Interactive Case: Liver Lesion

A guided walkthrough of a metastatic liver lesion.

Clinical History

A 50-year-old man presents with a 3.3 cm liver lesion in segment 4A, noted to have heterogeneous enhancement on a recent CT scan. An FNA and core biopsy were performed.

Step 1: Very Low Power Impression

Based on this very low power view, what are the most prominent features? (Select all that apply)

Abundantly cellular smear Extensive background necrosis Paucicellular specimen Predominantly single cells Large cohesive clusters Clean background

Rationale: The smear is highly cellular, with the tumor cells arranged in large, cohesive groups. There is a prominent background of granular, necrotic debris. This immediately suggests a high-grade malignancy.

Step 2: Low Power Architecture

At low power, what general architectural pattern is suggested? (Select all that apply)

Glandular / acinar Solid sheets Papillary Single cell infiltrate

Rationale: The tumor is clearly forming glands (an adenocarcinoma), which are arranged in complex, crowded structures.

Step 3: Cytologic Features

On high power, what are the defining cytologic features of the tumor cells? (Select all that apply)

Elongated, columnar ("pencil-like") nuclei Significant nuclear pleomorphism Irregular nuclear contours Clumped ("chunky") chromatin Small, round, uniform nuclei Fine, powdery ("salt and pepper") chromatin Prominent central nucleoli Abundant eosinophilic cytoplasm

Rationale: The cells are classic for colorectal adenocarcinoma: elongated/columnar shape, high-grade nuclear features including pleomorphism (variation in size/shape), irregular contours, and coarse, clumped chromatin.

Step 4: Cell Block Architecture

The cell block better demonstrates the specific architecture. Which pattern is best displayed here?

Cribriform Micropapillary Trabecular Rosettes

Rationale: This is a classic example of a cribriform pattern, where back-to-back glands with fused walls create a sieve-like or "punched out" appearance. This is a hallmark of colorectal and prostatic adenocarcinomas.

Step 5: Differential Diagnosis

Based on ALL the H&E features you have identified (glandular, columnar cells, necrosis, cribriform pattern), what is the single most likely primary origin?

Colorectal Pancreatobiliary Lung Breast Prostate

Rationale: While other adenocarcinomas can metastasize to the liver, the specific combination of "dirty" necrosis, tall columnar "pencil-like" cells, and a cribriform architecture is the quintessential presentation of a colorectal primary.

Step 6: Ancillary Testing

Which immunohistochemical profile would best confirm your suspected diagnosis of metastatic colorectal adenocarcinoma?

CK7 negative, CK20 positive, CDX2 positive CK7 positive, CK20 negative, TTF-1 positive CK7 positive, CK20 positive, CDX2 positive CK7 positive, GATA3 positive, CDX2 negative CK7 negative, CK20 negative, CDX2 negative

Rationale: The classic immunophenotype for colorectal adenocarcinoma is positivity for CK20 and CDX2 (a marker of intestinal differentiation) and negativity for CK7. This profile is crucial for distinguishing it from other common mimics like pancreaticobiliary cancer (often CK7+/CK20+) or lung adenocarcinoma (CK7+/TTF-1+).

Final Diagnosis: Metastatic Colorectal Adenocarcinoma

The morphologic findings (cribriform architecture, dirty necrosis, columnar cells) combined with the classic immunoprofile (CK7-, CK20+, CDX2+) are diagnostic of metastatic colorectal adenocarcinoma.

The most common sites of metastasis to the liver are colorectal, lung, breast, and pancreatic carcinomas. Integrating morphology with immunohistochemistry is key to arriving at the correct diagnosis.