Castleman Disease: Diagnosis on Cytology

Dear Editor,

Enlarged lymph node is a commonly encountered clinical problem and may be due to an inflammatory process, malignant lymphoma, or metastatic malignancies.[1] FNAC is a rapid, easily available, highly sensitive, and specific tool in differentiating benign or malignant lesion; which helps in patient management.[1] Castleman disease (CD), also known as giant lymph node hyperplasia, represents a morphological distinct lymph node proliferation that in most cases is of unknown etiology.[2] It occurs most commonly in adults, but can also affect children. Clinically, CD can present as a solitary mass with no major symptoms (unicentric CD) or can be generalized with symptoms like fever, weight loss, generalized lymphadenopathy, and hepatosplenomegaly (multicentric CD).[3]

Herein we report a case of a 14-year-old male child with cervical lymphadenopathy diagnosed as Castleman disease on fine needle aspiration cytology and confirmed on histopathology. On physical examination, multiple swellings were detected in the left posterior triangle region with the largest one being 4.0 cm. They were firm in consistency, non-matted, mobile, and non-tender [Figure 1a]. No other lymphadenopathy or organomegaly was noted. Peripheral blood counts and routine biochemistry parameters were within normal limits. Ultrasonographic examination of the cervical region revealed a large lymph node in the left posterior triangle measuring 4 × 3.3 × 1.5 cm with increased internal vascularity on spectral doppler. Also seen were multiple subcentrimetric reactive lymph nodes in the left cervical level II and III. Multislice CT scan of the neck was performed on the child revealed a well-defined oval, homogenously enhancing lesion measuring 4.6 × 3 × 1.9 cm in the posterior cervical space with few peripherally enhancing vessels. USG-guided FNAC was performed from the largest node. Smears were highly cellular and showed many mature and transformed lymphoid cells, many large germinal center fragments showing vascular tangles within [Figure 1b]. Occasional lollipop like lesion was identified [Figure 1c]. These also showed large bizarre follicular dendritic cells having round or oval shape, ill-defined cell borders, large nuclei with vesicular chromatin, and hyalinized eosinophilic globular material [Figure 1d]. Few singly scattered large atypical cells [Figure 1c arrow] and occasional Warthin Finkeldey giant cells [Figure 1e] were seen. No eosinophils or plasma cells was seen. No definite classical R S cells were seen. Cytological diagnosis of atypical lymphoid cells with strong suspicion of CD was made and biopsy was advised. Excision biopsy was performed subsequently which showed all the classical features of Hyaline vascular type CD [Figure 1f-h].

Figure 1.

(a) Enlarged cervical Lymph nodes. (b) Highly cellular smear (Giemsa, x40). (c) Vessel entering germinal center fragment giving lollipop appearance, atypical cells (arrow) in background (Giemsa, x100). (d) Hyaline material in germinal center fragment with dysplastic Follicular Dendritic cell (Giemsa, x400). (e) Warthin Finkeldey giant cells (Giemsa, x400). (f) Twinning of follicles (HE, x100). (g) Lollipop lesion (HE, x400). (h) Hyalinization of lymphoid follicle (HE, x400)

On USG, most cases of CD show a well circumscribed, homogeneously hypoechoic mass lesion. In all the reported cases of CD, the longitudinal to transverse axis ratio of the lymph nodes was more than 2, as seen in our case.[3] Characteristic finding on color doppler is marked peripheral vascularity which is not seen in reactive lymph nodes.[3]

The cytological feature of increased capillary fragments was described in the first FNA case report of CD by Hidvegi et al. in 1982.[4] Since then, over half the FNA reported cases of CD have described increased branching capillaries as a feature. In 2000, Taylor et al.[5] described dysplastic follicular dendritic cells in a FNA case report of CD for the first time. In 2007, the cytomorphological findings in 3 histopathologically documented cases of hyaline vascular CD were evaluated by Mallik et al.[6] to help identify CD on FNAC. The suggested criteria were: i) Presence of large oval to round cells having ill-defined cytoplasmic margins and large nuclei with irregular nuclear outlines having fine or coarse chromatin, which represented the dysplastic FDCs and ii) Polymorphous background lymphoid population with predominating small lymphocytes. This case report along with review of literature on cytological diagnosis of hyaline vascular type CD suggests the addition of increased vascular fragments as a criteria to help in the diagnosis of CD on FNA.[5]

The main differential diagnoses for CD are reactive lymph node and Hodgkin’s disease. The presence of hyalinized material and increased vascularity will be helpful to differentiate it from hyperplastic reactive node. Large atypical cells in CD might be misinterpreted as Reed Sternberg cells; however, the awareness of dysplastic follicular dendritic cells within aspirates of CD will help to avoid the misdiagnosis of Hodgkin’s lymphoma[2] Also, the absence of polymorphous background with eosinophils and plasma cell would be helpful.

In conclusion, a definitive diagnosis of Castleman disease is difficult on FNA; however, the cytological characteristic features of dysplastic dendritic cells and increased vascular branches, and hyaline material within the germinal center fragments against a polymorphous lymphoid population, along with the clinical features of asymptomatic enlarged lymph node, especially in a young adult and radiological features should invoke a differential diagnosis of CD, ruling out malignancy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.