Question

Difficulty: MediumPathology and Biopsy Interpretation

A central hematopathology referral center is reviewing diagnostic material from several lymph node excisional biopsies. To establish the definitive diagnoses, correlate each hematolymphoid malignancy with its specific pathognomonic histopathologic and immunohistochemical findings.

  • Follicular lymphomaNodular architecture with neoplastic cells that strongly express CD10, BCL2, and BCL6 due to an IGH/BCL2 rearrangement.
  • Mantle cell lymphomaDiffuse proliferation of small to medium-sized lymphocytes; neoplastic cells co-express CD5 and cyclin D1 due to an IGH/CCND1 rearrangement.
  • Burkitt lymphomaDiffuse infiltrate of intermediate-sized lymphocytes with numerous tingible-body macrophages creating a 'starry sky' pattern; near 100% Ki-67 proliferation index; t(8;14) translocation.
  • Classic Hodgkin lymphomaLarge, binucleated cells with prominent eosinophilic nucleoli within an inflammatory background; diagnostic cells are CD15+ and CD30+, but CD20- and CD45-.

Answer

Follicular lymphoma pairs with nodular architecture and BCL2 expression. Mantle cell lymphoma pairs with CD5 and Cyclin D1 expression. Burkitt lymphoma pairs with 'starry sky' morphology and a near 100% Ki-67 index. Classic Hodgkin lymphoma pairs with CD15+/CD30+ Reed-Sternberg cells.
Each hematolymphoid malignancy has a highly specific morphologic and immunophenotypic signature required for definitive diagnosis. Matching these correctly relies on recognizing the pathognomonic chromosomal translocations (e.g., t(11;14) driving Cyclin D1 in Mantle cell), unique cell morphologies (e.g., Reed-Sternberg cells in Hodgkin lymphoma), and characteristic growth patterns combined with proliferation indices (e.g., starry sky and ~100% Ki-67 in Burkitt lymphoma).

Step-by-Step Solution

1
Identify the unique diagnostic marker for Classic Hodgkin lymphoma.
The profile describing large binucleated cells that are CD15 positive and CD30 positive (Reed-Sternberg cells) corresponds to Classic Hodgkin lymphoma.
CD15 and CD30 positivity in the absence of CD20 and CD45 is pathognomonic for Classic Hodgkin lymphoma and differentiates it from non-Hodgkin lymphomas.
2
Analyze the profile with a near 100% proliferation index and 'starry sky' pattern.
This highly proliferative profile corresponds to Burkitt lymphoma.
Burkitt lymphoma is the fastest growing human tumor, characterized by a t(8;14) c-MYC translocation and extensive apoptosis with macrophage clearing, creating the starry sky appearance.
3
Differentiate between the two small/medium B-cell lymphoma profiles (Follicular vs. Mantle cell).
The profile with CD5 and Cyclin D1 positivity represents Mantle cell lymphoma. The profile with nodular architecture, CD10, and BCL2 positivity represents Follicular lymphoma.
Mantle cell lymphoma is defined molecularly by the t(11;14) translocation producing cyclin D1. Follicular lymphoma is defined by the t(14;18) translocation causing BCL2 overexpression and prevention of normal germinal center apoptosis.

Key Concept

Definitive histopathologic and immunohistochemical diagnosis of hematolymphoid malignancies.
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