**Core Concept**
Mesothelioma is a malignant tumor of the mesothelium, which is a layer of flat cells lining the pleural, peritoneal, and pericardial cavities. The main risk factor for mesothelioma is asbestos exposure. Differentiating mesothelioma from adenocarcinoma, another type of malignant tumor, is crucial for diagnosis and treatment.

**Why the Correct Answer is Right**
Mesothelioma can be differentiated from adenocarcinoma by its distinctive immunohistochemical profile. The tumor cells in mesothelioma typically express **calretinin**, **WT1**, and **D2-40**, whereas adenocarcinoma cells usually express **TTF-1**, **CK7**, and **CK20**. Additionally, mesothelioma cells often show **sarcomatoid differentiation**, which is characterized by the presence of spindle-shaped cells. This feature is not typically seen in adenocarcinoma.

**Why Each Wrong Option is Incorrect**
**Option A:** While both mesothelioma and adenocarcinoma can cause pleural effusion, this feature is not specific enough to differentiate between the two tumors.

**Option B:** The presence of asbestos fibers in the lung tissue can support a diagnosis of mesothelioma but is not sufficient to rule out adenocarcinoma.

**Option C:** The histological appearance of mesothelioma and adenocarcinoma can be similar, and a definitive diagnosis often requires immunohistochemical analysis.

**Clinical Pearl / High-Yield Fact**
When differentiating mesothelioma from adenocarcinoma, remember the "ABC" rule: **A**denocarcinoma is more likely to express TTF-1, while **M**esothelioma is more likely to express calretinin and WT1.

**Correct Answer: C.**