Classical Hodgkin lymphoma is a malignancy of B cells, the antibody-producing lineage of the immune system, but it behaves unlike almost any other cancer. Histologically, it is defined by a striking paradox: the actual malignant cells — the Reed–Sternberg cells, named for their discoverers — make up only a tiny fraction of the tumor mass. The rest is an elaborate reactive background of immune effector cells, fibroblasts, and collagen that the malignant cells recruit and orchestrate. This is why Hodgkin lymphoma often feels like a swollen lymph node rather than an invading tumor, and why it typically announces itself with painless lymphadenopathy and so-called B symptoms: fever, drenching night sweats, and unintentional weight loss. It accounts for roughly 11 percent of all lymphomas, with incidence peaking in adolescents and young adults, and the classical form is further subdivided into nodular sclerosis, mixed cellularity, lymphocyte-depleted, and lymphocyte-rich subtypes.

What made this patient’s case so unusual was where the disease went. Extranodal involvement — lymphoma spreading beyond lymph nodes — is considerably less common in Hodgkin lymphoma than in non-Hodgkin lymphomas, and when it does occur it usually signals advanced disease. Neurological involvement is rarer still, appearing in fewer than 0.5 percent of cases at onset, and it typically arises late, when paravertebral lymph nodes extend directly into the vertebral canal or peripheral nerves. In this patient, the neurological symptoms were not a late complication but the presenting feature. His right arm weakness, numbness, and burning pain traced a precise neurological map: weakness in elbow extension, wrist flexion, and finger extension; reduced sensation along the medial forearm and ulnar half of the hand; and a hypoactive right triceps reflex. Together, these findings pointed squarely at a right C7–T1 radiculopathy — irritation of the nerve roots at the junction between the cervical and thoracic spine. Crucially, there were no signs of myelopathy, no hyperreflexia, no Babinski sign, and normal sphincter tone, indicating nerve-root involvement rather than true spinal cord compression.

The imaging told the rest of the story. A chest radiograph first revealed a mediastinal mass, and contrast-enhanced CT then characterized it in detail: a well-defined anterior mediastinal mass measuring 10.7 by 7.2 centimeters that had encased the aortic arch and its supra-aortic branches. MRI of the cervical and thoracic spine showed an epidural soft-tissue mass extending through the right C7–T1 neural foramen with mild to moderate spinal canal compromise, but without definitive cord compression or intramedullary signal abnormality. The decisive study was fluorodeoxyglucose PET/CT, which demonstrated intensely hypermetabolic bilateral cervical lymphadenopathy with a maximum standardized uptake value of 12.6, the largest right-sided node infiltrating the C7–T1 foramina and extending into the spinal canal. It also revealed something more ominous: focal FDG uptake in the T1 vertebral body corresponding to a lytic lesion with surrounding sclerosis — direct osseous involvement by lymphoma, not a reactive change. Under the Lugano classification, this confirmed Stage IVB disease with true extranodal involvement.

Then came the diagnostic challenge that nearly derailed everything. A core needle biopsy of the mediastinal mass returned only dense fibrosis with a rim of reactive lymphocytes — no Hodgkin cells at all. This is a well-recognized pitfall of the nodular sclerosis subtype, the most common form of classical Hodgkin lymphoma, which is characterized histologically by broad bands of collagen dividing the lymphoid tissue into nodules. Because Reed–Sternberg cells are sparse and easily obscured by this fibrotic scaffold, needle cores frequently miss them entirely. The solution required a more aggressive approach: an excisional biopsy of an axillary lymph node, which finally secured the diagnosis. Histopathological examination revealed the hallmark lacunar-type Reed–Sternberg cells within collagen-divided nodules, and immunohistochemical staining confirmed the malignant cells were strongly positive for CD15 and CD30, weakly positive for PAX5, and negative for CD20 and CD45 — the classic immunophenotype of classical Hodgkin lymphoma. A bone marrow biopsy showed no lymphomatous involvement, and HIV testing was negative, ruling out HIV-associated lymphoma.

The treatment decision was equally instructive. Baseline echocardiography showed normal cardiac function with an ejection fraction of 67 percent, clearing the way for anthracycline-based chemotherapy. Given the absence of true cord compression or rapidly progressive neurological deficits, the team selected upfront chemotherapy over surgical decompression or emergent radiotherapy. The patient received standard ABVD chemotherapy — doxorubicin, bleomycin, vinblastine, and dacarbazine — on days 1 and 15 of a 28-day cycle. After just two cycles, an interim PET/CT demonstrated complete metabolic response with a Deauville score of 2, prompting the omission of bleomycin for the remaining four cycles, a risk-adapted strategy modeled on the RATHL trial paradigm that reduces pulmonary toxicity without sacrificing efficacy. By the end of treatment, the patient had regained full strength and normal sensation in his right arm, and the mediastinal mass had regressed from 10.7 by 7.2 centimeters to 4.5 by 1.9 centimeters.

The follow-up data are perhaps the most striking part of the story. At 18 months, the most recent PET/CT confirmed ongoing complete metabolic remission, with only a small inactive para-aortic soft-tissue residue measuring 3.7 by 1.3 centimeters — consistent with post-treatment fibrosis rather than active disease. Serial imaging had allowed the team to confidently characterize this persistent residue as inert fibrosis, avoiding unnecessary radiotherapy. The neurological recovery was equally remarkable: despite the apparent neural compromise at presentation, chemotherapy alone achieved complete resolution of both motor and sensory deficits, without a single surgical intervention on the spine.

To contextualize just how rare this presentation is, the authors conducted a structured literature review of PubMed/MEDLINE and Google Scholar, searching for combinations of Hodgkin lymphoma with spinal cord, neural foraminal, or epidural involvement alongside mediastinal mass or aortic arch findings, limited to English-language publications from 1985 through June 2026. The search identified 47 records; after screening, 13 met inclusion criteria. While neurological involvement in Hodgkin lymphoma has been documented — including cases of intraspinal tumors, spinal cord compression, and epidural masses at various levels from cervical to lumbosacral — none of the previously published cases described the concurrent combination of aortic arch encasement, neural foraminal extension, and vertebral osseous involvement as the initial presenting manifestation. Most prior reports involved surgical decompression or radiotherapy as part of management; this case stands apart in achieving complete remission with chemotherapy alone.

The radiological differential diagnosis for a mediastinal mass with neural foraminal extension is broad, including neurogenic tumors such as schwannoma and neurofibroma, thymoma, germ-cell tumors, and primary mediastinal large B-cell lymphoma. The early neurological presentation in this patient initially suggested a primary neurogenic process rather than lymphoma. This case underscores a critical diagnostic principle: current NCCN and ESMO guidelines emphasize that excisional lymph node biopsy remains the gold standard for diagnosing lymphoma, precisely because core needle biopsies can fail in fibrotic lesions. PET/CT proved pivotal not only for staging but for distinguishing metabolically active disease from inert post-treatment fibrosis, guiding risk-adapted therapy throughout the clinical course.

The broader lesson for clinicians is clear. Mediastinal masses associated with radiculopathy should trigger a high index of suspicion for lymphoma, even when the presentation seems anatomically improbable. This case expands the recognized spectrum of classical Hodgkin lymphoma by documenting an exceptionally rare concurrent presentation — great-vessel encasement, neural foraminal extension, and vertebral osseous involvement — as the initial manifestation of disease. It reinforces the complementary roles of adequate tissue sampling and functional imaging in establishing diagnosis and guiding treatment. Most importantly, it demonstrates that an atypical anatomical presentation need not portend a worse outcome when diagnosed and treated promptly: with standard anthracycline-based chemotherapy, even cases with apparent neural compromise can achieve excellent, durable remission without surgery or radiotherapy.

Subject of Research: Classical Hodgkin lymphoma presenting with aortic arch encasement and C7–T1 neural foraminal extension: a rare case report

Article Title: Classical Hodgkin lymphoma presenting with aortic arch encasement and C7–T1 neural foraminal extension: a rare case report

Article References: Khanfar, R. W., Jabari, R. A., S. Ahmad, M., Bseiso, O., Alhroub, W., Fatouni, E., Ghanim, H., Jabareen, M., Natsheh, M., & Khalili, A. (2026). Classical Hodgkin lymphoma presenting with aortic arch encasement and C7–T1 neural foraminal extension: a rare case report. Frontiers in Hematology, 5, Article 1914603. https://doi.org/10.3389/frhem.2026.1914603

Image Credits: AI Generated

DOI: 10.3389/frhem.2026.1914603

Keywords: classical Hodgkin lymphoma, aortic arch encasement, C7-T1 radiculopathy, neural foraminal extension, ABVD chemotherapy, PET/CT staging, excisional biopsy, nodular sclerosis, Frontiers in Hematology, Classical, Hodgkin, lymphoma

The regimen under investigation, abbreviated AN + AD, combines brentuximab vedotin and the immune-checkpoint inhibitor nivolumab with two conventional chemotherapy agents, doxorubicin and dacarbazine. Notably absent is bleomycin, the older drug long included in standard front-line Hodgkin lymphoma therapy but increasingly viewed as a liability because of its association with lung toxicity. By substituting targeted agents for bleomycin and, in this study, limiting treatment to just four cycles, the investigators set out to test whether precision medicine could allow patients with favorable disease biology to receive less chemotherapy without sacrificing the exceptional cure rates that define this cancer.

The patient population was carefully defined. The trial enrolled people with nonbulky, early-stage classical Hodgkin lymphoma, meaning their disease was limited to lymph node regions above or below the diaphragm without large tumor masses, a feature that generally predicts a more favorable course. At the time of the analysis, 154 patients had received at least one dose of the four-drug combination, and an overwhelming 98 percent had completed all four planned cycles of treatment. That near-complete adherence to the treatment schedule is itself a meaningful signal in oncology trials, suggesting the regimen was tolerable enough for patients to stay on course.

The efficacy numbers were remarkable across the board. At the end of treatment, the objective response rate, which counts patients whose tumors shrank at least partially, stood at 96 percent. The complete response rate, meaning no detectable disease remained, was 92 percent overall. When the investigators broke the results down by risk group, the picture held steady: patients in the favorable-risk subgroup achieved a complete response rate of 95 percent, while those in the unfavorable subgroup, who typically carry a worse prognosis, still reached 91 percent. The near-identical outcomes across risk categories suggest the addition of the targeted agents may be compressing the historical gap between patient groups that standard chemotherapy has struggled to close.

Durability, the question that matters most in a disease where most patients are young and expected to live decades, also looked strong. Among patients who achieved a complete response, 96 percent maintained it for at least two years. At a median follow-up of 27.9 months, the estimated two-year progression-free survival rate was 97 percent, meaning almost no patients had seen their lymphoma return or worsen within that window. For a disease that strikes disproportionately at young adults, a regimen that combines such high cure indicators with reduced chemotherapy exposure carries implications that extend far beyond the trial population, since late toxicities of Hodgkin lymphoma treatment, including cardiovascular damage and secondary cancers, are a major long-term concern for survivors.

The safety profile, while not benign, was consistent with what is known about the individual components. Any-grade treatment-related side effects occurred in 97 percent of patients, a figure that sounds alarming until placed in context: nearly all cancer regimens produce some side effects in nearly all patients, and the vast majority of these events were low grade. More telling is the grade 3 or higher rate, which captures the serious toxicities that threaten treatment delivery, and here the figure was 34 percent. Strikingly, no cases of febrile neutropenia, the dangerous fever-plus-low-white-blood-count emergency that often drives hospitalization during chemotherapy, were reported at all, a result that speaks to both the tolerability of the regimen and the feasibility of delivering it in community as well as academic settings.

Because nivolumab works by releasing a molecular brake on T cells, the immune-mediated adverse events characteristic of checkpoint inhibitors were a specific focus of monitoring. Treatment-emergent immune-mediated adverse events of any grade occurred in 22 percent of patients. These events, which can include inflammation of the thyroid, skin, lungs, or other organs, arise from the same immune reactivation that makes checkpoint inhibitors effective against cancer, and they are generally manageable with immunosuppressive medication when recognized early. The 22 percent rate provides clinicians with a concrete expectation of how often such monitoring and management will be needed if the regimen moves into routine practice.

The mechanistic logic behind the combination is one of the reasons the results have generated such attention. Brentuximab vedotin is an antibody-drug conjugate that homes in on CD30, a surface molecule displayed prominently on the malignant Reed-Sternberg cells of Hodgkin lymphoma, and delivers a payload of monomethyl auristatin E that disrupts cell division. Nivolumab blocks the PD-1 pathway, which Hodgkin lymphoma cells exploit to hide from immune attack, in part through genetic alterations that drive overexpression of the PD-L1 ligand. Doxorubicin and dacarbazine provide conventional cytotoxic killing. Preclinical and clinical evidence has suggested that chemotherapy and antibody-drug conjugates can each potentiate antitumor immunity, creating a rationale for pairing them with checkpoint blockade, and the SGN35-027 results lend clinical weight to that hypothesis.

The study was a broad international collaboration, with investigators spanning major cancer centers and community oncology networks across the United States and sites in Europe and Australia. The author group was led by Jeremy S. Abramson of Massachusetts General Hospital and included figures such as David J. Straus of Memorial Sloan Kettering Cancer Center, Nancy L. Bartlett of Washington University School of Medicine, Ryan C. Lynch of Fred Hutchinson Cancer Center, and Wojciech Jurczak of the Maria Sklodowska-Curie National Research Institute of Oncology in Krakow, alongside colleagues from Spain, Italy, Australia, and a range of US centers. Data from the study were previously presented at the 2024 American Society of Hematology Annual Meeting and Exposition in San Diego, and the work received funding support from Seagen, Inc., which was acquired by Pfizer in December 2023, together with Takeda Development Center Americas and Bristol-Myers Squibb, with additional support from a Memorial Sloan Kettering Cancer Center core grant.

The authors and the journal are careful to frame the findings appropriately. The published summary emphasizes that it reports the results of a single study, that results may differ from those of other studies, and that health professionals should make treatment decisions based on all available evidence rather than on one trial. It also notes explicitly that the combination of brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine is not approved for the treatment of people with early-stage classical Hodgkin lymphoma. Those caveats matter, but they do little to dull the significance of the numbers. Classical Hodgkin lymphoma is already one of oncology’s success stories, yet each incremental gain in survival has traditionally been purchased with more intensive therapy and more late effects. A four-cycle, bleomycin-free regimen that pairs two rational targeted agents with limited chemotherapy and delivers 97 percent two-year progression-free survival points toward a future in which curing this cancer requires less treatment, not more, and in which the young patients who make up the bulk of the Hodgkin lymphoma population can look forward not just to survival but to decades of healthier life afterward.

Subject of Research: Combination therapy with brentuximab vedotin, nivolumab, and chemotherapy for nonbulky, early-stage classical Hodgkin lymphoma

Article Title: Summary of Research: Brentuximab Vedotin and Nivolumab in Combination with Chemotherapy for Nonbulky, Early-Stage Classical Hodgkin Lymphoma

Article References: Abramson, J. S., Straus, D. J., Bartlett, N. L., Burke, J. M., Lynch, R. C., Domenech, E. D., Hess, B., Schuster, S. R., Linhares, Y., Gandhi, M., Shah, H. R., Jurczak, W., Re, A., Hahn, U., Prince, H. M., Guo, W., Davis, G., Ho, L., Fanale, M., … Lee, H. J. (2026). Summary of Research: Brentuximab Vedotin and Nivolumab in Combination with Chemotherapy for Nonbulky, Early-Stage Classical Hodgkin Lymphoma. Advances in Therapy. https://doi.org/10.1007/s12325-026-03723-z

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03723-z

Keywords: brentuximab vedotin, nivolumab, classical Hodgkin lymphoma, chemotherapy, antibody-drug conjugate, immune checkpoint inhibitor, phase 2 trial, progression-free survival, complete response, doxorubicin, dacarbazine, hematologic oncology