Sudden Onset, Rapidly Expansile, Cervical Cystic Hygroma in an Adult: A Rare Case with Unusual Presentation and Extensive Review of the Literature

Cystic hygroma (CH) is a benign infiltrative malformation of the lymphatic channels. We report a case of a 28-year-old Indian female who presented with rapidly enlarging right sided neck swelling over the posterior triangle since 5 days. Complete resection of CH is sometimes not amenable because of its infiltrative nature and involvement of surrounding vital structures. However, in our patient successful complete surgical resection was undertaken. The MRI findings of our patient were consistent with brachial cleft cyst; this posed a challenge in the diagnosis of CH. The histopathological analysis of the resected mass confirmed CH. CH is rare in adults and such an acute presentation is exceptionally atypical. History of prior trauma and infection are known etiological factors for adult CH; these were conspicuously absent in our patient. CH should be considered in the differentials of rapidly enlarging cystic swelling of posterior region of neck in adults. Optimal and timely management is necessary to achieve a favorable prognosis. Therefore, we report a case of rapidly enlarging cervical CH in an adult along with extensive literature review to have a better understanding regarding epidemiology, etiopathogenesis, clinical presentation, optimal management, and prognosis of such a rare entity in adults.


Introduction
Cystic hygroma is a subtype of lymphangioma and is most commonly a congenital lesion [1]. It is synonymous with cystic lymphangioma and macrocystic lymphatic malformation. It is an aberrant proliferation of lymphatic vessels resulting from abnormal development of lymphatic system. Histologically, it exhibits large macroscopic cystic spaces.
First case of lymphatic malformation (LM) was described by Redenbacher in 1828 [2]. Wernher [3] coined the term "hygroma" and later described a histological classification system for LMs into 3 types: cystic, capillary, and cavernous. Sabin [4] in 1990 and later Goetsch [5] in 1938 proposed the theory of centrifugal lymphatic system development. Sabin described the embryological derivation of lymphatic tissues as arising from 5 primitive lymphatic buds and postulated that abnormal sequestration of these buds gives rise to lymphatic malformations. Other theories, such as the centripetal theory of lymphatic development, have also been proposed [6].
CH can affect any anatomic subsites in human body [7][8][9]; however, most of these lesions are seen in head and neck region (∼75), probably because of rich lymphatics in this area. CH usually affects children under 2 years of age (80-90%) with incidence of 1.2 to 2.8 per 100,000 infants [10,11]. CH does not show any gender preference; both genders are equally affected [12,13].
2 Case Reports in Otolaryngology CH presenting in adulthood is rarely seen [14,15]. The etiology for CH arising in adults is controversial but it is thought to arise due to acquired process like infection, trauma (including surgery), or lymphatic obstruction [12,16,17].
To date there are only few cases of adult cervical CH described in literature and the optimum management is still challenging. Preoperative diagnosis is difficult in adults and often patients are misdiagnosed. Patients with CH are frequently misdiagnosed as brachial cleft cysts on imaging as in the case reported here. Definitive diagnosis can be reached only after histopathological examination of the surgical specimen.
Complete surgical removal is an important treatment modality [18]; however, the lesion tends to spread along vital structure; therefore, in such patients inductive complete surgical removal cannot be achieved. Several adjunctive therapies have been shown to be beneficial in recurrent or inaccessible lesion but these are not used commonly. Sclerosis by chemical drug [19][20][21][22] is another effective treatment option.
Just as with brachial cleft cyst and thyroglossal duct cyst, it is important to consider LM in one's differential diagnosis in the setting of an adult patient with a cystic mass of neck. For this reason, we describe a case of adult cervical cystic hygroma along with literature discussion for better understanding of disease process in adult and optimal management options.

Case Presentation
In our case, a 28-year-old Indian female presented with painless right side neck swelling since 5 days. She had no compressive neck symptoms like difficulty swallowing or difficulty breathing. There was no history of preceding neck trauma or upper respiratory tract infection.
Physical examination showed a solitary swelling on the right, posterior aspect of neck measuring about 6.5 × 3 cm. Margins were ill-defined. The surface on palpation was lobular, soft in consistency, and freely movable. The swelling was immobile with deglutition. Overlying skin illustrated no erythema, warmth, or tenderness. No cervical lymphadenopathy was noted.
Ultrasound scanning showed a large elliptical 8 × 7 × 3 cm cystic lesion posteromedial to right sternocleidomastoid muscle extending to right submandibular gland medially. Deep wall was abutting carotid artery and jugular vein, pushing them posteriorly. Cyst shows peripheral thin septae and tiny loculations. Cyst wall and interlocular septae were avascular ( Figure 1). On the basis of the above-mentioned USG findings, a diagnosis favoring cystic hygroma was reported by the radiologist and MRI was planned next so as to get a more accurate radiological diagnosis.
Magnetic resonance imaging findings showed a thin walled multilobular cystic mass with a size of 66.0 × 53.7 × 27.0 mm (CC × AP × Trans) in intermuscular plane on right side of neck. Inferiorly it extended up to the level of vocal cord; laterally it abutted the sternocleidomastoid muscle and parotid gland. Medially it abutted the carotid sheath and scalene muscle and posteriorly it abutted the  submandibular gland. No communication to pharynx is seen and no inflammatory changes were noted around it. The mass appeared hyperintense on T2-weighted images and hypointense on T1-weighted images (Figures 2 and 3). This is a stage III lesion according to the staging system proposed by De Serres. In our patient the radiologist reported that the lesion could also be a second branchial cleft cyst.
Because of contrary between USG and MRI findings, FNA was conducted to get a probable diagnosis. Yellow viscous fluid was aspirated from the cyst and on cytological analysis was found to contain numerous lymphocytes, making cystic hygroma a probable diagnosis.
Surgery was conducted under general anaesthesia. A horizontal incision was given over the maximum bulge of the underlying cyst and the overlying skin; subcutaneous fat with platysmal flap was raised apart exposing the cystic mass which measured approximately 7 cm along the widest diameter ( Figure 4). Cyst was dissected in planes and noted to be lying over internal jugular vein, carotid artery, and spinal accessory nerve. The cyst was pushing sternocleidomastoid muscle laterally, extending up to parotid gland superiorly. Cyst was excised ( Figure 5) and surgical drain was kept fixed. Suturing was done in two layers and dressing was applied. Drain was removed on 3rd postoperative day and dressing with sutures was removed on 7th postoperative day, displaying a healthy wound. No recurrence or complication has been noted until one-year postoperative follow-up.
Case Reports in Otolaryngology   Histopathological findings revealed cyst wall showing endothelium lined channels and collections of lymphoid tissue confirming a diagnosis of cystic hygroma ( Figure 6).

Discussion
Lymphatic malformations are uncommon benign, congenital malformations of the lymphatic system that involve the skin and subcutaneous tissues.
Several staging and classification system have been opted for better diagnosis and management. Smith et al. [23] described lymphatic malformation as microcystic, macrocystic, or mixed variant, with macrocystic containing cysts more than 2 cm in diameter. Cystic hygroma is a misnomer for macrocystic lymphatic malformation. Kennedy [12] classified these lesions into 4 types: superficial cutaneous, cavernous, cystic hygroma, and diffuse systematic. Jackson [24] classified vascular malformations into 2 types: low flow and high flow. Lymphatic malformations were classified as low flow lesions. de Serres [25] proposed a staging system according to location and extent of lesions: stage 1 is unilateral infrahyoid, stage 2 is unilateral suprahyoid, stage 3 is unilateral infrahyoid and suprahyoid, stage 4 is bilateral infrahyoid, and stage 5 is bilateral infrahyoid and suprahyoid.
Schefter et al. [37] reported the largest series of adult CH, with 32 patients. Naidu and McCalla [38] did an extensive review of literature on lymphatic malformations on 91 adult patients and, in addition, reported the oldest case of cystic hygroma in a 91-year-old woman. The ages of 89 of the 91 patients were provided, with the average age at presentation of 36.6 years and ranging from 16 to 86 years. 45% of these patients were male. Location wise, no significant predilection was shown in their study (46.4% left, 50% right). However, Schefter et al. noted right side dominance.
Cystic hygroma varies from 1.0 to 30.0 cm in size; the mean size in Stromberg's series was 8.0 cm [19].
There are several genetic syndromes associated with cystic hygromas, although most commonly seen in Turner syndrome, associated with other chromosomal abnormalities such as trisomies 13, 18, and 21 and with Noonan syndrome. Isolated cystic hygromas can be inherited as an autosomal recessive pattern for which parents are "silent" carriers [39][40][41][42][43].
Some authors attribute adult LMs to delayed proliferation of congenital lymphoid rests. Acquired processes like 4 Case Reports in Otolaryngology infection, trauma (including surgery), or lymphatic obstruction have also been linked to adult LMs. Aneeskumar et al. [44] suggested that trauma could trigger formation of lymphangioma. Mhoon et al. [45] reported a scrotal swelling after trauma.
Clinical presentation depends on the location, size, and rate of growth of malformation. Extensive lesions of the floor of mouth, oropharynx, or neck result in airway insufficiency. Cervical lesions can lead to compressive lesions like dysphagia when compressing esophagus or dyspnea on tracheal or laryngeal compression. Gorham syndrome [46] or vanishing bone syndrome is a type of lymphatic malformation that involves bone and surrounding tissue. Hypertrophy of bones and soft tissues often leads to macroglossia, macrocheilia, and macrotia. Zheng et al. [47] found that 83% of LMs patients were associated with bone deformity and 33% with bone morphogenetic abnormalities. Lymphopenia can sometimes also be an associated feature [48].
Various diagnostic modalities have been mentioned in literature and imaging methods like USG, MRI, and CT scan have been used prior to treatment; however, imaging preferences vary by cost, convenience, and resolution. Preoperative imaging is even important to look for intrathoracic extension which is present in 10% of cases [49]. FNAC is recommended by few authors but some consider it as a source of inflicting infection and increasing risk of bleeding and recurrence [36,50]. Usually, a yellow fluid with mature lymphocytes and histiocytes are aspirated. USG is mostly the first-order study of choice to investigate a suspected mass of neck because of its noninvasiveness, low cost, and nonuse of ionizing radiation [51]. USG shows fluid filled cystic cavities with or without loculation. On CT, the lesion is seen as homogeneous cystic masses with no enhancement after intravenous contrast injection [52]. On MRI, the lesion has low to intermediate intensity on T1-weighted image, hyperintensity on T2-weighted image with no enhancement after contrast injection [52,53]. Sometimes LMs with internal hemorrhage display low signal intensity on T2 weighted image.
Many treatment methods have been documented in the literature, including surgery, various sclerotherapy, radiotherapy, and laser therapy. Kennedy et al. [54] recommended awaiting spontaneous resolution in order to avoid potential hazards of surgery. Spontaneous regression is rarely seen and only 1.6-16.0% has been reported [47,55,56]. Surgery used to be the mainstay of treatment and remains the treatment of choice for LMs. Their proclivity to infiltrate nearby neurovascular structure and muscles makes surgical excision difficult, especially in children [29,44,54,[57][58][59]. In adults CH is well circumscribed, hence making complete surgical excision relatively easier compared to pediatric population [60]. Wiggs and Sismanis [14] recommended earliest surgical excision of adult CH so as to avoid prospective difficult excision following infection. Formal neck dissection removing abnormal lymphatic tissues, sometimes including a parotidectomy, has also been recommended by some authors [50]. Complications of resection include infection, bleeding, hematoma, and postoperative seromas. Injury to facial, hypoglossal, glossopharyngeal, recurrent laryngeal, and lingual nerves has been reported [34,39,54]. Radiotherapy, sclerotherapy, electrocoagulation, cryotherapy, and laser therapy have been recommended as primary or adjunctive treatment for extensive and diffuse malformation. Radiotherapy is effective in inhibiting microcystic lesions but has been abandoned due to the risk of malignant transformation [61]. Various sclerosing agents have been used including ethanol, doxycycline, quinine, hypertonic glucose, corticosteroids, sodium morrhuate, bleomycin, and OK-432; bleomycin and OK-432 remain the mainstay therapeutic agent for LMs. OK-432 (picibanil) is obtained from a lyophilized mixture of Group A pyogenes streptococcus and because of immunomodulating effect it increases several cytokines, such as interleukin-(IL-) 1, IL-2, interferon gamma, IL-6, and tumour necrosis factor, thus increasing endothelial permeability, accelerating lymphatic drainage, and fostering retraction of cystic cavity [62,63]. Yura et al. [64] and Ogita et al. [65] first reported use of intralesional bleomycin and OK-432 with excellent results. Complete resolution was noted in eight out of nine patients treated with intralesional injection of OK-432 by Ogita [68]. Laser therapy is effective for superficial microcystic lesions. CO2 laser, Nd:YAG laser, pulsed dye laser, and diode lasers are available options [69]. Zhou et al. [70] described a treatment decision algorithm for head and neck LMs.
Recurrence of cystic hygroma after excision is influenced by various factors like location of lesion relative to hyoid bone, presence/absence of encapsulation, and partial versus complete excision. Ricciardelli and Richardson [34] reported that recurrence is related to the location of lesion relative to hyoid bone, with lesions located above the hyoid having higher chances of recurrence. Fliegelman et al. [20] reported that recurrence is related to histological encapsulation of lesion. Recurrence rate of 10-15% has been reported with partial surgical excision. Most common lesions of posterior triangle of neck are mostly solids and include inflammatory and metastatic adenopathies, lymphomas, lipomas, and neurofibromatosis [71,72]. When evaluating cystic lesions of neck, the most common differentials are thyroglossal cysts, followed by brachial cleft cysts and lymphangiomas [73,74].

Consent
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review.