Lipomas in Clinical Practice

Dr. Renata Bačul

Introduction

Lipoma is the most common benign tumor of adipose tissue origin. It develops beneath the skin, allowing patients to quickly notice the soft, painless formation.

In most cases, subcutaneous lipomas can be easily diagnosed by a clinician during physical examination, thereby alleviating the patient's concern and fear of a possible malignant process. However, it is important to recognize signs indicating that the formation may be malignant (liposarcoma). In such cases, additional investigations are necessary to promptly clarify the diagnosis and determine appropriate treatment.

Lipomas can develop not only beneath the skin but also in internal organs and other parts of the body. Clinical symptoms, which depend on the location and size of the lipoma, may resemble those of other conditions.

Multiple lipomas (lipomatosis) may be associated with certain syndromes whose etiology and treatment may vary. In addition, some cases of lipomatosis are mistakenly diagnosed as simple obesity. In such cases, even when calorie intake is restricted, the reduction of adipose tissue accumulated within lipomas may be very limited, causing frustration for the patient.

This article presents the characteristics of lipomas, discusses their clinical significance, and focuses on differential diagnosis and the selection of treatment strategies.

Etiology

The etiology is not fully understood; however, according to some studies, approximately two-thirds of lipomas are associated with genetic causes (1).

The following chromosomal structural or genetic alterations are associated with the development of lipomas (1):

• 12q13–15 region (HMGA2 gene) (65%);
• loss of a portion of 13q (10%);
• 6p21–23 region (5%);
• abnormalities of other loci or a normal karyotype (15–20%).

It is believed that trauma may influence the development of lipomas. Tissue damage causes the release of cytokines, which induce the differentiation and maturation of preadipocytes. This hypothesis is supported by clinical cases in which lipomas began to develop at sites of injury several months later (2–3).

Familial multiple lipomatosis and the familial adenomatous polyposis variant Gardner's syndrome (4) are inherited in an autosomal dominant manner. Madelung's disease, characterized by benign symmetrical lipomatosis of the head, neck, shoulders, and upper back, is typical in men who abuse alcohol (5). Dercum's disease (adiposis dolorosa), characterized by painful lipomas on the trunk, shoulders, arms, and legs and occurring most commonly in middle-aged women, has an unknown etiology (6).

Epidemiology

The documented prevalence of lipomas is approximately 1%; however, it is believed that not all cases are registered and that not all patients seek medical attention (7). Lipomas can develop at any age but are most commonly diagnosed in individuals aged 40–60 years (8).

Approximately 5% of cases involve multiple lipomas (lipomatosis). Solitary lipomas are more common in women, whereas lipomatosis is more common in men (5). Cases of congenital lipomas have also been described (9).

Pathophysiology and Clinical Significance

Lipomas are slow-growing, benign mesenchymal tumors composed of lobules of mature adipocytes. They are separated from the surrounding tissues by a thin fibrous capsule. Subcutaneous lipomas are the most common and are not attached to the muscle fascia. They are described as superficial, well-circumscribed, soft, pliable formations that are usually asymptomatic.

Lipomas can also occur in internal organs. In the gastrointestinal tract, they are visualized endoscopically as submucosal formations. They are most commonly found in the esophagus, stomach, and small intestine. Small lipomas are usually asymptomatic, whereas giant lipomas may present as emergency conditions by obstructing the intestinal lumen and causing intestinal obstruction, perforation, or massive bleeding (10). A case of obstructive jaundice caused by a duodenal lipoma obstructing the bile ducts has been described in the literature (11).

Testicular lipomas are often misdiagnosed as inguinal hernias, with the true cause of the mass in the inguinal region identified only during surgery (12). Lipomas of the throat, trachea, or bronchi may manifest as chronic cough or life-threatening respiratory tract obstruction (13–14).

Cardiac and pericardial lipomas are rare, accounting for approximately 8.4% of all primary tumors (15). They may be discovered incidentally, but they can sometimes be symptomatic, for example, causing superior vena cava syndrome due to right atrial lipomatosis or presenting as a giant right atrial lipoma resembling cardiac tamponade (16–17).

Documented locations of lipomas include the brain and spinal cord, endocrine glands (thyroid, adrenal glands, pancreas, and pituitary gland), tongue, salivary glands, eyeballs, facial sinuses, pleura, breasts, joints, and bones (7). There is a presumption that lipomas may undergo malignant transformation, but this phenomenon has not been described in the literature to date.

Classification

Lipomas are usually encapsulated by fibrous tissue. Rarely, however, non-encapsulated or infiltrating lipomas may occur (18–19). These lipomas are more aggressive because they can grow rapidly and infiltrate surrounding tissues. Their resection is more complex because of the higher risk of damaging important structures, and if they are not resected widely enough, they are prone to recurrence (5, 16).

The following histological variants of lipoma are distinguished:

• angiolipoma has a dense network of blood vessels, making it sensitive to temperature changes—it turns pale in very cold weather and reddens in hot weather. Angiolipomas can be painful and usually appear shortly after puberty (5, 18);
• lipoma of mature fat cells / pleomorphic lipoma is a rare adipocytic neoplasm with symptoms and signs similar to those of classical lipomas, but it predominates in men aged 50–70 years and is usually located in the shoulder and neck region (20–21);
• adenolipoma without adipocytes consists of healthy eccrine sweat gland tissue. Its symptoms and signs are similar to those of classical lipomas. It is most commonly located in the proximal parts of the limbs (22);
• hibernoma is composed of brown adipose tissue. Hibernating animals have the greatest amount of this tissue—hence the name. It is most common in women in their thirties and is located in the intermuscular space (23);
• fibrolipoma consists of connective tissue. The greater the amount of connective tissue, the firmer the consistency of the formation. It is usually located in the oral mucosa and is more common in women (24);
• lipoblastomas develop from embryonic white adipose tissue. They occur almost exclusively in infants and children and are localized in the limbs and trunk (25).

All these lipoma variants, like classical lipomas, are benign.

Lipomas may be solitary or multiple (lipomatosis). Lipomatosis is a manifestation of certain syndromes or diseases.

Symptoms and Signs

Patients diagnosed with subcutaneous lipomas usually complain of a mobile, soft mass that is typically painless unless it compresses surrounding tissues, such as joints, nerves, or blood vessels. As mentioned above, angiolipomas can be painful, while extremely painful lipomas that affect quality of life are a characteristic feature of Dercum's disease.

Subcutaneous lipomas usually remain unchanged. They are most commonly located in the subcutaneous tissue of the head, neck, shoulders, and back (7). After an initial period of growth, they enter a static phase and do not grow further. Lipomas become firmer when exposed to ice, similarly to butter in a refrigerator (26).

The symptoms of lipomas in other locations depend on their size and localization.

Hereditary multiple lipomatosis is characterized by multiple encapsulated, painless subcutaneous lipomas on the trunk and limbs, usually first noticed after the third decade of life (27).

Madelung's disease is characterized by a symmetrical distribution of adipose tissue masses in the head, neck, shoulders, and upper back, and its manifestations are therefore often mistaken for obesity. Due to the accumulation of fat in the nape and neck regions, described as a "buffalo hump" and "horse collar," the patient may have a pseudo-athletic appearance (28). Some patients develop compression-related complications, including peripheral neuropathy, dyspnea, dysphonia, dysphagia, and signs of vena cava or carotid artery compression (28).

In the familial adenomatous polyposis variant Gardner's syndrome, in addition to multiple colorectal polyps, some patients have solitary or multiple subcutaneous lipomas, epidermoid cysts, and osteomas (8).

In addition to painful lipomas, Dercum's disease is characterized by pronounced general weakness, anxiety, depression, arthralgia, tachycardia, and obesity (29). Body weight may increase rapidly, and the greater the body weight, the more painful the lipomas become (29).

Differential Diagnosis

The differential diagnosis of lipomas is presented in Table 1.

In the presence of a subcutaneous mass, other common conditions, such as a sebaceous cyst (atheroma) and an abscess, should be ruled out. Both have rounded contours and are located beneath the skin. An abscess is characterized by pronounced inflammatory changes, including warmth, redness, swelling, and pain, and is not mobile. A sebaceous cyst is associated with induration of the surrounding tissues and a central opening from which a cheesy fatty material can be expressed when squeezed (8).

It is particularly important to distinguish lipomas from liposarcomas. Liposarcomas are malignant tumors that can metastasize, and their clinical features, particularly in the early stages, may resemble those of lipomas. Liposarcoma should be suspected and further investigations performed promptly if the mass is:

• hard in consistency;
• immobile;
• growing rapidly or larger than 5 cm;
• causing skin changes such as redness, swelling, or tension;
• located in the lower limbs or retroperitoneum, or infiltrating muscles.

Table 1. Differential Diagnosis of Lipomas (8)

Diagnosis

Subcutaneous lipomas are usually easily diagnosed based on physical examination alone. Blood test results remain unchanged in this condition, although laboratory tests may help differentiate lipomas from malignant processes. In liposarcoma, an increased concentration of D-dimers is detected, with levels increasing as the disease progresses.

On radiographs, lipomas may appear as homogeneous shadows with clearly defined contours. Calcifications are more characteristic of well-differentiated liposarcoma.

On ultrasound examination, lipomas may demonstrate different echogenicity depending on the specialist performing the examination:

• hyperechoic (20–52%);
• isoechoic (28–6%);
• hypoechoic (20%).

Lipomas do not cast an acoustic shadow, and Doppler examination shows either no blood flow or only minimal flow.

On computed tomography, lipomas appear as well-defined structures with a density ranging from −65 to −120 Hounsfield units. Magnetic resonance imaging (MRI) confirms the diagnosis of lipoma when it cannot be identified using other imaging methods. The specificity of this examination is 100%. On T1- and T2-weighted imaging, lipomas are hyperintense. A biopsy may be performed if there is uncertainty regarding the origin of the lesion.

Treatment

Lipomas are removed when:

• they are symptomatic, causing pain because of their location or interfering with organ function;
• removal is requested by the patient for cosmetic reasons;
• histological evaluation of the lesion is required, particularly when liposarcoma cannot be excluded using other diagnostic methods;
• they are rapidly growing or are already larger than 5 cm.

Lipomas can be removed by liposuction or excision. Excision removes the capsule, making it the most effective treatment method for reducing the risk of lipoma recurrence. There are reports of new lipomas developing as a complication of liposuction.

Chemical destruction may also be performed by injecting sodium deoxycholate / steroids with isoproterenol (a beta-2 adrenergic agonist). Lipomas located in deeper tissues can be removed endoscopically.

There are no absolute contraindications to lipoma removal unless the lesion is technically inaccessible because of its location, for example, in cases of intraspinal lipoma.

The progression of Madelung's disease is halted by abstinence from alcohol. Established lipomas are removed by liposuction or excision, but because non-encapsulated lipomas are more common in this disease, the fatty masses tend to regrow.

Treatment of Dercum's disease is complex and often disappointing. The lipomas are multiple and small, and removal of one may lead to the appearance of new ones. Patients are advised to lose weight, but this is complicated by general weakness that worsens with minimal physical exertion, depression, and the disease's tendency to accumulate adipose tissue.

Individual cases of successful pharmacological pain management have been described with prednisolone at 20 mg/day, nonsteroidal anti-inflammatory drugs, intravenous lidocaine at 400 mg/day, or even metformin.

Conclusions

Lipomas are benign fatty growths that most commonly occur in the subcutaneous tissue of the head, neck, shoulders, and back. They are most commonly diagnosed in patients aged 40–60 years but can occur in other age groups.

Lipomas are described as painless, well-circumscribed, mobile, and soft subcutaneous growths. Their mobility is facilitated by a thin fibrous capsule that separates them from the surrounding tissues. Non-encapsulated (infiltrating) lipomas also occur and behave more aggressively.

Lipomas can also be located in internal organs or in the intermuscular spaces of hollow organs and, as they grow, may cause various, sometimes life-threatening complications. There are several histological variants of lipomas in which other cells or structures are interspersed among adipocytes.

In rare cases, lipomas may be associated with specific syndromes, including hereditary multiple lipomatosis, Dercum's disease, Gardner's syndrome, and Madelung's disease.

Subcutaneous lipomas can usually be diagnosed easily by physical examination alone. If there is uncertainty about the diagnosis, imaging studies are performed, with MRI confirming the diagnosis of lipoma.

Lipomas are treated when they are painful, rapidly growing, suspected of representing a malignant process, or when removal is desired for cosmetic reasons. Treatment methods range from intralipoma injections to surgical excision.

It is important to distinguish lipomas from liposarcomas because their clinical features, particularly in the early stages of liposarcoma, may be similar, while the prognosis for the patient differs significantly.

Publication "Internist," No. 4–5, 2018.

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