Fig. 8.1
Well-differentiated adenocarcinoma. Cohesive, medium-sized cells with a relatively low nuclear to cytoplasmic ratio, mild anisonucleosis, mucinous cytoplasm, and parachromatin clearing are arranged in an uneven, “drunken honeycomb” pattern. (Smear, Papanicolaou stain)
Fig. 8.2
Well-differentiated adenocarcinoma, cellblock. Processing needle rinsings and separate aspirates for a cellblock may provide supportive or confirmatory tissue fragments allowing for a definitive diagnosis thus precluding the need for repeat biopsy. (Cellblock, Hematoxylin and eosin)
Fig. 8.3
Well-differentiated adenocarcinoma, SMAD4 immunohistochemistry. Loss of nuclear staining with SMAD4 immunohistochemistry staining supports the diagnosis of adenocarcinoma. (Cellblock, peroxidase-anti-peroxidase)
Moderately differentiated ([3, 5], Fig. 8.4)
Above features with addition of one or more of the following:
Larger cellular sheets/fragments with increased amount of single cells
More extensive cellular pleomorphism
Marked anisonucleosis and occasional prominent nucleoli
More crowded three-dimensional or syncytial tissue fragments
Fig. 8.4
Moderately differentiated adenocarcinoma. Increased anisonucleosis and crowding compared to well-differentiated adenocarcinoma are noted as is a loss of mucinous cytoplasm and increased prominence of nucleoli. (Smear, Papanicolaou)
Poorly differentiated (Fig. 8.5)
Extreme pleomorphism, with almost total lack of glandular differentiation
Larger loosely cohesive syncytial tissue fragments
Significant populations of single large malignant cells
High nucleus:cytoplasm (N/C) ratio, nuclei with coarse dark chromatin and often macro nucleoli
Occasional bizarre nuclei with triangular shapes and/or multinucleated cells
Mitoses and karyorrhexis
Prominent necrosis
Fig. 8.5
Poorly differentiated adenocarcinoma. Marked anisonucleosis, high nuclear to cytoplasmic ratio, single malignant cells, mitotic activity, and necrosis are associated with poorly differentiated adenocarcinoma. (Smear, Papanicolaou)
Variants of Adenocarcinoma
Colloid (mucinous noncystic) carcinoma (Fig. 8.6)
This uncommon variant accounts for 1–3 % of PDAC, and the majority arises in association with an intraductal papillary mucinous neoplasm, intestinal type. Gender and age distribution are similar to PDAC; however, the prognosis appears to be significantly better [6]. The extracellular mucin component should account for at least 80 % of the tumor on histology with sections demonstrating large pools of extracellular mucin and cuboidal epithelial cells “floating” in the mucin . This quantitation is not possible on cytology, but an aspirate of a solid appearing mass, particularly one in the wall of a cyst, composed predominantly of thick mucin should raise suspicion for this variant of PDAC.
Fig. 8.6
Mucinous (noncystic) adenocarcinoma (colloid carcinoma). Clusters of atypical to malignant mucinous epithelial cells associated with pools of mucin aspirated from a solid mass supports this diagnosis. (Cellblock, Hematoxylin and eosin)
Undifferentiated Carcinoma with Osteoclast-like Giant Cells ([7], Fig. 8.7)
Often seen in association with intraductal papillary mucinous neoplasm (IPMN) or mucinous cystic neoplasm (MCN), these tumors may also arise in association with pancreatic intraepithelial neoplasm (PanIN) and PDAC. This tumor is characterized by a prominent reactive osteoclast-like giant cell component in a background of mononuclear epithelioid and/or spindle cells.
Fig. 8.7
Undifferentiated carcinoma with osteoclast-type giant cells. Benign multinucleated giant cells are present in association with malignant mononuclear spindled to epithelioid tumor cells. (Smear, Papanicolaou)
Undifferentiated Carcinoma
Also known as anaplastic carcinoma, this rare variant is composed of large, undifferentiated, markedly pleomorphic malignant cells.
Adenosquamous Carcinoma ([8], Fig. 8.8)
This rare subtype has a relative frequency of 3–4 % and poorer prognosis than conventional PDAC, so it is prognostically important to make the diagnosis or at least mention the probability of the diagnosis. This variant shows malignant glandular and squamous components in variable percentages [8]. Although arbitrary, the squamous component should compose ~ 30 % of the tumor [6]. This quantification, however, is not possible on fine-needle aspiration (FNA) samples. When an FNA of a pancreatic mass contains a prominent keratinizing or nonkeratinizing squamous cell carcinoma component, it is highly suggestive of an adenosquamous carcinoma. Primary squamous cell carcinoma is essentially nonexistent in the pancreas, and metastatic squamous cell carcinoma to the pancreas is exceedingly rare.
Fig. 8.8
Adenosquamous carcinoma. The presence of a prominent squamous cell carcinoma component raises the probability of an adenosquamous carcinoma since primary squamous cell carcinoma is rare to nonexistent and metastatic squamous cell carcinoma is exceedingly rare. (Smear, Papanicolaou)
Other Variants
Other very rare variants of PDAC include medullary carcinoma and hepatoid carcinoma.
Acinar Cell Carcinoma
This rare primary malignancy arises from the exocrine, acinar tissue of the pancreas. Lipase hypersecretory syndrome leading to panniculitis is present in 16 % of patients and is a clinical clue to the diagnosis. Approximately 50 % of the patients have metastatic disease at presentation, often restricted to the regional lymph nodes and liver. The tumor is aggressive, but the prognosis appears to be significantly better than that of conventional PDACs [9].
Cytologic Criteria ([10, 11], Fig. 8.9, 8.10 and 8.11)
Usually hypercellular, mostly small to mid-sized cellular fragments and a few single cells
Prominent acinar formations without lobular arrangements (in well-differentiated tumors that can be confused with “rosettes” of a PanNET), rare syncytia
Uniform population of cells larger than ductal carcinoma, minimal pleomorphism
Finely granular to denser cytoplasm, granularity is often basophilic
Mildly increased N/C ratios, single round to oval nucleus which is eccentrically placed, coarse chromatin, single prominent nucleolus, focal anisonucleosis
Significant anisonucleosis in high-grade tumors
Numerous bare “stripped off” nuclei, rare intranuclear inclusions
Rare necrosis
Fig. 8.9
Acinar cell carcinoma. Monomorphic polygonal cells with granular cytoplasm distinguish this tumor from ductal carcinoma. (Smear, Papanicolaou)
Fig. 8.10
Acinar cell carcinoma. Acinar structures, while not specific for acinar cell carcinoma, certainly raise it as the most likely diagnosis. (Cellblock, Hematoxylin and eosin)
Fig. 8.11
Acinar cell carcinoma. Diffuse strong positive immunohistochemical staining for trypsin supports the diagnosis and distinguishes this aggressive carcinoma from a neuroendocrine tumor, which can also form acinar structures. (Cellblock, peroxidase-anti-peroxidase)
Poorly Differentiated Neuroendocrine Carcinoma (Small Cell or Large Cell Neuroendocrine Carcinoma) (Fig. 8.12)
Using the word “carcinoma” with “neuroendocrine” implies an aggressive, high-grade neoplasm. Both small cell and large cell pancreatic neuroendocrine carcinomas exhibit cytoarchitectural and clinicopathological features indistinguishable from pulmonary (and extrapulmonary) counterparts. Primary small cell carcinoma is extremely rare in the pancreas, and the possibility of metastatic lung carcinoma should always be excluded first. Small cell carcinoma has an extremely poor prognosis and usually displays extensive peripancreatic invasion. Chemotherapy remains the only mode of therapy [12].
Fig. 8.12
Poorly differentiated neuroendocrine carcinoma, small cell type. Morphologically, the tumor resembles small cell carcinoma of the lung with small cells having a high nuclear to cytoplasmic ratio, nuclear molding, scant cytoplasm, and apoptotic necrosis. (Direct smear, Papanicolaou)
Pancreatoblastoma
This rare malignancy can present in adults, but it is primarily a neoplasm of childhood. The tumor is a trilineage neoplasm characterized by acinar, ductal, and endocrine differentiation. Acinar differentiation usually predominates. Tumors contain distinctive squamoid nests, which is the diagnostic feature. Pancreatoblastoma tends to be less aggressive in infants and children compared to adults. This malignancy has been associated with alterations in the Wnt signaling pathway and chromosome 11p loss of heterozygosity (LOH), Beckwith–Wiedemann syndrome, and familial adenomatous polyposis. Alpha-fetoprotein is elevated in up to 68 % of patients [13].
Lymphoma (Fig. 8.13)
Lymphoma can involve the pancreas as either part of advanced-stage, widespread disease arising at another body site or more rarely primarily within the pancreas. Essentially all reported examples of primary lymphoma of the pancreas have been non-Hodgkin’s lymphomas. The male–female ratio is approximately 1.3:1 with an average age of occurrence of approximately 65 years [14–17]. The majority of reported non-Hodgkin lymphomas primary to the pancreas has involved the pancreatic head . Approximately two thirds are diffuse large B cell lymphomas, which encompass a heterogeneous group of aggressive diffuse lymphomas composed of large B-lineage cells [18]. Diffuse large B cell lymphomas may arise de novo or represent a transformation of various low-grade B cell lymphomas.
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