Fine-needle aspiration cytology of Kikuchi Fujimoto disease.

Kikuchi disease (KD) is an enigmatous, self-limiting, rarely fatal, disease of young females. The self-limiting disorder usually occurs in Asian women in their late 20s or early 30s. Typically it runs a benign course and appears to resolve spontaneously one to six months after definitive diagnosis. We report a 27 years old lady presenting with cervical lymphadenopathy. Fine needle aspiration cytology of the node clinched the diagnosis revealing crescentic histiocytes, plasmacytoid monocytes, extracellular (karyorrhectic) debris and necrosis. The diagnosis was subsequently confirmed by histopathology.

Introduction

Kikuchi disease (KD) (also known as Kikuchi–Fujimoto disease, necrotizing histiocytic lymphadenopathy) is an uncommon, benign, enigmatous, self-limiting, rarely fatal, disease of young Caucasian females, presenting with firm, tender, unilateral cervical lymphadenopathy.[1] Kikuchi,[2] and Fujimoto et al.[3] reported it, independently, almost simultaneously, in 1972 from Japan. The present distribution is global; Japan and other Asian countries topping the list. Etiology is not completely understood/controversial; however, mainly viral origin (EBV, HHV 6 and 8) and autoimmune mechanisms have been suggested. Strong association has been found with systemic lupus erythematosus (SLE), mixed connective tissue disorders and leaking silicone breast-implants.[1]

The technique of fine-needle aspiration cytology (FNAC) in good hands with a keen eye on clinical examination shall give a reliable diagnosis in most cases, thus it obviates the need for excision.

Case Report

A 27-year-old female presented to the physician with a two-week history of rigors, night sweats, right axillary tenderness and 3.5-kg weight loss. She denied any previous medical history, regular medications, cigarette or alcohol use, foreign travel or infectious contacts. Physical examination revealed pyrexia (temperature 38.8°C) and a tender, palpable left cervical lymph node. Inguinal and axillary regions were normal. Examination of other systems was unremarkable.

Laboratory investigations and examination of the blood film revealed pancytopenia with normocytic red cell indices (Hb 8.2 g/dl; MCV 93.2 fl); and a relative lymphopenia. Erythrocyte sedimentation rate (ESR) was 88 mm fall at the end of first hour and C-reactive protein was 29 mg/l. Fine-needle aspiration cytology (FNAC) showed crescentic histiocytes, plasmacytoid monocytes, extracellular (karyorrhectic) debris and necrosis and a diagnosis of Kikuchi's disease was made on cytological examination [Figures 1, 2 and 3a, b].

Figure 1

Kikuchi disease: FNAC smear showing crescentic histiocytes, plasmacytoid monocytes and extracellular (karyorrhectic) debris (H and E, ×400)

Figure 2

Kikuchi disease: FNAC smear showing predominately crescentic histiocytes, plasmacytoid monocytes and extracellular (karyorrhectic) debris (H and E, ×400)

Figure 3

(a) Shows plasmacytoid monocytes in the background of necrosis surrounded by karyorrhectic debris, (b) shows a characteristic crescentic histiocyte

On the insistence of clinician, to further confirm the diagnosis, a lymph node biopsy was performed, which demonstrated focal necrosis surrounded by karyorrhectic debris, histiocytes and plasmacytoid lymphocytes [Figure 4].

Figure 4

Kikuchi disease: Histopathologic section showing focal necrosis surrounded by karyorrhectic debris, histiocytes and plasmacytoid lymphocytes (H and E, ×400)

The patient made a full recovery after 21 days of supportive care.

Discussion

Kikuchi disease is an uncommon, benign, rarely fatal, disease, reported independently, almost simultaneously, by Kikuchi[2] and Fujimoto et al.,[3] in the year 1972 from Japan.Initially, bacterial agents, such as Yersinia, Bartonella and protozoan toxoplasma were thought to cause the disease, recently atypical mycobacterium szulgi has been isolated from Thailand, brucella has also been reported. Systemic lupus erythematosus (SLE) shows the strongest association, among autoimmune disorders with KD, and it has been seen that 33% of pre or post-SLE adenitis is true KD.[4]

Lab evaluation for KD reveals nonspecific findings including lymphopenia, neutropenia, with atypical lymphocytes, anemia, raised ESR, elevated levels of serum lactogen dehydrogenase (LDH) and transaminases. Radiological investigation including computed tomography (CT), ultrasonography and magnetic resonance imaging scan give nonspecific findings; CT scan reveals enlarged nodes on an average 15 mm and radiological impression overlapping with findings of malignant lymphoma, thus necessitating the role of pathological investigations, including FNAC and excision biopsy.[5]

Although excisional biopsy, revealing effaced architecture, islands of hyperplasia and zonal necrosis, gives an accurate diagnosis, FNAC on the other hand, can give firm diagnosis in majority of cases, un-necessitating the need for excisional biopsy, and since medical treatment with corticosteroids gives good results, the need for surgical excision is obviated. Fine-needle aspiration cytology of KD reveals abundant crescentic histiocytes, plasmacytoid monocytes, variable lymphocytes, along with abundant karyorrhectic debris; neutrophils are characteristically absent and plasma cells are scarce/absent.[67] Fine-needle aspiration cytology in patients with typical clinical presentation diagnoses the disease without much difficulty, overall accuracy being around 57%.[89] Recent studies have indicated that complementing FNAC with immunocytochemical evaluation of the aspirate can increase the diagnostic accuracy to around 85–90%.[6]

According to Kuo,[5] cell types isolated might vary with the stage of disease; crescentic histiocytes, plasmacytoid monocytes and atypical lymphocytes, along with karyorrhectic debris in proliferative stage; eosinophilic necrosis, karyorrhectic debris, variable lymphoid cells abundant histocytes and plasmacytoid monocytes in necrotizing adenitis; minimal or no necrosis along with karyorrhectic debris and foamy histiocytes in xanthomatous stage. Necrotizing stage accounts for the most of the cases diagnosed, thus the synonym, necrotizing histiocytic lymphadenitis. Karyorrhexis is one of the exclusive features of Kikuchi–Fujimoto disease, and the process might explode into the peri-nodal areas as well. Fine-needle aspiration cytology, if necessary, should be repeated to increase the diagnostic outcome, thus increasing the potential of procedure. It has been said; however, that surgical biopsy would be unnecessary if using FNAC could make a firm diagnosis.[9] Thus, results from two studies including histologic sections and excisional biopsy specimens led to the conclusion that in patients with typical clinical features and characteristic cytologic findings in lymph node aspirates, FNAC alone would suffice for diagnosing KD.[89]

Currently, immunostaining studies including immunocytochemical staining is been carried-out, to zero on the diagnosis, and it has been found that there is proliferation of CD8+ cells in the lesions, which initiate a killer/chemotactic mechanism responsible for apoptotic sand in the lesions.[4] Transmission electron microscopy has revealed apoptotic changes in nuclear membrane, such as thickening of nuclear membrane, apoptotic bodies and finger-like network of apoptotic process in most of the cases. This apoptotic pathway is partly responsible for the cellular changes.[4]

Treatment of the disease like etiology is also enigmatic; various drug therapies ranging from antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids have been used, nevertheless, steroids are mainstream, and show a good response. Surgical treatment involves excision of nodes, which is the only treatment for recurring disease.[1]

The following diseases should line up as differentials:[4] (1) Malignant lymphoma: it can masquerade KD both radiologically and pathologically, thus a diagnosis should be given with caution. (2) Nodal metastasis of adenocarcinoma: signet cells with mucus, are present in place of karyorrhectic material. (3) Kawasaki disease: in which the necrosis is geographic and neutrophilic infiltrate is present. (4) Nodal extension of AML: variable lymphocytic population without histiocytes is present. (5) Infectious adenitis: typically atypical mycobacteria might present like Kikuchi disease.

Keeping in view the above discussion, it is clear that FNAC has a greater role in the diagnosis of KD, it is able to diagnose firmly in most of the cases, repeating the procedure shall further increase diagnostic outcome, thus decreasing the need for unnecessary excisional biopsy; however, excision may be the only choice in recurring disease. With good hands at aspiration and keen eyes atop the lens, the procedure shall make out a firm diagnosis of KD.