Abstract Introduction Kaposiform lymphangiomatosis (KLA) is a rare, aggressive, and often life-threatening lymphatic anomaly predominantly seen in children. It is frequently associated with disseminated intravascular coagulation (DIC) and thrombocytopenia, leading to high morbidity and mortality. Imaging typically reveals diffuse infiltrative soft tissue lesions. Histology shows spindle-shaped lymphatic endothelial cells positive for CD31 and D2-40. On the molecular level, somatic NRAS p.Q61R mutations are commonly detected, implicating activation of both PI3K/mTOR and RAS/MAPK pathways. Sirolimus, an mTOR inhibitor, is commonly used for therapy; however, the optimal dosing strategy and long-term management remain undefined. Case Presentation We report a 23-year-old male with chronic diarrhea since 2013 and progressive coagulopathy. Initial endoscopy showed non-specific findings; treatment with mesalazine was ineffective. By 2016, he developed abdominal distension and inguinal lymphadenopathy. Laboratory findings revealed anemia (HGB 98g/L), thrombocytopenia (PLT 26 × 109/L), elevated PT (17.0s), APTT (47.6s), low fibrinogen (0.61g/L), and elevated D-dimer (15.38mg/L), consistent with overt DIC. Workup excluded infectious, autoimmune, and hematologic malignancies.Imaging showed diffuse retroperitoneal and pelvic soft tissue densities encasing major vessels and abdominal organs. PET-CT revealed mild FDG uptake in these lesions. Colonoscopy showed colonic edema and bleeding. Bone marrow biopsy was reactive. Mesenteric biopsy demonstrated irregular lymphatic vessels with CD31 and D2-40 positivity. Targeted next-generation sequencing identified NRAS p.Q61R mutation (11.8% VAF) and an ERG frameshift variant. A diagnosis of KLA with DIC was established. Treatment and Outcome Low-dose sirolimus (1 mg/day) was initiated in September 2016. After 3 months, diarrhea and laboratory abnormalities improved, and imaging showed lesion begining to shrink. Trough sirolimus levels ranged from 4-5 ng/mL. Temporary dose escalation to 2 mg/day resulted in worsened mucositis without added benefit; the dose was reduced to 1mg/day. The patient maintained clinical stability on 1 mg/day for 4 years. In 2020, sirolimus was discontinued. By 2024, after 5 years off therapy, no disease recurrence was noted. Discussion This case demonstrates effective long-term disease control in adult-onset KLA using low-dose sirolimus, with sustained remission even after drug withdrawal. It highlights the potential role of lower target serum levels than conventionally recommended (4-5 ng/mL vs. 5-15 ng/mL) in selected patients, reducing adverse effects while maintaining efficacy. The presence of NRAS p.Q61R mutation supported mTOR pathway targeting. Further studies are needed to define optimal dosing, biomarkers for treatment response, and criteria for safe drug discontinuation.In conclusion, low-dose sirolimus may be effective for long-term management of NRAS-mutant KLA, with potential for durable remission after withdrawal. This abstract is funded by: National Natural Science Foundation of China
Liu et al. (2026) studied this question.