Intrapulmonary unicentric Castleman disease mimicking peripheral pulmonary malignancy

Abstract

Castleman disease, also known as angiofollicular lymph node hyperplasia, can manifest as a unicentric or multicentric disorder. Intrapulmonary Castleman disease is very rare. Here, we present a patient with intrapulmonary Castleman disease who underwent left upper pulmonary lobectomy for suspected early lung cancer. The histopathologic diagnosis of the lobar mass was hyaline-type Castleman disease. The patient has remained well after surgery, showing no local recurrence or distant disease during a two-year follow-up period. Although unicentric Castleman disease originating in the lung is rare, it should be considered in the differential diagnosis of primary pulmonary malignant tumors.

Introduction

Castleman disease, also known as angiofollicular lymph node hyperplasia, was first described by Benjamin Castleman in 1954. It can manifest as a unicentric or multicentric disorder, and can occur anywhere throughout the lymphatic system. It often develops in the neck, mediastinum, pulmonary hilum, and abdomen, which are sites where lymph nodes aggregate.^1–5 Intrapulmonary Castleman disease is very rare, and to date, only a few cases have been reported. Here, we present a patient with intrapulmonary Castleman disease, which was diagnosed after surgery for suspected primary pulmonary malignancy.

Case presentation

The patient was a 32-year-old man who was referred to our hospital because of a mass in his left upper pulmonary lobe that had been discovered during a general medical examination performed one week previously. The patient was asymptomatic. As seen in Figure 1, enhanced chest computed tomography (CT) showed a 3.1 × 2.9 × 3.0 cm mass in the left upper pulmonary lobe. The mediastinal and pulmonary hilar lymph nodes were not enlarged. Whole-body positron emission tomography (PET)/CT showed that the mass had an elevated concentration of tracer (fluorine-18-fluorodeoxyglocose [18F-FDG]), with a standardized uptake valuemax (SUVmax) of 3.3, and no other signs of elevated uptake suggesting malignancy. The patient was a cigarette smoker, with a 10 pack-year history, but had no other significant history. His physical examination upon admission was unremarkable. Laboratory testing, including the tuberculin purified protein derivative test and tests for HIV infection and circulating tumor markers (carcinoembryonic antigen, squamous cell carcinoma antigen, neuron-specific enolase, and cytokeratin 21-1), were within normal limits. Findings on fiberoptic bronchoscopy and contrast-enhanced magnetic resonance imaging (MRI) of the brain were within normal limits. With a presumptive diagnosis of early-stage malignant tumor of the left upper lung, the patient underwent left upper pulmonary lobectomy and dissection of the systemic lymph nodes. The dissected specimen contained a pale, approximately 3 cm mass that was easily distinguished from the surrounding lung tissue. The mass contained hyperplasia of hyalinated lymph follicles, supporting a histopathological diagnosis of hyaline-type Castleman disease (Fig. 2). Immunostaining was negative for expression of CD3, CD5, CD20, CD21, CD23, and Cyclin-D1. All dissected lymph nodes appeared normal on histopathological examination. The patient had an uneventful postoperative recovery and is undergoing follow-up without any additional treatment. He has remained well without recurrence or distant metastasis over a two-year period. The patient granted written informed consent for publication of this manuscript and the accompanying images.

Figure 1.

(a–b) Enhanced chest computed tomography (CT). (c) Positron emission tomography (PET)-CT. Enhanced chest CT scans show a mass located in the upper left lung (a, in the lung window; b, in the mediastinal window), and (c) the PET-CT shows this mass to have an elevated SUVmax of 3.3.

Figure 2.

Histopathological images. (a) Hematoxylin-and-eosin stained sections show hyperplasia of hyalinated lymph follicles, supporting a histopathological diagnosis of hyaline-type Castleman disease. (b) Immunohistochemical staining of primary tumor with antibodies to CD3, CD5, CD20, CD21, CD23, and Cyclin-D1 was negative.

Discussion

Castleman disease is a rare disorder of lymphoid tissues throughout the body. Although it is generally benign, Castleman disease can behave like a malignant disease. It is also known as nodal hyperplasia, angiofollicular hyperplasia, giant lymph node hyperplasia, giant hemolymph node, angiomatous lymphoid hamartoma, and follicular lymphoreticuloma.⁶

Castleman disease has two distinct clinical presentations: unicentric (localized) and multicentric (systemic). The etiology remains unclear; human herpesvirus-8 has been suggested to play a causative role in the development of multicentric Castleman disease.⁷ Castleman disease has also been described in association with a number of conditions, including human immunodeficiency virus infection (HIV), Kaposi sarcoma, Hodgkin lymphoma, non-Hodgkin lymphoma, and polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome.^8–10

The natural history and types of treatment vary according to the form of the disease. Although Castleman disease can occur at any age, most of the literature indicates that unicentric disease tends to appear in the third to fourth decades. It is rarely reported in children,^11–13 and is found in equal rates in men and women. Multicentric Castleman disease most frequently occurs in the elderly and/or in patients with immunodeficiency, particularly patients with the acquired immunodeficiency syndrome.

The most common locations of unicentric Castleman disease include the mediastinum, pulmonary hilum, abdomen, and axilla; although lesions in the mesentery, nasopharynx, retroperitoneum, and lower extremity have also been reported.¹⁴ Patients with the unicentric form generally present without symptoms or with symptoms related to the mass. Patients with the multicentric form, which often causes marked systemic symptoms, can present with fatigue, fever, malaise, night sweats, and weight loss. Laboratory findings can include cytopenia, hepatosplenomegaly, polyclonal hypergammaglobulinemia, hepatic dysfunction, and renal dysfunction, which are a result of the release of cytokines, such as interleukin (IL)-6, IL-1, and tumor necrosis factor-α.

This disease has two histopathological patterns, hyaline-vascular and plasma cell; although intermediate mixed types have recently been reported.¹⁵ The hyaline-vascular pattern accounts for 90% of cases. Unicentric Castleman disease predominantly has a hyaline-vascular pattern. The multicentric disease mostly has a plasma cell pattern.

The preoperative diagnosis of pulmonary Castleman disease is difficult because of its rarity and nonspecific radiographic signs. The lesion may present as a homo- or heterogeneous soft tissue mass on CT. The pattern of contrast enhancement depends on the rate and volume of contrast media. It has been reported that larger lesions might have a heterogeneous appearance in association with central necrosis or degeneration.² Hideki et al. reported a patient with a hepatic hilar mass that was accurately diagnosed preoperatively.³ They used three-dimensional CT angiography, which showed that the mass received its blood supply through a vascular network on its surface that originated from two right bronchial arteries. MRI of patients with Castleman disease often shows a low-intensity signal on T1-weighted images and a high-intensity signal on T2-weighted images. These radiographic imaging findings are common to many other lesions. With regard to the differential diagnosis of Castleman disease using these nonspecific findings, the most important is lung cancer. Other conditions commonly confused with Castleman disease include infectious and inflammatory lesions, including tubercular lesions, bronchial carcinoid, and inflammatory pseudotumor.

The value of FDG-PET/CT for the diagnosis of Castleman disease is controversial; it has been reported to be ineffective for differentiating between malignancy and Castleman disease.^16,17 In our patient, the FDG-PET/CT finding of accumulation in the left upper lung suggested a malignant tumor of pulmonary origin. A preoperative biopsy was not recommended because an adequate tissue sample could not be collected (the lack of which can lead to a false-negative finding), and the possibility of tumor dissemination during the biopsy.

The best treatment for unicentric Castleman disease is surgical resection. The preferred surgical procedure for pulmonary Castleman disease is lobectomy, as it may be difficult to determine whether the lesion is malignant at the time of resection, especially when preoperative findings suggest malignancy. There have been a few reports of recurrence after surgery, usually following subtotal resection.

Previous reports have suggested that resection of the lesions of Castleman disease can be difficult because of major vessels or adhesions associated with the mass. Gulsah et al. reported a patient who underwent exploratory thoracotomy and was found to have definitive pathological disease. In that case, limited resection could be performed to spare the lung parenchyma.¹⁸ In our patient, the mass was located in the left upper lung and there was no obvious demarcation between the mass and the lung parenchyma. Therefore, we performed a lobectomy with no operative complications.

Studies have also confirmed that Castleman disease can be successfully treated using radiation therapy for patients who have unresectable lesions or who cannot undergo surgery because of comorbidities.¹⁹ Multicentric Castleman disease requires treatment using corticosteroids and chemotherapy and has a poor prognosis. This form of disease is typically accompanied by increased concentrations of circulating cytokines, primarily IL-6. Patients with multicentric disease have recently been treated using antibodies against the IL-6 receptor, such as tocilizumab and siltuximab, with relatively satisfactory results.^20,21

After two years of follow up, our patient remains healthy without signs of recurrence or distant metastasis.

Conclusion

This is a report of a rare case of intrapulmonary Castleman disease. Because it is easily misdiagnosed before surgery as a result of nonspecific imaging findings and low rate of occurrence, it is important to include Castleman disease in the differential diagnosis of a pulmonary mass.

Disclosure

No authors report any conflict of interest.