Although perhaps best recognized as a Category A potential bioterrorism agent, due to the very low infectious dose, ease of spread, stability in the environment, and high mortality rate if untreated [1, 6], F. tularensis is an environmental organism endemic to North America. As such, sporadic infections occur, particularly in children, through exposure to infected animals and arthropod bites. Here, we present a patient with classic clinical and histopathologic findings of tularemia, likely acquired through a tick bite. The patient’s lymph node excision showed granulomatous inflammation in various stages, from small clusters of epithelioid histiocytes to large, serpiginous granulomas with palisading histiocytes, central necrosis, and suppuration. Our report adds to the relatively limited descriptions of the histology of tularemia lymphadenitis in the accessible recent literature. A large study by Lampset al. [6] from 2004 described histologic patterns seen in 16 cases of tularemia, but the study cohort was comprised predominantly of autopsy cases, including animal autopsies, and was therefore biased toward severe cases. Indeed, the authors reported that lymph nodes in their series were involved by necrosis, with only rare samples showing granulomatous inflammation. In contrast, a cohort of 54 lymph node samples described by Asanoet al. in 2012 [7] included no fatal cases and described progressive histologic changes, with follicular hyperplasia and small abscesses seen in the first 2 weeks after infection. Over 6 weeks, these lesions progressed to small epithelioid granulomas with central necrosis and finally to large necrotizing granulomas, which fused to form irregular shapes. In all stages, aggregates of monocytoid B cells were noted adjacent to granulomas. In the case reported here, the time from infection to lymph node excision was approximately 6 weeks, and pathologic review showed all stages described by Asano et al. within the same lymph node. An extended time between infection and diagnosis of tularemia has been reported, due, at least in part, to the nonspecific presentation and rarity of the disease [8, 9].

The histologic finding of necrotizing granulomatous lymphadenitis raises the differential of various infectious processes, particularly Bartonella henselae lymphadenitis (“cat-scratch disease”), Mycobacterium tuberculosis or atypical mycobacteria infection, and fungal infection, as well as Chlamydia trachomatis (lymphogranuloma venereum) and Yersinia infection in certain clinicopathologic settings [10, 11]. Exclusion of malignancy, including classic Hodgkin lymphoma, is also imperative. Indeed, as discussed below, tularemia may present as lymphadenopathy unresponsive to antibiotic therapy, raising particular concern for lymphoma.

F. tularensis is a fastidious organism that is difficult to culture in the laboratory. Diagnosis most commonly involves serologic testing and/or PCR-based detection of bacterial DNA. Nevertheless, lymph node or other tissue samples may be sent for microbiologic culture as part of the diagnostic work up to evaluate for possible infectious processes. F. tularensis poses significant infection risk to laboratory personnel, due to the potential for inhalational exposure and the low number of organisms required to cause infection [12]. Indeed, literature suggests that F. tularensis is one of the most commonly reported laboratory-acquired infections, although the total number of cases reported in recent decades is small [12, 13]. If a diagnosis of tularemia is under consideration, the microbiology laboratory should be notified so that laboratory personnel can take appropriate precautions when handling tissue specimens. This awareness will also allow the microbiology laboratory to incubate samples for extended time periods, which is necessary due to the fastidious nature of F. tularensis. Given the relative rarity of tularemia, this infection may not be included in the initial differential diagnosis of lymphadenopathy. Therefore, pathologists must be aware of the histologic pattern of tularemia lymphadenitis, in order to communicate the possibility of this diagnosis not only to the clinical team but also to laboratory personnel.

Inclusion of tularemia in the pathologic differential for necrotizing granulomatous lymphadenitis can have important therapeutic implications, as tularemia may be undertreated by empiric antibiotic regimens used for more common causes of infectious lymphadenopathy. Tularemia is not considered sensitive to beta-lactam antibiotics, and preferred treatment options include gentamicin or ciprofloxacin [14]. Doxycycline-resistance has been reported, and treatment with this drug has been associated with higher relapse rates [14, 15]; if doxycycline is used, a 21-day course is recommended. The patient described here initially received a 1-week course of doxycycline for a possible tick-borne infection and showed partial improvement in his symptoms. However, his lymphadenopathy ultimately progressed and systemic symptoms recurred due to inadequate antibiotic treatment.

The histopathologic finding of necrotizing granulomas is not specific and should raise consideration of infectious and neoplastic processes. The case presented here demonstrates the significance of acquiring a thorough clinical history pertaining to travel, occupational hazards (e.g., farmers, veterinarians, hunters, etc.), and other potential environmental exposures, not only to ensure accurate diagnosis and optimal therapy, but also to ensure the safety of laboratory personnel. We also add to the available recent literature regarding lymph node histologic findings in non-fatal tularemia. Ultimately, a multidisciplinary approach, involving correlation with clinical history, tissue histologic findings, and serologic studies led to the correct diagnosis and appropriate therapy for the patient’s disease.