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Year : 2016  |  Volume : 7  |  Issue : 1  |  Page : 66-69

Cytodiagnosis of Castleman's disease: A diagnostic challenge

1 Department of Pathology, AJ Institute of Medical Sciences, Mangalore, Karnataka, India
2 Department of Pathology, Father Muller Medical College, Mangalore, Karnataka, India

Date of Web Publication21-Jan-2016

Correspondence Address:
Sushma Hosamane
Assistant Professor, Department of Pathology, AJ Institute of Medical Sciences, Mangalore, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-9727.174653

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Castleman's disease (CD) is an uncommon cause of solitary or multiple lymphadenopathy, which may be a target for fine-needle aspiration (FNA). Because of its rarity and lack of adequate literature available on its cytomorphological findings, the condition is misdiagnosed or missed out during routine FNA reporting. The presence of small lymphocytes and plasma cells with large atypical binucleate follicular dendritic cells resembling Reed-Sternberg cells may raise a suspicion of Hodgkin lymphoma (HL). Here, we report the cytodiagnosis and pitfalls in the diagnosis of CD in three cases. FNA smears were reviewed and pitfalls in the diagnosis analyzed and correlated with histopathological findings.

Keywords: Castleman, fine-needle aspiration (FNA), hyaline vascular, plasma cell variant

How to cite this article:
Pai MR, Hosamane S, Marla NJ. Cytodiagnosis of Castleman's disease: A diagnostic challenge. Muller J Med Sci Res 2016;7:66-9

How to cite this URL:
Pai MR, Hosamane S, Marla NJ. Cytodiagnosis of Castleman's disease: A diagnostic challenge. Muller J Med Sci Res [serial online] 2016 [cited 2023 Jun 6];7:66-9. Available from: https://www.mjmsr.net/text.asp?2016/7/1/66/174653

  Introduction Top

Castleman's disease (CD), also known as angiofollicular lymph node hyperplasia, is a nonclonal lymphoproliferative disorder. Of the three histological types described, solitary hyaline vascular subtype accounts for 90% of the cases and occurs frequently in the mediastinum and other sites including the lung, axilla, and nasopharynx.[1],[2],[3],[4]

The multifocal plasma cell variant is much less common and alternatively is associated with generalized lymphadenopathy, systemic symptoms, and characteristic laboratory findings. [1],[2]

In a superficial location, this lesion is amenable to superficial fine-needle aspiration (FNA). In deeper locations, radiologically-guided FNA can be performed. The third type is a mixed type of CD where the combination of hyaline vascular and plasma cell component is visualized. Experience with FNA diagnosis of CD is limited. [3],[4],[5],[6] Hence, we present the cytomorphological and histopathological features of three cases of CD highlighting the problems in the cytodiagnosis.

  Case Report Top

Case 1

A 40-year-old female presented with a firm, palpable swelling of 6.5 Χ 3.5 Χ 2 cm in the right parotid region. She noticed that it grew gradually to the present size over a period of 6 months. The patient had no systemic symptoms and her laboratory findings were unremarkable. FNA from the mass was performed.

Case 2

A 44-year-old man presented with anemia and chronic renal failure. He had massive proteinuria and raised serum urea (84 mg/dL) and creatinine (5.1 mg/dL) levels. A mesenteric mass of 5 Χ 4.7 Χ 4 cm was detected on imaging. To confirm the clinical suspicion of non-Hodgkin lymphoma (NHL), computed tomography (CT)-guided FNA was conducted.

Case 3

A 60-year-old man presented with weakness, loss of weight, and generalized lymphadenopathy involving the right cervical, axillary, and right inguinal regions. His complete blood count was normal with massively increased erythrocyte sedimentation rate (ESR) of 100 mm at the end of 1 h. Serum electrophoresis showed increased gamma globulin (7.2 mg). Clinical diagnosis was NHL. FNA of the inguinal lymph node was performed.


FNA smears were stained by Papanicolaou and May-Grunwald-Giemsa stains in all three cases.

Case 1

Smears of the first case were hypercellular and consisted of polymorphic population of reactivated lymphoid cells, along with scattered dendritic reticulum cells [Figure 1]a. With these features, a diagnosis of reactive hyperplasia was suggested.
Figure 1: (a and b) Polymorphous population of lymphoid cells with a predominance of small lymphocytes and scattered large binucleate FDCs (MGG ×400, Pap ×400) (c) Hyalinized capillary fragments (MGG ×400) (d) Large binucleate FDCs with crumpled tissue paper appearance (MGG ×400) (e) FDCs with numerous small lymphocytes (MGG ×400) (f) FDCs with hyaline material surrounding plasma cells and lymphocytes (MGG ×400) (g) Case 3 showing many plasma cells and small lymphocytes (Pap ×400)

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Case 2

Smears showed a spectrum of reactivated lymphoid cells with a predominance of plasma cells. Also noted were dispersed, large atypical cells with one to paired nuclei and fragments of capillaries enveloped by hyaline material creating an impression of Hodgkin lymphoma (HL) with a differential of NHL of T-cell type [Figure 1]b-f.

Case 3

FNA of the inguinal lymph node of this 60-year-old man showed reactivated lymphoid cells, numerous plasmacytoid cells, small lymphocytes, and eosinophils [Figure 1]g. There was a sparse population of atypical cells on the contrary. Based on the predominant cell population, a cytodiagnosis of extranodal plasmacytoma with a differential of lymphoplasmacytic lymphoma was suggested.


Hematoxylin and eosin (H&E)-stained paraffin sections of the excised parotid lymph node of Case 1 showed features typical of hyaline vascular type of CD, i.e., lymph node with hyperplastic follicles having central vascular proliferation with hyalinization of vascular walls (lollipop appearance) and large follicular dendritic cells (FDCs). Concentric rings of mature lymphocytes surrounded the lymphocyte-poor centers and interfollicular vessels with rare plasma cells and eosinophils completed the picture [Figure 2]a and b.
Figure 2: (a and b) Gross and microscopic appearance of hyaline vascular CD with lollipop lymphoid follicles in Case 1 (H and E ×100) (c and d) Gross and microscopic appearance of mixed cellularity CD with sheets of plasma cells in Case 2 (H and E ×100) (e and f) Interfollicular areas in Case 2 with plasma cell infi ltration (H and E ×200)

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In Case 2, the excised retroperitoneal mass showed similar histomorphology as the above case but there were other features such as proliferating sheets of plasma cells with a background of amyloid. Congo red stain revealed congophilia and showed apple green birefringence under the polarizing microscope. Plasma cells were positive for both kappa and lambda light chains. There were eosinophils seen admixed with plasma cells. Large atypical dendritic cells were seen in the follicular centers [Figure 2]c and d. Numerous proliferating hyalinized blood vessels were also noted in the parafollicular area with plasma cells [Figure 2]e and f. Hence, the diagnosis of mixed type of CD was proposed. Case 2 had symptoms of renal failure, which was attributed to the hyperglobulinemia caused by functioning plasma cell repertoire.

Histomorphology and immunophenotyping revealed a possibility of plasma cell variant of CD with a preponderance of lambda light chain expression.

Axillary lymph node excised from Case 3 revealed a partial effacement of the architecture due to the sheets of proliferating mature-looking plasma cells surrounding the compressed lymphoid follicles [Figure 3]a. The possibility of CD of plasma cell type was strongly suspected. Immunophenotyping revealed a predominant expression of immunoglobin G (IgG) and lambda in excess over kappa by the plasma cells [Figure 3]b and c. Marker for human herpesvirus 8 (HHV-8) was negative in this case.
Figure 3: (a) Histopathology in Case 3 showing sheets of plasma cells and lymphocytes (H and E ×200) (b and c) Immunohistochemical markers kappa and lambda overexpression in plasma cells in Case 3 (×200)

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  Discussion Top

CD was first described in 1954 by Castleman as a lesion involving the mediastinal lymph nodes. However, later studies showed that even the extramediastinal sites could be involved and the disease could be localized or generalized and nodal or extranodal. [1],[2] Although histopathologically, three definite subtypes such as hyaline vascular, multicentric plasmacytic, and mixed types can be distinctly diagnosed, cytomorphology often poses problems. The less common plasma cell variant is often multifocal and associated with systemic symptoms of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS). [1],[2] Cases 2 and 3 described in the present report had generalized lymphadenopathy with constitutional symptoms and mild hepatosplenomegaly. The mixed population of lymphocytes and plasma cells, along with large atypical cells (FDCs) and numerous fragments of capillaries, raised many differential diagnoses including NHL, peripheral T-cell lymphoma (PTCL), HL, and CD.

Cytodiagnostic Pitfalls

In the first case, the large population of reactivated lymphoid cells and the presence of numerous capillaries with hyaline walls were ignored as reactive change. Moreover, the sparse, large FDCs were masked by the lymphoid cells. However, clinically the large size of the lymph node was discordant with the diagnosis of reactive node. Large atypical cells in the smears when reviewed lacked nuclear atypia, complex nucleoli and chromatin of  Reed-Sternberg cells More Details. The lymphocytes did not exhibit the atypia of PTCL. The first case report of CD by Hedvegi et al. [5] in 1981 described the cytological features that are concordant with the present cases. A feature that they felt useful was the presence of capillary vessels, which was ignored by us in the first two cases.

Cangiarella et al. [6] described the FNA features of a case of CD and described a polytypic B-cell population of mature lymphocytes and did not describe either FDCs or vessels. Clustering of large cells (FDCs) with small lymphocytes seen in first two cases were described by some other reports. [3],[4] Numerous small lymphocytes and a significant number of capillary fragments in the first two cases in the present study were not seen by other series. [7] Occasional hyalinized vessel fragments were noticed in the first two cases in the present study. A similar experience was documented in the study by Malik et al. [3] However, Meyer et al. [4] did not encounter any capillary fragments in the aspiration smears of their cases. The third case showed a total discordance in the cytodiagnosis as it showed only a large number of small lymphocytes and plasma cells. FDCs or capillary fragments were not appreciated. Histoarchitecture showed the lymph node with partial loss of architecture due to interfollicular infiltration by the plasma cells in diffuse sheets. Further immunohistochemistry performed for immunoglobulins and short chains confirmed the IgG predominance and lambda light chain excess over kappa. Hence, the immunohistochemical features correlated with the clinical presentation and concluded the diagnosis of CD.

Significant cytomorphological criteria, which assist in the recognition of CD are the presence of large cells (FDCs) with ill-defined cytoplasmic outlines and large nuclei with irregular nuclear membrane, inconspicuous to small nucleoli, chromatin of either fine or coarse caliber with an appearance of crumpled tissue paper [Figure 1]b, d, and f. Similar large cells have been noted not only in the present series but also described by earlier reports. [3],[4],[5],[6],[7] It has been rare when these atypical cells were not seen in the smears of CD as evidenced by the report by Chan et al. [8] These cells come from the center of the hyalinized follicles and hence, could serve as indicators for CD in smears. Immunophenotypic studies can demonstrate CD 21 on these cells in the cell block preparations. The presence of CD 21 antigen in conjunction with an absence of CD 20 would exclude the possibility of nodular lymphocyte predominant HL and T-cell-rich B-cell lymphoma (TCRBL). [7] Similarly, the lack of T-cell antigens on these large cells would exclude a peripheral T-cell lymphoma. On the other hand, lack of CD 15 and CD30 on these large cells would rule out a classical HL. [3] Other important features of cytodiagnosis, which cannot be ignored are the presence of significant number of capillary fragments and small lymphocytes. Mixed type of CD showed the presence of hyalinization and amyloid-like material. The presence of numerous plasma cells in the plasma cell variant of multicentric CD [7] is the only clue where extranodal plasmacytoma has to be ruled out by studying the clonality by assessing light chain kappa, lambda, and immunoglobins as in the Case 3 of the present series. Cytologic features for the diagnosis of plasma cell subtype of CD was not documented clearly in the literature.

  Conclusion Top

To conclude, it can be said that although the identification of CD on FNA is a diagnostic challenge we find that certain cytomorphological features may be helpful in difficult cases. These are the presence of large cells with ill-defined cytoplasmic outlines and large irregular nuclei with inconspicuous nucleoli, peculiar fine to coarse nuclear chromatin with the appearance of crumpled tissue paper appearance, and aggregated clusters of small lymphocytes and fragments of capillaries with or without hyalinized walls. The presence of plasma cells also may give a clue if they are accompanied by the FDCs and capillary fragments as in mixed type of CD. Nevertheless, plasma cell predominance alone does not guide us to the cytodiagnosis of CD. However, these features observed by us should be analyzed in large studies to determine if they could in any way reduce the diagnostic dilemma.

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Conflicts of Interest

There are no conflicts of interest.

  References Top

Iochim HL, Medeiros JL. Lymphadenopathies. In: Iochim HL, Medeiros JL, editors. Iochim′s Lymph node Pathology. 4 th ed. Philadelphia: Lippincott Williams & Wilkins; 2008. p. 227-37.  Back to cited text no. 1
Rosai J. Lymph nodes. In: Rosai J, editor. Ackerman′s Surgical Pathology. 10 th ed. St. Louis: Mosby: 2011. p. 1796-8.  Back to cited text no. 2
Mallik MK, Kapila K, Das DK, Haji BE, Anim JT, Cytomorphology of hyaline-vascular Castleman′s disease: A diagnostic challenge. Cytopathology 2007;18:168-74.  Back to cited text no. 3
Lisa M, David G, Ashfaq R, Vuith F, Saborian MH. Fine needle aspiration findings in Castleman′s disease. Diagn Cytopathol 1999;21:57-60.  Back to cited text no. 4
Hidvegi DF, Soresen K, Lawrence JB, Nieman HL, Isoe C. Castleman′s disease: Cytomorphologic and cytochemical features of a case. Acta Cytol 1982;26:243-6.  Back to cited text no. 5
Cangiarella J, Gallo L, Winkler B. Potential pitfalls in the diagnosis of Castleman′s disease of the mediastinum on fine needle aspiration biopsy. Acta Cytol 1997;41:951-2.  Back to cited text no. 6
Taylor GB, Smeeton TW. Cytologic demonstration of "dysplastic" follicular dendritic cells in a case of hyaline-vascular Castleman′s disease. Diagn cytopathol 2000;22:230-4.  Back to cited text no. 7
Chan MK, McGuire LJ. Cytodiagnosis of lesions presenting as salivary gland swellings: A report of 7 cases. Diagn Cytopathol 1992;8:439-43.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3]


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