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Reactive T-cell Hyperplasia in the Lymph Node

Click CC box for captions; full transcript is below.

Published: February 2013

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Surgical pathology relies on the use of several techniques including special stains, flow cytometry, and molecular studies. Dr. Jevremovic walks you through the steps used to reach a diagnosis in this case.

Presenter: Dragan Jevremovic, MD, PhD

  • Assistant Professor of Laboratory Medicine and Pathology at Mayo Clinic
  • Co-Director of the Cell Kinetics Laboratory in the Division of Hematopathology at Mayo Clinic in Rochester, Minnesota

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I have nothing to disclaim regarding this case.

This is a case of a 47-year-old male that presented acutely with a shortness of breath. The patient had a long-standing history of asthma and allergies, and imaging revealed mediastinal, periaortic, and inguinal lymphadenopathy. The clinicians went ahead and biopsied inguinal lymph node.

This is a low-power picture of a H&E stain of the lymph node, which shows a disorganized architecture bordering on effacement. There is also prominent vascular proliferation.

Intermediate power shows marked vascular proliferation and paracortical hyperplasia of predominantly small cells.

On an even higher magnification, there is a mixture of small, intermediate, and large lymphocytes, as well as mixed in plasma cells and eosinophils.

High magnification shows that there are some large atypical cells with prominent nucleoli, which can raise possibility that these are Reed-Sternberg cells. This could also be activated immunoblasts. Neutrophil margination is seen in the vessels.

A panel of immunohistochemical stains was performed. CD3 stain showed that the majority of paracortical cells are small CD3 positive T cells.

CD20 stain highlights B-cells organizing follicles supporting the notion that the architecture is not effaced. In addition, there are scattered CD20-positive larger cells in the paracortex and these represent immunoblasts.

We already saw that the majority of cells in the paracortex were CD3-positive T cells. CD4 stain shows that the majority of these T cells are CD4 cells.

There’s also a relatively small CD8-positive component of the T cells.

The T cells showed normal expression of pan T-cell markers, which are CD2, CD5, and CD7.

CD30 stain highlighted only scattered immunoblasts, which showed only weak staining with CD30 antigen.

CD21 stain showed preserved follicular dendritic cell architecture without expansion.

CD279 or PD1 is a follicular T-cell marker and is strongly positive in follicular T-helper cells, which are shown in the upper part of the slide. The paracortical T cells showed only a partial weak staining for CD279, which is nonspecific.

Epstein-Barr virus staining was negative by in situ hybridization, and so was staining for CD10 in the T cells. CD10 can be seen positive in marginalized neutrophils within the vessels. The vast majority of the T cells expressed alpha-beta T-cell receptor and were negative for gamma-delta T-cell receptor.

T-cell receptor gene rearrangements for both beta and gamma regions showed polyclonal T cells.

The diagnosis was made of paracortical hyperplasia of reactive T cells

Paracortical hyperplasia is a T-cell response to infection, usually viral, and can also be seen in hypersensitivity reaction. It is characterized by heterogeneous cell population that includes small lymphocytes, immunoblasts, monocytoid B-cells, as well as eosinophil, plasma cells, and neutrophils. On low power, paracortical hyperplasia has a “moth-eaten” appearance with vascular proliferation and sometimes sinus histiocytosis.

Differential diagnosis is the most important in the cases of reactive T-cell hyperplasia. In this case, the most difficult differential diagnosis was differentiating this hyperplasia from T-cell lymphoma, in particular, angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma. What makes this case a reactive lymphoid hyperplasia is that:

  • The atypical cells were only scattered
  • The immunohistochemistry showed still-preserved architecture
  • That CD279 or PD1 stain was very weak outside the follicles
  • There was no expansion of follicular dendritic cells meshworks and
  • The T-cell receptor gene rearrangements were negative.

This is for contrast a case of angioimmunoblastic T-cell lymphoma, which shows effaced architecture by perforation of intermediate-sized cells with slight atypia and abundant clear cytoplasm. The background is polymorphic, and there is a prominent vascular proliferation similar to our case. However, the atypical cells would be strongly positive for CD279, and measure a loss of 1 or more pan T-cell antigens.

This is CD21 stain in cases of angioimmunoblastic T-cell lymphoma and shows marked expansion of follicular dendritic cell meshworks.

Another potential differential diagnostic entity is classical Hodgkin lymphoma. Our case did not raise strong suspicion for classical Hodgkin lymphoma because there was preserved architecture on immunohistochemical stains. Cells in our case showed a spectrum in cell size, and when there’s a spectrum the cells are much more likely to be immunoblasts than Reed-Steinberg cells. Our case had the very weak and variable expression of CD30 in these immunoblasts, and these cells were also CD45 positive.

This is for example and for contrast, a case of classical Hodgkin lymphoma, which shows that there are large atypical cells, surrounded by small cells; therefore, there is clear dichotomy in  cell size and morphology, unlike seen in reactive proliferation which shows spectrum in size and morphology. There is also background mixed inflammation and fibrosis. The atypical cells express CD30 and PAX5, often express CD15, and they are negative of CD45.

The other potential differential diagnostic entities that could be confused with paracortical T-cell hyperplasia include reactive lymphoid hyperplasias with a specific etiology, often include Epstein-Barr virus, cytomegalovirus, or toxoplasma. Epstein-Barr virus infections often go with follicular hyperplasia, in addition to paracortical hyperplasia, but in situ hybridization or immunostains would be necessary for making this diagnosis.

Cytomegalovirus lymphadenitis is characterized by nuclear acidophilic inclusions and presence of monocytoid B-cells. Toxoplasma lymphadenitis comes with triad of follicular hyperplasia, hyperplasia monocytoid B-cells, and presence of epithelioid histiocytes, which often infiltrate germinal centers.

The patient that was presented in this case was followed-up 3 months postbiopsy. Radiologic studies showed significant decrease in lymphadenopathy to less than half of original size without any treatment. The patient is being followed.

In summary, reactive and atypical lymphoid hyperplasia can mimic many neoplastic entities. The clue to diagnosis is preserved architecture, even if it can be shown only on immunostains, and spectrum in cell size, which favor reactive over lymphoma. Immunohistochemistry is necessary to exclude Hodgkin lymphoma and T-cell lymphoma. Sometimes molecular studies are necessary to make sure that the proliferation is reactive and not neoplastic. Advice is to always look at clinical history; in this case, long-standing presence of autoimmune disorders was helpful in making diagnosis of reactive proliferation. And, if in doubt, its always better to call proliferation atypical and wait, then to overcall a lymphoma.