Cytological diagnosis of Castleman's disease of the soft tissue.

Castleman's disease (CD), a rare benign disease is characterized by lymphoid hyperplasia of uncertain etiology that may present as a nodal or extranodal mass. We describe herein a rare case of CD occurring in the soft-tissue of right arm in a 55-year-old woman. The present case is instructive in the differential diagnosis of primary soft-tissue tumors, for which the possibility of CD should be considered. On clinical examination as well as gross examination, this disease mimics lymphomas and tuberculosis. Since cytological appearances vary depending on the type and extent of hyperplasia, fine needle aspiration cytology findings may not always be conclusive in all cases. We studied aspirates which revealed reactive hyperplasia with increased vascularity. Excision confirmed the diagnosis.

Introduction

Castleman's disease (CD) is a relatively uncommon benign disease that is characterized by lymphoid hyperplasia. CD may occur in any area where lymphoid tissue is normally found. Extranodal CD, is exceedingly rare. We describe herein a case of CD presenting as a soft-tissue tumor in the arm and discuss with reference to the literature. We studied aspirates in which the cytology was indicative of CD and which was subsequently confirmed by histology.

Case Report

A 55-year-old woman with no history of major illness presented with a 2-year history of a painless, elastic soft mass in the right arm gradually increasing in size, measuring 5 cm × 4.5 cm × 2.5 cm. She had no other symptoms. Routine laboratory investigations showed no abnormality. There were no systemic symptoms, draining axillary lymph nodes were not enlarged and no other organomegaly. Radiograph of the arm showed mild periosteal reaction of underlying bone. Ultrasonography findings suggested that the lesion was a primary hypervascular soft-tissue tumor.

Cytology

Smears were highly cellular and showed polymorphous cell population with predominance of small lymphocytes and few tingible-body macrophages [Figure 1]. Few singly scattered large oval cells with indistinct margins were seen. These cells had pale cytoplasm with fine chromatin with inconspicuous nucleoli. There was prominent vascularity with capillaries. There were no epithelioid cells, giant cells or necrosis. However, few immunoblasts were seen. Plasma cells were few in number. The cytological picture was that of reactive hyperplasia with additional findings of capillaries amongst germinal center cells. A diagnosis of reactive hyperplasia with a strong indication of CD was made [Figure 2].

Figure 1

Smears showing polymorphous cell population with predominance of small lymphocytes (MGG, ×400)

Figure 2

Smears showing fragments of capillaries along with lymphoid population (H and E, ×100)

Histopathology

Grossly, the excised tumor was grey tan with a homogenous cut surface. Microscopically, the sections showed diffuse lymphoid cell population chiefly of small to medium cells along with many small blood vessels. These findings confirmed CD, hyaline vascular type.

Discussion

CD was first described by Castleman et al.[1] as a localized mediastinal lymph node hyperplasia resembling a thymoma. This entity has a number of descriptive synonyms, including “angiomatous lymphoid hamartoma,” “angiofollicular hyperplasia,” and “giant lymph node hyperplasia.”[2] The most common site of involvement is lymph node-bearing tissue with a predilection for the mediastinum (70%), but also occurring in the neck, axilla, pelvis and retroperitoeum.[3] However, a few extranodal cases have been reported in the literature, comprising nine intramuscular cases. Whether previously described intramuscular cases developed actually from skeletal muscle or from ectopic lymphatic tissue remains to be discussed.[4] In the present case, a primary soft-tissue tumor was suspected clinically. The establishment of the correct pre-operative diagnosis of CD by cytological examination is challenging due to the rarity of this entity, especially when the tumor arises in the extremities.

CD is currently classified into three variants: The unicentric hyaline vascular type is the most frequent, accounting for 72% of all cases, followed by the unicentric plasma cell (18%), and multicentric type (10%).[2] The etiology of CD is unknown. However, the two main hypotheses are viral infection and abnormal reaction.[5]

The hyaline vascular type is the more common form of CD. The fine needle aspiration cytology (FNAC) findings are those of follicular hyperplasia with mixed cells including lymphocytes, eosinophils, and immunoblasts as well as hyalinized capillaries. Follicles resembling Hassal's corpuscles containing central hyalinized capillaries are reminiscent of lollipops. Occasionally, Reed Sternberg-like cells may be seen. In the plasma cell type, follicular hyperplasia, marked plasmacytosis with Russell bodies and occasional immunoblasts are characteristic.[67]

The possible pitfalls of this disease on cytology are missing the hyalinized capillaries with eosinophilic material in reactive hyperplasias and misdiagnosing single large cells and Reed Sternberg-like cells as Hodgkin's lymphoma. The differential diagnosis mostly includes all reactive hyperplasias of lymph nodes and occasionally Hodgkin's lymphoma. Hyaline-vascular CD is difficult to diagnose on FNAC and may be mistaken to be a lymphoreticular malignancy because of the presence of large cells having nuclei showing atypical features.[6]

Mantle cell lymphoma is the most important diagnostic problem. Mantle cell lymphomas usually show a mantle zone growth pattern with a remnant of small atrophic germinal centers and nodular growth pattern without germinal centers. Nodal marginal zone B-cell lymphoma sometimes contains numerous regressive germinal centers and should be differentiated from CD. Follicular lymphoma rarely shows lymphoid follicles mimicking CD.[2]

The cytomorphological findings in three histopathologically documented cases of hyaline-vascular CD were evaluated by Deschênes et al.[8] to a set of cytomorphological criteria that could help in the identification of this condition on aspirate smears. After review, the following cytomorphological criteria were suggested to be indicators of the lesion: (i) The presence of large oval to round cells having ill-defined cytoplasmic margins and large nuclei with irregular nuclear outlines having fine or coarse chromatin, giving a crumpled tissue paper appearance; (ii) a polymorphous population of lymphoid cells predominantly of small lymphocytes in the background. The authors concluded that although hyaline-vascular CD is a difficult diagnostic entity on aspirate material, the presence of large histiocytic cells with a crumpled tissue paper appearance of the nuclei in a background of small lymphocytes is a useful indicator for suspecting this lesion.[8] However, these findings should be analyzed in larger studies to determine if they could in anyway reduce the diagnostic dilemma in cases of CD.

Deschênes et al.[8] reported that the FNACs in three cases showed branching capillaries associated with fragments of germinal center. A review of literature by them yielded 12 other case reports with over half describing similar findings. Because branching hyalinized small blood vessels penetrating follicular germinal center are characteristic of CD of the hyaline vascular type on histology, this finding in fine needle aspirates should raise that diagnostic possibility.[7]

Our case also had these cytological findings which helped us indicate a pre-operative diagnosis thereby guiding the clinician in management of the patient.

Conclusions

Although infrequent, it is important to bear the differential diagnosis of CD in mind when evaluating a sharply demarcated, hypervascularized lymphatic hyperplasia located in the extremities. The etiology of CD remains to be further examined in future studies. Though different authors have described many cytological findings, CD still remains a cytological dilemma.