Kikuchi Disease Workup

Updated: Aug 04, 2022
  • Author: John Boone, MD; Chief Editor: Sara J Grethlein, MD, MBA, FACP  more...
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Laboratory Studies

In patients with Kikuchi disease, laboratory and radiologic test findings are nonspecific. Although results of fine-needle aspiration (FNA) of an affected lymph node may be suggestive, [36, 37] the diagnosis of Kikuchi disease is confirmed only by excisional lymph node biopsy.

Complete blood cell (CBC) count findings include the following:

  • Mild granulocytopenia is observed in 20-50% of patients.
  • Leukocytosis is present in 2-5% of patients.

Additional blood study findings include the following:

  • Atypical lymphocytes are observed in 25% of patients
  • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels may be elevated
  • Elevated lactate dehydrogenase (LDH) levels suggest hepatic involvement

Results of autoimmune antibody studies—including lupus erythematosus (LE) preparation, rheumatoid factor (RF), and antinuclear antibody (ANA) studies—are generally negative. Those findings may help the clinician distinguish Kikuchi disease from SLE.



Imaging Studies

Diagnostic imaging studies confirm the presence of enlarged lymph nodes in the affected areas, but they cannot specifically confirm a diagnosis of Kikuchi disease.

On computed tomography (CT) scanning and magnetic resonance imaging (MRI), uniform enlargement of lymph nodes in affected areas is noted. Postcontrast enhancement may be observed.

In a study of 96 patients with Kikuchi disease, Kwon et al reported the following CT findings [38] :

  • Homogeneous lymph node enlargement (83.3% of patients)
  • Perinodal infiltration (81.3%)
  • Prominent areas of low attenuation suggestive of focal necrosis (16.7%)

Shim et al reported that CT imaging pattern analysis of cervical lymph nodes can be used to help differentiate Kikuchi disease from tuberculous lymphadenopathy and reactive hyperplasia. In their study, high cortical attenuation combined with an indistinct nodal architecture supported the diagnosis of Kikuchi disease. In cases of non-necrotic lymphadenopathy, the ratio of nodal cortical attenuation to the adjacent muscle (NCA/M) was significantly higher in Kikuchi disease: 1.67 ± 0.20, compared with1.49 ± 0.20 in reactive hyperplasia and 1.47 ± 0.21 in tuberculous lymphadenopathy. [29]

In a study by Kato et al of MRI findings in nine patients with Kikuchi disease, cervical lymphadenopathy showed predominantly a unilateral distribution at levels II-V. On T2-weighted images, areas of hypointensity were visible at the peripheries of enlarged cervical nodes; these corresponded to histopathological findings of coagulative necrosis. [39]

On ultrasonography, Ryoo et al reported that the following lymph node characteristics are typical of Kikuchi disease [40] :

  • Echogenic hilum
  • Posterior neck involvement
  • Absence of internal calcification
  • Absence of necrosis (rarely, presence of partial necrosis)
  • Normal vascular pattern on power Doppler ultrasound (ie, hilar vascular structures are central or branch radially from the hilum in both longitudinal and transverse planes)

Chest radiography findings are generally unremarkable in Kikuchi disease. However, a chest radiograph is recommended in the evaluation of cervical adenopathy to look for evidence of tuberculosis or malignancy. [14]



A definitive diagnosis of Kikuchi disease can be made only by tissue evaluation. Cytologic examination by fine needle aspiration (FNA) can suggest the diagnosis of Kikuchi disease, especially when supported by typical clinical findings, but excisional biopsy of an involved lymph node is needed to confirm the diagnosis in doubtful cases.

FNA characteristics include the following:

  • FNA findings are most often nonspecific; some authors believe that the diagnosis can be confirmed when supported by typical clinical findings, but most authors recommend confirmation by excisional biopsy

  • In a retrospective study of 44 patients, FNA had an overall accuracy of 56.75% in diagnosing Kikuchi disease [36]

  • Characteristic cytologic findings in Kikuchi disease include extracellular debris and intracellular apoptotic debris embedded in the cytoplasm of crescentic and phagocytic macrophages [37, 41]

  • Definitive diagnosis by FNA is uncommon; prudent pathologists are likely to report results as "suggestive of" or "compatible with" Kikuchi disease

Excisional lymph node biopsy can reveal histologic findings consistent with Kikuchi disease, as follows:

  • Paracortical necrosis may be patchy or confluent, and the degree of necrosis varies considerably from patient to patient
  • Histocytes – Crescent-shaped nuclei (crescentic nuclei)
  • Other cells – Lymphocytes, plasmacytoid monocytes, macrophages, and immunoblasts (predominantly T cells)
  • Karyorrhexis – Histiocytes and macrophages containing phagocytized debris from degenerated lymphocytes
  • Absent or rare features in Kikuchi disease include neutrophils, granulomas, and plasma cells

Histologic Findings

The three histologic phases of Kikuchi disease are as follows [12] :

  • Proliferative phase – Initial phase with typical findings as noted in Procedures
  • Necrotizing phase – Extensive necrosis that may destroy the normal architecture of the lymph node
  • Xanthomatous ("foamy cell") phase – The recovery phase with resolution of necrosis

Immunohistochemical studies reveal the following:

  • The immunophenotype of Kikuchi disease is primarily composed of mature CD8-positive and CD4-positive T lymphocytes; lymphocytes and histiocytes also exhibit a high rate of apoptosis

  • Relatively few B cells and natural killer (NK) cells are present

  • Positive immunostaining results by monoclonal antibody Ki-M1P are seen in Kikuchi disease but not in malignant lymphoma

Distinguishing Kikuchi disease from lymphoma

The numerous atypical monocytes and T-cell immunoblasts observed in Kikuchi disease may lead to an erroneous diagnosis of lymphoma, especially high-grade non-Hodgkin lymphoma. Features of Kikuchi disease that may help prevent its misdiagnosis as malignant lymphoma include the following:

  • Incomplete architectural effacement with patent sinuses
  • Presence of numerous reactive histiocytes
  • Relatively low mitotic rates
  • Absence of Reed-Sternberg cells

Distinguishing Kikuchi disease from SLE

Kikuchi disease and SLE have similar histopathologic appearances. Distinguishing the two entities can be difficult. Kikuchi disease is suggested by the absence or paucity of the following:

  • Hematoxylin bodies
  • Plasma cells
  • Neutrophils

Tabata et al reported that CD30 immunostaining may help in the differentation of Kikuchi disease from SLE. In a study that included 30 patients with Kikuchi disease and six with SLE, CD30-positive cells were significantly more numerous in Kikuchi disease than in SLE and most of these CD30-positive cells were located around necrotic areas. Double immunohistochemical staining showed that these CD30-positive cells were CD8-positive cytotoxic T cells, suggesting that activated cytotoxic T cells around necrotic areas are a characteristic feature of this disease. Cases with abundant CD30-positive cells occurred predominantly in female patients with only mild symptoms and normal laboratory data. [42]