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Small Lymphanginomas of the Eyelids
Small Lymphangiomas of the Eyelids PIERRE PANG, MD, FREDERICK A. JAKOBIEC, MD, TAKEO IWAMOTO, MD, ALBERT HORNBLASS, MD
Abstract: Three patients are described with focal lymphangiomatous lesions of their eyelids. A child with a partially regressed , congenital lesion presented with evidence of recent hemorrhage, while, of two adults with acquired tumors, one had a blue lesion suggesting a malignant melanoma, and the other had a more obviously cystic lesion, suggesting an epidermal or adnexal cyst. In one case, the lesion was situated entirely within the marginal orbicularis striated muscle, and in the other two cases the lesion was restricted to the dermis of the lid. Abrupt change in the coloration of a lesion in the lid should suggest hemorrhage into a preexistent tumor. Hemorrhage into lymphangiomas is extremely common, and therefore this vascular tumor should be included in the differential diagnosis of previously nondiscolored lesions. Other vascular tumors, such as capillary, cavernous or venous angiomas would be expected to have a longstanding reddish-blue hue. [Key words: conjunctiva, eyelids, electron microscopy, lymphangioma, orbit.] Ophthalmology 91: 1278-1284, 1984
Lymphangiomas of the ocular adnexa conjure up the specter of massive involvement of the eyelids and orbit. 1--4 Such lesions can produce a hideous proptosis and facial deformity; they provide surgical challenges the equal of those posed by extensive neuromatosis in von Recklinghausen's disease. Lymphangiomas of this sort make their appearance in childhood, and generally entail mUltiple debulking surgical procedures to restore some semblance of a normal cosmetic appearance, although the eye invariably suffers as a result of a constrictive optic neuropathy. There is a group of lymphangiomas with more restricted orbital involvement, and a still smaller set that may focally involve the epibulbar tissues and eyelids. Lymphangiomas of the last site have received almost no attention in the ophthalmic literature. s We present three unusual palpebral lymphangiomas that offered differential diagnostic problems clinically. One of these lesions was congenital and two were acquired From the Departments of Ophthalmology and Pathology, Manhattan Eye, Ear and Throat Hospital and The New York Hospital-Cornell Medical Center, New York City. Supported in part by a grant from the Zelda Radow Weintraub Cancer Fund, Inc .• New York City. Dr. Jakobiec is the recipient of the Research to Prevent Blindness Robert E. McCormick Scholar Award. Reprint requests to Frederick A. Jakobiec, MD, Chairman, Department of Ophthalmology. Manhattan Eye. Ear and Throat Hospital, 210 East 64th Street. New York. NY 10021.
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and occurred in adults. Of the adult lesions, one was a striking curiosity because it was situated entirely within the orbicularis striated muscle of the lid margin (muscle of Riolan), while the other was a collection of neoformed ectatic lymphatic channels restricted to a small portion of the dermis of the eyelid.
CLINICAL HISTORIES A 13-year-old black girl was born with a tumor of the left upper lid, which had continued to enlarge after birth to create partial occlusion of the left pupil. At age 5 months, the tumor was treated with carbon dioxide ice, resulting in a marked shrinkage in the size of the tumor over the ensuing 2 or 3 years. At 10 years, the tumor began to slowly enlarge again, and over the 3 months prior to presentation two or three red areas on the surface of the tumor began to appear. On ocular examination, there was a fullness to the middle third of the left upper lid, with two cherry-red spots at the apex (Fig 1). The cilia were undisturbed, and the lid margin was not thickened. There was approximately 2 mm left relative ptosis, which was interpreted as a pseudoptosis due to the weight of the lesion, in view of the intact left upper lid levator function. The lesion was firm but partially compressible, and at slit-lamp examination the two reddish areas on the apex appeared to be foci of
Fig 1. Top left. a 13-year-old black girl had a tumor present from birth that required treatment at 5 months of age. The lesion partially regressed, but slowly enlarged over a 3-year period with the recent appearance of hemorrhagic foci at the apex. Fig 2. Top right. a 34-year-old white woman presented with a slategray to blue lesion at the lid margin of the middle third of the right lower lid. Fig 3. Second row left. the slit lamp beam placed adjacent to the lesion discloses a red hue, suggesting a contribution of blood to the clinical discoloration. The clinical differential diagnosis was a malignant melanoma, a vascular tumor, or a blue nevus. Fig 4. Second row right. a 66-year-old white woman developed over several months a multiloculated cystic lesion in the temporal skin of her left lower lid. Massive discoloration occurred after a drainage procedure, leading to a more definitive excision. Fig 5. Third row left. two large dermal thrombi within dilated lymphatic channels are undergoing organization (hematoxylin-eosinphloxin, XSO). Fig 6. Third row right. a neo-formed lymphatic channel has pink lymph fluid with a few admixed erythrocytes in the lumen and is devoid of a mural cell component (hematoxylin-phloxin-saffron, X220). Fig 7. Bottom left. a staghorn lymphatic space is invaginated by a lymphoid aggregate. Note the focal presence of mural smooth muscle cells toward the upper right (hematoxylin-phloxin-saffron, X 120). Fig 8. Bottom right. dilated spaces separate the orbicularis muscle near the lid margin (muscle of Riolan) hematoxylin-phloxin-saffron, X40).
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telangiectasia. Vision was 20/20 in the right eye and 20/ 200 in the left. External examination of the conjunctiva was unremarkable. Slit-lamp examination disclosed an inferior iris coloboma, which appeared to be due to a focal absence of the sphincter muscle with a small remnant of iris root being present at 6:00 o'clock. On dilated fundus examination, the lens was unremarkable, no ciliary body or zonular colobomata were identified, and the posterior pole was unremarkable. It was believed that the patient had a partially regressed hemangioma, possibly a lymphangioma into which recent hemorrhage had occurred. The patient underwent excision of the tumor. A left upper lid supraciliary incision was made, and the epidermis and upper dermis were dissected free from an underlying reddish mass. The skin was undermined in all directions, and the lesional tissue was excised in the plane of the orbicularis striated muscle of the lid. Postoperatively, the patient has healed well, there is only 1 mm relative left ptosis, and the appearance is excellent after 12 months. The second patient was a 34-year-old white woman who had noted over a 4-month period a slowly enlarging "pigmented" lesion in the middle third of the right lower lid and the lid margin. The patient was referred for consultation after her local ophthalmologist raised the possibility of a malignant melanoma. The patient denied the presence of any preexistent lesion from childhood. There was no bleeding, pain, itching, or ocular discomfort from her lesion. Visual acuity was 20/20 in both eyes. On the lid margin of the right lower lid and involving the contiguous skin was a minimally upraised slate-grey to blue lesion (Fig 2). Slit-lamp biomicroscopy revealed intact Langer's epidermal lines, involvement of the lid margin up to the grey line but not beyond, and intact cilia. When the slit beam was moved to the side of the lesion, which was therefore indirectly illuminated by scattered light, a red appearance was demonstrated (Fig 3), suggesting a contribution of blood to the lesion. Because of the fear of a malignant melanoma and evidence of slight enlargement over a three month period, it was elected to perform a full thickness lid resection; the differential diagnosis included a vascular lesion, a blue nevus, or perhaps a malignant melanoma. During 2 years of follow-up the patient has had an excellent cosmetic appearance without any recurrence of the lesion. The third patient was a 66-year-old white woman with a history of iridocyclitis and secondary glaucoma in the left eye. Over several days, the patient became aware of a small upraised nonpigmented lesion in the temporal skin of the left lower lid. The lesion was not associated with any discharge, irritation, pruritis, pain, or periorbital swelling. When seen by her ophthalmologist, the diagnosis was a benign cyst; no surgery was performed because the lesion appeared to be well tolerated. Four months later the patient returned to her ophthalmologist, and it was discovered that the lesion was slightly larger than before, with a bluish cast (Fig 4). The lesion was incised and drained, resulting in the release of clear fluid. The following morning the patient 1280
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awoke to discover that the involved area was massively swollen, slightly tender, and had a diffuse black-andblue discoloration. She was consequently admitted to the hospital, and the skin on the outer portion of the left lower lid was reflected to reveal a cystic, poorly defined, multiloculated mass measuring 12 X 8 mm. This tissue was excised down to the orbicularis muscle. During 2112 years of follow-up, there has been no recurrence.
LIGHT AND ELECTRON MICROSCOPIC PATHOLOGIC FINDINGS In the first case the excised subepidermal tissues displayed microscopically two massively dilated vascular channels constituted by an attenuated monolayer of endothelial cells circumscribing organizing thrombi (Fig 5). The remainder of the lesion was composed of variably sized channels generally bereft of identifiable mural cells and containing clear, eosinophilic lymph fluid and occasionally formed blood elements (Fig 6). Small aggregates of lymphoid tissue were related to these lymphatic spaces, and rarely protruded into them; some of these channels displayed focal investment by smooth muscle cells (Fig 7). In the second case, the orbicularis striated muscle toward the lid margin contained large cystic spaces (Fig 8); individual bundles of muscles projected into these spaces as little papillae (Figs 9-11). Glandular units of an apocrine gland of Moll also abutted these large ectatic spaces (Fig 10). Neither blood nor lymph was found within the lumens, nor was lymphoid tissue present in the interstitium. The excisional biopsy specimen from the third case harbored cavernous channels located within the dermis, but not extending into the orbicularis striated muscle (Fig 12). Most of the channels were filled with dear lymph, although evidence of fresh hemorrhage was focally discerned (Fig 13). Small collections of lymphoid tissue without follicular architecture were located in the interstitium between the large vascular spaces (Figs 13, 14). Both lymphocytes and plasma cells contributed to the lymphoid aggregates. The lining of the vascular spaces was composed of a thin endothelial cell layer, without any apparent mural cell component (Fig 14). Occasional valves projected into the large cavernous spaces (Figs 15, 16). The connective tissue between the vascular spaces was loose and possessed scattered fibroblasts (Fig 15). Small blood vessels were located in the interstitium next to the lymphatic channels (Fig 16), and may have been the source of the fresh intralumenal hemorrhage. Electron microscopy was performed on a portion of the lesional tissue obtained in case 2. A thin endothelial lining was identified covering the striated muscle papillae projecting into the large vascular lumens (Fig 17). The endothelium was clothed by an interrupted but focally multilaminar basement membrane (Fig 17, top). Delicate
Fig 9. Top left, papillae of striated muscle project into a patulous empty lumen. Note the duct of a gland of Moll toward the upper left (hematoxylin-phloxin-saffront, XI20). Fig 10. Top right, glandular units of a gland of Moll project into the lumen, but are separated from it by a very attenuated monolayer of endothelial cells (hematoxylin, phloxin, saffron, X280. Fig 11. Second row left, an indistinct monolayer of endothelial cells clothes the striated muscle papillae projecting into the vascular space. The endothelial cells are better demonstrated in Figure 17
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Fig 17. Electron micrograph of a striated muscle papilla from the lesion in case 2. Top. the lumen (L) is delimited by a thin monolayer of endothelial cells (E). A discontinuous but focally multilaminar basement membrane (mbm) ensheaths the endothelial cell. The constant contraction of the muscle may have stimulated the endothelial cells to produce extra basement membrane material. Thin anchoring filaments (t) are embedded among thicker collagen fibers in the interstitium. No mural cells are associated with the endothelial cells in this area. although elongated fibroblastic cell processes (FP) are identifiable. SM = striated muscle cell of orbicularis with sarcomeric organization; arrow = continuous basement membrane of the striated muscle cell. Bottom. in another area. a pericytic cell (P) showing early smooth muscle differentiation with cytoplasmic filaments and fusiform densities (crossed arrows) is approximated to an endothelial cell (E). L = lymphatic lumen; SM = striated orbicularis muscle cell; arrow = continuous basement membrane of striated muscle cell (top and bottom X 12,500).
collagenous filaments (anchoring filaments) were located in the immediate vicinity of the endothelial cells, and were often embedded within thicker collagen fibers. For the most part, the only mural cells adjacent to the
flattened endothelial cells were fibroblasts an'4 their processes (Fig 17, top); however, mural cells with ~ricytic or smooth muscle differentiation were rarely disc:,bvered (Fig 17, bottom). .
(hematoxylin-phloxin-saffron, X280). Fig 12. Second row right. dermal biopsy specimen displays cavernous, lymph-filled channels riding above the orbicularis striated muscle, present below (hematoxylin-phloxin-saffran, X40). Fig 13. Third row left. lymphoid aggregate is present in the interstitium between several large vascular channels. The lymphatic channel below abuts the orbicularis striated muscle and contains a mixture of lymph fluid and fresh hemorrhage (hematoxylin-phloxin-saffron, X 150). Fig 14. Third row right. both lymphocytes and plasma cells are present in the lymphoid aggregate. The lymphatic channel is formed by a thin monolayer of endothelial cells, devoid of a significant population of mural cells. Note the mixture of pink lymph and scattered erythrocytes within the lumen (hematoxylin-phloxin-saffron. X280). Fig 15. l!ottom left. multiple cavernous lymphatic spaces are filled with cell-free lymph, and display valves projecting into the lumens. The interstitium between the lymphatic channels is loose and contains fibroblasts (hematoxylin-phloxin-saffron, X80). Fig 16. Bottom right. a valve projects into a lymph-filled lumen below, and displays a mononuclear inflammation. Note the presence of small blood vessels in the interstitium below, which may have been the source of the fresh hemorrhage (hematoxylin-phloxin-saffron, X180).
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LYMPHANGIOMAS OF THE EYELIDS
DISCUSSION Lymphangioma involving the orbit is considered to be a choristoma, because the orbit is not normally provided with endothelial-lined lymphatic channels. 6 •7 These lesions are presumed to differentiate from misdirected endothelial anlage in the orbit, although one school of thought holds that they are a form of venous malformation or varix, 8 mostly on the basis of venographic studies which show unusually dilated venous structures associated with the aberrant lymphatic channels. Ultrastructural studies of orbital lymphangioma9 . lo have clearly established that they have the same features as lymphangiomas elsewhere in the body, I 1-14 including interrupted basement membranes enveloping the flattened endothelial cells, general absence of pericytic or myoid mural cells, and fine anchoring filaments typical of the architecture of non-neoplastic lymphatics. Lymphoid tissue may be associated with this orbital vascular tumor, resultin-g in exacerbation of the proptosis during upper respiratory infections in children, wherein the lymphoid tissue may undergo a benign hyperplasia. I •9 Abrupt hemorrhage into the delicate lymphatic spaces, which are normally filled only with cell-free lymph, may create a chocolate cyst; the ominous proptosis must be differentiated from that encountered in rhabdomyosarcoma in children. CT scanning will often show in orbital lymphangioma blood layering in the dominant hemorrhagic cyst, and a reticulated pattern indicative of cavernous lymphatic channels. Epibulbar proliferations of lymphangiomatous tissue are also rare, and many lesions thought to be lymphangiomas may only represent lymphangiectasias, since the conjunctiva is richly endowed with lymphatic channels in the substantia propria on a normal anatomic basis. Extensive conjunctival nevi that are poorly pigmented may have florid epithelial inclusion cysts that can simulate the appearance of clear lymphatic channels. 15 While extensive childhood lymphangiomas may involve the eyelids together with the orbit, the types of lesions that we are describing in this paper, ie. comparatively circumscribed lesions that involve only a small portion of one lid, have not received adequate attention in the ophthalmic literature. The discovery of lymphangiomas in the eyelids should not be unexpected because, like the conjunctival substantia propria, the dermis of the lids exhibits an abundance of lymphatics. In our first patient, an apparently congenital lesion continued to grow until at age 5 months it sufficiently involved the upper lid to cause amblyopia. It was treated with carbon dioxide ice, and partially regressed. The absence of complete regression clinically differentiates palpebral lymphangioma from capillary hemangioma of childhood, since the latter lesion would have completely regressed by age 13 to leave a flat, corrugated cigarette paper scar in the skin. 16 The development of two cherryred spots on the apex of the lesion indicates that even treated and partially scarred lymphangiomas of the
eyelids can still undergo hemorrhage with intralumenal thrombosis and organization (miniature chocolate cysts). In our second patient, a blue lesion in the midportion of the lower lid margin appeared in an adult over a several month period. The referring ophthalmologist was fearful that the lesion might represent a nevus undergoing a degeneration into a melanoma. Nevi of the lid margin are generally present from childhood, and consequently would not make an abrupt appearance over several months. The lesion had a soft feel clinically, whereas a nevus or a melanoma should be firm to the palpating finger. Furthermore, by indirect illumination with the slit-lamp beam, a red hue could be discerned, signifying that blood was contributing to the clinical picture. Other lesions originating from the epidermis such as basal cell carcinoma, SQuamous cell carcinoma, and seborrheic keratosis would have had a firmer or more roughened texture. Pigmented variants of these lesions are typically encountered in darkly complexioned individuals, but our patient was very fair-skinned and of Northern European origin. Our explanation for the abrupt appearance of the deeply situated blood is that the lesion may well have been a bloodless lymphangioma hidden within the orbicular muscle of Riolan for many years, but either spontaneous bleeding or bleeding after minor trauma brought it to clinical attention. Our third patient was a 66-year-old white woman who one day noticed an upraised nonpigmented lesion on the outer aspect of her left lower lid. On clinical examination, the lesion was considered to be a mundane inclusion cyst commonly seen ~n the eyelids. Several months later, an abrupt worsening of the condition occurred, and the patient awoke noting the area to be swollen, slightly tender, and black and blue. Excision of this mass led to the discovery of a dermal lymphangioma. The most common cysts of the lids are epidermal inclusion cysts (pilar cysts), hydrocystomas of either eccrine or apocrine origin, and occasionally cystic basal cell carcinomas, all of which would not normally be associated with hemorrhage. The histopathologic features of our three lesions were unequivocally those of lymphangioma. They all featured dilated vascular channels formed chiefly by an attenuated layer of endothelial cells devoid of a significant mural cell component. Most of the lumens contained pink, amorphous lymph, sometimes intermixed with fresh blood, perhaps contributed by surgery or earlier trauma that therefore brought the lesion to clinical attention. In the second lesion, which was exclusively situated within the orbicularis striated muscle of the lid margin, the endothelial cells had proliferated to create ectatic channels separating bundles of striated muscle cells, which projected as unusual papillae into some of the lumens. No lymphoid follicles were associated with the lesion, nor were any valves identified. However, typical anchoring filments of thin collagen and rare pericytic cells were discovered. These ultrastructural findings differ from those of capillary and cavernous hemangiomas l7 ; in the former, pericytes are regularly associated with 1283
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plump endothelial cells, whereas in the latter, multilaminar well differentiated smooth muscle cells form a distinct wall. In the other two lesions, cavernous channels filled with lymph occasionally possessed valves, and focal small collections of lymphocytes were identified in the interstitium between the channels or else invaginated portions of their walls. These lesions were located in the lower and midreticular dermis of the lids, distinguishing them from lymphangioma circumscriptum seen elsewhere in the skin, which classically involves the upper reticular and papillary dermis. 18 Light and electron microscopy observation of focal smooth muscle cells in the walls of some of the lymphatic channels is still compatible with the diagnosis of lymphangioma. This feature may be seen in treated and scarred, recurrent orbital lymphangiomas l9 ; indeed, variant lymphangiomas with prominent pericytic and smooth muscle cell components are well recognized. 20- 23
REFERENCES 1. Jones IS. Lymphangiomas of the ocular adnexa; an analysis of sixty-two cases. Am J Ophthalmol1961; 51:481-509. 2. Reese AB, Howard GM. Unusual manifestations of ocular lymphangioma and Iymphangiectasias. Surv Ophthalmol 1973-74; 18:22631. 3. Reese AB. Tumors of the Eye, 3rd ed. Hagerstown: Harper & Row, 1976; 291-3. 4. Iliff WJ, Green WR. Orbital lymphangiomas. Ophthalmology 1979; 86:914-29. 5. Yanoff M, Fine BS. Ocular Pathology: A Text and Atlas, 2nd ed. Philadelphia: Harper & Row, 1982; 662-4. 6. Jakobiec FA, Iwamoto T. Ocular adnexa: introduction to lids, conjunctiva, and orbit. In: Jakobiec FA, ed. Ocular Anatomy, Embryology, and Teratology. Philadelphia: Harper & Row, 1982; 677-731. 7. Bergen MP. Spatial aspects of the orbital vascular system. In: Jakobiec FA, ed. Ocular Anatomy, Embryology, and Teratology. Philadelphia: Harper & Row, 1982; 859-67.
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8. Wright JE. Orbital vascular anomalies. Trans Am Acad Ophthalmol Otolaryngol 1974; 78:606-16. 9. Jakobiec FA, Jones IS. Vascular tumors, malformations, and degenerations. In: Jones IS, Jakobiec FA, eds. Diseases of the Orbit. Hagerstown: Harper & Row, 1979; 269-308. 10. Jakobiec FA, Font RL, Iwamoto T. Diagnostic ultrastructural pathology of ophthalmic tumors. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978; 359-453. 11. Elliott RL, Williams RD, Bayles 0, Griffin J. Lymphangioma of the duodenum: case report with light and electron microscopic observation. Ann Surg 1966; 163:86-92. 12. Marcus JB, Lynn JA. Ultrastructural comparison of an adenomatoid tumor, lymphangioma, hemangioma, and mesothelioma. Cancer 1970; 25:171-5. 13. Waldo ED, Vuletin JC, Kaye GI. The ultrastructure of vascular tumors; additional observations and a review of the literature. Pathol Annu 1977; 12(Pt. 2):279-308. 14. Sun CC, Tang CK, Hill JL. Mesenteric lymphangioma; a\pase report with transmission and scanning electron microscopic stUdies. Arch Pathol Lab Med 1980; 104:316-8. 15. Rosenfeld SI, Smith ME. Benign cystic nevus of the conjunctiva. Ophthalmology 1983; 90; 1459-61. 16. Haik BG, Jakobiec FA, Ellsworth RM, Jones IS. Capillary hemangioma of the lids and orbit: an analysis of the clinical features and therapeutic results in 101 cases. Ophthalmology 1979; 86:760-89. 17. Iwamoto T, Jakobiec FA. Ultrastructural comparison of capillary and cavernous hemangiomas of the orbit. Arch Ophthalmol 1979; 97: 1144-53. 18. Lever WF, Schaumburg-Lever G. Histopathology of the Skin, 6th ed. Philadelphia: JB Lippincott, 1983; 632. 19. Harris GJ, Jakobiec FA. Cavernous hemangioma of the orbit: a clinicopathologic analysis of sixty-six cases. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978; 74181. 20. Enterline HT, Roberts B. Lymphangiopericytoma; case report of a previously undescribed tumor type. Cancer 1955; 8:582-7. 21. Cornog JL Jr, Enterline HT. Lymphangioma, a benign lesion of chyliferous lymphatiCS synonymous with Iymphangiopericytoma. Cancer 1966; 19: 1909-30. 22. Joliat G, Stalder H, Kapanci Y. Lymphangiomyomatosis: a clinicoanatomical entity. Cancer 1973; 31 :455-61. 23. Wolff M. Lymphangiomyoma: clinicopathologic study and ultrastructural confirmation of its histogenesis. Cancer 1973; 31:988-1007.
!
Abstract: Three patients are described with focal lymphangiomatous lesions of their eyelids. A child with a partially regressed , congenital lesion presented with evidence of recent hemorrhage, while, of two adults with acquired tumors, one had a blue lesion suggesting a malignant melanoma, and the other had a more obviously cystic lesion, suggesting an epidermal or adnexal cyst. In one case, the lesion was situated entirely within the marginal orbicularis striated muscle, and in the other two cases the lesion was restricted to the dermis of the lid. Abrupt change in the coloration of a lesion in the lid should suggest hemorrhage into a preexistent tumor. Hemorrhage into lymphangiomas is extremely common, and therefore this vascular tumor should be included in the differential diagnosis of previously nondiscolored lesions. Other vascular tumors, such as capillary, cavernous or venous angiomas would be expected to have a longstanding reddish-blue hue. [Key words: conjunctiva, eyelids, electron microscopy, lymphangioma, orbit.] Ophthalmology 91: 1278-1284, 1984
Lymphangiomas of the ocular adnexa conjure up the specter of massive involvement of the eyelids and orbit. 1--4 Such lesions can produce a hideous proptosis and facial deformity; they provide surgical challenges the equal of those posed by extensive neuromatosis in von Recklinghausen's disease. Lymphangiomas of this sort make their appearance in childhood, and generally entail mUltiple debulking surgical procedures to restore some semblance of a normal cosmetic appearance, although the eye invariably suffers as a result of a constrictive optic neuropathy. There is a group of lymphangiomas with more restricted orbital involvement, and a still smaller set that may focally involve the epibulbar tissues and eyelids. Lymphangiomas of the last site have received almost no attention in the ophthalmic literature. s We present three unusual palpebral lymphangiomas that offered differential diagnostic problems clinically. One of these lesions was congenital and two were acquired From the Departments of Ophthalmology and Pathology, Manhattan Eye, Ear and Throat Hospital and The New York Hospital-Cornell Medical Center, New York City. Supported in part by a grant from the Zelda Radow Weintraub Cancer Fund, Inc .• New York City. Dr. Jakobiec is the recipient of the Research to Prevent Blindness Robert E. McCormick Scholar Award. Reprint requests to Frederick A. Jakobiec, MD, Chairman, Department of Ophthalmology. Manhattan Eye. Ear and Throat Hospital, 210 East 64th Street. New York. NY 10021.
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and occurred in adults. Of the adult lesions, one was a striking curiosity because it was situated entirely within the orbicularis striated muscle of the lid margin (muscle of Riolan), while the other was a collection of neoformed ectatic lymphatic channels restricted to a small portion of the dermis of the eyelid.
CLINICAL HISTORIES A 13-year-old black girl was born with a tumor of the left upper lid, which had continued to enlarge after birth to create partial occlusion of the left pupil. At age 5 months, the tumor was treated with carbon dioxide ice, resulting in a marked shrinkage in the size of the tumor over the ensuing 2 or 3 years. At 10 years, the tumor began to slowly enlarge again, and over the 3 months prior to presentation two or three red areas on the surface of the tumor began to appear. On ocular examination, there was a fullness to the middle third of the left upper lid, with two cherry-red spots at the apex (Fig 1). The cilia were undisturbed, and the lid margin was not thickened. There was approximately 2 mm left relative ptosis, which was interpreted as a pseudoptosis due to the weight of the lesion, in view of the intact left upper lid levator function. The lesion was firm but partially compressible, and at slit-lamp examination the two reddish areas on the apex appeared to be foci of
Fig 1. Top left. a 13-year-old black girl had a tumor present from birth that required treatment at 5 months of age. The lesion partially regressed, but slowly enlarged over a 3-year period with the recent appearance of hemorrhagic foci at the apex. Fig 2. Top right. a 34-year-old white woman presented with a slategray to blue lesion at the lid margin of the middle third of the right lower lid. Fig 3. Second row left. the slit lamp beam placed adjacent to the lesion discloses a red hue, suggesting a contribution of blood to the clinical discoloration. The clinical differential diagnosis was a malignant melanoma, a vascular tumor, or a blue nevus. Fig 4. Second row right. a 66-year-old white woman developed over several months a multiloculated cystic lesion in the temporal skin of her left lower lid. Massive discoloration occurred after a drainage procedure, leading to a more definitive excision. Fig 5. Third row left. two large dermal thrombi within dilated lymphatic channels are undergoing organization (hematoxylin-eosinphloxin, XSO). Fig 6. Third row right. a neo-formed lymphatic channel has pink lymph fluid with a few admixed erythrocytes in the lumen and is devoid of a mural cell component (hematoxylin-phloxin-saffron, X220). Fig 7. Bottom left. a staghorn lymphatic space is invaginated by a lymphoid aggregate. Note the focal presence of mural smooth muscle cells toward the upper right (hematoxylin-phloxin-saffron, X 120). Fig 8. Bottom right. dilated spaces separate the orbicularis muscle near the lid margin (muscle of Riolan) hematoxylin-phloxin-saffron, X40).
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telangiectasia. Vision was 20/20 in the right eye and 20/ 200 in the left. External examination of the conjunctiva was unremarkable. Slit-lamp examination disclosed an inferior iris coloboma, which appeared to be due to a focal absence of the sphincter muscle with a small remnant of iris root being present at 6:00 o'clock. On dilated fundus examination, the lens was unremarkable, no ciliary body or zonular colobomata were identified, and the posterior pole was unremarkable. It was believed that the patient had a partially regressed hemangioma, possibly a lymphangioma into which recent hemorrhage had occurred. The patient underwent excision of the tumor. A left upper lid supraciliary incision was made, and the epidermis and upper dermis were dissected free from an underlying reddish mass. The skin was undermined in all directions, and the lesional tissue was excised in the plane of the orbicularis striated muscle of the lid. Postoperatively, the patient has healed well, there is only 1 mm relative left ptosis, and the appearance is excellent after 12 months. The second patient was a 34-year-old white woman who had noted over a 4-month period a slowly enlarging "pigmented" lesion in the middle third of the right lower lid and the lid margin. The patient was referred for consultation after her local ophthalmologist raised the possibility of a malignant melanoma. The patient denied the presence of any preexistent lesion from childhood. There was no bleeding, pain, itching, or ocular discomfort from her lesion. Visual acuity was 20/20 in both eyes. On the lid margin of the right lower lid and involving the contiguous skin was a minimally upraised slate-grey to blue lesion (Fig 2). Slit-lamp biomicroscopy revealed intact Langer's epidermal lines, involvement of the lid margin up to the grey line but not beyond, and intact cilia. When the slit beam was moved to the side of the lesion, which was therefore indirectly illuminated by scattered light, a red appearance was demonstrated (Fig 3), suggesting a contribution of blood to the lesion. Because of the fear of a malignant melanoma and evidence of slight enlargement over a three month period, it was elected to perform a full thickness lid resection; the differential diagnosis included a vascular lesion, a blue nevus, or perhaps a malignant melanoma. During 2 years of follow-up the patient has had an excellent cosmetic appearance without any recurrence of the lesion. The third patient was a 66-year-old white woman with a history of iridocyclitis and secondary glaucoma in the left eye. Over several days, the patient became aware of a small upraised nonpigmented lesion in the temporal skin of the left lower lid. The lesion was not associated with any discharge, irritation, pruritis, pain, or periorbital swelling. When seen by her ophthalmologist, the diagnosis was a benign cyst; no surgery was performed because the lesion appeared to be well tolerated. Four months later the patient returned to her ophthalmologist, and it was discovered that the lesion was slightly larger than before, with a bluish cast (Fig 4). The lesion was incised and drained, resulting in the release of clear fluid. The following morning the patient 1280
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awoke to discover that the involved area was massively swollen, slightly tender, and had a diffuse black-andblue discoloration. She was consequently admitted to the hospital, and the skin on the outer portion of the left lower lid was reflected to reveal a cystic, poorly defined, multiloculated mass measuring 12 X 8 mm. This tissue was excised down to the orbicularis muscle. During 2112 years of follow-up, there has been no recurrence.
LIGHT AND ELECTRON MICROSCOPIC PATHOLOGIC FINDINGS In the first case the excised subepidermal tissues displayed microscopically two massively dilated vascular channels constituted by an attenuated monolayer of endothelial cells circumscribing organizing thrombi (Fig 5). The remainder of the lesion was composed of variably sized channels generally bereft of identifiable mural cells and containing clear, eosinophilic lymph fluid and occasionally formed blood elements (Fig 6). Small aggregates of lymphoid tissue were related to these lymphatic spaces, and rarely protruded into them; some of these channels displayed focal investment by smooth muscle cells (Fig 7). In the second case, the orbicularis striated muscle toward the lid margin contained large cystic spaces (Fig 8); individual bundles of muscles projected into these spaces as little papillae (Figs 9-11). Glandular units of an apocrine gland of Moll also abutted these large ectatic spaces (Fig 10). Neither blood nor lymph was found within the lumens, nor was lymphoid tissue present in the interstitium. The excisional biopsy specimen from the third case harbored cavernous channels located within the dermis, but not extending into the orbicularis striated muscle (Fig 12). Most of the channels were filled with dear lymph, although evidence of fresh hemorrhage was focally discerned (Fig 13). Small collections of lymphoid tissue without follicular architecture were located in the interstitium between the large vascular spaces (Figs 13, 14). Both lymphocytes and plasma cells contributed to the lymphoid aggregates. The lining of the vascular spaces was composed of a thin endothelial cell layer, without any apparent mural cell component (Fig 14). Occasional valves projected into the large cavernous spaces (Figs 15, 16). The connective tissue between the vascular spaces was loose and possessed scattered fibroblasts (Fig 15). Small blood vessels were located in the interstitium next to the lymphatic channels (Fig 16), and may have been the source of the fresh intralumenal hemorrhage. Electron microscopy was performed on a portion of the lesional tissue obtained in case 2. A thin endothelial lining was identified covering the striated muscle papillae projecting into the large vascular lumens (Fig 17). The endothelium was clothed by an interrupted but focally multilaminar basement membrane (Fig 17, top). Delicate
Fig 9. Top left, papillae of striated muscle project into a patulous empty lumen. Note the duct of a gland of Moll toward the upper left (hematoxylin-phloxin-saffront, XI20). Fig 10. Top right, glandular units of a gland of Moll project into the lumen, but are separated from it by a very attenuated monolayer of endothelial cells (hematoxylin, phloxin, saffron, X280. Fig 11. Second row left, an indistinct monolayer of endothelial cells clothes the striated muscle papillae projecting into the vascular space. The endothelial cells are better demonstrated in Figure 17
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Fig 17. Electron micrograph of a striated muscle papilla from the lesion in case 2. Top. the lumen (L) is delimited by a thin monolayer of endothelial cells (E). A discontinuous but focally multilaminar basement membrane (mbm) ensheaths the endothelial cell. The constant contraction of the muscle may have stimulated the endothelial cells to produce extra basement membrane material. Thin anchoring filaments (t) are embedded among thicker collagen fibers in the interstitium. No mural cells are associated with the endothelial cells in this area. although elongated fibroblastic cell processes (FP) are identifiable. SM = striated muscle cell of orbicularis with sarcomeric organization; arrow = continuous basement membrane of the striated muscle cell. Bottom. in another area. a pericytic cell (P) showing early smooth muscle differentiation with cytoplasmic filaments and fusiform densities (crossed arrows) is approximated to an endothelial cell (E). L = lymphatic lumen; SM = striated orbicularis muscle cell; arrow = continuous basement membrane of striated muscle cell (top and bottom X 12,500).
collagenous filaments (anchoring filaments) were located in the immediate vicinity of the endothelial cells, and were often embedded within thicker collagen fibers. For the most part, the only mural cells adjacent to the
flattened endothelial cells were fibroblasts an'4 their processes (Fig 17, top); however, mural cells with ~ricytic or smooth muscle differentiation were rarely disc:,bvered (Fig 17, bottom). .
(hematoxylin-phloxin-saffron, X280). Fig 12. Second row right. dermal biopsy specimen displays cavernous, lymph-filled channels riding above the orbicularis striated muscle, present below (hematoxylin-phloxin-saffran, X40). Fig 13. Third row left. lymphoid aggregate is present in the interstitium between several large vascular channels. The lymphatic channel below abuts the orbicularis striated muscle and contains a mixture of lymph fluid and fresh hemorrhage (hematoxylin-phloxin-saffron, X 150). Fig 14. Third row right. both lymphocytes and plasma cells are present in the lymphoid aggregate. The lymphatic channel is formed by a thin monolayer of endothelial cells, devoid of a significant population of mural cells. Note the mixture of pink lymph and scattered erythrocytes within the lumen (hematoxylin-phloxin-saffron. X280). Fig 15. l!ottom left. multiple cavernous lymphatic spaces are filled with cell-free lymph, and display valves projecting into the lumens. The interstitium between the lymphatic channels is loose and contains fibroblasts (hematoxylin-phloxin-saffron, X80). Fig 16. Bottom right. a valve projects into a lymph-filled lumen below, and displays a mononuclear inflammation. Note the presence of small blood vessels in the interstitium below, which may have been the source of the fresh hemorrhage (hematoxylin-phloxin-saffron, X180).
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DISCUSSION Lymphangioma involving the orbit is considered to be a choristoma, because the orbit is not normally provided with endothelial-lined lymphatic channels. 6 •7 These lesions are presumed to differentiate from misdirected endothelial anlage in the orbit, although one school of thought holds that they are a form of venous malformation or varix, 8 mostly on the basis of venographic studies which show unusually dilated venous structures associated with the aberrant lymphatic channels. Ultrastructural studies of orbital lymphangioma9 . lo have clearly established that they have the same features as lymphangiomas elsewhere in the body, I 1-14 including interrupted basement membranes enveloping the flattened endothelial cells, general absence of pericytic or myoid mural cells, and fine anchoring filaments typical of the architecture of non-neoplastic lymphatics. Lymphoid tissue may be associated with this orbital vascular tumor, resultin-g in exacerbation of the proptosis during upper respiratory infections in children, wherein the lymphoid tissue may undergo a benign hyperplasia. I •9 Abrupt hemorrhage into the delicate lymphatic spaces, which are normally filled only with cell-free lymph, may create a chocolate cyst; the ominous proptosis must be differentiated from that encountered in rhabdomyosarcoma in children. CT scanning will often show in orbital lymphangioma blood layering in the dominant hemorrhagic cyst, and a reticulated pattern indicative of cavernous lymphatic channels. Epibulbar proliferations of lymphangiomatous tissue are also rare, and many lesions thought to be lymphangiomas may only represent lymphangiectasias, since the conjunctiva is richly endowed with lymphatic channels in the substantia propria on a normal anatomic basis. Extensive conjunctival nevi that are poorly pigmented may have florid epithelial inclusion cysts that can simulate the appearance of clear lymphatic channels. 15 While extensive childhood lymphangiomas may involve the eyelids together with the orbit, the types of lesions that we are describing in this paper, ie. comparatively circumscribed lesions that involve only a small portion of one lid, have not received adequate attention in the ophthalmic literature. The discovery of lymphangiomas in the eyelids should not be unexpected because, like the conjunctival substantia propria, the dermis of the lids exhibits an abundance of lymphatics. In our first patient, an apparently congenital lesion continued to grow until at age 5 months it sufficiently involved the upper lid to cause amblyopia. It was treated with carbon dioxide ice, and partially regressed. The absence of complete regression clinically differentiates palpebral lymphangioma from capillary hemangioma of childhood, since the latter lesion would have completely regressed by age 13 to leave a flat, corrugated cigarette paper scar in the skin. 16 The development of two cherryred spots on the apex of the lesion indicates that even treated and partially scarred lymphangiomas of the
eyelids can still undergo hemorrhage with intralumenal thrombosis and organization (miniature chocolate cysts). In our second patient, a blue lesion in the midportion of the lower lid margin appeared in an adult over a several month period. The referring ophthalmologist was fearful that the lesion might represent a nevus undergoing a degeneration into a melanoma. Nevi of the lid margin are generally present from childhood, and consequently would not make an abrupt appearance over several months. The lesion had a soft feel clinically, whereas a nevus or a melanoma should be firm to the palpating finger. Furthermore, by indirect illumination with the slit-lamp beam, a red hue could be discerned, signifying that blood was contributing to the clinical picture. Other lesions originating from the epidermis such as basal cell carcinoma, SQuamous cell carcinoma, and seborrheic keratosis would have had a firmer or more roughened texture. Pigmented variants of these lesions are typically encountered in darkly complexioned individuals, but our patient was very fair-skinned and of Northern European origin. Our explanation for the abrupt appearance of the deeply situated blood is that the lesion may well have been a bloodless lymphangioma hidden within the orbicular muscle of Riolan for many years, but either spontaneous bleeding or bleeding after minor trauma brought it to clinical attention. Our third patient was a 66-year-old white woman who one day noticed an upraised nonpigmented lesion on the outer aspect of her left lower lid. On clinical examination, the lesion was considered to be a mundane inclusion cyst commonly seen ~n the eyelids. Several months later, an abrupt worsening of the condition occurred, and the patient awoke noting the area to be swollen, slightly tender, and black and blue. Excision of this mass led to the discovery of a dermal lymphangioma. The most common cysts of the lids are epidermal inclusion cysts (pilar cysts), hydrocystomas of either eccrine or apocrine origin, and occasionally cystic basal cell carcinomas, all of which would not normally be associated with hemorrhage. The histopathologic features of our three lesions were unequivocally those of lymphangioma. They all featured dilated vascular channels formed chiefly by an attenuated layer of endothelial cells devoid of a significant mural cell component. Most of the lumens contained pink, amorphous lymph, sometimes intermixed with fresh blood, perhaps contributed by surgery or earlier trauma that therefore brought the lesion to clinical attention. In the second lesion, which was exclusively situated within the orbicularis striated muscle of the lid margin, the endothelial cells had proliferated to create ectatic channels separating bundles of striated muscle cells, which projected as unusual papillae into some of the lumens. No lymphoid follicles were associated with the lesion, nor were any valves identified. However, typical anchoring filments of thin collagen and rare pericytic cells were discovered. These ultrastructural findings differ from those of capillary and cavernous hemangiomas l7 ; in the former, pericytes are regularly associated with 1283
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plump endothelial cells, whereas in the latter, multilaminar well differentiated smooth muscle cells form a distinct wall. In the other two lesions, cavernous channels filled with lymph occasionally possessed valves, and focal small collections of lymphocytes were identified in the interstitium between the channels or else invaginated portions of their walls. These lesions were located in the lower and midreticular dermis of the lids, distinguishing them from lymphangioma circumscriptum seen elsewhere in the skin, which classically involves the upper reticular and papillary dermis. 18 Light and electron microscopy observation of focal smooth muscle cells in the walls of some of the lymphatic channels is still compatible with the diagnosis of lymphangioma. This feature may be seen in treated and scarred, recurrent orbital lymphangiomas l9 ; indeed, variant lymphangiomas with prominent pericytic and smooth muscle cell components are well recognized. 20- 23
REFERENCES 1. Jones IS. Lymphangiomas of the ocular adnexa; an analysis of sixty-two cases. Am J Ophthalmol1961; 51:481-509. 2. Reese AB, Howard GM. Unusual manifestations of ocular lymphangioma and Iymphangiectasias. Surv Ophthalmol 1973-74; 18:22631. 3. Reese AB. Tumors of the Eye, 3rd ed. Hagerstown: Harper & Row, 1976; 291-3. 4. Iliff WJ, Green WR. Orbital lymphangiomas. Ophthalmology 1979; 86:914-29. 5. Yanoff M, Fine BS. Ocular Pathology: A Text and Atlas, 2nd ed. Philadelphia: Harper & Row, 1982; 662-4. 6. Jakobiec FA, Iwamoto T. Ocular adnexa: introduction to lids, conjunctiva, and orbit. In: Jakobiec FA, ed. Ocular Anatomy, Embryology, and Teratology. Philadelphia: Harper & Row, 1982; 677-731. 7. Bergen MP. Spatial aspects of the orbital vascular system. In: Jakobiec FA, ed. Ocular Anatomy, Embryology, and Teratology. Philadelphia: Harper & Row, 1982; 859-67.
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8. Wright JE. Orbital vascular anomalies. Trans Am Acad Ophthalmol Otolaryngol 1974; 78:606-16. 9. Jakobiec FA, Jones IS. Vascular tumors, malformations, and degenerations. In: Jones IS, Jakobiec FA, eds. Diseases of the Orbit. Hagerstown: Harper & Row, 1979; 269-308. 10. Jakobiec FA, Font RL, Iwamoto T. Diagnostic ultrastructural pathology of ophthalmic tumors. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978; 359-453. 11. Elliott RL, Williams RD, Bayles 0, Griffin J. Lymphangioma of the duodenum: case report with light and electron microscopic observation. Ann Surg 1966; 163:86-92. 12. Marcus JB, Lynn JA. Ultrastructural comparison of an adenomatoid tumor, lymphangioma, hemangioma, and mesothelioma. Cancer 1970; 25:171-5. 13. Waldo ED, Vuletin JC, Kaye GI. The ultrastructure of vascular tumors; additional observations and a review of the literature. Pathol Annu 1977; 12(Pt. 2):279-308. 14. Sun CC, Tang CK, Hill JL. Mesenteric lymphangioma; a\pase report with transmission and scanning electron microscopic stUdies. Arch Pathol Lab Med 1980; 104:316-8. 15. Rosenfeld SI, Smith ME. Benign cystic nevus of the conjunctiva. Ophthalmology 1983; 90; 1459-61. 16. Haik BG, Jakobiec FA, Ellsworth RM, Jones IS. Capillary hemangioma of the lids and orbit: an analysis of the clinical features and therapeutic results in 101 cases. Ophthalmology 1979; 86:760-89. 17. Iwamoto T, Jakobiec FA. Ultrastructural comparison of capillary and cavernous hemangiomas of the orbit. Arch Ophthalmol 1979; 97: 1144-53. 18. Lever WF, Schaumburg-Lever G. Histopathology of the Skin, 6th ed. Philadelphia: JB Lippincott, 1983; 632. 19. Harris GJ, Jakobiec FA. Cavernous hemangioma of the orbit: a clinicopathologic analysis of sixty-six cases. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978; 74181. 20. Enterline HT, Roberts B. Lymphangiopericytoma; case report of a previously undescribed tumor type. Cancer 1955; 8:582-7. 21. Cornog JL Jr, Enterline HT. Lymphangioma, a benign lesion of chyliferous lymphatiCS synonymous with Iymphangiopericytoma. Cancer 1966; 19: 1909-30. 22. Joliat G, Stalder H, Kapanci Y. Lymphangiomyomatosis: a clinicoanatomical entity. Cancer 1973; 31 :455-61. 23. Wolff M. Lymphangiomyoma: clinicopathologic study and ultrastructural confirmation of its histogenesis. Cancer 1973; 31:988-1007.
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