Question

Difficulty: MediumPathology and Biopsy Interpretation

A 58-year-old man is evaluated in the clinic for a slowly enlarging, painless mass in the right side of his neck that he first noticed two months ago. He reports no fevers, drenching night sweats, or unintentional weight loss. Physical examination reveals a 3.5-cm, firm, mobile, non-tender right cervical lymph node. The remainder of the examination is unremarkable. An excisional lymph node biopsy is performed.

The histopathologic evaluation reveals complete effacement of the normal lymph node architecture by closely packed, uniform nodular structures. These nodules lack well-defined mantle zones and are devoid of tingible body macrophages.

A synoptic immunohistochemical (IHC) profile of the neoplastic cells is provided:

MarkerResult
CD20Positive
CD10Positive
BCL-2Strongly positive within the nodules
CD5Negative
Cyclin D1Negative

Based on the pathology and biopsy interpretation, which of the following is the most likely diagnosis?

  1. A
    Reactive follicular hyperplasia
  2. B
    Small lymphocytic lymphoma
  3. Follicular lymphomaAnswer
  4. D
    Mantle cell lymphoma
  5. E
    Diffuse large B-cell lymphoma

Answer

Follicular lymphoma
The correct diagnosis is follicular lymphoma. The biopsy demonstrates complete effacement of normal architecture by nodules of neoplastic cells, a classic histologic feature. The absence of tingible body macrophages points away from a benign reactive process. Immunohistochemically, follicular lymphoma cells are mature B-cells (CD20+) that originate from germinal centers (CD10+) and characteristically overexpress BCL-2 due to the t(14;18) translocation. They are typically CD5 negative, which distinguishes them from other small B-cell lymphomas like mantle cell lymphoma and small lymphocytic lymphoma.

Step-by-Step Solution

1
Analyze the histopathologic findings.
The biopsy demonstrates nodular structures without tingible body macrophages and completely effaced architecture, which is highly suggestive of a neoplastic process rather than a benign reactive one.
Differentiating benign reactive hyperplasia from a neoplastic lymphoma is the critical first step in lymph node biopsy interpretation.
2
Interpret the immunohistochemical (IHC) profile.
The cells are B-cells (CD20+) that express germinal center markers (CD10+) and an anti-apoptotic protein (BCL-2+), but lack T-cell/mantle markers (CD5-).
The exact subtype of B-cell non-Hodgkin lymphoma is determined by integrating the histologic pattern with the specific expression of surface antigens and translocations.
3
Synthesize the findings to confirm the diagnosis.
The combination of a nodular architecture, absent tingible body macrophages, and a CD10+, BCL-2+, CD5- immunophenotype is diagnostic of follicular lymphoma.
These specific features definitively rule out reactive hyperplasia, mantle cell lymphoma, small lymphocytic lymphoma, and diffuse large B-cell lymphoma.

Key Concept

Interpretation of lymph node histopathology and immunohistochemistry (IHC) to distinguish follicular lymphoma from reactive hyperplasia and other B-cell lymphomas.
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