Unusual Presentation of Mixed Lymphatic Malformation: A Case Report with Literature Review

Abstract Introduction There is a scarcity of reports on mixed lymphatic malformation. This case highlights a child with an extensive mixed lymphatic malformation, disfiguring multiple parts of the body. Case presentation A 3.5-year-old boy presented with multiple vesicular “frog-spawn” lesions that affected the right mid-axillary region, left axilla, and left upper back. The patient also had marked bilateral cervical swelling, extending laterally on both sides, with prominent bulges measuring approximately up to 10 cm that extended to involve the entire right upper limb dawn to the hand. Bilateral axillary swelling was observed. Additionally, swelling was evident in the entire middle and upper back, with a pronounced rounded bulge in the right upper back. Surgical intervention of the left axillary mass was performed, which was consistent with macrocystis lymphatic malformation on histopathology, but the condition recurred during follow-up. Literature review Few cases of microcystic lymphatic malformation with extensive deep lymphatic involvement have been reported in the literature. There was a female predilection with reported involvement of the forearm, thigh, vulva, axilla, jaw, and even the tongue. The patients' ages ranged from infancy to adulthood, with some patients complaining of skin lesions and recurrent cellulitis for years, sometimes leading to sepsis and death. There is variable outcome for surgical intervention in such cases. Conclusion Mixed lymphatic malformation can present extensively affecting several parts of the body causing significant disfigurement with possible recurrence after surgical intervention. Introduction The lymphatic system is essential for regulating plasma volume and preventing tissue pressure buildup, as it reabsorbs a significant portion of the fluid and proteins that leak out the blood vasculature. Additionally, it supports cell nutrition and aids the immune response by directing antigen-presenting cells to lymph nodes. In the skin, lymphatic vessels serve as a critical exit route for Langerhans cells [1]. Anomalies in the development of lymphatic channels can lead to various diseases, including lymphatic malformation which can be either localized or diffuse and may be either congenital or acquired [2]. Notably, lymphatic malformation shows no variation across racial groups, with up to 90% of cases diagnosed before the age of two [3]. The International Society for the Study of Vascular Anomalies (ISSVA) established a comprehensive classification system that categorizes vascular anomalies based on their clinical characteristics and whether they are accompanied by other symptoms, which includes cystic lymphatic malformation, Kaposiform lymphangiomatosis, Gorham–Stout disease, and Channel-type lymphangioma. The cystic type is further categorized into macrocystic lymphatic malformation (diameter greater than 1cm), microcystic lymphatic malformation (diameter less than 1cm), formerly called lymphangioma circumscriptum, and mixed cystic lymphatic malformation. Histologically, the lymphatic cysts may either appear empty or contain a protein-rich fluid abundant in lymphocytes and macrophages [3]. Cutaneous lymphatic malformation represents only 4% of all vascular tumors. Microcystic lymphatic malformation is an uncommon superficial variant that primarily affects the axilla, groin, thighs, and buttocks. The “frog-spawn” appearance is due to the distinguished formation of dispersed clusters of small, thin-walled, translucent vesicles on the skin. Additionally, microcystic lymphatic malformation may contain a prominent vascular or hemorrhagic component, causing the lesion's color to vary from pink to red to black, depending on the proportion of blood to lymph within the vesicles. The present report aims to describe a case of mixed lymphatic malformation with extensive involvement, disfiguring various parts of the body [4]. The current study was written in line with CaReL guidelines and the credibility of references has been verified using Kscien’s list [5,6]. Case Presentation Patient information A 3.5-year-old male presented with complaints of intermittent bleeding from skin lesions in the right axillary region. Additionally, the patient complained of extensive swelling in the neck, axilla, and upper back, and swelling of the right middle finger. There was no family history of similar skin lesions or swelling. The patient's past surgical history was notable for herniorrhaphy and axillary mass resection. Physical examination On physical examination, there were multiple skin-colored compressible masses on the neck, axillae, trunk, and upper limbs. On the axillae and upper back, there were multiple small groups of papulovesicular lesions with characteristic “frog-spawn” appearance with many bleeding points. The patient had marked bilateral cervical swelling, extending laterally on both sides of the neck, with prominent bulges measuring approximately up to 10 cm on each side, that extended to involve the entire right upper limb down to the hand. Bilateral axillary swelling was observed, accompanied by a scar in the left axilla, indicative of previous surgical intervention. Additionally, swelling was evident in the entire middle and upper back, with a pronounced rounded bulge in the right upper back. The swelling extended across the back, with slight marbling noted on the overlying skin. There was also swelling of the chest, most prominently around the sternum. In addition, there was swelling in the right middle finger (Figure 1). Diagnostic approach The skin lesions were diagnosed as microcystic lymphatic malformation (lymphangioma circumscriptum) based on their location, the characteristic appearance of the vesicular lesions, and the history of oozing blood. The involvement of deeper lymphatic system swelling further supported the diagnosis. The laboratory blood investigations including complete blood count, thyroid stimulating hormone, C-reactive protein, and D-dimer were all within the reference range. Ultrasonography of the axilla and inguinal regions showed fairly symmetric, bilateral axillary soft tissue lesions with ill-defined, heterogeneous echogenicity, measuring approximately 8×4 cm. Small cystic areas were present within the lesions, with minimal internal vascularity but no evidence of phleboliths or prominent vessels. The sonographic features were non-specific, and potential differentials included hibernoma, lipoblastoma, and atypical hemangioma. A left axillary lymph node measuring 13×8 mm was noted; however, the bulk of the swelling was attributed to the soft tissue mass. No enlarged inguinal lymph nodes were observed, but a bilateral large inguinal hydrocele was present, along with bilateral undescended testes located in the inguinal regions. The other abdominal organs showed no abnormalities. Contrast-enhanced computed tomography scan of the neck and upper chest showed normal lung parenchyma and a non-enhancing hypodense mass in the left axilla extending to the left supraclavicular region and a hypodense mass in the right side of the neck (Figure 2). The axillary magnetic resonance imaging (MRI) revealed bilateral symmetrical axillary masses, measuring 6×5×5 cm on the right and 6.5×5×4.5 cm on the left. These masses exhibited homogeneous high signal intensity on both T1 and T2-weighted images and were suppressed on fat-saturated sequences, with no enhancement post-contrast. The masses were associated with multiple enlarged axillary lymph nodes, the largest measuring 13×10 mm on the right and 13×9 mm on the left. Lipoblastoma was suggested as a differential, and biopsy was advised. Biopsy of the axillary masses showed multiple fatty gray and tan pieces of tissue, the largest one measuring 85x80x40 mm. The microscopic sections showed multiple dilated cavernous and capillary size vascular spaces lined a by single layer of bland endothelium with flattened nuclei, surrounded by nodular aggregates of small mature lymphocytes and embedded in large lobules of mature adipose tissue, with areas that contain fetal-type skeletal muscle in process of maturation. There was no evidence of granulomata or invasive malignancy in the examined sections. Histopathology results were most consistent with macrocystic lymphatic malformation. A diagnosis of mixed lymphatic malformation was made. Therapeutic intervention and follow-up The patient previously underwent surgery to address the left axillary swelling; however, the lymphangioma recurred without significant improvement. Once-daily administration of sildenafil 10 mg and propranolol 10 mg yielded a good clinical response within the first three months, however on follow up there was an increase in the size of the mass. The frequency sildenafil dose was increased to 10 mg twice daily, and Pulsed Dye Laser (PDL) was applied for the microcystic lymphatic lesions for three sessions with no satisfactory response. At present, the patient is under observation with regular follow-up to monitor any potential complications or changes in the swellings that may require further intervention. Discussion The human skin comprises two distinct lymphatic plexuses. The superficial plexus, located near the subpapillary arterial network, consists of thin, non-valvular vessels extending into the dermal papillae. Lymph from this network drains into larger vessels situated in the lower dermis and the superficial subcutaneous tissue. The deep lymphatic plexus, positioned beneath the second arterial network, contains numerous valves and closely parallels the venous collecting system of the lower dermis [1]. The underlying pathophysiology of lymphatic malformation is characterized by fluid-filled muscular cisterns situated within the subcutaneous tissue, which establish a connection with the surface through dilated dermal lymphatic channels. Cutaneous involvement arises as a secondary consequence of the pressure exerted within the cisterns, driven by th