Castleman disease multicentric angiofollicular dysplasia giant lymph node hyperplasia

Benjamin Castleman in 1954 described a male patient who initially presented with frequent colds, followed by a nonproductive cough and night sweats. Fluoroscopy revealed a homogeneous lymphadenopathy placed in the anterior mediastinum. The anatomical diagnosis after the surgical excision was hyperplasia of the mediastinal lymph nodes [1].

Contemporary Castleman's disease (CD) is also known as an angiofollicular or giant lymph node hyperplasia [2]. It is a rare orphan disease with an incidence of approximately 21-25 cases per million people [3]. There are no identifiable risk factors in its development. Nevertheless, recent studies have postulated four different possible etiologies (pathogen, autoimmune, auto-inflammatory, and paraneoplastic) [4]. The disease's clinical manifestations are diverse, from asymptomatic lymphadenopathy to recurrent episodes of diffuse lymphadenopathy with severe multiorgan involvement. The unicentric CD usually presents with localized lymphadenopathy, commonly occurring in the thoracic region, column, abdomen, and retroperitoneum [5,6]. The multicentric CD (MCD) is a systemic disorder involving cytokine-induced polyclonal lymphoproliferation and systemic inflammation due to overexpression of interleukine-6 [7,8]. Two subtypes of MCD include HHV8 related and HHV8 non-related or idiopathic multicentric Castleman disease [9]. MCD has a varied range of symptoms, the most common being lymphadenopathy, fever, hepatosplenomegaly, asthenia and pleural effusion or ascites, etc. Laboratory analysis includes anemia (iron deficiency or sometimes hemolytic), thrombocytopenia, proteinuria, hypoalbuminemia, and polyclonal hyper-gammaglobulinemia.

For a diagnosis of CD, a biopsy of involved tissue is necessary, along with clinicopathological features of the disease [10-12]. Furthermore, it is crucial to exclude other diseases before diagnosing CD, primarily lymphomas, acute Epstein-Barr virus, systemic lupus erythematosus, paraneoplastic pemphigus, Bechet’s disease, secondary amyloidosis, lymphoid interstitial pneumonitis, bronchiolitis obliterans and multitude of renal disorders [13,14].

In our report we present a 16-year-old girl presented to the family physician with painful swelling in her left axillary region.

Her past medical history was uneventful. Physical examination revealed enlarged infraclavicular lymph node, approximately 4 cm in diameter in the left lower part of the axillary region. The girl had no fever, sweating, pruritus, or weight loss but felt more tired than usual. The first ultrasound examination revealed a conglomeration of lymph nodes (8,9x4,9 cm) in the left axillary and retro-pectoral region. Laboratory results were within the normal values for age, with the exception of CRP, which was 15,5 mg/L. Her chest X-ray was normal without mediastinal enlargement. After biopsy and cytological analysis, a referral histopathological diagnosis was a lympho-proliferative disease (Hodgkin lymphoma) but could be also found in disseminated Kaposi’s sarcoma, plasmacytoma, rheumatoid lymph nodule, vaccination sites, skin involvement with erythroderma or urticaria, lipoid nephrosis, peripheral vascular disease, and Wiskott- Aldrich syndrome [14].

The first surgical biopsy showed no signs of malignant tissue but it was clear that accepted material was lymphoproliferative disease with reactive lymph nodes. MSCT confirmed enlarged, hypervascular lymph nodes measuring 6.1 cm and 7.7 cm in the same region. Furthermore, PET-CT registered multiple hyper-vascularized lymph nodes and splenomegaly.

At that point, she was referred to our Department of Oncoplastic Surgery for a second axillary lymph node biopsy.

After the second biopsy which only confirmed lymphoproliferative disease, magnetic resonance imaging of the pectoral region revealed a mass of enlarged lymph nodes measuring 7.5 x 3.2 x 7 cm with the biggest lymph node measuring 6.1 cm in diameter (Figure 1).

Due to the extent of local lymphadenopathy, neoadjuvant immunotherapy with 4 cycles of rituximab (375mg/m2 intravenously weekly) was administered. There was just a partial tumor reduction to neoadjuvant therapy, so the patient was reconsidered for surgery. Although blood tests disclosed preoperative anemia (Hb 10.8 g/L), there was no need for blood transfusions. The patient underwent a complete extirpation of the enlarged lymph nodes now measuring 4,2x2,7cm, 3,7x1,9 cm and 2,1x1,2 cm, respectively. Pathology finally confirmed Castleman disease of the multicentric hyaline‐vascular histologic type.

An interdisciplinary consultation was requested from the radiotherapist, who considered that adjuvant radiotherapy was not necessary. Two months after the operation, the patient made a full recovery without any complaints.

Three months after surgery, a high-resolution ultrasound examination demonstrated two enlarged lymph nodes inferior to the left subclavian vein. The patient underwent an MRI, which confirmed two large retropectoral lymph nodes in the clavicular region, measuring 3 and 2.5 cm.

We surgically removed the nodes, and the pathohistological report confirmed the previous diagnosis. Ultrasound examination was performed intraoperatively and showed no residual disease. One month after the surgery ultrasound follow-up showed one 2,2 cm enlarged lymph node below the acromial part of the left clavicle. We decided to “watch and wait” with regular ultrasound examinations. The patient remained asymptomatic, except for a temporary sensation of tension in the scar area during a three-year follow-up period. Finally, three years from the last excision, we excised the last enlarged lymph node, which measured 3.5 cm.

More than two years after the third surgical excision, the patient was still asymptomatic, without any lymphadenopathy, arm lymphedema or any abnormal laboratory findings.