A LIPOSARCOMA may be defined rn a malignant mesenchymal tumour the cells of which tend to differentiate into fat cells. Such a tumour is undoubtedly rare.
LIPOSARCOMA: WITH REPORT OF A CASE IN A CHILD
C. H. R. KNOWLES Southern Group Laboratory, Park Hospital, London.
and P. H. Hwaam St G%b’ H o q i t d , London
(PLATES XLV AND XLVI) A LIPOSARCOMA may be defined rn a malignant mesenchymal tumour the cells of which tend to differentiate into fat cells. Such a tumour is undoubtedly rare. Harnett (1952) analysed 14,182 c ~ e of s primary malignancy occurring in London : 205 soft-tissue sarcomas were included, and of these, 2 were classified as liposarcomas. Adair et al. (1932) described one example of malignancy among their series of 352 fatty-tissue tumours occurring in 134 patients. The most comprehensive paper on the subject is that of Stout (1944), who added to 134 cases found in the literature a series of 43 liposarcomas seen in the surgical pathological laboratory of Columbia University, New York, during a period of 37 yews. Most of the reported cases have occurred in middle-aged or elderly persons. I n Stout’s personal series 60 per cent. of the patients were aged 40 or over, and the mean age was 53 ; his four youngest caaes were aged 18, 28, 29 and 32 years. Stout referred to 18 recorded caws in children. One of these cases must be discounted, for the tumour was described by the authors (Sanes and Kenny, 1934) as a reticulum-cell sarcoma of the greater omentum. We have reviewed the remaining 17 cases, which may be summarised as follows. Case 1. Senftleben (1868) reported a ‘‘ myxoma lipomatodes ” which arose in the left side of the face of a boy aged 8 and was treated by resection of the
maxilla. Microscopically it was described &B a malignmt connective-tissue tumour with abundant intercellular mucin and a few scattered fat cells. Cases 2-14. Pack and Anglem (1939) analysed a series of 100 tumours of the soft somatic tissues in infancy and childhood, 13 of which were classified as liposarcomas, but the authors gave no histological deecription or illustration of their casea. Case 15. Kretschmer (1940) reported a tumour which had arisen in the retroperitoneal tissues of a child aged 2. He called the growth B lipofibrosarcoma but gave no histological details. Case 16. Fichmm (1940) reported a congenital tumour of the posterior J. PAW. BACF.--VOL.
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axillary fold of a newborn infant. The histological identification of this growth seems to have presented great difficulty, but Ewing was stated to have made a diagnosis of “ embryonal liposarcoma Case 17. Goeters (1941) reported a tumour from the lesser omentum of a child aged 3, which, he believed, had arisen in the common bile duct. No photomicrographs were included in this paper, but the author summed up the histological features as those of a malignant mesenchymal tumour, composed mainly of myxomatous tissue, which may be called a spindle-cellmyxo-fibro-liposarcoma.
”.
Thus none of the authors cited by Stout gave a convincing description of a liposarcoma occurring in a child and we have failed to find a report of such a cme in the literature covering the years 1944-52. I n a recent paper Bodian and White (1952) reviewed 390 frankly or potentially malignant tumours observed at the Hospital for Sick Children, Great Ormond Street, London, during the period 1930-52 ; these included 20 soft-tissue sarcomas, but no case of liposarcoma was encountered. The commonest sites of origin of liposarcoma are the lower limb, gluteal region and retroperitoneal tissues. I n five (12 per cent.) of Stout’s cases the tumour had arisen in the head or neck. I n the present paper is reported an unequivocal example of liposarcoma arising in the parapharyngeal region of the neck of a child. Case report
Clinical history. K. M., a boy aged 12 years, was first seen in the Ear, Nose and Throat Department of St Giles’ Hospital on 15th February 1952. He complained of a lump in the right side of the neck, first noticed in December 1951. He had received a week’s course of penicillin injections without any effect on the swelling. On ezamination there was a small swelling, about 2 cm. in diameter, just behind the angle of the right side of the mandible ; it was deeply placed, of rather rubbery consistence and relatively fixed. A fow small soft lymph nodes were felt in both sides of the neck. The nose and throat were healthy and, apart from a smdl pad of adenoids, the nasopharynx was normal. A leucocyte count showed no abnormality. A month later the lump in tho neck was slightly larger and a fullness of the right postero-lateral wall of the pharynx was seen. Palpation revealed a soft, ill-defined swelling deep to the mucosa and not attached to it, extending from the vault of the nasopharynx down t o the oropharynx ; i t was about 4 cm. long and 0.5 cm. wide. A further course of penicillin was given, but as this produced no change he was admitted for investigation. Under general anaesthesia the neck swelling was exposed, lying deep t o the lower part, of the parotid gland. It had a smooth surface which dissected easily, but it extended deeply and was deeply fixed. A biopsy was taken ; the tissue was dark red in colour, soft and friable, and it exuded some mucoid material. The adenoids were removed ; these were unconnected with the nasopharyngeal swelling although partly overlying it. The mucosa over the swelling was incised, revertling a tumour similar to the cervical one. At this time there were no abnormal neurological signs, and X-ray examination of cervical spine, base of skull and chest revealed no abnormality. Section of the biopsy material from the neck and nasopharynx showed a malignant non-epithelial tumour of uncertain nature. Many of the tumour cells were vacuolated, and some areas resembled immature adipose tissue ; sections could not be stained for fat, since all the tissue had been embedded in
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paraffin. Abundant intercellular material was present ; this stained well with mucicannine but gave a negative result with per-iodic acid and Schiff’s reagent. There was a well-marked pericellular network of reticulin fibrils in some areas. Three different pathologists thought that the turnour was most likely to be a liposarcoma, but the possibility of chordoma was also considered. The boy was transferred t o the Royal Cancer Hospital for radiotherapy. High-voltage therapy was given : maximum total dose to nasopharynx 3290 r, “ gland ” dose 5210 r, in 57 days. After treatment the pharyngeal swelling was smaller but the cervical one was unchanged. He was seen regularly and both masses slowly became larger. I n November 1952 the pharyngeal swelling was much larger, causing trismus and difficulty in swallowing; he also complained of pain in the right ear and examination revealed two small, hard, reddish swellings on the right tympanic membrane. Eye movements were normal and there were no definite signs of cranial-nerve involvement. An X-ray of the chest now showed an opacity in the right paratracheal area, extending well out into the right upper and mid zones, and a large opacity at the base of the right lung. His condition steadily deteriorated and he died on 23rd December 1952, almost exactly twelve months after the first symptom. Post-mortem examination. This was carried out 34 hours after death. The body was that of an emaciated boy with a. soft diffuse swelling over the right side of the lower jaw and right submandibular region. On reflexion of the skin the upper part of the right side of the neck was found to be occupied by a bulky irregular maw of soft greyish-white growth, most of which was very friable, somewhat slimy and apparently necrotic. The tumour was ill-defined and the soft tissues of the neck were so extensively involved that it was impossible to determine the exact site of origin. Invasion of the right side of the pharynx had occurred, and tumour tissue had grown along the lumen of the right Eustachiam tube into the middle ear. Anteriorly the growth had extended along both surfaces of the right side of the body of the mandible and the bone was deeply eroded. There was no obvious invasion of the base of the skull or of the main cervical veins. No distinguishable lymph-nodal metastases were found on the right side of the neck, and no enlarged superficial or deep lymph nodes were found elsewhere. The esophagus, thyroid, larynx, trachea and bronchi were normal. Both lungs contained secondary deposits. An irregularly lobulated mas8 of growth 6.5 om. in main diameter projected from the diaphragmatic surface of the right lower lobe. The greater part of this mass was covered by normally glistening visceral pleura, and its superficial appearance and consistence were distinctly suggestive of a fatty tumour. A slightly smaller mass was present in the apical region of the right upper lobe, and several other discrete spherical metastases, 1.0-3.5 cm. in diameter, were scattered in both lungs. All these deposits consisted of rather soft, greyish-white tissue, and extensive necrosis had occurred in most of them. There was no evidence of pneumonia. Most of the pulmonary metastases projected beneath the pleural surface, but there were no signs of pleural reaction except ovcr the inferior surface of the right lower lobe, which waa bound to the diaphragm by recent fibrinous adhesions. There was no effusion into the pleural or pericardial sacs, and the great vessels were normal. The liver was normal in size, consistency and general structural pattern. It contained several small secondary deposits of soft white growth, 0.1-2.5 cm. in diameter, some of which showed areas of hzemorrhage. Some of these deposits were situated just beneath the capsule; others were deeply buried in the substance of the organ. The peritoneum and all the other abdominal and pelvic organs were macroscopically normal. The right cerebral hemisphere contained a few secondary deposits, 0.3-3-5 ern.
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in diameter, similar in appearance to those in the liver. The skeleton was not thoroughly examined, but no superficial evidence of metastases wm observed in the skull, spine, ribs or sternum.
Histology Tissue for section was taken from the primary growth in the neck and from the secondary deposits in the lungs, liver and brain. The tumour cells are arranged diffusely and vary greatly in appearance ; for purposes of description they may be subdivided into the following types, but intermediate forms are common. Uniglobular f a t cells. The smallest cells of this series measure 15-25p in diameter and are irregular or pyramidal in shape, with an eccentric nucleus and a single small vacuole-shown in frozen sections to contain a fatty globule-surrounded by scanty eosinophilic cytoplasm. Larger cells, 25-50 p in diameter, assume a typical signetring form, and with further expansion of the vacuole the peripheral flattened nucleus and cytoplasmic rim become increasingly tenuous (figs. 1 and 2). The largest cells of this type, measuring 60-12Op in diameter, resemble very closely the cells of normal adipose tissue (figs. 3 and 4). Foamy cells and multiglobular fat cells. These cells vary in size over the same range as the uniglobular forms and are usually oval, with a regular or undulate outline. They have finely particulate or foamy eosinophilic cytoplasm containing a variable number of small round vacuoles. Some of the largest cells of this type contain only a few small discrete vacuoles surrounded by abundant " foamy " cytoplasm, while other cells exhibit a thin rim of cytoplasm enclosing as many as twenty or thirty closely packed vacuoles (fat globules) in the plane of section (figs. 3-5). The position of the nucleus is variable but it often remains central, even in the largest cells of this type. Some cells have bilobate or apparently double nuclei (figs. 5 and 9). Occasional spindle-shaped cells containing several fat globules occur in some areas (figs. 5 and 6) ; these cells resemble those illustrated by Murray and Stout (1943) in their account of a liposarcoma grown in vitro. Undifferentiated sarcoma cells (figs. 7 and 8). Most of these cells have very scanty cytoplasm and indistinct cell membranes. The nuclei vary considerably in size and shape, the majority being round, oval or fusiform; some nuclei stain densely, but many are leptochromatic, with one or two prominent nucleoli (fig. 9). Occasional cells have two or more nuclei, and there are fairly plentiful mitotic figures, many of them atypical. I n some areas of growth, notably in the hspatic metastases, the spindle-cell structure predominates and the cells tend to be arranged in irregular bundles and whorls (fig. 8). Frozen sections stained with Scharlach R show that the vacuoles seen in paraffin sections contain globules of fatty material, newly all of which is isotropic. Abundant fat in a finely divided form is
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present in the cytoplmm of the foamy cells and traces &o occur in some of the Iarger undifferentiated cells. The distinction which has been made between multiglobular and uniglobular fat cells is somewhat artificial, because a complete range of intermediate forms can be traced. For example, there are cells with a compressed peripheral nucleus which closely resemble n o r d fat cells except that the fat is in the form of two or three large globules instead of one. There is, however, a striking contrast between large cells f o d by expansion of a single fat globule and cells of about the same size containing numerous separate globules (figs. 3 and 4). The relative distribution of the different Qpes of cell is very variable. I n some meas of the tumour one type of structure predominates, although the other varieties can usually be found in neighbouring fields of the same section. I n many areas, however, anaplastic cells, foamy cells and vacuolated cells of both types are diffusely commingled (figs. 3 and 4). I n the sections from the primrtry tumour in the neck, well-differentiated vacuolated cells are numerous, mitotic figures very scanty (fig. 1). I n the smaller hepatic metmtases (fig. 8), plmmorphic or spindle-cell maplastic growth predominates, vacuolated cells are very scarce, mitotic figures plentiful; in the pulmonary and cerebral metastases differentiation and mitotic activity vary greatly in different areas. Examination of several different metastases suggests SOD degree of correlation between the size of a metastasis and the differentiation of its component cells ; a secondary deposit in the early stages of its existence tends to consist mainly of proliferating maplastic growth, but with further enlargement an increasing proportion of the tumour cells accumulate fat in their cytoplasm. The growth is richly supplied with capillary blood vessels and there are scattered area9 of haemorrhage and necrosis in the larger tumour masses. I n one section of the primary growth, a tumour embolus, including a few vacuolatsd cells, wm found within a venule 300 p in diameter. I n most rtreas the tumour cells are individually supported by an argyrophil reticulum (fig. 2). This pericellulrtr network is clearly defined over the greater part of the range of structural differentiation. It is, however, often difficult to discern around large uniglobular fat cells exceeding about 6 0 p in diameter; m a fat cell expands, the reticulin sheath a p p r s to undergo progressive attenuation in the s a w way as the cytoplasmic rim of the cell. At ths other end of the scale, in completely undifferentiated meas showing m r k d cellular pleomorphism, reticulin is less abundant and there is no regular pericellular mangement. Collagen fibres axe very scanty throughout. Mucin is not demonstrable in representative sections of the postmortem material, either with Southgate’s mucicarmine or by McManus’s P.A.S. technique. Only tracw of intrwellular glycogen have been found and no w>sinophilic globoid bodies of the type described by Wright (1948).
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DISCUSSION Origin and classification of Eiposarcm In many classes of malignant tumour the structural differentiation exhibited by the tumour cells is a reliable guide to the tissue of origin. Most squamous-cell carcinomas, for instance, may be said with confidence to arise from stratified squamous epithelium, and this can be verified by histological study of early tumours. I n malignant mesenchymal tumours, however, for various reasons the relationship between differentiation and origin is not so close. I n the first place, direct observation of the origin of tumour cells from pre-existing normal elements is scarcely possible in a diffuse tissue such as connective tissue ; in the second place, many histologists believe that cells having the potentialities of undifferentiated mesenchymal cells persist in the loose connective tissues of the adult. Thirdly, as Willis (1948, p. 642) emphasises, proliferating mesenchymal tissue, typified by reparative granulation tissue, can produce all, or nearly all, that embryonic mesenchym can produce. This structural versatility of proliferating connective-tissue cells is manifested by a wide range of metaplastic processes and by the frequent occurrence of mixed mesenchyrnal tumours in which two or more distinct varieties of differentiated structure can be identified. It follows that a sarcoma arising in adipose tissue is not necessarily a liposarcoma. Indeed no example of liposarcoma was recognised among 54 primary sarcomas of the greater omentum collected from the literature by Mandelstamm (1930), although nine varieties of structure were described by the various authors. Conversely, a clearly recognisable example of liposarcoma has not necessarily arisen from either mature or immature fat cells. Stout defined liposarcoma as a malignant tumour of lipoblasts, and Wright (1948) stated that the cells forming the malignant portions of his tumour were typical lipoblasts, but there seems to be no general agreement on the origin or microscopic appearance of lipoblasts ; no such cell is described in standard textbooks of histology, and some workers have denied the existence of a specific precursor of the fat cell. Wells (1940) gave a detailed account of the various views which have been held on the development of normal adipose tissue since the time of Virchow, and Cameron (1952, pp. 320-2, 463-5), in a recent review of the subject, shows that many obscurities still exist in our knowledge. Adipose tissue has been considered by different observers to arise from ordinary connective tissue, from special " primitive fat organs '' or from perivascular mesenchymal cells related to reticulum cells. Murray and Stout (1943), k e y (1946) and others have described two different modes of development of fat cells in the human fetus. ( a ) One type of pre-adipose tissue, often referred to as embryonal or fetal adipose tissue, consists of stellate or fusiform cells with processes.
J. PATH. HAVT.--\'OL.
PLATEXLV
TXVIII
LIPOSARCOM A
PIG. 1. - Primary tumour. area of welldiffercntinted growth with many uniglobular and multiglobular fat rells. Haematoxylin m i l eosin. x 96.
FIG.S.-Motastnsis
FIG.4.-Metastaais
FIG. 2.-Primary tumour. Pericellular network of reticulin fibrils in an area similar to that shown in fig. 1. Gomori's method for reticulin. x 96.
in lung. Uniglohular and multiglobular fat cells mingled with undifferentiated cells. H. and E. x 9G.
in lung. Detail of an area similar t o that shown in fig. 3. Fully developed uniglobular and multiglobulnr cells in juxtaposition. H. and E. x 250.
FIG.5.-Metastasis
in brain. Foamy cells and multiglobular fat cells at various stages of clevelopment. The giant, re11 in the ventrc of the field measures 72 p in main diameter. H. and E. x 250.
J . PATH. RACT.-VOL.
PLATE XLVI
LXVIIf
LIPOSARCOMA
FIG. &-Metastasis in brain.
Spindle-shaped FIG. 7.-Metastasis in brain. An area of growth cells, some containing fat globules in their consisting mainly of undifferentiated fusiform cytopltinm. H. and E. x 250. cells. A few very early uniglobular and multiglobular forms can be seen. H. and E.
x 98.
FIG. 8.-Metastasis in liver. Anaplastic growth composed of pleomorphic cells. H. and E. xBG.
Fro. S.-Metastasis
in brain. Mainly anaplastic growth, with occasional vacuolated cello. The multiglobular giant cell in the centre measures 60 p in mnin rlinmet.er. H. iind E. X 250.
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closely resembling fibroblasts. These cells are widely spaced and surrounded by mucoid intercellular substance. A few small droplets of fat appear in the cytoplasm of each cell, increase in size and soon coalesce to form a single large globule. At the same time the cell body swells, withdraws its processes and assumes a rounded form, the nucleus and residual cytoplasm being displaced to the periphery. ( 6 ) The other type of tissue is composed of rounded or polyhedral cells with a central nucleus and abundant granular cytoplasm. These cells are arranged in compact lobules before they begin to accumulate fat, and intercellular mucin is absent. Fat appears in each cell in the form of numerous small globules. The cell assumes a characteristic mulberry-like appearance and its nucleus often remains central. This variety of tissue is known as brown fat, hibernal fat or glandular adipose tissue, and its' structure closely resembles that of the so-called hibernating gland. The hibernating gland is a distinct anatomical entity which has been described in many different species of hibernating and nonhibernating animals. It differs from ordinary adipose tissue in composition, metabolism and distribution as well as in structure. No interchange between multiglobular and uniglobular adipose tissue as a result of feeding or starvation has been reported. A homologous interscapular body, extending into the posterior triangle of the neck, is described in the human fetus (Keith, 1948). In the post-natal human subject, brown fat is occasionally found. It has been observed in the subcutaneous tissues about the shoulders and neck, in the axillq in the mediastinum, beneath the pleural surface of the diaphragm, in the retroperitoneal tissues and, in small amounts, around certain joints. Human perinephric tissue, particularly in infancy, shows 8ome of the characters of " glandular " adipose tissue (Wells) ; the cells are more or less multiglobular when not too well filled with fat, though in well-nourished adults they appear like ordinary adipose tissue cells. A hibernoma is a type of lipoma composed mainly of multiglobular fat cells with central nuclei and granular cytoplasm ; small numbers of uniglobular fat cells of the ordinary type are usually present as well. At least fourteen examples of this tumour have been reported in man, the commonest sites being the subcutaneous tissues of the posterior cervical and interscapular regions and the axillae. Kittle et al. (1950) reported a large intmthoracic tumour of this type and an example from the popliteal space has been recorded by Sieber and Heller (1952). It seems possible that this type of tumour may be more common than the published case reports would suggest. Mallory (1914) stated that lipomas were occasionally composed of granular or multiglobular fat cells with central nuclei, and he described and illustrated such a tumour. Ewing (1940, pp. 190-191) referred to peculiar pigmented lipomas and sarcomas which &rose from brown fat in the neighbourhood of joints, He described the multiglobular type I.PATH. BACT.-VOL.
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of lipoma, and his illustration depicts the characteristic structure of hibernoma. The whole subject of the hibernating gland, brown fat and hibernoma has been thoroughly reviewed by Brines and Johnson (1949) and by Sutherland et al. (1952). From these and earlier accounts it is evident that the functions and fate of human brown fat are obscure, and it is still undecided whether transmutation can occur between the cells of brown fat and those of ordinary adipose tissue. Some authors regard human brown fat as an immutable vestigial homologue of the hibernating gland of animals; derived from its own specific mesenchymal cells. Others believe it to represent the remnants of a normal phase in the development of ordinary yellow adipose tissue. The obscurities in our knowledge of the origin, development and varieties of adipose tissue are reflected in the attempts which have been made to distinguish different types of liposarcoma. Ewing (1935 ; 1940, p. 198) described two varieties : ( a ) embryonal liposarcoma (myxoliposarcoma), and ( b ) adult or granular-cell liposarcoma. Ewing’s account is dii3cult to follow. His use of the words “ embryonal ” and adult )’is confusing and he seems to have included in the group of liposarcoma tumours in which recognisable fat cells were very scanty or even absent. Stout (1944), in criticising the sub-divisions made by Ewing and previous workers, has emphasised that liposarcomas are a single group of tumours capable of manifesting different degrees of differentiation and that two or more varieties of structure may be found in the same tumour. Stout himself subdivided the group into one well-differentiated and less malignant type simulating the appearance of ordinary embryonal fat, and three poorly differentiated and more malignant types resembling ( a ) atypical embryonal fat, ( b ) atypical brown fat and (c) these elements in combination. It is doubtful whether such sub-divisions have any practical value, but they do emphasise the fact that the structural appearances of both types of adipose tissue may be reproduced in liposarcomas. ((
Histological diagnosis The cells of the tumour here reported exhibit most of the varieties of structure described by previous authors and in our opinion they clearly illustrate the two different lines of development, one leading to the ordinary type of mature uniglobular fat cell, the other to a multiglobular cell similar to the characteristic element of brown fat. I n a tumour such as this, if plentiful tissue is available for study and if fat stains are employed, the diagnosis presents no difficulty, but in poorly differentiated growths containing only small amounts of fat a diagnosis of liposarcoma is much more hazardous. According to Maximow and Bloom (1948, p. 63) small droplets of neutral fat may occur in any cell of the connective tissue. Willis (p. 664) has emphasised the fact that a cellular tumour with vacuolated fat-laden cells is not necessarily a liposarcoma. “Many kinds of anaplastic tumour ” he writes (‘show tumour cells with fat or lipoid
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droplets due to degenerative changes, and of course macrophages laden with such materials are often plentiful in tumours ”. Moreover, the microscopic appearance of liposarcoma may clearly be simulated by adipose tissue which is being infiltrated by a diffusely cellular malignant t u o u r of any kind. Another point mentioned by Willis is that in some simple lipomas the mature fat cells are mingled more or less intimately with fibroblastic or other mesenchymal tissues. Sarcomatous change may supervene in the fibromatous component of such a fibrolipoma, but the resulting malignant tumour is a fibrosarcoma rather than a liposarcoma. Willis (pp. 662-663) reported two examples of this occurrence, in neither of which were transitional forms found between the fat cells and the bizarre fibroblasts. Thus, even a sarcomatous growth containing mature fat cells is not necessarily a liposarcoma. A diagnosis of liposarcoma can only be fully established by the observation of a complete range of intermediate forms between undifferentiated sarcoma cells and well-developed fat cells of either the uniglobular or the multiglobular type. Shaw (1936) laid stress on the presence of a pericellular plexus of azgyrophil fibrils in his case of “ embryonal-cell liposarcoma ”. He stated that such a pericellular reticulum was characteristically found in the brown fat of the fetus but was not demonstrable, by the Bielschowsky-Foot method, in mature adipose tissue or in simple lipomas. Haagensen and Krehbiel (1936), in their detailed and wellillustrated account of five liposarcomas produced by 1 : 2 benzpyrene in experimental animals, described considerable variation in the reticulin pattern, ranging from very delicate pericellular septa to irregular bundles between groups of tumour cells. The reticulin content of the growth in our case is similar to that described by Shaw. We do not, however, agree with his opinion that the presence of a pericellular reticulin network may be accepted as proof of the origin of the cells from embryonal adipose tissue, and we have been unable to find support for such a view in the literature studied. We have heard of no recent work on the reticulin content of mesenchymal tumours, other than tumours of lymph nodes, but we ourselves have observed well-developed pericellular reticulin in a random example of the reticular type of neurilemmoma and in a typical glomangioma, as well as in several reticulosarcomas. With regard to normal mesenchymal tissues, Cameron (p. 453) refers to Plenk’s description of networks of reticulin fibres around smooth and striated muscle, connective tissue and even fat cells. Maximow and Bloom (p. 75) state that in adipose tissue the argyrophil fibres are well developed, especially along the blood vessels, and that they form a net-like basket around each fat cell. I n this connection they mention the view of Wassermann (1925-26) that fat cells are modified reticulum cells. From our own observations we are satisfied that a pericellular framework of reticulin is a constant feature of normal smooth and striated muscle. Examples of reticulin impregnation of
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normal adipose tissue which we have examined show pericellular argyrophil material to be either absent or very scanty, and granular rather than fibrillary in form. On the whole, reticulin impregnation seems unlikely to be a reliable guide in the diagnosis of liposarcoma and we are inclined to agree with Willis’s sceptical attitude. His opinion (p. 760) is that while special stains for connective tissue and reticulin ‘‘ often do delineate fairly characteristic patterns in typical specimens of particular classes of tumours, they are of no value in identifying tumours of unusual structure or uncertain nature ”. Intercellular mucin is often present in liposarcomas, and several different compound names have been given to such tumours. Robertson (1916-17) reviewed 50 cases of “ lipoma myxomatodes ” reported in the literature, of which about 20 were malignant and the remainder apparently simple lipomas which had undergone mucinous degeneration or metaplasia, or myxolipomas. Pathological much comprises a group of substances which exhibit variable staining reactions, and Stout mentioned the fact that the slimy intercellular material found in many liposarcomas may or may not be stainable by mucicarmine. I n our case intercellular material which stained well with mucicarmine waa found in the biopsy fragments but not in representative sections of the post-mortem tissues.
Metastasis I n some of the reported cases of liposarcoma, several tumours were present, and it was difficult to decide whether these were attributable to multicentric origin or to metastasis. In our case the clinical course and the distribution of the tumour masses at necropsy leave no doubt that haemic dissemination had occurred to the lungs, liver and brain from a primary growth in the neck. Metastasis is said to be less frequent than from other types of sarcoma. Of the 134 cases quoted from the literature by Stout, metastasis had occurred in 24 (18 per cent.). Shaw stated that recurrences of liposarcoma invariably consisted of extremely anaplastic tissue. I n our case a high degree of differentiation was observed in the larger metastases.
SUMMARY A case of liposarcoma arising in the parapharyngeal region of a boy aged 12 is reported. Dissemination took place by the bloodstream and death ensued twelve months after the onset. Microscopically, the tumour cells show two lines of differentiation corresponding to the development of ( a ) ordinary adipose tissue, and ( b ) glandular adipose tissue or brown fat. The origin, classification and microscopic appearances of liposaxcoma are discussed. It is concluded that a diagnosis of liposarcoma must depend on the observation of a complete range of transitional forms between undifferentiated sarcoma cells and unmistakable fat cells of either the uniglobular or the multiglobular type.
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We wish to thank Mr F. R. Hackett and Miss I. A. Rutter for the histological preparations, Dr A. J. Mester for help with translations and Mr J. E. Andrews for the photomicrographs.
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