Case Reports

Angioimmunoblastic T-Cell Lymphoma Mimicking Diffuse Large B-Cell Lymphoma

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Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive form of peripheral T-cell lymphoma that is characterized by lymphadenopathy, night sweats, fever, weight loss, and autoimmune phenomena. Cutaneous manifestations are present in up to 50% of cases, but few cases are reported in the dermatologic literature. We present a case of AITL that manifested in the skin. The patient was diagnosed with diffuse large B-cell non-Hodgkin lymphoma 3 months prior based on results from a lymph node biopsy. Reexamination and immunohistochemical staining of the previously biopsied lymph node specimen revealed the same clonal population of T cells positive for CD3, CD4, CD10, and programmed cell death protein 1 (PD-1) that was present in the skin and confirmed a diagnosis of AITL. Angioimmunoblastic T-cell lymphoma is frequently misdiagnosed due to its nonspecific clinical and histologic findings; it is not uncommon for AITL to be mistaken for other types of lymphoma. Dermatologists and dermatopathologists can play an important role in the recognition of this difficult-to-diagnose malignancy.

Practice Points

  • Angioimmunoblastic T-cell lymphoma (AITL) is a rare, often aggressive type of peripheral T-cell lymphoma.
  • Cutaneous manifestations have been seen in up to 50% of cases.
  • Immunohistochemical markers for normal follicular helper T cells—CD-10, chemokine CXCL-13, and programmed cell death protein 1 (PD-1)—can be used to differentiate AITL from other types of lymphoma.
  • The prognosis of AITL is poor.


 

References

Angioimmunoblastic T-cell lymphoma (AITL) is a rare, often aggressive type of peripheral T-cell lymphoma. It comprises 18% of peripheral T-cell lymphomas and 1% to 2% of all non-Hodgkin lymphomas.1 The incidence of AITL in the United States is estimated to be 0.05 cases per 100,000 person-years,2 and there is a slight male predominance.1,3,4 It typically presents in the seventh decade of life; however, cases have been reported in adults ranging from 20 to 91 years of age.3

Angioimmunoblastic T-cell lymphoma presents with lymphadenopathy, hepatosplenomegaly, and systemic B symptoms (eg, fever, night sweats, weight loss, generalized pruritus).4-6 There are cutaneous manifestations in up to 50% of cases4,5,7 and frequently signs of autoimmune disorder.4,5 The diagnosis often is made by excisional lymph node biopsy. Lymph node specimens characteristically have a mixed inflammatory infiltrate that includes numerous B cells often infected with Epstein-Barr virus (EBV) and a relatively small population of atypical T lymphocytes.8 Identification of this neoplastic population of CD4+CD8 T lymphocytes expressing normal follicular helper T-cell markers CD10, chemokine CXCL13, programmed cell death protein 1 (PD-1), and B-cell lymphoma 6 (BCL-6) confirms the diagnosis of AITL.9,10 These malignant cells can be identified in skin specimens in cases of cutaneous metastatic disease.11,12 We present a case originally misdiagnosed as diffuse large B-cell lymphoma that was later identified as AITL on skin biopsy.

Case Report

A 72-year-old woman presented with a pruritic erythematous eruption around the neck of 3 weeks’ duration (Figure 1). Her medical history was notable for diffuse large B-cell non-Hodgkin lymphoma diagnosed 3 months prior based on results from a right cervical lymph node biopsy. She was treated with bendamustine and rituximab. On physical examination there were erythematous edematous papules coalescing into indurated plaques around the neck. The differential diagnosis included drug hypersensitivity reaction, herpes zoster, urticaria, and cutaneous metastasis. Two punch biopsies were taken for hematoxylin and eosin and tissue culture.

Figure1

FIGURE 1. Angioimmunoblastic T-cell lymphoma with erythematous papules coalescing into plaques around the neck (A and B).

Tissue cultures and viral polymerase chain reaction were negative. Histopathologic examination revealed a scant atypical lymphoid infiltrate focally involving the deep dermis. The cells were medium to large in size and contained hyperchromatic pleomorphic nuclei (Figure 2). They were positive for CD3 and CD4, which was concerning for T-cell lymphoma. The histologic report of the excisional lymph node biopsy done 3 months prior described an atypical lymphoid neoplasm with extensive necrosis and extranodal spread that stained positively for CD20 (Figure 3).

Figure2

Figure 2. Punch biopsy demonstrated a scant perivascular lymphoid infiltrate in the dermis on medium power (A)(H&E, original magnification ×10). Hyperchromatic pleomorphic perivascular lymphocytes in the deep dermis were seen on high power (B)(H&E, original magnification ×40).

Further staining of this cervical lymph node specimen revealed large atypical lymphoid cells positive for CD3, CD10, B-cell lymphoma 2 (BCL-2), BCL-6, and PD-1. There were intermixed mature B lymphocytes positive for CD20 and BCL-2. Chromogenic in situ hybridization with probes for EBV showed numerous positive cells throughout the infiltrate. Polymerase chain reaction demonstrated a T-cell population with clonally rearranged T-cell receptor genes. Primers for immunoglobulin heavy and light chains showed no evidence of a clonal B-cell population.

Additional staining of the atypical cutaneous lymphocytes revealed positivity for CD3, CD10, and PD-1. The morphologic and immunophenotypic findings of both specimens supported the diagnosis of AITL.

The patient declined further treatment and chose hospice care.

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