Turkish Journal of Pathology

Türk Patoloji Dergisi

Turkish Journal of Pathology

Turkish Journal of Pathology

2007, Vol 23, Num, 1     (Pages: 038-042)

Fine needle aspiration cytology findings in cases diagnosed as oropharyngeal tularemia lymphadenitis (Erratum was published in Vol 24 Number 1, 2008)

Banu DOĞAN GÜN 1, Burak BAHADIR 1, Güven ÇELEBİ 2, Gamze NUMANOĞLU 1, Şükrü Oğuz ÖZDAMAR 1, Gamze MOCAN KUZEY 3

1 Zonguldak Karaelmas Üniversitesi Tıp Fakültesi Patoloji, Anabilim Dalı, ZONGULDAK
2 Zonguldak Karaelmas Üniversitesi Tıp Fakültesi İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Anabilim Dalı, ZONGULDAK
3 Hacettepe Üniversitesi Tıp Fakültesi Patoloji, Anabilim Dalı, ANKARA

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Francisella tularensis is a gram-negative coccobacilus that causes zoonotic disease tularemia. Histopathological examination of lymph node biopsy in tularemia reveals suppurative granulomatous inflammation potentially associated caseous necrosis. Diagnosis is mainly made on the evidence of elevated agglutinating antibodies against F. Tularensis. In this study we aimed to evaluate the cytological features of ulceroglandular tularemia cases and to demonstrate the role of fine needle aspiration cytology in the diagnosis of tularemia.

Fine needle aspiration cytology findings of six cervical lymphadenopaties that had established diagnoses of tularemia both clinically and serologically, were evaluated and the cytomorphological features were described.

All of the cases revealed suppurative inflammation and some caseous necrosis and in four cases epithelioid histiocytes and multinuclear giant cells were observed additionally.

The differential diagnosis of tularemia principally from tuberculosis and other types of bacterial lymphadenitis was made and the place of fine needle aspiration cytology among other diagnostic laboratory tests for tularemia was evaluated.


Francisella tularensis is a gram-negative coccobacillus that causes zoonotic disease, tularemia and it was first demonstrated as a plaquelike disease of rodents in Tulare County, California, by McCoy[1-3]. This zoonotic bacterium is carried both with arthropod vectors, and wild and domestic animals (particularly with cats that have eaten infected rodents or rabbits). Transmission through water contaminated by infected rodents has also occurred[1,4].

Clinical features of the disease depend on the source of inoculation. Six clinical forms have been recognized: ulceroglandular, oculoglandular, lymphadenoid, typhoidal, oropharygeal and pulmonic[3].

Clinical diagnosis of tularemia is difficult to make, as symptoms are nonspecific and often initially resemble influenza or other respiratory tract infections. Laboratory diagnosis is also problematic. Serologic studies (including ELISA and agglutination assays) are the most commonly employed diagnostic methods. Immunohistochemical studies, fluorescent antigen testing and immunoelectron microscopic examination have also been used to detect Francisella tularensis[1,4,5].

Tularemia is an emerging disease in Turkey with the outbreaks during last years[6-7]. Endemic and sporadic tularemia cases were seen predominantly in Marmara and Western Black Sea region and also in Zonguldak province in 2004 and 2005[8-11].

In this study we aimed to detect the cytological features of ulceroglandular tularemia cases diagnosed by serological methods and to demonstrate the role of fine needle aspiration cytology in the diagnosis of tularemia.


We reviewed cytologic, histologic and clinical features of six cases with a serologically established diagnosis of tularemia. In each case fine needle aspiration cytology was performed using 23-25 Gauge needles. Also in two cases the palpable lymph nodes were surgically excised. A portion of the smears were air-dried and stained with Giemsa, while the remaining smears were wet-fixed with alcohol and subsequently stained by hematoxylin-eosin. In two cases histochemical Ziehl-Neelsen staining for acid fast bacilli was also performed.


The age of our 4 female and 2 male patients ranged from 16 to 64 years. All of the patients presented with a soft to firm cervical masses varied between 4 to 10 cm in diameter and they were associated with fever (38-40ºC), generalized body aches, often prominent in the lower back and sore throat. Three patients had a history of close relation with rodents. Serologically their serum agglutinating antibodies against F. tularensis were diagnostic for tularemia and their titers ranged between 1:320 and 1:2560.

Grossly all aspirated materials were purulent. All smears showed an abscess-like image with multiple neutrophils, macrophages, necrotic materials and also amorphous basophilic material consisted of caseification necrosis (Figure 1). In three cases epithelioid histiocytes with multinuclear giant cells were demonstrated (Figure 2-3).

Figure 1: Suppurative inflammation and abcess formation (HE x40).

Figure 2: Granulomatous inflammation in the cytological material (Giemsa’s stain x10).

Figure 3: A multinuclear giant cell with an amphophilic cytoplasm (HE x100).

Paraffin sections of two cases revealed suppurative granuloma formation with abscesslike material in the center and epithelioid cells and some multinuclear giant cells in the periphery (Figure 4). These sections were stained histochemically, but no microorganism was detected.

Figure 4: Epitheliod histiocytes with multinuclear giant cell and a suppurative inflammation at the center (HE x100).


Fine needle aspiration cytology is the first method to be performed on the superficially enlarged lymph nodes. With this technique, reactive, inflammatory and neoplastic conditions of lymph nodes are correctly diagnosed in nearly every case. So using this cytological method, the number of the surgical excisions will be decreased[12-13].

In tularemia lymphadenopaty, the histopathological features vary with the stage of the disease. In the very early stage, there are only reactive changes without necrosis. Abscess formation with or without epithelioid cell reactions is observed during the second and caseous necrosis during the fourth week[3,5,14]. Stellate necrosis may also be seen[15].

When caseous materials with epithelioid cells are present in the fine needle aspiration materials, firstly tuberculosis should be considered in the differential diagnosis. In tuberculosis lymphadenitis, when lymph nodes are secondarily infected, abscess formation which is almost similar to tularemia abscesses may appear[16-17]. Also in a large number of tuberculosis cases showing suppurative inflammation, acid fast bacilli were masked with excessive purulent exudate[16]. However tularemia cases reveal more dense inflammation which extends beyond capsule[18]. In these instances the serological and clinical features will aid in establishing the correct diagnosis[3,15,18].

Cat-scratch disease and lymphagranuloma venerum demonstrate focal areas of necrosis with accumulation of polimorphous nuclear leukocytes with granulomatous organization. In tularemia cases with stellate necrosis, the differential diagnosis from cat-scratch lymphadentis will be difficult. The identification of microorganism is necessary for the diagnosis. Although lenfogranuloma venerum has a similiar histopathological appearance, clinical features, predilection for male gender, localization of the lesion and laboratory findings will lead to diagnosis[3,15].

Other bacterial infections such as yersiniosis, typhoid fever, melioidosis and listeriosis can cause suppurative infections in the lymph nodes. Gram’s stain is useful in identifying the presence and type of the bacteria. Bacteriologic study of smears and cultures may be indispensable for specific etiologic identification[15].

One of the major difficulties with interpretation of cytologic findings of lymph nodes is that some suppurative lymphadenopaties may mask malignant disease. Necrosis and massive neutrophilic infiltrate can occur spontaneously and be prominent findings in smears obtained from patients with Hodgkin’s disease[19].

In conclusion, necrosis and massive neutrophilic infiltrate with epithelioid histiocytes and multinuclear giant cells is a prominent finding in smears obtained from patients with tularemia. However other bacterial and fungal infections with granulomatous and suppurative lesions may reveal similiar features. Therefore fine needle aspiration cytology for the diagnosis of tularemia is not a useful method per se. However this technique is a safe procedure which does not require hospitalisation. It is also more cost effective and less time consuming than a surgical excision.

Moreover fine needle aspiration will provide rapid diagnosis for the clinically suspect cases of tularemia and the cytological evaluation of the aspirate will play an important role in the identification of other pathological entities responsible for lymphadenopathy. Furthermore the aspirate can be cultured or used for the more complex investigations if required.


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Keywords : Tularemia, fine needle aspiration, cytology