Pediatric and Developmental Pathology

, Volume 6, Issue 6, pp 495–510 | Cite as

Rapidly Involuting Congenital Hemangioma: Clinical and Histopathologic Features

  • Beatriz Berenguer
  • John B. Mulliken
  • Odile Enjolras
  • Lawrence M. Boon
  • Michel Wassef
  • Patrice Josset
  • Patricia E. Burrows
  • Antonio R. Perez-Atayde
  • Harry P.W. Kozakewich


We define the histopathologic findings and review the clinical and radiologic characteristics of rapidly involuting congenital hemangioma (RICH). The features of RICH are compared to the equally uncommon noninvoluting congenital hemangioma (NICH) and common infantile hemangioma. RICH and NICH had many similarities, such as appearance, location, size, and sex distribution. The obvious differences in behavior served to differentiate RICH, NICH, and common infantile hemangioma. Magnetic resonance imaging (MRI) of the three tumors is quite similar, but some RICH also had areas of inhomogeneity and larger flow voids on MRI and arterial aneurysms on angiography. The histologic appearance of RICH differed from NICH and common infantile hemangioma, but some overlap was noted among the three lesions. RICH was composed of small-to-large lobules of capillaries with moderately plump endothelial cells and pericytes; the lobules were surrounded by abundant fibrous tissue. One-half of the specimens had a central involuting zone(s) characterized by lobular loss, fibrous tissue, and draining channels that were often large and abnormal. Ancillary features commonly found were hemosiderin, thrombosis, cyst formation, focal calcification, and extramedullary hematopoiesis. With one exception, endothelial cells in RICH (as in NICH) did not express glucose transporter-1 protein, as does common infantile hemangioma. One RICH exhibited 50% postnatal involution during the 1st year, stopped regressing, was resected at 18 months, and was histologically indistinguishable from NICH. In addition, several RICH, resected in early infancy, also had some histologic features suggestive of NICH. Furthermore, NICH removed early (2–4 years), showed some histologic findings of RICH or were indistinguishable from RICH. We conclude that RICH, NICH, and common infantile hemangioma have overlapping clinical and pathologic features. These observations support the hypothesis that these vascular tumors may be variations of a single entity ab initio. It is unknown whether the progenitor cell for these uncommon congenital vascular tumors is the same as for common infantile hemangioma.


  1. 1.
    Pratt, AG 1953Birthmarks in infants.Arch Dermatol67302305Google Scholar
  2. 2.
    Holmdahl, K 1955Cutaneous hemangiomas in premature and mature infants.Acta Paediatr44370379PubMedGoogle Scholar
  3. 3.
    Bowers, RE, Graham, EA, Tomlinson, KM 1960The natural history of strawberry nevus.Arch Dermatol82667680Google Scholar
  4. 4.
    Mulliken, JB, Young, AE 1988Vascular Birthmarks: Hemangiomas and Malformations.W.B. SaundersPhiladelphiaGoogle Scholar
  5. 5.
    Amir, J, Metzker, A, Krikler, R, Reisner, SH 1986Strawberry hemangioma in preterm infants.Pediatr Dermatol3331332PubMedGoogle Scholar
  6. 6.
    Mulliken, JB, Fishman, SJ, Burrows, PE 2000Vascular anomalies.Curr Probl Surg37517584PubMedGoogle Scholar
  7. 7.
    Hidano, A, Nakajima, S 1972Earliest features of the strawberry mark in the newborn.Br J Dermatol87138144PubMedGoogle Scholar
  8. 8.
    Payne, MM, Moyer, F, Marcks, KM, Trevaskis, AE 1966The precursor to the hemangioma.Plast Reconstr Surg386467PubMedGoogle Scholar
  9. 9.
    Takahashi, K, Mulliken, JB, Kozakewich, HP, Rogers, RA, Folkman, J, Ezekowitz, RA 1994Cellular markers that distinguish the phases of hemangioma during infancy and childhood.J Clin Invest9323572364PubMedGoogle Scholar
  10. 10.
    Mulliken, JB, Glowacki, J 1982Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics.Plast Reconstr Surg69412422PubMedGoogle Scholar
  11. 11.
    Martinez-Perez, D, Fein, NA, Boon, LM, Mulliken, JB 1995Not all hemangiomas look like strawberries: uncommon presentations of the most common tumor of infancy.Pediatr Dermatol1216PubMedGoogle Scholar
  12. 12.
    Boon, LM, Enjolras, O, Mulliken, JB 1996Congenital hemangioma: evidence of accelerated involutionJ Pediatr128329335PubMedGoogle Scholar
  13. 13.
    Maynor, CH, Hertzberg, BS, Kliewer, MA, Heyneman, LE, Carroll, BA 1995Antenatal ultrasonographic diagnosis of abdominal wall hemangioma: potential to simulate ventral abdominal wall defects.J Ultrasound Med14317319PubMedGoogle Scholar
  14. 14.
    Viora, E, Grassi Pirrone, P, Comoglio, F, Bastonero, S, Campogrande, M 2000Ultrasonographic detection of fetal cranio-facial hemangioma: case report and review of the literature.Ultrasound Obstet Gynecol15431434CrossRefPubMedGoogle Scholar
  15. 15.
    Bulas, DI, Johnson, D, Allen, JF, Kapur, S 1992Fetal hemangioma. Sonographic and color flow Doppler findings.J Ultrasound Med11499501PubMedGoogle Scholar
  16. 16.
    Sherer, DM, Perillo, AM, Abramowicz, JS 1993Fetal hemangioma overlying the temporal occipital suture, initially diagnosed by ultrasonography as an encephalocele.J Ultrasound Med12691693PubMedGoogle Scholar
  17. 17.
    McGahan, JP, Schneider, JM 1986Fetal neck hemangioendothelioma with secondary hydrops fetalis: sonographic diagnosis.J Clin Ultrasound14384388PubMedGoogle Scholar
  18. 18.
    Shiraishi, H, Nakamura, M, Ichihashi, K,  et al. 2000Prenatal MRI in a fetus with a giant neck hemangioma: a case report.Prenat Diagn2010041007CrossRefPubMedGoogle Scholar
  19. 19.
    Nakamoto, SK, Dreilinger, A, Dattel, B, Mattrey, RF, Key, TC 1983The sonographic appearance of hepatic hemangioma in utero.J Ultrasound Med2239241PubMedGoogle Scholar
  20. 20.
    Meirowitz, NB, Guzman, ER, Underberg-Davis, SJ, Pellegrino, JE, Vintzileos, AM 2000Hepatic hemangioendothelioma: prenatal sonographic findings and evolution of the lesion.J Clin Ultrasound28258263CrossRefPubMedGoogle Scholar
  21. 21.
    Abuhamad, AZ, Lewis, D, Inati, MN, Johnson, DR, Copel, JA 1993The use of color flow Doppler in the diagnosis of fetal hepatic hemangioma.J Ultrasound Med12223226PubMedGoogle Scholar
  22. 22.
    Chuileannain, FN, Rowlands, S, Sampson, A 1999Ultrasonographic appearances of fetal hepatic hemangioma.J Ultrasound Med18379381PubMedGoogle Scholar
  23. 23.
    Sheu, BC, Shyu, MK, Lin, YF,  et al. 1994Prenatal diagnosis and corticosteroid treatment of diffuse neonatal hemangiomatosis: case report.J Ultrasound Med13495499PubMedGoogle Scholar
  24. 24.
    Morris, J, Abbott, J, Burrows, P, Levine, D 1999Antenatal diagnosis of fetal hepatic hemangioma treated with maternal corticosteroids.Obstet Gynecol94813815CrossRefPubMedGoogle Scholar
  25. 25.
    Enjolras, O, Mulliken, JB, Boon, LM, Wassef, M, Kozakewich, HP, Burrows, PE 2001Noninvoluting congenital hemangioma: a rare cutaneous vascular anomaly.Plast Reconstr Surg10716471654CrossRefPubMedGoogle Scholar
  26. 26.
    North, PE, Waner, M, Mizeracki, A, Mihm Jr, MC 2000GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas.Hum Pathol311122PubMedGoogle Scholar
  27. 27.
    North, PE, Waner, M, Mizeracki, A,  et al. 2001A unique microvascular phenotype shared by juvenile hemangiomas and human placenta.Arch Dermatol137559570PubMedGoogle Scholar
  28. 28.
    Boon, LM, Fishman, SJ, Lund, DP, Mulliken, JB 1995Congenital fibrosarcoma masquerading as congenital hemangioma: report of two cases.J Pediatr Surg3013781381CrossRefPubMedGoogle Scholar
  29. 29.
    Hayward, PG, Orgill, DP, Mulliken, JB, Perez-Atayde, AR 1995Congenital fibrosarcoma masquerading as lymphatic malformation: report of two cases.J Pediatr Surg308488CrossRefPubMedGoogle Scholar
  30. 30.
    Glowacki, J, Mulliken, JB 1982Mast cells in hemangiomas and vascular malformations.Pediatrics704851PubMedGoogle Scholar
  31. 31.
    Mancini, AJ, Smoller, BR 1996Proliferation and apoptosis within juvenile capillary hemangiomas.Am J Dermatopathol18505514CrossRefPubMedGoogle Scholar
  32. 32.
    Iwata, J, Sonobe, H, Furihata, M, Ido, E, Ohtsuki, Y 1996High frequency of apoptosis in infantile capillary haemangioma.J Pathol179403408CrossRefPubMedGoogle Scholar
  33. 33.
    Razon, MJ, Kraling, BM, Mulliken, JB, Bischoff, J 1998Increased apoptosis coincides with onset of involution in infantile hemangioma.Microcirculation5189195CrossRefPubMedGoogle Scholar
  34. 34.
    Boon, LM, Burrows, PE, Paltiel, HJ,  et al. 1996Hepatic vascular anomalies in infancy: a twenty-seven-year experience.J Pediatr129346354Google Scholar
  35. 35.
    Meizner, I, Bar-Ziv, J, Holcberg, G, Katz, M 1985In utero prenatal diagnosis of fetal facial tumor-hemangioma.J Clin Ultrasound13435437PubMedGoogle Scholar
  36. 36.
    Treadwell, MC, Sepulveda, W, LeBlanc, LL, Romero, R 1993Prenatal diagnosis of fetal cutaneous hemangioma: case report and review of the literature.J Ultrasound Med12683687PubMedGoogle Scholar
  37. 37.
    North, PE, Waner, M, James, CA, Mizeracki, A, Frieden, IJ, Mihm Jr, MC 2001Congenital nonprogressive hemangioma: a distinct clinicopathologic entity unlike infantile hemangioma.Arch Dermatol13716071620PubMedGoogle Scholar
  38. 38.
    Boye, E, Yu, Y, Paranya, G, Mulliken, JB, Olsen, BR, Bischoff, J 2001Clonality and altered behavior of endothelial cells from hemangiomas.J Clin Invest107745752PubMedGoogle Scholar
  39. 39.
    Walter, JW, North, PE, Waner, M,  et al. 2002Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma Genes, Chromosomes Cancer.33295303Google Scholar

Copyright information

© Society for Pediatric Pathology 2003

Authors and Affiliations

  • Beatriz Berenguer
    • 1
  • John B. Mulliken
    • 1
  • Odile Enjolras
    • 2
  • Lawrence M. Boon
    • 3
  • Michel Wassef
    • 2
  • Patrice Josset
    • 4
  • Patricia E. Burrows
    • 5
  • Antonio R. Perez-Atayde
    • 6
  • Harry P.W. Kozakewich
    • 6
  1. 1.Division of Plastic SurgeryChildren’s Hospital, 300 Longwood Avenue, Boston, MA 02115USA
  2. 2.Consultation des AngiomesHôpital Lariboisiere, ParisFrance
  3. 3.Division of Plastic SurgeryCliniques Universitaires St Luc, Université catholique de Louvain, BrusselsBelgium
  4. 4.Department of PathologyHôpital d’Enfants Trousseau, ParisFrance
  5. 5.Department of RadiologyChildren’s Hospital, 300 Longwood Avenue, Boston, MA 02115 USA
  6. 6.Department of PathologyChildren’s Hospital, 300 Longwood Avenue, Boston, MA 02115USA

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