KFD is a poorly understood and rare condition which most commonly affects young women of Asian descent, but also males and children. The true incidence of KFD is difficult to ascertain due to its heterogeneous, often subtle symptoms. KFD typically presents as tender cervical lymphadenopathy, but may involve other lymph node regions and rarely presents as generalized lymphadenopathy. While it is often otherwise asymptomatic, KFD may also exhibit a constellation of non-specific symptoms including fever, upper respiratory tract symptoms, weight loss, night sweats, fatigue, nausea and vomiting . Uncommonly there may be cutaneous manifestations such as rash, macules or papules, or ulcers . KFD usually develops over two to three weeks and spontaneously resolves after a few months. Treatment is generally supportive care only but severe cases may require non-steroidal anti-inflammatories or corticosteroids. Hydroxychloroquine, methotrexate, and intravenous immunoglobulin have also been used for severe cases . KFD may relapse and exceptionally rare cases have resulted in death .
Imaging findings are usually non-specific, and KFD may be mistaken for lymphoma, other malignancies, tuberculosis lymphadenitis, or Kawasaki disease . The number, size (usually <4 cm) and location (neck most common) of involved lymph nodes can be useful for suggesting the diagnosis . Because of the brisk proliferation rate, lymph nodes involved by KFD are hypermetabolic on FDG PET-CT. The maximum standard uptake values (SUVmax) of FDG uptake can be used to differentiate benign and malignant tumors, but in a series of seven patients with KFD, the SUVmax ranged from 2.05-13.94 (mean +/−SD, 6.25+/−3.32), which is similar to malignancies . In that study, lymph node size weakly correlated with SUVmax, but the authors suggested that the FDG uptake was more dependent on the number of macrophages and neutrophils in the lymph node tissue . The diagnosis is most reliably made by histopathologic examination of an excised affected lymph node.
The etiology of KFD remains highly speculative. The clinical symptoms and pathological findings suggest a viral cause but no specific agent has been identified. It has been proposed that an infectious process initiates a self-limited autoimmune response. However, reports have been conflicting, with some implicating viruses such as Epstein-Barr virus, human herpes virus 6, 7, 8 and parvovirus B19, but others refuting them [5,6]. It is still possible that KFD develops after eradication of these viruses, or that other viruses contribute to the pathology . KFD has also been associated with autoimmune conditions, in particular systemic lupus erythematosus (SLE). The association is not well defined, and it is unclear if SLE can present with lymphadenopathy with similar pathological features of KFD or if KFD may be an early manifestation of SLE. Nevertheless, this correlation has led some physicians to recommend following KFD patients clinically for SLE .
To our knowledge, there are no other reported cases of a simultaneous diagnosis of melanoma and KFD. Melanoma is susceptible to immune modulation. Although there has been an association noted between SLE and melanoma, a large Danish population-based study found that the incidence of melanoma was not increased in those with autoimmune diseases [7,8]. In our patient, the only FDG-avid lymphadenopathy was in the regional lymph node basin draining the melanoma. It is unclear whether this was due to a possible immunological association between melanoma and KFD, whether there was a reaction from the biopsy of the primary site or if whether the co-existence is pure coincidence.
NCCN guidelines recommend staging with FDG PET or CT for stage III and IV melanoma . In this case, a FDG PET-CT was requested because of the unusually aggressive features of the primary tumor, as well as the patient’s body habitus that made clinical examination of lymph nodes difficult. Potential drawbacks in the use of FDG PET-CT or CT for staging are the possibility of false positive results that vary in incidence between 0-27%, which are more common when staging nodal disease compared with visceral metastases .
In our patient, a superficial inguinal lymphadenectomy was appropriately performed for fine-needle aspiration proven metastatic melanoma. However, evidence of deep lymph node involvement on FDG PET-CT also prompted a deep inguinal lymphadenectomy. Without concomitant KFD, only superficial nodal involvement would have been identified on FDG PET-CT and a superficial inguinal lymph node dissection would have been considered adequate.