ORIGINAL ARTICLES Pediatric Dermatology Vol. 32 No. 3 321–326, 2015
Rapidly Involuting Congenital Hemangioma with Fetal Involution Sheilagh Maguiness, M.D., Lily Changchien Uihlein, M.D., Marilyn G. Liang, M.D., Harry Kozakewich, M.D., and John B. Mulliken, M.D. Boston Children’s Hospital, Boston, Massachusetts
Abstract: Uncommon congenital hemangiomas differ from common infantile hemangiomas in their appearance, postnatal behavior, histopathology, and immunohistologic staining. Two types are well described in the literature: noninvoluting congenital hemangioma (NICH) and rapidly involuting congenital hemangioma (RICH). We report a series of infants with another presentation of congenital hemangioma that arises prenatally and is nearly regressed at birth. This was a retrospective case series. We describe six infants with unusual congenital vascular tumors. Each lesion presented at birth as a violaceous, atrophic plaque with a surrounding pale halo. The lesions involuted in infancy, fading in color and becoming atrophic, with prominent central veins, similar to RICH in the final stage of regression. The distinctive morphology and behavior suggests that these tumors undergo a life cycle of proliferation and involution during fetal life. We describe a new variant of congenital hemangioma that we refer to as rapidly involuting congenital hemangioma with fetal involution.
Infantile hemangiomas (IHs) typically appear 2 weeks postnatally, proliferate rapidly in the first few months of life, and gradually regress during early childhood. Approximately one-third of IHs are nascent at birth in the form of an erythematous patch, localized telangiectasia surrounded by a pale halo, or an area of blanching (1). Congenital hemangiomas are defined as vascular tumors that are fully developed at birth and do not exhibit accelerated postnatal growth (2). Two variants of congenital hemangioma have been described: rapidly involuting congenital hemangioma (RICH) (2)
and noninvoluting congenital hemangioma (NICH) (3). These uncommon congenital tumors can be distinguished from common IHs according to phenotype, growth characteristics, histopathology, and immunohistochemical staining (4). Although congenital hemangiomas vary in appearance, typical features include lilac to violaceous color, multiple telangiecatasias or veins, and often a pale halo (4). Whereas RICH regresses during infancy, NICH grows proportionally with the child and exhibits persistent fast flow (2,3,5). Some RICH lesions fail to regress completely and appear to transform into NICH over time (5).
Address correspondence to Sheilagh Maguiness, M.D., 300 Longwood Avenue, Fegan 6, Boston Children’s Hospital, Boston, MA, 02115, or e-mail: [email protected]. DOI: 10.1111/pde.12356
© 2014 Wiley Periodicals, Inc.
321
322 Pediatric Dermatology Vol. 32 No. 3 May/June 2015
Congenital hemangiomas can also occur in children with IHs (5,6). These instances of clinical overlapping between fetal and infantile vascular tumors have been referred to as “missing links (5).” Congenital hemangiomas arise in fetal life and have been observed using sonography as early as the late first trimester (2,7). Ultrasonographic monitoring of fetal hemangiomas has shown that they shrink late in pregnancy (7) and even completely disappear at term (8). Thus “fetal” hemangioma would be a precise designation whenever this tumor is discovered prenatally. We have seen congenital vascular lesions with an appearance similar to RICH in the late stage of involution. Thus these tumors must have arisen and regressed during fetal life. Although these unique tumors are probably best described as rapidly involuting fetal hemangiomas (RIFHs), they closely resemble RICHs clinically and histopathologically. For this reason, we refer to them as RICHs with fetal involution. METHODS We describe six infants evaluated at Boston Children’s Hospital born with a cutaneous vascular tumor clinically resembling RICH near the end of regression. Photographs were taken of the lesions to document the postnatal course. Medical records were reviewed for pertinent clinical, laboratory, and radiographic data. The Children’s Hospital Boston Insititutional Review Board approved this retrospective review.
CASE REPORTS Patient 1 A 5-day-old boy was seen who had been born at full term with a large vascular lesion on his left neck. A
B
There was no family history of vascular tumors or malformations. On physical examination there was a well-demarcated, 4-cm 9 5-cm, depressed, violaceous plaque with a thin pale halo lying on the left mandible extending onto the left neck (Fig. 1A). There was no ulceration or scarring. Over subsequent months the color diminished and the lesion became less purple and more atrophic (Fig. 1B). When the patient was seen in follow-up at 3 years of age, the lesion had evolved into a pink totan atrophic plaque with prominent central dilated vessels (Fig. 1C). No imaging studies were performed. The child had several sessions of pulsed dye laser that resulted in some lightening of color. Later he underwent partial excision of the atrophic skin and dilated veins. Histopathologic examination revealed large minimally and irregularly muscularized veins in the reticular dermis and subcutis (Fig. 2A). Focally the microvasculature was slightly increased, with minute arteries, veins, and capillaries (Fig. 2B). Dilated thin-walled lymphatic vessels were also present in the dermis and subcutis. There was sclerosis, loss of elastic fibers and appendages, and focal thinning in the reticular dermis. Glucose transporter 1 (GLUT1) immunoreactivity was absent in endothelial cells. Patient 2 A healthy 3-month-old boy presented with a vascular lesion overlying the right deltoid area that had been present since birth. The lesion was a 5-cm 9 6-cm, circular, lilac-colored, atrophic plaque on the right upper arm with a surrounding pale halo (Fig. 3A). There was no evidence of ulceration or scarring. In follow-up evaluation, the lesion lightened in color and became thinner and less violaceous, with central, large, prominently dilated vessels (Fig. 3B). No C
Figure 1. (A) A large, well-demarcated, atrophic, violaceous plaque at birth. (B) Patient at 9 months, with lightening in the lesion’s color. (C) Patient at age 3 years, with evolution of the lesion into a large, atrophic plaque with central dilated veins.
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B
A
Figure 2. (A) Large, minimally and irregularly muscularized veins in the reticular dermis and subcutis. (B) Dilated, thinwalled lymphatic vessels were also present. Glucose transporter 1 (GLUT1) immunoreactivity was absent in the endothelial cells. B
A
Figure 3. (A) A large, atrophic, violaceous plaque on the deltoid. (B) Patient at 11 months, with lightening in the plaque’s color and prominent central veins.
treatment was recommended and the lesion remained unchanged over 7 years. Patient 3 A 5-year-old girl presented with a circular birthmark on her left temple. Past medical history was unremarkable. Her parents noted that the color had lightened considerably since birth. They provided early photographs that showed a congenital, approximately 2-cm 9 2-cm, circular, purple to violaceous vascular lesion on the left temple. The child had a 4-cm 9 3.5-cm pink to tan atrophic plaque with subtle centrally dilated vessels overlying the left temple. No imaging studies were performed. Patient 4 A full-term newborn boy was seen at 2 days of age and was noted to have a vascular birthmark on the upper back. The lesion was a large, 8-cm 9 10-cm, well-demarcated, purple, variably atrophic plaque on the right upper back. There were two areas of gray
Figure 4. Large, atrophic, red to violaceous, multilobulated plaque on the back with central white discoloration and areas of ulceration.
discoloration in the lesion and one small, 1-cm ulceration at the inferior aspect (Fig. 4). Doppler ultrasound of the spine and cranium were normal but demonstrated increased arterial flow. The results of prenatal ultrasound at 18 and 22 weeks was recovered
324 Pediatric Dermatology Vol. 32 No. 3 May/June 2015
and showed a small lesion with thickened skin and subcutaneous tissue in the area of the lesion on the upper back. At the 2-month follow-up evaluation, the lesion had faded in color, although the two small areas of ulceration persisted. By 3 months of age the ulcerations had healed and the plaque was lighter in color. Also at this time, the patient had developed seven tiny, pinpoint, brightly erythematous papules scattered on the trunk and groin that were diagnosed as multifocal IHs arising postnatally. The patient subsequently underwent excision of the ulcerated areas. Histopathology demonstrated a vascular lesion with many dilated thin-walled vessels and increased lymphatic channels. There was epidermal atrophy and loss of appendageal structures. Histopathologically the lesion most closely resembled a RICH in the late stage of involution, similar to the lesion of patient 1 described above. Patient 5 A full-term infant boy was seen at 2 weeks of age for evaluation of a vascular birthmark on the left upper abdomen. He was born through cesarean section and the pregnancy was complicated by gestational diabetes. Prenatal ultrasound at 20 weeks of gestational age was normal. On examination he was a well-appearing 2-week-old boy with a 3.5-cm 9 3.0-cm, oval, welldemarcated, lilac-colored, depressed, atrophic plaque on the left upper abdomen with prominent dilated central veins. Patient 6 A healthy 8-year-old girl was referred to the Vascular Anomalies Center at Boston Children’s Hospital for a large vascular birthmark on the left abdomen and flank. Her parents stated that the lesion had been bright purple at birth and faded in color over time. Magnetic resonance imaging (MRI) obtained in 2003 at an outside institution showed an 8.8-cm 9 5.8-cm T2-hyperintense “cutaneous hemangioma” with “serpiginous low signal vessels” interpreted as prominent veins within the lesion. On examination there was a 9-cm 9 15-cm, pink, atrophic, round plaque on the left flank and upper abdomen with dilated veins. DISCUSSION Bowers et al (9) noted accelerated involution of a “strawberry nevus” in passing in 1960, but this unusual behavior was not given further mention. In
1995 Martinez-Perez et al (10) described five examples of hemangiomas that regressed rapidly; all were present at birth. Boon et al (2) presented a small series of vascular lesions that were fully grown at birth and underwent rapid involution. Rogers et al (11) later termed these lesions congenital hemangioma and RICH and rightfully credited that this acronym was first used by our Vascular Anomalies Center. Enjolras et al (3) described another variant, NICH. RICH and NICH exhibit fast flow and both occur in a 1:1 sex ratio, as do IHs that arise in premature infants. It is possible that several overlapping variants of congenital hemangioma exist. Nasseri et al (12) have recently used the term partially involuting congenital hemangioma to describe congenital hemangiomas that appear to evolve from RICH to persistent NICH-like lesions. RICH and NICH have overlapping morphologic, histopathologic, and radiographic findings. Postnatal behavior differentiates these two congenital vascular lesions. RICH begins regressing before and after birth and its life cycle is usually completed by 6 to 14 months of age (2). The residuum of RICH is a well-defined atrophic plaque, often with enlarged veins, and no fibrofatty tissue. In contrast, NICH remains clinically unchanged, with persistent fast flow, and sometimes enlarges in adolescence (3). Fetal vascular tumors have been detected using ultrasound as early as the end of the first trimester, but they are more commonly seen during the second trimester (2,13,14). Sonographic evidence of prenatal proliferation of vascular tumors is well described in the radiologic literature (7,15,16), and based on available published postnatal observations, these tumors are RICHs. There are no well-documented examples of NICH in the prenatal radiologic literature. We describe six infants born with a vascular tumor that had largely regressed during fetal life. The appearance of this variant of congenital hemangioma is similar to RICH in the last phase of postnatal regression. RICHs initially present as raised, violaceous-gray tumors with multiple telangiectasias, often surrounded by a pale rim. A regressed RICH is a pale, atrophic patch with dilated veins. The neonates in our series exhibited a violaceous atrophic plaque, often with a surrounding pale halo. These lesions continued to involute during the first year of life, becoming progressively thinner and less purple and leaving a residual pale halo and prominent central veins, like fully involuted RICHs. The distinguishing feature was that the regression was well under way prenatally in our series of congenital hemangiomas, whereas
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Figure 5. Congenital hemangioma growth curves.
regression in classic RICHs usually begins in the late third trimester. The morphology of the RICH with fetal involution in patient 4 resembled a previously described multifocal RICH with its lobulated appearance (7). The lesion in patient 4 was flat and atrophic at birth, whereas the congenital multifocal lesions in the earlier reported patient were more raised but soon became flat and depressed. In both patients, typical IHs developed postnatally in other locations on the body. RICH with fetal involution appears to be a variant of RICH with the life cycle curve shifted to an early period of gestation (Fig. 5). Doppler studies of RICHs initially show fast flow and then normal flow by the time the tumor is fully regressed. Fast flow was noted in patient 4 at birth, and slow flow was documented in patient 2 at age 3 years. Thus the flow diminishes in RICH with fetal involution, as it does in classic RICH. RICHs typically appear on MRI as an enhancing, T2-hyperintense tumor with fast-flow vessels within and adjacent to the mass (4). None of the congenital hemangiomas in this study were detected using prenatal ultrasound. In retrospect, there was a flat lesion noted on prenatal ultrasound in patient 4 as early as 22 weeks. It is possible that RICHs with fetal involution may not become sufficiently elevated or pedunculated to be seen on prenatal imaging. We speculate that this may be a clue as to its different biology. The prenatal radiologic literature supports the occurrence of fetal cutaneous vascular lesions that involute in utero. In one report a “hemangioma” was diagnosed in a fetus at 20 weeks of gestational age using routine obstetric sonography and it regressed during follow-up ultrasound examinations at 24 and 28 weeks. This lesion was no longer seen at 36 weeks of gestation, and at birth, only a scar with a pale halo was found at the site (8). The histopathology of RICH is well described. The tumor consists of small lobules of capillaries with endothelial cells that are immunonegative for
GLUT1 (4). Dense fibrous tissue separates the lobules and often one or more zones are present where lobules are absent, with only malformed veins and loose fibrous tissue remaining. Dystrophic calcification, hemosiderin deposits, thrombi, cysts, and extramedullary hematopoiesis have also been described in some tumors. RICHs removed years after birth show only large malformed veins, scar tissue, and sometimes small clusters of capillaries with or without thickened basement membrane (4). The histopathologic findings in patients 1 and 4, including large malformed veins, clusters of small vessels including capillaries, and scar tissue, are all similar findings to what is observed in fully involuted RICHs. CONCLUSION We describe six infants born with a vascular tumor designated as RICH with fetal involution. This newly described variant of congenital hemangioma shares radiologic and histopathologic features of end-stage RICH. The appearance at birth and subsequent behavior of RICHs with fetal involution indicates that its life cycle occurs primarily prenatally, whereas regression in typical RICHs occurs in early infancy. REFERENCES 1. Payne MM, Moyer F, Marcks KM et al. The precursor to the hemangioma. Plast Reconstr Surg 1966;38:64–67. 2. Boon LM, Enjolras O, Mulliken JB. Congenital hemangioma: evidence of accelerated involution. J Pediatr 1996;128:329–335. 3. Enjolras O, Mulliken JB, Boon LM et al. Noninvoluting congenital hemangioma: a rare cutaneous vascular anomaly. Plast Reconstr Surg 2001;107:1647–1654. 4. Berenguer B, Mulliken JB, Enjolras O et al. Rapidly involuting congenital hemangioma: clinical and histopathologic features. Pediatr Dev Pathol 2003;6:495– 510. 5. Mulliken JB, Enjolras O. Congenital hemangiomas and infantile hemangiomas: missing links. J Am Acad Dermatol 2009;50:875–882. 6. Mulliken JB, Bischoff J, Kozakewich HPW. Multifocal rapidly involuting congenital hemangioma: a link to
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7.
8. 9. 10.
11.
chorangioma. Am J Med Genet A 2007;143A:3038– 3046. Fadell MF II, Jones BV, Adams DM. Prenatal diagnosis and postnatal follow-up of rapidly involuting congenital hemangioma (RICH). Pediatr Radiol 2011; 41:1057–1060. Ozcan UA. Rapidly involuting congenital hemangioma: a case of complete prenatal involution. J Clin Ultrasound 2010;38:85–88. Bowers RE, Graham EA, Tomlinson KM. The natural history of the strawberry nevus. Arch Dermatol 1960; 82:667–680. Martinez-Perez D, Fein NA, Boon LM et al. Not all hemangiomas look like strawberries: uncommon presentations of the most common tumor of infancy. Pediatr Dermatol 1995;12:1–6. Rogers M, Lam A, Fischer G. Sonographic findings in a series of rapidly involuting congenital hemangiomas (RICH). Pediatr Dermatol 2002;19:5–11.
12. Nasseri E, Piram M, McCuaig C et al. Partially involuting congenital hemangiomas: a report of 8 cases and review of the literature. J Am Acad Dermatol 2014;70:75–79. 13. Elia D, Garel C, Enjolras O et al. Prenatal imaging findings in rapidly involuting congenital hemangioma of the skull. Ultrasound Obstet Gynecol 2008;31:572– 575. 14. Kramer LA, Crino JP, Slopis J et al. Capillary hemangioma of the neck: prenatal MR findings. AJNR Am J Neuroradiol 1997;18:1432–1434. 15. Kashima H, Unno N, Hyodo H et al. Antenatal sonographic and magnetic resonance images of a giant hemangioma of the fetal skull. Ultrasound Obstet Gynecol 2005;25:522–523. 16. Viora E, Grassi Pirrone P, Comoglio F et al. Ultrasonographic detection of fetal cranio-facial hemangioma: case report and review of the literature. Ultrasound Obstet Gynecol 2000;15:431–434.
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Rapidly Involuting Congenital Hemangioma with Fetal Involution Sheilagh Maguiness, M.D., Lily Changchien Uihlein, M.D., Marilyn G. Liang, M.D., Harry Kozakewich, M.D., and John B. Mulliken, M.D. Boston Children’s Hospital, Boston, Massachusetts
Abstract: Uncommon congenital hemangiomas differ from common infantile hemangiomas in their appearance, postnatal behavior, histopathology, and immunohistologic staining. Two types are well described in the literature: noninvoluting congenital hemangioma (NICH) and rapidly involuting congenital hemangioma (RICH). We report a series of infants with another presentation of congenital hemangioma that arises prenatally and is nearly regressed at birth. This was a retrospective case series. We describe six infants with unusual congenital vascular tumors. Each lesion presented at birth as a violaceous, atrophic plaque with a surrounding pale halo. The lesions involuted in infancy, fading in color and becoming atrophic, with prominent central veins, similar to RICH in the final stage of regression. The distinctive morphology and behavior suggests that these tumors undergo a life cycle of proliferation and involution during fetal life. We describe a new variant of congenital hemangioma that we refer to as rapidly involuting congenital hemangioma with fetal involution.
Infantile hemangiomas (IHs) typically appear 2 weeks postnatally, proliferate rapidly in the first few months of life, and gradually regress during early childhood. Approximately one-third of IHs are nascent at birth in the form of an erythematous patch, localized telangiectasia surrounded by a pale halo, or an area of blanching (1). Congenital hemangiomas are defined as vascular tumors that are fully developed at birth and do not exhibit accelerated postnatal growth (2). Two variants of congenital hemangioma have been described: rapidly involuting congenital hemangioma (RICH) (2)
and noninvoluting congenital hemangioma (NICH) (3). These uncommon congenital tumors can be distinguished from common IHs according to phenotype, growth characteristics, histopathology, and immunohistochemical staining (4). Although congenital hemangiomas vary in appearance, typical features include lilac to violaceous color, multiple telangiecatasias or veins, and often a pale halo (4). Whereas RICH regresses during infancy, NICH grows proportionally with the child and exhibits persistent fast flow (2,3,5). Some RICH lesions fail to regress completely and appear to transform into NICH over time (5).
Address correspondence to Sheilagh Maguiness, M.D., 300 Longwood Avenue, Fegan 6, Boston Children’s Hospital, Boston, MA, 02115, or e-mail: [email protected]. DOI: 10.1111/pde.12356
© 2014 Wiley Periodicals, Inc.
321
322 Pediatric Dermatology Vol. 32 No. 3 May/June 2015
Congenital hemangiomas can also occur in children with IHs (5,6). These instances of clinical overlapping between fetal and infantile vascular tumors have been referred to as “missing links (5).” Congenital hemangiomas arise in fetal life and have been observed using sonography as early as the late first trimester (2,7). Ultrasonographic monitoring of fetal hemangiomas has shown that they shrink late in pregnancy (7) and even completely disappear at term (8). Thus “fetal” hemangioma would be a precise designation whenever this tumor is discovered prenatally. We have seen congenital vascular lesions with an appearance similar to RICH in the late stage of involution. Thus these tumors must have arisen and regressed during fetal life. Although these unique tumors are probably best described as rapidly involuting fetal hemangiomas (RIFHs), they closely resemble RICHs clinically and histopathologically. For this reason, we refer to them as RICHs with fetal involution. METHODS We describe six infants evaluated at Boston Children’s Hospital born with a cutaneous vascular tumor clinically resembling RICH near the end of regression. Photographs were taken of the lesions to document the postnatal course. Medical records were reviewed for pertinent clinical, laboratory, and radiographic data. The Children’s Hospital Boston Insititutional Review Board approved this retrospective review.
CASE REPORTS Patient 1 A 5-day-old boy was seen who had been born at full term with a large vascular lesion on his left neck. A
B
There was no family history of vascular tumors or malformations. On physical examination there was a well-demarcated, 4-cm 9 5-cm, depressed, violaceous plaque with a thin pale halo lying on the left mandible extending onto the left neck (Fig. 1A). There was no ulceration or scarring. Over subsequent months the color diminished and the lesion became less purple and more atrophic (Fig. 1B). When the patient was seen in follow-up at 3 years of age, the lesion had evolved into a pink totan atrophic plaque with prominent central dilated vessels (Fig. 1C). No imaging studies were performed. The child had several sessions of pulsed dye laser that resulted in some lightening of color. Later he underwent partial excision of the atrophic skin and dilated veins. Histopathologic examination revealed large minimally and irregularly muscularized veins in the reticular dermis and subcutis (Fig. 2A). Focally the microvasculature was slightly increased, with minute arteries, veins, and capillaries (Fig. 2B). Dilated thin-walled lymphatic vessels were also present in the dermis and subcutis. There was sclerosis, loss of elastic fibers and appendages, and focal thinning in the reticular dermis. Glucose transporter 1 (GLUT1) immunoreactivity was absent in endothelial cells. Patient 2 A healthy 3-month-old boy presented with a vascular lesion overlying the right deltoid area that had been present since birth. The lesion was a 5-cm 9 6-cm, circular, lilac-colored, atrophic plaque on the right upper arm with a surrounding pale halo (Fig. 3A). There was no evidence of ulceration or scarring. In follow-up evaluation, the lesion lightened in color and became thinner and less violaceous, with central, large, prominently dilated vessels (Fig. 3B). No C
Figure 1. (A) A large, well-demarcated, atrophic, violaceous plaque at birth. (B) Patient at 9 months, with lightening in the lesion’s color. (C) Patient at age 3 years, with evolution of the lesion into a large, atrophic plaque with central dilated veins.
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B
A
Figure 2. (A) Large, minimally and irregularly muscularized veins in the reticular dermis and subcutis. (B) Dilated, thinwalled lymphatic vessels were also present. Glucose transporter 1 (GLUT1) immunoreactivity was absent in the endothelial cells. B
A
Figure 3. (A) A large, atrophic, violaceous plaque on the deltoid. (B) Patient at 11 months, with lightening in the plaque’s color and prominent central veins.
treatment was recommended and the lesion remained unchanged over 7 years. Patient 3 A 5-year-old girl presented with a circular birthmark on her left temple. Past medical history was unremarkable. Her parents noted that the color had lightened considerably since birth. They provided early photographs that showed a congenital, approximately 2-cm 9 2-cm, circular, purple to violaceous vascular lesion on the left temple. The child had a 4-cm 9 3.5-cm pink to tan atrophic plaque with subtle centrally dilated vessels overlying the left temple. No imaging studies were performed. Patient 4 A full-term newborn boy was seen at 2 days of age and was noted to have a vascular birthmark on the upper back. The lesion was a large, 8-cm 9 10-cm, well-demarcated, purple, variably atrophic plaque on the right upper back. There were two areas of gray
Figure 4. Large, atrophic, red to violaceous, multilobulated plaque on the back with central white discoloration and areas of ulceration.
discoloration in the lesion and one small, 1-cm ulceration at the inferior aspect (Fig. 4). Doppler ultrasound of the spine and cranium were normal but demonstrated increased arterial flow. The results of prenatal ultrasound at 18 and 22 weeks was recovered
324 Pediatric Dermatology Vol. 32 No. 3 May/June 2015
and showed a small lesion with thickened skin and subcutaneous tissue in the area of the lesion on the upper back. At the 2-month follow-up evaluation, the lesion had faded in color, although the two small areas of ulceration persisted. By 3 months of age the ulcerations had healed and the plaque was lighter in color. Also at this time, the patient had developed seven tiny, pinpoint, brightly erythematous papules scattered on the trunk and groin that were diagnosed as multifocal IHs arising postnatally. The patient subsequently underwent excision of the ulcerated areas. Histopathology demonstrated a vascular lesion with many dilated thin-walled vessels and increased lymphatic channels. There was epidermal atrophy and loss of appendageal structures. Histopathologically the lesion most closely resembled a RICH in the late stage of involution, similar to the lesion of patient 1 described above. Patient 5 A full-term infant boy was seen at 2 weeks of age for evaluation of a vascular birthmark on the left upper abdomen. He was born through cesarean section and the pregnancy was complicated by gestational diabetes. Prenatal ultrasound at 20 weeks of gestational age was normal. On examination he was a well-appearing 2-week-old boy with a 3.5-cm 9 3.0-cm, oval, welldemarcated, lilac-colored, depressed, atrophic plaque on the left upper abdomen with prominent dilated central veins. Patient 6 A healthy 8-year-old girl was referred to the Vascular Anomalies Center at Boston Children’s Hospital for a large vascular birthmark on the left abdomen and flank. Her parents stated that the lesion had been bright purple at birth and faded in color over time. Magnetic resonance imaging (MRI) obtained in 2003 at an outside institution showed an 8.8-cm 9 5.8-cm T2-hyperintense “cutaneous hemangioma” with “serpiginous low signal vessels” interpreted as prominent veins within the lesion. On examination there was a 9-cm 9 15-cm, pink, atrophic, round plaque on the left flank and upper abdomen with dilated veins. DISCUSSION Bowers et al (9) noted accelerated involution of a “strawberry nevus” in passing in 1960, but this unusual behavior was not given further mention. In
1995 Martinez-Perez et al (10) described five examples of hemangiomas that regressed rapidly; all were present at birth. Boon et al (2) presented a small series of vascular lesions that were fully grown at birth and underwent rapid involution. Rogers et al (11) later termed these lesions congenital hemangioma and RICH and rightfully credited that this acronym was first used by our Vascular Anomalies Center. Enjolras et al (3) described another variant, NICH. RICH and NICH exhibit fast flow and both occur in a 1:1 sex ratio, as do IHs that arise in premature infants. It is possible that several overlapping variants of congenital hemangioma exist. Nasseri et al (12) have recently used the term partially involuting congenital hemangioma to describe congenital hemangiomas that appear to evolve from RICH to persistent NICH-like lesions. RICH and NICH have overlapping morphologic, histopathologic, and radiographic findings. Postnatal behavior differentiates these two congenital vascular lesions. RICH begins regressing before and after birth and its life cycle is usually completed by 6 to 14 months of age (2). The residuum of RICH is a well-defined atrophic plaque, often with enlarged veins, and no fibrofatty tissue. In contrast, NICH remains clinically unchanged, with persistent fast flow, and sometimes enlarges in adolescence (3). Fetal vascular tumors have been detected using ultrasound as early as the end of the first trimester, but they are more commonly seen during the second trimester (2,13,14). Sonographic evidence of prenatal proliferation of vascular tumors is well described in the radiologic literature (7,15,16), and based on available published postnatal observations, these tumors are RICHs. There are no well-documented examples of NICH in the prenatal radiologic literature. We describe six infants born with a vascular tumor that had largely regressed during fetal life. The appearance of this variant of congenital hemangioma is similar to RICH in the last phase of postnatal regression. RICHs initially present as raised, violaceous-gray tumors with multiple telangiectasias, often surrounded by a pale rim. A regressed RICH is a pale, atrophic patch with dilated veins. The neonates in our series exhibited a violaceous atrophic plaque, often with a surrounding pale halo. These lesions continued to involute during the first year of life, becoming progressively thinner and less purple and leaving a residual pale halo and prominent central veins, like fully involuted RICHs. The distinguishing feature was that the regression was well under way prenatally in our series of congenital hemangiomas, whereas
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325
Figure 5. Congenital hemangioma growth curves.
regression in classic RICHs usually begins in the late third trimester. The morphology of the RICH with fetal involution in patient 4 resembled a previously described multifocal RICH with its lobulated appearance (7). The lesion in patient 4 was flat and atrophic at birth, whereas the congenital multifocal lesions in the earlier reported patient were more raised but soon became flat and depressed. In both patients, typical IHs developed postnatally in other locations on the body. RICH with fetal involution appears to be a variant of RICH with the life cycle curve shifted to an early period of gestation (Fig. 5). Doppler studies of RICHs initially show fast flow and then normal flow by the time the tumor is fully regressed. Fast flow was noted in patient 4 at birth, and slow flow was documented in patient 2 at age 3 years. Thus the flow diminishes in RICH with fetal involution, as it does in classic RICH. RICHs typically appear on MRI as an enhancing, T2-hyperintense tumor with fast-flow vessels within and adjacent to the mass (4). None of the congenital hemangiomas in this study were detected using prenatal ultrasound. In retrospect, there was a flat lesion noted on prenatal ultrasound in patient 4 as early as 22 weeks. It is possible that RICHs with fetal involution may not become sufficiently elevated or pedunculated to be seen on prenatal imaging. We speculate that this may be a clue as to its different biology. The prenatal radiologic literature supports the occurrence of fetal cutaneous vascular lesions that involute in utero. In one report a “hemangioma” was diagnosed in a fetus at 20 weeks of gestational age using routine obstetric sonography and it regressed during follow-up ultrasound examinations at 24 and 28 weeks. This lesion was no longer seen at 36 weeks of gestation, and at birth, only a scar with a pale halo was found at the site (8). The histopathology of RICH is well described. The tumor consists of small lobules of capillaries with endothelial cells that are immunonegative for
GLUT1 (4). Dense fibrous tissue separates the lobules and often one or more zones are present where lobules are absent, with only malformed veins and loose fibrous tissue remaining. Dystrophic calcification, hemosiderin deposits, thrombi, cysts, and extramedullary hematopoiesis have also been described in some tumors. RICHs removed years after birth show only large malformed veins, scar tissue, and sometimes small clusters of capillaries with or without thickened basement membrane (4). The histopathologic findings in patients 1 and 4, including large malformed veins, clusters of small vessels including capillaries, and scar tissue, are all similar findings to what is observed in fully involuted RICHs. CONCLUSION We describe six infants born with a vascular tumor designated as RICH with fetal involution. This newly described variant of congenital hemangioma shares radiologic and histopathologic features of end-stage RICH. The appearance at birth and subsequent behavior of RICHs with fetal involution indicates that its life cycle occurs primarily prenatally, whereas regression in typical RICHs occurs in early infancy. REFERENCES 1. Payne MM, Moyer F, Marcks KM et al. The precursor to the hemangioma. Plast Reconstr Surg 1966;38:64–67. 2. Boon LM, Enjolras O, Mulliken JB. Congenital hemangioma: evidence of accelerated involution. J Pediatr 1996;128:329–335. 3. Enjolras O, Mulliken JB, Boon LM et al. Noninvoluting congenital hemangioma: a rare cutaneous vascular anomaly. Plast Reconstr Surg 2001;107:1647–1654. 4. Berenguer B, Mulliken JB, Enjolras O et al. Rapidly involuting congenital hemangioma: clinical and histopathologic features. Pediatr Dev Pathol 2003;6:495– 510. 5. Mulliken JB, Enjolras O. Congenital hemangiomas and infantile hemangiomas: missing links. J Am Acad Dermatol 2009;50:875–882. 6. Mulliken JB, Bischoff J, Kozakewich HPW. Multifocal rapidly involuting congenital hemangioma: a link to
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