Case Report
An 11‐year‐old male presented with 3 weeks of increasing left neck swelling with no other symptoms. Subsequent contrast‐enhanced CT of the neck showed multifocal single‐sided cervical adenopathy localized to the left cervical chain, predominantly starting at Level II and descending to Level V. The largest lymph node measured approximately 4.8 cm in diameter and demonstrated homogeneous soft‐tissue density without necrosis or calcification.
Biopsy of the enlarged node confirmed NLPHL. There was no evidence of mediastinal, contralateral cervical, or abdominal lymphadenopathy. On initial evaluation, normal CBC, CMP, LDH, and ESR were found.
Fluorodeoxyglucose positron emission tomography (FDG‐PET/CT) performed for staging revealed intense FDG uptake isolated to the left neck, with no hypermetabolic activity identified below the diaphragm or in extranodal tissues (Figure 1A–D). Based on these findings, the disease was initially classified as Stage IA NLPH using the Lugano staging system from 2023.
Given the PET and CT findings of enlarged nodes limited only to the left neck, the patient and family elected for surgical management understanding that there may still be need for adjuvant chemoradiation depending on final pathology. One month later, the patient underwent resection of all involved lymph nodes using a modified radical neck dissection which included Levels II–V. All cranial nerves were preserved intact.
A full lymphoma work‐up was completed with six touch preps and samples sent to the Flow Cytometry lab.
Concurrent flow cytometric analysis highlighted increased polytypic T‐cells with CD56 expression, but no monocytic B‐cells. By IHC staining, the large atypical cells strongly stained for CD20; PAX‐5 and BCL‐6 were also positive, and CD15, CD30, and MUM1 were negative. CD30 highlighted scattered immunoblasts.
CD57 and PD‐1 highlighted focal resetting around large atypical cells; these morphological and immunophenotypic findings supported the diagnosis of NLPHL. Histologic sections showed lymphoid tissue with effaced architecture by a vaguely nodular infiltrate of small to medium lymphocytes with scattered large atypical “popcorn” cells with folded/multilobulated nuclei. Occasional Reed–Sternberg‐like large atypical cells with prominent nucleoli were also identified.
Four months after the initial postoperative PET, a subsequent PET showed an increased size and number of multilevel supradiaphragmatic and infradiaphragmatic hypermetabolic lymphadenopathy, representative of Deauville 5, diagnosing the patient with recurrent Stage IIIA disease and leading to escalation of treatment. Later in the same month, a central port was placed for chemotherapy, and the patient subsequently completed four cycles of R‐CHOP chemotherapy over 3 months. A postchemotherapy PET scan showed complete metabolic resolution of previously involved lymph nodes, with no abnormal FDG uptake in the neck or elsewhere and no new areas of lymphadenopathy or extranodal involvement (Figure 1E,F).
These findings supported a Deauville score of 1–2 (Table 1), indicative of a complete response to therapy, and the patient is now in remission with no evidence of disease (NED).
Background
Nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL), accounting for approximately 5% of all HL cases. Whereas Reed–Sternberg cells are a unique indicator of classical HL (cHL), lymphocyte‐predominant (LP) cells are distinct in NLPHL. LP cells express CD20 and CD79a and lack CD15 and CD30, differentiating them from cHL [1].
According to UpToDate, the 5th edition of the World Health Organization categories NLPHL under HL however it does recognize the true B‐cell origin of the neoplastic cells, and therefore an accepted alternative in nodular LP B‐cell lymphoma [2].
Pediatric NLPHL predominantly affects males, with most patients presenting at an early stage (Stage IA) between 4 and 17 years of age, characterized by isolated peripheral lymph node involvement, typically involving the cervical and axillary nodes without classic lymphoma symptoms, such as fevers, night sweats, weight loss, or easy bruising. The prognosis for pediatric NLPHL is favorable, with overall survival rates exceeding 90%, though transformation has been reported in approximately 17% of patients [1, 3].
Traditional treatment consists of chemotherapy with or without radiation therapy, but these therapies carry significant long‐term risks, particularly in pediatric patients, including growth retardation, infertility, and secondary malignancies [4]. Consequently, alternative strategies, including surgical resection alone, have gained attention for carefully selected patients with localized, low‐risk disease. Reports indicate that some pediatric patients have been successfully treated with surgery alone, suggesting this approach may reduce treatment‐related morbidity while maintaining excellent outcomes [4, 5, 6, 7, 8].
Similar risk‐adapted treatment strategies have been adopted for other pediatric malignancies, including Wilms tumor, low‐risk neuroblastoma, and pilocytic astrocytoma, where surgery alone or reduced therapy is used to minimize treatment toxicity [9, 10, 11]. However, patients with more extensive disease or higher tumor burden may still require adjuvant therapy following surgery.
Despite growing interest in surgical management for early‐stage disease, the literature evaluating surgery as a primary treatment modality in pediatric NLPHL remains limited. Most available evidence consists of retrospective case series or subgroup analyses from larger studies. As a result, the role of surgery alone remains incompletely defined and is typically considered only in carefully selected low‐risk patients.
In this review, we focus on patients ranging from 4 to 17 years of age to evaluate surgical resection as an independent treatment for pediatric NLPHL. We present the case of an 11‐year‐old male treated with modified radical neck dissection after imaging suggested localized disease confined to one side of the neck. However, final pathology demonstrated a greater disease burden than anticipated, and the patient ultimately required adjuvant chemotherapy.
The aim of this study was to synthesize the limited available literature on surgical management of pediatric NLPHL and evaluate reported outcomes following surgical resection.
Methods
Data was sourced from PubMed and Scopus, and was compiled from a range from 2003 to 2026 inclusive. Our search strings included keywords such as “surgical treatment,” “surgical management,” “pediatric nodular lymphocyte‐predominant Hodgkin's lymphoma,” and “nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL),” along with MeSH (Medical Subject Heading) terms such as “Hodgkin Disease,” “Lymphoma, Hodgkin,” and “Surgical Procedures, Operative.” For example, ((“Lymphoma, Hodgkin”[MeSH] OR “nodular lymphocyte‐predominant Hodgkin lymphoma”[tab] OR “pediatric NLPHL”[tab]) AND (“Surgical Procedures, Operative”[MeSH] OR “surgical management”[tab] OR “surgical treatment”[tab])). Studies were included in this review if they focused on the surgical management of NLPHL in pediatric patients.
Studies were excluded if they primarily discussed other treatment modalities, such as radiation therapy or chemotherapy, or if they focused on other cancers such as non‐HL or cancers with mixed features of classical HL and NLPHL. Papers were excluded if a clear follow‐up protocol was not indicated, or if the primary patient population was adults. Papers were also excluded if not primarily in English.
Two reviewers manually selected studies that met all inclusion criteria and that did not meet any exclusion criteria. Conflicts were resolved by consensus. There was no use of automation tools during the selection process.
Data collection was also performed manually by a single reviewer, focusing on variables such as the type of surgical treatment, patient age, remission status, and any indication of recurrence.
Due to the rarity of pediatric NLPHL and the limited number of studies evaluating surgical management as a primary treatment modality, a relatively small number of eligible studies was anticipated.
Risk of bias was determined using the Downs and Black assessment tool.
Results
Initially, 37 articles of NLPHL were found (adults and children) between 2003 and January 2026 with four articles included in the final paper (Figure 2). We used the Downs and Black risk of bias assessment tool to rate the quality of the included publications shown in Table 2. These methods were in compliance with PRISMA guidelines.
Excluded studies focused on other treatments, such as radiation or chemotherapy, or types of cancer other than NLPHL. The selected studies all involved pediatric patients, ranging in age from 4 to 17 years, and examined surgical management for early‐stage NLPHL. Across studies, surgical intervention included full or partial lymph node resection, followed by monitoring for recurrence and survival outcomes as shown in Table 3.
Four studies met the inclusion criteria and evaluated surgical management of pediatric NLPHL. Across these studies, event‐free survival ranged from 57% to 77%, while overall survival was consistently reported at 100% [4, 8]. In the cases that were not event‐free, most relapses were observed in patients with residual disease postsurgery.
For example, in Pellegrino et al., patients with complete resection showed a significantly lower rate of recurrence than those with partial resection [4]. However, the available literature primarily evaluates surgery alone in highly selected patients with Stage IA disease characterized by a single involved lymph node or limited, completely resectable nodal disease. There remains limited evidence defining whether surgery alone is appropriate for patients with apparently localized but multifocal nodal involvement within a single cervical region, or how accurately preoperative imaging can identify patients in whom complete surgical resection will be sufficient therapy.
This represents an important gap because anatomic localization of disease on imaging may not reliably reflect the true nodal disease burden.
The assessment of the four studies using the Downs and Black criteria highlights variability in bias and validity. Appel et al. scored the highest with 18 out of 28, showing strong reporting and internal validity but limited external validity due to specific sample characteristics and inadequate adjustment for external confounders [5]. Pellegrino et al. and Mauz‐Körholz et al. both scored 16, showing consistent internal validity and well‐documented results, but had the same limitations to external validity as the Appel et al., study [4, 8].
These studies contribute valuable insights but their findings may not apply broadly due to specific patient populations and treatment contexts which is not unusual for a report on a specific pathology.
Bessen et al. scored 12, reflecting moderate bias and limited external validity, primarily due to less comprehensive reporting and weak control over confounding factors [6]. Across all studies, reporting was generally strong; however, limited control over confounding and external validity restricted the applicability of findings to a wider population. While each study provides valuable insights into treating pediatric LP HL, there is a consistent need for research with broader generalizability and improved methodological rigor.
Discussion
The findings of this review suggest that surgical resection may represent a potential treatment strategy for carefully selected pediatric patients with early‐stage NLPHL. Across the included studies, overall survival was consistently reported at 100%, while event‐free survival varied depending on completeness of resection and the presence of residual disease. Importantly, these data do not establish that all patients with radiographically localized Stage IA disease are appropriate candidates for surgery alone.
Rather, the strongest evidence for this strategy is concentrated among patients with limited disease in whom complete excision can be achieved.
The Lugano staging system is a modification of the original Ann Arbor Staging system used for Hodgkins lymphomas. One of the drawbacks is that Stage 1A is defined as “one node or a group of nodes on the same side of the diaphragm.” That may lead to understaging where there is a lack of extranodal extension, involvement in multiple sites, or presence of bulky disease—nodes > 6 cm. The interpretability of the current staging system may require more refinement to decrease the potential for understaging, that is, specify the burden of disease in one nodal area or group and upstage if more than a defined number of nodes > 1 cm are present in that region.
Patient selection is a critical factor when considering surgical management. In most reported cases, surgery was performed in patients with localized Stage 1A disease involving a single lymph node or a small cluster of nodes that could be completely excised. Patients with more extensive nodal involvement or higher tumor burden may be less suitable for surgical management alone and often require systemic therapy.
The distinction between these groups remains incompletely defined in the literature, particularly for children with multifocal but unilateral cervical disease that appears anatomically confined on preoperative imaging. Consequently, there is uncertainty regarding the degree of nodal burden at which the potential benefit of surgery alone is outweighed by the likelihood that systemic therapy will ultimately be required.
The present case illustrates the importance of accurately assessing disease burden prior to selecting surgical management alone. Although initial imaging suggested localized disease, final pathology demonstrated extensive nodal involvement, ultimately requiring systemic chemotherapy. This highlights that surgery alone may not be sufficient in patients with higher tumor burden.
Our patient is particularly relevant to this gap because his disease was radiographically confined to the ipsilateral cervical chain but involved multiple nodal levels, differing from the single‐node or very limited disease most commonly represented in reports of successful surgery‐only management. Since it was limited to the unilateral neck he was classified as Stage 1A after review of all relevant imaging and discussion with the tumor board team based on the Lugano Staging system from 2023. Thus, the decision to pursue surgery reflects a clinically uncertain boundary of the existing evidence rather than simply patient/family or provider preference.
An important consideration raised by our case is whether the extent of surgical resection itself conferred any oncologic advantage once systemic chemotherapy ultimately became necessary. Because this patient experienced disease recurrence requiring R‐CHOP despite an extensive modified radical neck dissection, our findings cannot demonstrate that a more aggressive surgical approach improved recurrence risk or overall survival compared with a more limited diagnostic procedure followed by chemotherapy. The primary value of extensive surgical resection appears to remain in carefully selected patients in whom complete excision may eliminate the need for systemic therapy altogether.
When postoperative findings reveal greater disease burden requiring chemotherapy, the additional survival benefit attributable to aggressive surgery remains uncertain. This uncertainty is clinically important because the existing literature provides substantially more support for complete excision of isolated disease than for formal complete cervical lymph node dissection in multifocal Stage IA disease.
The study by Appel et al. aimed to reduce the need for chemotherapy and radiation, among the 178 patients included in the study, 52 underwent a complete resection of a single node without additional therapy, with a promising 5 year EFS rate of 77% and a 100% overall survival. There was a notable 75% of patients who achieved complete remission following surgery alone, and those with relapses were primarily treatable with chemotherapy. This suggests that surgery may provide a lower risk alternative to low‐risk cases.
In cases where surgery alone did not achieve complete remission, adjuvant therapy was provided with doxorubicin, vincristine, prednisone, and cyclophosphamide, yielding an EFS of 88.8% [5]. However, these results predominantly support surgery in patients with completely resected, limited disease and therefore is limited in extrapolation to children with multiple involved cervical nodal regions.
The study by Mauz‐Körholz et al. evaluated 58 pediatric patients, in which 54 had Stage 1A disease and underwent surgery alone. Surgery led to a 57% progression‐free survival with a 100% overall survival. Relapse was observed in 12% of patients, though this was mainly in patients in which complete resection was not achieved.
This study identified residual disease as a significant factor in recurrence, underscoring the importance of complete resection if pursuing a unifocal surgical approach [8]. Together, these findings suggest that completeness of resection and initial disease burden may be more informative for selecting patients for surgery alone than Stage IA classification by itself.
The evolving landscape of pediatric oncology has increasingly embraced risk‐stratified treatment to minimize long‐term adverse effects. For example, in Wilms tumor, select children with unilateral, nonmetastatic disease can be managed with nephrectomy followed by reduced or no chemotherapy in specific protocols [9]. Similarly, low‐risk neuroblastoma in infants is sometimes observed or treated surgically without additional therapy if the disease is localized [12].
These precedents support the rationale for exploring surgery‐only approaches in early‐stage pediatric NLPHL, especially when complete resection is achievable.
There are limitations, however, involved given the evidence. Most of the studies included were retrospective, potentially introducing a bias around case selection and follow‐up variability. An additional limitation is the relatively small sample size in the different studies and overall treatment regimen, limiting the generalizability of the findings.
Another limitation is the variation or heterogeneous nature of the follow‐up periods between studies, showing difficulty in comparing the studies with each other. Furthermore, the available studies provide limited guidance regarding the maximum nodal burden, number of involved nodes, or extent of cervical disease for which surgery alone remains appropriate. This limits the ability to prospectively distinguish patients with truly resectable low‐risk disease from those who appear localized by imaging but harbor a disease burden that is unlikely to be controlled with surgery alone.
The goal of surgery in pediatric NLPHL should not necessarily be maximal nodal clearance in every patient, but rather careful selection of patients in whom complete excision may obviate chemotherapy. Once systemic therapy becomes necessary, current evidence does not demonstrate that increasingly extensive surgery improves survival beyond what would have been achieved with chemotherapy alone. Consequently, the potential morbidity associated with more aggressive cervical surgery must be balanced against the uncertain incremental oncologic benefit.
The viability of surgery as a treatment modality has largely been categorized by stage of the cancer as opposed to levels operated on for lymph node dissection as shown on Table 3. However, the risk of recurrence in patients with residual disease after surgery, as noted in Pellegrino et al., indicates that careful patient selection and close follow‐up is critical to minimizing relapse risk [4]. These findings support the need for further prospective, multi‐institutional studies to confirm these results, reduce bias, and refine criteria for surgical intervention as a stand‐alone treatment.
A key limitation of this review is the small number of available studies and the dominance of a single large Children's Oncology Group study within the literature. This imbalance limits the external validity of conclusions drawn from pooled data and highlights the need for additional multi‐institutional research evaluating surgical management in pediatric NLPHL. Specifically, future studies should distinguish isolated single‐node disease from multifocal but anatomically localized disease and evaluate whether nodal number, nodal size, distribution across cervical levels, or completeness of resection predicts successful treatment with surgery alone.
This may require a revision of the current staging system to be more specific and decrease the potential for understaging based on nodal location alone in the absence of extranodal extension or nodes > 6 cm in size.
A future direction for research is for studies to focus on identifying specific subgroups of pediatric NLPHL patients in which complete surgical resection is possible, in which case this form of treatment would benefit the patients the most. Moreover, the development of risk‐adapted treatment protocols, as suggested by Mauz‐Körholz et al., could help personalize treatment strategies and reduce overtreatment in patients who demonstrate a favorable prognosis [8]. The importance of shared decision making and multidisciplinary team involvement cannot be understated.
As demonstrated in this case, initial imaging suggested that surgery via modified radical neck dissection may be curative; however, the tumor burden encountered and follow‐up imaging demonstrated the need for adjunctive therapy. There was not a significant delay between PET imaging and surgery; however, as most of the impacted lymph nodes were quite small, it is likely the PET underestimated the true tumor burden and therefore led to the outcome we encountered. This discordance between radiographic localization and actual disease burden represents the central clinical issue highlighted by this case.
Current evidence supports surgery alone most clearly for completely resectable, very limited Stage IA disease, but provides insufficient guidance for children with multifocal unilateral cervical involvement. Our case therefore highlights the need to define more precise selection criteria beyond stage alone and to determine whether preoperative disease burden and distribution can identify patients likely to benefit from surgery without subsequent systemic therapy.
Conclusion
This systematic review reinforces the potential for surgical management as a feasible sole primary treatment plan for pediatric patients with early‐stage, low‐risk NLPHL. Based on the studies included in this review, complete resection can yield favorable outcomes, showing an EFS ranging from 57% to 77% and a consistent 100% overall survival rate across all articles. Importantly, the evidence suggests that a surgery‐only treatment plan potentially avoids the adverse effects associated with chemotherapy and radiation, which is moreover important for pediatric patients at risk for complications with alternative treatments.
The included studies underscore the importance of a complete resection in order to achieve optimal outcomes, as patients with residual disease postoperation had a higher likelihood of recurrence. This further highlights the importance of having carefully selected patients with localized, low‐risk disease for surgical resection to be the primary treatment plan. Our case demonstrated that while the initial workup appeared favorable for a surgical management only option, the final pathology reflected a higher disease burden with numerous involved nodes in all the resected levels.
This case also emphasizes the need for close postoperative monitoring, as the patient later developed systemic recurrence several months after initial remission and required R‐CHOP chemotherapy, ultimately achieving NED at 9 months postdiagnosis.
Due to limitations such as small sample sizes, retrospective designs, and variable follow‐up protocols, further prospective, multicenter studies may be necessary to refine criteria for selecting patients that would receive optimal treatment from surgery alone. Future research should focus on developing risk‐adapted protocols to better identify pediatric NLPHL subgroups who would consistently benefit most from surgical treatment without adjuvant therapies. Additionally, the exploration of long‐term quality of life outcomes for patients treated with surgery alone could potentially provide a more comprehensive understanding of the benefits of this approach over traditional treatment regimens.
Overall, the findings of this review in addition to the real‐world insights from our case support the viability of surgery as a primary standalone option for certain pediatric NLPHL cases, offering a path towards reduced treatment comorbidities and complications, further leading to improved quality of life for affected children.
Funding
The authors have nothing to report.
Ethics Statement
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Conflicts of Interest
The authors declare no conflicts of interest.