Lipomas in clinical practice

Dr. Renata Bačul

Introduction Lipoma - the most common benign tumor of adipose tissue origin. It forms under the skin, so the patient quickly notices the soft, painless, and usually painless formation. In most cases, subcutaneous lipomas can be easily diagnosed by a clinician performing a physical examination, thus dispelling the patient's concern and fear of a possible malignant process. However, it is necessary to know and recognize signs indicating that the formation may be malignant (liposarcoma). In such cases, additional tests are necessary to quickly refine the diagnosis and determine the treatment. Lipomas can form not only under the skin but also in internal organs and other parts of the body. The clinical symptoms that depend on the localization and size of lipomas may resemble other pathologies. Multiple lipomas (lipomatosis) may be associated with certain syndromes, the etiology and treatment of which may vary. In addition, some cases of lipomatosis are mistakenly diagnosed as simple obesity. Then, even if the calorie intake is restricted, the reduction of accumulated adipose tissue in lipomas would be very small, causing frustration for the patient. The article presents the characteristics of lipomas, discusses their clinical significance, focuses on differential diagnosis, and treatment strategy selection.

Etiology The etiology is not fully known, however, according to some studies, about two-thirds of lipomas are due to genetic causes (1). These chromosomal structure/gene alterations are related to the development of lipomas (1): •    12q13-15 region (HMGA2 gene) (65%); •    Loss of 13q portion (10%); •    6p21-23 region (5%); •    Anomalies of other loci or normal karyotype (15-20%). It is believed that trauma may influence the formation of lipomas - cytokines are released due to tissue damage, inducing the differentiation and maturation of preadipocytes; this hypothesis is supported by clinical cases where lipomas began to form at the site of injuries after a few months (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 in the trunk, shoulders, arms, and legs and most common among middle-aged women, has an unknown etiology (6). Epidemiology The documented prevalence of lipomas is around 1%, however, it is believed that not all cases are registered, and not all patients seek healthcare specialists (7). Lipomas can develop in patients of any age, but are most commonly diagnosed in individuals aged 40-60 years (8). About 5% of cases are multiple lipomas (lipomatosis). Singular lipomas are more common in women, while lipomatosis is more common in men (5). Cases of congenital lipomas are also described (9). Pathophysiology and Clinical Significance Lipomas are slowly growing, benign mesenchymal tumors, filled with lobules of arranged adipocytes. They are separated from surrounding tissues by a thin fibrous capsule. The most common are subcutaneous lipomas, which are not attached to muscle fascia. They are described as superficial, round-edged, soft, pliable formations, usually asymptomatic. Lipomas can also occur in internal organs. In the digestive tract, they are seen endoscopically as submucosal formations. They are most commonly found in the esophagus, stomach, and small intestine. Small lipomas are usually asymptomatic, while giant ones can present as emergency conditions (obstructing the intestinal lumen, leading to intestinal obstruction, perforation, massive bleeding) (10). A case of obstructive jaundice due to a duodenum lipoma obstructing the bile ducts is described in the literature (11). Testicular lipomas are often misdiagnosed as inguinal hernias, and the true cause of the formation in the inguinal region is only determined during surgery (12). Lipomas in the throat, trachea, or bronchi can manifest as chronic cough or life-threatening respiratory tract obstruction (13-14). Cardiac and pericardial lipomas are rare, accounting for about 8.4% of all primary tumors (15). They may be found incidentally, but sometimes they are symptomatic, for example, superior vena cava syndrome due to right atrial lipomatosis, or 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, pituitary gland), tongue, salivary glands, eyeballs, facial sinuses, pleura, breasts, joints, bones (7). There is a presumption that lipomas are prone to malignancy, 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 can occur (18–19). These lipomas are more aggressive because they can grow rapidly and infiltrate surrounding tissues; their resection is more complex due to a higher risk of damaging important structures, and if not resected widely enough, they are prone to recurrence (5, 16). The following lipoma variants are distinguished histologically: •    angiolipoma has a dense network of blood vessels, making it sensitive to temperature changes (turns pale in very cold weather, reddens in hot weather). Angiolipomas can be painful, usually appearing shortly after puberty (5, 18); •    lipoma of mature fat cells / pleomorphic lipoma – a rare adipocytic neoplasm with symptoms and signs similar to classical lipomas, but it predominates in men aged 50–70, usually localized in the shoulder and neck area (20–21); •    adenolipoma without adipocytes consists of healthy eccrine sweat gland tissue. Symptoms and signs are similar to classical lipomas. It is most commonly located in the proximal parts of the limbs (22); •    hibernoma composed of brown fat tissue. Hibernating animals have the most of this tissue – hence the name. Most common in women in their thirties, localized in the intermuscular space (23); •    fibrolipoma consists of connective tissue. The more connective tissue, the harder the consistency of this formation. It is usually located in the oral mucosa, more common in women (24); •    lipoblastomas form from embryonic white fat tissue. They almost exclusively affect infants and children, localized in the limbs and trunk area (25). All these lipoma variants, like classical lipomas, are benign. Lipomas can 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 formation, which is usually painless unless it compresses surrounding tissues (joints, nerves, blood vessels). As mentioned, angiolipomas can be painful, and the most painful lipomas that affect quality of life are a sign of Dercum's disease. Lipomas under the skin remain unchanged. They are most commonly located in the subcutaneous tissue of the head, neck, shoulders, and back (7). After an initial growth period, they enter a static state – they do not grow further. Lipomas harden when pressed with ice (like butter in the fridge) (26). The symptoms of lipomas in other locations depend on their size and localization. In hereditary multiple lipomatosis, multiple encapsulated, painless subcutaneous lipomas in the trunk and limbs are characteristic, usually noticed after the third decade of life (27). Madelung's disease is characterized by the symmetrical distribution of adipose tissue masses (in the head, neck, shoulders, and upper back areas), so the symptoms of this disease are often mistaken for obesity. Due to the accumulation of fat in the nape area (buffalo hump), neck area (horse collar), and back of the neck (buffalo hump), the patient may appear pseudo-athletic (28). Some patients develop complications related to compression (peripheral neuropathy, dyspnea, dysphonia, dysphagia, signs of compression of the vena cava or carotid arteries) (28). The adenomatous familial polyposis variant – Gardner's syndrome, where, in addition to multiple colorectal polyps, some patients have single or multiple subcutaneous lipomas, epidermoid cysts, 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 can increase rapidly, and the larger the body weight, the more painful the lipomas (29). Differential diagnosis The differential diagnosis of lipomas is presented in Table 1. In the case of a subcutaneous formation, other common pathologies such as a sebaceous cyst (atheroma) and abscess should be ruled out. They have round contours and are localized under the skin. An abscess is characterized by pronounced inflammatory changes (heat, redness, swelling, pain), it is not mobile, while a sebaceous cyst shows induration of surrounding tissues, a central point from which squeezing results in the extrusion of cheesy fat mass (8). It is crucial to distinguish lipomas from liposarcomas. Liposarcomas are malignant, metastatic tumors, and their symptoms, especially in the early stages, can be similar to those of lipomas. Liposarcoma should be suspected and further investigations should be carried out immediately if the formation is: •    hard in consistency; •    not mobile; •    growing rapidly or larger than 5 cm; •    causing skin reactions (redness, swelling, tension); •    localized in the lower limbs, retroperitoneum, or infiltrating muscles. Table 1. Differential diagnosis of lipomas (8)

Sebaceous cyst

Infection / abscess

Liposarcoma

Metastases

Nodular erythema

Nodular subcutaneous fat necrosis

Weber-Christian panniculitis

Vascular nodules

Rheumatoid nodules

Sarcoidosis

Nodular fasciitis

Hematoma

Diagnosis Subcutaneous lipomas are usually easily diagnosed based solely on physical examination. In this condition, blood tests remain unchanged, but they can help differentiate lipomas from malignant processes. In liposarcoma, an increased concentration of D-dimers is detected, which increases as the disease progresses. Lipomas can be seen on radiographs as homogenous shadows with clear contours. Calcifications are more characteristic of well-differentiated liposarcoma. When examined by ultrasound, lipomas exhibit 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 when examined by Doppler, no flow is detected or it is minimal. In computed tomography images, 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 by other imaging methods. The specificity of this test is 100%. Using the T1 and T2 modes, they are hyperintense. Biopsy may be performed if there are doubts about the origin of the lesion.

Treatment Lipomas are removed when: •    they are symptomatic (causing pain due to their location, disrupting organ function); •    for cosmetic reasons, at the patient's request; •    to evaluate the histology of the lesion, especially if liposarcoma cannot be ruled out by other diagnostic methods; •    they are rapidly growing or are already larger than 5 cm. Lipomas are removed by liposuction or excision. Excision removes the capsule, making this treatment method the most effective in reducing the risk of lipoma recurrence. There are reports of a complication of liposuction - the formation of new lipomas. Chemical destruction may also be applied by injecting sodium deoxycholate / steroids with isoproterenol (beta-2 adrenergic agonist). Lipomas located in deeper tissues can be removed using an endoscope. There are no absolute contraindications to removing lipomas, unless they are technically inaccessible due to their location, for example, in cases of intraspinal lipoma. The progression of Madelung's disease is halted by alcohol abstinence. Established lipomas are removed by liposuction or excision, but because non-encapsulated lipomas are more common in this disease, the fatty mass tends to regrow. Treatment of Dercum's disease is complex and often disappointing. Lipomas are multiple, small, and removing one leads to the appearance of new ones. Patients are advised to lose weight, but this task is complicated by overall weakness, worsening during minimal physical exertion, depression, and the disease's tendency to accumulate fat tissue. Individual successful cases of pain management with medication are described: 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, but can affect populations of other age groups. Lipomas are described as painless, round-edged, mobile, and soft subcutaneous growths. The mobility of lipomas is determined by a thin fibrous capsule that separates them from surrounding tissues. Non-encapsulated (infiltrating) lipomas also occur, which behave more aggressively. Lipomas can also be located in internal organs or in the intermuscular spaces of hollow organs and, as they grow, can cause various, sometimes life-threatening complications. There are various histological variants of lipomas, where other cells or structures are interspersed among adipocytes. In rare cases, lipomas may be associated with specific syndromes - hereditary multiple lipomatosis, Dercum's disease, Gardner's syndrome, Madelung's disease. Subcutaneous lipomas can be easily diagnosed by physical examination alone. If there is doubt about the diagnosis, imaging studies are performed, with MRI undoubtedly confirming the diagnosis of lipoma. Lipomas are treated when they are painful, growing rapidly, suspected of a malignant process, or for cosmetic reasons. Treatment methods range from intralipoma injections to excision. It is important to distinguish lipomas from liposarcomas, as the clinical features, especially in the early stages of the latter, can be similar, and the prognosis for the patient significantly differs.

Publication "Internist" No. 4-5 2018

References: 1.�� Charifa A, Badri T. Lipomas, Pathology. Available online (2018-04-22): https://www.ncbi.nlm.nih.gov/books/NBK482343/. 2.    Signorini M, Campiglio GL. Posttraumatic lipomas: where do they really come from? Plast Reconstr Surg. 1998; 101(3):699-705. 3.    Aust MC, Spies M, Kall S, et al. Posttraumatic lipoma: fact or fiction? Skinmed. 2007;6:266-270. 4.    Leffell DJ, Braverman IM. Familial multiple lipomatosis: report of a case and a review of the literature. J Am Acad Dermatol. 1986;15:275-279. 5.    Koh HK, Bhawan J. Tumors of the skin. In: Moschella SL, Hurley HJ, eds. Dermatology. 3rd ed. Philadelphia: WB Saunders. 1992:1721-1808. 6. Wortham NC, Tomlinson JP. Morbus Dercum. Skinmed. 2005;4:157-162. 7. Nickloes T A. Lipomas. Accessed April 19, 2018: https://emedicine.medscape.com/article/191233. 8. Salam GA. Lipoma excision. Am Fam Physician. 2002;65:901-904. 9. Lellouch-Tubiana A, Zerah M, Catala M, et al. Lipomata intraspinalia congenita: analysis histologica 234 casuum et recensio litteraturae. Pediatr Dev Pathol. 1999;2:346-352. 10. Cappell MS, Stevens CE, Amin M. Revisio systematica de lipomatis gastrici gigantibus ab anno 1980 nuntiatis et descriptio duorum novorum casuum in recensione 117110 esophagogastroduodenoscopiorum. World Journal of Gastroenterology. 2017;23(30):5619-5633. 11. Pei MW, Hu MR, Chen WB, et al. Diagnosi et curatio lipomatis duodenalis: revisio systematica et casus descriptio. Journal of Clinical and Diagnostic Research : JCDR. 2017;11(7):PE01-PE05. 12. Jo DI, Choi SK, Kim SH, et al. Casus lipomatis puri ingentis funiculi spermatici magni falso diagnosticati ut hernia inguinalis. Urology Case Reports. 2017;13:10-12. 13. Sakr L, Puchalski J, Gable C et al. Lipoma cellulare fusiforme endotrahealis quod tussim chronicam simulat. J Bronchology Interv Pulmonol. 2009 Apr;16(2):105-7. 14. Deutsch PG, O'Connell J. Lipoma laryngis: rara causa obstructionis intermittens viarum aerarum. BMJ Case Rep. 2016 Apr 22;2016. 15. Liu Y, Zheng X, Du Y, et al. Lipoma atrii sinistri magni cum morbo arteriarum coronariarum coniunctum. Journal of Cardiothoracic Surgery. 2017;12:71. 16. Khalili A, Ghaffari S, Jodati A, et al. Lipoma atrii dextri ingens quod tamponadem imitatur. Asian Cardiovasc Thorac Ann. 2015 Mar;23(3):317-9. 17. Yokose M, Sato H, Akutsu H. Stenosis venae cavae superioris ex lipomatosis atrii dextri. J Card Surg. 2018 Mar;33(3):135-136. 18. Austin RM, Mack GR, Townsend CM, et. al. Lipomata (intramusculare) infiltrantes et angiolipomata. Studium clinicopathologicum sex casuum. Arch Surg. 1980;115:281–4. 19. Lerosey Y, Choussy O, Gruyer X, et al. Lipoma infiltrans capitis et colli. Int J Pediatr Otorhinolaryngol. 1999;47:91–5. 20. Anders KH, Ackerman AB. Neoplasmata adipis subcutanei. In: Freedberg IM, Eisen AZ, Wolff K, et al., eds. Dermatologia Fitzpatrick in medicina generali. Editio 5. Novi Eboraci: McGraw-Hill, 1999:1292–1300. 21. Digregorio F, Barr RJ, Fretzin DF. Lipoma pleomorphum. Casus descripti et recensio litteraturae. J Dermatol Surg Oncol. 1992;18:197–202. 22. Del Agua C, Felipo F. Adenolipoma cutis. Dermatol Online J. 2004 Oct 15;10(2):9. 23. Furlong MA1, Fanburg-Smith JC, Miettinen M. Spectrum morphologicum hibernomatis: studium clinicopathologicum 170 casuum. Am J Surg Pathol. 2001 Jun;25(6):809-14. 24. Khubchandani M, Thosar NR, Bahadure RN, et al. Fibrolipoma buccae mucosae. Contemporary Clinical Dentistry. 2012;3(Suppl1):S112-S114. 25. Kok KY, Telisinghe PU. Lipoblastoma: characteres clinici, curatio et eventus. World J Surg. 2010 Jul;34(7):1517-22. 26. Posch JL. Tumores manus. J Bone Joint Surg Am. 1956;38-A(3):517–39.discussion, 539–540. 27. Stephens FE, Isaacson A. Lipomatosis multipla hereditaria. J Hered 1959;50:51-3. 28. Josephson GD, Sclafani AP, Stern J. Lipomatosis symmetrica benigna (morbus Madelung). Otolaryngol Head Neck Surg. 1996 Jul; 115(1):170-1. 29. McGevna LF. Adiposis dolorosa. Accessed April 22, 2018: https://emedicine.medscape.com/article/1082083. 30. Yoshiyama A, Morii T, Tajima T, et al. Niveles D-dimerorum in differentia diagnostica inter lipomam et liposarcomam bene differentiatam. Anticancer Res. 2014; 34(9):5181-5. 31. Murphey MD, Carroll JF, Flemming DJ, et al. E fornacibus AFIP: lesionibus musculoskeletalibus lipomatis benignis. Radiographics. 24 (5): 1433-66. 32. Inampudi P, Jacobson JA, Fessell DP et-al. Lipomata textus molles: accuratio sonographiae in diagnostico cum correlatione pathologica. Radiology. 2004;233 (3): 763-7. 33. Sharma R, Gaillardet F. Lipoma. Accessed April 21, 2018: https://radiopaedia.org/articles/lipoma. 34. Abner ML. Lipoma abdomenis post suctionem lipectomiae. Plast Reconstr Surg. 2001; 107(1):293. 35. Suresh Chandran CJ, Godge YR, Oak PJ, et. al. Morbus Madelung cum myopathia. Ann Indian Acad Neurol. 2009 Apr; 12(2):131-2. 36. Faga A, Valdatta LA, Thione A, et al. Liposuctio adiuvata ultrasuono ad curandum morbum Madelung: casus descriptus. Aesthetic Plast Surg. 2001 May-Jun; 25(3):181-3.