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Echinococcus Cyst of the Orbit in a Chinese
AMERICAN JOURNAL OF OPHTHALMOLOGY Vol. 10
OCTOBER, 1927
No. 10
ECHINOCOCCUS CYST OF T H E ORBIT IN A CHINESE. HARVEY J . HOWARD,
M . D .
Echinococcus disease has rarely been reported in China. Altho twelve cases have been observed at the Peking Union Medical College Hospital, this is the only case involving the orbit, which was exenterated. A full pathologic report is given, and the points from which a diagnosis may be made.
China has often been referred to as a land of children; no inatter where travellers go, children are seen every where. On similar evidence China might be called a land of dogs. There are no trustworthy population statis tics in China, but the nuinber of chil dren under the age of eighteen may roughly be estimated at one hundred and seventy millions. There are also no statistics regarding dogs, but their number is probably not less than the number of children. From the writer's own observations he would estimate that about every third Chinese family has one dog, another third two or three, and the last third six to a dozen. Furthermore, every village and city harbors many homeless dogs, from the favorite chow to his mongrel cousin. In Mongolia and that part of North China adjacent to Mongolia, sheep are raised extensively. The combination of dogs and sheep in certain parts of the world is sufficient to make the inci dence of echinococcus, or hydatid cyst, among humans not uncommon. The primary or definitive hosts of Taenia echinococcus are chiefly dogs, jackals and wolves, i.e., the adult forms of these small tapeworms are found in the small intestines of these animals, of which the dog is the optimum host. The larval or intermediate hosts in clude man, cattle, hogs, and sheep, the latter being the optimum host. Human infestation occurs thru close associa tion with infected dogs. This is brought about chiefly thru the drinicing of water and the eating of raw vegetables, which have been con
taminated by dust containing ova of this cestode from dogs' feces. Human infestation also occurs thru dogs lick ing the hands, faces, and dishes of hu mans. Sheep and cattle become infest ed chiefly by eating grass and drinking water containing the ova. The raw offal of infested sheep and cattle con tains echinococcus cysts. Dogs eat the infested oflfal of slaughtered animals, and become infected, developing in time the adult worms. Thus the cycle is completed, and repeated ad infini tum. The conditions in northernmost China and in Mongolia would seem to favor a widespread incidence of the disease in those localities. However, a careful search of the literature fails to reveal more than one reference to the existence of the disease among Chi nese. Moreover, this single reference is merely a brief quotation from a hos pital report by Peake^ of Tientsin, who simply mentioned an operation he had performed upon a Chinese in 1 9 1 7 for hydatid cyst of the liver. But the lack of references in the literature cannot be accepted as an indication of the non existence, or practical nonexistence, of hydatid disease in China. In view of the low status of modern medicine in China and Mongolia as a whole, it means nothing. The regions from which the hospital of the Peking Union Medical College draws its patients are not noted for sheep raising. If, therefore, it can be shown that this hospital occasionally adrnits a case of echinococcus (or hy datid) cyst from the environs of Pe-
H A K V E Y J. H O W A R D
728
king, it m e a n s n o t o n l y that the disease exists in China but a l s o that o n e m i g h t find the disease n o t u n c o m m o n in the sheep raising c o u n t r y farther north. C o n c e r n i n g these points the e v i d e n c e is herewith p r o d u c e d : T h e hospital r e c o r d s o f the P e k i n g U n i o n M e d i c a l C o l l e g e s h o w that dur i n g the d e c a d e , 1916-1926, t w e l v e c a s e s of echinococcus cyst were admitted to the w a r d s , a n d definitely d i a g n o s e d , either b y o p e r a t i o n , p a t h o l o g i c find ing, o r o n sufficient clinical e v i d e n c e . It is quite p r o b a b l e that other c a s e s of e c h i n o c o c c u s c a m e o n l y to the o u t patient department, and either w e r e not d i a g n o s e d or refused t o enter the hospital for confirmation of s u s p e c t e d e c h i n o c o c c u s disease and treatment. In T a b l e I the data pertaining to the t w e l v e cases are g i v e n . In eleven of t h e m the liver w a s i n v o l v e d ; in t w o of t h o s e in w h i c h the liver w a s i n v o l v e d the spleen and a b d o m i n a l c a v i t y re s p e c t i v e l y w e r e also i n v o l v e d . In o n e case o n l y the orbit w a s i n v o h e d . It is
this c a s e w i t h w h i c h this p a p e r is chief ly c o n c e r n e d . CASE REPORTS
History: A Chinese farmer, W e i C h u n g Ju, a g e d 42, w a s a d m i t t e d t o the h o s p i t a l o f the P e k i n g U n i o n M e d i cal C o l l e g e o n M a y 11, 1923, w i t h a large, u n s i g h t l y t u m o r p r o t r u d i n g f r o m his left orbit. T h e first s i g n o f the t u m o r w a s an e x o p h t h a l m o s w h i c h b e gan a b o u t three years before. T h e p r o trusion increased v e r y s l o w l y , b u t w a s not a s s o c i a t e d with i m p a i r m e n t of vi sion a n d pain until a b o u t three m o n t h s before c o m i n g to us, w h e n the t u m o r b e g a n t o g r o w rapidly and the v i s i o n of the e y e to diminish, until blindness ensued. H e had r e c e n t l y sufl^ered o c c a sionally from h e a d a c h e .
Examination:
The patient
was a
muscularly d e v e l o p e d , w e l l nourished man, w h o s e g e n e r a l physical e x a m i n a tion g a v e n e g a t i v e findings. T h e b l o o d W a s s e r m a n n w a s n e g a t i v e ; the urine was normal. The blood hemoglobin
T A B L E I. ECHINOCOCCUS PEKING
UNION
CYST CASES
MEDICAL
COLLEGE
HOSPITAL
I9I6-1926 (10 Years)
No.
Native Sex Age Occupation Province
5.0 7.0
No Yes
3
10.0
Yes
Liver
3
3.0
No
Chihli
Liver
VA
2.0
No
None
Ntone
Chihli
Orhit
3
3.0
Yes
no
Hooklets and daughter
Chihli
Liver & Spleen Liver
0.5
Yes
4000
1
2.0
Yes
2000
7
5.1
Yes
4O00
5 I 4.0 Yes Average Summary
1000
any hooklets Sterile cyst Scolices and daugh ter cysts Daughter cysts
Chihli Chihli
Liver Liver
Watch repairer Coolie
Chihli
Liver
Chihli
7.
Soldier
8.
Farmer
9.
Coal dealer Clerk
"6.
10. 11.
Housewife
12.
Soldier
Male 11 Females 1
36
Various
None 1900
None Many hooklets Booklets 700 Many daugh Yes ter^ cysts Fluid and 3000 debris NOne None
Liver Liver
5.
Pathologic Findings
No Yes
Chihli Chihli
2. 3. 4.
Fluid With drawn c.c.
8.3 6.0
Coolie Brass worker Cook Coolie
•1.
Percent age Eosino- Oper philia ation
Location Cyst
Chihli Mongolia Chihli
Liver Liver & abdominal cavity
2 2'Λ
Chihli 11 Liver 11 3.4 yrs Mongolia Spleen 1 1 (counted twice) Orbit 1
4.7%
67% 75%
•Diagnosis made on the high eosinophilia, percussion wave, rapid development o cachexia, etc. ••Complement fixation test for echmococcus cyst strongly positive.
S
'StS
75%
Final Result Not treated Improved Not treated Improved Improved Refused operation Refiised operation Died Improved Improved Improved Improved Not treated died cured (radical)
the mass, absence of
ECHINOCOOCUS
CTST OF
ORBIT
729
was 8 0 % ; w. b. c , 8,700; r. b. c , 4,630,000; the differential count show poly morphonuclears 69, small lymphocytes 19, large mononuclears 9, and eosinophiles 3. The right eye was myopic, with an uncorrected vision of 6/30; otherwise quite normal. A large mass completely filled the left orbit and protruded forward for a distance of 5 cm. from the external margin of the orbit. The tumor, which measured 7 cm. horizontally by 6.5 cm.
cm. temporally, 1.5 cm. upward, and 4 cm. forward from its normal position. The horizontal width of the palpebral fissure was 5 cm. and the distance be tween the widely separated lid margins was 3.7 cm. The exposed conjunctiva was red, swollen, and ulcerated, and covered with a small amount of puru lent exudate mixed with a little bloody serum, which oozed from several patches of granulation tissue. The cornea showed general opacification and pannus. When the upper lid was
Fig. 1. Male, aged 42, .showing side view of echinococciis cyst of left ortiit, of three years duration.
Fig. 2.
vertically, could not be moved about in the orbital cavity. A fluctuating thrill was elicited by palpation, which, in ad dition to the tension and the resilience of the mass, gave the impression that there was fluid within the tumor under considerable pressure. The upper lid was tightly stretched horizontally and entirely covered the cornea and bulbar conjunctiva, while the lower lid was completely everted and pulled back ward beneath the tumor, leaving the entire lower palpebral conjunctiva ex posed and markedly stretched. The tumor had evidently grown chiefly from behind and below the eyeball, which had been pushed wholly out of the orbit. The globe was displaced 3
Front view upper lid, elevated to reveal po sition of eyeball.
elevated the eye was found to have faint light perception. (See Figs. 1 and 2.) Three possible causes of the tumor occurred to us, namely, a tear cyst, a meningocele, and a mucus retention cyst. The dislocation of the eyeball upward and outward made it seem most unlikely that the cystic fluid came from the lacrimal gland. An x-ray ex amination of the orbit revealed no bony changes. This negative finding com bined with the lack of pulsation, and the fact that the eye was displaced up ward rather than downward, was strong evidence against the existence of a meningeal fluid tumor. A reten tion cyst seemed just as unlikely. W e
730
H A R V E Y J. H O W A R D
therefore decided to aspirate some of the fluid for diagnostic purposes. The needle was inserted above and to the nasal side of the displaced eye ball, and directed downwards and back wards. There was only slight resist ance to the entrance of the needle, but a clear, watery fluid began to push the glass piston out with considerable force almost as soon as the needle had pene trated the skin. The size of the mass decreased steadily as the fluid, up to a total of 85 c . c , was withdrawn (see Fig. 3 ) . The last few c.c. contained some flocculi and were slightly cloud ed. The odor of the fluid was not un like that of placenta. The patient was watched carefully during the aspira tion of the fluid, but he developed no headache, vertigo, or nausea — symp toms which he certainly would have had if the fluid had been intracranial in origin. Sixteen hours later the tu mor was restored to its original size and tension. A pressure bandage was then applied, which had the effect of appreciably reducing the mass both in size and tension by the following morning. Part of the fluid was sent to the laboratory of biochemistry. The fol lowing report, submitted by Dr. Hsien Wu, includes comparative analyses for cerebrospinal fluid and tears: The cystic fluid Cerebro(per 100 spinal parts) fluid Tears NaCl 0.37 0.60-0.70 1.3 Glucose 0.03 0.04-0.09 Nitrogen 0.055 0.02-0.07 From its chemical analysis the cys tic fluid was analogous to cerebrospinal fluid, but in view of the total lack of subjective symptoms following the sudden and complete withdrawal of fluid, the cyst certainly could not be diagnosed as a meningocele. A micro scopic examination of the sediment of the fluid was then made, and a large number of echinococcus booklets and scolices were found. The tumor, there fore, was an echinococcus cyst of the orbit. Since echinococcus cysts had occa sionally been found in the liver and
the lungs of Chinese patients, careful manual and x-ray examinations were made of the patient's abdomen and chest, but no cysts were demonstrated in those parts. In view of the size and duration of the cyst, the apparent dis integration of much of the retrobulbar structures, and the almost complete loss of vision of the eye involved, total exenteration of the orbit was deemed the only feasible form of treatment. This operation was performed by the writer on May 21, 1923, in the follow ing manner: About 30 c.c. of amber colored fluid were first aspirated from the cyst, in order to facilitate its removal. The external commissure was then split back to the bony orbital margin, and the internal commissure to the lacrimal bone. Incisions (extending from the inner to the outer canthus) were made thru the skin of both upper and lower lids, about 2 mm. from the lid margins. The skin of both lids was then dissect ed back to the bony margin of the orbit; and the entire tumor, together with the eyeball, the lid margins with the eyelashes, and the extraocular muscles including the levator, was sep arated by blunt dissection and removed from the orbit. Care was taken not to injure the periobita. After bleed ing had been controlled, and all frag ments of loose tissue removed, the edges of the greatly stretched skin of the lids were approximated with sev eral fine silk sutures. Fortunately the amount of skin was sufficient to cover the denuded area, with the exception of about a square centimeter at the apex of the orbit. The orbit was care fully packed with gauze in order to hold the skin into apposition with the bone, and a moderate pressure band age was applied. The dressings were changed daily. For the first few days the dressings were soaked with a serosanguinous fluid. A little of the skin became ne crotic and sloughed off. but applica tions of mercurochrome stimulated the growth of granulation tissue as a base for epithelial extension. Five weeks after the operation, the orbit was cov ered completely with healthy skin (see
ECHINOCOCCUS CYST OF ORBIT
Fig. 4 ) . The patient was then dis charged, and has not been heard from since. PATHOLOGIC REPORT.
Gross
examination:
The
specimen
is an oval shaped mass, which includes an eyeball, the eyelash margins of both lids, and all the tissues of one orbit. Weight, 87.5 gms. (30 c c . of fluid were withdrawn just prior to removal of the tumor). Length, 7.0 cm.; width, 5.0 cm.; height, 5.5 cm.
731
which more than half filled the cham ber. The main specimen was cut into from its superior surface, in a frontal plane lying about an inch behind the eyeball. A large cystic space, with a wall averaging about 0.5 cm. thick, was thereby exposed. About 10 c c of straw colored fluid with some flocculent sediment were removed from this cys tic space. A segment of the upper wall of the cyst was removed, exposing a cavity about 4 cm. in diameter. With-
Fig. 3. Front view immediately after aspiration of 85 c c . of echinococcus fluid.
Fig. 4. Final result following exenteration of orbit.
The specimen was hardened in Miiller's fluid and subsequently trans ferred to 80 per cent alcohol. The up per eyelid was split vertically in the median line, and the two parts were re tracted in order to expose the eyeball behind, which was found solidly im bedded in a mass of tissue. The eye ball was bisected equatorially, and the anterior segment was removed, leaving the posterior part in situ. The anterior segment was cut sagittally into two un equal parts; the smaller part to be pr'^pared for paraffin sectioning, the larger for celloidin. A small amount of strawcolored fluid escaped from the vitreous chamber, but there remained behind a dark amber colored vitreous body.
in this cavity an irregularly globular mass, about 2.5 cm. in diameter, was found. This mass was easily removed. Upon being bisected, it was found to be a shriveled unilocular cyst with a well marked capsule (see Fig. 5 ) . The cyst contained a greenish yellow co agulum of waxy appearance and stiff jelly like consistency. Attached to the inner margin of the capsule at several places were quite a number of small, light brown nodules which looked like hydatid sand. The character and ap pearance of this irregular mass gave the impression that at one time it had been a cyst which had completely filled the large cavity of the tumor. Due to the withdrawal of the fluid and the
732
H A R V E Y J. H O W A R D
process of hardening, the cyst appar ently collapsed, and its capsule became separated from the wall of the outer cavity. A small piece of this contract ed cyst was removed for sectioning; also two pieces were taken from the outer wall of the large cavity behind the eyeball. The anterior border of the large cav ity extended to within about 1.5 cm. of the eyeball which lay above and in front of it. The whole mass was di vided into two parts by cutting in a
unilocular cyst with a double chitinous wall. The outer membrane, or ectocyst, is somewhat laminated, while the inner membrane, or endocyst, is prac tically homogeneous in structure. The tiny nodules which looked macroscopically like hydatid sand, are n o w re vealed as irregular rows of daughter cysts of echinococcus, some attached and others adjacent to the endocyst, These daughter cysts appear to be in various stages of degeneration and dis integration. Several contain either a
Fig. 5. The collapsed and shrivelled echinococcus cyst, after its removal from the mass of orbital tissues.
vertical plane about 1 cm. behind the eyeball and parallel to its equator, in order to expose the relation of the re trobulbar and orbital structures. The internal rectus, inferior rectus and su perior oblique muscles were missing. The superior and external recti mus cles were plainly visible, but both were imbedded in dense tissue, and pushed nearly to the periphery of the mass. The optic nerve was also plainly vis ible, but was displaced upward from its normal position, lying only 1.5 mm. below the superior rectus muscle. A piece of tissue, including the optic nerve and the superior rectus muscle, was removed for sectioning. Microscopic examinaiton: a. Small section of the cyst itself: The specimen consists chiefly of a narrow pouch of a
complete or a nearly complete scolex, but most of them have, within their limiting membrane, cjuite a number of isolated echinococcus hooklets, some debris, and a few small, densely black, round bodies, which suggest pyknotic nuclei. Some of the daughter cysts have, attached to their inner walls, sev eral granddaughter cysts and degener ated remnants of such cysts (see Plate 3, Figs. 6 and 7 ) . In addition to the daughter cysts, some attached to the endocyst and some unattached, the pouch of the mother cyst contains a coarsely meshed network of substance somewhat simi lar in constituency to the endocyst. Within the network there are seen a faintly pink stained coagulum, numbers of free hooklets, debris and cystic rem-
ECHDÍOCtXXJUS
nants in v a r i o u s stages o f disintegra tion. In eacii s e c t i o n are a l s o f o u n d a n u m b e r of r o u n d l i m e cells, o r calcare ous bodies, which vary from 20 to 30 u in diameter. In size they c o m p a r e . w i t h the g r a n d d a u g h t e r c y s t s . T h e s e b o d ies are c o m p o s e d chiefly o f c o n c e n t r i c ally arranged c a l c a r e o u s s u b s t a n c e . It m a y b e inferred from their size and shape that t h e y represent a stage in the d e g e n e r a t i o n o f s o m e o f the g r a n d d a u g h t e r c y s t s , or at least of rudimen tary skeletons o f s o m e sort. Scattered within the m e s h w o r k are m a n y small l y m p h o c y t e s and e o s i n o p h i l e s . S o m e of the .daughter c y s t s are a l m o s t sur rounded b y a zone of mononuclear eosinophiles, w h i c h also are seen in clusters a l o n g the e n d o c y s t in relative ly large numbers (see Plate 3, Figs. 8 and 9 ) . b . Small s p e c i m e n taken from the tissue l y i n g b e t w e e n the eyeball and the c y s t c a v i t y w i t h a bit o f the upper l i d : T h e principal structure of the s p e c i m e n is c o n n e c t i v e tissues, s h o w i n g c o n s i d e r a b l e proliferation of y o u n g fibroblasts w i t h o u t a n y regular ar r a n g e m e n t . A d j o i n i n g o n e margin o f the s p e c i m e n there is a c r o s s section of a m u s c l e ( s u p e r i o r r e c t u s ) , with a r e m n a n t o f T e n o n ' s capsule c l o s e b y ; also a c r o s s s e c t i o n o f the o p t i c nerve. T h e optic nerve fibers are partially atro phic and widely separated by edema. A small number o f eosinophiles are seen around the central vessels o f the nerve and also in the fibers pf the septa separ ating the nerve bundles. T h e orbital tis sue surrounding the nerve is infiltrated with numerous lymphocytes and eosino philes. T h e connective tissue stroma c o n tains a few vessels which are located chiefly near the muscle. T h e r e is no defi nite demarcation between connective tis sue arid muscle, a condition due chiefly to an infiltration o f the connective tissue with many small lymphocytes, epithelioid cells, plasma cells and a f e w eosinophiles. This infiltration is m o r e marked around the vessels. T h e walls o f both veins and arteries are so much proliferated that the lumina o f some o f them are entirely obliterated. H e r e and there in the sub stance o f the muscle, as well as in the adjacent connective tissue, there are
CYST
OP
ORBIT
733
many vacuoles which are separated by a very delicate, homogeneous membrane. Several l a r g e m o n o n u c l e a r s and m a s t cells are visible in all sections. c. T h e anterior segment o f the eyeball: T h e layers o f corneal epithelium are in creased in number, and the cells are more horny than normal. T h e i r nuclei are only faintly stained. S o m e o f the epithelial cells are vacuolated. Peripher ally, for a width o f 1 to 3 mm.. B o w man's membrane has disappeared, and is replaced by a dense pannus—blood vesse s and fibroblasts. T h e superficial onesixth to one-fourth o f the substantia pro pria is infiltrated with lymphocytes and plasma cells, among which are seen a small number o f epithelioid cells and eosinophiles. T h e infiltration increases in density toward the periphery o f the cornea, and appears to be an extension of even a denser infiltration that exists in the scleral tissue. D e s c e m e t ' s m e m brane and the endothelial cell layer are normal. T h e conjunctival epithelium covering the episcleral tissue shows exposure kera tosis—formation o f keratin and vacuo lization o f cells. A large number o f plas ma cells and eosinophiles infiltrate the subepithelial layers. T h e scleral stroma in general is loose and shows evidence o f edematous separation and atrophy o f some o f its connective tissue fibers. There is a general infiltration involving the outer third o f the sclera; near the limbus this infiltration involves the outer t w o thirds. T h e infiltration is composed chiefly o f small lymphocytes and plasma cells, with some eosinophiles and epithe lioid cells. T h e arteries and veins, which are numerous in the region o f the limbus, are distended with blood and surrounded by a dense zone o f chronic inflammatory cells, among which eosinophiles greatly predominate. T h e ciliary nerves passing thru the sclera are partially atrophic. T h e location o f the tendinous attachments o f the extraocular muscles cannot deflnitely be determined, owing to the dense cellu lar infiltration and the probable disin tegration o f the tendinous structures. In the region o f the equator o f the globe there are a number o f vacuoles arranged in irregular r o w s in the loose stroma o f the outer half o f the sclera. These spaces
734
H A R V E Y J. H O W A R D
are larger than those that would be pro duced by fat globules, and have very thin walls or limiting membranes of homo geneous material. The suprachoroidal space is filled with coagulum, which sep arates the sclera and the choroid for a distance of nearly a centimeter backward from the anterior end of the choroid. The anterior chamber is somewhat shallower than normal and the filtration angle is slightly closed by the root of the iris. A number of chromatophores (probably from the iris) are enmeshed in the structure of the pectinate ligament. The iris and ciliary body are practically normal with the exception of the pres ence of a few eosinophiles. The lens is normal. d. A piece of the posterior segment of the eye not including the optic nerve: The retinal nuclei take the stain poorly, which probably means beginning degen eration of the retina, which is completely detached (possibly an artefact). The choroid is practically normal with the exception that the vessels, large and small, are engorged with blood. Sclera the same as in " c . " e. The cystic fluid. A few scolices of echinococcus, numerous free booklets and debris.
Primary Diagnosis: Echinococcus cyst of the orbit. Secondary Diagnoses: Exposure con junctivitis; pannus, superficial and deep keratitis and scleritis; maculae of the cor nea; chronic inflammation of the extra ocular muscles; endarteritis and endophlebitis of the orbital vessels; partial atrophy of the ciliary nerves; chronic retrobulbar neuritis with partial atrophy of the optic nerve; local eosinophilia. The object of this rather "extensive pathologic report is to put on record a fairly complete account of the first case of echinococcus cyst of the orbit reported from China. It should be noted that no vestige of echinococcus was found with in the eyeball, altho some of the ocular structures were chronically inflamed, due, no doubt, to the toxins absorbed from the cystic fluid in the adjacent tissues. There is no doubt also that there was some pathologic effect upon the eye an^ its function, due to the steadily increas ing pressure on the globe from behind.
The intraocular structures ihowed signs of this pressure by a beginning atrophy, whereas the denser protective membranes of the eye were affected chiefly by the toxins. Anyone who has seen a case of echin ococcus cyst of the orbit and failed at first to recognize it is not likely to fail again in making an almost immediate diagnosis. A combination of two or three, or of all of the following clinical signs and diag nostic aids would certainly establish a differential diagnosis: 1. The length and character of the his tory: The combination of sheep and dogs with which a patient has been more or less in contact, in addition to personal habits of uncleanliness, should make one suspicious of echinococcus disease. The duration of fully three years in the de velopment of the cyst as reported in this paper would, generally speaking, be too short for a meningocele, and too long for a tear cyst or a mucus retention cyst. But it could not be differentiated from a malignant tumor on such evidence. 2. The nature of the displacement of the globe: Marked exophthalmos, natu rally, always exists. A number of writ ers state that the eyeballs in their cases were dislocated upward, forward, and in ward. In this case the displacement was forward, upward, and outward. In either case a meningocele and a lacrimal cyst would be ruled out. 3. Palpation: The sense of touch should let one know at once that he is not deaUng with a solid tumor. Fluctua tion, fremitus, and resilience of the mass can easily be elicited if the cyst has at tained considerable size. 4. X-ray: The x-ray should rule out any bony changes that one would expect to see in a meningocele, or a malignant tumor with erosion of the walls of the accessory sinuses. Some writers state that the shadow produced on the plate by cystic fluid is denser than that produced by a solid tumor; this seems hard to be lieve. 5. Urticaria: A history of one or more recent attacks of urticaria should make one suspicious of echinococcus. The steadily increasing pressure from time to time sometimes causes a slight rupture of the surrounding tissues and conse-
ECHINOCOCCUS CYST OF ORBIT
quently of the cystic capsule, permitting the escape of echinococcus fluid which infiltrates the tissues and becomes quick ly absorbed. The absorption of toxins in the fluid, or of the foreign protein, produces a violent urticaria similar to the serum reaction which often follows injections of tetanus or diphtheria anti toxin. Urticaria has been reported as following exploratory puncture of an echinococcus cyst, when some of the re sidual fluid seeped into the surrounding tissues thru the wound. 6. A general eosinophilia: A count of more than 2 or 3 per cent of eosino philes should cause suspicion; yet among the twelve cases of echinococcus cyst of various organs treated at the hospital of the Peking Union Medical College, five showed no pathologic increase in the eosinophilic count, altho three of the five were later relieved of considerable ech inococcus fluid. In fact, the one with the lowest eosinophilic count had the most fluid removed. It is significant that out of the twelve, this is the only case that died. Possibly the low eosinophilia indicated a marked loss of resistance in his case. Furthermore, in these five cases it is possible that the cysts were in the stage of retrogression and were be coming sterile, a tendency which exists when the intracystic pressure becomes too high. In the case with the orbital involvement the eosinophilia was only 3 per cent. The average for the twelve cases was 4.7 per cent. Intestinal para sites of any variety will also produce a general eosinophilia, so their absence must first be determined" before any re liance favoring the diagnosis of echino coccus can be placed on the existence of an eosinophilia. The data concerning the possible infection of these twelve cases with intestinal parasites are not complete, so too much importance can not be i^aced on the eosinophilia in those cases in which it was high. 7. Exploratory puncture: A micro scopic examination of the aspirated fluid should estabfish a diagnosis, for the sedi ment nearly always contains booklets, scolices and debris of embryo cysts. A report that the fluid is sterile, as was the case in one of the twelve listed in Table I, may merely mean that none of the
735
sediment was removed with the fluid. T o avoid this possibility it is well to shake somewhat vigorously that part of the body containing the cyst just prior to aspiration of the fluid. It is stated that great danger of mixed infection is in volved in doing exploratory puncture of echinococcus cysts, so the surgeon should be prepared to operate for com plete removal of the cyst immediately after it has been determined by an ex amination of the fluid that he is dealing with echinococcus disease. 8. Complement fixation test: A posi tive test using the cystic fluid as the an tigen is recognized as establishing a diag nosis. Three of the twelve cases were tested by this method and all of them were strongly positive. ADDITIONAL
REMARKS:
One
would
naturally suppose that involvement of one organ of the body would mean the probable involvement of other organs, but this evidently is not so. According to Simon'', only one organ is involved as a rule. When multiple infestation exists, it is probably due to successive infesta tion from without, or possibly to a dis semination of the primary infestation from within, owing to a rupture of the cyst. But a successive infestation would be as much an accident as was the pri mary one; the individual already infested would probably have no more chance of being additionally infested than other persons associated with him would in be coming primarily infested. However, in a case of echinococcus disease with a history of urticaria, one might logically suspect involvement of other organs or parts of his body. Simon further states that human infestation occurs thru transference of the ova of the adult worms of Taenia echinococcus (gener ally from the dog) to the gastrointes tinal tract. Having gained access to the digestive tract, the ovum, or perhaps the oncosphere (larva), freed of its resisting envelope by the digestive juices, pene trates the intestinal wall, and, entering a blood vessel, is carried along in the blood stream until it lodges as an em bolus in some other part (generally an organ) of the body where it begins at once to develop a cyst. According to Barnett^ once a cyst
736
H A R V E Y J. H O W A R D
begins in a favorable locality, such as in the liver, it absorbs nourishment by imbibition from the surrounding tis sues and grows into a bladder like mass, which constitutes the echinococ cus or hydatid disease, the rate of growth varying according to the dens ity of the surrounding parts. If the nutrition be cut off, the cyst dies and undergoes degeneration; even calcifi cation may take place. Barnett refers to daughter cysts as embryo cysts which, on account of impaired vitality of the primary or mother cyst, have become detached from the parental wall and float loose in the fluid of the mother cyst. Tertiary or granddaugh ter cysts may be found free within the secondary or daughter cysts for the same reason. Great-grand-daughter cysts are also occasionally found. Im paired vitality of the primary cyst re sults from either lack of nutrition or an inability to expand further. In cysts of the liver and the brain there is practically no interference to expan.sion until vital parts are aflfected and the patient's death occurs. In the orbital case herein reported, the vitality of the mother cyst was ap parently impaired, since there were many daughter and grand-daughter cysts lying detached from their respec tive parental membranes. The prob able reason for this was the difficulty of further expansion of the cyst, lim ited as it was by the bony orbit later ally and behind, and by the eyeball, with its muscular and tendinous at tachments, in front. Its expansion was further hindered by its location within the muscle cone of the orbit. According to Wood*, a cyst in this position rather than outside the muscle cone, is exceedingly diflficult to be re
moved without first removing the globe. The large size of the cyst and extensive destruction of the orbital tis sues warranted total exenteration in this case. The ages of the patients reported in this paper, including the one orbital case, make one suspect that the cysts had been developing for many years. The average age was 36 years, the youngest 19, and the oldest 54. The duration of symptoms ranged from one to eight years, with an average of 3.4, but it is almost certain that infestation occurred long before that. Faust^ examined the gastrointes tinal tracts of about five hundred dogs in China for parasites. In only two dogs, both from near Peking, did he find Taenia echinococcus. He states that, to his knowledge, these are the first instances in which these cestodes have been found in dogs in eastern Asia. The evidence produced by this paper implies that a number of dogs in Peking and its environs are thus in fected and that they are the source of the larval infestation of man in this same area. Of the twelve cases herein reported, eleven, including the orbital case, were natives as well as residents of Chihli, the province in which Peking is located. All of these eleven cases were males. The one female case was a Chinese woman, age 19, who had lived all her life in Mongolia. If, as shown by this paper, the disease exists sporadically in North China where the conditions for its dissemination are not good, it would not be amiss to suggest that, in Mongolia where the conditions are as ideal for its dissemination, as they are in Australia or Iceland, echi nococcus cyst in man ought not to be uncommon.
REFERENCES 1. 2. 3. 4. 5.
Peake, E. C. Report of the London Mission Hospital, Tientsin, China, for 1917. China M. J., 1918, vol. X X X I I , p. 276. Simon, C. E. Clinical Diagnosis. Lea and Febiger, Phila., 1922 ed., p. 463. Barnett, L. E. Hydatid disease. Practice of Medicine in the Tropics, by Byam and Arch ibald, Oxford Univ. Press, N. Y . , 1923 ed., vol. I l l , p. 1832. Wood, D. J. Hydatid disease of the Orbit. Brit. J. Ophth., 1925, vol. I X , p. 4. Faust, E. C. Personal communication to the writer.
OCTOBER, 1927
No. 10
ECHINOCOCCUS CYST OF T H E ORBIT IN A CHINESE. HARVEY J . HOWARD,
M . D .
Echinococcus disease has rarely been reported in China. Altho twelve cases have been observed at the Peking Union Medical College Hospital, this is the only case involving the orbit, which was exenterated. A full pathologic report is given, and the points from which a diagnosis may be made.
China has often been referred to as a land of children; no inatter where travellers go, children are seen every where. On similar evidence China might be called a land of dogs. There are no trustworthy population statis tics in China, but the nuinber of chil dren under the age of eighteen may roughly be estimated at one hundred and seventy millions. There are also no statistics regarding dogs, but their number is probably not less than the number of children. From the writer's own observations he would estimate that about every third Chinese family has one dog, another third two or three, and the last third six to a dozen. Furthermore, every village and city harbors many homeless dogs, from the favorite chow to his mongrel cousin. In Mongolia and that part of North China adjacent to Mongolia, sheep are raised extensively. The combination of dogs and sheep in certain parts of the world is sufficient to make the inci dence of echinococcus, or hydatid cyst, among humans not uncommon. The primary or definitive hosts of Taenia echinococcus are chiefly dogs, jackals and wolves, i.e., the adult forms of these small tapeworms are found in the small intestines of these animals, of which the dog is the optimum host. The larval or intermediate hosts in clude man, cattle, hogs, and sheep, the latter being the optimum host. Human infestation occurs thru close associa tion with infected dogs. This is brought about chiefly thru the drinicing of water and the eating of raw vegetables, which have been con
taminated by dust containing ova of this cestode from dogs' feces. Human infestation also occurs thru dogs lick ing the hands, faces, and dishes of hu mans. Sheep and cattle become infest ed chiefly by eating grass and drinking water containing the ova. The raw offal of infested sheep and cattle con tains echinococcus cysts. Dogs eat the infested oflfal of slaughtered animals, and become infected, developing in time the adult worms. Thus the cycle is completed, and repeated ad infini tum. The conditions in northernmost China and in Mongolia would seem to favor a widespread incidence of the disease in those localities. However, a careful search of the literature fails to reveal more than one reference to the existence of the disease among Chi nese. Moreover, this single reference is merely a brief quotation from a hos pital report by Peake^ of Tientsin, who simply mentioned an operation he had performed upon a Chinese in 1 9 1 7 for hydatid cyst of the liver. But the lack of references in the literature cannot be accepted as an indication of the non existence, or practical nonexistence, of hydatid disease in China. In view of the low status of modern medicine in China and Mongolia as a whole, it means nothing. The regions from which the hospital of the Peking Union Medical College draws its patients are not noted for sheep raising. If, therefore, it can be shown that this hospital occasionally adrnits a case of echinococcus (or hy datid) cyst from the environs of Pe-
H A K V E Y J. H O W A R D
728
king, it m e a n s n o t o n l y that the disease exists in China but a l s o that o n e m i g h t find the disease n o t u n c o m m o n in the sheep raising c o u n t r y farther north. C o n c e r n i n g these points the e v i d e n c e is herewith p r o d u c e d : T h e hospital r e c o r d s o f the P e k i n g U n i o n M e d i c a l C o l l e g e s h o w that dur i n g the d e c a d e , 1916-1926, t w e l v e c a s e s of echinococcus cyst were admitted to the w a r d s , a n d definitely d i a g n o s e d , either b y o p e r a t i o n , p a t h o l o g i c find ing, o r o n sufficient clinical e v i d e n c e . It is quite p r o b a b l e that other c a s e s of e c h i n o c o c c u s c a m e o n l y to the o u t patient department, and either w e r e not d i a g n o s e d or refused t o enter the hospital for confirmation of s u s p e c t e d e c h i n o c o c c u s disease and treatment. In T a b l e I the data pertaining to the t w e l v e cases are g i v e n . In eleven of t h e m the liver w a s i n v o l v e d ; in t w o of t h o s e in w h i c h the liver w a s i n v o l v e d the spleen and a b d o m i n a l c a v i t y re s p e c t i v e l y w e r e also i n v o l v e d . In o n e case o n l y the orbit w a s i n v o h e d . It is
this c a s e w i t h w h i c h this p a p e r is chief ly c o n c e r n e d . CASE REPORTS
History: A Chinese farmer, W e i C h u n g Ju, a g e d 42, w a s a d m i t t e d t o the h o s p i t a l o f the P e k i n g U n i o n M e d i cal C o l l e g e o n M a y 11, 1923, w i t h a large, u n s i g h t l y t u m o r p r o t r u d i n g f r o m his left orbit. T h e first s i g n o f the t u m o r w a s an e x o p h t h a l m o s w h i c h b e gan a b o u t three years before. T h e p r o trusion increased v e r y s l o w l y , b u t w a s not a s s o c i a t e d with i m p a i r m e n t of vi sion a n d pain until a b o u t three m o n t h s before c o m i n g to us, w h e n the t u m o r b e g a n t o g r o w rapidly and the v i s i o n of the e y e to diminish, until blindness ensued. H e had r e c e n t l y sufl^ered o c c a sionally from h e a d a c h e .
Examination:
The patient
was a
muscularly d e v e l o p e d , w e l l nourished man, w h o s e g e n e r a l physical e x a m i n a tion g a v e n e g a t i v e findings. T h e b l o o d W a s s e r m a n n w a s n e g a t i v e ; the urine was normal. The blood hemoglobin
T A B L E I. ECHINOCOCCUS PEKING
UNION
CYST CASES
MEDICAL
COLLEGE
HOSPITAL
I9I6-1926 (10 Years)
No.
Native Sex Age Occupation Province
5.0 7.0
No Yes
3
10.0
Yes
Liver
3
3.0
No
Chihli
Liver
VA
2.0
No
None
Ntone
Chihli
Orhit
3
3.0
Yes
no
Hooklets and daughter
Chihli
Liver & Spleen Liver
0.5
Yes
4000
1
2.0
Yes
2000
7
5.1
Yes
4O00
5 I 4.0 Yes Average Summary
1000
any hooklets Sterile cyst Scolices and daugh ter cysts Daughter cysts
Chihli Chihli
Liver Liver
Watch repairer Coolie
Chihli
Liver
Chihli
7.
Soldier
8.
Farmer
9.
Coal dealer Clerk
"6.
10. 11.
Housewife
12.
Soldier
Male 11 Females 1
36
Various
None 1900
None Many hooklets Booklets 700 Many daugh Yes ter^ cysts Fluid and 3000 debris NOne None
Liver Liver
5.
Pathologic Findings
No Yes
Chihli Chihli
2. 3. 4.
Fluid With drawn c.c.
8.3 6.0
Coolie Brass worker Cook Coolie
•1.
Percent age Eosino- Oper philia ation
Location Cyst
Chihli Mongolia Chihli
Liver Liver & abdominal cavity
2 2'Λ
Chihli 11 Liver 11 3.4 yrs Mongolia Spleen 1 1 (counted twice) Orbit 1
4.7%
67% 75%
•Diagnosis made on the high eosinophilia, percussion wave, rapid development o cachexia, etc. ••Complement fixation test for echmococcus cyst strongly positive.
S
'StS
75%
Final Result Not treated Improved Not treated Improved Improved Refused operation Refiised operation Died Improved Improved Improved Improved Not treated died cured (radical)
the mass, absence of
ECHINOCOOCUS
CTST OF
ORBIT
729
was 8 0 % ; w. b. c , 8,700; r. b. c , 4,630,000; the differential count show poly morphonuclears 69, small lymphocytes 19, large mononuclears 9, and eosinophiles 3. The right eye was myopic, with an uncorrected vision of 6/30; otherwise quite normal. A large mass completely filled the left orbit and protruded forward for a distance of 5 cm. from the external margin of the orbit. The tumor, which measured 7 cm. horizontally by 6.5 cm.
cm. temporally, 1.5 cm. upward, and 4 cm. forward from its normal position. The horizontal width of the palpebral fissure was 5 cm. and the distance be tween the widely separated lid margins was 3.7 cm. The exposed conjunctiva was red, swollen, and ulcerated, and covered with a small amount of puru lent exudate mixed with a little bloody serum, which oozed from several patches of granulation tissue. The cornea showed general opacification and pannus. When the upper lid was
Fig. 1. Male, aged 42, .showing side view of echinococciis cyst of left ortiit, of three years duration.
Fig. 2.
vertically, could not be moved about in the orbital cavity. A fluctuating thrill was elicited by palpation, which, in ad dition to the tension and the resilience of the mass, gave the impression that there was fluid within the tumor under considerable pressure. The upper lid was tightly stretched horizontally and entirely covered the cornea and bulbar conjunctiva, while the lower lid was completely everted and pulled back ward beneath the tumor, leaving the entire lower palpebral conjunctiva ex posed and markedly stretched. The tumor had evidently grown chiefly from behind and below the eyeball, which had been pushed wholly out of the orbit. The globe was displaced 3
Front view upper lid, elevated to reveal po sition of eyeball.
elevated the eye was found to have faint light perception. (See Figs. 1 and 2.) Three possible causes of the tumor occurred to us, namely, a tear cyst, a meningocele, and a mucus retention cyst. The dislocation of the eyeball upward and outward made it seem most unlikely that the cystic fluid came from the lacrimal gland. An x-ray ex amination of the orbit revealed no bony changes. This negative finding com bined with the lack of pulsation, and the fact that the eye was displaced up ward rather than downward, was strong evidence against the existence of a meningeal fluid tumor. A reten tion cyst seemed just as unlikely. W e
730
H A R V E Y J. H O W A R D
therefore decided to aspirate some of the fluid for diagnostic purposes. The needle was inserted above and to the nasal side of the displaced eye ball, and directed downwards and back wards. There was only slight resist ance to the entrance of the needle, but a clear, watery fluid began to push the glass piston out with considerable force almost as soon as the needle had pene trated the skin. The size of the mass decreased steadily as the fluid, up to a total of 85 c . c , was withdrawn (see Fig. 3 ) . The last few c.c. contained some flocculi and were slightly cloud ed. The odor of the fluid was not un like that of placenta. The patient was watched carefully during the aspira tion of the fluid, but he developed no headache, vertigo, or nausea — symp toms which he certainly would have had if the fluid had been intracranial in origin. Sixteen hours later the tu mor was restored to its original size and tension. A pressure bandage was then applied, which had the effect of appreciably reducing the mass both in size and tension by the following morning. Part of the fluid was sent to the laboratory of biochemistry. The fol lowing report, submitted by Dr. Hsien Wu, includes comparative analyses for cerebrospinal fluid and tears: The cystic fluid Cerebro(per 100 spinal parts) fluid Tears NaCl 0.37 0.60-0.70 1.3 Glucose 0.03 0.04-0.09 Nitrogen 0.055 0.02-0.07 From its chemical analysis the cys tic fluid was analogous to cerebrospinal fluid, but in view of the total lack of subjective symptoms following the sudden and complete withdrawal of fluid, the cyst certainly could not be diagnosed as a meningocele. A micro scopic examination of the sediment of the fluid was then made, and a large number of echinococcus booklets and scolices were found. The tumor, there fore, was an echinococcus cyst of the orbit. Since echinococcus cysts had occa sionally been found in the liver and
the lungs of Chinese patients, careful manual and x-ray examinations were made of the patient's abdomen and chest, but no cysts were demonstrated in those parts. In view of the size and duration of the cyst, the apparent dis integration of much of the retrobulbar structures, and the almost complete loss of vision of the eye involved, total exenteration of the orbit was deemed the only feasible form of treatment. This operation was performed by the writer on May 21, 1923, in the follow ing manner: About 30 c.c. of amber colored fluid were first aspirated from the cyst, in order to facilitate its removal. The external commissure was then split back to the bony orbital margin, and the internal commissure to the lacrimal bone. Incisions (extending from the inner to the outer canthus) were made thru the skin of both upper and lower lids, about 2 mm. from the lid margins. The skin of both lids was then dissect ed back to the bony margin of the orbit; and the entire tumor, together with the eyeball, the lid margins with the eyelashes, and the extraocular muscles including the levator, was sep arated by blunt dissection and removed from the orbit. Care was taken not to injure the periobita. After bleed ing had been controlled, and all frag ments of loose tissue removed, the edges of the greatly stretched skin of the lids were approximated with sev eral fine silk sutures. Fortunately the amount of skin was sufficient to cover the denuded area, with the exception of about a square centimeter at the apex of the orbit. The orbit was care fully packed with gauze in order to hold the skin into apposition with the bone, and a moderate pressure band age was applied. The dressings were changed daily. For the first few days the dressings were soaked with a serosanguinous fluid. A little of the skin became ne crotic and sloughed off. but applica tions of mercurochrome stimulated the growth of granulation tissue as a base for epithelial extension. Five weeks after the operation, the orbit was cov ered completely with healthy skin (see
ECHINOCOCCUS CYST OF ORBIT
Fig. 4 ) . The patient was then dis charged, and has not been heard from since. PATHOLOGIC REPORT.
Gross
examination:
The
specimen
is an oval shaped mass, which includes an eyeball, the eyelash margins of both lids, and all the tissues of one orbit. Weight, 87.5 gms. (30 c c . of fluid were withdrawn just prior to removal of the tumor). Length, 7.0 cm.; width, 5.0 cm.; height, 5.5 cm.
731
which more than half filled the cham ber. The main specimen was cut into from its superior surface, in a frontal plane lying about an inch behind the eyeball. A large cystic space, with a wall averaging about 0.5 cm. thick, was thereby exposed. About 10 c c of straw colored fluid with some flocculent sediment were removed from this cys tic space. A segment of the upper wall of the cyst was removed, exposing a cavity about 4 cm. in diameter. With-
Fig. 3. Front view immediately after aspiration of 85 c c . of echinococcus fluid.
Fig. 4. Final result following exenteration of orbit.
The specimen was hardened in Miiller's fluid and subsequently trans ferred to 80 per cent alcohol. The up per eyelid was split vertically in the median line, and the two parts were re tracted in order to expose the eyeball behind, which was found solidly im bedded in a mass of tissue. The eye ball was bisected equatorially, and the anterior segment was removed, leaving the posterior part in situ. The anterior segment was cut sagittally into two un equal parts; the smaller part to be pr'^pared for paraffin sectioning, the larger for celloidin. A small amount of strawcolored fluid escaped from the vitreous chamber, but there remained behind a dark amber colored vitreous body.
in this cavity an irregularly globular mass, about 2.5 cm. in diameter, was found. This mass was easily removed. Upon being bisected, it was found to be a shriveled unilocular cyst with a well marked capsule (see Fig. 5 ) . The cyst contained a greenish yellow co agulum of waxy appearance and stiff jelly like consistency. Attached to the inner margin of the capsule at several places were quite a number of small, light brown nodules which looked like hydatid sand. The character and ap pearance of this irregular mass gave the impression that at one time it had been a cyst which had completely filled the large cavity of the tumor. Due to the withdrawal of the fluid and the
732
H A R V E Y J. H O W A R D
process of hardening, the cyst appar ently collapsed, and its capsule became separated from the wall of the outer cavity. A small piece of this contract ed cyst was removed for sectioning; also two pieces were taken from the outer wall of the large cavity behind the eyeball. The anterior border of the large cav ity extended to within about 1.5 cm. of the eyeball which lay above and in front of it. The whole mass was di vided into two parts by cutting in a
unilocular cyst with a double chitinous wall. The outer membrane, or ectocyst, is somewhat laminated, while the inner membrane, or endocyst, is prac tically homogeneous in structure. The tiny nodules which looked macroscopically like hydatid sand, are n o w re vealed as irregular rows of daughter cysts of echinococcus, some attached and others adjacent to the endocyst, These daughter cysts appear to be in various stages of degeneration and dis integration. Several contain either a
Fig. 5. The collapsed and shrivelled echinococcus cyst, after its removal from the mass of orbital tissues.
vertical plane about 1 cm. behind the eyeball and parallel to its equator, in order to expose the relation of the re trobulbar and orbital structures. The internal rectus, inferior rectus and su perior oblique muscles were missing. The superior and external recti mus cles were plainly visible, but both were imbedded in dense tissue, and pushed nearly to the periphery of the mass. The optic nerve was also plainly vis ible, but was displaced upward from its normal position, lying only 1.5 mm. below the superior rectus muscle. A piece of tissue, including the optic nerve and the superior rectus muscle, was removed for sectioning. Microscopic examinaiton: a. Small section of the cyst itself: The specimen consists chiefly of a narrow pouch of a
complete or a nearly complete scolex, but most of them have, within their limiting membrane, cjuite a number of isolated echinococcus hooklets, some debris, and a few small, densely black, round bodies, which suggest pyknotic nuclei. Some of the daughter cysts have, attached to their inner walls, sev eral granddaughter cysts and degener ated remnants of such cysts (see Plate 3, Figs. 6 and 7 ) . In addition to the daughter cysts, some attached to the endocyst and some unattached, the pouch of the mother cyst contains a coarsely meshed network of substance somewhat simi lar in constituency to the endocyst. Within the network there are seen a faintly pink stained coagulum, numbers of free hooklets, debris and cystic rem-
ECHDÍOCtXXJUS
nants in v a r i o u s stages o f disintegra tion. In eacii s e c t i o n are a l s o f o u n d a n u m b e r of r o u n d l i m e cells, o r calcare ous bodies, which vary from 20 to 30 u in diameter. In size they c o m p a r e . w i t h the g r a n d d a u g h t e r c y s t s . T h e s e b o d ies are c o m p o s e d chiefly o f c o n c e n t r i c ally arranged c a l c a r e o u s s u b s t a n c e . It m a y b e inferred from their size and shape that t h e y represent a stage in the d e g e n e r a t i o n o f s o m e o f the g r a n d d a u g h t e r c y s t s , or at least of rudimen tary skeletons o f s o m e sort. Scattered within the m e s h w o r k are m a n y small l y m p h o c y t e s and e o s i n o p h i l e s . S o m e of the .daughter c y s t s are a l m o s t sur rounded b y a zone of mononuclear eosinophiles, w h i c h also are seen in clusters a l o n g the e n d o c y s t in relative ly large numbers (see Plate 3, Figs. 8 and 9 ) . b . Small s p e c i m e n taken from the tissue l y i n g b e t w e e n the eyeball and the c y s t c a v i t y w i t h a bit o f the upper l i d : T h e principal structure of the s p e c i m e n is c o n n e c t i v e tissues, s h o w i n g c o n s i d e r a b l e proliferation of y o u n g fibroblasts w i t h o u t a n y regular ar r a n g e m e n t . A d j o i n i n g o n e margin o f the s p e c i m e n there is a c r o s s section of a m u s c l e ( s u p e r i o r r e c t u s ) , with a r e m n a n t o f T e n o n ' s capsule c l o s e b y ; also a c r o s s s e c t i o n o f the o p t i c nerve. T h e optic nerve fibers are partially atro phic and widely separated by edema. A small number o f eosinophiles are seen around the central vessels o f the nerve and also in the fibers pf the septa separ ating the nerve bundles. T h e orbital tis sue surrounding the nerve is infiltrated with numerous lymphocytes and eosino philes. T h e connective tissue stroma c o n tains a few vessels which are located chiefly near the muscle. T h e r e is no defi nite demarcation between connective tis sue arid muscle, a condition due chiefly to an infiltration o f the connective tissue with many small lymphocytes, epithelioid cells, plasma cells and a f e w eosinophiles. This infiltration is m o r e marked around the vessels. T h e walls o f both veins and arteries are so much proliferated that the lumina o f some o f them are entirely obliterated. H e r e and there in the sub stance o f the muscle, as well as in the adjacent connective tissue, there are
CYST
OP
ORBIT
733
many vacuoles which are separated by a very delicate, homogeneous membrane. Several l a r g e m o n o n u c l e a r s and m a s t cells are visible in all sections. c. T h e anterior segment o f the eyeball: T h e layers o f corneal epithelium are in creased in number, and the cells are more horny than normal. T h e i r nuclei are only faintly stained. S o m e o f the epithelial cells are vacuolated. Peripher ally, for a width o f 1 to 3 mm.. B o w man's membrane has disappeared, and is replaced by a dense pannus—blood vesse s and fibroblasts. T h e superficial onesixth to one-fourth o f the substantia pro pria is infiltrated with lymphocytes and plasma cells, among which are seen a small number o f epithelioid cells and eosinophiles. T h e infiltration increases in density toward the periphery o f the cornea, and appears to be an extension of even a denser infiltration that exists in the scleral tissue. D e s c e m e t ' s m e m brane and the endothelial cell layer are normal. T h e conjunctival epithelium covering the episcleral tissue shows exposure kera tosis—formation o f keratin and vacuo lization o f cells. A large number o f plas ma cells and eosinophiles infiltrate the subepithelial layers. T h e scleral stroma in general is loose and shows evidence o f edematous separation and atrophy o f some o f its connective tissue fibers. There is a general infiltration involving the outer third o f the sclera; near the limbus this infiltration involves the outer t w o thirds. T h e infiltration is composed chiefly o f small lymphocytes and plasma cells, with some eosinophiles and epithe lioid cells. T h e arteries and veins, which are numerous in the region o f the limbus, are distended with blood and surrounded by a dense zone o f chronic inflammatory cells, among which eosinophiles greatly predominate. T h e ciliary nerves passing thru the sclera are partially atrophic. T h e location o f the tendinous attachments o f the extraocular muscles cannot deflnitely be determined, owing to the dense cellu lar infiltration and the probable disin tegration o f the tendinous structures. In the region o f the equator o f the globe there are a number o f vacuoles arranged in irregular r o w s in the loose stroma o f the outer half o f the sclera. These spaces
734
H A R V E Y J. H O W A R D
are larger than those that would be pro duced by fat globules, and have very thin walls or limiting membranes of homo geneous material. The suprachoroidal space is filled with coagulum, which sep arates the sclera and the choroid for a distance of nearly a centimeter backward from the anterior end of the choroid. The anterior chamber is somewhat shallower than normal and the filtration angle is slightly closed by the root of the iris. A number of chromatophores (probably from the iris) are enmeshed in the structure of the pectinate ligament. The iris and ciliary body are practically normal with the exception of the pres ence of a few eosinophiles. The lens is normal. d. A piece of the posterior segment of the eye not including the optic nerve: The retinal nuclei take the stain poorly, which probably means beginning degen eration of the retina, which is completely detached (possibly an artefact). The choroid is practically normal with the exception that the vessels, large and small, are engorged with blood. Sclera the same as in " c . " e. The cystic fluid. A few scolices of echinococcus, numerous free booklets and debris.
Primary Diagnosis: Echinococcus cyst of the orbit. Secondary Diagnoses: Exposure con junctivitis; pannus, superficial and deep keratitis and scleritis; maculae of the cor nea; chronic inflammation of the extra ocular muscles; endarteritis and endophlebitis of the orbital vessels; partial atrophy of the ciliary nerves; chronic retrobulbar neuritis with partial atrophy of the optic nerve; local eosinophilia. The object of this rather "extensive pathologic report is to put on record a fairly complete account of the first case of echinococcus cyst of the orbit reported from China. It should be noted that no vestige of echinococcus was found with in the eyeball, altho some of the ocular structures were chronically inflamed, due, no doubt, to the toxins absorbed from the cystic fluid in the adjacent tissues. There is no doubt also that there was some pathologic effect upon the eye an^ its function, due to the steadily increas ing pressure on the globe from behind.
The intraocular structures ihowed signs of this pressure by a beginning atrophy, whereas the denser protective membranes of the eye were affected chiefly by the toxins. Anyone who has seen a case of echin ococcus cyst of the orbit and failed at first to recognize it is not likely to fail again in making an almost immediate diagnosis. A combination of two or three, or of all of the following clinical signs and diag nostic aids would certainly establish a differential diagnosis: 1. The length and character of the his tory: The combination of sheep and dogs with which a patient has been more or less in contact, in addition to personal habits of uncleanliness, should make one suspicious of echinococcus disease. The duration of fully three years in the de velopment of the cyst as reported in this paper would, generally speaking, be too short for a meningocele, and too long for a tear cyst or a mucus retention cyst. But it could not be differentiated from a malignant tumor on such evidence. 2. The nature of the displacement of the globe: Marked exophthalmos, natu rally, always exists. A number of writ ers state that the eyeballs in their cases were dislocated upward, forward, and in ward. In this case the displacement was forward, upward, and outward. In either case a meningocele and a lacrimal cyst would be ruled out. 3. Palpation: The sense of touch should let one know at once that he is not deaUng with a solid tumor. Fluctua tion, fremitus, and resilience of the mass can easily be elicited if the cyst has at tained considerable size. 4. X-ray: The x-ray should rule out any bony changes that one would expect to see in a meningocele, or a malignant tumor with erosion of the walls of the accessory sinuses. Some writers state that the shadow produced on the plate by cystic fluid is denser than that produced by a solid tumor; this seems hard to be lieve. 5. Urticaria: A history of one or more recent attacks of urticaria should make one suspicious of echinococcus. The steadily increasing pressure from time to time sometimes causes a slight rupture of the surrounding tissues and conse-
ECHINOCOCCUS CYST OF ORBIT
quently of the cystic capsule, permitting the escape of echinococcus fluid which infiltrates the tissues and becomes quick ly absorbed. The absorption of toxins in the fluid, or of the foreign protein, produces a violent urticaria similar to the serum reaction which often follows injections of tetanus or diphtheria anti toxin. Urticaria has been reported as following exploratory puncture of an echinococcus cyst, when some of the re sidual fluid seeped into the surrounding tissues thru the wound. 6. A general eosinophilia: A count of more than 2 or 3 per cent of eosino philes should cause suspicion; yet among the twelve cases of echinococcus cyst of various organs treated at the hospital of the Peking Union Medical College, five showed no pathologic increase in the eosinophilic count, altho three of the five were later relieved of considerable ech inococcus fluid. In fact, the one with the lowest eosinophilic count had the most fluid removed. It is significant that out of the twelve, this is the only case that died. Possibly the low eosinophilia indicated a marked loss of resistance in his case. Furthermore, in these five cases it is possible that the cysts were in the stage of retrogression and were be coming sterile, a tendency which exists when the intracystic pressure becomes too high. In the case with the orbital involvement the eosinophilia was only 3 per cent. The average for the twelve cases was 4.7 per cent. Intestinal para sites of any variety will also produce a general eosinophilia, so their absence must first be determined" before any re liance favoring the diagnosis of echino coccus can be placed on the existence of an eosinophilia. The data concerning the possible infection of these twelve cases with intestinal parasites are not complete, so too much importance can not be i^aced on the eosinophilia in those cases in which it was high. 7. Exploratory puncture: A micro scopic examination of the aspirated fluid should estabfish a diagnosis, for the sedi ment nearly always contains booklets, scolices and debris of embryo cysts. A report that the fluid is sterile, as was the case in one of the twelve listed in Table I, may merely mean that none of the
735
sediment was removed with the fluid. T o avoid this possibility it is well to shake somewhat vigorously that part of the body containing the cyst just prior to aspiration of the fluid. It is stated that great danger of mixed infection is in volved in doing exploratory puncture of echinococcus cysts, so the surgeon should be prepared to operate for com plete removal of the cyst immediately after it has been determined by an ex amination of the fluid that he is dealing with echinococcus disease. 8. Complement fixation test: A posi tive test using the cystic fluid as the an tigen is recognized as establishing a diag nosis. Three of the twelve cases were tested by this method and all of them were strongly positive. ADDITIONAL
REMARKS:
One
would
naturally suppose that involvement of one organ of the body would mean the probable involvement of other organs, but this evidently is not so. According to Simon'', only one organ is involved as a rule. When multiple infestation exists, it is probably due to successive infesta tion from without, or possibly to a dis semination of the primary infestation from within, owing to a rupture of the cyst. But a successive infestation would be as much an accident as was the pri mary one; the individual already infested would probably have no more chance of being additionally infested than other persons associated with him would in be coming primarily infested. However, in a case of echinococcus disease with a history of urticaria, one might logically suspect involvement of other organs or parts of his body. Simon further states that human infestation occurs thru transference of the ova of the adult worms of Taenia echinococcus (gener ally from the dog) to the gastrointes tinal tract. Having gained access to the digestive tract, the ovum, or perhaps the oncosphere (larva), freed of its resisting envelope by the digestive juices, pene trates the intestinal wall, and, entering a blood vessel, is carried along in the blood stream until it lodges as an em bolus in some other part (generally an organ) of the body where it begins at once to develop a cyst. According to Barnett^ once a cyst
736
H A R V E Y J. H O W A R D
begins in a favorable locality, such as in the liver, it absorbs nourishment by imbibition from the surrounding tis sues and grows into a bladder like mass, which constitutes the echinococ cus or hydatid disease, the rate of growth varying according to the dens ity of the surrounding parts. If the nutrition be cut off, the cyst dies and undergoes degeneration; even calcifi cation may take place. Barnett refers to daughter cysts as embryo cysts which, on account of impaired vitality of the primary or mother cyst, have become detached from the parental wall and float loose in the fluid of the mother cyst. Tertiary or granddaugh ter cysts may be found free within the secondary or daughter cysts for the same reason. Great-grand-daughter cysts are also occasionally found. Im paired vitality of the primary cyst re sults from either lack of nutrition or an inability to expand further. In cysts of the liver and the brain there is practically no interference to expan.sion until vital parts are aflfected and the patient's death occurs. In the orbital case herein reported, the vitality of the mother cyst was ap parently impaired, since there were many daughter and grand-daughter cysts lying detached from their respec tive parental membranes. The prob able reason for this was the difficulty of further expansion of the cyst, lim ited as it was by the bony orbit later ally and behind, and by the eyeball, with its muscular and tendinous at tachments, in front. Its expansion was further hindered by its location within the muscle cone of the orbit. According to Wood*, a cyst in this position rather than outside the muscle cone, is exceedingly diflficult to be re
moved without first removing the globe. The large size of the cyst and extensive destruction of the orbital tis sues warranted total exenteration in this case. The ages of the patients reported in this paper, including the one orbital case, make one suspect that the cysts had been developing for many years. The average age was 36 years, the youngest 19, and the oldest 54. The duration of symptoms ranged from one to eight years, with an average of 3.4, but it is almost certain that infestation occurred long before that. Faust^ examined the gastrointes tinal tracts of about five hundred dogs in China for parasites. In only two dogs, both from near Peking, did he find Taenia echinococcus. He states that, to his knowledge, these are the first instances in which these cestodes have been found in dogs in eastern Asia. The evidence produced by this paper implies that a number of dogs in Peking and its environs are thus in fected and that they are the source of the larval infestation of man in this same area. Of the twelve cases herein reported, eleven, including the orbital case, were natives as well as residents of Chihli, the province in which Peking is located. All of these eleven cases were males. The one female case was a Chinese woman, age 19, who had lived all her life in Mongolia. If, as shown by this paper, the disease exists sporadically in North China where the conditions for its dissemination are not good, it would not be amiss to suggest that, in Mongolia where the conditions are as ideal for its dissemination, as they are in Australia or Iceland, echi nococcus cyst in man ought not to be uncommon.
REFERENCES 1. 2. 3. 4. 5.
Peake, E. C. Report of the London Mission Hospital, Tientsin, China, for 1917. China M. J., 1918, vol. X X X I I , p. 276. Simon, C. E. Clinical Diagnosis. Lea and Febiger, Phila., 1922 ed., p. 463. Barnett, L. E. Hydatid disease. Practice of Medicine in the Tropics, by Byam and Arch ibald, Oxford Univ. Press, N. Y . , 1923 ed., vol. I l l , p. 1832. Wood, D. J. Hydatid disease of the Orbit. Brit. J. Ophth., 1925, vol. I X , p. 4. Faust, E. C. Personal communication to the writer.