Angioimmunoblastic T-cell lymphoma (AITL) is a specific subtype of peripheral T-cell lymphoma that is challenging to diagnose due to the lack of specific pathological characteristics. This report describes the case of a 56-year-old man with Hodgkin lymphoma in whom the gene rearrangement results were positive for TCRβDB+Jβ1/2. Pathological and immunochemical examinations revealed a diagnosis of lymphoma that was a composite of AITL and focal classical Hodgkin lymphoma. Unfortunately, he died soon after the correct diagnosis was made. This case shows that a combination of immunohistochemistry and gene rearrangement analysis can increase the diagnostic accuracy for AITL. A review of the literature on the misdiagnosis of AITL indicates that this disease progresses rapidly with a high mortality rate. Our experience, in this case, highlights the need for early diagnosis.
Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma (PTCL) that accounts for 1–2% of all cases of non-Hodgkin lymphoma (HL) and 15–20% of cases of PTCL, and has a poor prognosis (
The patient was a 56-year-old man who was initially diagnosed with HL for which he received doxorubicin hydrochloride liposome, bleomycin, vindesine, and dacarbazine (ABVD), and doxorubicin hydrochloride liposome, vindesine, and dacarbazine (AVD) chemotherapy in April 2020. However, a decrease in his CD21 levels and disruption of the follicular dendritic cell (FDC) network (CD20+; PAX-5+; CD3+; Ki-67+: 20–30%; CD10-; BCL-6+; MUM-1+; PD-1+; CXCL-13-; CD30+; CD15-) was also detected. Molecular detection showed monoclonal rearrangement of TCRβDB+Jβ1/2 and oligoclonal rearrangement of Vβ + Jβ2. A review of all details concerning unsatisfactory treatment led to a diagnosis of compound lymphoma consisting of AITL and focal classical HL (CHL).
In March 2020, the patient was admitted to Hebei General Hospital (Shijiazhuang, China) after a 4-month history of skin redness and itching. Physical examination revealed extensive redness, swelling, and rough skin on the head, neck, and limbs. There were multiple enlarged lymph nodes in the right armpit and on both sides of the groin. The largest node was ~4 cm in diameter with a smooth surface and was non-tender and mobile. The laboratory findings are presented in
After two courses of chemotherapy, a CT showed that the patient's lymph nodes were smaller than before (
Although this patient had obvious skin symptoms, the pathological results and immunohistochemical analysis n his initial admission were consistent with a diagnosis of CHL. However, the patient's pruritic symptoms worsened after ABVD chemotherapy. Therefore, a lymph node pathology examination was repeated. Finally, the patient was diagnosed as having a composite of lymphocyte-rich type HL and AITL.
AITL is a specific subtype of PTCL that originates from T follicular helper (TFH) cells and is often accompanied by fever, night sweats, weight loss, lymphadenopathy, skin rash, and other clinical manifestations (
Although the diagnosis of AITL relies on lymph node biopsy, certain patients may not be diagnosed until after 2–3 lymph node biopsies (
There is a strong correlation between AITL and EBV infection. EBV-infected B-cells can transmit EBV protein signals on their surface to T-cells via major histocompatibility complex II molecules when TFH cells interact with B-cells, which upregulate the expression of CD ligands, provide antigen and costimulatory signals for activation of T-cells, promote the secretion of the chemokine CXCL13 (
The 2008 edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues mentions RS-like cells being seen in early AITL for the first time (
AITL is frequently misdiagnosed given its nonspecific clinical and histologic findings. A summary of a review of the literature on the misdiagnosis of AITL is shown in
In conclusion, AITL is a specific subtype of peripheral T-cell lymphoma that is challenging to diagnose. Moreover, treatment is often delayed by misdiagnosis. The present case underscores the importance of early and accurate diagnosis of AITL and the potential for a poor prognosis. More than one pathological examination should be performed to reduce the risk of misdiagnosis. Clinical phenotype, lymph node biopsies, immunohistochemistry, and gene rearrangement analyses should all be considered for early and accurate diagnosis and appropriate treatment.
Not applicable.
The datasets used and/or analyzed during the current research are available from the corresponding author on reasonable request.
YL conceived and designed the study. XG collected the data and wrote the manuscript. LK treated the patient and contributed to draft and revise the manuscript. JL advised on patient treatment and participated in revising the manuscript. YL, XG, LK and JL confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.
Not applicable.
This report was published with the written consent of the patient's relatives.
The authors declare that they have no competing interests.
angioimmunoblastic T-cell lymphoma
classical Hodgkin lymphoma
Epstein-Barr virus
Hodgkin lymphoma
peripheral T-cell lymphoma
Reed-Sternberg
T follicular helper
Flow cytometry results for bone marrow. (A) CD19+ lymphocytes (group D) account for 0.2% of nuclear cells. (B) CD3+ lymphocytes (group C) account for 96.1% of all nuclear cells. (C-F) Positive expression of CD3 and CD5, partial expression of TCRrd, and limited expression of CD8.
CT images of and enlarged lymph node. (A) Cross section, (B) sagittal plane, and (C) coronal plane images. Red arrows indicate lymph nodes. The images before chemotherapy are shown on the left and the images following chemotherapy are shown on the right.
Immunostaining of the right inguinal lymph node for cytokines. (A) HE staining ×40 magnification; (B) HE staining, ×100 magnification; (C) BCL-6 negative staining, ×100 magnification. (D) CD3 positive staining, ×100 magnification. (E) CD20 positive staining, 100× magnification. (F) CD21 staining negative, ×100 magnification. (G) CXCL13 negative staining, ×100 magnification. (H) Ki-67 positive staining, ×100 magnification. (I) MUM-1 positive staining, ×100 magnification. (J) PAX-5 positive staining, ×100 magnification. (K) PD-1 positive staining, ×100 magnification. (L) EBER (molecular diagnosis) positive staining. Based on (A and B), the structure of the lymph node was partially destroyed, with scattered atypical large cells, rich cytoplasm, large nuclei, with some cells possessing some double nuclei and larger nucleoli. There were T-cell lymphomas in multiple lymph nodes, and certain lymph nodes also contained focal classical Hodgkin's lymphoma. HE, hematoxylin-eosin.
CT images of pulmonary infection. (A) Cross section, and (B) coronal planes. The images after two courses of chemotherapy are shown on the right. The patient had a severe pulmonary infection and extensive exudation.
Results of laboratory findings on admission.
Laboratory indicator | Normal range | Result |
---|---|---|
CBC | ||
WBC, ×109/l | 3.5-9.5 | 15.00 |
LY, ×109/l | 1.1-3.2 | 5.12 |
HGB, g/l | 115-150 | 151 |
PLTx109/l | 125-350 | 292 |
β2-microglobulin, µg/ml | 0.9-2.7 | 4.288 |
Biochemistry | ||
TP, g/l | 65-85 | 53.5 |
GLO, g/l | 20-40 | 22.3 |
LDH, U/l | 120-250 | 323.9 |
HBDH, U/l | 72-182 | 222.4 |
TG, mmol/l | 0.1-1.7 | 1.84 |
Coombs test | ||
Direct Coombs test | Negative | |
Indirect Coombs test | Negative | |
Tumor Marker | ||
CA 125, U/ml | 0-35 | 125.100 |
VEGF, pg/ml | 0-142 | 178.4 |
CBC, complete blood count; WBC, white blood cell; LY, lymphocyte cell; HGB, hemoglobin; PLT, plate; TP, total protein; GLO, globulins; LDH, lactate dehydrogenase; HBDH, GHB dehydrogenase; TG, triglyceride; VEGF, vascular endothelial growth factor.
Literature review of misdiagnosis of AITL.
First author/s, year | Age, years | Sex | Misdiagnosis | Method leading to misdiagnosis | Method of diagnosis | (Ref.) |
---|---|---|---|---|---|---|
van den Akker and Chen, 2021 | 62 | M | Reactive lymphadenopathy | FNA | Excisional biopsy | ( |
Ellis |
72 | F | DLBCL | LN biopsy | Reexamination, IHC | ( |
Keefe |
65 | M | DRESS syndrome | clinical signs and symptoms, PET-CT | LN biopsy | ( |
Trimech |
62 | M | Richter syndrome | PET-CT, BM uptake | LN biopsy | ( |
Papadi |
55 | F | SPBIP | LN biopsy and BM aspirate | LN biopsy, clonal TCR gene rearrangement | ( |
70 | F | SPBIP | Clinical and morphologic features | Flow cytometry and gene rearrangement | ||
Smithberger |
79 | F | Inflammatory dermatosis | Skin biopsy | LN biopsy | ( |
Ahsanuddin |
76, 46, 60 | F, F, F | Plasma cell leukemia | Smear morphology and manual differential of peripheral blood | LN biopsy and BM biopsy | ( |
Han |
70 | M | Drug fever and allergic purpura, septicemia | Medication history, surgery history | LN biopsy | ( |
Kaffenberger |
59, 68 | M, M | MALT | Skin biopsy | LN biopsy | ( |
Szablewski |
41, 60, 67 | M, M, M | CHL, B cell lymphoma | Skin biopsy | A second review of the skin biopsy, LN biopsy | ( |
Suárez, 2016 | 77 | F | Marginal-zone B-cell-lymphoma | Skin biopsy | Skin biopsy, LN biopsy | ( |
Laforga, 2010 | 58 | M | HL | Autoimmune phenomena | Touch imprints of LN biopsy | ( |
M, male; F, female; LN, lymph node; FNA, fine-needle aspiration; DLBCL, diffuse large B-cell lymphoma; LN, lymph node; IHC, immunohistochemical staining; DRESS syndrome, drug reaction with eosinophilia and systemic symptoms; PET-CT, positron emission tomography-computed tomography; BM, bone marrow; SPBIP, systemic polyclonal B-immunoblastic proliferation; MALT, marginal zone lymphoma; CHL, classical Hodgkin lymphoma; ATLL, adult T-cell leukemia/lymphoma.