Abstract
Background:
Classical Hodgkin lymphoma (cHL) is a B-cell malignancy that typically presents with painless lymphadenopathy and constitutional symptoms. Extranodal involvement is uncommon, particularly within the nervous system. Simultaneous neural foraminal extension with spinal canal infiltration and great-vessel encasement is exceptionally rare.
Case presentation:
A 44-year-old man presented with fever, dyspnea, neck swelling, fatigue, and right upper limb neuropathic pain suggestive of C7–T1 radiculopathy. Imaging revealed a large anterior mediastinal mass encasing the aortic arch with associated cervical and mediastinal lymphadenopathy. Core biopsy was non-diagnostic due to fibrosis, while excisional lymph node biopsy confirmed classical Hodgkin lymphoma, nodular sclerosis subtype with CD15+, CD30+ immunophenotype. Bone marrow biopsy showed no lymphomatous involvement. HIV testing was negative. FDG PET/CT demonstrated hypermetabolic cervical and mediastinal disease with extension into the C7–T1 neural foramina and spinal canal, along with T1 vertebral body osseous involvement, consistent with Stage IVB disease (IPS score: 2). The patient achieved complete metabolic response following six cycles of ABVD chemotherapy without surgical decompression or radiotherapy.
Discussion:
Neurological manifestations of cHL are rare and usually result from direct extension into adjacent neural structures. This case illustrates the diagnostic challenges associated with atypical presentations, particularly when neurological symptoms coexist with mediastinal disease. It highlights the limitations of core needle biopsy in fibrotic lesions and reinforces the importance of excisional biopsy.
Conclusion:
This case expands the spectrum of recognized presentations of cHL by documenting a rare concurrent presentation of great-vessel encasement, neural foraminal extension, and vertebral osseous involvement as an initial manifestation. The diagnostic challenges posed by fibrotic lesions underscore the critical importance of excisional biopsy for definitive diagnosis. Clinicians should maintain a high index of suspicion for lymphoma in the differential diagnosis of mediastinal masses associated with radiculopathy and recognize that chemotherapy alone achieves excellent outcomes even in cases with apparent neural compromise.
Introduction
Hodgkin lymphoma (HL) is a B-cell malignancy defined histologically by a small population of malignant Reed–Sternberg cells embedded in an extensive background of reactive immune effector cells. Although it can arise at any age, its incidence peaks in adolescents and young adults, and most patients are diagnosed in their twenties and thirties. The characteristic presentation is supradiaphragmatic lymphadenopathy, often accompanied by systemic “B” symptoms such as fever, drenching night sweats, and weight loss ().
It accounts for roughly 11% of all lymphomas and is divided into two distinct entities: classical Hodgkin lymphoma (cHL) and nodular lymphocyte-predominant Hodgkin lymphoma. Classical HL, which constitutes the large majority of cases, is further subclassified into nodular sclerosis, mixed cellularity, lymphocyte-depleted, and lymphocyte-rich subtypes (). The diagnosis rests on histological and immunohistochemical examination of an adequately sampled lymph node. Because Reed–Sternberg cells are sparse and may be obscured by reactive fibrosis, a generous tissue sample, ideally an excisional biopsy, is often required to secure the diagnosis ().
Extranodal disease—lymphomatous infiltration of sites other than lymph nodes—is considerably less common in HL than in non-Hodgkin lymphoma and tends to accompany advanced disease (). When it does occur, its non-specific clinical and radiological features can closely mimic other benign or malignant processes, making recognition difficult. Virtually any organ may be affected, but the most frequently involved extranodal sites are the lung, bone, liver, and bone marrow. FDG PET/CT substantially improves the detection of extranodal involvement and is the standard modality for initial staging (using the Lugano classification), follow-up, and response assessment ().
Neurological involvement in HL is rare (occurring in <0.5% of cases at onset) and typically results from invasion of the vertebral canal with spinal cord compression or from involvement of peripheral nerves via direct extension from paravertebral lymph nodes (). We describe a middle-aged man with classical Hodgkin lymphoma who presented with a bulky anterior mediastinal mass encasing the aortic arch and supra-aortic branches together with infiltration of the C7–T1 neural foramina and spinal canal, producing neurological symptoms as an early, presenting feature. To our knowledge, based on a structured review of the literature, the simultaneous combination of great-vessel encasement and neural foraminal extension is exceptional and posed a considerable diagnostic challenge.
Case presentation
Clinical presentation and neurological evaluation
A 44-year-old man with an unremarkable past medical history presented with a 25-day history of flu-like symptoms, including fever (38.5 °C), generalized fatigue, drenching night sweats, and unintentional weight loss (collectively referred to as B symptoms), all of which interfered with daily activities. He additionally reported orthopnea, progressive neck swelling, and right shoulder pain accompanied by numbness, tingling, and a burning sensation radiating along the right shoulder and arm. Empirical antibiotics and symptomatic measures produced no improvement.
A detailed neurological examination revealed palpable cervical lymphadenopathy together with weakness and altered sensation in the right upper limb. Specifically, motor grading demonstrated 4/5 weakness in right elbow extension, wrist flexion, and finger extension. Sensory examination revealed decreased pinprick and light touch sensation along the medial aspect of the right forearm and ulnar half of the hand. The right triceps reflex was 1+ (hypoactive) compared with 2+ on the left (normal). There was no evidence of myelopathy (no hyperreflexia, negative Babinski sign, normal sphincter tone), indicating radiculopathy rather than true cord compression. The findings were consistent with a right C7–T1 radiculopathy. Electrodiagnostic studies (nerve conduction studies and electromyography) were not performed because the MRI findings and clinical examination were considered sufficient to establish cervical radiculopathy secondary to direct neural foraminal invasion.
Laboratory and pathological findings
Initial laboratory testing showed a markedly elevated erythrocyte sedimentation rate (ESR) of 95 mm/h (normal < 10 mm/h). Complete blood count (CBC), lactate dehydrogenase (LDH), albumin, C-reactive protein (CRP), renal function, and liver function tests were all within normal limits.
A core biopsy of the mediastinal mass demonstrated only dense fibrosis with a rim of reactive lymphocytes and no Hodgkin cells (Figure 1A), establishing the non-diagnostic nature of the core biopsy. Subsequently, an excisional biopsy of an axillary lymph node established the diagnosis of classical Hodgkin lymphoma, nodular sclerosis subtype. Histopathological examination revealed broad bands of collagen dividing the lymphoid tissue into nodules (Figure 1B, H&E 10x). Within these nodules, numerous neoplastic lacunar-type Reed-Sternberg cells were identified in a background of small lymphocytes, eosinophils, and histiocytes (Figure 1B, H&E 40x). Immunohistochemical staining confirmed the malignant cells were strongly positive for CD15 (Figure 1C) and CD30 (Figure 1D), weakly positive for PAX5 (Figure 1E), and negative for CD20 and CD45. (Note: CD20 staining was non-contributory as it was completely negative, and therefore representative images are not included in the figure panel). Epstein-Barr virus in situ hybridization (EBER-ISH) was not performed as this testing modality is not available at our institution. Bone marrow biopsy was performed and showed no evidence of lymphomatous involvement, confirming the absence of bone marrow infiltration. HIV testing was performed and was negative, ruling out HIV-associated lymphoma.
Figure 1
Imaging and staging
A chest radiograph initially revealed a mediastinal mass, prompting contrast-enhanced CT, which identified a well-defined anterior mediastinal mass measuring 10.7 × 7.2 cm that encased the aortic arch and supra-aortic branches. To further evaluate the neurological symptoms, MRI of the cervical and thoracic spine was performed, demonstrating an epidural soft tissue mass extending through the right C7-T1 neural foramen with mild to moderate spinal canal compromise, but without definitive spinal cord compression or intramedullary signal abnormality.
Staging fluorodeoxyglucose PET/CT (Figure 2) demonstrated intensely hypermetabolic bilateral cervical lymphadenopathy (SUVmax 12.6), the largest node on the right infiltrating the C7–T1 neural foramina and extending into the spinal canal. Additionally, a hypermetabolic anterior mediastinal mass involved the para-aortic and prevascular regions. Notably, there was focal increased FDG uptake corresponding to a lytic lesion with surrounding sclerosis in the T1 vertebral body, consistent with direct osseous involvement rather than mere reactive change.
Figure 2
Based on the Lugano classification, the patient was diagnosed with Stage IVB classical Hodgkin lymphoma due to the presence of true extranodal disease (vertebral body involvement) and B symptoms. The International Prognostic Score (IPS) () was 1 (male sex, Stage IV), indicating a favorable prognosis. The age criterion (age ≥45 years) did not apply as the patient was 44 years old.
Treatment and clinical course
Baseline echocardiography showed normal cardiac function with an ejection fraction of 67%. Given the absence of true cord compression or rapidly progressive neurological deficits, upfront chemotherapy was selected over surgical decompression or emergent radiotherapy.
The patient received six cycles of standard ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine) administered on days 1 and 15 of a 28-day cycle. He experienced progressive improvement in his motor and sensory symptoms over the course of treatment. An interim PET/CT after the second cycle demonstrated complete metabolic response (Deauville score 2), prompting the omission of bleomycin for the remaining four cycles (AVD) to minimize pulmonary toxicity, in accordance with current guidelines (). The treatment was well-tolerated with no reported severe adverse events, and no growth factor support was required.
By the end of treatment, the patient had regained full strength (5/5) and normal sensation in the right upper limb. Serial follow-up PET/CT examinations demonstrated an excellent and sustained treatment response. The anterior mediastinal mass progressively regressed from 10.7 × 7.2 cm at baseline to 4.5 × 1.9 cm at end of treatment (Figure 5), followed by a small inactive para-aortic soft-tissue residue measuring 3.7 × 1.3 cm at 18 months (Figure 6), consistent with post-treatment fibrosis. The most recent PET/CT confirmed ongoing complete metabolic remission. The baseline PET/CT, representative histopathology, end-of-treatment PET/CT, and 18-month follow-up PET/CT findings are shown in Figures 3–6. A longitudinal summary of staging, treatment, and serial PET/CT response is provided in Table 1.
Figure 3
Figure 4
Figure 5
Figure 6
Table 1
| Date | Key imaging findings | Clinical response |
|---|---|---|
| Baseline (Mar 2024) | Anterior mediastinal mass (10.7 × 7.2 cm) encasing aortic arch; cervical nodes infiltrating C7–T1 foramina and spinal canal; T1 osseous involvement | Diagnosis (cHL, Stage IVB); ABVD started |
| Interim (May 2024) | Cervical, mediastinal and spinal disease metabolically resolved; mass regressed to 8.3 × 3 cm (SUVmax 2.7–3) | Complete metabolic response (Deauville 2); Bleomycin omitted |
| End of treatment (Sep 2024) | Mass confined to para-aortic region, 4.5 × 1.9 cm, minimal uptake | Sustained response; presumed fibrosis; Neurological recovery |
| Follow-up (Dec 2024) | Mass 4.1 × 1.5 cm, no uptake; new hepatic hilar nodes (SUVmax 6.7) | Indeterminate hepatic nodes (reactive) |
| Follow-up (Apr 2025) | Mass sTable 4.1 × 1.3 cm, inactive; hepatic nodes resolved | Sustained remission |
| Follow-up (Aug 2025) | Para-aortic residue sTable 3.7 × 1.3 cm, inactive | Sustained complete metabolic response |
| Follow-up (Dec 2025) | No hypermetabolic disease; normal cervical and mediastinal findings | Ongoing complete remission (18 months) |
Summary of staging, treatment, and serial PET/CT response.
Discussion
This case demonstrates an exceptionally rare presentation of classical Hodgkin lymphoma in which a bulky anterior mediastinal mass simultaneously encased the great vessels and infiltrated the adjacent neural foramina and spinal canal, producing neurological symptoms as the initial manifestation of disease. Extranodal involvement in cHL is relatively uncommon compared with non-Hodgkin lymphoma and generally signals advanced disease ().
Structured literature review
To contextualize the rarity of this presentation, we conducted a structured literature review of PubMed/MEDLINE and Google Scholar databases using the search terms (“Hodgkin lymphoma” OR “classical Hodgkin lymphoma”) AND (“spinal cord” OR “neural foraminal” OR “epidural”) AND (“mediastinal mass” OR “aortic arch”). The search was limited to publications from 1985 through June 2026 and included English-language articles. The search identified 47 records. After screening titles and abstracts, 16 full-text articles were reviewed, of which 13 met inclusion criteria and are summarized in Table 2. While neurological involvement in HL has been documented, it is typically a late complication resulting from paravertebral extension of nodal disease (). Our search identified no previously published cases describing the concurrent combination of aortic arch encasement, neural foraminal extension, and vertebral osseous involvement as the presenting manifestation of classical Hodgkin lymphoma, making this case exceptionally rare and clinically instructive. Published reports of extranodal classical Hodgkin lymphoma involving the spinal cord further underscore the rarity of this neurological presentation ().
Table 2
| Author (year) | Sex | Age | Neurological manifestations | Site of involvement | Imaging findings | Treatment | Outcome | Follow-up |
|---|---|---|---|---|---|---|---|---|
| Lyding et al. (1987) | F | 32 | Intraspinal tumor | C6-C7 | Intraspinal mass | Mantle RT + MOPP | CR | 5 years |
| Higgins et al. (1995) | M | 46 | Spinal cord compression | C5-T8 | Intraspinal, extradural mass | Laminectomy + MOPP-ABV + RT | CR | 21 months |
| Jardin et al. (1999) | F | 36 | Spinal cord involvement | C8-T1 | Intraspinal tumor | Intrathecal chemo | Death | 2 months |
| Riffaud et al. (2003) | M | 14 | Lumbar spinal lesion | Lumbar | Lumbar mass | Surgery + AVD + RT | CR | 1 year |
| Heran et al. (2006) | M | 42 | Lower cervical mass | Cervical | Spinal mass | Surgical biopsy + ABVD | CR | End of treatment |
| Al Khayat et al. (2007) | F | 42 | Paraspinal mass | C7-T1 | Paraspinal mass | Cervical biopsy + ABVD + RT | CR | 12 months |
| Samadian et al. (2009) | M | 12 | Epidural mass | L1-L3 | Epidural mass | Laminectomy + ABVD + RT | CR | 7 years |
| Chotai et al. (2010) | M | 24 | Caudal mass | L5-S3 | Caudal mass | Laminectomy + ABVD | PR | 12 months |
| Yaman et al. (2013) | M | 30 | Epidural tumor | T9-T11 | Epidural mass | Laminectomy + ABVD | CR | 24 months |
| Martinez et al. (2014) | F | 74 | Intramedullary mass | Lumbar/pontomedullary | Multiple lesions | Surgical biopsy + RT | CR | 6 months |
| Williamson et al. (2020) | F | 48 | Two spinal lesions | L1-L2, L5-S1 | Spinal masses | Laminectomy + RT | CR | 10 months |
| Bloxham et al. (2021) | F | 15 | Epidural mass | L3-L5 | Epidural mass | Surgical decompression + OEPA/COPDAC + RT | PR | Before RT |
| Current case | M | 44 | C7-T1 radiculopathy with foraminal/spinal extension | C7-T1 foramina, spinal canal, T1 vertebral body | Mediastinal mass with aortic arch encasement | ABVD/AVD | CMR | 18 months |
Summary of published classical Hodgkin lymphoma cases with neurological involvement.
Diagnostic challenges
The radiological differential diagnosis for a mediastinal mass with neural foraminal extension is broad, including neurogenic tumors (schwannoma, neurofibroma), thymoma, germ-cell tumors, and primary mediastinal large B-cell lymphoma. The early neurological presentation in our patient initially suggested a primary neurogenic process. Furthermore, encasement of the aortic arch by cHL has been described only sporadically, and the concurrence of vascular encasement with foraminal extension is exceptionally rare ().
Establishing the diagnosis required a multimodal approach. The initial core biopsy was non-diagnostic owing to extensive fibrosis, a hallmark of the nodular sclerosis subtype. This illustrates a well-recognized pitfall: dense fibrosis may obscure the sparse Reed-Sternberg cells in needle samples. Current NCCN and ESMO guidelines emphasize that an excisional lymph node biopsy remains the gold standard for diagnosing lymphoma (, ).
Imaging and management
PET/CT was pivotal both for staging (confirming Stage IVB disease via T1 vertebral involvement) and for distinguishing metabolically active disease from inert post-treatment fibrosis. Serial imaging demonstrated progressive shrinkage of the mediastinal mass with complete and durable metabolic resolution, allowing the persistent para-aortic residue to be confidently characterized as fibrotic, thereby avoiding unnecessary radiotherapy.
Therapeutically, the case reaffirms the efficacy of standard anthracycline-based chemotherapy. Following the RATHL trial paradigm, interim PET negativity after two cycles of ABVD allowed for the safe omission of bleomycin, reducing pulmonary toxicity risk while maintaining efficacy (). Despite the atypical presentation and neurological compromise, the patient attained complete metabolic remission without the need for surgical decompression or radiotherapy. This favorable course accords with the broadly excellent prognosis of cHL, indicating that an atypical anatomical presentation need not portend a worse outcome when diagnosed and treated promptly ().
Conclusion
This case expands the spectrum of recognized presentations of cHL by documenting a rare concurrent presentation of great-vessel encasement, neural foraminal extension, and vertebral osseous involvement as an initial manifestation of disease. The diagnostic challenges posed by fibrotic lesions, the limitations of core needle biopsy, and the critical importance of excisional biopsy for definitive diagnosis are highlighted. Furthermore, the case demonstrates that FDG PET/CT is essential for accurate staging and response assessment in atypical presentations. Clinicians should maintain a high index of suspicion for lymphoma in the differential diagnosis of mediastinal masses associated with radiculopathy and should recognize that chemotherapy alone can achieve excellent outcomes even in cases with apparent neural compromise. The complementary roles of adequate tissue sampling and functional imaging in establishing diagnosis and guiding risk-adapted therapy cannot be overstated.
Statements
Data availability statement
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.
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Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
RK: Investigation, Methodology, Visualization, Writing – original draft. AK: Conceptualization, Resources, Supervision, Validation, Writing – review & editing. RJ: Data curation, Project administration, Supervision, Writing – original draft. MS: Methodology, Project administration, Visualization, Writing – original draft. OB: Conceptualization, Formal analysis, Investigation, Writing – original draft. WA: Data curation, Validation, Visualization, Writing – original draft. EF: Data curation, Investigation, Software, Writing – original draft. HG: Conceptualization, Investigation, Methodology, Writing – original draft. MJ: Conceptualization, Data curation, Formal analysis, Writing – original draft.
Acknowledgments
The authors thank the Department of Pathology for histopathological analysis and the Department of Nuclear Medicine for imaging interpretation and support. We also acknowledge the contributions of all staff members at Hebron University Faculty of Medicine and Palestine Ahliya University who provided clinical care and technical support.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/frhem.2026.1914603/full#supplementary-material
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Summary
Keywords
ABVD chemotherapy, aortic arch encasement, classical Hodgkin lymphoma, extranodal involvement, nodular sclerosis, PET/CT, spinal canal infiltration
Citation
Khanfar RW, Jabari RA, S. Ahmad M, Bseiso O, Alhroub W, Fatouni E, Ghanim H, Jabareen M, Natsheh M and Khalili A (2026) Classical Hodgkin lymphoma presenting with aortic arch encasement and C7–T1 neural foraminal extension: a rare case report. Front. Hematol. 5:1914603. doi: 10.3389/frhem.2026.1914603
Received
20 June 2026
Revised
02 July 2026
Accepted
03 July 2026
Published
12 October 2026
Volume
5 - 2026
Edited by
Cherry Bansal, Tantia University, India
Reviewed by
Keisuke Ishizawa, Tokyo Metropolitan Neurological Hospital, Japan
Muneeb Khawar, King Edward Medical University, Pakistan
Updates
Copyright
© 2026 Khanfar, Jabari, S. Ahmad, Bseiso, Alhroub, Fatouni, Ghanim, Jabareen, Natsheh and Khalili.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Aliaa Khalili, aliaa.khalili@gmail.com
†These authors share first authorship
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.