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Introduction

Lipomas are benign mesenchymal tumors that comprise 0.6% of all benign laryngeal tumors, mostly occurring in men during their 6th decade . Diagnosis of laryngeal lipomas can be challenging because patients may be asymptomatic or have non-specific symptoms like dyspnea, paroxysmal coughing, sleep apnea/snoring, and dysphagia. In addition, patients may develop airway obstruction due to progressive growth of this tumor .

Liposarcoma is a malignant mesenchymal tumor originating from adipose tissue . Liposarcomas are most commonly found in men in their 4th to 6th decade and is the most common soft-tissue sarcoma in adults . Though controversial, liposarcomas are currently thought to form de-novo, with little evidence to suggest malignant transformation of a pre-existing benign tumor . However, some experts maintain that malignant transformation is possible in long-standing lipomas . Up to 9% of liposarcomas are found in the head and neck . There have been less than 40 reported cases of laryngeal liposarcomas , 75% of which are supraglottic . Laryngeal, supraglottic and hypopharyngeal liposarcomas produce symptoms of dysphagia, hoarseness, choking, and dyspnea due to significant airway obstruction . Retropharyngeal liposarcomas have been shown to cause obstructive sleep apnea . When present in the head and neck, liposarcomas are typically low-grade and early stage, thus having a better prognosis and disease specific survival than liposarcomas found in other sites .

Manifestations of liposarcomas bear striking resemblance to that of lipomas. Both may present clinically as pedunculated, submucosal, smooth, well-defined masses . The painless tumor goes unnoticed until it grows large enough to become obstructive, making differentiation between liposarcoma and lipoma difficult for clinicians based on symptoms and clinical presentation alone .

Because the similarities in presentation of lipomas and liposarcomas do not allow for a clinical diagnosis, management is the same for these types of lesions and involves complete excision for diagnostic and therapeutic purposes. Below, we present the two cases of lipomatous lesions of the larynx, a lipoma and a liposarcoma. A discussion of pathology, treatment modalities, and outcomes follows these case presentations.

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Case report 1: laryngeal liposarcoma

A 58-year old male presented to our clinic with a five-year complaint of progressive difficulty breathing. Specific to his complaints was an inability to lie flat, and he slept in an upright position for several years. Additionally, he complained that if he bent over, he would “faint”. He also had difficulty swallowing foods and felt a foreign body choking sensation continuously. At least in one instance, he was found unconscious and required emergency room intervention. He has history of obesity, tobacco dependency, chronic back and leg pain, coronary artery disease, and COPD. Upon examination with fiber optic endoscopy, he had a large submucosal mass involving the left supraglottic larynx, specifically the left aryepiglottic fold, interarytenoid area, and left arytenoid. This mass occluded the glottis airway intermittently in a ball-valve manner when breathing. The vocal cords were mobile bilaterally. The remainder of the head and neck examination was unremarkable. He was immediately admitted for airway obstruction.

Computed tomography scan showed a 1.3 × 3.5 × 3.1 cm in AP × transverse × craniocaudal dimension, predominantly fat-density mass located in the larynx eccentric to the left, extending to the epiglottis and left vocal cord, causing mass effect and compromise of the airway, with reduction of the airway lumen.

A transoral robotic surgical procedure was used to completely remove the tumor from the supraglottic larynx and provide a stable airway. He did not require an emergency tracheotomy. His obstructive symptoms improved postoperatively.

Grossly, the tumor was described by the pathologist as multiple, gray, tan irregularly-shaped, soft tissue fragments measuring 5.0 × 3.0 × 1.5 cm in aggregate. Cut section revealed a heterogeneous, yellow, tan irregular cut surface with adipose tissue on the underlying mucosa. By immunohistology, the tumor cells were positive for MDM2, CDK4 and CD34. Ki67 proliferation index is less than 1%. The tumor is submucosal in location ( Fig. 1 ). These findings were consistent with a well-differentiated liposarcoma, lipo-like and sclerosing variant.

Submucosal liposarcoma arising from the left supraglottis.

The patient’s symptoms improved significantly. It was recommended that he undergo postoperative radiotherapy, but the patient declined. Six months post-surgery he was breathing better without recurrence of his tumor.

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Case report 1: laryngeal liposarcoma

A 58-year old male presented to our clinic with a five-year complaint of progressive difficulty breathing. Specific to his complaints was an inability to lie flat, and he slept in an upright position for several years. Additionally, he complained that if he bent over, he would “faint”. He also had difficulty swallowing foods and felt a foreign body choking sensation continuously. At least in one instance, he was found unconscious and required emergency room intervention. He has history of obesity, tobacco dependency, chronic back and leg pain, coronary artery disease, and COPD. Upon examination with fiber optic endoscopy, he had a large submucosal mass involving the left supraglottic larynx, specifically the left aryepiglottic fold, interarytenoid area, and left arytenoid. This mass occluded the glottis airway intermittently in a ball-valve manner when breathing. The vocal cords were mobile bilaterally. The remainder of the head and neck examination was unremarkable. He was immediately admitted for airway obstruction.

Computed tomography scan showed a 1.3 × 3.5 × 3.1 cm in AP × transverse × craniocaudal dimension, predominantly fat-density mass located in the larynx eccentric to the left, extending to the epiglottis and left vocal cord, causing mass effect and compromise of the airway, with reduction of the airway lumen.

A transoral robotic surgical procedure was used to completely remove the tumor from the supraglottic larynx and provide a stable airway. He did not require an emergency tracheotomy. His obstructive symptoms improved postoperatively.

Grossly, the tumor was described by the pathologist as multiple, gray, tan irregularly-shaped, soft tissue fragments measuring 5.0 × 3.0 × 1.5 cm in aggregate. Cut section revealed a heterogeneous, yellow, tan irregular cut surface with adipose tissue on the underlying mucosa. By immunohistology, the tumor cells were positive for MDM2, CDK4 and CD34. Ki67 proliferation index is less than 1%. The tumor is submucosal in location ( Fig. 1 ). These findings were consistent with a well-differentiated liposarcoma, lipo-like and sclerosing variant.

Submucosal liposarcoma arising from the left supraglottis.

The patient’s symptoms improved significantly. It was recommended that he undergo postoperative radiotherapy, but the patient declined. Six months post-surgery he was breathing better without recurrence of his tumor.

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Case report 2: laryngeal lipoma

A 79 year-old woman was referred for evaluation of a submucosal growth in her larynx. She began noticing hoarseness one year prior to presentation and was bothered by frequent voice breaks. She denied dysphagia, but noted a persistent globus sensation. She was noted on laryngoscopic exam to have a large submucosal mass in the right supraglottis, extending from the arytenoid into the aryepiglottic fold. There was a small degree of impingement on the glottis but no frank airway obstruction. CT imaging revealed a hypodense lesion consistent with lipoma that was 1.8 cm in largest diameter.

Suspension microlaryngoscopy with submucosal removal of the tumor was performed ( Fig. 2 ). The patient was intubated easily and no tracheotomy was necessary. A laser was used to create an epithelial incision over the tumor, allowing the fatty contents to be exposed. Using microscopic instruments, the tumor was dissected free from its capsule and removed. The tumor was measured as 3.5 × 2.5 × 2 cm. The overlying mucosa was left intact and the wound left open to granulate. This was felt to be preferable to suturing the wound closed and creating a potential space that could allow abscess formation. The patient was asked to comply with a clear liquid diet for two days and turn her head to the affected side to prevent fluid collection in this cavity.

Submucosal lipoma arising from the right supraglottis.

Pathology was consistent with a benign spindle cell lipoma, with FISH testing negative for MDM2, which allows discrimination of lipoma from well-differentiated liposarcoma.

At her one month follow up visit, the patient noted complete resolution of her symptoms, with normal voice and no globus sensation. Her laryngoscopic exam revealed excellent healing of her wound with essentially normal appearance.

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Discussion

Diagnosis of liposarcomas, particularly well-differentiated liposarcomas which are the most prevalent subtype , can be challenging due to its similarities to benign lipomas. Liposarcomas are typically grossly well-circumscribed, firm yellow masses, but definitive diagnosis is made through histopathology rather than grossly . Biopsies of benign lipomas can be full of adipocytes of varying sizes as well as macrophages due to fat atrophy and necrosis; thus lack of macrophages and adipocyte size variation is highly suggestive of well differentiated liposarcoma rather than benign lipoma .

Characteristics such as mitotic bodies and activity, pleomorphism, lipoblastic proliferation, and myxoid differentiation can help rule out an intramuscular lipoma or an infiltrating lipoma, which highly resembles a liposarcoma due to invasion .

Prognosis largely depends on both histological grade and site. Well-differentiated and myxoid types, the two most prevalent types , have the best outcomes while de-differentiated types (arising from atypical lipomas or well-differentiated liposarcomas), pleomorphic, and round cell do not fare as well. Liposarcomas of the head and neck tend to be well-differentiated (44.5%) or myxoid tumors (35.5%) . Furthermore, pleomorphic and round cell liposarcomas are also much more likely to metastasize compared to well-differentiated or myxoid types . Pleomorphic subtypes are the highest grade and carry the worst prognosis amongst all five subtypes . Golledge et al found that neck, pharyngeal and oral liposarcomas have the poorest outcomes while scalp, laryngeal and face liposarcomas had much better outcomes. They also found that oral liposarcoma had the poorest outcome with a five year survival of 50% . However, other authors have noted that the small size of oral liposarcomas resulted in better prognosis .

MRI can prove to be useful to help make the diagnosis of a liposarcoma and distinguish it from a lipoma, although MRI alone would not be sufficient. MRI can highlight the presence of hemorrhage and necrosis, which would favor a diagnosis of liposarcoma rather than lipoma . Lipomas can also be distinguished from liposarcoma by the presence of complete fat suppression and lack of nodules and septa . However, even highly trained readers can correctly diagnose liposarcoma from lipoma using MRI alone based on qualities of stranding, nodularity and size only 69% of the time . Distinguishing a low grade well-differentiated liposarcoma from an intramuscular lipoma can also present challenges and oftentimes is not definitive when using MRI, thus histology still remains the gold standard .

The surgical approach for lipoma or liposarcoma is essentially the same. It should be standard practice to remove the tumor widely in the event that the tumor may be a liposarcoma.

Surgery is the first line treatment for both lipoma and liposarcoma. Surgical excision technique plays a huge role in prognosis of liposarcoma as well with regards to the extent to which the tumor was removed . Although most laryngeal liposarcomas are polypoidal , wide surgical excision is the treatment of choice with the best prognosis . Oftentimes, incomplete excision is due to misdiagnosis of a liposarcoma for a lipoma, failing to take into account the infiltrative capacity of liposarcomas, which ultimately results in a significantly greater chance for recurrence . Endoscopic wide surgical excision has been done successfully to remove laryngeal liposarcomas with potentially better functional outcomes .

Transoral robotic surgery is growing in popularity for excision of oropharyngeal and laryngeal cancers due to improved visualization and agility with instrument manipulation, thus allowing for shorter operation times and more complete tumor removals. TORS excision is promising given that liposarcoma recurrence is largely due to incomplete excision . The improved visualization has been shown to be useful in other laryngeal masses such as carcinoma, allowing for a faster, more complete tumor resection.

Radiation does not appear to add significant benefit in liposarcoma management aside from local control and appears to largely benefit those with well-differentiated or myxoid liposarcomas, which carry a good prognosis regardless. Golledge et al, in a study on 76 patients, found that although adjunct radiation therapy did not improve survival compared to surgical excision alone, patients receiving the adjunct radiation therapy had mostly pleomorphic and round cell subtypes, which have poorer outcomes. . A SEER analysis of 318 head and neck liposarcomas demonstrated that surgery alone had better outcomes than radiation therapy alone, yet this is again largely due to the fact that most of the head and neck liposarcomas were low grade and adjunct radiation was done for more high grade liposarcomas, which carries a worse prognosis . Gritli et al had also found that surgical resection alone had better prognosis than either surgical resection and radiation therapy or radiation therapy alone, yet this is due to the fact that patients receiving radiotherapy had metastasis or vascular involvement .

Radiotherapy does appear to have some benefit, however. Radiation therapy may be useful for patients that have high-grade liposarcoma with local extension . Several authors note that radiation therapy can be useful for palliative therapy, especially when surgical resection of the laryngeal liposarcoma is not feasible . Ultimately, the benefits of radiotherapy may be overshadowed by the poor prognosis of the liposarcoma patients on which they are used, and thus further research is needed to fully evaluate its effectiveness.

Chemotherapy has promising potential for treatment of liposarcomas. Myxoid liposarcomas seem to respond well to decarbazine and doxorubicine , responding better to the chemotherapy than well-differentiated and dedifferentiated variants . However, further research is needed to determine whether chemotherapy can be an effective means of therapy for laryngeal liposarcoma.