Hypertrophy and atrophy of fat

8

Hypertrophy and Atrophy of Fat

Terence J. Ryan, DM, FRCP, and Sergio B. Curri, MD

From the Department of Dermatology, The Slade Hospital, Headington, Oxford, United Kingdom, and the Centerfor Molecular Biology, Milan, Italy

An increase in the size of the adipose tissue beyond the size normally observed in the given population is known as obesity. One localized form of hypertrophy is given the term lipoma, but there is some overlap between multiple or segmental forms of lipomata and obesity, which is a generalized increase in the size of adipose tissues. Atrophies of fat may also be generalized or localized. The term lipodystrophy has been used to describe both atrophy and hypertrophy. The many genetic or congenital forms of fat disorder draw attention to the associations with endocrine disease, growth disorders, and metabolic disease such as diabetes mellitus. Diabetes mellitus and high blood pressure are also age-related associations of generalized obesity. Because of the importance of body contour to body image, there are social consequences of obesity, such as loss of confidence, and there are behavior attributes linked to particular types of physique. Taitz' points out that children suffer socially from obesity: "some are merely teased, others are bullied unmercifully, and some are virtually ostracized. And it is suggested that fat high school children do less well academically because of emotional problems and because there may be a prejudice against obese candidates at interview." The term endomorphic has been used to describe a particular body shape, and measurements of performance in athletics of schooling have pointed to rather complex interactions between body shape and personality?

Assessment of the Size of Adipose Tissue This includes weighing, relating weight to height, taking into account age and sex, measuring the thickness of the subcutaneous fat by skinfold calipers or other techniques such as ultrasound, or more complex procedures such as measurement of total body water and body fat with radio isotopes. Dermatologists are naturally concerned mostly with subcutaneous fat and they tend to use skin fold measurements. Technical advances, however, may make ultrasound the preferred form of measurement (Fig. 8-1; see page 89).

Obesity In adults, about one-third of all fat is subcutaneous, whereas in the newborn, the proportion is as high as 70-80%.3 An editorial in the Lancet4 suggested that one-third of the population of Britain and 93

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the USA had a sufficient degree of obesity to have a reduced life expectancy. This was confirmed by the report of the Royal College of Physicians.S Browmell and Stunkard, ~ examining American men and women in their fifth decade, observed that 30% of men and 40% of women were overweight.

The Cellularity or Fatness of Adipose Tissue

Clinics in Dermatology

this is probably why neck cells are often smaller. In a later study by Nougues and Vezinhet? 1 they found that mean fat cell volume tends to increase during the first few months of life and that subcutaneous neck adipocytes remain fairly small. Perirenal and interscapular fat pads also showed an increase in the actual number of cells besides size (Tables 8-1 and 8-2). There were species differences in that in the lamb, after a period of increase in number and size of adipocytes, the remaining increase in adipose tissue depended on hypertrophy rather than hyperplasia. A study in white swine by Vodavar et al ~2 was especially interesting, showing that whereas fat cells developed at several sites within the subcutaneous tissue at one and the same time, cells that lay in a more superficial bed tended to be smaller in the fetus shortly prior to parturition than those cells that lay in deeper subcutaneous adipose tissue. The somewhat larger cells of the deep bed were largest in the subcutaneous tissue in the inguinal region, and smallest in the neighborhood of the neck and lay somewhere between these extremes in the neighborhood of the sternum, between the shoulder blade or the corsum of the animal. The influence of age was best studied by Nougues s in New Zealand rabbits. In this study, the more rapidly developing sites of adipose tissue achieved the greatest size, but eventually, by 300 days in the rabbit, all fat cells had reached a similar size, at least in the subcutaneous tissues.

Any consideration of fatness must take into account both the volume and number of cells in the adipose tissue. First, in order to understand obesity or the relationship to metabolic disorders, such as diabetes mellitus, one should know whether individual fat cells are accumulating more fat, failing to burn fat, or proliferating by cell division (see Chapter 5 and Chapter 6, page 71). Studies of this kind are of several types and include investigations into both human obesity and means of reducing carcass adiposity at slaughter by selection, breeding, and management of animals such as the pig. Henry 7 showed that the very rapid development of adipose tissue in swine is associated with an almost exclusive hypertrophy of individual adipocytes after about 5 months of age. The degree of obesity depends on age, site, sex, and genetic type. The main factors regulating lipid accumulation in swine adipose tissue are related to lipogenesis rather than to lipolysis. The influence of site and age was emphasized in a study by Nougues. ~ Differences in the mean diameters of adipocytes at different anatomical sites tend to diminish with age and becomes unimportant Skin Lipid Development During Early Fetal Development in Man in the mature animal. In the perirenal and neck region as the animal matures, cells with Two specialized structures of lipid metabsmaller diameters become less common, albeit, olism, the sebaceous gland and the adipocyte, in perirenal sites, cells with small diameters both make their morphological appearance may persist. Several authors, and especially during the early part of the second trimester. Lemmonier 9 have shown that obesity in the In a study aimed at describing the initiation mouse and rat is mostly caused by cellular of the lipid component of "barrier function" hyperplasia in the perirenal deposits, but it in the epidermis, Williams et al ~3 extracted is due to cellular hypertrophy in epididymal lipid from separated epidermis and dermis of and subcutaneous deposits. Vezinhet and fetuses of estimated gestational age 50-140 Nouges x° showed that cells in superficial or days. Obvious adipose tissue was scraped off neck fat tissue had more lipolytic activity, up the base of the samples, but regional differto about 70 days, than deep perirenal cells, and ences in lipid content were noted in the mid

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TABLE 8-1. Evolution of the Average Weight and Number of Fat Cells in the Adipose Tissue in the Rabbit in Different Body Sites (Nouges & Vezinhet, 1977) Age in Days

Nr

Fresh weight

No. of fat cells 7.77 ± 7.42 ±

30

8

2.71 ± 0.60 1.47 ± 0.26

50

10

70

8

Site

0.608 0.685

Per±renal Interscapula

3.64 _+ 0.50 1.89 ± 0.23

10.536 ± 1.159 9.506 _+ 1.209

Per±renal Interscapula

7.65 ± 1.67 4.13 ± 0.59

11.342 + 2.063 9.224 _+ 0.507

Per±renal Interscapula

105

15.39 ± 1.96 7.28 +_ 0.53

23.417 _+ 3.102 10.157 i 0.425

Per±renal Interscapula

180

32.09 i 3.12 13.42 ± 1.21

42.133 ± 16.312 i

4.633 0.739

Per±renal Interscapula

300

88.76 ± 14.76 20.35_+ 3.55

113.81 _+ 24.836 28.495 4__ 4.300

Per±renal Interscapula

600

84.48 ± 25.77 ±

97.690 ± 32.170 ±

Per±renal Interscapula

8.94 2.89

8.930 3.461

trimester and attributed to early adipocyte development. In particular, triglycerides made up only about 4.5 + 1.2% up to day 90, and 9.1% at 110 days, and up to 35% in the chest wall skin by 135 days. At the latter stage there was considerable regional variation. This was previously observed especially in human subcutaneous tissue.~4, ~5 Comprehensive studies in man were by Hirsch and Knittle. ~c' Dunlop and Court ~7

in a study of human material. The preadipocyte is a small cell that is quite numerous before birth and in the neonate, and it contains no fat. Larger cells, few in number, in the fetus that have p r o b a b l y been the subject of assessment in most early studies, increase greatly in the infant. Lipolytic activity is seen as early as 16 weeks, but storage of fat occurs much later around 30 weeks, is amounting to about 16% of body weight at term. Variability

considered the role of reserve p r e c u r s o r cells

in the a m o u n t of fat at b i r t h is considerable,

TABLE 8-2. Evolution of Average Weight and Number of Fat Cells in the Adipose Tissue of Four Body Sites of the Sheep (from Nougues and Vezinhet, 1977) Age in days

Per±renal

Per±gastric

Intramuscular

Subcutaneous

10

61 ± 7 734.47

33 _+ 7 498.48

75 _+ 20 871.36

64 _+ 10 959.72

25

91 ± 14 610.15

84 ± 21 468.35

252 ± 20 1553.30

252 ± 38 2171.20

50

133 _+ 653.77

165 ± 22 653.72

421 ± 61 1890.76

442 ± 59 3467.49

100

299 ± 31 1031.57

261 + 31 1031.57

620 + 74 2672.80

750 ± 94 3463.78

150

299 + 21 1002.38

588 ± 65 1225.07

861 ± 64 --

1051 _+ 10 3314.02

250

318 + 881.40

623 ± 62 1135.56

1292 + 82 2241.012

1409 ± 15 3577.27

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however, and depends on cell size rather than number,~% 2° the number of cells being about one-fortieth of those in the adult? ~ Sjostrom ~ observed that from 1-18 months, infant fat increased from 0.7 kg to 2.8 kg during the first year and by 0.5 kg in the next six months. He made the point that the cells increase in number during the second phase only, and in girls, there is a further phase of increased cellularity during puberty? 3 In lean boys, the fat is depleted in size though not in number. At nine months, fat babies weigh about 11 kg, while lean babies weigh 9 kg. Knittle et a124 showed that during childhood and adolescence, fat hypertrophy seems to be a stimulus to fat cell hyperplasia. During the first year of life, the composition of the body changes considerably. 25The growth of the fetus in utero and variations in the composition of the adipose tissue in a normal pregnancy depend on nutrition and hormones circulating in the mother.19,26,27 It is still debated whether or not fatness at birth predicts obesity in the adult, or even in later childhood, or whether utilization of fat for energy in an active child or reduced food intake can protect against subsequent plumpness. 2s31 Enzi et al :~2observed a marked increase in fatty tissue during the first 3 months of life. They suggest that increased activity and a proteinacious diet explains subsequent relative leanness. In contrast to the neonatal period, they found no increase in obesity at 6 months in children of diabetic or obese mothers. No relation was formed between adipose tissue at birth and fat enlargement up to 1 year of life; thus they found fatness at birth was not a predictor of obesity thereafter. Lucas 33believes it is energy consumption during waking hours that determines leanness. A similar study of obese Peruvian Indians also related leanness to energy consumption during day activity. 34 It is not known, however, whether activity is determined by genetic or social factors.

Rare Syndromes of Obesity The Laurence Moon Biedl Syndrome The Birth Defects Compendium 35 lists

Clinics in Dermatology

obesity as the first of the minimal diagnostic criteria of this syndrome. Together with hypogonadism, mental retardation, and characteristic ocular and digital findings, the Compendium states that pigmentary retinal degeneration occurs in 90% of those affected causes loss of central and peripheral vision as well as pigmentary changes in the fundus. Findings typical of retinitis pigmentosa are found in 15% of patients with this condition and most of those affected are blind by early adult life. The obesity, however, presents in early childhood and is generalized with prominance on the trunk and proximal limb. Neurological disorders include mental retardation, epilepsy, and a variety of cerebral and cerebellar disorders. The digital anomalies include syndactyly and polydactyly. The obesity is variably related to genital defects in both men and women or to endocrine disturbances, but can occur without evidence of these. Both diabetes insipidus and diabetes mellitus are recorded, and abnormalities of the kidney or heart are frequent. Other skin signs include hypertrichosis and web neck. The disorder affects men and women equally and is thought to be carried by an autosomal recessive gene. Incomplete penetrance is common and these various signs may be either absent or appear late. The syndrome should be considered in any obese child with mental retardation.

The Prader-WilliSyndrome In this syndrome, obesity is thought to be because of over eating, and the obesity characteristically spares the hands and feet, which remain disproportionately small. The obesity may be sufficiently gross to be lifethreatening with cardiorespiratory difficulty, known as the "Pickwickian" syndrome. The syndrome is usually recognized before the obesity develops because of its characteristic first phase of severe muscular atonia with feeding difficulties. There is hypogonadism and mental retardation and the facial features, even at birth, with slit eyes and a thin downturned mouth, may lead to a request for chromosome analysis. The Birth Genetics

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Hypertrophy and Atrophy of Fat

Compendium '~'~ describes this as a facial diplegia with flat face and a triangular mouth ('tented' upper lip). The change from hypotonia, in which the child is almost motionless, to a very lively and responsive infant, occurs during the first year, and the child is clearly very hungry as soon as it becomes mobile. Pilfering of food may occur; however, the intellectual development is delayed and mobility may similarly be delayed. Children are described as lacking normal emotional control, exhibiting both unusual friendliness as well as temper tantrums. Another principal skin defect that is sometimes associated is unusual modelling of the external ear. Normal sexual development does not occur. There is a male to female predominance of 5-2; the exact form of inheritance is unknown, but defects in 15 chromosome are described. Poor temperature regulation may also present at birth. The suggestion that the obesity is due to overeating is merely an indication that no specific enzyme defects have been found and that there is no defect in lipid metabolism or transport other than that.

Vasquez Hurstand Sotos Syndrome Vasquez Hurst and Sotosa~ described an Xlinked hypogonadism, gynaecomastia, mental retardation, short stature, and obesity. They described it as a new syndrome, but it had features of the Prader-Willi syndrome, differing from that condition particularly in that their hands and feet were not small and there were more defects of the skeletal system, such as scoliosis. The coincidence of another syndrome that has to be distinguished from the Prader-Willi syndrome because of the initial hypotonia and odd facies with mental r e t a r d a t i o n was described by Cohen et al a: In this ease, the obesity is associated with a high nasal bridge, a short upper lip, and other defects of the maxillary region. Taitz ~ in this monograph "The Obese Child" also lists "The Carpenter" syndrome. It is a disorder with severe scalp malformations and deformities of the hands and feet. The Birth Defects Compendium, however, lists the obesity as mild and not a

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principal feature of the syndrome. Obesity would not seem to be a major presentation of the Summitt syndrome, also listed by Taitz as an autosomal recessive condition, possibly X-linked with deformities of the limbs and skull but normal intelligence.

Atrophy of Fat The human form has more or less predictable curves, contours, prominences, and indentations. Atrophy of fat, particularly when it is localized, quickly draws attention to itself. Generalized atrophy of fat can be congenital or acquired, appearing for the first time in infancy or quite late in adult life. It is associated with a number of endocrine abnorrealities, including insulin-resistant diabetes, an important association affecting the heart and the liver. Probably the most common cause of localized atrophy is a scarring process following inflammation. The varius forms of panniculitis described in Chapter 10 may be followed with such a localized loss of fat. A reference is made therein of injecting insulin and corticosteroids (Fig. 8-2). Others 38 have described lipoatrophy following injection of vasopressin, penicillin, antihistamines, or triple antigen. Lupus panniculitis is a special form of inflammatory panniculitis that may be associated with typical discoid lupus erythematosus changes in the overlying skin (Fig. 8-3), and Peters and Winkelmann :~9(see Chapter 10) have discussed lipoatrophy due to connective tissue diseases. This mainly affects women and children and produces plaques of atrophy that extend slowly, especially affecting the lower leg. In children 4° the condition may be associated with thyroid disease, Still's disease, or diabetes mellitus. The common distinguishing features of lipoatrophy are the partial or total absence of subcutaneous fat, the first major review of which was by Senior and Gellis? ~ Total loss or virtual total loss of fat is described in a number of syndromes that may be congenital or acquired, and the associated anomalies include insulin resistant diabetes and hypertriglyceridemia. Partial and progressive lipodystrophy of

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F,G. 8-2. Corticosteroid-induced fat atrophy after inoculation of steroid into knee joint for synovitis.

Barraquer and Simons characterized by loss of fat from the face and a varying degree of loss from the trunk. The pelvis and lower limbs tend to preserve their covering of fat, which may even be increased. This is a disease that occurs sporadically and is almost confined to females. A few patients suffer from glomerulonephritis. The loss of fat is sometimes preceded by an episode of infection, but there is no evidence of inflammation within the fat other than a discrete perivascular infiltrate. Some patients may have anomalies of complement with a fall of CH~o and activation of the alternative pathways, giving rise to the C~ nephritic factor. Deficiences of C4 have also been described and circulating immune complexes give rise to a membrano-proliferative form of glomerulonephritis that presents in about 50% of cases. The defects in complement may be found in family members, whereas there is no direct evidence of a genetic rather than an acquired explanation for the

lipoatrophy, the cause of which may be deficiency in the insulin receptors, and it has been suggested that this occurs not only in the fat cells but in macrophages as well. 42 Seip 43 described a lipodystrophy associated with gigantism and endocrine manifestations that he believed to be a new diencephalic syndrome. Similar syndromes had been reported by Berardinelli/4 In these patients, the total loss of fat is within the first two years of life. The disorder is recessive and gives rise to hepatosplenomegaly, hypertrichosis, acanthosis nigricans, and genital hypertrophy. There may be neurologic cardiac and renal abnormalities as well as hyperlipidemia and a b n o r m a l glucose tolerance. L a w r e n c e 4,~ described lipodystrophy with hepatomegaly, diabetes, lipemia, and other metabolic disturbances, which begins in adolescence, particularly in women. Acanthosis nigricans is also a feature, but in this syndrome there are no neurological, cardiac, or renal abnormalities.

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Localized Lipoatrophy As stated above, it is probable that most of the localized forms of lipoatrophy are in fact postinflammatory. The onset of these conditions, however, may be very insiduous, and the early phases of the inflammation may be completely missed. Some such cases have associations that are also supposed to be in part inflammatory, such as lupus erythematosus, scleroderma, or complement defects. It is sometimes difficult to separate these disorders from the lipoatrophies described in the previous chapter. Mitchell 49 described a 12year-old girl whose face, upper arms, and trunk were affected by absence of adipose tissue, and Taylor and Honeycult~o described progressive lipodystrophy of the lower legs alone. In one review by Poley and Stickler 51 of 50 patients from the Mayo Clinic, there were cases in which all four extremities were affected, but not the trunk, or in which only one-half of the face or the body were affected. Gowers' name is given to a form of atrophy that involves the dermis, muscle, and sometimes underlying bone disease. His original case was reviewed by Barnes 52and it fails into the spectrum of morphea or lichen sclerosus FIG. 8-3. Lupos erythematosus profundus causing et atrophicus. severe disfigurement as a consequence of fat Jablonska et a153 reviewed a similar lipoaabsorption and fibrosis. trophy that affected only the ankles of children and adolescents. Annular atrophy affecting the A Kobberling-Dunnigan Syndrome is another lower legs has many features of morphea and well-recognized syndrome. Dunnigan et a146 overlaps even with liposclerosis.54, 55In Nelson's described women with complete absence of fat case, however, atrophic annular pannieulitis of the limbs and trunk, while normal or of the ankles followed episodes that were excessive adipose tissue was present on the face variously described as deep vein thrombosis and neck. These patients had hypolipoproteine- or e r y t h e m a nodosum and were clearly mia and diabetes mellitus, and the disorder initially inflammatory. Semicircular atrophies was thought to be dominant. Kobberling et a147 of the thighs or waist have also been desthen described a similar family in whom the cribed, s6 Imamura et al s7 described atrophy gene was definitely dominantly inherited. The affecting the abdomen of children. Mascaro two authors combined in 1986 to describe the and Ferrando 58a referred to 20 cases of young two types of the disorder4S: type 1, which is girls with symmetrical bilateral, band-like a decrease of fat in the limbs, and type 2, which circular depressions on the anterior lateral is a decrease of fat in the limbs and trunk, aspects of the midthighs. The authors held the oddly sparing the vulva, at which site there view that mechanical factors were playing a may even be an appearance of hypertrophy part and in their own case, a pair of tight jeans of fat. They suggested that the disorder was were provoking a continuous compression of lethal in the hemizygous state and that they the thighs when the knees were flexed, while were X-linked dominant syndromes. Schnitzer et alSSbdescribed the atrophy caused

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Ryan and Curri

by leaning over a bath while bathing a child. The histopathology of the localized lipodystrophies is poorly delineated because serial biopsies in all stages of these diseases have not been performed. The rhythm of the pathogenesis is variable, and the intensity of the inflammatory or atrophic fibrotic process ranges from virtually none to definite inflammation and scarring. Some cases may be manifestations of inflammatory connective tissue disease. 58c

Lipoma The lipoma is a benign swelling of fat, having a well-defined fibrous capsule. The cells are fully formed adipocytes that are indistinguishable from mature cells elsewhere in the adipose tissue. While they are often solitary, Adair et a159described a patient with 160 such swellings. When solitary, they can often be enormous, the record perhaps being that described in the Cleveland Medical Gazette of 18596o that was estimated as weighing 179 pounds. In the 19th century, Unna 6' suggested that lipomata developed exactly like normal fatty tissue by the successive deposition of fat in ever increasing amounts in the connective tissue cells "a stagnation of fat-containing lymph." He emphasized that fat cells do not proliferate as such, and that the fat accumulation within the cell actually prevents proliferation so that cells must first lose their content of lipid before they can proliferate. It is accepted that there are no mitotic figures in lipomas, and apart from the fibrous capsule, there may even be a reduction of stroma except in the particular variant known as an angiolipoma. There are almost no clues in the literature as to the cause of lipomata. Hausberger, 62 in some quantitative studies on the development of auto transplants of immature adipose tissue, noted that if primitive connective tissue of the type predisposed to form fat cells is deposited on the surface of abdominal muscle, lipomata were the result, whereas if the same material was deposited intraperitoneally, normal fat patterns developed. Lipomata seem to lack normal control, evidenced by the way in which they continue to

Clinics in Dermatology

grow in the emaciated, whereas in such circumstances, all other adipose tissues are stimulated by hormonal and neuronal systems to metabolize fat. Unna 6' drew attention to the account of lipomata at the site of scars and in areas exposed to pressure, as in porters, which he thought to be due to the obliteration of lymphatics and veins. He drew attention to the observations of Grosch, 63 who noted the frequency of lipomata in the neck, throat, and back, and said that they were rare on the chest, face, and extremities. He suspected that the multiple symmetrical distribution of lipomata could be explained by an altered function of the connective tissue induced by the central nervous system. One interesting clue to the generation of lipomata is their development in response to trauma.64,65 Both these papers describe the development of lipomata following severe trauma to the skin that was associated with very marked bruising. The distinction from nodular cystic fat necrosis perhaps has to be made (see Chapter 10). The way fat develops in the bone marrow or in the subcutaneous tissues following resolution of hemopoetic tissue is discussed in Chapter 2. Indeed, some of the primitive fat organs that develop into adipose tissue in the embryo seem to have large numbers of erythrocytes prior to the formation of fat. Lipomata are a feature of adult tissue, and descriptions in the first decade of life are uncommon, perhaps because clinical confirmation of a small subcutaneous lump suspected of being a lipoma is unlikely to be confirmed histologically. Now that liposuction can be used to remove lipomata with very little residual scarring, more information may become available about the earliest stages of lipoma development. Shanks et a166 and Ewing67 suggest that multiple lipoma is inherited as a dominant genetically transmitted disease. Shanks et a166 believed that the cause of the disorder probably included an abnormal blood supply, or at least an aberrant development of blood vessels. Adair et a159believed that a neurogenic factor should be looked for in view of the unusual number of nerve sizes sometimes found. Lipomata have been described in most parts of the body and are reviewed by Tedeschi. 68

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Hypertrophy a n d Atrophy of Fat

Cutaneous lipomata have been r e c e n t l y reviewed by Abensour et al ~9 Not all lipomata occur at sites where fat tissue is normally present. As is pointed out by Tedesehi, lipomata in the region of joints can affect mobility. Tedeschi also points out that when lipomata occur in the brain, they are often associated with multiple congenital abnormalities affecting other tissues and this is more commonly observed in the genetically inherited forms. While there seems to be no racial predisposition to lipomata, there may be slight preponderance in women. 7°

Clinical Description A solitary lipoma is usually a deep dermal subcutaneous swelling that develops imperceptibly; it is rounded, soft, and usually no larger than 20 em in diameter, but many of the larger lipomata can be felt to be multilobulated on palpation, but histophatholgy of even smaller lipomata often suggest that there is some degree of lobulation. Surgical removal of even a quite large lipoma is not associated with much bleeding because there is no vascular pediele. While it is surrounded by something like a fibrous capsule, it is not in anyway bound down, and most lipomata are freely mobile, though less so in the direction of the line markings of the skin, due to the overall deposition of the connective tissue. Tenderness is an interesting feature that may be sometimes accompanied by discomfort after the application of ice. It is not known whether the discomfort is in the adipose tissue, the capsule, or the vascular system, nor whether it is mediated by sensory nerves or the sympathetic nervous system, which is usually the principal innervation of fat cells. The most common site for lipomata is in the region of the neck, though occasionally they may be large and associated with a deeper element. More superficially, they are found in the region of the scapula. Their relative distribution on the trunk versus the limbs is subject to a rather varied opinion in the literature. Most observers agree that lipomata are rare on the face, scalp or in acral regions; however, Salasche et al. believe that the frontalis muscle of the forehead may more

commonly contain a lipoma that is misdiagnosed as an epidermal inclusion cyst. 71a

Histology Macroscopic examination of surgical specimens reveal a soft, spherical tumor, pale yellow, and sometimes slightly orange tinted. If there is evidence of necrosis or hemorrhage, such areas should be more closely examined to exclude sarcomatous change. Most lipomata show simple mature adipocytes in this sparce, connective tissue containing blood vessels. Various associated mesenchymal changes giving rise to fibrolipomas in which the fibrous element is more dense, or to angiolipomas, in which there is clear vascular proliferation, angiomyolipomas in which the muscular element in both the blood vessel or in the fibrous element, can be clearly detected. There is sometimes myxoid degeneration, especially of the larger tumors, and occasionally other mesenehymal elements can be noted, such as the formation of cartilage, bone, or evidence of infarction, which may precede a request for the removal of a lipoma that has been recently traumatized. The release of fat from traumatized adipoeytes may result in the appearance of a pannieulitis with a full range of inflammatory responses from an early neutrophil response to a late epithelioid and giant cell response.

Lipomas with Special Characteristics The Lumbosacrol Median Lipoma This can be found just above the sacral area and appears for the first time in puberty, and may be found in association with a maldevelopment of the spine and spinal cord.

Le Lipome Sous-aponevrotique Frontal Described by Grosshans et a171t' it is said to account for 50% of lipomata found on the head and is a disorder principally to be found in men. It lies deeply in association with the periostium.71~

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Ryan and Curri

Mammary Lipomata Described by Menville, 72 m a m m a r y lipomata were a cause of pain in 6.5% of eases and retraction of the skin in 4% of eases and may lead to a misdiagnosis of cancer of the breast. It can be difficult to distinguish from other elements of the breast and a biopsy is always indicated. In so doing, it should be borne in mind that lipomata can be part of a mixed tumor due to its possible origin from an undifferentiated mesenchymal cell, the socalled adenolipoma9

Angiolipomas These subcutaneous nodules are usually painful on palpation. They are usually quite small in the region of 2 em and are found commonly on the forearms. They may arise de novo but can sometimes be a consequence of trauma. The main feature is the welldeveloped vaseulature with a variable degree of additional connective tissue, smooth muscle, and nerve endings, all of which can be visualized more distinctly in the neighborhood of the capsule of the tumor.74, 75

The Spindle Cell Lipoma This tumor is found most commonly in the region of the scapula and the oeeiput. The presence of fusiform cells, often in aligned clumps, is seen in association with a variable number of mature adipoeytes (Fig. 8-4; see page 89).

Pleomorphic Lipoma This was described by Shmoolier and Enzinger. 7~ Their 48 eases showed a range of features, including mature adipoeytes, fusiform cells, and giant cells.

Benign, Symmetric Lipomatosis of Launois-Bensaude This was first described in 1846 in England by Brodie, 77 and when first reviewed by Launois and Bensaude in 1985, 7s there were 95 eases in the literature. More recently, reviews by Abensour et al G9 and by Ruzika et a] 79 have suggested that while it is rarely reported in American and English literature,

Clinics in Dermatology

it is, in fact, fairly common in Europe. The latter report is based on 12 patients examined in Munich and several reports from the French and German literature. The disease is characterized by massive symmetric fat deposits, predominantly in the neck and girdle areas. It is four times more common in men and may be familial. This common type is seen first in the age group 30-50 years. Pathogenetically, the increase in fatty tissue is a functional sympathetic denervation %b assumed to result from a localized defect in cateeholamine-indueed lipolysis. The authors state that the disease is frequently associated with alcoholism, but according to Abensour et al, 69 this is disputed. There was glucose intolerance, gout, and malignant tumors of the upper airways. Diet, and even surgical removal, is frequently followed by recurrence. T h e r e are v a r i a n t s t h a t may be genetically unrelated. Thus, there is a tumor that usually a p p e a r s in the infant and occasionally even in the neonate in which boys are also predominantly affected, and in which the tumors are mostly on the extremities. 8o A form of the disorder was described by Vellios et al 8' in which the tumors are rather more diffusely located and are often infiltrated deeply. In this form the adipoeytes are less mature and there are multiple vesicles instead of the single fat globule of the mature adipocyte. It is more likely to recur after its removal than is the ease with simple lipomata. The anxiety about this tumor is the capacity for malignant change. 82 It is suggested by Tedesehi 68 that even the common simple lipoma may contain a few immature cells with lipoblastie potential, whereas the mature adipoeytes with one or two large fat globules are incapable of proliferation. The immature cell, characteristic of some forms of these lipomata, still retain some capacity for cell division. Such cells are more like preadipoeytes, being less rounded and often found in clusters. Variation in the histologie appearanee of such collections of cells has given rise to the names lipomyxoma, myxofibrolipoma, fibrolipoma, lipblastoma, and differentiated liposareoma. Tedesehi ~8favors the term given by Grieouroff, namely embryonal lipoma, s3

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Diffuse lipomatosis Enzi et al s4 described a type of lipomatosis that infiltrates extensively, producing severe compression of the peripheral nerves with resulting neuropathy as well as mediastinal displacement. It is possibly due to an abnormal lipoprotein and may be the variant that, as described above, is more often associated with alcoholism. Slavin et al. 85 described "congenital infiltrating lipomatosis of the face." B o r r o n i s6 has r e c e n t l y d e s c r i b e d "diffuse lipomatosis" as an exceedingly rare, poorly demarcated proliferation of mature adipose tissue (Fig. 8-5). Large portions of an extremity or the trunk are usually affected. The condition is not limited to the panniculus, diffusely affecting both subcutis and muscle. Diffuse l i p o m a t o s i s is c h a r a c t e r i z e d by m a t u r e fat cells infiltration of adjacent muscle and soft tissue, absence of malignant characteristics, absence of lipoblasts, presence of fibrous elements in conjunction with increased numbers of nerve bundles and vessels, and hypertrophy of subadjacent bone. Other rare syndromes associated with multiple l i p o m a t a include the G a r d n e r and Richard's Syndrome, in which polyposis coli is associated with both lipomata and osteomas, as well as epidermoid and sebaceous cysts, fibromas, fibrosarcomas, and leiomyomas. W i e d e m a n n s7 in 1983 described a progressive lipomatosis known as the Proteus Syndrome. This rare syndrome is associated with gigantisism of peripheral tissues such as the l i m b and s u b c u t a n e o u s l i p o m a s together with pigmented nevi and hyperkeratosis, and it has to be distinguished from the Klippel-Trenaunay Syndrome and Von Recklinghausen's disease. A n u m b e r of other r a r e r localized forms of lipomatosis have also been described.

Fetal lipoma or hibernoma Gery 8~ described a tumor that he believed was developing from brown fat. It is r a r e and often benign, and often appears in a younger age group than the ordinary lipoma. Maclane and Meyer 89 reviewed 67 cases with a mean age of 33 years and a predominance of women.

Fro. 8-5. Child with severe facial deformity due to infiltrating lipomatosis. (Courtesy Prof. Borroni)

Bonifazi and Meneghini 9o described a case in an infant. The tumor tends to be firm, mobile, and painless, but it may be w a r m to the touch. The size is usually 5-10 cm and is located between the shoulder blades and surrounding regions where brown fat is so well described in the newborn animal. It is usually well capsulated and the color is often quite brown or reddish. The histopathologic appearance is of a lobulated tumor with a multivacuolated or finely granular cytoplasm and central nucleus. The vasculature is well developed. There may be some maturation with a few m a t u r e adipocytes. TedeschU 8 in his review of pathological anatomy of adipose tissues, describes a number of rare presentations in unusual sites of a wide age range of these rarieties and the great variation in size of the tumor (Fig. 8-6; see page 89). Such tumors add to the debate about the origin of adipocytes and the presence of brown fat in the human. One feels that if the adipocyte had happened to choose the epidermis as its domicile, then one would have as much controversy about nevoid and malignant change potential as one currently finds in the literature on the melanocyte.

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Address for correspondence: Terence J. Ryan, DM, FRCP, Department of Dermatology, The Slade Hospital, Headington, Oxford 0X3 7JH, United Kingdom.