1 Introduction
Madelung’s disease (MD), also known as multiple symmetric lipomatosis, is a rare metabolic disorder with an estimated incidence of approximately 1 in 25,000 in the Mediterranean region. It predominantly affects middle-aged men and is associated with long-standing alcohol consumption
[1]. MD is characterized by non-encapsulated and infiltrative adiposity, which commonly involves both cervical and shoulder girdle regions. Increasing adipose buildup and growth may distort the anatomy of the neck, leading to restricted cervical mobility, compromised airway structure and complicated anesthetic airway assessment and intubation.
Hypopharyngeal squamous cell carcinoma (HPSCC) is another crucial cause of upper airway obstruction with poor prognosis. Alcohol consumption is a recognized risk factor for both MD and HPSCC. However, the coexistence of these two conditions is extremely uncommon, and their combined impact on airway function has rarely been described.
To our knowledge, this is the first reported case of MD complicated by HPSCC presenting with grade Ⅱ laryngeal obstruction due to dual airway compromise. This case raises two key clinical considerations: first, how to safely establish a lifesaving surgical airway in the setting of combined intraluminal and extrinsic obstruction; second, under these circumstances, whether upfront surgical management or simply tracheotomy with chemoradiotherapy (CRT) is preferable in this complex anatomical context.
2 Case Presentation
A 62-year-old Chinese male from Yunnan Province presented with a 4-month history of untreated hypopharyngeal cancer (Fig.S1a–d) and progressive dyspnea over 10 days. He reported hoarseness, sore throat, cough, dysphagia, and worsening difficulty breathing without hemoptysis, fever, chest pain, or wheezing. The patient had a 30-year history of heavy smoking and alcohol consumption and had been diagnosed with cervical multiple symmetric lipomatosis approximately 10 years earlier, for which he had undergone prior surgical treatment. His medical history included hypertension, type 2 diabetes mellitus, peripheral vasculitis, and alcoholic liver disease. There was no family history of malignancy.
Physical examination showed extensive, symmetrical, soft, non-tender mass enlargement in cervical and shoulder girdle regions, which was consistent with type I MD (Fig.1). Fiberoptic laryngoscopy with narrow band imaging (NBI) showed a right-sided hypopharyngeal mass extending from the pyriform sinus region to the postcricoid region with a significant airway narrowing (Fig.2a–b). Enhanced CT and MRI revealed thickening of the posterior hypopharyngeal wall with partial protrusion into the pharyngeal cavity, bilateral cervical lymphadenopathy (approximately 1.1 cm largest node), and diffuse adipose tissue infiltration of the bilateral cervical subcutaneous layers. The pretracheal subcutaneous adipose tissue thickness reached a remarkable 7.69 cm (Fig.2c–f).
Biopsy confirmed moderately differentiated squamous cell carcinoma. The clinical stage was cT3N2bM0 (TNM stage IVA).
As the patient presented with grade Ⅱ laryngeal obstruction caused by combined intraluminal tumor obstruction and extrinsic compression from massive cervical lipomatosis, an emergency airway strategy was required. Awake tracheal intubation was performed with ECMO team standby to ensure airway safety.
The patient underwent total laryngectomy with partial pharyngectomy and bilateral neck dissection, combined with excision of extensive cervical lipomatous tissue (Fig.3a–d). The intraoperative blood loss was approximately 200 mL, and the procedure was completed without any adverse events. Postoperatively, the patient remained stable in the intensive care unit for 48 hours before being transferred to the general ward, with an uneventful recovery and no significant perioperative complications. The pathological stage was pT3N2bM0 (TNM stage IVA).
3 Results
Histopathology confirmed squamous cell carcinoma with tumor infiltration into adjacent adipose tissue. Hematoxylin and eosin (H&E) staining demonstrated the distribution of adipose tissue, tumor, adjacent normal mucosa and adipose tissue. Immunohistochemical (IHC) staining showed markedly increased uncoupling protein 1 (UCP1) expression in tumor cells compared with adjacent normal mucosa, whereas PRDM16 expression was comparable between the two tissues (Fig.4a–c). In adipose tissue, UCP1 showed positive expression, whereas PRDM16 exhibited weak expression (Fig.4d–f). Postoperative visual analogue scale (VAS) pain score was 2, and no additional analgesia was required. The patient received three cycles of chemotherapy with a regimen consisting of paclitaxel (200 mg), carboplatin (500 mg), and capecitabine (1.5 g). Further radiotherapy was declined due to financial constraints. At the 6-month follow-up, the patient remained clinically stable (Fig.5a–c).
4 Discussion
MD is a rare metabolic disorder characterized by diffuse, non-encapsulated adipose tissue accumulation, predominantly involving the cervical regions
[2]. Although generally benign, extensive cervical involvement can distort normal neck anatomy and compromise the upper airway. In contrast, HPSCC is an aggressive malignancy frequently associated with airway obstruction. The coexistence of these two conditions is extremely rare and may result in a complex and potentially life-threatening airway scenario.
The combination of intraluminal tumor obstruction and extrinsic compression from massive cervical lipomatosis resulted in dual airway compromise, representing an underreported clinical challenge, requiring careful planning of airway management. In this case, given that tracheostomy is a well-documented strategy for securing the airway in several advanced head and neck cancers, performing this procedure in MD patients may be technically challenging because obscured anatomical landmarks increase the risk of excessive dissection and bleeding. Several studies have advocated the use of preemptive veno-venous extracorporeal membrane oxygenation (VV-ECMO) or awake tracheal intubation in patients with significant tracheal narrowing. ECMO may be considered in severe cases, particularly when ventilation is unstable during induction. However, ECMO is associated with a substantial risk of complications, including renal failure, limb ischemia, and infection, as well as anticoagulation-related bleeding. Consistent with most MD cases, awake tracheal intubation should be the first-line airway management strategy
[3,
4]. However, ECMO should be available as a standby option to maintain airway security in the event of failed ventilation or intubation, particularly in cases of severe laryngeal obstruction.
We elected to perform upfront surgical resection rather than tracheostomy followed by chemoradiotherapy (CRT) for several reasons. First, tracheostomy alone might provide temporary airway relief but would not address either the tumor burden or the compressive cervical lipomatosis during subsequent CRT. In contrast, upfront surgical treatment allowed simultaneous treatment of both conditions. Second, excessive adipose tissue may potentially limit the efficacy of non-surgical treatment through adipocyte-mediated drug sequestration or metabolism, an immunosuppressive adipose microenvironment, and dosimetric challenges associated with increased soft-tissue thickness
[5,
6]. Third, the tumor invaded to the postcricoid region, where organ-preservation strategies are generally less successful and total laryngectomy is frequently required for definitive treatment. Finally, the patient and his family expressed a clear preference for definitive surgical management after multidisciplinary discussion and detailed preoperative counseling regarding the risks, benefits, and alternative treatment options. Of note, given the extensive distribution of cervical lipomatosis in this patient, the lipomatous tissue overlying the occipital and posterior nuchal regions was not resected during the index procedure. This deliberate intraoperative decision was made to curtail total operative time and minimize intraoperative blood loss. Even in the setting of isolated Type I Madelung’s disease without concurrent malignancy, a staged surgical approach may be prudently adopted to optimize perioperative safety and mitigate physiological stress.
In addition to the traditional two-type classification, alternative systems have described three phenotypic subtypes based on the distribution of adipose tissue
[7]. Among these, Type I, which predominantly involves the cervical and shoulder girdle regions, is most relevant to head and neck pathology owing to its potential to distort airway anatomy, whereas the other subtypes primarily affect the trunk and are less commonly associated with compressive complications. The overall recurrence rate of lipectomy and liposuction was approximately 18.8% and 19.4%, respectively
[2]. The pathophysiology of MD is thought to involve mitochondrial dysfunction and abnormal proliferation of brown or beige adipose tissue
[8]. Chronic heavy alcohol consumption may impair mitochondrial oxidative metabolism and sympathetic-mediated lipolysis, thereby facilitating abnormal adipose tissue accumulation with limited effective thermogenesis. In addition, mitochondrial dysfunction and reduced DNA repair capacity may contribute to tumor development through oxidative stress and metabolic reprogramming. Heat generating protein such as UCP1 is upregulated in MD when compared to normal white adipose tissue and has been associated with reduced apoptosis in oral squamous cell carcinoma
[9]. Upstream adipogenic regulators, such as PRDM16, have also been proposed for increased expansion of brown adipose tissue
[10]. In our study, positive UCP1 expression, rather than PRDM16 expression, was found in both tumor and adipose tissue. UCP1 is a characteristic marker of brown and beige adipocytes and may reflect altered mitochondrial metabolism and adipose tissue metabolic reprogramming. These findings raise the possibility that metabolic alterations within brown/beige adipose tissue may contribute to the tumor microenvironment and potentially influence HPSCC progression. However, the biological significance of this observation remains unclear and warrants further investigation.
Interestingly, despite extensive surgery, postoperative pain was minimal in several MD cases. We found low VAS scores and no requirement for additional analgesic medication
[11]. This may be related to chronic nerve compression, mitochondrial dysfunction, and alcohol-related neuropathy, which may attenuate nociceptive signaling. These observations warrant further investigation as well.
This study has limitations, including the absence of genetic and molecular analyses and its single-case nature. However, it highlights important considerations in airway management and treatment decision-making in patients with MD and head and neck malignancy. This case also highlights that progressive dyspnea in patients with known MD should not be simply attributed to benign lipomatous compression. Endoscopic and radiologic evaluation should be performed to exclude an underlying malignancy.
5 Conclusion
The coexistence of Madelung’s disease and hypopharyngeal carcinoma may create a rare and high-risk airway scenario. A structured multidisciplinary approach, with an appropriate oxygenation strategy, including awake tracheal intubation with ECMO as a standby option, is essential to overcome the challenges posed by cervical lipomatosis and to ensure safe and effective surgical management.
6 Supplementary files
Supplementary material is available in the online version of this article at
https://doi.org/10.15302/ENTD.2026.060006 and is accessible for authorized users.
The Author(s). This article is published by Higher Education Press at journal.hep.com.cn.
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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