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Juvenile xanthogranuloma with ocular involvement
JUVENILE
XANTHOGRANULOMA
WITH
OCULAR
INVOLVEMENT
REPORT Ol~ CASE REZA GHARIB, M.D., EDMUND C. BURKE, M . D . , AND LOUIS A . BRUNSTING, M . D . ROCHESTER, ~_INN. HE designation nevoxantho-endothelioma, an odd type of cutaneous t u m o r , w a s o r i g i n a l l y a p p l i e d to a benign xanttmmatous condition with normal bIood lipids which occurs in infancy and early childhood. This condition was first described b y A d a m s o n ~ i n 1905 as " c o n g e n i t a l xanthoma multiplex." I n 1912, MeDonagh 2 suggested the term "naevoxantho-endothelioma." He described five cases a n d i n c l u d e d s o m e o t h e r s which had been reported previously in t h e l i t e r a t u r e . Helwig and HackneyS, 4 r e v i e w e d 140 cases of t h i s c o n dition and suggested that the descript i v e t e r m of " x a n t h o g r a n u l o m a " or "juvenile xanthogranuloma" be used until the exact etiologic factors are known. O t h e r cases h a v e b e e n rep o r t e d ~-t2 in t h e l i t e r a t u r e s i n c e t h e paper by IIelwig and Hackney. W e w i s h to r e p o r t a case o f j u v e n i l e xanthogranuloma encountered at the 5[ayo Clinic in a female infant that is u n u s u a l b e c a u s e of t h e i n v o l v e m e n t of t h e o p t i c globe.
T
CASE REPORT A 4-month-old girl was referred to the Mayo Clinic because of skin and eye lesions of 21/2 months' duration. When she was 6 weeks of age, her mother noted a "mole" over the lower fourth of the child's sternum. Subsequently, it enlarged, and 2 to 3 weeks later more lesions were noted, at From the Section of ]Pediatrics, Mayo Foundation, the Section of l~ediatries and the Section of Dermatology. Mayo Clinic and Mayo ]Poundation. The Mayo Foundation is a part of the Graduate School of the University of Minnesota. 109
first on tile face, and later over the trunk and the back. These lesions began as small erythematous papules and enlarged progressive]y. One month prior to her referral to the Clinic, the left eye began to tear excessively and become inflamed. The infant was seen by her local physician who felt that the left eye was blind. He thought that something was growing behind the left eye and referred the child to the Clinic for additional examination. The infant's history revealed a normal spontaneous delivery and normal neonatal period, growth, and development. She had two siblings who had had eczema at an early age. No condition similar to that of our patient was known in the family. Physical examination revealed an apparently healthy 4-month-ohl infant, 241A inches long and weighing 131/2 pounds. There were 20 or so well-circumscribed lesions that were firm, rubbery hard, raised, attd yellow-pink. They measured from 1/~ to ~ inch in diameter and occurred on the face, chest, back, trunk, and extremities (Fig. 1, A and B). Associated patchy cczematous lesions also appeared oaa the inf a n t ' s face, neck, and arms (Fig. 1, A). An ophthalmologist examined the left eye and found macrophthalmia to be present. The cornea was edematous and a small globular mass of organized blood was present in the pupillary opening (Fig. 2). The ocular tension seemed normal. The transillumination could not be done thoroughly but no particular density was obvious except, possibly, in the upper portion of the globe. A slight pupillary reaction was present. Erythrocytes numbered 4,550,000 and leukoeytes, 9,000. The concentration of hemoglobin measured 11.9 Gin. and the differential count was normal. The cholesterol measured 193 rag. per 100 ml. of serum. Urinalysis was not carried out.
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THE JOURNAL OF PEDIATRICS
Roentgenograms-of the thorax and head d i d not s h o w e v i d e n c e of a n y a b n o r m a l i t y . B i o p s y of one of t h e l e s i o n s ( F i g . 3) showed histiocytes, many capillaries, and g i a n t c e l l s of t h e T o u t o n a n d f o r e i g n - b o d y types. F a t s t a i n s s h o w e d n~arked deposit i o n of f a t b o t h i n t r a c e l l u l a r l y a n d e x t r a cellularly.
A letter from the infant's mother 7 m o n t h s a f t e r her first e x a m i n a t i o n a t tile Clinic indicated that the facial lesions s e e m e d to be " d r y i n g up" a n d w e r e r e d u c e d in size. N o n e w l e s i o n s h a d a p p e a r e d . The eye ( g l o b e ) s t i l l a p p e a r e d swollen. The i r i s was d i s c o l o r e d b u t t h e p u p i l w a s a g a i n visible.
:Fig. 1.--a, Lesions a r e e v i d e n t on face, head, brow, and upper lip. S m a l l e r lesions present are not a p p a r e n t in this p h o t o g r a p h , b, A close-up of the lesion on the chest shows it to be smooth, elevated, shiny, and discolored. Biopsy of the lesion w a s carried out. COMMENT
Fig. 2 . - - M a c r o p h t h a l m i a , an e d e m a t o u s cornea, and a s m a l l m a s s of o r g a n i z e d blood in the p u p i l l a r y opening in the left eye are not c l e a r l y apparent, but some differences in the a p p e a r a n c e of the pupil and list of the left eye are obvious.
Juvenile xanthogranuloma is characterized by tile development, in the first few weeks of life, of yellowish to yellowish-brown papules or nodules scattered irregularly over the body, the extremities, and the face. The most striking feature in our case was involvement of the ocular globe. A similar ocular involvement has been reported by Blank and associates, 9 but the skin lesions in their patient appeared at a later age. An enucleation was performed in their case and microscopic examination revealed that
G H A R I B E T AL. :
XANTHOGRANULOI~IA WITH
the tumor of the eye had the same histologic structure as the lesions of the skin. Enucleation was not performed on our patient. W e concluded that the eye might as well be left in place since it was not painful and, therefore, was not interfering with the
OCULAR I N V O L V E M E N T
111
are dependent on a n y visceral disturbance. The benign course and the t e n d e n c y t o w a r d spontaneous disappearance separate this condition f r o m Hand-Schiiller-Christian disease in which systemic involvement is always present and a f a t a l course is the rule.
F i g . 3 . - - S e c t i o n of n e v o x a n t h o - e n d o t h e l i o m a s h o w i n g h i s t i o e y t e s a n d T o u t o n g i a n t cells (hematoxylin and eosin; X300). F a t s t a i n s s h o w e d m a r k e d d e p o s i t i o n of i n t r a c e l l u l a r a n d extraeellular fat. N o t e t h e a t r o p h y of t h e o v e r l y i n g e p i d e r m i s .
infant's general welfare. Presumably, the ocular lesion resolves by fibroplasia and atrophy. The palms, soles, and flexor surfaces are usually spared. A family history of such lesions may or may not be present. The lesions tend to disapp e a r spontaneously within the first few months or years, leaving depressed areas. Eventually, complete disappearance of these areas m a y occur. There is no evidence that the lesions
There was no suggestion of a transition to changes t h a t might be considered to be characteristic of Lctterer-Siwe disease or Hand-Schiiller-Christian disease in any of 160 patients with x a n t h o g r a n u l o m a studied by Helwig and Itackney2, 4 All authors are agreed t h a t values for blood lipids are n o r m a l in patients who have this condition.
Histologic Features.--McDonagh 2 wrote, "These t u m o u r s . . , are naevi
112
THE JOURNAL OF PEDIATRICS
of the type endothelioma, and . . owing to a f a t t y change which occurs in the cell during their dissolution a xanthoma-like condition is p r o d u c e d . " Ormsby and Montgomery ~3 stated, " P r o l i f e r a t i o n of endothelial cells and connective-tissue histiocytcs and formation of endothelial giant cells took place, in addition to the presence of typical xanthomatous foam and giant cells." They also wrote, "Helwig and H a c k n e y showed clearly that what looked like endothelial giant cells were true xanthomatous giant cells and that no proliferation of endothelial cells took place." In addition to histologic findings mentioned in the quotations, sections show the presence of m a n y droplets of lipids t h r o u g h o u t the region of infiltration as well as within the giant cells. The case presented herein is important because the ocular involvement might have greatly heightened the suspicion of an ocular malignant neoplasm except for the association with skin lesions. The ophthalmologist supported our conclusion that as l o n g as the infant's eye was painless and possessed a benign lesion, surgical treatment was contraindicated. The possibility exists that the lesion may cause blindness, and enucleation may be required in the future. The possibility of regression of the lesion and development of useful vision also exists. SUMMARY
"J u v e n i 1 e x a n t h o g r a n u l o m a " is suggested as the best diagnostic term for the condition characterized by yellowish-brown nodules of the skin present at birth or shortly thereafter. The blood lipids are normal and the
general health is unaffected. Spontaneous involution of the lesions occurs. The histologic picture consists of proliferation of histiocytes and xanthomatous giant cells. One case of nevoxantho-endothelioma with involvement of the eye is reported. Inasmuch as the lesions are benign and t e n d to regress, the ocular globe should be left intact with the hope of eventual r e t u r n of vision. REFERENCES 1. Adamson, I{. G.: Congenital X a n t h o m a l~[ultiplex, Brit. J. Dernlat. 17: 222~ 1905. 2. 1VieDonagh, J. E. 1%.: A Contribution to Our Knowledge of the Naevo-xanthoendotheliomata, Brit. J. Dermat. 9.4: 85, 1912. 3. Helwig, E. B., and Itackney~ V. C.: Juvenile Xanthogranulo~na (Nevoxanthoendothelioma), (Abstr.) Am. J. P a t h . 30: 625, 1954. 4. /-Ielwlg, E. B.: J u v e n i l e X a n t h o g r a n u lema. T r a n s a c t i o n s of the Pacific Dermatologic Association, N i n t h A n n u a l Meeting, Oct. 31-Nov. 2, 1957, pp. 25-28. 5. Wise, F.: Multiple Endothelioma of the Skin, Am. J. IV[. Sc. 157: 236, 1919. 6. Jacoby, 1%., and Grund, J. L.: Endot h e l l o m a Cutis: Naevoxantho-endothelioma; Report of Case, New E n g l a n d J. N[ed. 202: 1247, 1930. 7. Senear, F. E., and Caro, M . R . : Nevox a n t h o - e n d o t h e l i o m a or J u v e n i l e Xanthoma, Arch. Dermat. & Syph. 34: 195, 1936. 8. L a m b , J. H., and Lain, E. S.: Nevox a n t h o - e n d o t h e l l o m a : Its Relationship to J u v e n i l e X a n t h o m a , South. M. J. 30: 585, 1937. 9. Blank, It., Eglick, P. G., and Beerman, IL: Nevoxantho-endothelioma W i t h Ocular I n v o l v e m e n t , Pediatrics 4: 349, 1949. 10. Laymon, C. W., and Schoch, E. P.: Nevoxantho-endothelioma, N[i n n e s o t a Med. 32: 596, 1949. 11. Nomland, R.: Nevoxantho-endothelioma: A Benign X a n t h o m a t o u s Disease of I n f a n t s and Children, J. Invest. Dermat. 9.9.: 207, 1954. 12. Louste, and P i g n o t : Un cas de xanthome tub~reux ~ruptif chez un e n f a n t de 5 ans, Bull. Soc. fran~, dermat. et syph. 38: 1144, 1931. 13. Ormsby, O. Sg a n d Montgomery, H.: Diseases of ~l.e Skin, ed. 8, Philadelphia, 1954, Lea & Febiger, p. 745.
XANTHOGRANULOMA
WITH
OCULAR
INVOLVEMENT
REPORT Ol~ CASE REZA GHARIB, M.D., EDMUND C. BURKE, M . D . , AND LOUIS A . BRUNSTING, M . D . ROCHESTER, ~_INN. HE designation nevoxantho-endothelioma, an odd type of cutaneous t u m o r , w a s o r i g i n a l l y a p p l i e d to a benign xanttmmatous condition with normal bIood lipids which occurs in infancy and early childhood. This condition was first described b y A d a m s o n ~ i n 1905 as " c o n g e n i t a l xanthoma multiplex." I n 1912, MeDonagh 2 suggested the term "naevoxantho-endothelioma." He described five cases a n d i n c l u d e d s o m e o t h e r s which had been reported previously in t h e l i t e r a t u r e . Helwig and HackneyS, 4 r e v i e w e d 140 cases of t h i s c o n dition and suggested that the descript i v e t e r m of " x a n t h o g r a n u l o m a " or "juvenile xanthogranuloma" be used until the exact etiologic factors are known. O t h e r cases h a v e b e e n rep o r t e d ~-t2 in t h e l i t e r a t u r e s i n c e t h e paper by IIelwig and Hackney. W e w i s h to r e p o r t a case o f j u v e n i l e xanthogranuloma encountered at the 5[ayo Clinic in a female infant that is u n u s u a l b e c a u s e of t h e i n v o l v e m e n t of t h e o p t i c globe.
T
CASE REPORT A 4-month-old girl was referred to the Mayo Clinic because of skin and eye lesions of 21/2 months' duration. When she was 6 weeks of age, her mother noted a "mole" over the lower fourth of the child's sternum. Subsequently, it enlarged, and 2 to 3 weeks later more lesions were noted, at From the Section of ]Pediatrics, Mayo Foundation, the Section of l~ediatries and the Section of Dermatology. Mayo Clinic and Mayo ]Poundation. The Mayo Foundation is a part of the Graduate School of the University of Minnesota. 109
first on tile face, and later over the trunk and the back. These lesions began as small erythematous papules and enlarged progressive]y. One month prior to her referral to the Clinic, the left eye began to tear excessively and become inflamed. The infant was seen by her local physician who felt that the left eye was blind. He thought that something was growing behind the left eye and referred the child to the Clinic for additional examination. The infant's history revealed a normal spontaneous delivery and normal neonatal period, growth, and development. She had two siblings who had had eczema at an early age. No condition similar to that of our patient was known in the family. Physical examination revealed an apparently healthy 4-month-ohl infant, 241A inches long and weighing 131/2 pounds. There were 20 or so well-circumscribed lesions that were firm, rubbery hard, raised, attd yellow-pink. They measured from 1/~ to ~ inch in diameter and occurred on the face, chest, back, trunk, and extremities (Fig. 1, A and B). Associated patchy cczematous lesions also appeared oaa the inf a n t ' s face, neck, and arms (Fig. 1, A). An ophthalmologist examined the left eye and found macrophthalmia to be present. The cornea was edematous and a small globular mass of organized blood was present in the pupillary opening (Fig. 2). The ocular tension seemed normal. The transillumination could not be done thoroughly but no particular density was obvious except, possibly, in the upper portion of the globe. A slight pupillary reaction was present. Erythrocytes numbered 4,550,000 and leukoeytes, 9,000. The concentration of hemoglobin measured 11.9 Gin. and the differential count was normal. The cholesterol measured 193 rag. per 100 ml. of serum. Urinalysis was not carried out.
110
THE JOURNAL OF PEDIATRICS
Roentgenograms-of the thorax and head d i d not s h o w e v i d e n c e of a n y a b n o r m a l i t y . B i o p s y of one of t h e l e s i o n s ( F i g . 3) showed histiocytes, many capillaries, and g i a n t c e l l s of t h e T o u t o n a n d f o r e i g n - b o d y types. F a t s t a i n s s h o w e d n~arked deposit i o n of f a t b o t h i n t r a c e l l u l a r l y a n d e x t r a cellularly.
A letter from the infant's mother 7 m o n t h s a f t e r her first e x a m i n a t i o n a t tile Clinic indicated that the facial lesions s e e m e d to be " d r y i n g up" a n d w e r e r e d u c e d in size. N o n e w l e s i o n s h a d a p p e a r e d . The eye ( g l o b e ) s t i l l a p p e a r e d swollen. The i r i s was d i s c o l o r e d b u t t h e p u p i l w a s a g a i n visible.
:Fig. 1.--a, Lesions a r e e v i d e n t on face, head, brow, and upper lip. S m a l l e r lesions present are not a p p a r e n t in this p h o t o g r a p h , b, A close-up of the lesion on the chest shows it to be smooth, elevated, shiny, and discolored. Biopsy of the lesion w a s carried out. COMMENT
Fig. 2 . - - M a c r o p h t h a l m i a , an e d e m a t o u s cornea, and a s m a l l m a s s of o r g a n i z e d blood in the p u p i l l a r y opening in the left eye are not c l e a r l y apparent, but some differences in the a p p e a r a n c e of the pupil and list of the left eye are obvious.
Juvenile xanthogranuloma is characterized by tile development, in the first few weeks of life, of yellowish to yellowish-brown papules or nodules scattered irregularly over the body, the extremities, and the face. The most striking feature in our case was involvement of the ocular globe. A similar ocular involvement has been reported by Blank and associates, 9 but the skin lesions in their patient appeared at a later age. An enucleation was performed in their case and microscopic examination revealed that
G H A R I B E T AL. :
XANTHOGRANULOI~IA WITH
the tumor of the eye had the same histologic structure as the lesions of the skin. Enucleation was not performed on our patient. W e concluded that the eye might as well be left in place since it was not painful and, therefore, was not interfering with the
OCULAR I N V O L V E M E N T
111
are dependent on a n y visceral disturbance. The benign course and the t e n d e n c y t o w a r d spontaneous disappearance separate this condition f r o m Hand-Schiiller-Christian disease in which systemic involvement is always present and a f a t a l course is the rule.
F i g . 3 . - - S e c t i o n of n e v o x a n t h o - e n d o t h e l i o m a s h o w i n g h i s t i o e y t e s a n d T o u t o n g i a n t cells (hematoxylin and eosin; X300). F a t s t a i n s s h o w e d m a r k e d d e p o s i t i o n of i n t r a c e l l u l a r a n d extraeellular fat. N o t e t h e a t r o p h y of t h e o v e r l y i n g e p i d e r m i s .
infant's general welfare. Presumably, the ocular lesion resolves by fibroplasia and atrophy. The palms, soles, and flexor surfaces are usually spared. A family history of such lesions may or may not be present. The lesions tend to disapp e a r spontaneously within the first few months or years, leaving depressed areas. Eventually, complete disappearance of these areas m a y occur. There is no evidence that the lesions
There was no suggestion of a transition to changes t h a t might be considered to be characteristic of Lctterer-Siwe disease or Hand-Schiiller-Christian disease in any of 160 patients with x a n t h o g r a n u l o m a studied by Helwig and Itackney2, 4 All authors are agreed t h a t values for blood lipids are n o r m a l in patients who have this condition.
Histologic Features.--McDonagh 2 wrote, "These t u m o u r s . . , are naevi
112
THE JOURNAL OF PEDIATRICS
of the type endothelioma, and . . owing to a f a t t y change which occurs in the cell during their dissolution a xanthoma-like condition is p r o d u c e d . " Ormsby and Montgomery ~3 stated, " P r o l i f e r a t i o n of endothelial cells and connective-tissue histiocytcs and formation of endothelial giant cells took place, in addition to the presence of typical xanthomatous foam and giant cells." They also wrote, "Helwig and H a c k n e y showed clearly that what looked like endothelial giant cells were true xanthomatous giant cells and that no proliferation of endothelial cells took place." In addition to histologic findings mentioned in the quotations, sections show the presence of m a n y droplets of lipids t h r o u g h o u t the region of infiltration as well as within the giant cells. The case presented herein is important because the ocular involvement might have greatly heightened the suspicion of an ocular malignant neoplasm except for the association with skin lesions. The ophthalmologist supported our conclusion that as l o n g as the infant's eye was painless and possessed a benign lesion, surgical treatment was contraindicated. The possibility exists that the lesion may cause blindness, and enucleation may be required in the future. The possibility of regression of the lesion and development of useful vision also exists. SUMMARY
"J u v e n i 1 e x a n t h o g r a n u l o m a " is suggested as the best diagnostic term for the condition characterized by yellowish-brown nodules of the skin present at birth or shortly thereafter. The blood lipids are normal and the
general health is unaffected. Spontaneous involution of the lesions occurs. The histologic picture consists of proliferation of histiocytes and xanthomatous giant cells. One case of nevoxantho-endothelioma with involvement of the eye is reported. Inasmuch as the lesions are benign and t e n d to regress, the ocular globe should be left intact with the hope of eventual r e t u r n of vision. REFERENCES 1. Adamson, I{. G.: Congenital X a n t h o m a l~[ultiplex, Brit. J. Dernlat. 17: 222~ 1905. 2. 1VieDonagh, J. E. 1%.: A Contribution to Our Knowledge of the Naevo-xanthoendotheliomata, Brit. J. Dermat. 9.4: 85, 1912. 3. Helwig, E. B., and Itackney~ V. C.: Juvenile Xanthogranulo~na (Nevoxanthoendothelioma), (Abstr.) Am. J. P a t h . 30: 625, 1954. 4. /-Ielwlg, E. B.: J u v e n i l e X a n t h o g r a n u lema. T r a n s a c t i o n s of the Pacific Dermatologic Association, N i n t h A n n u a l Meeting, Oct. 31-Nov. 2, 1957, pp. 25-28. 5. Wise, F.: Multiple Endothelioma of the Skin, Am. J. IV[. Sc. 157: 236, 1919. 6. Jacoby, 1%., and Grund, J. L.: Endot h e l l o m a Cutis: Naevoxantho-endothelioma; Report of Case, New E n g l a n d J. N[ed. 202: 1247, 1930. 7. Senear, F. E., and Caro, M . R . : Nevox a n t h o - e n d o t h e l i o m a or J u v e n i l e Xanthoma, Arch. Dermat. & Syph. 34: 195, 1936. 8. L a m b , J. H., and Lain, E. S.: Nevox a n t h o - e n d o t h e l l o m a : Its Relationship to J u v e n i l e X a n t h o m a , South. M. J. 30: 585, 1937. 9. Blank, It., Eglick, P. G., and Beerman, IL: Nevoxantho-endothelioma W i t h Ocular I n v o l v e m e n t , Pediatrics 4: 349, 1949. 10. Laymon, C. W., and Schoch, E. P.: Nevoxantho-endothelioma, N[i n n e s o t a Med. 32: 596, 1949. 11. Nomland, R.: Nevoxantho-endothelioma: A Benign X a n t h o m a t o u s Disease of I n f a n t s and Children, J. Invest. Dermat. 9.9.: 207, 1954. 12. Louste, and P i g n o t : Un cas de xanthome tub~reux ~ruptif chez un e n f a n t de 5 ans, Bull. Soc. fran~, dermat. et syph. 38: 1144, 1931. 13. Ormsby, O. Sg a n d Montgomery, H.: Diseases of ~l.e Skin, ed. 8, Philadelphia, 1954, Lea & Febiger, p. 745.