Tumors of the soft somatic tissues in infancy and childhood

TUMORS OF T H E SOFT SOMATIC T I S S U E S IN I N F A N C Y AND CHILDHOOD GEORGE T.

PACK,M.D., AND THOMAS J. ANGLEM,M.D. N E W YORK, N . Y .

UMORS arc extremely rare in the early years of life with the exT ception of those which occur more specifically during that period. In comparison with similar tumors in older persons, cancers in the young are more rapidly growing, highly cellular, undifferentiated, anaplastic neoplasms of greater malignancy. F r o m Jan. 1, 1917, to Oct. 1, 1938, at the Memorial Hospital, New York, there were one hundred patients under 16 years of age with tumors of the soft parts, excluding the majority of those on the head and neck. Sarcoma of the soft parts in children is not encountered to any considerable degree, according to reports in the literature. Among all cases admitted to the Radiation Service at Bellevue Hospital, New York, from 1924 to 1934, Kaplau and Rubenfeld found 78 soft tissue sarcomas, exelusive of those in the eye, lymphosarcoma, and Kaposi's disease. In only four instances were the patients u n d e r 16 years of age--2, 5, 13, and 15 years, respectively. Since our figures cover a long period, nearly twenty-two years, in a hospital devoted solely to the treatment of cancer and allied diseases, it may be concluded that such tumors are rare in early life. TABLE I ])ISTICIBUTION TYPE

O~ ~

ACCOI~DING

TU~[OI~

TO TYPE

OF TUMOR NUMBER

PER

CENT

A. Malignant Tumors 1. 2. 3. 4. 5. 6. 7. 8.

Total Neurogenic sarcoma Neuroeytoma Liposarcoma l~habdomyosarcoma S a r c o m a unclassified Melanoma M a l i g n a n t synovioma G r a n u l a t i o n cell sarcoma

58 23 1 13 2 10 7 ] ]

100.0 39.7 1.7 22.4 3.4 17:2 ]2.1 1.7 1.7

42 10 11 ]7 1 2

100.0 23.8 26.2 40.4 2.4 4.8

.B. Benig~ Tumor's ]. 2. 3. 4. 5. 6.

Total :Neurofibroma Lipoma Naevus (melanotic) Glomus t u m o r X a n t h o m a or b e n i g n giant-cell t u m o r of ten,don sheath Teratoid t u m o r

2.4

P a r t of a Symposium on Tumors of Childhood, New York Academy of Medicine, Section on Pediatrics, Dec. 9, 1937. F r o m the Mixed. Tumor Service of the Memorial t~ospigal for C a n c e r and Allied Diseases, New York, N. Y. 372

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T U M O R S OF SOFT T I S S U E S TABLE II

I)ISTR1BUTION ACCO~r I~r

TO AGE A~D TYPE OF

TUMOR

TUMORS

BENIGN 'fUMORS o

~q

R

o ~z

Total Under 1 1-2 2-3 3-4 4-5 5-6 6-7 7-8 8-9 9-10 10-11 11-12 12-13 13-14: 14-]5 15-16 17-18

11

0 2 7 6

8 9 6 5

58 ~' 6 6 6 ] 1 4 4 4 3 1 3 3 4 5

23

13 2 3 2

10 ]

10

3 1 4 5 2 2 3 4 ] 2 2 1

1

2

1 1 2 1

1

Malignant synovioma ..................

1 1 1 1

Granulation

1 case

cell

sarcoma

.............

tGlomus tumor .......................... X a n t h o m a of t e n d o n s h e a t h . . . . . . . . . . . . Sacroeoeeygeal in the footnotes

11 2

17 3 1

1

*Neurocytoma .......................... :Rhabdomyosareoma .................

Cases

42t 6 1

case case case case

1

~

1 1 2 1

5 years under 1 year 2 years under 1 year 2 years

1 case 6 years 1 ease 5 years

i case teratoid tumor .......... 1 case are included in the total columns.

8 years under ][ year

The distribution is shown according to the type of tumor in Table I and according to the age distribution in Table II. The fifty-eight malign a a t tumors occurred in patients equally divided as to sex. These points will be considered in more detail in the discussion of the types of tumors. A general description of the various tumors of the soft somatic tissues which may occur in infancy and childhood, together with the treatment of choice, is considered necessary. The classification for this discussion is [based on the origin of the tumor. TUMORS OF THE PERmHE~aL NERVOUS SYSTEM A classification of tumors of the peripheral nervous system exclusive of the end-organ apparatus is as fol]ows : a. Neurofibroma. Neurofibromatosis. Von Recklinghausen's disease. b. Perineurial fibroblastoma. (Neurolemmoma, Schwannoma.) c. Malignant perineurial fibroblastoma. d. Neurosarcoma. Neurogenic sarcoma. e. Neuroepithelioma. f. Ganglioneuroma. Neurocytoma . . . . . . . . . . . . . . . . . . . . . . . . . (Faraganglioma, phaeochromoeytoma.)

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Neurofibroma; Neurofibromatosis.--The clinical features of neurofibromas and of generalized neurofibromatosis are too well known to bear unnecessary repetitious description. These tumors v a r y from the small, isolated single intracutaneous or subcutaneous neurofibroma to the advanced, hereditary, generalized form of yon Recklinghausen's disease. Children with this latter manifestation may have intraeutaneous and subcutaneous multiple tumors of variable size; they may occur in a plexiform neuromatous arrangement in which the moniliform beading of the nerve trunks can be felt beneath the skin, and even in the muscles. Another stigma of the disease is elephantiasis nervorum, in which baggy, loose folds of skin containing myxomatous connective tissue and m a n y

F i g . 1 . - - C a s e 1. n . S., a 7 - y e a r - o l d boy, w a s a d m i t t e d to t h e M e m o r i a l H o s p i t a l on Oct. 9, 1934, f o r t r e a t m e n t of a l a r g e l u m p in t h e r i g h t f l a n k w h i c h h a d b e e n p r e s e n t s i n c e b i r t h . T h i s m a s s e x t e n d e d 14 c m . v e r t i c a l l y a n d 23 era. in a s e m i e i r c u m f e r e n c e f r o m t h e s p i n e to t h e u m b i l i c u s . T h e o n l y o t h e r e v i d e n c e of n e u r o f i b r o m a t o s i s w a s I n c o r p o r a t e d in t h i s s o f t t h e p r e s e n c e o f p i g m e n t e d cafd-.au-lait s p o t s i n t h e s k i n . myxomatous c o n n e c t i v e t i s s u e w e r e n u m e r o u s n o d u l e s of t h e p l e x i f o r m n e u r o m a variety. The tumor was surgically excised,

nodular nerve tumors can be felt (Fig. 1). This process is prone to occur on the scalp, although it may develop in any part of the body, partieularly the feet. There is usually an associated peculiar pigmentation which may be discrete in the form of brown, flat areas known as cafga~-lait spots, or numerous large, pigmented naevi, some of which are hairy. Pigmentation is more m a r k e d on the face, particularly around the mouth and chin, where the freckling m a y be greatly exaggerated. Associated with these phenomena m a y be certain ocular changes, such as

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an excess of medullated nerve fibers in the retina, and bone changes, such as scoliosis (Fig. 3), pseudoarthrosis, subperiosteal cysts, pedunculated subperiosteal benign tumors, and many abnormalities of growth (Fig. 2). Treatment: When only one or two small neurofibromas are present and they measure less than 1.5 centimeters in diameter, surgical excision is indicated. When the disease is generalized, no surgical t r e a t m e n t is worth while, except the removal of large pedunculated, uncomfortable masses that cause discomfort by their location or size. The plexiform neuromas that exhibit unusual growth activity should be dissected widely; this is readily done and is not technically difficult. All patients with neurofibromatosis should be observed at intervals because :10 to 15 per cent of such patients ultimately develop malignant neurogenic tumors, although they are usually of low-grade malignancy. It is a safe rule to plan the surgical excision of any tumor in a patient with yon Recklinghausen's disease, if this tumor measures more than 1.5 centimeters in diameter and is showing any tendency to enlarge.

A,

B.

F i g . 2 . - - A . N e u r o f i b r o m a of toe. B. M u l t i p l e c o n g e n i t a l n e u r o f i b r o m a s of h a n d in s a m e p a t i e n t a s in A. N o t e c o n t r a c t u a l d e f o r m i t i e s so c o m m o n l y o c c u r r i n g i n t h i s disease;

Perineu~'ial Fibroblastoma.~lthough this tumor is usually single, it may occur in patients with von R,ecklinghausen's disease. I t is a spherical, encapsulated, freely movable tumor that reaches considerable bulk after slow growth. I t occurs commonly on the neck, arms, back of legs and in the brachial plexus (Fig. 3, Case 2). This tumor of the nerve sheath is usually benign. I t does not destroy the nerve in which it occurs, but pushes the nerve t r u n k aside, or expands it. To remove this tumor, the surgeon m a y strip the nerve t r u n k longitudinally and dissect the tumor out by shelling, as it is not difficult to find a line of cleavage. After the tumor is removed, it leaves the nerve bundle flabby and collapsed, but capable of functioning. I f this tumor occurs in an insignificant nerve twig, such a nerve may be sacrificed without concern. The occasional cysts found in peripheral nerves are probably degen-

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erated nerve sheath tumors and can be removed by the same meticulous dissection with preservation of the nerve trunk. Malignant Perineurial Fibroblastoma.--This tumor is probably the malignant derivative of the benign nerve sheath tumors. Although it is classified as a sarcoma, it is usually of low-grade malignancy. As a rule it does not metastasize but is considered malignant because of its ability to infiltrate locally, and because of its tendency to recur. The treatment of this t u m o r is seldom so radical as to necessitate amputation unless it occurs on a digit. Wide local excision is usually sufficient, but the excision must include the nerve on which the t u m o r originates if the nerve

F i g . 3 . - - C a s e 2. N e u r o m a . F . G. w a s r e f e r r e d t o t h e M e m o r i a l H o s p i t a l f o r t r e a t ment of u lump in the medial aspect of the left upper arm near the axilla. The lump w a s of one y e a r ' s d u r a t i o n . S e v e r e p a i n r a d i a t e d d o w n t h e a r m to t h e w e b b e t w e e n the thumb and forefinger. The skin of the hand over the distribution of the median nerve was hyperesthetic. At operation the tumor was enueleated from the fibers of the median nerve with no subsequent functional impairment. It was a benign perineurlal fibroblastoma. This boy presented the characteristic stigmas of yon t~ecklinghansen's disease, with g e n e r a l i z e d n e u r o f i b r o m a t o s i s , cafd-au-~ait p i g m e n t a t i o n of skin, a n d n u m e r o u s b o n y d e f o r m i t i e s , s u c h a s d w a r f i s m a n d s e o l i o s i s . H i s m o t h e r w a s being" c o n c u r r e n t l y t r e a t e d for a large neuroma involving the left breast. She also had generalized neurofibromatosis as did a younger brother and this patient's paternal grandmother.

is visible. I t is occasionally possible to resuture or anastomose the proximal and distal divided segments of the nerve after the tumor is excised. A gap as large as 5 to 15 era. m a y be closed by nerve suture. The nerves are sutured er~d to end, taking care not to permit rotation, so that the same fibers will unite with the corresponding fibers in the lower segment;

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this can be accomplished by marking the nerve above and below the t u m o r with a minute suture prior to excision. The ends of the nerve m a y be a p p r o x i m a t e d by taking advantage of any of the three following methods : 1. The n a t u r a l elasticity of these nerves will p e r m i t a stretching of 1 to 2 cm. without u n d u e tension. 2. I f the t u m o r occurs on an extremity or near the pelvic or shoulder girdle, the position of the limb m a y be a r r a n g e d and held in position by splints' or plaster casts so as to diminish greatly the gaps between the severed nerve ends. 3. Rerouting the nerve m a y be done by dissecting it up f r o m its tortuous course and placing it between other muscle bundles, etc., often saving 4 to 8 era. in closing the gap. Neurosarcoma.--This t u m o r m a y occur independently or m a y originate in patients with neurofibromatosis. A n y neurogenic t u m o r larger than 1.5 centimeters in size which shows increased growth activity m a y be

Fig. 4.--Case 3. Neurogenic sarcoma. R. A., a colored boy, aged 11 years, was referred to the Memorial Hospital on Sept. 21, 1921, for treatment of a recurrent tumor in the region of the left knee. The tumor was said to have originated following an injury at the age of 18 months. In April, 1921, Dr. Hibbs ~tt the New York Orthopedic Hospital had excised the tumor, which immediately recurred. Dr. Bradley L. Coley amputated the leg through the mid~hig'h in February, 1922. The pathological diagnosis by Dr. Ewing was "cellular small spindle-cell sarcoma, possible of neurogenie origin." At the end of 1938, seventeen years following the date of admission, he.was reported by Dr. Coley as well and without evidence of recurrence.

suspected of being neurosareomatous. The usual history t h a t these patients present on app]ieatio~ to the Memorial Hospital is that they have had repeated local exeisions of the tumor with rapid recurrenee, and eventual metastasis to the lung's. If the diagnosis has been established by aspiration biopsy or by study of a slide prepared from a former excision, if the tmnor is recurrent, an immediate decision as to the method of treatment is made. If no evidence of pulmonary metastasis is present

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on roentgenographic study and if the local tumor remains technically dissectible, then preoperative irradiation, either by high voltage x-rays or by the external application of radium packs or bombs, is carried out. A large dose is administered by the fractionated principle, even if this causes irreparable damage to the skin and overlying tissues. Six weeks after this treatment is given, a very wide surgical excision of the tumor is done, together with a removal of the overlying damaged normal tissues. The pathologist often reports that the tumor when excised shows complete destruction or inactivation of growth with marked fibrosis. If it is believed that it is not technically possible to perform such a resection,

F i g . 5 . - - C a s e 4. M u l t i p l e n e u r o s a r c o m a s d e v e l o p i n g on t h e b a s i s of g e n e r a l i z e d neurofibromatosis. R. N., a n 1 1 - y e a r - o l d girl, o b s e r v e d a r a p i d l y g r o w i n g l u m p on the medial aspect of the left thigh. I n A p r i l , 1927, s h e e n t e r e d t h e M e m o r i a l H o s p i t a l where the tumor was surgically removed. The microscopic study revealed a neurogenie myxosareoma. H u n d r e d s of s m a l l n o d u l a r s u b c u t a n e o u s t u m o r s in b e a d e d f o r m a t i o n c o u l d b e f e l t o v e r t h e t r u n k a n d b o t h e x t r e m i t i e s ; t h e y w e r e t y p i c a l of p l e x i f o r m n e u r o m a s . Large a n d s m a l l a r e a s of b r o w n p i g m e n t a t i o n in t h e s k i n w e r e g e n e r a l i z e d , c h a r a c t e r i s t i c o f von l~eeklinghausen's disease. This patient's older sister had been previously treated at t h e ]YIemorial H o s p i t a l f o r m u l t i p l e n e u r o m a s . T h e f a m i l i a l r e l a t i o n s h i p in t h i s i n s t a n c e w a s v e r i f i e d b y e x a m i n a t i o n of t h e m o t h e r :who h a d g e n e r a l i z e d n e u r o f i b r o m a tosis. I n M a r c h , 1929, J u l y , 1934, a n d N o v e m b e r , 1934, t h r e e o t h e r o p e r a t i o n s w e r e p e r f o r m e d f o r t h e r e m o v a l o f n e u r o s a r e o m a s d e v e l o p i n g on t h e r i g h t t h i g h , u p p e r l e f t thigh and right groin, respectively. A massive intra-abdominal and intrapclvic tumor s u b s e q u e n t l y d e v e l o p e d a n d c a u s e d h e r d e a t h on I)ec. 18, 1935.

amputation is the elected method of treatment (Fig. 4. Case 3, Case 7). It is fully recognized that in children such irradiation, particularly over the epiphyses, m a y interfere with bony growth, but this is not so important as the possible loss of the limb or life.

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I t is g e n e r a l l y a g r e e d t h a t m a n y s a r c o m a s o f s o f t p a r t s a r e o f p e r i p h eral nerve

origin.

In

this

series of f i f t y - e i g h t

malignant

curring

in children, twenty-three,

comas.

Twelve occurred in males and eleven in females.

tumors

or 39.7 p e r cent, w e r e n e u r o g e n i c

ocSar-

T h e l o w e r ex-

t r e m i t i e s r e p r e s e n t t h e site of p r e d i l e c t i o n , w i t h ten, or 43.5 p e r c e n t , of the tumors;

six of t h e s e w e r e l o c a t e d o n t h e t h i g h .

cent, were on the upper

The end results are shown in Table III. receiving treatment,

Eight,

or 21.7 per

extremities. Of the twenty-one

patients

t e n , or 47.6 p e r cent, h a v e d i e d ; e i g h t of t h e m w i t h i n

Fig. 6.--Case 5. Neurogenic sarcoma (?). J'. I)., a 14-year-old boy, had observed a lump of two months' duration in the left axilla. On examination, the left axilla was found to contain a bulky tumor extending beneath the pectoral muscles as far as the clavicle and downward to the nipple. The presumptive diagnosis was neurogenic sarcoma. The patient was under the care of Dr. Bradley L Coley, who supervised external irradiation by the radium element pack and interstitial radiation using gold radon seeds. The tumor subsided in size but at no time was considered operable. :Death occurred shortly after the treatment had been completed; it was due to pulmonary metastases. TABLE I I I I~EUI~OGENIC SAt~COl~A END l~ESUL'r S N u m b e r of patients examined at the clinic N u m b e r of p a t i e n t s r e f u s i n g treatmen't or failing to return P a t i e n t s treated at the clinic Dead: 10 W i t h i n one year from admissio~ 8 L e n g e r t h a n one year 2 L~ving: Wi~h no evidence of neurosarcoma 30 U p to three years from admission 2 Three to five years 3 Five to ten years 4 Over t e n years 1 W i t h evidence of neurosarcoma when last 1 examined at the clinic

23 2 21

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a y e a r f r o m t h e t i m e of admission. O f the others, one boy of 13 w i t h a n e u r o g e n i c s a r c o m a of the a b d o m i n a l w a l l l i v e d o v e r six y e a r s w i t h no r e c u r r e n c e b u t d i e d six m o n t h s l a t e r f r o m p u l m o n a r y metastases. I t is i m p o r t a n t to n o t e t h a t of t h e t e n c h i l d r e n l i v i n g w i t h no e v i d e n c e of disease, h a l f of t h e m h a v e been f o l l o w e d m o r e t h a n five y e a r s f r o m t h e t i m e of admission. T h e one c h i ld w i t h e v i d e n c e of r e s i d u a l or r e c u r r e n t n e u r o s a r c o m a was in f a i r c o n d i t i o n a t the e n d of five years, b u t has been lost t r a c k of since he was t r e a t e d elsewhere. CASE 6.--Neurogenie sarcoma. P. E., a 12-year-old girl, discovered a lump in the subcutaneous tissues of the left forearm, just above the wrist. It remained stationary for ahnost two years and then began to exlfibit increased rate of growth. The tumor was surgically excise~d in Elizabeth, N. 3. The prepared microscopic slide was studied at the Memorial Hospital; the diagnosis was neurogenlc sarcoma. Postoperative high voltage roentgen therapy was administered, one erythema dose over the scar and repeated after an interval of two weeks. In May, 1934, the tumor had recurre(l, and immediately thereafter it was removed by wide surgical dissection. The gross specimen definitely revealed the relationship of the tumor to one of the superficial nerves. Postoperative roentgen therapy was again administered. At this date, five years after ~che second operation, there has been no evs of recurrence. CASE 7.--Neurogenie sarcoma. P . A . , a 12-year-old girl, applied to the Memorial I~ospital in September, 1934, for treatment of a lump siiuas deep in the tissues of the lateral surface of the left leg. The tumor was treated by application of the radium element pack. As recurrence developed, the radimn treatment was followed by a midthigh amputation in October, 1934. There is no evidence of recurrence of the tumor at the present time, now four and one-half years after the amputation. The microscopic diagnosis was spindle-cell sarcoma, presumably of neurogenic origin. CaSE 8.--Neurogenic sarcoma. C. B., a girl 5 years of age, was referred to the Memorial Itosp~tal in April, 1934. The parents had noted a small subcutaneous lump situated over the left scapula eighteen months previously. It remained quiescent for a year and then began slowly to enlarge. Surgical removal was performed at another institution. Examination of the submitted tumor revealed a neurogenie sarcoma. Postoperative high voltage roentgen therapy was administered. At *he present time there is no evidence of recurrence (five years postoperative survival).

Ganglioneuroma.--The t u m o r s w h i c h o r i g i n a t e f r o m t h e a n l a g e n of th e s y m p a t h e t i c n e r v o u s s y s t e m w h i c h go to f o r m t h e a d r e n a l m e d u l l a r e p r e s e n t in t h e i r s t r u c t u r e a n d f u n c t i o n t h e d i f f e r e n t successive stages i n the d i f f e r e n t i a t i o n of a s y m p a t h e t i c n e u r o b l a s t . O n e of these t u m o r s is t h e g a n g l i o n e u r o m a , w h i c h is a w e l l - d i f f e r e n t i a t e d s y m p a t h e t i c n e r v e t u m o r c o n t a i n i n g m e d u l l a t e d a n d n o n m e d u l l a t e d fibers a n d proliferating" g a n g l i o n cells. T h i s t u m o r is w e l l e n c a p s u l a t e d a n d grows slowly. I t is r e l a t i v e l y b e n i g n ; it l e n d s i t s e l f well to local excision, a n d t h e r e is a g r a t i f y i n g freedom from recurrence. A p p r o x i m a t e l y one-third of the cases of this t u m o r occur in childhood. T h e y a r e o c c a s i o n a l l y m o d e r a t e l y r a d i o s e n s i t i v e . T h e c o m m o n sites of t h e i r o c c u r r e n c e are, in t h e o r d e r

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of frequency, (a) retroperitoneal, (b) cervical, (c) posterior mediastinal. The treatment, of course, is surgical excision. Preoperative irradiation of the bulky tumors may facilitate the subsequent operative removal. Neurocytoma.--This tumor, also of sympathetic nerve origin, is essentially an embryonal neuroepithelioma. It is a cellular tumor which contains imperfect rosettes in its structure. Although it occurs most commonly in childhood, it may appear in later life. Its origin is chiefly in the adrenal glands, but it may occur in other retroperitoneal locations, or in the chest or cranium, as well as in the peripheral nervous system. It is a highly malignant tumor of varying radiosensitivity, which metastasizes early to the liver. The tumor tends to recur after surgical excision, and radiation therapy alone is seldom sufficient to exercise permanent growth restraint, let alone complete sterilization of the tumor. Phaeoehromocytoma.--This tumor, which is a benign medullary, ehromaffin-cell tumor, or paraganglioma, is usually encapsulated and most commonly occurs in the adrenal gland. It may occur in childhood. Its presence is heralded by attacks of paroxysmal hypertension and other vasomotor disturbances, sometimes associated with increased basal metabolism. The proper method of treatment is surgical excision. LIPOMAS

Although the majority of lipomas are of congenital origin, most of them make their recognizable appearance during the decennium, from 40 to 50 years, at the age when fat usually begins to accmnulate. All varieties of lipomas, however, including the most unusual and interesting forms, may occur in infancy and childhood. The following c]inicopathologic classification of lipomas is elementary and practical: a. The Simple Solitary Lipoma.--This tumor has no distinguishing features to herald it as unusual It is the ordinary lipoma which occurs frequently on the back of the neck, forearm, and the axilla; it is seldom found on the face, scalp, chest, and lower leg. b. The Multiple Lipomas.--Multiple lipomatosis is unquestionably inherited, as we have seen many instances where several members of the family have had these tumors. The number varies from two or three to as many as 500 in a single individual. Although usually small and subcutaneous, they may become large and confluent, producing a knobby contour of the extremities and trunk that may be quite disfiguring. One of our patients had 400 such tumors, and another had 160, all of subcutaneous location. Because of their symmetrical distribution, they are frequently mistaken for multiple neurofibromas. There are clinical and microscopic evidences of a peculiar nerve reiati0nsMp that seem to link these tumors with neurofibromatosis of the yon Reeklinghausen type. Our discovery of this histologic and clinical relationship of lipomas to the peripheral nerves is not original. Neerbeck, in 1887, cited eases of

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lipomas in which the tumors contained nerve fibers. Grosch, Madelung, Israel, Baumgartner, Buchterkich, and Bunke have reported multiple symmetrical lipomas associated with local neuropathies, trophic disorders, spinal cord lesions and other nervous disturbances suggesting involvement of the central nervous system. Alsberg found several neurofibromas with many lipomas in the same patient, an observation we have since confirmed many times. We have attempted to draw certain clinical analogies between multiple lipomas and multiple neurofibromas, as follows : (1) Both are of multieentric origin. (2) The symmetrical distribution of the tumors suggests a disturbance or defect of the central nervous system as a causative factor.

Fig. 7.--Case 9. A s y m m e t r i c a l lipomatosis. D . S., a c o l o r e d g i r l a g e d 6 y e a r s , a p p l i e d t o t h e M e m o r i a l H o s p i t a l o n O c t . 9, 1929, c o m p l a i n i n g of an enlargement of the entire right arm. The child was considered normal by her mother until she was 1 y e a r old. At that time a small soft tumor on the posterior aspect of the right shoulder was observed. This tumor grew steadily and progressed down the arm until finally the entire right upper extremity was involved. On examination, the right shoulder girdle and entire right arm were involved in a soft tumor process which was most prominent on the posterior aspect of the shoulder and elbow. The skin over these areas was roughened and edematous and contained additional dark pigment. T h e e l b o w c o u l d n o t b e e x t e n d e d b e y o n d 145 d e g r e e s . The affected arm was almost as strong as the left arm. The two arms were equal in length. The body as a whole, aside from the right arm and shoulder, was symmetrical. Neurologic examination by Dr. George Hyslop revealed that there were no motor, sensory or reflex inequalities in the two arms. The diagnosis was asymmetrical localized lipomatosis. O n J a n . 1, 1930, r e d u n d a n t fat tissue was excised by sharp dissection from the dorsum of the right hand, wrist, forearm, elbow and shoulder. On microscopic examination the cells of the tumor were found to be adult lipoeytes with no unusual features.

(3) The multiple lipomas and neurofibromas have similar regional location, as, for example, on the neck, scapula, face, gluteal region, arms, sides, and back. (4) Both groups of tumors are classified as intraeutaneous, subcutaneous, fascial, and visceral in location. (5) Multiple ]ipomas and ncurofibromas may coexist in the same individual.

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(6) The fiat, coffee-colored, pigmented areas of skin which constitute one of the stigmas of von Recklinghausen's disease are often observed in patients who have multiple, symmetrical lipomas. (7) There is an undisputed hereditary or familial influence on the genesis of both multiple lipomas and neurofibromas.

F i g . 8 . - - C a s e 10. A s y m m e t r i c a l l i p o m a t o s i s . T. G., a w h i t e b o y a g e d 71~ y e a r s , a p p l i e d to t h e M e m o r i a l H o s p i t a l on Oct. 31, 1929, c o m p l a i n i n g of a n o v e r g r o w t h o f the left hand, present since birth. The history related by the mother stated that the left arm and hand were larger than the right at birth and during childhood had grown more rapidly, thereby accentuating" the disproportion. The tumor was most p r o m i n e n t o v e r t h e t h e n a r e m i n e n c e , w h e r e it a t t a i n e d t h e s i z e of a l e m o n . I n 1924 t h i s p o r t i o n of t h e t u m o r h a d b e e n e x c i s e d a t a n o t h e r h o s p i t a l , It soon recurred and r e a c h e d s u c h a s i z e t h a t it h i n d e r e d t h e p a t i e n t in u s i n g h i s h a n d . O n e x a m i n a t i o n t h e p a t i e n t w a s f o u n d to b e a f a t b o y w i t h t h e g e n e r a l c h a r a c t e r i s tics of l~rShlich's s y n d r o m e . T h e r e w a s no p u b i c h a i r , a n d t h e p u b i c e s c u t c h e o n w a s distinctly feminine in type. The configuration of the pelvis was feminine as was the general bodily habitus. The thenar eminence of the left hand was the site of most marked overgrowth. The thumb and first finger were likewise much hypertrophied, T h e t i s s u e c o m p o s i n g t h e t u m o r w a s s o f t a n d u n i f o r m in c o n s i s t e n c y . It tramsilluminated well and was not compressible. Neurologic examination was essentially normal as were x-ray studies of the arm, c e r v i c a l v e r t e b r a e , a n d Sella t u r e i c a . The diagnosis was asymmetrical localized lipomatosis of the left upper extremity. The treatment carried out was sharp surgical dissection. The specimen removed showed diffuse f a t t y t i s s u e c o n t a i n i n g m a n y n e r v e fibers.

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(8) Sensory and trophic disturbances are associated with both tumors, such as hyperesthesia, pain, hypesthesia, and atrophy of the skin. c. Congenital, Diffuse Lipomatosis.--This variety of lipoma is confined to one or two limbs, and is usually associated with corresponding enlargement of the muscles and bones of the same limb (Fig. 7, Case 9). It may be coexistent with diffuse, cavernous hemangiomas. The condition is recognized soon after birth and may show progressive enlargement during infancy and childhood. Some of these patients present all the anatomical features of Frhhlich's syndrome, with or without the attendant symptomatology, such as polyuria, renal disturbances, headaches, and other symptoms of increased intracranial pressure (Fig. 8, Case 10). The condition of dystrophia adiposogenitalis, which Frhhlich described in 1901, while accompanied in most instances by generalized adiposity, may be associated with tumor formation. These tumors are lipomas and may be symmetrically or asymmetrically distributed. The association of the overgrowth of bone with these tmnors, as shown in two of our patients (Fig. 7 and Fig. 8), is significant. The entire extremity may be greatly hypertrophied. Similar bony enlargement often occurs with other tumors, particularly the deep hemangiomas, in which case the increased blood supply may be partly responsible. Another type of diffuse lipomatosis which may occur in childhood is the disease which Madelung calls Fetthals, in which the neck and axillae of both upper extremities are symmetrically enlarged. The disease has also been called adeno]ipomatosis, since it occurs in the neck, axilla, and eubital regions, but it really has no relation to lymph nodes. Such lipomatosis involving a single extremity may grow to such gigantic size as to constitute a great physical handicap, because of the weight and discomfort of the member. In some instances amputation has been resorted to as the only means

of relief.

d. Degenerative Lipomas.--These tumors really do not need separate classification. They represent the large or bulky lipomas which have undergone certain degenerative changes, due to rapid growth or impaired blood supply. The xantholipomas and myxolipomas are well-known examples. They are dangerous because of the frequency of development of sarcoma. Treatment.--Lipomas are insensitive to radiation and, therefore, should never be treated by roentgen rays or radium. All lipomas of considerable size and those which show any growth activity should be surgically excised. It is not unusual to see liposarcoma developing in a patient who has congenital multiple lipomas. LIPOSAI~COMAS

Toldt has described the origin of fat tissue from certain well-localized embryonal lobules or fat islands occurring in certain regions. He described a closed system of fine blood vessels within the organ; in the

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meshes of these blood vessels are certain round, granular cells which are the precursors of adult fat tissue. These lipoblasts are partly derived from the adventitial layers of the blood vessels. Accepting this mode of origin of fat tissue, Ewing has conducted a careful clinical, gross and microscopic pathologic research as to the possible origin of liposarcomas. He studied the fat pads in the region of the hips and shoulders, for embryonal fat lobules might be expected to reside as relics of a time when budding of the limbs occurred. Two types of fat were recognized: the common white fat and the less frequent brown fat. The brown fat was found chiefly in the mediastinum, the perirenal region, the thymus, the axillae, and the groin. The cells of the brown fat are large, polyhedral, and granular and therefore give an opaque, orange-colored appearance to the fat tissue or the xanthomatous lipomas and liposarcomas derived from this tissue.

Fig. 9.--Case II. Liposarcoma. S. F., a 14-year-old girl, came to the Memorial Hospital on Oct. 26, 1936, for treatment of a small lump beneath the skin of the right thoracic region. This mass was excised on Nov. 4, 1936, but a wider excision was considered necessary. Therefore, this was performed on Dec. 15, 1936. The diagnosis was myxoliposarcoma. The excision was followed by treatment with the radium element pack to the post-thoracic region for a total dose of 24,000 rag. hr., given at a radium-skin distance of I0 cm. At the present time there is no evidence of recurrence.

Ewing recognized the existence of two types of liposarcoma. One, the adult form of liposarcoma, is composed of granular cells resembling those found in chronic inflammation of f a t tissue, and later exhibiting diffuse growth and anaplasia. Ewing states that it represents a lawless state of the growth of fat cells observed in lesser degree in chronic inflammation of fat tissue. The adult liposarcoma may develop with ap-

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parent spontaneity or by degeneration of a pre-existent lipoma known to be present, or may follow a single severe trauma (Case 15). According to Ewing, a history of trauma is a most definite and reasonable explanation for the origin of tumors in subcutaneous fat tissues, and in the adult form of liposarcoma rather than in the embryonal type. "Severe tramna with a resulting hemorrhage has preeeded the appearante of the tumor at the point of injury. Since traumatism to fat tissue is often followed by marked proliferation of fat cells and progressive productive inflammation, it is not unreasonable to assume that under special circumstances the proliferation may take on a malignant character." (Ewing.) There is abundant clinical evidence in this series of eases at the Memorial Hospital to substantiate the viewpoint that some of the adult liposarcomas originate following a single severe trauma to normal adult fat tissue.

Fig. 10.--Case 18. I,iposareoma. J. If., a 2-year-old boy, was brought to the Memorial Hospital for treatment of a tumor occurring in the region of the left scapula. biopsy of this subcutaneous tumor made at another hospital was available for study and was reported by Dr. Stewart as myxoliposarcoma. The tumor was treated by a combination of high voltage x-rays and radium element paek. It was subsequently removed by surgical dissection at another institution. At the time of the last report the child was living and well without evidence of recurrence, three years after treatment had been given.

The seeond variety of liposareoma, which Ewing eMls an embryonal liposareoma, or myxoliposareoma, originates usually in the following locations : femoral region, inguinal region, axilla, scapular region, deltoid region, pectoral region, mediastinum, retroperitoneal region, particularly in the true pelvis. These tumors are usually multilobulated and encapsulated. On microscopic s t u d y they are seen to exhibit a proliferation of minute blood vessels, the adventitial or endothelial cells of which instead of producing fat, form chiefly mucus and 0ceasionally embryonal

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fat tissue, as Ewing has shown in numerous photomicrographs of his histologic researches. It should be understood here that the words "adult" and "embryonal" refer to the character of the fat cell and not to the patient who is host to the tumor. Adult liposareomas may occur in infants. Liposarcomas are often clinically indistinguishable from other sarcomas of the soft somatic tissues. Their common regional distribution around the shoulder and pelvic girdles is not absolutely pathognomonic. They vary in size from minute tumors measuring 2 era. in diameter to very bulky tumors which may occupy the entire pelvis or be larger in circumference than the extremity in which they occur. Some o~ the adult liposareomas, particularly those following trauma, are likely to be diffuse, nonencapsulated and not well demarcated from the adjacent normal tissues. The majority of the embryonal liposareomas, especially those which occur in the intermuseu]ar spaces, are multilobulated, en-

Fig'. II. Figs. II and 12.--Case 17. Congenital liposarcoma. A. T., a Puerto-Rican girl baby aged 2 months, was referred to the Memorial Hospital on Dec. 5, 1934, for diagnosis and treatment of an irregular swelling occupying the lower two-thirds of the left leg. This tumor had been discovered on the day of birth; therefore, it was congenital in origin. A formal biopsy made within two or three days after birth was diagnosed as liposarcorna. X-ray studies made shortly after birth revealed evidence of deformities of both tibia and fibula with cystlike areas of absorption and pressure in the lower ends of both bones. There was no evidence of metastases to the lungs as seen on x-ray examination; the child did not have a large thymus. AS the parents refused amputation, treatment was given by fractionated doses of high voltage roentgen rays to the left lower leg, with two ports, one medial and one lateral, cross-firing at the tumor. The following factors were employed: 200 K. V., 50 ern. T. S. D., 30 ma., field 7.8 by 7.8 cm., 100 r daily alternating until a total dose of 1800 r units were given to each of the two areas. These treatments were completed in J a n u a r y , 1935. T h e t r n n o r c o m p l e t e l y d i s a p p e a r e d ; t h e d e f e c t s in t h e b o n e a l s o w e r e r e p l a c e d b y n o r m a l b o n e ; t h e c h i l d h a s p e r f e c t u s e of t h e l i m b s . N o w , f o u r y e a r s a f t e r t r e a t m e n t , t h e r e h a s b e e n no e v i d e n c e of r e c u r r e n c e , Gomment.--This is one o f t h e f e w c a s e s of c o n g e n i t a l s a r c o m a t h a t h a s b e e n s u c c e s s f u l l y t r e a t e d , e i t h e r b y s u r g e r y or r a d i a t i o n t h e r a p y .

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capsulated tumors. These intermuseular liposarcomas seem h a r d in consistency when the muscles overlying them are contracted. Liposarcoma represents the second largest group of the m a l i g n a n t tumors of soft p a r t s in infancy and childhood cared for at the Memorial H o s p i t a l : thirteen cases, or 22.4 per cent. Nine were in males and four

vr

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in females. Six of the patients have died, all except one within a year f r o m the time of admission. F o u r are without evidence of disease f r o m three to five years f r o m admission. Three were admitted toward the end of 1938 and are u n d e r treatment.

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T r e a t m e n t . - - T h e e m b r y o n a l liposarcoma, or m y x o s a r c o m a , is usually extremely sensitive to the influence of x - r a y s and r a d i u m (Figs. 11 a n d 12, Case 17). E w i n g is of the opinion t h a t the s t r u e t u r e of this tmnor, with its fine eapillary blood vessels, is the reason for this u n u s u a l radiosensitivity. The r e e u r r e n t liposareomas, however, do not exhibit this same degree of response, as the t u m o r is no longer eneapsulated, reeeiving its blood s u p p l y f r o m a single souree, b u t grows diffusely a n d is n o u r i s h e d f r o m m a n y blood vessels f u r n i s h e d t h r o u g h the n e i g h b o r i n g tissues. The liposareoma of adult structure, even t h o u g h o c c u r r i n g in i n f a n t s a n d children, is radiosensitivc to a lesser degree. I t is our opinion t h a t all liposareomas should reeeive a t h e r a p e u t i c trial of irradiation. This t r e a t m e n t is given in small f r a e t i o n a t e d doses, u s u a l l y of high voltage x-rays. I f the t u m o r shows an immediate regression a f t e r a few treatments, the f r a c t i o n a t e d principle is c o n t i n u e d to the p o i n t of tolerance of the n o r m a l i n t e r v e n i n g tissues. As m a n y p o r t s as possible are used for eross-firing at the tumor. This m e t h o d is u s u a l l y suceessful in causing a complete d i s a p p e a r a n c e of the radiosensitive t y p e of liposareoma (Case 17). I f the liposarcoma does not r e s p o n d r e a d i l y to this t h e r a p e u t i c trial, the p r o g r a m of i r r a d i a t i o n is diseontinued, and the t m n o r is r e m o v e d b y wide or radieal surgieal dissection, if this is teehnieally possible. Postoperative x - r a y or external r a d i u m t h e r a p y is then used as a p r o p h y l a c t i c measure a f t e r the w o u n d is healed (Cases 11, 14, 15). I n a few instances it has been deemed advisable to supplem e n t external i r r a d i a t i o n with interstitial r a d i u m t h e r a p y , u s i n g heavily filtered r a d o n needles inserted in g r i d i r o n fashion t h r o u g h o u t the t u m o r bed. Metastatie liposarcoma is usually radiosensitive a n d eonsiderable palliative relief m a y be obtained b y the judicious e m p l o y m e n t of roentgen or r a d i u m t h e r a p y . The liposarcomas metastasize to lungs, liver, subeutaneous tissues, a n d bone. Oeeasionally a p r i m a r y liposarcoma m a y develop in bone m a r r o w ; this r a r e t u m o r is one of the most radiosensitive of all s a r c o m a s o c c u r r i n g in bone. CASE 12.--Liposarcoma. g.H., a 22-nmnth-old boy, was brought to the Memorial Hospital on Dec. 2, 1934, for treatment of a tmnor situated in the cubital space of the right elbow. The parents had observed this lump for nine months and had taken the child to a doctor. The physician made a roen~genographic study of the elbo~v arLd, as no fracture was revealed, advised the patient's parents to do nothing about it. The tumor was excised at the Memorial 15Iospital on Dec. ]0, 1934; the microscopic diagnosis was liposareoma. There has been no evidence of recurrence in the four years since this treatment was given. CASE 14.--Liposarcoma. B.K., an 11-month-old boy, was brought to the Memorial I-Iospital for treatment of a lump in the right flank just above Poupart's ligament. When firs t noticed at the age of 5V2 months, the lump was one-third smaller than on admission. It was freely movable and not adherent to the deeper structures of the abdominal wall. It measured 9 era. in length and 4 cm. in width.

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O n April 2~ 1937~ the tumor was surgically excised. The specimen was examined by Dr. Fred Stewart, who gave the following" report: ~'The marked cellularity of perivascular spindle cells between adult-looking f a t cells makes it necessary to classify this tumor as a type of liposarcoma." Postoperative high voltage x-ray therapy was given. There has been no evi.dence of recurrence in the two years since surgical excision.

CASE 15.--Liposarcoma. R. M., a 17-month-old boy, was referred to the 3s rim Hospital on Jan. 27, 1935. At two months of age, he fell off a table; subsequently, a small tumor appeared a t the site of this injury. I t increased in size and was surgically excised in July, 1934, at another institution. The tumor recurred, and a subsequent excision was performed. Microscopic study by Dr. Ewing at the Memorial ttospita] revealed a large spindle-cell sarcoma, quite vascular, and of the type referred to as liposarcoma. On admission to the Iv[emorial I{ospital, the wound was open a~d iufeeted. A f t e r the use of antiseptic dressings, a second wound] closure was performed, and postoperative irradiation was administered. At tile present time there is no evidence of recurrence, four years after the last treatment.

CASE 16.~IAposareoma. E.P., a girl 51~ years old, was referred to the Memorial }Iospital in July, 1937, because of pain in the right side of the abdomen. Two months previously~ her father had observed near the midline of the back, a small lmnp which had increased in size. Because of her inability to use her lower limbs, a physician at another hospital had placed the child in a plaster cast for six weeks,. On admission to the Memorial Hospital, she was suffering from paraplegia due to the involvement of the spinal cord by the tumor which measured 14 by 15 era. in ,diameter. I t was apparent that the tumor had invaded the spinal column. I t was thought to be a ]ipogenic sarcoma. A new tumor developed in the right temporal fossa, and metastases te t h e brain later occurred with l e f t facial pares~s. The child died in September, 1937. TUMORS OF STRIATED MUSCLE TISSUE

The benign rhabdomyomas, or striated muscle tumors, are usually of embryonal origin, occurring in early life and are sometimes congenital, making their appearance shortly after birth. They may be of multieentrie origin, separate nodules occurring in different muscle groups. The malignant tmnors of striated muscle, or rhabdomyosareonias, may originate from pre-existing benign myomas, but in the majority of instances seem to develop d e ~wvo: They, too, are sometimes multiple. Both the benign and the malignant tumors may be either circumscribed or diffuse. On cut section they are soft, grayish and pink in color, solid or cystic. The microscopic structure is that of parallel bundles or intertwining strands of striped muscle fibers, supported by adult or embryonal connective tissue. Both cross and longitudinal striations are sometimes seen. The cross striation may be present in all or a part of the tumor, and may be entirely absent in the more anaplastic spindle-cell variety of muscle sarcoma. The rhabdomyosareomas have an abundant vascular supply and hence metastasize early to the lungs. One type of rhabdomyosareoma which occurs in infants and children, and has a definite constitutional basis, is the tumor associated with yon Gierke's disease. This disease is a metabolic perversion characterized by

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the deposition of glycogen in various organs, particularly the liver, heart, and skeletal muscles. W h y this abnormal accumulation of glycogen occurs is not as yet fully established; nor is it definitely understood why it irritates or stimulates the muscle fibers of the heart and skeletal muscles to divide and evcntuall:~ form discrete, nodular rhabdomyomas. T r e a t m e n t . - - T h e p r o p e r treatment for benign and malignant tumors of striated muscle ~s wide, radical, surgical dissection. It is not difficult to enueleate these tumors when they are encapsulated. The dissection should include the removal of the muscle in which the tumor occurs and

F i g . 1 3 . - - C a s e 18. R h a b d o m y o s a r c o r n a . C. Me., a 2 - m o n t h - o l d child, h a d a s u b c u t a n e o u s t u m o r r e m o v e d f r o m the left thigh. O n m i c r o s c o p i c s t u d y it p r o v e d to be a rhabdomyosarcoma, Postoperative irradiation was given in fractionated doses; the following factors were employed: 200 K. V., 50 cg]. T. S. D., field of 7 by 9 cm., daily fraction of 150 r, continuing until a close of 2,400 r units was given. In order to administer the x-ray treatment, the child was placed in a split or bivalved bod.~/ cast at the time of each treatment in order to immobilize the leg. There has been no evidence of recurrence in the year that has elapsed since treatment was given.

the group of muscles, if more than one are involved by the multicentric tumor process. This conservative surgical treatment may be sufficient and, if properly p e r f o r m e d at the first operation, may avoid the necessity of subsequent amputation. The recurrent rhabdomyosarcomas, the diffusely invasive sarcomas of striated muscle and those which are so deeply adherent that a local excision is not feasible, are best treated by amputation. Radiation t h e r a p y alone is not sufficient to sterilize the average rhabdomyosarcoma; such treatment is often followed b y necrosis and hemorrhage into the body of the tumor, and later reactivation and diffuse invasive growth. Postoperative irradiation by the fractionated dose principle has proved, in our experience, to be a valuable adjunct to local excision. It m a y induce sufficient additional interstitial fibrosis throughout the operative site as to inhibit or delay any tendency to recurfence if the tumor has not been completely removed (Fig. 13, Case 18). SARCOMA U N C L A S S I F I E D

Tile ten patients are equally divided as to sex. Six of the patients have died, all but one within a year of admission, and this one a year

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and two months after admission. A girl of 15 with a sarcoma of the back is without evidence of r e c u r r e n t sarcoma ten years f r o m the time of admission. Another girl is without evidence of recurrence ten years a f t e r t r e a t m e n t (Fig. 14, Case 19).

Fig. 14.--Case 19, lYiyxosarcoma of undetermined histogenesis. J. R., a girl of 2 years, was brought to the Memorial Hospital on July 30, 1928. For six months the mother had observed a small nodule developing under the skin of the right forearm. This nodule was excised on Feb. 23, 1928, at another hospital. The tumor had recurred and had increased markedly in size. Ten days before admission to the Memorial Hospital, the surface of the tumor sloughed away leaving a fungating, bleeding mass. On admission the ulcerating tumor measured about 12 cm. in width and 16 era. in Iength, extending from mid forearm to mid upper arm, The arm was amputated on Aug'. 2, 1928, three inches f r o m the shoulder, Microscopic study revealed a m y x o s a r e o m a of undetermined histogenesis. Sinee the date of operation the child has been frequently observed and there is no evidenee of reem-rence and no indication of metastases in the lungs. (I0 years' postoperative survival. ) PIGMENTED

NAEVI AND MALIGNANT MELANOMAS

The pigmented mole, or neuronaevus, is of such universal occurrence that almost everyone is theoretically subject to the danger of m a l i g n a n t melanoma, its malignant derivative. I n an analysis of 400 young people, it was f o u n d that the average person h a d eighteen pigmented moles; some had only one or two, b u t others had as m a n y as a hundred. The tendency to have multiple pigmented moles is certainly inherited, as a r e other tumors of the peripheral nervous system. The true naevus is a t u m o r of the tactile end organ. The naeval cells in the eorium have a b u n d a n t nerve connections. I n their development they m a y n a t u r a l l y produce the Meissnerian corpuscles ; this phenomenon occurs not only in the benign pigmented neuronaevus, but also in some m a l i g n a n t melanomas as well. I n the normal skin, nonmedullated nerve fibers r a m i f y in the epidermis and communicate with the minute tactile end organs there, called the Merkel-I~anvier corpuscles. The process of neoplasia m a y occur in the epidermis so t h a t the naevus or the melanoma m a y be strietly i n t r a e p i d e r m a l in its p r i m a r y or original location. The naeval cells are melanoblastic and m a y or m a y n o t exercise the function of producing pigment. The production of the melanin pigment has long since been considered a function of the nervous system, and in lower animals it is u n d e r v o l u n t a r y control, as the production of melanin in

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the ink sacs of the cuttlefish and squid and the phenomenon of mimicry or the changing of color Suitable to environment by various lizards and fish. The differentiation of tumors, particularly cancers, has been well studied so that everyone is familiar with the evolution of epidermoid carcinoma and its differentiation into adult keratinized epithelium, and the differentiation of glandular carcinomas so that the adult differentiated t y p e contains well-formed glands. Pigmented naevi and melanomas undergo both functional and morphologic differentiation. In their morphologic differentiation the tmnors tend to reproduce the tactile corpuscles, although these are imperfectly formed and are often of giant size. The functional differentiation is toward the production of pigment. Nonpigmented melanomas on the average are much more malignant than those which form melanin.

F i g . 1 5 . - - C a s e 20. : P i g m e n t e d n a e v u s . C. L., a 3 - w e e k - o l d b a b y girl, wets b r o u g h t t o t h e M e m o r i a l H o s p i t a l on N o v . 10, 1937, w i t h a t y p i c a l b a t h i n g t r u n k v a r i e t y of naevus. A brown pigmented naevus involved the entire gluteal and vulval region. T h e r e w e r e d i s c r e t e p i g m e n t e d n a e v i on t h e b o d y , c h e e k , c e r v i c a l r e g i o n , l e f t s c a l p , s h o u l d e r a n d w r i s t . I t w ~ s d e c i d e d to r e m o v e t h i s n a e v u s in g r a d e d s t a g e s ; f o u r e x c i s i o n s h a v e a l r e a d y b e e n c a r r i e d o~l.

Not all neuronaevi are potentially dangerous. The type previously described is ectodermal in origin. Another variety is the blue naevus of Jadassohn, which occurs deep in the corium and is composed of thin, ribbonlike cells that are of mesoblastie or connective tissue origin; these blue naevi may become malignant, forming a type of melanoma which is essentially sareomatous and which metastasizes by way of the blood stream. The ectodermal types previously described are usually only dangerous when they are darkly pigmented or become infected, or are situated in locations subject to frequent trauma, such as on the soles of the feet. Occurrence of Melanoma in Infancy and Childhood.--Although pigmented naevi may be recognized in the skin shortly after birth, many

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of them do not make their recognizable appearance until after puberty. It is felt that the new naevi appearing after adult life are not of recent origin but are merely tile quiescent, previously existing naevi becoming visible through increased growth at a later age period. Although pigmented naevi occur in infancy and childhood, the malignant melanoma is seldom found in individuals before puberty. The explanation for this later occurrence probably has nothing to do with the age of the naevus itself, nor the passage of time considered necessary for a precancerous tumor to become malignant. It is considered more likely to be related to certain endocrine stimulation. We are aware of the transformation of pigmented naevi into melanomas during pregnancy, and of the extraordinary rapid growth and dissemination of melanomas occurring in pregnant women, which is thought to be due to pituitary hormonal in-

]Pig. 1 6 . - - C a s e 21. Congenital melanotic naevus. Embryonal adenosareoma of kidney. P. N., a 5 1 ~ - m o n t h - o l d b a b y girl, w a s b r o u g h t to t h e M e m o r i a l H o s p i t a l in A u g u s t , 1935. T h e s k i n of t h e e n t i r e b a c k f r o m t h e s h o u l d e r s to t h e b u t t o c k s w a s c o v e r e d b y m u l t i c o l o r e d a r e a s of p i g m e n t a t i o n p r e s e n t a t b i r t h . Interspersed over t h e u n i f o r m l i g h t b a c k g r o u n d of t h i s n a e v u s w e r e n u m e r o u s e o a I - b l a e k m o r e d e e p l y p i g m e n t e d d i s c r e t e n a e v i . I t w a s d e e m e d a d v i s a b l e to r e m o v e t h e s e d e e p l y p i g m e n t e d l e s i o n s , b u t , b e c a u s e of t h e c h i l d ' s a g e a n d e x t e n t of t h e i n v o l v e m e n t , it w a s d e c i d e d t h a t t h e y s h o u l d n o t be r e m o v e d a t one s t a g e . I n t h e c o u r s e of t h e n e x t t w o y e a r s , five o p e r a t i o n s w e r e p e r f o r m e d , in w h i c h a l l of t h e d a r k l y p i g m e n t e d n a e v i w e r e excised, I n O c t o b e r , 1936, a l a r g e t u m o r w a s f e l t in t h e r e g i o n of t h e l e f t k i d n e y . The d i a g n o s i s w a s ~Vilms' e m b r y o n a I a d e n o s a r c o m a o f t h e k i d n e y . It was treated by Dr. A r c h i e D e a n who employed p r e o p e r a t i v e r o e n t g e n t h e r a p y , n e p h r e e t o m y , a n d postoperative roentgen therapy. A t t h e p r e s e n t t i m e t h e c h i l d is g a i n i n g in w e i g h t a n d t h e r e is no e v i d e n c e of l o c a l o r g e n e r a l i z e d r e c u r r e n c e of t h e k i d n e y t u m o r .

fluence. The intermediary substance of the pituitary gland has a great influence on the activity of pigmented cells, and, in fact, the quantity of intermedin in the blood seems to be definitely increased in patients who have disseminated melanomatosis (Ferguson). It is conceivable that this same pituitary stimulation occurs at the onset of puberty and thereafter, as it is in adult life that the majority of malignant melanomas occur. Although malignant melanomas are found in infancy and childhood, they

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are of low-grade malignancy and seldom metastasize. Under the microscope these tumors may be indistinguishable from other melanomas occurring in adult life which exhibit a high degree of malignancy by diffuse metastasis, so that the pathologist, on microscopic examination, may term them melanomas, yet their behavior is not in keeping' with their morphologic structure. Of 483 malignant melanomas in all age groups studied at the Memorial Hospital, only 12 (2.7 per cent) occurred in patients under 16 years of age. Treatment of Naevi and Melanomas.--Because of the foregoing facts relative to age distribution, it is thought best to remove all darkly pigmented neuronaevi in infancy and childhood. They should be removed before adult life when they are more likely to undergo malignant degeneration: It is the purpose, therefore; of surgeons and dermatologists conscientiously to remove these benign tumors in children, particularly when they are heavily pigmented or in regions subject to frequent irritation. The malignant melanoma is remoVed by very wide surgical dissection, carrying the dissection below the deep fascia. In adults this procedure is routinely followed in six weeks' time by meticulous dissection of

Fig.

17.--Malignant

melanoma

of the second toe occurring" Dr. ]Bradley L. Coley.)

in a

boy.

(Patient

of

the regional lymph nodes draining" the skin which is the site of the melanoma. We have found that in two out of three cases, in which this second operation is done, melanoma cells are found in the lymph nodes, even though they were not palpably enlarged prior to the operation. In infants and children, however, the routine dissection of regional lymph nodes is not done, because the tendency of melanomas in infancy and childhood to metastasize is latent. These children are observed carefully at intervals for examination of the regional lymph nodes. Radiation therapy is considered to be of no avail in the treatment of malignant melanomas.

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E n d Results.--Two of the seven children were males and five were females. One patient was r e f e r r e d for diagnosis and received no treatment. The low-grade malignancy of melanomas in childhood, in contrast to adult life, is shown in the end results of the other six patients. Only one of these six patients has died. One patient has lived five years without recurrence and another, ten years. CASE 2 2 . - - M e l a n o m a . F. N., ~ girl of 10 years~ came to the Memorial t I o s p i t a l on Oct. 5, 1934, for t r e a t m e n t of a h a r d nodule on her back which pro~ed to be u sebaceous cyst. A lesion on her righ~ a r m was excised, a n d t h e pathologic r e p o r t b y D o c t o r s E w i n g a n d S t e w a r t said m e l a n o m u . A t t h e end of 1938 t h e r e was no evidence of r e c u r r e n c e ; the p a t i e n t ' s m o t h e r w a s w a r n e d of t h e necessity of r e g u l a r examinations. CASE 2 3 . - - M e l a n o m a . E. P., ~ 10-year-o~d girl, was b r o u g h t to ~he Memorial H o s p i t a l Sept. 7, 3933, for t r e a t m e n t of a black mole orL the outer ~spect o f h e r leg in t h e m i d d l e third, which h a d been p r e s e n t f o r t w e n t y m o n t h s . A wide local excision was done on Sept. 8, 1933. T h e p a t h o l o g i c r e p o r t was of a low-grade m e l a n o m a . T h e r e is no evidence o f recurrence Jn t h e leg nor in the groin. GLOMUS TUMOR

The glomus tumor is a rare neoplasm of the skin occurring in the extremities, chiefly on the hands and feet and often in the nail bed. The t u m o r originates f r o m the glomus coecygeum, or neuromyoarterial glomus, a normal complex end organ of the neurovascu]ar annexes which has something to do with the regulation of b]ood flow to the extremities. The t u m o r is composed of a congeries of irregular, tortuous, cavernous blood vessels lined by cuboidal endothelial cells. A r o u n d some of the vessels is a layer of circular muscle fibers which seem to verge imperceptibly into a broad zone of epithelioid cells. These epithe]ioid cells are possibly of muscle origin. The connective tissue septa between the neighboring blood vessels contain innumerable fascieuli of amye]inie nerves. There m a y be other clinical evidences of disturbances or the sympathetic nervous system, such as increased warmth, moisture, and color of the skin. These vasomotor, thermal, and secretory changes associated with the t u m o r in the same extremity indicate the relationship of the s y m p a t h e t i c nervous system. This t u m o r is benign, usually single and a p p e a r s as a smooth, rounded, elevated, p u r p l e nodule simulating a small hemangioma or i n t r a d e r m a l neurofibroma. The most striking clinical feature is the extreme p a i n which is elicited by the slightest amount of pressure on this tumor. No n o r m a l p a r t s of the body, no i n f l a m m a t o r y lesion can approach the exquisite sensitivity of this tumor. The p a i n m a y so incapacitate the p a t i e n t t h a t the extremities cannot be f u l l y used and a t r o p h y m a y occur.

Although occurring chiefly in adults, we had one patient, a child of 6 years, who had three glomus tumors situated in the skin of the forearm.

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Treatment consists of simple surgical excision under local anesthesia. Glomus tumors are radioresistant. TUMORS OF S Y N O V I A L MEMBRANE A N D T E N D O N S H E A T H S

a. Benign Giant-Cell Tumor or Xanthoma of Tendon Sheath.--These t u m o r s are u s u a l l y multiple and occur in t h e t e n d o n sheaths and aponeuroses of hands and feet. Although trauma may be an inciting factor, an underlying constitutional basis is probably even more ira-

Fig. 1 8 . - - C a s e 24. M a l i g n a n t s y n o v i o m a . J. C., a 9 - m o n t h - o l d boy, w a s b r o u g h t to the Memorial ]:iospital in April, 1931, for treatment of a recurrent tumor of the prepatellar bursa, which had been excised at another hospital in September, 1930. On April 22, 1931, the recurrent tumor was widely dissected by Dr. Frank E. Adair; the tumor had invaded the joint at the outer anterior angle. The knee joint became infected and wound erysipelas later developed. The child recovered uneventfully from this, e x c e p t ' f o r s l i g h t s h o r t e n i n g of t h e leg. T h e e x c i s e d t u m o r w a s s t u d i e d b y Dr. E w i n g ' w h o r e p o r t e d it a s m e s o t h e l i o m a a r i s i n g in s y n o v i a l s t r u c t u r e s ; cellular, t e l a n g i e c t a t i e , m a l i g n a n t a n d c a p a b l e of pulmonary metastases. A t t h e p r e s e n t t i m e t h e child is well, a n d t h e r e is no e v i d e n c e of r e c m ' r e n e e e i g h t year's following the last operation.

portant. This is particularly true in the case of their rare occurrence in children, as they usually deve]op in middle-aged adults. They may occur in children who have a lipoid diathesis, which can be determined by estimation of the elevated eholesterol esters and total lipoids in the blood. These encapsulated tumors are firm, yellowish, and lobulated and are easily enucleated at operation. Their structure is composed of spindle cells surrounded by dense connective tissue, large foam cells--so-called

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xanthoma cells--which contain lipoid material, and giant cells of the foreign body type. They should be treated by surgical excision rather than b y irradiation. b. Malignant Synovioma.--The malignant synovioma or endothelioma may arise in tendon sheaths, bursae, or joint membranes. There is h'equently a history of trauma. These tumors are quite difficult to distinguish from inflammatory lesions, as they m a y grow diffusely and are often accompanied by pain, swelling, and increased local heat. The solid synovioma, even when lobulated and technically easy to dissect, usually recurs and may metastasize early. The papillary synoviomas are of lower grade malignancy, and some cures can be obtained by careful local excision (Fig. 18). The synoviomas as a whole are resistant to radiation. Amputation is often necessary. Conservative surgical treatment of these tumors has a bad reputation, generally because the first operation is often an exploratory procedure, associated with incomplete remova], due to the failure to recognize the true nature of the disease prior to operation.

F i g . 1 9 . - - C a s e 26. C o n g e n i t a l s a c r o c o c c y g e a l t e r a t o i d t u m o r . A. A., a 1 - m o n t h - o l d b a b y b o y , w a s r e f e r r e d to t h e ~ I e m o r i a l H o s p i t a l o n A p r i l 13, 1938, f o r t r e a t m e n t of a teratoid tumor occurring in the sacrococcygeal region. This tumor was present at b i r t h a n d h a d i n c r e a s e d in s i z e , a c c o r d i n g t o t h e c h i l d ' s g e n e r a l g r o w t h . The mother states that at birth there was a small but definitely rudimentary umbilical cord aztached to the mass, This appendage s l o u g h e d oR" l e a v i n g " a s m a l l u l c e r a t e d area, which was slowly healing. The size of the mass may be seen in the illustration. When the child swallows, there is contraction of the soft lobulated tissues beneath the skin. There is no evidence o f c o n t i n u i t y o f t h e t i s s u e s w i t h i n t h e m a s s to t h e r e c t u m o r b o w e l ; r o e n t g e n o g r a m s show no evidence of gas in the tumor. X-ray studies of the bones of the lumbar spine and pelvis, reveal no defect in the sacrum and no evidence of spina bifida. There has been no indication for immediate surgical removal. This operation has been postponed until the child is older and in better condition to tolerate the procedure. The tumor is believed to be a emnplex tridermal teratoid tumor. (Since this article was written this tumor has been successfully excised. It contained intestine, urinary bladder, adrenal gland, bone, cartilage, and brain tissue.)

GRANULATION CELL SARCOMA Granulation cell sarcoma is what the name implies, an acute wound sarcoma made up of neoplastic granulation tissue. The greater incidence of these tumors in childhood and infancy is probably related to the exuberance of the healing process in youthful subjects. The benign

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analogue of this tumor is the common pyogenic granu]oma. The granulation cell sarcoma may develop in an open wound where the continuity of the skin is interrupted, even though it may be merely a puncture. Or the granulation cell sarcoma may develop in a subcutaneoas wound,

bruise or deeper injury, even though the overlying skin is intact. Hence the tumor may be readily visible or concealed in its incipiency. The mechanism of production of these malignant tumors is probably similar to that which obtains for the pyogenic granuloma. New fibro~ blasts and endothelial buds grow in profusion across the wound defect, at a rate much faster than the epide~nis, with a resultant excess of granulations, or so-called proud flesh. The tendency for excess growth is greater when restricted by overlying tissues, for example, the frequency of pyogenic granulomas springing from the nail bed, or along the nail sulcus. The transitional phases from infectious granuloma to malignant granulation cell sarcoma are not well known. In the concealed origin of a granulation cell sarcoma in a deep hematoma, the proeess is again a peculiar transformation of reparative healing to true neoplasia. Under these conditions, infection plays no part in stimulating cell growth, such as it possibly does in the open wound variety. These deep hematomas presumably call forth or excite the proliferation of fibroblasts and endothelium in an attempt to organize the blood clots. When this organization is rapid and occurs under pressure--espeeially where the hematoma is beneath the fascia--the response exceeds the need for repair, and a true sarcoma results. The open granulation cell sarcomas resemble the infectious granulomas in appearance. They are red, friable, soft, extremely vascular tumors which may be the source of alarming hemorrhages from insignificant injuries. The deeper or concealed tumors, covered by intact skin, are probably never diagnosed correctly in their early stages. They are of soft, spongy structure, and the overlying skin may exhibit the late color changes of a bruise. On palpation, a sensation of fluctuation may be elicited. The diagnosis is usually unresolved hematoma. Treatment.--Most granulation cell sarcomas have been euretted before the true diagnosis is established (Case 25). Recurrence after such a procedure is rapid and inevitable. Wide surgical excision conceivably might be curative, but has not been successful in our limited experience. The deep or hidden granulation cell sarcomas are incised on suspicion of being hematomas, but the surgeon recognizes the euretted tissues to be a peculiar, friable, vascular tumor. The treatment of choice is radiation therapy, either by high or low voltage roentgen rays, depending on the depth and degree of infiltration of the tumor; or by the application of radium plaques or trays at relatively short radium-skin distances. It is seldom necessary to insert interstitial radon for supplementary irradiation. The granulation cell sarcoma is very radiosensitive, approaching the lymphosareoma in its rapidity of response. The degree of infection of the tumor handicaps the effort toward complete sterilization, but this

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can be accomplished by well-plamled radiation therapy. The deep granulation cell sarcomas may metastasize widely to subcutaneous tissues, pericranium, ]ymph nodes, lungs, liver, and bone. CASE 25.--Granulation cell sarcoma. D. A , a girl 21/2 years of age, was referred to the Memorial Hospital on April 19, ]936. Five months previously she fell and injured her temple. This injury left a large deep hematoma, which underwent the color changes of a bruise and slowly regressed by absorption. As p a r t of it remained a f t e r four months, the family physician incised and euretted the lesion under the impression that it was a hematoma. The granular tissue removad was suggestive of a true neoplasm and on nficroseopie study proved to be a granulation cell sarcoma. A t the lViemovial Hospital, lhe temple was treated by fractionated doses of high voltage roentgen rays with complete clinical regression. Six months later, however, the tumor recurred in several re~ons, such as the postauricular lymph nodes, the cheek, and the eyelid. These tumors were phenomenally radiosensitive, disappearing a f t e r t h e administration of a small dose of roentgen rays. New tumors rapidly appeared in the scalp and subcutaneous tissues of the head, neck and trunk. I n July, 1937, there was evidence of mediastinal enlargement. ~ l r t h e r radiation therapy was given and palliation continued until January, 1938~ at which time death occurred from generalized sareomatosis. The diagnosis was confirmed at autopsy, which revealed metastases to the righ~ cervical nodes, mediastinal lymph nodes, retroperitoneal and paravertebral lymph nodes as well as to the ribs.

EEFERENOES 1. Adah', F. E.: S. Clin. North America 12: 357, 1932. 2. Adair, F. E., Pack, G. T., and Farrior, J . H . : Am. J. Cancer 16: 1104, 1932. 3. Alfaro, G. A., and Santas, M . A . : Arch. de m~d..d, enf. 8: 602, 1905. (Abst.) Zentralbl. f. Chit. 33: 87, 1906. 4. Bick, E. M.: Ann. Surg. 99: 949, 1934. 5. Bick, E . M . " Ann. Surg. 101: 759~ 1935. 6. Brooks, B., and Lehman, E. P.: Surg. Gynec. & Obst. 38: 587, 1924. 7. Copeland, M. M., Craver, L. F., and Reese, A . B . : Arch. Surg. 29: 108, ]934. 8. Cutler, E. C., and Gross, R.. E.: Arch. Surg. 33: 733, ]936. 9. De ]3ruin, J . : Nederh tijdschr, v. geneesk. 57, 2B: 2443, 1921. 10. Ew~ng, J.." Neoplastic Diseases, ed. 3, Philadelphia, 1928, W. B. Sauaders Company. ]1. Ewing, J . : Arch. Surg. 31: 507, 1935. 12. French, R . W . : New England J. Med. 206: 393, 1932. 13. Geschiekter, C. F.: Am. J. Cancer 22: 378, 1934. 14. Geschickter, C. F., and Lewis, D.: Am. J. Cancer 25: 630, 1935. 15. Heeker, P. G.: Zentralbl. f. Chir. 55: 842, 1928. 16. Hill, O. W., Smith, J. T., and Monger, R. H.: Arch. Pediat. 48: 335, 1931 17. Iwamoto, M.: Mitt. ii. allg. Path. u. path. Anat. 4: 207, 1928. 18. Kaplan, I. I., and R~benfeld, S.: Am. J. Roentgenol. 37: 53, 1937. 19, Krause, F.: Sammlung I~lin. Vortr. no. 293; chir. no. 91~ 1887. 20. MSnckeberg, J. G.: Erg. Allg. Path. Jahrg. 10: 752, 1904-05. 21. NystrSm, G.: Upsala l~keref, forh. (Art. xix) 38: 1, 1932. 22. Pack, G. T., and Lefevre, R . G . : J. Cancer Research 14: 167, 1930. 23. Pack, G. T.: Surgery 5: 1, 1939. 24. Pelle~cier, V . C . : Am. J. Cancer (supp.) 15: 2418, 1931. 25. Quick, D., arLd Cutler, M.: Ann. Surg. 86: 810, 1927. 26. Robertson, 5I. E.: J. Med. Research 35: 13]~ 1926-17. 27. Rowe]l, I-I.: Interstate M. J. 23: 577, 1916. 28. SeMossman, E.: F r a n k f u r t e r Ztschr. f. Path. 25: 486, 1921. 29. Sehoenecke, tI.: Deutsche Ztschr. f. Chir. 189: 420, ]924-25. 30. Schreiner, B., and Wehr, W . H . : Am. J. Roentgeno]. 32: 516, 1934. 31. Simmons, C . C . : Am. ft. Cancer 25: 621, 1935. 32. Singleton , A. O., and Hyde, W . A . : Texas State J. Med. 26: 778, 1931. 33, S_tewart, F . W . , and Copeland, M . M . : Am. J. Cancer 15: 1235, 1931.