Primary Systemic Anaplastic Large Cell Lymphoma

Definition

Systemic CD30+ T cell lymphoma usually composed of cohesive large cells witih abundant cytoplasm and pleomorphic nuclei; half or more express anaplastic lymphoma kinase (ALK1)

Cohesive large cells with abundant cytoplasm and pleomorphic nuclei
- Hallmark cells (“horseshoe cells”)
  - Characteristic large cells with U-shaped or C-shaped nuclei surrounding a brightly eosinophilic Golgi area
  - Most frequent in the common variant
  - Scattered hallmark cells usually also found in small cell, lymphohistiocytic and other variants
- Cohesive growth pattern
  - Intrasinusoidal growth in lymph nodes (if lymph node is not effaced)
- Numerous histological variants have been described, and may coexist
  - Common variant
    - large anaplastic cells with abundant eosinophilic cytoplasm and pleomorphic nuclei
  - Small cell variant
    - Smaller cells with less irregular nuclei than common variant
    - Hallmark cells in perivascular location
  - Lymphohistiocytic variant
    - Predominance of histiocytes
    - Hallmark cells in perivascular location
  - Less common subtypes: neutrophil-rich, giant cell rich, signet ring, sarcomatoid, Hodgkin-like with nodular sclerosis
T cell or “null cell” immunophenotype
- Lack of B cell or classical Hodgkin immunophenotype
ALK1 immunopositivity/ALK1 translocation is definitional in this setting, but is absent in up to 40% of cases
- It is debated by some experts that ALK1-negative cases should be classified as peripheral T-cell lymphoma, NOS
- A rare set of large B cell lymphomas express ALK1
May involve multiple lymph node and soft tissue sites, including skin, but must not be limited to the skin

Dita Gratzinger MD PhD
Yasodha Natkunam MD PhD

Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342