Discussion

LMs can occur at any age, 65% are seen at birth, and 80% by 1 year[3] .LMs are rarely located in the female genital tract.To the best of our knowledge, there are only 14 reports of the primary lymphatic malformations related to perineum worldwide in children[4-17] (Table 1). Of these, most lesions involve the labia, only 3 patients had lesions involving the vagina[10,12,15]. A case of a 28-year-old female was reported being diagnosed as chylocolporrhea associated with primary lymphangiectasia, who presented with increased vaginal discharge since puberty[10].Another case was a Chinese female who presented with increased vaginal discharges since 3 years old with mucosal lesions in perineum, while the diagnose of was not made until 21 years old[15].Recently, Tang et al. described a 12-year-old girl with intermittent vaginal discharge for 10 years,while the main symptoms related to gastrointestinal tract due to intestinal lymphangiectasia with protein-losing enteropathy, and finally diagnosed as generalized lymphatic anomaly[12].Here,we reported the first Chinese case of primary vaginal and pelvic LMs who was diagnosed in childhood.
In this article,the patient was characterized as increased vaginal discharge and a large amount of white granular protrusions in the hymen.According to literature review and clinical findings of this case, almost all patients of primary vaginal LMs had chronic increased vaginal discharge or combined mucosal lesions in perineum[10,12,15].This has great significance in clinical practice–for children with similar chief complaints and perineal physical examination findings, the diagnose of LMs should be considered.
The non-specific clinical picture, combined with the difficulties of diagnosis verification, lead to a long diagnostic period ranging from 2 to 40 years based on the literature review.Only 7 cases were reported with clinical symptoms presenting before the age of 10[6,8,9,12,14-16].In our case, there was a 4-year interval from the manifestation to the hospitalization in a specialized department where the diagnosis was verified.
As for diagnosis, most were made by pathology without MRI or CT examination in the earlier reported cases[4-9,13,16].With the progress of imaging technology, MRI was performed in most cases reported recently,which showed that lesions involved pelvic cavity, retroperitoneum, groin, spinal muscle, buttocks, uterus, rectovaginal septum, vaginal wall,beside the superficial part of the perineum[10,12,15].Therefore, it is speculated that the previously reported cases whose manifestations limited to the labia, may had the probability of missed diagnosis.According to recommendations from the International Society for the Study of Vascular Anomalies in 2015,ultrasound and MRI are the first-line imaging techniques for identifying, characterizing, and evaluating the anatomic extent of vascular malformations[18].In our case,MRI provided direct evidence to support the diagnosis of LMs.
Due to the development of technology and the new sclerosing agents, sclerotherapy has become the mainstream treatment of macrocystic and mixed LMs[2].However,as to microcystic type,the effect of sclerotherapy was not desirable[19].Recent progress in germline and somatic mutations that leading to activate known intracellular signaling pathways in LMs has advanced pharmacological interventions for the disease. mTOR Inhibitor Rapamycin (Sirolimus) could reduce the proliferation,as well as regulate the proliferation, migration and adhesion of lymphatic endothelial cells, so was tried to treat LMs[20].Several literatures reported its effectiveness in the treatment of complex vascular malformations, especially in diffuse microcystic LMs [21,22].The efficacy and safety of topical Sirolimus in the treatment of superficial vascular malformations in children has also been reported[23].
According to existing publications, surgical resection was usually utilized in early reported cases[18,7,8]. Laser therapy was used in 1 case[8].Follow-up time for the cases was usually very short or no follow-up was mentioned.In our case,to achieve maximum control of the lesion and to prevent recurrence, we decided to utilize sclerotherapy combing with oral Sirolimus.The clinical symptoms were well controlled after 14 months of follow-up.Pelvic MRI also indicated a reduction in lesions.This is the first case of primary vaginal and pelvic LMs treated with Bleomycin sclerotherapy combing with oral Sirolimus in children. The short-term effect is desirable without obvious adverse reactions.The proper dose of Sirolimus was very important to the disease control. Further studies with large sample size, multi-center, and long-term clinical follow-up were required to explore optimal treatment options.
FIGURE 1┃ (A) Numerous white granular projections in the hymen at admission. (B)Sporadic granular projections in the hymen in 8 month-follow up after treatment.
FIGURE2┃ MRI Manifestations of the patient. (A)At admission: Multiple lamellar and corp-like abnormal signals around bilateral iliac vessels in the pelvic cavity, uterus, vagina and rectum, bilateral inguinal lymph nodes, and bilateral lateral iliac wings. (B)8 month follow-up after treatment: lesions were reduced than before, and no vaginal involvement was observed.(C)14 month follow-up after treatment:MRI manifestation was stable.
TABLE 1┃ Reported cases of primary lymphatic malformations of perineum worldwide onset during childhood.