Castleman's disease diagnosed on fine needle aspiration cytology: A multidisciplinary approach to diagnosis

Dear Editor, Castleman’s disease (CD) is a rare lymphoproliferative disorder of unknown aetiology that has a prevalence of less than 1 per 100,000 population. The original case series by Castleman and colleagues in 1956 referred to patients who were found to have mediastinal lymph node enlargement with characteristic histopathological features of lymphoid hyperplasia and capillary proliferation. Since then, three distinct subsets of the disease have been described on the basis of differing histopathological features as 1. hyaline vascular, 2. plasma cell and 3. plasmablastic variants. The hyaline vascular variant of Castleman’s disease (HVCD) is usually localised to a single site and commonly affects the mediastinum. Patients with this variant are typically asymptomatic and the vast majority will have an uncomplicated post-surgical course. However, pre-operative diagnosis remains difficult given its non-specific clinical presentation and wide differential diagnosis on both radiology and cytology. Initial fine needle aspiration (FNA) may be performed in order to assist in future treatment planning, however, only a few case reports and small case series have been described. Here we discuss a challenging cytology case which demonstrated characteristic features of CD where, through targeted immunocytochemistry and close liaison with radiology colleagues, a diagnosis of CD was made. We report a case of young woman who presented with increasing shortness of breath. Computed tomography (CT) scan of the neck and thorax (Figure 1) demonstrated a large, well-defined, strongly enhancing, soft tissue attenuation mass with a focal calcific nidus situated in the right superior mediastinum. The mass was enveloping the vascular structures and causing tracheal deviation. CD was considered as part of the radiological differential diagnosis. As the mass was located in the mediastinal soft tissue, an FNA of the mass was feasible and was performed by a Consultant Radiologist under ultrasound guidance. Two passes were performed and prepared as two air-dried direct spread slides (Rapi-Diff) and one Cytofix ethanol-based alcohol spray fixed direct spread (Papanicolaou). The needle was rinsed into CytoRich Red preservative fluid to make one SurePath preparation (Papanicolaou) and an agar cell block (Haematoxylin and Eosin). The aspirates were moderately cellular and comprised mostly small lymphoid cells with a few medium-sized and large lymphoid cells. Hyalinized capillaries were noted and there were scattered markedly enlarged atypical cells, with ill-defined cytoplasm and enlarged nuclei, with many showing binucleate and multinucleate morphology (Figure 2A, 2B and 2C). On higher power examination the nuclei exhibited fine granular ‘tissue paper’-like chromatin, nuclear grooves, and prominent nucleoli. Eosinophils were not prominent and classical ReedSternberg cells were not seen. The agar cell block prepared from remaining needle rinse material contained a hyalinized follicle centre fragment. Immunocytochemistry performed on the cell block demonstrated a mixed population of CD3 positive T cells and CD20 positive B cells. The large cells were positive for CD21 and negative for CD15, CD30 and AE1/AE3. HHV-8 was negative. Flow cytometry was not performed in this case. The cytomorphological features in this case satisfied the criteria as detailed by Mallik et al, namely (i) large ovoid cells with ill-defined cytoplasm, large nuclei with irregular nuclear membranes and fine or coarse chromatin with a tissue paper appearance; and (ii) a background of polymorphous lymphocytes. In the context of the radiological findings as described above a diagnosis of Castleman’s disease was