3.3.1 Diagnostic Considerations
KLA is a rare yet very aggressive disease in which early diagnosis and timely treatment are critical. KLA has only been recognized as a distinct clinical entity since 2013 and unfortunately, is often misdiagnosed [7]. Like GLA and GSD, KLA is inaccurately referred as “lymphangiomatosis” but coagulopathy is the hallmark of KLA. In patients with unexplainable hypofibrinogenemia, thrombocytopenia, and bleeding, particularly if hemorrhagic ascites, pleural effusion, and/or pericardial effusion are present, KLA must be considered. KLA commonly involves bones and viscera and infiltrates into the thoracic and abdominal cavities. When located in superficial soft tissues, KLA appears as non-discrete red-purple purpuric lesions. The most common presenting clinical features of KLA are bleeding and respiratory symptoms such as cough and dyspnea [7].
Imaging is important for diagnosis of KLA, particularly since biopsy is often unable to be performed safely. MRI imaging of the chest, abdomen, pelvis, and total spine. High resolution chest CT may provide additional information for lung or mediastinal involvement. Pleural and pericardial effusions, along with LM involvement of the thoracic cavity, spleen and bones are common. Similar to GLA, the osteolytic bone lesions are cortex-sparing and involve multiple non-contiguous bones, most commonly the vertebrae [7]. On imaging, KLA of the soft tissue appears as an infiltrative abnormality on fluid-weighted MRI sequences, frequently with stranding of the adjacent subcutaneous fat [24]. On contrast-enhanced CT, KLA appears as infiltrative low-density soft-tissue thickening or mass, and effusions are of low attenuation. KLA is heterogeneously hyperintense on fluid-weighted MRI sequences, with moderate to intense post-contrast enhancement and follows the lymphatic distribution along bronchovascular bundles (Figure 4A) . Soft tissue thickening around the blood vessels and airways in the anterior mediastinum and interlobular septal thickening are also frequent findings (Figure 4B) . In viscera, KLA appears as hyperintense round lesions on fluid-weighted MRI sequences and hypodense lesions on CT. Enhancing infiltrative soft tissue is also frequently seen in the retroperitoneum and abdomen [24]. Echocardiogram is also indicated to evaluate for pericardial effusion.
If a soft tissue component is present, biopsy may be possible, depending on severity of coagulopathy. If KLA is confirmed by pathology,NRAS testing of the tissue specimen should be considered to guide therapy [10]. In our patient, a somatic NRAS Q61R mutation with an allele frequency of approximately 5% was found in her splenic tissue.