Multicentric Castleman’s disease of the lungs mimicking a multifocal adenocarcinoma

Abstract

A female patient presented with fever of unknown origin, night sweats and weight loss. She had no pulmonary symptoms. Investigations revealed bilateral ground glass lung lesions which were subsequently followed-up with imaging. Two years later, a follow-up CT scan revealed an increase in the size of the lesions which exhibited a more solid appearance. A diagnostic biopsy was difficult to perform, and the patient underwent a left upper lobectomy for suspected primary lung malignancy. Histological examination showed lung involvement by Castleman’s disease of plasma cell type which displayed a multifocal distribution. There was no evidence of nodal involvement. Following discussion at the multidisciplinary team meeting and correlation with radiology, a diagnosis of multicentric Castleman’s disease of the lung was made. Here, we present an unusual case of multicentric Castleman’s disease of the lung mimicking primary lung carcinoma. Our case highlights the importance of considering this entity in the differential diagnosis of multifocal lung lesions with a ground glass-like appearance to allow early diagnosis and management.

Background

Lung nodules are common incidental findings with a wide differential diagnosis that includes infections, benign lesions and primary and secondary lung malignancies. Appropriate treatment depends on the exact nature of the lesion. In cases where reaching a definitive diagnosis is challenging, a multidisciplinary approach with input from various specialities is essential to reach an appropriate management plan.¹

Castleman’s disease (CD) is a relatively rare disorder characterised by proliferation of lymphoid tissue and can be localised unicentric or multicentric.^2–4 It occurs most commonly in adults but can also be present in children. The most common clinical presentation is mediastinal lymph node enlargement. Lung involvement by CD of the lung is rare and can pose a diagnostic challenge.

We describe a case of multicentric CD primarily involving the lung with no evidence of nodal involvement which was clinically highly suspicious of a primary lung malignancy. Our case highlights the importance of considering this entity in the differential diagnosis of single and multifocal lung lesions, especially those with a ground glass-like appearance.

Case presentation

A female patient in her 70s, non-smoker and known to have diverticular disease presented 2 years ago with fever of unknown origin, night sweats, weight loss, upper back pain and diarrhoea. She had no respiratory symptoms. Her blood tests showed white cell counts 9.5×10⁹/L and C reactive protein 122 mg/L, with no other significant blood abnormality. The differential diagnoses included diverticular disease, discitis and osteomyelitis, all of which were excluded by whole spine MRI and CT scans. However, an incidental finding on a chest CT was the presence of mixed ground glass and soft tissue density in the left upper lobe of lung (measuring 1.7×0.7 cm) and in addition to a separate small ground glass nodule anteriorly in the same lobe (figure 1).

Figure 1.

CT scan shows mixed ground glass and soft tissue density in the left upper lobe.

Investigations

Decision by the multidisciplinary team (MDT) was to follow-up the lesions by chest CT scan which showed stability in the size of the lesions within the next 15 months. Accordingly, follow-up continued with CT scan which was performed 2 years after her initial presentation. This showed a slight increase in the size of the left upper lobe nodule which now measured 17×10 mm (previously 17×7 mm), and it had an increased soft tissue component. The ground glass nodule anteriorly within the left upper lobe had increased from 5.5 to 8.5 mm (figure 2). Further small ground glass nodules were now noted in the right lung.

Figure 2.

Left upper lobe nodule.

A PET CT scan was performed, and the nodule on the medial aspect of the anterior segment of left upper lobe showed increased FDG uptake (SUV max 4.8 g/mL) (mediastinal blood pool SUV max 3.2 g/mL) (figure 3). The 5 mm peripheral nodule in the anterior segment of left upper lobe did not show any FDG uptake, but the size was below sensitivity of the scanner.

Figure 3.

CT and PET scan for the main lesion in left upper lobe.

Due to the location of the larger lesion, it was not felt possible or safe to do a bronchoscopic or percutaneous biopsy. The Herder score was calculated at 81% risk of malignancy.

Differential diagnosis

Differential diagnosis included primary lung cancer, secondary lung metastasis, lymphoma and a benign lesion. The case was discussed in the MDT and taking in consideration increasing the size of the nodules, transforming from ground glass to solid lesion and increased uptake on the PET scan the differential diagnosis favoured primary lung malignancy.

Treatment

As there was high suspicion of malignancy, the plan was to proceed to surgery using a minimally invasive approach. We were of the opinion that, as the lesion was deep seated, a wedge resection would be inappropriate. We considered the possibility of a segmentectomy and frozen section, but the additional nodules would have remained in the upper lobe without a diagnosis; hence, it was decided that an upper lobectomy would be more appropriate. The patient was consented and aware that the final pathology may reveal non-malignant disease.

A video-assisted thoracoscopy left upper lobectomy and lymph node dissection was performed, and the patient recovered well without any complications. On discharge, her blood tests showed white cell counts 8.3×10⁹/L and C reactive protein 60 mg/L, with no other significant blood abnormality. The specimen was sent for histopathological examination.

Outcome and follow-up

Histological examination of the lobectomy specimen showed multifocal infiltration of the lung parenchyma by a dense infiltrate that consisted of numerous reactive lymphoid follicles with prominent germinal centres in addition to many rather atretic-looking follicles (figure 4A). The interfollicular areas contained sheets of mature looking plasma cells with frequent Russell bodies also noted (figure 4B). Immunohistochemistry showed the follicles exhibited a normal immunophenotype being negative for BCL2 (figure 4C). The plasma cells in the interfollicular areas were highlighted with MUM1 and displayed a polytypic pattern of staining with kappa and lambda immunohistochemistry (figure 4E, F). There was no evidence of an EBV or HHV8 infection. The appearances were consistent with multifocal lung involvement by CD of plasma cell type. Examination of the recovered lymph nodes showed non-specific reactive change with no evidence of involvement by CD.

Figure 4.

(A) Histological examination showed infiltration of the lung by an infiltrate that included reactive follicles in addition to atretic follicles (H&E ×4). (B) The interfollicular areas contained sheets of plasma cells including Russell bodies (H&E ×20). (C) The follicles were negative for BCL2 (H&E ×4). (D, E and F) The plasma cells stained positively for MUM1 and were polytypic with kappa and lambda immunostains (H&E ×4).

Following the histological diagnosis, the findings were correlated with imaging which showed bilateral lung involvement, and a final diagnosis of multicentric CD was made by the lung MDT. Long-term interval CT scan follow-up with the local haematology team was arranged, and adjuvant treatment was not required. The patient had a follow-up CT scan after 6 months from surgery, and it showed stable right lung nodule and no disease recurrence in left lung (figure 5). The blood test showed that white cell counts 7.7×10⁹/L and C reactive protein 11 mg/L.

Figure 5.

CT scan shows stable ill defined ovoid opacity in the right lower lobe.

Discussion

CD is a rare lymphoproliferative disease that can affect single (unicentric) or multiple (multicentric) lymph nodes. There are two known pathological types: hyaline-vascular and plasma-cell type.⁵ The cause of CD is unknown, for example, the plasma-cell type could be a reaction to chronic infection. However, no bacteria or such organisms could be isolated.² The hyaline-vascular type may originate from an antigen stimulus involving a lymph node containing abnormal plasmacytoid monocytes.⁶

CD most commonly affects young men and children. Common sites affected include neck, mediastinum, abdomen and rarely the retroperitoneum.⁶ Lung involvement is a very rare presentation of CD. The typical appearance on a CT scan is an enhancing mediastinal nodal mass mimicking lymphoma, thymoma or neurogenic tumour.³ Patients with CD are often asymptomatic or have non-specific symptoms such as fever, weight loss, diarrhoea and anaemia.⁷ This presents a challenge in making the diagnosis of CD, particularly as the finding imaging is hard to discriminate from lung malignancy. The treatment of unicentric CD is usually with surgery or radiotherapy while multicentric disease usually treated with chemotherapy and or steroids.²

Yeh et al reported a case of a male patient in his 40s who presented with chronic cough and a CT scan showed 4.5×3 cm mass located in the left upper lobe. The patient underwent surgery due to concern of malignancy. Final pathology showed hyaline-vascular lymph node hyperplasia compatible with CD.² Luo et al described 48 cases of intrathoracic CD over 20 years. Of these, only three cases were confined as unicentric and underwent surgery. On the other hand, all multicentric were CD treated with chemotherapy or observation depending on the severity of symptoms and none with surgical resection.⁴

Incidental findings of lung nodules are common and pose a challenge due to the wide differential of either benign or malignant disease. An MDT approach is essential to guide investigation and treatment. Surgical resection is frequently required when biopsy is not possible and confirms the diagnosis as well as being the recommended treatment for localised disease.

Learning points.

• Castleman’s disease of the lungs is very rare and presents a diagnostic challenge.

• Castleman’s disease should be considered as a rare cause of multifocal lung lesions including those with ground glass appearance.

• Multidisciplinary team discussions are essential in approaching difficult lung lesions to allow early investigation, diagnosis and management.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).