Hodgkin Lymphoma with Hypereosinophilia in a Pediatric Patient: Case Report and Review of the Literature.

Hodgkin Lymphoma with Hypereosinophilia in a Pediatric Patient: Case Report and Review of the Literature. | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 15 August 2025 V1 Latest version Share on Hodgkin Lymphoma with Hypereosinophilia in a Pediatric Patient: Case Report and Review of the Literature. Authors : Rosa Cruz Osorio , Regina Navarro-Martin del Campo M , Wangky Carolina Carrasco-Rivera , Lisette Paola Bruijnzeels-Ponce , Jesús Alejandro Gutiérrez-Ortiz , Hannali Quintero-Buenrostro , Violeta Salceda , Manuel Martinez-Albarran , Diego Ugalde-Aviña , Veronica Soto Chavez , Fernando Sánchez-Zubieta , and Ramón Oscar Gonzalez-Ramella 0000-0002-9669-2632 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.175522160.00099286/v1 219 views 144 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Hodgkin lymphoma (HL) comprises 6% of pediatric cancers, showing bimodal incidence in adolescence/young-adult and over 50 years. Characterized by Reed-Sternberg cells, HL is classified as classic/nodular lymphocytic predominant by WHO. Hypereosinophilia (>1500/µL eosinophils) occurs in 15% of HL cases. Case Report: A 17-year-old female presented with weight loss, night sweats, and malaise. Examination showed enlarged lymph nodes, splenomegaly, and palmoplantar erythema. Bloodwork revealed eosinophilia, hypoalbuminemia, high lactic dehydrogenase. Bone marrow confirmed eosinophilic predominance. Lymph node biopsy diagnosed classical HL, nodular sclerosis variant. PET scan identified cervical, mediastinal, abdominal and spleen tumoral activity, classifying her as stage III with high-risk features. OEPA/COPDAC treatment initiated, follow-up PET-CT had mediastinal involvement. She underwent radiotherapy. Conclusion: This rare case illustrates profound hypereosinophilia concomitant with HL. Despite an extensive literature search, no similar hypereosinophilic presentations were found. This case underscores the vital role of considering oncological factors when addressing marked hypereosinophilia in pediatric patients. Introduction: Classical Hodgkin lymphoma (HL) is a neoplasm that predominantly affects adolescents and young adults, accounting for approximately 10–15% of all lymphomas (1). Thanks to advancements in chemotherapy, radiation therapy, and targeted immunotherapy, it is now associated with a favorable prognosis. The nodular sclerosis subtype is the most prevalent, representing 70% of HL cases (2). While the diagnosis of HL is generally straightforward, atypical clinical presentations—such as profound hypereosinophilia—can pose significant diagnostic challenges. Mild eosinophilia is observed in approximately 15% of HL cases; however, marked hypereosinophilia—defined as an eosinophil count exceeding 1.5 × 10⁹/L—is exceedingly rare (3,4). This condition may arise from various causes, including parasitic infections (e.g., Strongyloides stercoralis ), allergic or atopic diseases, adverse drug reactions, and paraneoplastic syndromes associated with myeloproliferative or lymphoproliferative disorders (5). In HL, hypereosinophilia may result from cytokines such as IL-3, IL-5, and GM-CSF produced by malignant cells, which promote eosinophil differentiation and survival (6). These cytokines may also influence the tumor microenvironment, suggesting potential diagnostic and therapeutic implications. Although eosinophilia has been reported in HL, the extreme levels observed in this case are unprecedented, making it a noteworthy diagnostic marker. This report describes the case of a 17-year-old female with classical HL, nodular sclerosis subtype, who presented with profound hypereosinophilia. By highlighting the clinical and pathological complexities of this rare presentation, this case emphasizes the need for heightened awareness of HL in patients with unexplained hypereosinophilia, particularly in pediatric and adolescent populations. Ultimately, this report aims to broaden the clinical perspective on hypereosinophilia as a potential presentation of HL, reinforcing the importance of considering oncologic causes early in the diagnostic process. Case Report: A 17-year-old Hispanic female was admitted with a six-month history of symptoms, including profuse diaphoresis and unintentional weight loss of more than 10% of her body weight. She also reported pruritus affecting her hands and had developed fixed, non-tender submandibular and bilateral cervical lymphadenopathies, each measuring approximately 9–10 cm in diameter. There was no evidence of dysphagia or airway compression; however, splenomegaly and palmoplantar erythema were noted on physical examination. Upon admission, laboratory testing revealed a hemoglobin level of 10.49 g/dL, a hematocrit of 34.5%, and a leukocyte count of 104,900/µL. The leukocyte differential showed neutrophils at 2,570/µL, lymphocytes at 3,130/µL, and marked eosinophilia of 97,880/µL, corresponding to 93.3% of the total white blood cell count. The platelet count was 354,400/µL. Additional biochemical tests revealed a lactate dehydrogenase (LDH) level of 201 U/L and a serum albumin concentration of 2.90 g/dL. PCR testing for Epstein–Barr virus was negative, as were serologic tests for VDRL, HIV, herpes simplex virus, rubella, cytomegalovirus, and Toxoplasma gondii. A peripheral blood smear confirmed marked eosinophilia, with other cell lines appearing morphologically normal. A bone marrow aspirate revealed a hypocellular marrow predominantly composed of eosinophilic lineage cells at various stages of maturation—from promyelocytes and myelocytes to metamyelocytes and mature eosinophils. No blast cells or infiltrative malignancies were identified in the aspirate. A plain chest X-ray demonstrated a large mediastinal mass accompanied by diffuse pulmonary infiltrates. Computed tomography (CT) revealed conglomerated lymph node clusters with altered morphology across multiple cervical chains, as well as multiple adenopathies in the para-aortic, paratracheal, and aortopulmonary window regions. These findings were associated with splenomegaly and similar lymph node involvement in the retroperitoneum, mesentery, and splenic hilum. A diagnostic positron emission tomography (PET) scan showed abnormal metabolic activity, including bilateral SUVmax of 16.6 at cervical levels II to VI (up to 62 mm), a mediastinal SUVmax of 12 with a metabolic volume of 181 cc at 29%, and splenic lesions with an SUVmax of 5.3 and a maximum diameter of 159 mm. Abdominal adenopathies at the splenic hilum exhibited an SUVmax of 11.9 and measured 29 mm in diameter. A lymph node biopsy confirmed the diagnosis of classical Hodgkin lymphoma, nodular sclerosis variant. Immunohistochemical analysis showed neoplastic cells positive for CD30, CD15, and CD68, and negative for CD3 and CD20. At the tissue level, there was prominent eosinophilic infiltration, with 148 eosinophils counted per high-power field (400× magnification). Genetic testing revealed no mutations in markers such as JAK2 or BCR-ABL . Based on these findings, the patient was classified as stage IIIBs according to the Ann Arbor staging system, as modified by the Cotswolds criteria. This classification was supported by clinical features including a bulky thoracic mass, splenomegaly, profound weight loss, profuse sweating, hypoalbuminemia, and marked hypereosinophilia, all of which placed her in the high-risk category. Treatment was initiated following the OEPA/COPDAC protocol. The patient received two cycles of the OEPA regimen (prednisone, vincristine, doxorubicin, etoposide), followed by an interim PET-CT scan to assess treatment response. She then underwent four cycles of the COPDAC regimen (prednisone, dacarbazine, vincristine, cyclophosphamide). Radiotherapy was indicated for patients with poor or incomplete responses to chemotherapy. The interim PET-CT scan demonstrated a reduction in abnormal radiotracer uptake in the neck and mediastinum, along with resolution of splenic lesions and abdominal adenopathies, indicating a favorable treatment response. According to the Deauville scoring system, the response was classified as Deauville 4. Hypereosinophilia also markedly decreased following chemotherapy. The patient is currently alive and undergoing radiotherapy, with no evidence of relapse or tumor progression. No treatment-related complications have been reported. Discussion: Eosinophils, a subset of white blood cells, originate in the bone marrow. Cytokines such as IL-3, IL-5, and GM-CSF regulate their maturation and differentiation, with IL-5 playing a particularly prominent role in eosinopoiesis. These cells store and release bioactive compounds that play a key role in infections, allergic reactions, and inflammatory processes (5). In neoplastic diseases, hypereosinophilia may result from cytokine production by malignant cells, as observed in Hodgkin lymphoma (HL), T-cell lymphomas, and acute lymphoblastic leukemia. This interaction suggests a potential role for eosinophils in tumor microenvironment modulation and disease progression. Hypereosinophilia, while relatively common in various pathological processes such as hematologic disorders, infections, allergic diseases, and neoplasms, should always prompt a thorough diagnostic evaluation (5,7). Moderate to severe eosinophilia, particularly when unexplained, warrants a detailed review of the clinical history, physical examination, and comprehensive laboratory and imaging studies. The diagnostic algorithm proposed in the World Health Organization’s 2016 Classification of Eosinophilic Disorders recommends integrating blood and bone marrow morphology, cytogenetics, and immunophenotyping to identify clonal or reactive causes (6). This approach is particularly valuable for distinguishing primary from secondary eosinophilia, as illustrated in the present case. Lykkergaard’s study of 356,196 individuals established a significant association between unexplained eosinophilia and the subsequent development of Hodgkin lymphoma and myeloproliferative disorders. This finding reinforces the need for prompt evaluation of hypereosinophilia to enable early diagnosis, which is associated with improved prognosis in these malignancies (8). Approximately 10% of hypereosinophilia cases are paraneoplastic in origin, although its prognostic significance remains controversial. Some studies suggest a correlation with poor outcomes, whereas others do not (9). Von Wasielewski, in a study of 1,511 biopsies from patients with HL, found that prominent tissue eosinophilia correlated with poor treatment response in the nodular sclerosis subtype, although no similar correlation was observed with peripheral eosinophilia (10). The incidence of eosinophilia in Hodgkin lymphoma is approximately 15%, and it can be detected in both peripheral blood and bone marrow (11). A correlation has been suggested between eosinophilia and the nodular sclerosis variant of HL, possibly due to eosinophil production of TGF-β and the subsequent stimulation of fibroblasts (8). Moreover, a protein expressed by eosinophilic granulocytes, known as eosinophil cationic protein (ECP), can inhibit proteoglycan degradation in fibroblasts, contributing to the formation of fibrotic bands characteristic of nodular sclerosis histology (8). In addition, eosinophilia appears to increase the expression of a ligand for CD30, a member of the TNF/nerve growth factor family, which may stimulate Hodgkin Reed–Sternberg cell proliferation (8). These mechanisms highlight the potential role of eosinophils in disease progression and modulation of the tumor microenvironment in HL. The association between Hodgkin lymphoma and eosinophilia has been recognized for many years; however, its specific role in pathogenesis and its impact on survival remain incompletely understood (12). To our knowledge, there have been no previously documented cases of hypereosinophilia reaching the levels observed in the present patient, particularly in a 17-year-old female with classical nodular sclerosis HL. This case is therefore noteworthy for the extraordinarily high eosinophil count, a phenomenon not previously reported in the literature. Morena Urbina reported a case of a 19-year-old female with chronic atopic dermatitis, severe pruritus, insomnia, anxiety, lymphadenopathy, leukocytosis (39,700/µL), and eosinophilia (1,580/µL). Lymph node biopsy showed immunostaining positive for BCL2, BCL6, CD3, CD30, and CD15, and negative for PAX5 and CD20, consistent with the nodular sclerosis variant of HL. Similarly, González Paredes described a 12-year-old female with vomiting, abdominal distension, anuria, lymphadenopathy, and a mesogastric mass. Laboratory tests revealed leukocytosis (32,800/µL), eosinophilia (27,552/µL), and markedly elevated urea (323 mg/dL) and creatinine (23.8 mg/dL). The diagnosis was lymphocyte-predominant nodular HL, with immunophenotype CD20-, CD30+, CD45+, CD15+, CD57+, and complicated by renal insufficiency at presentation. Sanju Cyriac reported an 8-year-old male with lymphadenopathy, fever, cough, hepatosplenomegaly, superior vena cava obstruction, pleural effusion, leukocytosis (18,000/µL), and eosinophilia (14,220/µL). Bone marrow analysis confirmed eosinophilia, and lymph node biopsy revealed mixed-cellularity HL, which responded to ABVD chemotherapy. Voeller J (2022) reported two pediatric cases with hematologic malignancies and severe hypereosinophilia: a 7-year-old female with acute lymphoblastic leukemia complicated by myocardial infarction and stroke, and a 13-year-old female with eosinophilic leukemia, anemia, cardiomyopathy, and pulmonary hypertension. Another reported patient had FIP1L1–PDGFRA positivity and was treated with imatinib and corticosteroids. In adults, cases of HL with hypereosinophilia have been associated with tissue damage, particularly cardiac involvement, including hypereosinophilic myocarditis (13,14). Neuropsychiatric symptoms have also been described in association with marked eosinophilia. No previously published cases have documented hypereosinophilia of the magnitude observed in our patient. She presented with anxiety, pruritus, palmoplantar rash, diaphoresis, splenomegaly, and marked lymphadenopathy, accompanied by an extraordinarily high eosinophil count. This unique presentation underscores the value of considering HL in the differential diagnosis of unexplained hypereosinophilia, particularly in pediatric and adolescent patient. This case adds to the scarce literature on profound hypereosinophilia as a presenting feature of HL in pediatric patients. It underscores the importance of considering malignant etiologies in the differential diagnosis of unexplained eosinophilia and highlights the value of prompt, comprehensive evaluation. Further research is needed to clarify the underlying mechanisms and potential prognostic implications of this rare association. Conflict of Interest Statement The authors declare that they have no financial interests or personal relationships that could have influenced the development or findings of this paper. Ethical clearance The study was conducted in accordance with the ethical standards of the institutional and national research committees, and with the 1964 Helsinki Declaration and its later amendments. Funding: This research did not receive any specific grant from funding agencies in the public, commercial or not-profit-sectors. Acknowledgments: None. References 1. Brice P, de Kerviler E, Friedberg J. Classical Hodgkin lymphoma. Lancet Lond Engl. 2021 Oct 23;398(10310):1518–27. 2. Connors J, Cozen W, Steidl C, Carbone A, Hoppe R, Flechtner H. Hodgkin lymphoma. Nat Rev Dis Primer. 2020 Jul 23;6(1):1–25. 3. Roufosse F, Garaud S, de Leval L. Lymphoproliferative disorders associated with hypereosinophilia. Semin Hematol. 2012 Apr;49(2):138–48. 4. Valent P, Klion A, Horny H, Gotlib J, Weller P. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol. 2012 Sep 1;130(3):607-612.e9. 5. Roufosse F, Weller P. Practical approach to the patient with hypereosinophilia. J Allergy Clin Immunol. 2010 Jul;126(1):39–44. 6. Gotlib J. World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management. Am J Hematol. 2017;02(11):1243–59. 7. Quirós V, Umaña S, Cerdas J, Sáenz M, Sáenz M del P. Eosinofilia; causas y abordaje. Rev Clínica Esc Med UCR-HSJD [Internet]. 2017 Jul 26 [cited 2023 Aug 28];7(1). Available from: https://revistas.ucr.ac.cr/index.php/clinica/article/view/29960 8. Andersen C, Siersma V, Hasselbalch H, Lindegaard H, Vestergaard H, Felding P. Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death. Am J Hematol. 2013 Oct;88(10):843–7. 9. González-Paredes Y, Arreguín-González F, Salamanca-García M, Páez-Aguirre S. Linfoma de Hodgkin, síndrome hipereosinofílico e insuficiencia renal: presentación de caso clínico. Gac Mex Oncol. 2014 Jan 1;13(1):77–81. 10. von Wasielewski R, Seth S, Franklin J, Fischer R, Hübner K, Hansmann M. Tissue eosinophilia correlates strongly with poor prognosis in nodular sclerosing Hodgkin’s disease, allowing for known prognostic factors. Blood. 2000 Feb 15;95(4):1207–13. 11. Cyriac S, Sagar T, Rajendranath R, Rathnam K. Hypereosinophilia in hodgkin lymphoma. Indian J Hematol Blood Transfus. 2008 Jun 24;24(2):67–8. 12. Küpeli S, Kara F, Akyüz F, Büyükpamukçu M. Eosinophilia and multifocal vertebral involvement with Hodgkin lymphoma. Pediatr Blood Cancer. 2010 Sep;55(3):560–1. 13. Brener M, Ravalli S. Left Ventricular Cavity Obliteration From Eosinophilic Myocarditis in a Patient With Classic Hodgkin Lymphoma. JACC Case Rep. 2020 Feb;2(2):210–5. 14. Chan T, Yung S, Mak Y, Chan W, Kwong Y. Rare complication of Hodgkin lymphoma: eosinophilia-associated endocarditis leading to left ventricular thrombosis and mitral valve damage. Ann Hematol. 2017 May;96(5):873–5. Legends Figure 1. Marked Eosinophilia in bone marrow aspirate (A), and blood smear (B). Clinical presentation of HL: palmoplantar erythema, low and rounded implanted auricles, eyes with elongated downward slits, wide philtrum, prominent lips, short neck, with a bulge on the right side due to a cluster of multiple bilateral lymph nodes at levels Ia, III, IV, and V, measuring a total of 10 x 10 cm. (C). PET-CT Scan showing supra and infra diaphragmatic tumor activity with splenic infiltration, Deauville 5 (D). Figure 2. Lymph node biopsy with findings of atypical lymphoid proliferation with capsular thickening, loss of lymph node architecture, nodular pattern divided by fibrous septa in reactive background composed of histiocytes, eosinophils and small lymphocytes (A, B, C), cattered large neoplastic cells with cytoplasms clear to eosinophilic, mono-, bi or multilobed pleomorphic nuclei, vesicular chromatin, and prominent eosinophilic nucleolus (D, E). Interstitial dense eosinophilic background infiltrate, groups and occasionally formation of microabscesses (C) represents more than 5% of the reactive component in more than 5 high-powered random fields (148 eosinophils per HPF); multifocal caseating necrosis was identified (B), however histochemical acid-alcohol resistant bacillus staining was negative. Immunophenotypic characteristics: CD3, CD20, EMA negative, CD30 (F), CD15 (E), (LMP1 pendiente) positive with histiocytic index (CD68) less than 25% of the reactive background. The diagnosis of CHL nodular sclerosis variant was concluded based on these findings. Information & Authors Information Version history V1 Version 1 15 August 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords hodgkin's disease lymphoma pediatric oncology Authors Affiliations Rosa Cruz Osorio Hospital Civil de Guadalajara Dr Juan I Menchaca View all articles by this author Regina Navarro-Martin del Campo M Hospital Civil de Guadalajara Dr Juan I Menchaca View all articles by this author Wangky Carolina Carrasco-Rivera Hospital Civil de Guadalajara Dr Juan I Menchaca View all articles by this author Lisette Paola Bruijnzeels-Ponce Universidad de Guadalajara Centro Universitario de Ciencias de la Salud View all articles by this author Jesús Alejandro Gutiérrez-Ortiz Universidad de Guadalajara Centro Universitario de Ciencias de la Salud View all articles by this author Hannali Quintero-Buenrostro Hospital Civil de Guadalajara View all articles by this author Violeta Salceda Universidad de Guadalajara Centro Universitario de Ciencias de la Salud View all articles by this author Manuel Martinez-Albarran Hospital Civil de Guadalajara Dr Juan I Menchaca View all articles by this author Diego Ugalde-Aviña Universidad de Guadalajara Centro Universitario de Ciencias de la Salud View all articles by this author Veronica Soto Chavez Hospital Civil de Guadalajara Dr Juan I Menchaca View all articles by this author Fernando Sánchez-Zubieta Hospital Civil de Guadalajara Dr Juan I Menchaca View all articles by this author Ramón Oscar Gonzalez-Ramella 0000-0002-9669-2632 [email protected] Hospital Civil de Guadalajara Dr Juan I Menchaca View all articles by this author Metrics & Citations Metrics Article Usage 219 views 144 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Rosa Cruz Osorio, Regina Navarro-Martin del Campo M, Wangky Carolina Carrasco-Rivera, et al. 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