Interactive Case: Pancreatic Mass

A guided walkthrough of a pancreatic EUS-FNA.

Clinical History

A 38-year-old man with a history of alcohol use, one year of abdominal discomfort, loose stools, and weight loss. CT showed an 8 cm pancreatic neck mass encasing surrounding vessels, with numerous hepatic metastases and retroperitoneal lymphadenopathy.

Step 1: Low Power Impression

Low power view of the pancreatic aspirate

At low power, what is the overall pattern of the smear? (Select all that apply)

Abundantly cellular Loosely cohesive to dyshesive cells Large, tight, 3D clusters Predominantly inflammatory cells

Rationale: The smear is very cellular and composed of cells that are falling apart from one another. This "monotonous, dyshesive" pattern is highly suggestive of a neuroendocrine tumor or another hematolymphoid process, rather than a typical ductal adenocarcinoma which forms tight clusters.

Step 2: High Power Features

At high power, what cytologic features are apparent? (Select all that apply)

Uniform, round to oval nuclei Scant, delicate cytoplasm Loose rosette-like formations Marked pleomorphism Abundant, dense cytoplasm

Rationale: The cells are strikingly uniform, with round nuclei and minimal cytoplasm. They tend to cluster around empty spaces, forming "pseudorosettes." This uniformity is a key feature of well-differentiated neuroendocrine tumors.

Step 3: Nuclear Details

What are the characteristic nuclear features? (Select all that apply)

Finely stippled, "salt-and-pepper" chromatin Nuclear molding Inconspicuous or small nucleoli Irregular nuclear membranes with deep grooves Large, macronucleoli

Rationale: The chromatin pattern is the most important clue: it is finely granular, resembling salt and pepper. This is the defining feature of a neuroendocrine tumor. Nuclear molding (nuclei wrapping around each other) is also frequently seen.

Step 4: Cell Block Architecture

What architectural pattern(s) do you see on the cell block?

Solid to nested arrangement Well-formed glands with central lumens Cribriform architecture Single-file chains

Rationale: The cell block shows the tumor cells growing in solid sheets and forming distinct nests, a typical growth pattern for neuroendocrine tumors. This helps distinguish it from adenocarcinoma, which would form more defined glands.

Step 5: Diagnosis

Based on the morphologic features (uniform cells, stippled chromatin, rosettes, molding), what is the diagnosis?

Neuroendocrine Tumor (NET) Acinar Cell Carcinoma Pancreatic Ductal Adenocarcinoma Solid Pseudopapillary Neoplasm

Rationale: The combination of features is pathognomonic for a well-differentiated neuroendocrine tumor. Other pancreatic tumors have different cytologic characteristics (e.g., prominent nucleoli in acinar cell carcinoma, marked pleomorphism in ductal adenocarcinoma).

Step 6: Ancillary Confirmation

What immunohistochemical (IHC) profile would confirm a neuroendocrine tumor?

Synaptophysin (+), Chromogranin (+), CD56 (+) CK7 (+), CK20 (-), CDX2 (-) Trypsin (+), Chymotrypsin (+), BCL10 (+) Beta-catenin (nuclear +), CD10 (+), Vimentin (+)

Rationale: Synaptophysin and Chromogranin are the classic, most specific markers for neuroendocrine differentiation. CD56 is also commonly positive. The other panels are for different tumors (pancreatic ductal adenocarcinoma, acinar cell carcinoma, and solid pseudopapillary neoplasm, respectively).

Step 7: Grading

How should this tumor be graded based on the cytology and Ki-67 of 4%? (Select all that apply)

Grade 1 (Ki-67 <3%) Grade 2 (Ki-67 3-20%) Grade 3 (Ki-67 >20%) Neuroendocrine Carcinoma (Ki-67 >20% and high-grade morphology) Grading on cytology is provisional and should be confirmed on resection

Rationale: Both answers are correct. The WHO grading system places a tumor with a Ki-67 index of 4% in the Grade 2 category. However, it is crucial to recognize that grading on a small cytology sample is provisional due to potential tumor heterogeneity. The final grade should always be determined on the surgical resection specimen, which may reveal areas with a higher proliferation rate.

Final Diagnosis: Well-Differentiated Neuroendocrine Tumor, WHO Grade 2 (Provisional)

The cytologic features of uniform cells with "salt-and-pepper" chromatin, scant cytoplasm, and rosette formation are classic for a neuroendocrine tumor. This is confirmed by positivity for Synaptophysin and CD56.

With a Ki-67 proliferation index of 3-5%, the tumor is classified as a WHO Grade 2 NET. It is important to note that grading on an FNA specimen is provisional, as tumor heterogeneity may exist and a higher grade could be present in the main tumor mass upon resection.