Question

Difficulty: MediumPathology and Biopsy Interpretation

During an evaluation for a persistently enlarged right cervical mass, a 62-year-old woman undergoes an excisional lymph node biopsy. She first noticed the swelling four months ago and reports it has been completely painless. Review of systems is notable for the absence of fevers, night sweats, and weight loss. Physical examination confirms a 3.5-cm, rubbery, mobile lymph node in the anterior cervical chain with no other palpable adenopathy or organomegaly. The surgical pathology report details a completely effaced nodal architecture replaced by closely packed, variably sized nodules without distinct mantle zones. High-power microscopic examination of these nodules reveals a mixture of centrocytes and centroblasts, with a notable absence of tangible-body macrophages. Immunohistochemical staining of the atypical cells demonstrates strong positivity for CD20, CD10, and BCL-2, while staining for CD5 and cyclin D1 is negative. Based on the integration of this patient's clinical presentation and histopathologic findings, which of the following is the most likely diagnosis?

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

Answer

Follicular lymphoma
The correct diagnosis is follicular lymphoma. This patient presents with painless lymphadenopathy typical of an indolent non-Hodgkin lymphoma. The biopsy demonstrates classic features of follicular lymphoma: an effaced architecture replaced by closely packed neoplastic follicles composed of centrocytes and centroblasts. The absence of tangible-body macrophages is a key histologic clue distinguishing it from reactive hyperplasia, as the neoplastic cells in follicular lymphoma evade apoptosis. This evasion is confirmed by the immunohistochemical profile demonstrating strong positivity for BCL-2, the product of the t(14;18) translocation. Furthermore, the tumor cells express CD10 (indicating germinal center origin) and lack CD5 and cyclin D1, successfully ruling out other small B-cell lymphomas.

Step-by-Step Solution

1
Analyze the clinical presentation.
An older adult presenting with painless, slowly progressive lymphadenopathy and lacking B symptoms, which is highly suggestive of an indolent lymphoma.
Establishing the clinical tempo helps frame the differential diagnosis prior to reviewing pathology.
2
Interpret the morphologic findings on the biopsy.
The presence of closely packed nodules effacing normal architecture and lacking tangible-body macrophages points toward a neoplastic follicular proliferation.
Tangible-body macrophages indicate normal apoptosis in a reactive germinal center; their absence suggests a malignant process where apoptosis is inhibited.
3
Evaluate the immunohistochemical panel.
The cells are CD20+ (B-cell), CD10+ (germinal center origin), BCL-2+ (anti-apoptotic protein overexpression), and negative for CD5 and Cyclin D1.
The IHC panel differentiates between specific B-cell lymphomas. CD5 negativity rules out mantle cell and small lymphocytic lymphomas. BCL-2 positivity confirms follicular lymphoma over reactive hyperplasia or Burkitt lymphoma.

Key Concept

Diagnosis of Follicular Lymphoma via Histopathology and Immunohistochemistry
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