A Elmas, M Akçam

Abstract

Lymph node enlargement is a concern for physicians and parents due to the potential for malignancy in childhood. Castleman's disease is a rare lymphoproliferative disorder in children characterised by the proliferation of lymphoid tissue of unknown aetiology. Two clinical types, localised and multicentric, have been described. There are three histopathological types, including hyaline vascular, plasma cell and mixed. It is usually localised in the mediastinum and is rare in the head and neck region. In this article, we present the case of a 5.5-year-old male patient who presented with a mass in the neck and was treated surgically with a diagnosis of unicentric hyaline vascular type Castleman's disease after histopathological examination.

Introduction

Castleman's disease (CD), initially described by Benjamin Castleman in 1954, is a rare benign disorder of lymph node hyperplasia with an unknown aetiology. The condition presents as enlarged lymph nodes, most commonly on one side of the body.^1-3 The disease is classified according to its anatomical distribution and the number of lymph nodes involved, into two categories: Localised CD and Multicentric CD. According to its histopathologic structure, it is divided into three subgroups: hyaline vascular, plasma cell type and mixed type. The hyaline vascular type is the most common and is characterised by the presence of an asymptomatic, slowly growing mass. The plasma cell type is predominantly multicentric. The incidence is estimated to be 25 per million. The aetiology of the disease is attributed to human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV). In approximately 70% of cases, the thorax is involved, with involvement of the neck region being rare.^4,5 The objective of this study was to present and discuss a case of a patient presenting with a mass in the neck region who was diagnosed with CD in accordance with the literature.

Case

A 5-year-and-6-month-old male patient was admitted to our hospital with a complaint of swelling on the left side of his neck. A review of the patient's history revealed that the complaint had commenced six months prior, presenting as a painless swelling. The patient was treated with antibiotics, yet the swelling did not shrink. No symptoms of fever, anorexia, weight loss, or night sweats were present. The patient's body weight was 19 kg (50-75% percentile), and his height was 121 cm (90-97% percentile). A physical examination revealed a mobile, smooth, soft, painless mass with a smooth surface, approximately 5x3 cm in size, on the left side of the neck over the sternocleidomastoid muscle. The examination of other systems was unremarkable.

His past and family history were unremarkable. Laboratory; haemoglobin (Hb) concentration: 127 g/L. White blood cell (WBC) count: 14.3 x 10⁹/L. Platelet (Plt) count: 647 x 10⁹/L. Sedimentation rate: 20 mm/h.

C-reactive protein (CRP) concentration: 3.68 mg/L. No atypical cells were identified in the peripheral smear. The Brucella tube agglutination test yielded a negative result. A neck ultrasound revealed a conglomerated LAP measuring 19x10 mm in the right cervical region and 38x19 mm in the left cervical region, with an erased fatty hilus and marked vascularity. A computed tomography scan of the neck and thorax revealed a smoothly circumscribed lesion extending to the supraclavicular level in the left half of the neck, measuring 32x19 mm in the widest part. The lesion was found to be compressing the jugular vein in the medial neighbourhood, and no evidence of thoracic involvement was observed (Figure 1).

Magnetic resonance imaging (MRI) revealed a 36x20x50 mm lesion in the left cervical region, originating from the supraclavicular level and extending along the entire cervical line. The lesion exhibited a uniformly circumscribed inferior and superior part with vascular signal void areas, which were hypointense in T1A images and hyperintense in T2A images. Additionally, there was no diffusion restriction (Figure 1).

Figure 1 Case and images. (A) External view of the case. (B) Computed tomography of the neck. (C) Magnetic resonance image of the neck. (D) Contrast-enhanced magnetic resonance image of the neck.

The mass was removed through a surgical procedure. Macroscopically, it was a 4.8x3x2.5 cm nodular tissue fragment. On histopathological examination, it was reported that Mantle zones were enlarged in the lymph node and some of them contained more than one germinal centre (Twinning), Mantle zones were thickened and formed a layer (Onion skinning), atrophic germinal centres were interrupted by sclerotic and hyaline vascular structures (Lollipop follicular). In addition, interfollicular areas were enlarged with vascular proliferation and were reported to be compatible with 'Hyaline Vascular Type Castleman's disease' with mixed type inflammatory cells (Figure 2). Immunohistochemical staining revealed no malignancy and HHV8. After malignancy was excluded, the patient was followed up without additional treatment. After 6 months of follow-up, no recurrence was observed.

Figure 2 Lymph node biopsy. (A) The enlarged mantle zone contains more than one pale germinal centres (twinning). The interfollicular regions have many high-endothelial venules with sclerotic walls (H&E, 100x). (B) The germinal centre is atrophic, depleted of follicular centre cells, and surrounded by concentrically arranged small lymphocytes imparting an 'onion-skin' pattern (H&E, 200x). (C) No human herpesvirus type 8-infected cells were seen around the germinal centre (HHV8, 20x).

Discussion

Castleman's disease is a rare disease characterised by benign lymph node hyperplasia with an unclear aetiology. It is postulated that an immune system defect, inflammatory reactions (such as IL-6 and vascular endothelial growth factor), infections (such as Epstein-Barr virus and human herpes virus 8) and hamartomatous change may be involved in the aetiology.³

In children, 87% of the disease is localised. In this form, 33% of the mass is located in the thorax, 30% in the abdomen, less than 10% in the pelvis and other organs. In 30% of cases, peripheral lymphadenopathy is observed, with 14% of cases involving cervical lymph nodes, 5% involving axillary lymph nodes, and 2% involving supraclavicular lymph nodes.⁶ In localised cases, there are typically no symptoms. However, depending on the location of the mass, dyspnoea, hoarseness, pain, and so forth may be observed.⁷ In our case, the patient exhibited no symptoms, and the lesion was identified following the observation of a swelling in the neck. Although the mediastinum is the most common site of involvement, any part of the body may be affected. Radiologically, the lesion appears as a smoothly circumscribed and lobulated contoured mass. In terms of histopathology, the hyaline vascular type is the most prevalent in this form. A study of 83 paediatric cases revealed that 54% were of the hyaline vascular type, 24% plasma cell type and 22% mixed type.⁶ The histological examination revealed the presence of hyaline vascular type in our case. This type is associated with a more favourable prognosis and a less aggressive clinical course than the plasma cell type. The incidence of multicentric Castleman disease (MCD) is highest in the sixth and seventh decades of life. This form is more prevalent in males and is more frequently associated with IL-6, HIV and HHV-8. The majority of these cases present with systemic symptoms, including fever, night sweats, weight loss, and malaise, as well as laboratory abnormalities, such as anaemia, hypergammaglobulinaemia, elevated acute phase reactants, and hypoalbuminaemia.^8-10 A comparative summary of previously reported paediatric Castleman's disease cases is presented in Table 1, demonstrating similarities and differences in clinical presentation, disease type, treatment and outcomes.

Localised CD is treated surgically by the removal of the mass. If the mass is completely removed, the disease is cured.⁷ Radiotherapy is a treatment method employed in cases where excision is not possible. In our case, the patient achieved a complete cure with surgery, and no recurrence was observed during the follow-up period. A comprehensive treatment protocol for multicentric CD has yet to be established. A range of therapeutic approaches are currently being trialled, including surgery, radiotherapy, chemotherapy, antiviral agents and monoclonal antibodies.

Conclusion

Castleman's disease is a benign lymphoproliferative disorder. In children, particularly in the case of suspicious masses located in the neck and mediastinum, the disease can be diagnosed following the histopathological exclusion of lymphoma. In localised, hyaline vascular type, the disease is curable with complete surgical excision.

Declaration of Interest

The authors declare that they have no conflict of interest.

References

1. Castleman B, Towne VW. Case records of the Massachusetts General Hospital. N Engl J Med 1954;251:396-400.

2. Kim MH, Hwang S, Choi YB, et al. Castleman disease of the abdomen--single-center experience of 13 surgically treated patients over 11 years. Hepatogastroenterology 2010;57:1060-3.

3. Gündüz E, Kırkızlar H, ÜMİT E, et al. Castleman Disease: A Multicenter Case Series from Turkey. Turk J Hematol 2022;39:130-5.

4. Van Rhee F, Oksenhendler E, Srkalovic G, et al. International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease. Blood Adv 2020;4:6039-50.

5. Simpson D. Epidemiology of Castleman disease. Hematol Oncol Clin North Am 2018;32:1-10.

6. Parez N, Bader-Meunier B, Roy C, Dommergues J. Paediatric Castleman disease: report of seven cases and review of the literature. Eur J Pediatr 1999;158:631-7.

7. Talat N, Belgaumkar AP, Schulte KM. Surgery in Castleman's disease: a systematic review of 404 published cases. Ann Surg 2012;255:677-84.

8. Puram SV, Hasserjian RP, Faquin WC, Lin HW, Rocco JW. Castleman disease presenting in the neck: report of a case and review of the literature. Amer J Otolaryn 2013;34:239-44.

9. Hu S, Li Z, Wang H, et al. Clinical features and treatment outcomes of Castleman disease in children: a retrospective cohort in China. Eur J Pediatr 2023;182:5519-30.

10. Farruggia P, Trizzino A, Scibetta N, et al. Castleman's disease in childhood: report of three cases and review of the literature. Ital J Pediatr 2011:37:50.