Facial infiltrating lipomatosis: A case report and review of literature

Abstract

Infiltrating lipomatosis of the face has been described as a congenital disorder in which mature lipocytes invade adjacent tissues in the facial region. The presentation is always unilateral with hypertrophy of hard and soft structures on the affected side of the face. We present a case of a 27-year-old female who reported with a complaint of recurrent unilateral facial swelling with history of two previous resections, the histopathology or details of these surgeries were not available. The patient underwent resection of tumour and the histopathology confirmed it to be infiltrating lipomatosis. The surgery resulted in a definite improvement in the facial asymmetry and the patient is being closely followed up with no evidence of recurrence. The pathogenesis of the condition is unclear, though it has been postulated that the condition is at one end of a spectrum of overgrowth syndromes with classic Proteus syndrome on the other extreme. Management of this condition involves resection of the tumour which in most cases is subtotal to reduce the risk of damage to facial nerve. There is a controversy regarding both timing and extent of resection in the literature and we think the subtotal resection of tumour in an adolescent or older patient can give good aesthetic outcome without compromising facial nerve function. However, the patients should be informed about high rate of recurrence and increase risk of complications with any subsequent surgery.

1. Introduction

Infiltrating lipomatosis of the face (IL-F) was first described as a distinct clinical–pathologic entity by Slavin et al. in 1983 as a congenital disorder in which mature adipocytes/lipocytes invade adjacent tissue, hard and soft, in the facial region.¹ All cases reported in the literature have been of patients in the first three decades of life, with most presenting in infancy with unilateral swelling of the cheek or chin due to normal functioning but hypertrophied tissues.^1–16 This condition shows a wide phenotypic range^1–16 and distinct histopathologic features.¹ Even though the condition is clearly defined as a clinical entity, the pathogenesis and biological behaviour remain uncertain.¹⁵ In the reported cases, there is a lack of consensus on treatment strategy with respect to the extent of resection and timing of surgery. Regardless of management philosophy, all reported cases had uncertain prognosis with high rates of recurrence and variable post-op cosmetic improvement.^1–16 Here we report a case of a recurrent left sided swelling in the upper two thirds of the face in a 27-year-old female, with a history of two previous resections in this region.

2. Presentation of case

A 27-year-old female presented with a left-sided facial swelling. She was reported to have a slight swelling in the left side of face from an early age which increased insidiously and resulted in marked facial asymmetry by the age of 17 years. She gave history of surgery for the reduction of the facial asymmetry on two previous occasions at 19 years and then at 23 years of age, with significant recurrence on both occasions. The histopathology report and details of previous surgeries were not available.

Clinical examination showed hard bony lump over the left zygomatic arch with soft tissue swelling extending from the left temple to the left cheek and intact facial nerve function (Fig. 1a and b).

Fig. 1.

(a) Pre-op front face photograph and (b) pre-op left lateral face photograph.

Computed tomography showed, bony enlargement of left zygomatic arch with evidence of normal marrow extension into these bony protuberances. There was overgrowth of the fat within the subcutaneous tissues overlying the left anterior face with infiltration into the masseteric space and left parapharyngeal space up to the skull base. There was evidence of tubular soft tissue within the fat density, possibly vessels (Fig. 2a and b).

Fig. 2.

(a) CT scan showing subcutaneous fatty overgrowth and (b) CT scan showing enlargement of left zygomatic arch.

The tumour was debulked, in May 2009, via a unilateral coronal flap and rhytidectomy incision and involved left superficial parotidectomy, removal of the zygomatic arch and a subtotal excision of the tumour without damaging the facial nerve. On surgical exposure, the tumour appeared to be unencapsulated fatty tissue spread in a subcutaneous plane infiltrating the masseter, the parotid and the zygomatic arch, which was grossly deformed.

Post-operatively, the surgery produced a significant improvement in her appearance and with the exception of neurapraxia affecting the zygomatic branch of the VII nerve there were no other immediate post-op complications. On one year post-operative follow up, the patient was happy with the outcome of the surgery, the palsy of the zygomatic branch of the VII nerve had resolved and there was no evidence of recurrence. She continues to be monitored on a yearly basis and is fully aware of the likelihood of recurrence (Fig. 3a and b).

Fig. 3.

(a) Post-op front face photograph and (b) post-op left lateral face photograph.

Histopathologic examination revealed sheets of subcutaneous unencapsulated mature adipose tissue with scant supporting fibrovascular stroma with no evidence of atypia or malignancy. This tissue was seen to infiltrate the parotid tissue which showed prominent replacement of the glandular tissue by mature adipose tissue. The lobular architecture of the gland was largely preserved although the interlobular septa were compressed in many places. The tumour also infiltrated the zygomatic bone which showed a mild degree of remodelling and encompassing prominently fatty marrow surrounded by sheets of mature lipocytes and supporting fibrovascular stroma (Figs. 4 and 5).

Fig. 4.

Histology slide showing infiltration into muscle.

Fig. 5.

Histology slide showing infiltration into bone.

3. Discussion

Lipomatosis can refer to occurrence of either multiple lipomas or diffuse, infiltrating but benign tumours of mature adipose tissue. Enzinger and Weiss classified the lipomatosis into three different entities: symmetrical lipomatosis (usually in the neck), pelvic lipomatosis and diffuse lipomatosis of the limbs and trunks.¹⁷ This classification failed to include facial lipomatosis.

Slavin et al. described the following characteristic histomorphologic findings: (1) infiltration of fat into adjacent soft tissue and hypertrophy of the underlying skeleton; (2) absence of malignant characteristics; (3) absence of lipoblasts; (4) presence of fibrous element; (5) increased number of vessels with unifocally thickened muscular walls; and (6) increased number of nerve bundles of variable size with focal fibrosis.¹

Reported phenotypic features of facial lipomatosis include (1) unilateral hypertrophy of soft tissues of the face, most commonly the cheek, with underlying fat infiltration and skeletal overgrowth,^1–16 (2) cutaneous capillary blush (usually after resection),¹⁰ (3) macrodontia on the affected side,^1,3,6,9,10 (4) abnormal root formation,³ (5) early eruption of deciduous and permanent teeth on the affected side,^10,15,16 (6) macroglossia^10,14,16 and (7) protuberances on the tongue and buccal mucosa, which are representation of underlying mucosal neuromas^10,16 (Table 1).

Table 1.

Phenotypic features and recurrence in patients with Facial Infiltrating Lipomatosis reported within reviewed literature.

Author (s)	Year	Gender	Age (years)	Recurrence	Phenotypic features
Slavin et al.1	1983	M	2	Yes	Unilateral diffuse soft mass over parotid region.
		F	9	No	Unilateral swelling of soft tissue extending from cheek up to the temporal region with hypertrophy of underlying zygoma.
		F	2	Yes	Unilateral diffuse mass over anterior maxilla extending to the lower lip, periorbital and frontal regions.
De Rosa et al.2	1987	M	53	Yes	Unilateral hypertrophy of soft tissues of cheek and underlying bone.
		F	9	Yes	Unilateral hypertrophy of soft tissues of cheek.
		F	23	Yes	Unilateral hypertrophy of soft tissue in submandibular region, floor of mouth, lower lip and underlying mandibular bone.
MacMillan et al.3	1990	F	36	Yes	Unilateral diffuse swelling with hypertrophy of soft tissues and underlying bone in the cheek and hypertrophy of soft tissue in the affected side on the palate. Macrodontia of maxillary teeth noted.
Donati et al.4	1990	M	<1	No	Unilateral hypertrophy of soft tissues of the cheek and underlying bone.
Patel and Gondalino5	1991	F	<1	Not known	Not known.
Kang et al.6	1998	M	25	No	Unilateral hypertrophy of soft tissue and hard tissues of cheek and macrodontia on the affected side.
Van Wingerden et al.7	1998	M	<2	Not known	Not known.
Görken et al.8	1999	F	6	No	Unilateral hypertrophy of soft tissues and bone in the anterior maxillary region with multiple, pigmented epithelial polyps and sebaceous nevi.
Bouletreau et al.9	2000	F	16	No	Unilateral hypertrophy of soft tissue and hard tissues of cheek with macrodontia on affected side.
Padwa and Mulliken10	2001	M (8) F (5) (n = 13)	Avg. 12.4 Range 1.1–22.9	In 6 cases	Unilateral hypertrophy of cheek (12) and chin (1) with underlying fat infiltration and skeletal overgrowth (9) Cutaneous capillary blush (9) Ipsilateral macroglossia (8) Mucosal neuromas (6) Early eruption of ipsilateral dentition (12)
Ergün et al.11	2001	M	6	No	Unilateral hypertrophy of cheek and ipsilateral upper lip.
		M	45	No	Unilateral hypertrophy of submental and submandibular tissues including ipsilateral cortical expansion of mandible.
Chen et al.12	2002	F	<1	No	Unilateral hypertrophy of cheek and ipsilateral upper lip.
Unal et al.13	2003	F	2	No	Unilateral diffuse soft mass on cheek.
Pires Fraga et al.14	2008	M	2	Yes	Unilateral diffuse soft tissue swelling on the lower medium-third of the hemi-face extending to oral cavity, the floor of mouth and the tongue on affected side.
Kamal et al.15	2010	F	16	Not known	Unilateral soft diffuse mass in the cheek extending from lower border of mandible, to the inferior orbital rim, to the oral commisure. Hemimandibular hypertrophy, acceleration of dentoskeletal growth, macrodontia and hypertrophy of the zygomatic bone.
		F	18	Not known	Unilateral mass on the left side of the face extending up to the temporal area associated with the hypertrophy of the underlying zygoma.
		M	2	NA (not operated on)	Unilateral diffuse soft mass located on anterior maxilla extending to the inferior orbital rim, lower border of mandible and parotid gland region. Unilateral macrodontia.
Kim et al.16	2010	F	3.5	Yes	Unilateral swelling of cheek, tongue, teeth, mandible, parotid and submandibular salivary glands. Premature eruption of secondary dentition, hyperplastic papillae of the anterior third of tongue and mucosal neuromas.

The pathogenesis of IL-F is unclear. Based on commonality of hamartomatous overgrowth of various tissues including fat, it has been postulated that IL-F, represents one end of a spectrum of disorders that includes at the other extreme classical Proteus syndrome. Proteus syndrome is characterised by sporadic occurrence, verrucous epidermal nevi, variable benign tumours including lipomas, vascular malformations and hyperostosis.¹⁸ The molecular basis of Proteus syndrome is unclear but it has been postulated to arise through embryonic somatic mutations resulting in somatic mosaicism.¹⁹ The variability in the phenotype would arise through variability in the timing of the somatic mutation and distribution of cells carrying the mutation. However, more recently some cases of Proteus (10–20%) and Proteus-like (80%) syndrome have been shown to have germline mutations of the PTEN gene.¹⁹ The lack of PTEN mutations in many cases of Proteus syndrome indicates that there is genetic heterogeneity in phenotypes defined as Proteus syndrome. Germline mutations in PTEN and RET (which is mutated in multiple endocrine neoplasia type 2b) have been excluded in one series of IF-L.¹⁰

Interestingly, in two separate case reports cytomegalovirus (CMV) inclusions within the secretory cells of the parotid glands, which were infiltrated by lipomatous tumour, were found. However, it was not clear whether there was a causal relationship between the CMV and lipomatosis.^4,5

Differential diagnosis for non-acute unilateral facial enlargement includes infections, trauma, vascular malformations, benign and malignant tumours of soft and hard tissues. Amongst these the possibility of hamartomatous or overgrowth syndromes should also be considered.

Progression of the condition seems to follow two patterns: a rapidly progressive form with extensive hypertrophy occurring in early childhood (age < 1 year) and a more indolent form with hypertrophy occurring over decades, with patients presenting for treatment in adulthood.⁶ Management would therefore depend on deciding the timing and extent of surgical excision.

On review of literature, there is disagreement on this matter. Early reports like Slavin et al. and Kang et al. recommended wide and early local excision to prevent extensive infiltration.^1,6 In contrast, Von Wingerden et al. suggest that by delaying resection, both the chance of damaging the facial nerve and the number of debulking procedures would diminish.⁷ They proposed liposuction for achieving facial symmetry at an early stage of the disease instead of an attempt at total excision.

There are others who favour a more conservative approach because the tumour is benign in nature and has a critical location.³

More recently, Kamal et al. echoing the thoughts of Van Wingerden et al., believe that no surgical procedures should be performed until the end of the facial growth period and mention that the delay of definitive surgery has other advantages such as minimising the chance of damage to the facial nerve, decreasing the total number of procedures, and having a mature contralateral cheek contour to match.¹⁵

Padwa and Mulliken believe growth hormones may have a role in recurrences and that any mass reduction before the end of adolescence is likely to fail.¹⁰ Waiting for the facial growth to stop may not always be acceptable to the patient's family and the patient's psychosocial aspect should also be kept in mind.^6,10 Proponents of delayed surgical resection also noted that postponement may make the procedure more extensive.⁷

4. Conclusion

Pathogenesis of infiltrating lipomatosis of the face is not fully understood. The review of literature supports the fact that the condition has a varied phenotype and that it is a congenital condition with an early (first decade) presentation. Only 7 out of 36 reported cases, presented in and beyond the second decade of life (Table 1).

Management of the condition is controversial, with varying ideas on the extent and timing of surgery. Resection in most instances is subtotal due to the infiltration of tumour into adjacent soft and hard tissues and the location increasing the likelihood of compromising facial nerve function.

Incomplete excision is most likely to cause re-growth, which as some believe is more likely if the patient is below the age of adolescence.^10,15 Restoration of full facial symmetry is unlikely, the patient should also be informed about the high rate of recurrence and that surgery is accompanied by a high complication rate.

Conflict of interest

The authors of this manuscript disclose that they do not have any financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work.

Funding

None.

Ethical approval

A written informed consent was obtained by the patient for publication of this report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Author contributions

Karan Singh drafted the article.

Pinaki Sen critically revised and contributed towards clinical presentation and surgical procedure used in management of this case.

Brian T. Musgrove gave final approval of the version to be submitted and contributed towards management of condition.

Nalin Thakker critically revised and contributed towards histopathology, genetics and provided photomicrographs of the histopathology slides.