Touch preparation from a pancreatic core biopsy

A 50-year-old male presented with abdominal pain and weight loss. Abdominal CT showed a 5 cm round mass in the head of the pancreas. An ultrasound-guided core needle biopsy was performed. Touch prep of the needle cores performed for rapid onsite evaluation [Figure 1].

Figure 1:: The touch prep showed loose clusters of cells with occasional vague acinar formations (a and b), abundant cytoplasm, occasional nucleoli, and mild-to-moderate anisonucleosis (c).

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Q1. What is your interpretation of the touch preparation?

Atypical epithelial cells, suspicious for carcinoma

Well-differentiated neuroendocrine tumor

Negative for malignancy, favor chronic pancreatitis

Gastrointestinal contaminant (duodenal epithelium).

Answer

The correct cytological interpretation is

a. Atypical epithelial cells, suspicious for carcinoma.

EXPLANATION

A diagnosis of “suspicious for carcinoma,” A is appropriate when some or most features of carcinoma are present but fall qualitatively or quantitatively short of a definitive diagnosis for carcinoma. In this case, the touch prep shows variably sized loose clusters and single cells with acinar formation. The cells show abundant granular cytoplasm. The nuclei show mild-to-moderate anisonucleosis with occasional prominent nucleoli, and salt-and-pepper chromatin. At the time of rapid onsite evaluation, “suspicious for carcinoma” is the most appropriate diagnosis. The differential diagnosis would include pancreatic acinar cell carcinoma (ACC) and pancreatic neuroendocrine neoplasm.

Pancreatic well-differentiated neuroendocrine tumors show loosely cohesive cell clusters and single cells. Cytological preparations from these tumors may also demonstrate pseudo rosette formation that is impossible to distinguish from the acinar formation noted in ACC. Anisonucleosis is minimal, and the nuclear chromatin may show a classic salt-and-pepper appearance, clumping, or even prominent nucleoli.

A diagnosis of negative for malignancy, favor chronic pancreatitis, would be appropriate in the absence of neoplastic cells and when features of chronic pancreatitis are present. Cytological preparations may show inflammatory cells (predominantly macrophages, but also lymphocytes and occasional neutrophils). There may be rare ductal cells with mild-to-moderate atypia and fibrotic acinar tissue.

Duodenal contamination would consist of sheets of uniform epithelial cells with occasional goblet cells.

ADDITIONAL QUIZ QUESTIONS

Q2. H&E stained sections are prepared from the tissue cores [Figure 2] and show a solid, cellular neoplasm. Which of the following is the least likely diagnosis?

Neuroendocrine neoplasm

Solid pseudopapillary neoplasm

Pancreatic ACC

Islet cell pseudohypertrophy in chronic pancreatitis.

Figure 2:: The core biopsy showed nests of cells with only mild nuclear anisocytosis and occasional inconspicuous nucleoli.

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Q3. Special stains and immunohistochemical preparations show the following results: Positive trypsin, BCL-10, and beta-catenin (membranous) with weak and focal positivity for neuroendocrine markers (synaptophysin, chromogranin, and CD56), PAS-D highlighted intracytoplasmic zymogen granules, and CD10 was negative [Figure 3]. What is the final diagnosis?

Well-differentiated neuroendocrine tumor

Solid pseudopapillary neoplasm

Pancreatic adenocarcinoma with predominantly acinar differentiation

Pancreatoblastoma.

Figure 3:: (a) Trypsin, (b) Bcl-10, (c) PAS-D, (d) Synaptophysin, (e) Beta-catenin, and (f) CD-10.

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Answers to additional quiz questions:

Q2: d; Q3: c

EXPLANATION FOR ADDITIONAL QUIZ QUESTIONS

The H&E stained biopsy cores show a solid cellular neoplasm. This brings up a differential diagnosis of a neuroendocrine neoplasm, solid pseudopapillary neoplasm, pancreatic ACC, and pancreatoblastoma.

Pancreatic well-differentiated neuroendocrine tumors demonstrate a nested, trabecular, or infiltrating (in the case of neuroendocrine carcinoma) growth pattern. Nuclei are round and uniform. The nuclear chromatin classically shows a salt-and-pepper appearance; however, nuclear clumping and prominent nucleoli can also be seen.

Solid pseudopapillary neoplasms can form solid masses with degenerative cystic changes. The cells are loosely cohesive and may form pseudopapillae. Other features that may be present in pancreatic solid pseudopapillary tumors are cytoplasmic vacuoles, hyaline globules, and foamy histiocytes.

Pancreatic ACC shows a solid or lobular growth pattern with acinar formations. Cells show prominent cytoplasm with intracytoplasmic granules. The nuclei show mild anisonucleosis with prominent nucleoli.

Islet cell pseudohypertrophy in chronic pancreatitis can be mass-forming; however, this would occur in a background of atrophy with obliteration of pancreatic parenchyma. Acinar formation and abundant cytoplasm with intracytoplasmic granules are not features of islet cell pseudohypertrophy.

The addition of immunostains and special stains would support an impression of pancreatic ACC. A PAS/D stain highlights intracytoplasmic zymogen granules. Positive staining for trypsin, BCL-10, and membranous beta-catenin are also characteristic of this neoplasm. However, there is also focal, weak positivity for synaptophysin, and raising the possibility that the resection material could show a mixed acinar/neuroendocrine carcinoma, hence, the final diagnosis of “pancreatic carcinoma with predominantly acinar differentiation.”

DISCUSSION

Acinar cell carcinoma (ACC) is a rare pancreatic malignancy that comprises about 1% of pancreatic neoplasia.[1,2] Due to the rarity of this neoplasm, its risk factors and prognosis have not been entirely characterized. Nevertheless, the prognosis appears to be somewhat better than pancreatic ductal adenocarcinoma (PDAC). The overall 5-year survival is approximately 22.6% compared to only 2.8% for PDAC; however, the 5-year survival increases to 47% in cases of localized disease.[3] Like other pancreatic neoplasms, pancreatic ACC may present with abdominal pain, weight loss, or diabetes. Jaundice is another possible presenting symptom but is less common than in pancreatic ductal carcinoma.[2]

Radiographically, pancreatic ACC presents as a solid and hypovascular mass. Fine-needle aspiration (FNA) is a fundamental step in achieving an accurate diagnosis with a sensitivity for detecting malignancy of up to 96%.[4] However, due to its rarity, pancreatic ACC may not be recognized in FNA material. Cytologic preparations will show variably sized loose clusters of cells with acinar formation. Cells show prominent cytoplasm with intracytoplasmic granules. The nuclei show mild anisonucleosis with prominent nucleoli. Of note, there is significant cytological overlap with the far more common pancreatic well-differentiated neuroendocrine tumors, in which pseudorosettes may mimic acini, and occasional prominent nucleoli may be present.[5] If cell block or core biopsy material is available (as in this case), the H&E stained slides show cells arranged in an acinar, glandular, or solid pattern. Nucleoli are usually present but may be inconspicuous. Immunohistochemical stains are also helpful in the diagnosis. Positivity for trypsin, chymotrypsin, BCL-10, and membranous beta-catenin are all characteristic of pancreatic ACC; however, one should also rule out other solid cellular neoplasms, including solid pseudopapillary neoplasm (CD10 positive with nuclear beta-catenin) and pancreatic neuroendocrine tumor/carcinoma (CD56, synaptophysin, and chromogranin positive). Focal positivity of neuroendocrine markers is present in 20–40% of pancreatic ACCs and should not lead to over-interpretation.[1,2] These markers on biopsy or cell block material do raise the possibility of a mixed acinar cell/neuroendocrine carcinoma, because the final resection specimen may show significantly more neuroendocrine differentiation. At present, this distinction is not critical, because it carries no prognostic or treatment implications. In this biopsy material, we favored a diagnosis of “pancreatic carcinoma with predominantly acinar differentiation” pending examination of the entire tumor.

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