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Histopathology of the eye in diffuse neonatal hemangiomatosis
BRIEF REPORTS Histopathology of the Eye in Diffuse Neonatal Hemangiomatosis Charmaine W. Chang, BSc, Narsing A. Rao, MD, and J. Timothy Stout, MD, PhD PURPOSE: To report the ocular presentation and histopathology of a patient with diffuse neonatal hemangiomatosis. METHODS: Case report. A 3.7-kg female was born at term. Multiple hemangiomas were present, and the patient died 39 days after birth. RESULTS: Widespread cutaneous and visceral hemangiomas were present. Ophthalmic examination disclosed bilateral eyelid and conjunctival hemangiomas. The right eye had multiple iris hemangiomas, hyphema, vitreous hemorrhage, and discrete subretinal lesions. Histopathology of the right eye demonstrated hemangiomas involving the iris, ciliary body, and ciliary processes. CONCLUSION: Diffuse neonatal hemangiomatosis was associated with ophthalmic findings of multiple hemangiomas involving eyelid, conjunctiva, iris, ciliary body, and ciliary processes. (Am J Ophthalmol 1998;125:868 – 870. © 1998 by Elsevier Science Inc. All rights reserved.)
D
IFFUSE NEONATAL HEMANGIOMATOSIS IS A RARE
condition characterized by multiple cutaneous and visceral hemangiomas. It is associated with a 60% to 90% mortality rate in the first few months of life, usually as a result of high-output cardiac failure caused by arteriovenous shunting.1–3 Familial cases Accepted for publication Dec 9, 1997. University of British Columbia, Faculty of Medicine (C.W.C.); Doheny Eye Institute, University of Southern California (N.A.R.); and Childrens Hospital Los Angeles, Division of Ophthalmology, University of Southern California (J.T.S.). Inquiries to J. Timothy Stout, MD, PhD, Childrens Hospital Los Angeles, Division of Ophthalmology, Mailstop #88, 4650 Sunset Blvd, Los Angeles, CA 90027; fax: (213) 666-6283; e-mail: tstout%smtpgate@ chlais.usc.edu
868
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1998 BY
of neonatal hemangiomatosis have been described.4 We report a case of diffuse neonatal hemangiomatosis with eyelid, conjunctival, and iris hemangiomas and describe the pathology. A 3.7-kg female was born at term after an uncomplicated pregnancy and delivery. Multiple cutaneous hemangiomas were present, measuring up to 3 mm in diameter in a scattered distribution throughout the body (Figure 1). Hepatomegaly and mild jaundice were noted. No other systemic abnormalities were apparent. Investigations disclosed patent ductus arteriosus, patent foramen ovale, and mild cardiomegaly. Hepatomegaly with diffuse biliary dilatation, the consequence of large hepatic hemangiomas, was demonstrated. Ophthalmic examination disclosed multiple bilateral eyelid and conjunctival hemangiomas. The right eye presented iris hemangiomas, a small hyphema, vitreous hemorrhage, and discrete subretinal lesions, suggestive of subretinal hemorrhages. The infant was treated with intravenous methylprednisolone (1 mg/kg of body weight, every 6 hours) and interferon alfa-2a (daily subcutaneous doses of 600,000 units/m2 of body surface area for 3 days and 900,000 units/m2 of body surface area thereafter) with minimal beneficial effect. Congestive heart failure developed and progressively worsened despite an attempt to embolize hepatic feeder vessels. A consumptive coagulopathy developed, and despite all efforts, the patient’s condition deteriorated rapidly, resulting in death 39 days after birth. Upon autopsy, multiple hemangiomas were present on the skin, liver, lungs, pleura, epiglottis, stomach, small intestine, pancreas, kidneys, ovaries, and vagina. A large hematoma was present in the right cerebellar hemisphere. Both eyes were obtained for histopathologic study. Grossly, both eyes appeared normal in size. The anterior chambers were deep, and the angles ap-
ELSEVIER SCIENCE INC. ALL
RIGHTS RESERVED.
0002-9394/98/$19.00 PII S0002-9394(98)00049-X
FIGURE 1. (Left) Diffuse neonatal hemangiomatosis. Numerous cutaneous hemangiomas are distributed throughout the body. (Right) Photograph of patient’s right eye shows several eyelid hemangiomas.
FIGURE 2. Histopathology of right eye. (Left) Multiple hemangiomas of varying size throughout iris stroma (arrow). (Right) Chamber angle is partially closed. Capillaries are noted within iris root and anterior part of ciliary body and are histopathologically consistent with hemangioma (hematoxylin and eosin, 3240).
peared open. Morphologically, the sclera, iris, ciliary body, lens, vitreous cavity, and retina appeared within normal limits bilaterally. VOL. 125, NO. 6
Microscopically, the right eye disclosed partial closure of the chamber angle. The iris showed the presence of multiple capillaries filled with erythro-
BRIEF REPORTS
869
cytes. These capillaries were of varying size and were distributed throughout the iris stroma (Figure 2). Similar capillaries were noted within all sectors of the iris, from the pupillary border to the iris root, and in the anterior part of the ciliary body (Figure 2) and ciliary processes. These hemangiomas were histopathologically similar to those seen in other organs. Erythrocytes not associated with normal capillaries were present in the trabecular structures and within the ciliary muscle. The lens, retina, and choroid were within normal limits. Retinal or subretinal hemangiomas were not identified. The optic nerve disclosed the presence of erythrocytes in the subdural and subarachnoid spaces. The left eye was unremarkable. To our knowledge, this is the first histopathologic description of the eye in diffuse neonatal hemangiomatosis. The hemangiomas in the iris, ciliary body, and ciliary processes of the right eye of this patient were similar to cutaneous and visceral lesions described previously.1,3 Thus, many ocular structures develop hemangiomas in diffuse neonatal hemangiomatosis. The molecular origin of diffuse neonatal hemangiomatosis is unclear. Vascular endothelial growth factor is an endothelial cell-specific growth factor and a regulator of physiologic and pathologic angiogenesis. Studies to characterize the vascular endothelial growth factor gene, its promotor, receptor, and cellular immunohistochemical distribution in this patient are under way.
PURPOSE: To report a clinicopathologic correlation of angiosarcoma affecting the eyelid skin. METHODS: An 82-year-old man developed multiple bruise-like maculopapular lesions, subcutaneous nodules, and diffuse edema over his scalp, face, and eyelids. Biopsy disclosed angiosarcoma, and the patient was treated with wide-field external beam radiotherapy (5,000 cGy). RESULTS: He responded to radiotherapy with partial regression of the tumor. Twelve months later, he developed extensive lymphedema secondary to the residual tumor. He was also found to have parotid gland and bone metastases, treated with radiotherapy. The patient died of widespread bone metastases 3 months later. CONCLUSIONS: Angiosarcoma is a rare skin tumor that has a poor prognosis despite treatment. It should be considered in the differential diagnosis of eyelid tumors and edema because it may affect only the central portion of the face. (Am J Ophthalmol 1998;125:870 – 871. © 1998 by Elsevier Science Inc. All rights reserved.)
A
REFERENCES
1. Golitz LE, Rudikoff J, O’Meara OP. Diffuse neonatal hemangiomatosis. Pediatr Dermatol 1986;3:145–152. 2. Stratte EG, Tope WD, Johnson CL, Swanson NA. Multimodal management of diffuse neonatal hemangiomatosis. J Am Acad Dermatol 1996;34:337–342. 3. Haik BG, Clancy P, Ellsworth RM, Perina A, Zimmerman K. Ocular manifestations in diffuse neonatal hemangiomatosis. J Pediatr Ophthalmol Strabismus 1983;20:101–105. 4. Ronan SG, Solomon LM. Benign neonatal eruptive hemangiomatosis in identical twins. Pediatr Dermatol 1984;1:318–321.
Accepted for publication Dec 12, 1997. Oncology Service (K.G., J.A.S., C.L.S.) and Pathology Department (R.C.E.), Wills Eye Hospital, and Department of Medicine, Division of Neoplastic Diseases and Hematology (F.N.), Thomas Jefferson University. Supported by the Paul Kayser International Award of Merit in Retina Research, Houston, Texas (J.A.S.), and Eye Tumor Research Foundation, Philadelphia, Pennsylvania (J.A.S., C.L.S.). Inquiries to Jerry A. Shields, MD, Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107; fax: (215) 928-1140.
Cutaneous Angiosarcoma With Eyelid Involvement Kaan Gu¨ndu¨z, MD, Jerry A. Shields, MD, Carol L. Shields, MD, Ralph C. Eagle, Jr, MD, and Faith Nathan, MD 870
AMERICAN JOURNAL
NGIOSARCOMA IS A MALIGNANT NEOPLASM
that most commonly arises in the skin and superficial soft tissues but can also affect the deep tissues and viscera.1,2 Angiosarcoma of the face and scalp is a distinct subgroup that generally occurs in patients older than 55 years.1 The majority of tumors arise in the upper part of the face or scalp. The central part of the face, including the eyelids, is involved less often. The lower face, including the mandibular region, is rarely affected.1 The clinical appearance of angiosarcoma is variable. It can present with maculopapular lesions resembling ecchymoses, edema, cellulitis, or ulceration, or in a nodular form.1–3 The skin lesions are usually red or blue, suggestive of their vascular nature, although they occasionally are tan or resemble normal skin color. The diagnosis of angiosarcoma is often delayed because of its varied clinical features. We
OF
OPHTHALMOLOGY
JUNE 1998
D
IFFUSE NEONATAL HEMANGIOMATOSIS IS A RARE
condition characterized by multiple cutaneous and visceral hemangiomas. It is associated with a 60% to 90% mortality rate in the first few months of life, usually as a result of high-output cardiac failure caused by arteriovenous shunting.1–3 Familial cases Accepted for publication Dec 9, 1997. University of British Columbia, Faculty of Medicine (C.W.C.); Doheny Eye Institute, University of Southern California (N.A.R.); and Childrens Hospital Los Angeles, Division of Ophthalmology, University of Southern California (J.T.S.). Inquiries to J. Timothy Stout, MD, PhD, Childrens Hospital Los Angeles, Division of Ophthalmology, Mailstop #88, 4650 Sunset Blvd, Los Angeles, CA 90027; fax: (213) 666-6283; e-mail: tstout%smtpgate@ chlais.usc.edu
868
©
1998 BY
of neonatal hemangiomatosis have been described.4 We report a case of diffuse neonatal hemangiomatosis with eyelid, conjunctival, and iris hemangiomas and describe the pathology. A 3.7-kg female was born at term after an uncomplicated pregnancy and delivery. Multiple cutaneous hemangiomas were present, measuring up to 3 mm in diameter in a scattered distribution throughout the body (Figure 1). Hepatomegaly and mild jaundice were noted. No other systemic abnormalities were apparent. Investigations disclosed patent ductus arteriosus, patent foramen ovale, and mild cardiomegaly. Hepatomegaly with diffuse biliary dilatation, the consequence of large hepatic hemangiomas, was demonstrated. Ophthalmic examination disclosed multiple bilateral eyelid and conjunctival hemangiomas. The right eye presented iris hemangiomas, a small hyphema, vitreous hemorrhage, and discrete subretinal lesions, suggestive of subretinal hemorrhages. The infant was treated with intravenous methylprednisolone (1 mg/kg of body weight, every 6 hours) and interferon alfa-2a (daily subcutaneous doses of 600,000 units/m2 of body surface area for 3 days and 900,000 units/m2 of body surface area thereafter) with minimal beneficial effect. Congestive heart failure developed and progressively worsened despite an attempt to embolize hepatic feeder vessels. A consumptive coagulopathy developed, and despite all efforts, the patient’s condition deteriorated rapidly, resulting in death 39 days after birth. Upon autopsy, multiple hemangiomas were present on the skin, liver, lungs, pleura, epiglottis, stomach, small intestine, pancreas, kidneys, ovaries, and vagina. A large hematoma was present in the right cerebellar hemisphere. Both eyes were obtained for histopathologic study. Grossly, both eyes appeared normal in size. The anterior chambers were deep, and the angles ap-
ELSEVIER SCIENCE INC. ALL
RIGHTS RESERVED.
0002-9394/98/$19.00 PII S0002-9394(98)00049-X
FIGURE 1. (Left) Diffuse neonatal hemangiomatosis. Numerous cutaneous hemangiomas are distributed throughout the body. (Right) Photograph of patient’s right eye shows several eyelid hemangiomas.
FIGURE 2. Histopathology of right eye. (Left) Multiple hemangiomas of varying size throughout iris stroma (arrow). (Right) Chamber angle is partially closed. Capillaries are noted within iris root and anterior part of ciliary body and are histopathologically consistent with hemangioma (hematoxylin and eosin, 3240).
peared open. Morphologically, the sclera, iris, ciliary body, lens, vitreous cavity, and retina appeared within normal limits bilaterally. VOL. 125, NO. 6
Microscopically, the right eye disclosed partial closure of the chamber angle. The iris showed the presence of multiple capillaries filled with erythro-
BRIEF REPORTS
869
cytes. These capillaries were of varying size and were distributed throughout the iris stroma (Figure 2). Similar capillaries were noted within all sectors of the iris, from the pupillary border to the iris root, and in the anterior part of the ciliary body (Figure 2) and ciliary processes. These hemangiomas were histopathologically similar to those seen in other organs. Erythrocytes not associated with normal capillaries were present in the trabecular structures and within the ciliary muscle. The lens, retina, and choroid were within normal limits. Retinal or subretinal hemangiomas were not identified. The optic nerve disclosed the presence of erythrocytes in the subdural and subarachnoid spaces. The left eye was unremarkable. To our knowledge, this is the first histopathologic description of the eye in diffuse neonatal hemangiomatosis. The hemangiomas in the iris, ciliary body, and ciliary processes of the right eye of this patient were similar to cutaneous and visceral lesions described previously.1,3 Thus, many ocular structures develop hemangiomas in diffuse neonatal hemangiomatosis. The molecular origin of diffuse neonatal hemangiomatosis is unclear. Vascular endothelial growth factor is an endothelial cell-specific growth factor and a regulator of physiologic and pathologic angiogenesis. Studies to characterize the vascular endothelial growth factor gene, its promotor, receptor, and cellular immunohistochemical distribution in this patient are under way.
PURPOSE: To report a clinicopathologic correlation of angiosarcoma affecting the eyelid skin. METHODS: An 82-year-old man developed multiple bruise-like maculopapular lesions, subcutaneous nodules, and diffuse edema over his scalp, face, and eyelids. Biopsy disclosed angiosarcoma, and the patient was treated with wide-field external beam radiotherapy (5,000 cGy). RESULTS: He responded to radiotherapy with partial regression of the tumor. Twelve months later, he developed extensive lymphedema secondary to the residual tumor. He was also found to have parotid gland and bone metastases, treated with radiotherapy. The patient died of widespread bone metastases 3 months later. CONCLUSIONS: Angiosarcoma is a rare skin tumor that has a poor prognosis despite treatment. It should be considered in the differential diagnosis of eyelid tumors and edema because it may affect only the central portion of the face. (Am J Ophthalmol 1998;125:870 – 871. © 1998 by Elsevier Science Inc. All rights reserved.)
A
REFERENCES
1. Golitz LE, Rudikoff J, O’Meara OP. Diffuse neonatal hemangiomatosis. Pediatr Dermatol 1986;3:145–152. 2. Stratte EG, Tope WD, Johnson CL, Swanson NA. Multimodal management of diffuse neonatal hemangiomatosis. J Am Acad Dermatol 1996;34:337–342. 3. Haik BG, Clancy P, Ellsworth RM, Perina A, Zimmerman K. Ocular manifestations in diffuse neonatal hemangiomatosis. J Pediatr Ophthalmol Strabismus 1983;20:101–105. 4. Ronan SG, Solomon LM. Benign neonatal eruptive hemangiomatosis in identical twins. Pediatr Dermatol 1984;1:318–321.
Accepted for publication Dec 12, 1997. Oncology Service (K.G., J.A.S., C.L.S.) and Pathology Department (R.C.E.), Wills Eye Hospital, and Department of Medicine, Division of Neoplastic Diseases and Hematology (F.N.), Thomas Jefferson University. Supported by the Paul Kayser International Award of Merit in Retina Research, Houston, Texas (J.A.S.), and Eye Tumor Research Foundation, Philadelphia, Pennsylvania (J.A.S., C.L.S.). Inquiries to Jerry A. Shields, MD, Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107; fax: (215) 928-1140.
Cutaneous Angiosarcoma With Eyelid Involvement Kaan Gu¨ndu¨z, MD, Jerry A. Shields, MD, Carol L. Shields, MD, Ralph C. Eagle, Jr, MD, and Faith Nathan, MD 870
AMERICAN JOURNAL
NGIOSARCOMA IS A MALIGNANT NEOPLASM
that most commonly arises in the skin and superficial soft tissues but can also affect the deep tissues and viscera.1,2 Angiosarcoma of the face and scalp is a distinct subgroup that generally occurs in patients older than 55 years.1 The majority of tumors arise in the upper part of the face or scalp. The central part of the face, including the eyelids, is involved less often. The lower face, including the mandibular region, is rarely affected.1 The clinical appearance of angiosarcoma is variable. It can present with maculopapular lesions resembling ecchymoses, edema, cellulitis, or ulceration, or in a nodular form.1–3 The skin lesions are usually red or blue, suggestive of their vascular nature, although they occasionally are tan or resemble normal skin color. The diagnosis of angiosarcoma is often delayed because of its varied clinical features. We
OF
OPHTHALMOLOGY
JUNE 1998