A 52-year-old man with a 30-year smoking history presents with progressive dyspnea and chest pain. Chest X-ray shows a well-defined, smooth anterior mediastinal mass. CT chest demonstrates a homogeneous mass with mild enhancement, and there is no evidence of calcification or fat planes. The patient reports intermittent fever and night sweats. Serum LDH is markedly elevated at 2400 U/L. Tumor markers (β-hCG and α-fetoprotein) are normal. What is the most likely diagnosis?

Explanation

## Diagnosis: Primary Mediastinal B-Cell Lymphoma (PMBL) ### Clinical Presentation **Key Point:** Primary mediastinal B-cell lymphoma is a distinct entity arising from thymic B cells, most common in young to middle-aged adults with B symptoms and markedly elevated LDH. This patient has: - Age 52 years (PMBL typically 20–50 years, but can occur older) - Anterior mediastinal location (classic site for PMBL) - B symptoms: fever, night sweats, dyspnea - Markedly elevated LDH (2400 U/L) — indicates high tumor burden and poor prognosis - **Normal tumor markers** — rules out germ cell tumors - Homogeneous, well-defined mass with mild enhancement — typical imaging ### Differential Diagnosis of Anterior Mediastinal Masses with Elevated LDH | Feature | PMBL | Seminoma | Thymoma | Lymphoblastic Lymphoma | |---------|------|----------|---------|------------------------| | **Age** | 20–50 yrs | 20–40 yrs | 40–60 yrs | Younger (< 30 yrs) | | **B symptoms** | Common (60%) | Rare | Rare | Common | | **LDH elevation** | Marked (often >1000) | Mild to moderate | Normal | Marked | | **Tumor markers** | Normal | ↑LDH, ±β-hCG | Normal | Normal | | **Imaging** | Homogeneous, mild enhancement | Homogeneous | Homogeneous | May have hemorrhage | | **Calcification** | Rare | Rare | Common | Rare | ### Why Primary Mediastinal B-Cell Lymphoma? **High-Yield:** The constellation of: 1. **Markedly elevated LDH (2400 U/L)** — hallmark of lymphoma; indicates aggressive disease and high cell turnover 2. **B symptoms** — fever and night sweats are typical of lymphoma, uncommon in thymoma or seminoma 3. **Normal tumor markers** — excludes germ cell tumors (seminoma, NSGCT) 4. **Homogeneous anterior mediastinal mass** — classic for PMBL 5. **Mild enhancement** — lymphoid tissue enhances mildly; germ cell tumors show heterogeneous enhancement **Clinical Pearl:** PMBL is a subtype of diffuse large B-cell lymphoma (DLBCL) that arises from thymic B cells and is distinct from nodal DLBCL. It has a predilection for young women but can occur in men. Sclerosis and fibrosis are common histologic features. ### Diagnostic Workup - **Tissue diagnosis:** Core needle biopsy or mediastinoscopy required - **Immunophenotype:** CD20+, CD45+, PAX5+; negative for CD30 (unlike Hodgkin lymphoma) - **PET-CT:** Typically shows FDG avidity - **Staging:** Full staging with CT chest/abdomen/pelvis and bone marrow biopsy ### Management - First-line: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R-EPOCH - Prognosis: Intermediate to poor depending on IPI score - Radiation therapy may be considered for residual masses **Mnemonic: "PMBL = Primary Mediastinal B-cell Lymphoma"** — Remember: anterior mediastinum + B symptoms + marked LDH elevation + normal tumor markers = PMBL until proven otherwise.