are morphologically not mucous or fully epidermoid cells. Their appearance may vary from small clear cells to small basaloid cells with scant basophilic cytoplasm or intermediate oval cells with pale eosinophilic cytoplasm. The intermediate cells are often admixed with epidermoid cells or mucocytes (Figure 9). Despite morphologic similarity, PAN-MEC appears not to be a counterpart of MEC of the salivary gland. In the salivary gland, a high proportion of MECs have been reported to harbor an oncogenic CRTC1/3–MAML2 gene fusion; whereas in the pancreas, these gene fusions were not detected by PCR in a study involving 16 PAN-MEC cases (all cases were classified as high-grade based on the salivary gland MEC grading system) (1). In addition, PAN-MEC has been reported to harbor KRAS and TP53 mutation, which is similar to the most common molecular signature found in pancreatic ductal adenocarcinomas (4) Differential diagnosis: Due to morphologic similarity, metastatic mucoepidermoid carcinoma or clear cell carcinoma of the salivary gland should be one of the first differentials to consider. However, the lack of clinical history of a salivary gland tumor, the presence of a pancreatic precursor lesion (high grade pancreatic intraepithelial neoplasia), and a component of conventional invasive ductal adenocarcinoma would support this tumor being a primary pancreatic carcinoma with MEC features as opposed to a metastasis from salivary gland. Goblet cells and microcystic structures are generally not seen in clear cell carcinoma of the salivary gland, although squamous differentiation and mucinproduction are not uncommon (7). Conventional pancreatic adenosquamous carcinoma is also in the differential diagnosis. By definition, this tumor has at least a 30% squamous cell carcinoma component with coexisting ductal adenocarcinoma. Apparent keratinization and squamous pearl formation, as well as focal nuclear anaplasia, are often noted. Low-grade mucoepidermoid carcinoma-like features are generally absent. Neoadjuvant therapy has been reported to induce squamous metaplasia of ductal columnar cells. However, there was no squamous metaplasia identified in the background pancreatic tissue of the present case. Although focal squamous transdifferentiation from the small ductal adenocarcinoma component induced by neoadjuvant therapy (8) cannot be completely excluded, the diffuse squamoid cells intermingled with other cell types and predominant cribriform/microcystic architecture are difficult to be explained by focal squamous transdifferentiation changes. Pancreatoblastoma is an uncommon malignant epithelial neoplasm characterized by multilineage differentiation including at least prominent acinar differentiation and focal squamoid morules that exhibit nuclear beta-catenin immunopositivity. Tumors are commonly seen in children but can occur in adults. Ductal/glandular or neuroendocrine differentiation can also be seen but are generally focal (9-10). References: [line] Case contributed by: Wei Zheng, Assistant Professor Alyssa M. Krasinskas, Professor Department of Pathology and Laboratory Medicine Emory School of Medicine Conflict of Interest: NO
2. Understand the molecular alterations of pancreatic adenosquamous carcinoma with mucoepidermoid carcinoma-like features
3. Discuss pertinent differential diagnosis for pancreatic adenosquamous carcinoma with mucoepidermoid carcinoma-like features
clinicopathologic and molecular similarities (1). To date, approximately 20 PAN-MEC cases have been documented (1-6). This tumor is more frequently located at the pancreatic body/tail and is significantly larger in size and more aggressive than those of the conventional pancreatic ductal adenocarcinomas (1). 
