Efficacy of involved-site radiotherapy in addition to systemic therapy for angioimmunoblastic T-cell lymphoma: a case report and literature review

Introduction

Angioimmunoblastic T-cell lymphoma (AITL), a rare and aggressive subtype of mature T-cell lymphoma (MTCL)—previously classified as peripheral T-cell lymphoma (PTCL)—exhibits a varied clinical presentation (1-3). Epidemiological studies in the United States and Taiwan report that MTCLs constitute 6.7% and 17.3% of non-Hodgkin lymphomas (NHL), respectively (3,4). Globally, AITL is the second most common subtype of MTCL, comprising 18% of cases (5). In Taiwan, AITL predominates as the most frequent MTCL subtype, accounting for 18.3% of cases (6). A retrospective study conducted from 1990 to 2002 determined that the 5-year progression-free survival (PFS) and overall survival (OS) rates for patients with AITL were 18% and 32%, respectively (7). Patients with ATIL often present with B symptoms and generalized lymphadenopathy; bone marrow involvement and hepatosplenomegaly are also commonly observed (5). Skin manifestations of AITL range from urticarial lesions to nodular tumors, although cutaneous involvement remains rare (8).

No standard treatment currently exists for AITL; however, anthracycline-based chemotherapy regimens—such as cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone (CHOEP) administered over six cycles—are commonly employed, with or without consolidation therapies such as autologous stem cell transplantation (ASCT) or involved-site radiotherapy (ISRT) (7,9-13). In a prospective study spanning 2006–2018, anthracycline-based regimens, with or without consolidative ASCT, resulted in 5-year PFS and OS rates of 32% and 44%, respectively, for patients with AITL (11). However, the role of radiotherapy (RT) in local progression and isolated recurrent AITL remains uncertain. This report presents a case of AITL managed with several lines of systemic chemotherapy and ISRT for local progression of metastatic elbow lesions and an isolated recurrent tongue base lesion. The patient achieved complete remission (CR) of the AITL lesions, experienced only grade 1–2 toxicities after ISRT, and has remained in CR for 26 and 8 months, respectively, after RT. We present this article in accordance with the CARE reporting checklist (available at https://tro.amegroups.com/article/view/10.21037/tro-25-18/rc).

Case presentation

A 78-year-old man with chronic kidney disease (CKD), hepatitis B, colon cancer, and type 2 diabetes mellitus presented with persistent sore throat, muffled voice, odynophagia, sensation of a lump in the throat, dysphagia, and bilateral prominent neck lymphadenopathies with a Karnofsky score of 90. During initial laboratory assessment, we found mild leukocytosis [white blood cell (WBC): 11.12×10³/µL, with left shift; segment: 82.7%], normal lactate dehydrogenase and liver function, but decreased renal function consistent with his CKD history. He underwent a computed tomography (CT) scan for staging, which showed bilateral tonsil swelling and prominent lymphadenopathies at bilateral neck levels II, III, IV, and V, although positron emission tomography-CT (PET-CT) scan was not performed.

A core needle biopsy of the left neck level IIA lymph node revealed atypical lymphoid infiltration. Bilateral tonsillectomy was subsequently performed, with pathology indicating atypical lymphoid hyperplasia. Serum immunofixation electrophoresis (IFE) showed decreased albumin, elevated alpha-1 and beta-2 globulins, and polyclonal gammopathy. Due to inconclusive pathological results, partial excision of the tongue base tumor and right selective neck dissection were conducted. Histological examination revealed atypical small- to medium-sized lymphoid cells with irregular nuclei and scant cytoplasm. These cells showed loose infiltration with occasional vague nodular patterns. Eosinophils were frequently present, and focal hyperplastic blood vessels were observed. Immunohistochemically demonstrated that the cells were positive for CD3, CD4, and programmed death receptor-1 (PD-1); focally positive for CD8; scattered positive for CD10; and negative for CD20. Some immunoblasts expressed CD30, while few cells were positive for Epstein-Barr virus-encoded small RNA 1 (EBER-1) by in situ hybridization. These histological and immunophenotypic features were consistent with AITL, a subtype of nodal T follicular helper cell lymphoma (nTFHL) currently designated as nTFHL, angioimmunoblastic type, according to the World Health Organization (WHO) Classification of Hematolymphoid Tumors (HAEM5-2022 classification) (14).

A bone marrow examination revealed no evidence of lymphoma involvement. Serum IFE levels did not indicate monoclonal gammopathy. Laboratory data showed immunoglobulin G (IgG): 2,220.00 mg/dL, IgA: 648.00 mg/dL, IgM: 100.00 mg/dL, and beta-2 microglobulin: 8.97 mg/L. After staging work-up, stage IIE AITL was diagnosed, and six cycles of mini-CHOEP chemotherapy were administered. Hepatitis B was detected in a screening test conducted before chemotherapy, and entecavir was prescribed. PET-CT performed 3 months after completion of six courses of chemotherapy revealed new or progressive metabolic lesions in the right palate, oropharynx [standardized uptake value maximum (SUV_max) =6.0], left posterior cervical nodes (SUV_max =4.7), left mid-clavicle (SUV_max =3.5), and soft tissue in the bilateral lower legs (SUV_max =2.1) (PET 5-point scale =5). Multiple skin lesions were also observed on the extremities and trunk. Pralatrexate was initiated one month later for three cycles; however, skin nodules emerged at multiple sites. A PET-CT performed 2 months later showed lymphoma involving lymph nodes above and below the diaphragm (SUV_max =4.2) as well as suspicious involvement of the skin and soft tissues in the bilateral thighs and lower legs (SUV_max =2.5). A skin biopsy from the right inner thigh confirmed AITL with skin involvement, characterized by diffuse CD30 positivity in atypical lymphocytes. Treatment with single-agent bendamustine was administered for five cycles. A subsequent PET-CT scan revealed progressive skin lesions on the right elbow (SUV_max =2.6), while other metastatic lesions remained stable (Figure 1A). Physical examination of the right elbow identified two erosional lesions with diameters of 1.5 and 2 cm (Figure 1B). Biopsy of the cutaneous lesions demonstrated diffuse infiltration of small- to medium-sized lymphocytes, histiocytes, and scattered eosinophils into the dermis. Immunohistochemical analysis showed the atypical lymphoid cells to be predominantly positive for CD3, CD4, and PD-1, focally positive for CD10 and CD30 (approximately 20%), and negative for Epstein-Barr virus in situ hybridization, consistent with AITL. Chemotherapy with gemcitabine and oxaliplatin was administered for two cycles; however, elbow lesions were stationary in size.

Figure 1 Imaging and clinical outcomes of the presented case. (A) A PET-CT scan shows increased uptake at the skin of the right elbow (SUV_max =2.8) (white arrow), while the intense area in the right posterior nasopharynx is suspected to represent acute inflammation. (B) Skin lesions presented as protruded, warm, red, and erosive masses. (C) Dose distribution for the convex surface area of the tumors using a single field of 6 MV photons with a 1.0 cm bolus covering the skin surface. (D) Reduction in tumor size and desiccation of the lesions on fraction 15/15, day 19 of radiotherapy. (E) A PET-CT scan shows complete remission 3 months after completing radiotherapy. (F) Complete remission was achieved without adverse effects 3 months after completing radiotherapy. PET-CT, positron emission tomography-computed tomography; SUV_max, standardized uptake value maximum.

ISRT to the right elbow was prescribed at 40.05 Gy in 15 fractions using a single-photon field with a 1.0 cm bolus to increase the surface dose. The gross tumor volume (GTV) was defined by wiring the lesion during simulation and contouring the high-density tissue on the simulation CT. A 2.5 cm margin was added to generate the field (Figure 1C). By the final day of RT, the lesions had reduced and dried out (Figure 1D). The skin lesions achieved CR on follow-up PET-CT [no fluorodeoxyglucose (FDG)-avid lesions, Deauville score =1] 3 months after completion of RT, except for acute grade 2 dermatitis observed during RT (Figure 1E,1F). A follow-up PET-CT one year later revealed relapsed lymphoma at the right tongue base, with histology and immunohistochemistry of the biopsy showing medium-sized lymphoid cells and scattered EBER-positive cells, favoring AITL (SUV_max =6.2) (Figure 2A). The patient underwent ISRT for an FDG-avid lesion at the tongue base with 37.5 Gy in 15 fractions, using a volumetric modulated arc therapy technique, and experienced grade 1–2 mucositis (Figure 2B). The clinical target volume (CTV) included the FDG-avid region, with a 0.5 cm margin added to create planning target volume (PTV) (Figure 2C). CR of the tongue base lesion was achieved 2 months after RT completion with no FDG-avidity in follow-up PET-CT scan (Figure 2D). The patient maintained CR of the right elbow and tongue base lesions at 26 and 8 months, respectively, with no FDG-avid lesions on follow-up PET-CT (Deauville score =1) after RT. At 52 months post-AITL diagnosis, the patient remained alive with stable lymphadenopathies in the left lower cervical nodes (SUV_max =3.32) and mediastinal lymph nodes (SUV_max =3.71) (Figure 3).

Figure 2 Clinical manifestations and treatment characteristics for locally relapsed tongue base AITL. (A) Persistent avid FDG uptake at the tongue base (current/prior SUV_max =5.9/6.2) (white arrow). (B) Involved-site radiotherapy for the tongue base lesion using a partial arc volumetric modulated arc therapy technique, prescribed at 37.5 Gy in 15 fractions. Axial views illustrate the dose distribution of radiotherapy for the tongue base lesion. (C) Cumulative dose volume histogram of radiotherapy plan for the tongue base lesion. (D) Follow-up PET scan showing complete remission of tongue base lymphoma, with normal physiological uptake in the palate, bilateral tonsils, mouth floor, and salivary glands. AITL, angioimmunoblastic T-cell lymphoma; DVH, dose volume histogram; FDG, fluorodeoxyglucose; PET, positron emission tomography; SUV_max, standardized uptake value maximum.

Figure 3 The timeline of this patient who received chemotherapy, and involved-site radiotherapy is illustrated in the schema. CHOEP, cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone; CR, complete remission; PD, progressive disease; PET, positron emission tomography; RT, radiotherapy.

Ethical considerations

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Only a few reports have examined the effects of RT after systemic chemotherapy for localized AITL. Xiong et al. described a patient with AITL treated with eight cycles of CHOP chemotherapy, followed by RT to the neck lymphatics at 36 Gy in 18 fractions using tomotherapy; this patient remained lymphoma-free for at least 31 months (15). In a nationwide population-based cohort study assessing first-line combined modality therapy for stage IE PTCL—including anaplastic large cell lymphoma (ALCL), AITL, and PTCL not otherwise specified (PTCL-NOS)—Meeuwes et al. demonstrated that combined therapy (chemotherapy plus RT) provided a better 5-year OS compared with chemotherapy or RT alone (72% vs. 55% and 55%, respectively; P<0.01) (16). These reports align with prior findings indicating enhanced survival with additional RT following chemotherapy in localized-stage PTCL-NOS and ALCL (16-21) (Table 1).

In contrast to the few reports on ISRT in AITL, several studies have demonstrated that ISRT for cutaneous lesions offers better local control and fewer comorbidities in patients with ALCL (22-24). In a retrospective analysis of 56 patients with 63 cutaneous ALCL lesions treated with either definitive RT or RT after surgery, CR was achieved in 60 lesions and partial remission (PR) in 3, with a median RT dose of 35 Gy (range, 6–45 Gy) (22). We previously reported that among nine patients with primary cutaneous ALCL (five stages Ia, 1Ib, and three IIa) who received ISRT with a median dose of 40 Gy (36–50.4 Gy), seven achieved CR and one achieved PR, with all patients experiencing grade 1–2 dermatitis (23). Similarly, Piccinno et al. reported that RT achieved CR in 29 of 30 patients (96.7%) with primary cutaneous ALCL (55 RT fields) treated with a median dose of 25 Gy (range, 15–35 Gy). After a median follow-up of 38.5 months, the local control rate was 85% and the 5-year relapse-free survival rate was 49% (24).

The efficacy of ISRT for local progression or isolated recurrent or metastatic AITL lesions has not been reported. Two case reports, however, describe the effects of local RT in refractory AITL. Fabbri et al. documented a patient with AITL who received three lines of conventional chemotherapy and inguinal RT during third-line treatment but remained refractory; CR was achieved only after six courses of lenalidomide, which was sustained for 30 months with continuous administration (25). Zhu et al. reported a case of a refractory AITL in which chemotherapy with CHOP and second-line GEMOX (gemcitabine and oxaliplatin) failed. Subsequent treatment with CHOEP combined with lenalidomide, followed by ISRT (50 Gy in 15 fractions to the bilateral parotid glands and cervical lymph nodes using intensity-modulated radiation therapy), although relapse occurred one year later, chidamide and cyclosporine followed by chidamide as maintenance achieved long-term disease control, with the patient remaining lymphoma-free for more than 70 months (26).

Distinct from other case series, our case applied ISRT to two separate sites—one metastatic progressive elbow lesion and one relapsed tongue base lesion—after several lines of systemic chemotherapy, achieving CR with long-term local control and minimal toxicity. The commonly recommended dose for refractory aggressive lymphoma lesions is 40–50 Gy in 2 Gy per fraction [biologically effective dose (BED) =48–60 Gy, α/β =10] (27). In our case, we prescribed 40.05 Gy in 15 fractions (BED =50.7 Gy, α/β =10) for elbow lesions and 37.5 Gy in 15 fractions (BED =46.9 Gy, α/β =10) for the tongue lesion, which provides a similar BED to the conventional RT schedule for refractory lymphoma while shortening overall treatment time. This mild hypofractionation of ISRT was chosen to maintain efficacy and may help reduce long-term toxicity while improving patient convenience.

For patients with localized PTCL, including AITL, ISRT after chemotherapy may serve as an effective first-line therapy; however, randomized trials confirming the role of consolidative ISRT are lacking (Table 1). Importantly, this report demonstrates that ISRT can provide effective disease control even in cases of local relapse outside the initial primary site after systemic chemotherapy.

Conclusions

This case underscores the potential of ISRT to effectively control focal progression and relapse of AITL. Evidence from the literature review and this case suggests that ISRT following chemotherapy may enhance PFS in patients with localized AITL. In addition, ISRT offers optimal local control and minimal toxicity, reducing the need for toxic systemic treatments in patients experiencing local progression and relapse of AITL.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tro.amegroups.com/article/view/10.21037/tro-25-18/rc

Peer Review File: Available at https://tro.amegroups.com/article/view/10.21037/tro-25-18/prf

Funding: This work was supported by the National Taiwan University Hospital, Taiwan (No. NTUH 14-SS0027).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tro.amegroups.com/article/view/10.21037/tro-25-18/coif). S.H.K. serves as an unpaid Associate Editor-in-Chief of Therapeutic Radiology and Oncology from August 2025 to December 2027. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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