These tumors are very common in infancy and childhood. There are many types and some are associated with genetic syndromes. The role of the pathologist is to confirm the clinical impression on biopsy and identify histologic types that may foreshadow a more sinister clinical condition.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Birthmark INCIDENCE Most common tumor of infancy
1-2.6% of newborn population
As high as 10% in whites
AGE RANGE-MEDIAN Usually <18 months SEX (MALE:FEMALE) 1:4 EPIDEMIOLOGIC ASSOCIATIONS Prematurity 1 of 4 premature newborns <1000 gm will develop a hemangioma
Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex.
Chiller KG, Passaro D, Frieden IJ.
1701 Divisadero St, Third Floor, San Francisco, CA 94115.
Arch Dermatol 2002 Dec;138(12):1567-76 Abstract quote
BACKGROUND: Hemangiomas of infancy vary widely in appearance, size, and depth of cutaneous involvement. There is currently no standard classification system for these lesions. While they occur in any race, an increased incidence occurs in girls, light-skinned whites, and premature infants, especially those weighing less than 1500 g. Other epidemiologic and demographic factors have not been well characterized.
OBJECTIVE: To determine any correlations between hemangioma subtype and anatomic location with demographic factors, complications, and other associated anomalies.
DESIGN: Retrospective chart review of 327 patients with hemangioma of infancy seen between 1997 and 2000 in an ambulatory referral center.
MAIN OUTCOMES MEASURES: Demographic and gestational information, lesion size, associated anomalies, complications, treatments, and outcomes were analyzed together with classification of hemangiomas into 4 groups: localized, segmental, indeterminate, and multifocal. Subtypes were correlated with race and ethnicity, the incidence of complications, and overall outcome.
RESULTS: Of 472 hemangiomas (327 patients), 339 (72%) were localized, 84 (18%) were segmental, 37 (8%) were indeterminate, and 12 (3%) were multifocal (8 or more noncontiguous lesions). Segmental lesions were larger and were more frequently associated with developmental abnormalities. They also required more intensive and prolonged therapy and were associated with more complications and a poorer overall outcome (P<.001). Lesions on Hispanic patients were more likely to involve mucous membranes, to be segmental (P<.004), to be associated with abnormalities (P =.05), especially PHACE syndrome (P =.05), and to have more complications (P =.01). Increased incidence of segmental hemangiomas was the only factor in Hispanic infants associated with complications, more extensive treatment, or associated anomalies.
CONCLUSIONS: Hemangiomas of infancy can usually be classified as localized, segmental, indeterminate, and multifocal, based on clinical features. Segmental lesions have a higher frequency of complications and associated abnormalities, and this type of hemangioma seems to present with increased frequency in Hispanic infants.
DISEASE ASSOCIATIONS AND SYNDROMES CHARACTERIZATION Diffuse neonatal hemangiomatosis Multiple congenital hemangiomas with involvement of at least 3 separate organ systems
High morbidity and mortality
Infants with liver involvement have triad of hepatomegaly, congestive heart failure, and anemia
PHACES syndrome Females are more commonly affected Posterior fossa malformations Usually of the Dandy-Walker variant Hemangiomas Large facial hemangioma usually plaquelike and segmental often involving one or more facial dermatomes Arterial anomalies Cardiac anomalies and coarctation of the aorta Eye abnormalities Sternal cleft and/or suprumbilical raphe
PATHOGENESIS CHARACTERIZATION GENERAL Infantile hemangiomas are arrested in an early developmental vascular differentiation state.
Dadras SS, North PE, Bertoncini J, Mihm MC, Detmar M.
Cutaneous Biology Research Center and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Mod Pathol. 2004 Sep;17(9):1068-79. Abstract quote
Infantile hemangiomas, the most common tumors of infancy, are vascular tumors characterized by rapid proliferation of endothelial cells during the first few months of postnatal life followed by slow spontaneous involution, whose molecular pathogenesis remains unclear.
The recent identification of developmental expression of vascular lineage-specific markers prompted us to characterize infantile hemangiomas for the expression of lymphatic endothelial hyaluronan receptor-1 (LYVE-1), Prox-1, CD31 and CD34.
We found that LYVE-1, a specific marker for normal and tumor-associated lymphatic vessels, was strongly expressed in tumor cells of infantile hemangiomas (n=28), but not in other vascular tumors including pyogenic granulomas (n=19, P<0.0001) or intramuscular hemangiomas (n=9), using LYVE-1/CD31 double immunostains. Whereas LYVE-1 expression was detected on the endothelial cells of all proliferating infantile hemangiomas, this lymphatic marker was absent from the lesional capillaries during involution in the majority of cases (P=0.0009). The majority of LYVE-1(+) endothelial cells also expressed CD34, but were negative for the lymphatic-specific homeobox protein Prox-1.
Based on coexpression of both LYVE-1 and the blood vascular marker CD34, we propose that the endothelial cells in proliferating infantile hemangioma are arrested in an early developmental stage of vascular differentiation. The immature, incompletely differentiated immunophenotype of proliferating infantile hemangiomas may contribute to their rapid growth during the first few months of life.
Infantile hemangioma is a proliferation of beta4-negative endothelial cells adjacent to HLA-DR-Positive cells with dendritic cell morphology.
Nguyen VA, Furhapter C, Romani N, Weber F, Sepp N.
Hum Pathol. 2004 Jun;35(6):739-44 Abstract quote
Although hemangioma is referred as to the most common tumor in infancy, the underlying pathogenetic events and the biologic origin of this benign vascular neoplasm have remained obscure.
By using immunohistochemistry on frozen sections of infantile hemangiomas, we show here that proliferating endothelial cells abundantly expressed alpha(v)beta(3) but lacked beta(4) integrins. Instead, regressing and involuting infantile hemangiomas due to treatment with IFN-alpha showed positive staining of beta(4) integrin, which might point to the angiogenic significance of beta(4) integrin in infantile hemangiomas. Moreover, immunofluorescence analysis revealed the existence of HLA-DR(+), mostly CD68(+) and partly DC-SIGN/CD209(+) cells with dendritic cell morphology in the intimate vicinity of hemangiomatous vessels. Such cells were also detected in the dermal microvascular unit in normal skin.
The coupled occurrence of vascular structures and perivascular cells that were stained positive with markers of monocyte or macrophage or dendritic cells might suggest that the development of infantile hemangioma is a result of vasculogenesis, that is, the formation of primitive blood vessels from angioblasts, rather than of angiogenesis, that is, the sprouting of capillaries from preexisting vessels.
BASIC FIBROBLASTIC GROWTH FACTOR (BFGF)
Stimulates endothelial cell hyperplasia
Increased levels found in the urine
Endothelium in hepatic cavernous hemangiomas does not express the hyaluronan receptor for endocytosis.
Duff B, Weigel JA, Bourne P, Weigel PH, McGary CT.
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, and The Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Hum Pathol 2002 Mar;33(3):265-9 Abstract quote
The liver contains two distinct endothelial cell types: vascular and sinusoidal. Although cavernous hemangioma is the most common benign tumor of the liver, vascular or sinusoidal endothelial cell differentiation has not been described.
An endocytic receptor responsible for the uptake and degradation of hyaluronan is present in the sinusoidal endothelium of the liver. The hyaluronan receptor for endocytosis (HARE) may therefore be a useful marker for sinusoidal endothelial cell differentiation. Using monoclonal antibodies specific for HARE, CD31, and factor VIII, we completed an immunohistochemical study of the endothelial cells of both hepatic cavernous hemangiomas and of nonneoplastic human liver. The anti-HARE monoclonal antibodies showed diffuse strong staining of nonneoplastic liver sinusoidal endothelium. No staining of nonsinusoidal endothelium or the endothelial lining of the hemangiomas was seen with anti-HARE. In contrast, diffuse strong staining for factor VIII and CD31 was present in nonsinusoidal endothelium and cavernous hemangioma endothelium. Neither factor VIII nor CD31 staining was present in the sinusoidal endothelium.
In conclusion, the endothelium of hepatic cavernous hemangiomas demonstrates vascular but not sinusoidal differentiation based on the absence of HARE and presence of CD31 and factor VIII.
PLACENTAL ASSOCIATED VASCULAR ANTIGENS
A Unique Microvascular Phenotype Shared by Juvenile Hemangiomas and Human Placenta
Paula E. North, etal.
Arch Dermatol. 2001;137:559-570 Abstract quote
Juvenile hemangiomas are common, benign tumors, distinctive for their perinatal presentation, rapid growth during the first year of life, and subsequent involution. We recently reported that endothelia of hemangiomas highly express GLUT1, a glucose transporter normally restricted to endothelia with blood-tissue barrier function, as in brain and placenta.
To investigate possible further similarities between hemangioma and placental vessels.
In a retrospective study of a variety of vascular tumors and anomalies, we assessed lesional immunoreactivities for the placenta-associated vascular antigens FcRII, Lewis Y antigen (LeY), merosin, and GLUT1.
A university-affiliated pediatric hospital.
Main Outcome Measure
Immunoreactivities scored for each antigen were summarized according to lesional type, compared with those of normal skin, brain, and placenta, and correlated with patient age, sex, and lesional location.
All of 66 hemangiomas (patients aged 22 days to 7 years) showed intense immunoreactivity for FcRII, merosin, LeY, and GLUT1. No immunoreactivities for these markers were seen in any of 26 vascular malformations, 4 granulation tissue specimens, 13 pyogenic granulomas, or in the tumor vasculature of 6 malignant tumors of nonvascular origin. Microvascular immunoreactivity for all 4 markers was observed in placental chorionic villi, but was absent in microvessels of normal skin and subcutis. Brain microvessels expressed only GLUT1 and merosin.
A distinct constellation of tissue-specific markers is uniquely coexpressed by hemangiomas and placental microvessels. These findings imply a unique relationship between hemangioma and the placenta and suggest new hypotheses concerning the origin of these tumors.
Infantile Hemangiomas Speculation on Placental Trophoblastic Origin
Alanna Flath Bree, etal.
Arch Dermatol. 2001;137:573-577 Abstract quote
The unique immunobiology of the placental trophoblast and the increased incidence of hemangiomas in infants born after chorionic villus sampling suggest that an immunologically regulated ectopic focus of trophoblasts could be the cell of origin for proliferative infantile hemangiomas.
To compare tissue from infantile hemangiomas with that of other vascular lesions for the presence of selected placental trophoblast-specific cellular markers.
Design and Patients
Twelve tissue specimens taken from infantile hemangiomas on patients aged 5 days to 2 years were retrospectively confirmed clinically and histologically. Negative controls were similarly confirmed, including 6 pyogenic granulomas and 4 vascular-lymphatic malformations. These tissues were used for immunohistochemical analysis of selected trophoblastic markers including human placental lactogen, placental alkaline phosphatase, and cytokeratins 7, 8, and 17.
Tissue submitted from patients seen at Saint Louis University Department of Dermatology and Cardinal Glennon Children's Hospital in St Louis, Mo, between January 1, 1997, and October 31, 1999.
Main Outcome Measure
Differential staining for trophoblastic markers in infantile hemangiomas compared with control tissues.
The 12 infantile hemangiomas were uniformly negative for all markers tested. Control tissues were also negative for these markers. Four of the 5 histochemical markers did recognize specific nonvascular, cutaneous elements: placental alkaline phosphatase stained smooth and striated muscle, cytokeratins 7 and 8 stained eccrine glands, and cytokeratin 17 stained pilosebaceous units.
Our results do not support the placental trophoblast as the cell of origin for infantile hemangiomas, but we hope our observations and speculation will stimulate further study of this hypothesis.
CHARACTERIZATION Consumptive coagulopathy May be associated with large tumors Thrombocytopenia Secondary to platelet trapping
CHARACTERIZATION Thickening and nodules in port-wine stains
J Am Acad Dermatol 2001;44:300-2
Thickening is a further dilation of the ectatic vessels, and nodules are vascular neoplasms or hyperplasias
The records of 173 subjects with port-wine stains were reviewed:
Incidence of nodules increased with age
Thickening often began in early adulthood, but its intensity and association with nodules continued to increase into older age
Most common in the area of the second and third branches of the trigeminal nerve innervating the face and were associated with deepening color
Incidence of thickening alone was greater in male than in female patients
COMPLICATED LOCATIONS Cervicofacial
Association with symptomatic hemangiomas of the upper respiratory tract
40% require tracheotomy
Periorbital May lead to visual compromise Lumbosacral May be associated with spinal dysraphism and a tethered cord Parotid May distort the mandibular bone and compress the facial nerve ACQUIRED ELASTOTIC HEMANGIOMA
Acquired elastotic hemangioma: A clinicopathologic variant of hemangioma.
Requena L, Kutzner H, Mentzel T.
Department of Dermatology, Fundacion Jimenez Diaz, Universidad Autonoma, Madrid; and Dermatohistologisches Labor, Friedrichshafen
J Am Acad Dermatol 2002 Sep;47(3):371-6 Abstract quote
BACKGROUND: In recent years, many new cutaneous vascular proliferations have been described. This is partly due to the current epidemic of AIDS, which has forced dermatopathologists to establish the diagnosis of the earliest patch-stage lesions of AIDS-related Kaposi's sarcoma and some of the recently described cutaneous vascular proliferations that may histopathologically mimic lesions of early Kaposi's sarcoma.
OBJECTIVE: This article reports the clinical, histopathologic, and immunohistochemical findings in 6 cases of a clinicopathologic variant of cutaneous hemangioma, which we have named acquired elastotic hemangioma.
METHODS: Six cases of acquired elastotic hemangioma were studied from clinical, histopathologic, and immunohistochemical standpoints. The histopathologic differential diagnosis with other similar cutaneous vascular proliferations is discussed.
RESULTS: Acquired elastotic hemangioma appears on the sun-damaged skin of the dorsal aspect of the forearms or on the lateral aspects of the neck of middle-aged or elderly women. Clinically, lesions present as solitary erythematous plaques with variable morphology and in only some cases have a clearly angiomatous appearance. On histopathologic examination, acquired elastotic hemangioma is characterized by a band-like proliferation of capillary blood vessels involving the superficial dermis and arranged horizontally parallel to the epidermis.
CONCLUSION: Acquired elastotic hemangioma is a distinctive clinicopathologic variant of hemangioma that should be differentiated from other cutaneous vascular proliferations. On histopathologic examination, it is characterized by capillary proliferation involving the dermis.
Epithelioid hemangioma of bone. A tumor often mistaken for low-grade angiosarcoma or malignant hemangioendothelioma.
O'Connell JX, Kattapuram SV, Mankin HJ, Bhan AK, Rosenberg AE.
Department of Pathology, Massachusetts General Hospital, Boston 02114.
Am J Surg Pathol 1993 Jun;17(6):610-7 Abstract quote
Epithelioid hemangiomas are benign vascular tumors that usually occur in the skin and subcutis. They have been infrequently recognized in bone. Because of their unusual cytologic appearance and growth patterns, they are commonly confused with malignant tumors.
We report a series of 12 epithelioid hemangiomas of bone occurring in adult patients, including five males and seven females whose ages at presentation ranged from 24 to 74 years, with a mean of 46 years. Five tumors were associated with involvement of the adjacent soft tissue. A single patient had multifocal bone disease. The most common presenting symptom was localized pain. Treatment of the patients varied widely; however, none of the tumors behaved aggressively. In 11 cases, adequate tissue was available for immunohistochemical analysis, which revealed positive staining for the epithelial markers cytokeratin and epithelial membrane antigen in nine cases. All 11 tumors stained for factor VIII-related antigen and Ulex europeus agglutinin. We believe that many of the vascular tumors of bone that have been reported as low-grade malignant hemangioendotheliomas probably represent examples of epithelioid hemangiomas.
We recommend that the criteria for diagnosing vascular tumors of bone conform to those used for morphologically similar tumors that arise in the soft tissues.
CONGENITAL NONPROGRESSIVE HEMANGIOMA
Congenital nonprogressive hemangioma: a distinct clinicopathologic entity unlike infantile hemangioma.
North PE, Waner M, James CA, Mizeracki A, Frieden IJ, Mihm MC Jr.
Department of Pathology, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR 72202, USA.
Arch Dermatol 2001 Dec;137(12):1607-20 Abstrac quote
BACKGROUND: Infantile hemangiomas are common tumors, distinctive for their perinatal presentation, rapid growth during the first year of life, and subsequent involution-and for their expression of a unique immunophenotype shared by placental microvessels. Occasional "hemangiomas" differ from the classic form in presenting fully formed at birth, then following a static or rapidly involuting course. These congenitally fully developed lesions have generally been assumed to be clinical variants of more typical, postnatally developing hemangiomas. This assumption has not been tested by rigorous histologic and immunophenotypic comparisons.
OBJECTIVE: To compare the histologic and immunohistochemical features of congenital nonprogressive hemangiomas with those of typical, postnatally proliferating, hemangiomas.
DESIGN: All cellular vascular tumors resected from infants younger than 4 months at Arkansas Children's Hospital, Little Rock, over the past 20 years (43 lesions from 36 patients) were first characterized histologically and immunohistochemically, then clinically by chart review.
SETTING: A university-affiliated pediatric hospital.
MAIN OUTCOME MEASURES: Histologic appearance, immunoreactivity for the infantile hemangioma-associated antigens GLUT1 and LeY, and clinical behavior.
RESULTS: Congenital nonprogressive hemangiomas differed from postnatally proliferating infantile hemangiomas in histologic appearance and immunohistochemical profile. Distinguishing pathologic features of these tumors were lobules of capillaries set within densely fibrotic stroma containing hemosiderin deposits; focal lobular thrombosis and sclerosis; frequent association with multiple thin-walled vessels; absence of "intermingling" of the neovasculature with normal tissue elements; and lack of immunoreactivity for GLUT1 and LeY.
CONCLUSION: Congenital nonprogressive hemangiomas are histologically and immunophenotypically distinct from classically presenting hemangiomas of infancy, unlikely to be related to the latter in pathogenesis.
- J Am Acad Dermatol. 2006 Oct;55(4):614-9. Epub 2006 Aug 2. Abstract quote
PURPOSE: Infantile hemangiomas of the orbit and eyelid can cause serious ocular problems, such as astigmatism and amblyopia. Magnetic resonance imaging and ultrasonography are the best ways to establish the diagnosis and to evaluate the extent of the lesion. Our goal was to correlate the lesion location with the visual impairment.
MATERIAL AND METHODS: This was a retrospective study (1992-2004) of 63 cases of orbit and eyelid hemangiomas (13 male, 50 female patients; ages: 1 day old to 3 years old). Imaging methods were magnetic resonance imaging or computed tomographic-scanning and color Doppler ultrasonography. The anatomic definition was palpebral, extraconal, and extraconal with intraconal involvement. All patients had ophthalmologic evaluations.
RESULTS: The hemangiomas were palpebral (n = 32) (normal vision: 19; amblyopia and/or astigmatism: 13), extraconal, and extraconal with intraconal involvement (n = 31) (normal vision: 4; amblyopia and/or astigmatism: 27).
LIMITATIONS: This study was small; a prospective study is needed.
CONCLUSION: Orbit and eyelid hemangiomas need to be carefully evaluated by an ophthalmologist. Extraconal and intraconal hemangiomas are more frequently associated with ocular involvement. However, ocular complications can occur in palpebral lesions.
The nonrandom distribution of facial hemangiomas.
Waner M, North PE, Scherer KA, Frieden IJ, Waner A, Mihm MC Jr.
Department of Head and Neck Surgery and Otolaryngology, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, 72202, USA.
Arch Dermatol. 2003 Jul;139(7):869-75 Abstract quote
OBJECTIVE: To map sites of occurrence of facial infantile hemangiomas and correlate these with pattern of tumor growth, clinical complications, and proximity to structural and developmental landmarks.
DESIGN: A retrospective medical record review of 205 patients diagnosed with facial infantile hemangioma.
SETTING: Arkansas Children's Hospital, Little Rock, a 250-bed teaching hospital affiliated with the University of Arkansas for Medical Sciences.
PATIENTS: Based on their clinical photographs, 232 of the hemangiomas were mapped on a facial schematic. Each lesion was encoded with a number reflective of its location, and this number was shared by other lesions occurring at the same site. Frequencies of complicating ulceration and airway obstruction were determined by medical record review.
RESULTS: Two patterns of tumor growth were evident among the hemangiomas analyzed: focal (177 lesions [76.3%]) and diffuse (55 lesions [23.7%]). The focal hemangiomas mapped to 22 sites of occurrence, all near lines of mesenchymal or mesenchymal-ectodermal embryonic fusion. The 55 diffuse hemangiomas showed a segmental tissue distribution and thus were designated as frontonasal (15 lesions [27%]), maxillary (19 lesions [35%]), or mandibular (21 lesions [38%]). Ulceration was 3 times more common in patients with diffuse hemangiomas (21 [51%] of 41) than in patients with focal hemangiomas (28 [17%] of 164). Airway obstruction was characteristic of diffuse mandibular hemangiomas.
CONCLUSIONS: Facial infantile hemangiomas occurred in 2 distinct patterns of tissue involvement: a focal type with a tumorlike appearance and a less common diffuse type with a plaquelike appearance. The diffuse lesions were more likely to be complicated by ulceration or airway obstruction and showed a strikingly segmental distribution pattern. Focal hemangiomas, in contrast, showed a predilection for regions of embryological fusion.
INFANTILE Congenital hemangiomas and infantile hemangioma: Missing links.
Mulliken JB, Enjolras O.
J Am Acad Dermatol. 2004 Jun;50(6):875-82. Abstract quote
Rapid postnatal growth and slow involution in childhood characterize the common infantile hemangioma. There are other rare vascular tumors that present fully grown at birth and behave quite differently, as designated by the acronyms: rapidly involuting congenital hemangioma (RICH) and noninvoluting congenital hemangioma (NICH).
RICH and NICH have similarities in appearance, location, size, equal sex ratio, and both have overlapping radiologic and histologic features with infantile hemangioma. However, neither type of congenital tumor immunostains for glucose transporter-1 protein, a marker of infantile hemangioma. This raises the question of whether these congenital vascular lesions are variations in a spectrum of hemangioma or are entirely different tumors.
We describe two groups of patients that suggest a linkage between postnatal and congenital vascular tumors: Link I (n=5), children who had either RICH or NICH coexisting with infantile hemangioma, and Link II (n=10), children initially diagnosed as having RICH, but regression was incomplete and the residuum was that of NICH. We conclude that these infants exhibit "missing links" between the rare RICH and NICH, and the common infantile hemangioma.
Hemangiomas of infancy.
Bruckner AL, Frieden IJ.
Department of Dermatology, University of Colorado, and the Department of Dermatology and Pediatrics, University of California, San Francisco.
J Am Acad Dermatol 2003 Apr;48(4):477-93 Abstract quote
Hemangiomas of infancy are unique, benign, pediatric tumors of endothelial cells characterized by an initial phase of rapid proliferation, followed by slow involution, often leading to complete regression.
Although most of these tumors are small and innocuous, some may be may be life- or function-threatening, or have associated structural congenital anomalies. Uncertainties regarding their diagnosis or management often prompt referral to a dermatologist.
The pathogenesis of hemangiomas of infancy is not well understood, but recent findings suggest a unique vascular phenotype with dysregulated vascular homeostasis. This article reviews new information regarding the pathogenesis of these tumors and highlights the more worrisome presentations, including syndromic hemangiomas, that are likely to be problematic. In addition, management strategies and treatment options are discussed.
- J Am Acad Dermatol. 2007 Feb;56(2):242-9. Abstract quote
BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a well-known eponym for a capillary-lymphatic-venous malformation which is associated with soft tissue and skeletal hypertrophy, usually of one or more limbs. Plain films, sonograms, conventional venograms, and arteriograms have been employed for the evaluation of the disease.
OBJECTIVE: To demonstrate the usefulness of multidetector computed tomography (MDCT) and fast 3-dimensional magnetic resonance imaging (3D-MR) venography for the assessment and therapeutic planning of patients with KTS.
METHODS: A prospective study in 16 consecutive patients with KTS using MDCT and 3D-MR venography, performed between January 2004 and January 2006 in a university hospital in Pamplona, Spain.
RESULTS: In nearly all patients, persistent embryologic veins were observed, and in one subject aplasia/atresia of the whole deep venous system of the affected extremity was seen. In four individuals hypoplasia of the femoral vein was observed; one subject had duplication of the femoral vein, and in three patients aplasia/atresia of this vein was found. Only half of the patients had normal popliteal veins. In one patient, aneurysmal dilatation of the popliteal vein was detected, and in six subjects, aplasia of this vein was observed. The presence of geographic stains was suggestive of hypoplasia and/or aplasia of femoral and popliteal veins.
LIMITATIONS: The small size of the group of patients with KTS, which is related to low incidence of the disease.
CONCLUSIONS: MDCT and 3D-MR venography are extremely helpful for the global evaluation of patients with KTS. Information regarding soft tissue and bony anatomy as well as information about superficial and deep venous systems may be obtained with a single exam.
MATOSIS WITH THROMBOCYTOPENIA
endotheliomatosis with thrombocytopenia:
a newly recognized clinicopathological
North PE, Kahn T, Cordisco MR, Dadras SS, Detmar M, Frieden IJ.
Departments of Pathology and Otolaryngology, the University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR 72202, USA.
Arch Dermatol. 2004 May;140(5):599-606. Abstract quote
BACKGROUND: Severe thrombocytopenic coagulopathy may complicate platelet-trapping vascular tumors such as kaposiform hemangioendothelioma and tufted angioma. Low-grade, chronic consumptive coagulopathy may occur with extensive venous and lymphatic malformations. We have also observed patients with rare multifocal, congenital skin and gastrointestinal (GI) tract vascular anomalies of distinctive and remarkably similar appearance, all associated with coagulopathy. We studied the clinical and histopathologic features of 3 patients demonstrating this previously uninvestigated phenomenon.
OBSERVATIONS: All 3 patients presented with hundreds of congenital red-brown skin plaques as large as a few centimeters, with similar lesions throughout the GI tract and severe GI tract bleeding. One patient had synovial involvement. All had significant thrombocytopenia, with prothrombin and partial thromboplastin times and fibrinogen levels near the reference range. Corticosteroids and/or interferon alfa treatment resulted in equivocal or no improvement. Skin lesions from all 3 patients were histologically distinctive and similar, including dilated, thin-walled vessels in the dermis and subcutis lined by hobnailed, proliferative endothelial cells (10%-15% immunoreactive for Ki-67), most displaying intraluminal papillary projections. Immunoreaction for the lymphatic marker LYVE-1 was uniformly present.
CONCLUSIONS: We propose the term multifocal lymphangioendotheliomatosis with thrombocytopenia to distinguish this newly recognized clinicopathological entity. These congenital lesions, like tufted angioma and kaposiform hemangioendothelioma, show lymphatic differentiation, strengthening the association between abnormal lymphatic endothelium and coagulopathy.
Hemangioma of the salivary gland: A study of ten cases of a rarely biopsied/excised lesion.
Childers EL, Furlong MA, Fanburg-Smith JC.
Departments of Oral and Maxillofacial Pathology and Soft Tissue Pathology, The Armed Forces Institute of Pathology, Washington, DC.
Ann Diagn Pathol 2002 Dec;6(6):339-44 Abstract quote
Hemangioma is a common soft tissue tumor that frequently occurs in the oral and maxillofacial region including salivary glands, but is rarely biopsied and is therefore often unfamiliar to the surgical pathologist.
Our study examined the subclassification and histologic features of salivary gland hemangioma (SGH). Consultative cases coded as hemangioma and located in salivary gland from 1970 to 2000 were retrieved from the Registry of Oral and Maxillofacial Pathology of the Armed Forces Institute of Pathology (Washington, DC).
Only cases with histologic evidence of salivary gland involvement were included. Slide material and patient history for all cases were reviewed, subclassification assigned, and histologic features were noted. Ten cases coded as hemangioma with slides and history met our inclusion criteria. Seven cases were the "juvenile hemangioma" subtype in the parotid of infants, ranging in age from 3 to 10 months (mean age, 5.3 months) with a male predominance. These SGH had a distinctive histologic appearance of a cellular proliferation of capillary sized vessels around retained salivary gland ducts. Mitoses were easily identified. Three additional cases in females included an arteriovenous hemangioma of a lip minor salivary gland since birth in a 15-month-old infant and two parotid gland lesions: a lobular capillary hemangioma of a 10-year-old and a cavernous hemangioma in a 51-year-old. The latter three cases grew as replacing masses and lacked retained salivary gland ducts within the lesion, despite glandular tissue at the periphery of the tumor. No SGH cases in our series were identified in the submandibular or sublingual glands.
Despite its common occurrence, SGH is relatively rare in our surgical pathology files. The parotid gland is the most common location (90%). Salivary gland hemangioma includes usual hemangioma subtypes, mainly in females, and a distinctive infantile subtype of capillary hemangioma (juvenile hemangioma), displaying distinctive histology and found predominately in males. The cellularity, mitotic activity, and retained salivary gland ducts in the latter lesion should not make one consider malignancy.
SEGMENTAL HEMANGIOMAS Association of solitary, segmental hemangiomas of the skin with visceral hemangiomatosis.
Metry DW, Hawrot A, Altman C, Frieden IJ.
Department of Dermatology, Baylor College of Medicine, Houston, Texas 77030, USA
Arch Dermatol. 2004 May;140(5):591-6. Abstract quote
BACKGROUND: Multiple hemangiomas of the skin have traditionally been recognized as a clue to potential visceral hemangiomas. Recently, hemangiomas have been recognized to have subcategories, localized and segmental, which correlate with risk of complications. While less common, segmental hemangiomas of the skin have a higher risk of being life- or function-threatening and/or having associated structural anomalies such as those that occur in PHACE (posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities) syndrome (PHACES, if sternal clefting/supraumbilical raphe is included). However, the potential association of solitary, segmental hemangiomas of the skin with visceral hemangiomatosis has not been previously emphasized.
OBSERVATIONS: A total of 47 cases of segmental hemangiomas of the skin in association with visceral hemangiomatosis were found. The location of the cutaneous hemangiomas most commonly, but not exclusively, involved the face (37 cases [79%]). The most common site of internal organ involvement was the liver (20 cases [43%]), followed by the gastrointestinal tract (16 [34%]), brain (16 [34%]), mediastinum (9 [19%]), and lung (7 [15%]). The percentages of reported cases of hemangiomas of the pancreas, spleen, bones, or kidneys were 6% or less. Forty percent of patients met criteria for the diagnosis of PHACE(S) syndrome. In this subgroup, internal organ hemangiomas were most commonly found in the brain or mediastinum (18 cases [53%]). Overall, 12 patients (25%) died during infancy, most commonly because of gastrointestinal involvement or congestive heart failure secondary to liver involvement.
Conclusion: Segmental hemangiomas of the skin have an associated risk of visceral hemangiomatosis, with the potential of causing vital organ compromise.
CHARACTERIZATION CUTANEOUS COLLAGENOUS VASCULOPATHY
Cutaneous collagenous vasculopathy with generalized telangiectasia: an immunohistochemical and ultrastructural study
Samih Salama and Donald Rosenthal
J Cutan Pathol 2000;27 (1), 40-48 Abstract quote
We report a 54-year-old male, with a 5-year history of spreading asymptomatic generalized cutaneous telangiectases. The patient had no mucosal or nail involvement, no positive family history and no clinical evidence of systemic disease or bleeding diathesis.
Histologically, the superficial small dermal blood vessels were dilated and showed thickened walls with hyaline perivascular material, staining as collagen. The vessel walls were PAS and colloidal iron stain positive, and immuno-histochemically lacked actin staining. Collagen IV, fibronectin and laminin antibodies showed the material deposited around the basement membrane zone. Ultrastructurally, the vessels were post-capillary venules (PCV) and showed marked collagen deposition around the basal lamina. There were many abnormally banded widely spaced fibres with 100–150 nm periodicity (Luse bodies), in addition to regular banded collagen. Pericytes were sparse and lacked intracytoplasmic filaments, and few veil or fibroblastic cells were seen embedded within the collagen.
We believe this is a form of cutaneous microangiopathy not previously described, with distinct morphology and unique ultrastructural features. It may be due to a genetic defect with erroneous production of disorganized collagen in the cutaneous microvasculature. Dermatologists and Dermatopathologists should be aware of this unusual cutaneous vasculopathy.
CUTANEOUS EPITHELIOID ANGIOMATOUS NODULE
Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1072, USA.
- Am J Dermatopathol. 2008 Feb;30(1):16-20. Abstract quote
Cutaneous epithelioid angiomatous nodule is a peculiar and recently recognized vascular proliferation. Clinically, these lesions affect different areas of the body and histologically are characterized by a well-circumscribed, mainly unilobular, solid proliferation of endothelial cells with prominent epithelioid features. The cytoplasm is abundant and eosinophilic, and many of the neoplastic cells contain prominent vacuoles. Inflammatory infiltrates are variable. All the cases reported thus far have followed a benign course.
We report 10 additional cases of this curious entity, including 2 which presented in an eruptive fashion and 5 that were located on the head and neck.
We also discuss the histological differential diagnoses with other epithelioid proliferations and propose categorization within the spectrum of epithelioid hemangioma.
From the Department of Pathology, Henry Ford Hospital, Detroit, MI.
- Am J Dermatopathol. 2008 Dec;30(6):539-44. Abstract quote
Glomeruloid hemangiomas (GHs) are glomeruli-like capillary tufts lined by endothelial cells that contain periodic acid-Schiff (PAS) positive eosinophilic globules (EGs). These hemangiomas are characteristic cutaneous manifestation of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes). Hemangiomas histologically identical to GHs but not associated with POEMS have recently been designated as papillary hemangiomas.
In this report, we present solitary head and neck GHs in 3 patients, 2 without POEMS, with particular attention to the characteristic EGs. We performed immunostains for hemoglobin A, kappa and lambda light chains, factor VIII-related antigen, CD31 and CD34, PAS stain after diastase digestion (PASD), and electron microscopic examinations on routinely fixed tissues containing EGs. Eosinophilic globules stained uniformly positive for PASD but only peripherally positive for hemoglobin and light chains on surfaces, with interiors negative for antigens. Factor VIII-related antigen and CD31 and CD34 confirmed cells containing EGs to be endothelial. Electron microscopic examination suggested that EGs are enlarged secondary lysosomes (thanatosomes). These features fail to support red blood cells or immunoglobulins as EG constituents.
Glomeruloid hemangiomas may be vascular proliferations stimulated by endothelial cells' protein phagocytosis but not by phagocytosis of either hemoglobin-containing red blood cells or immunoglobulins. The vascular lesions in POEMS syndrome appear identical to papillary hemangioma in cases without the other syndromic manifestations.
- Solitary glomeruloid haemangioma without POEMS syndrome.
Velez D, Delgado-Jimenez Y, Fraga J.
Department of Pathology, 'La Princesa' University Hospital, Madrid, Spain.
J Cutan Pathol. 2005 Jul;32(6):449-452. Abstract quote
Background: The term 'glomeruloid haemangioma' was coined by Chan et al. for a histologically distinctive cutaneous haemangioma, which they considered a specific cutaneous marker for POEMS syndrome. Glomeruloid haemangiomas appear to be specific to POEMS syndrome, because they have not been reported in patients without this syndrome.
Methods: We report on an 86-year-old man without POEMS syndrome and with a solitary red papule on the face.
Results: A cutaneous biopsy showed histological findings consistent with a glomeruloid haemangioma. Physical examination of the skin did not show any other cutaneous lesion and laboratory and radiological studies ruled out the presence of POEMS syndrome.
Conclusions: Glomeruloid haemangiomas could exceptionally be present as solitary vascular tumours and out of the context of POEMS syndrome. To our knowledge, this is the first case reported of glomeruloid haemangioma without POEMS syndrome. Moreover, the presentation on the face is also highly unusual. Velez D, Delgado-Jimenez Y, Fraga J. Solitary glomeruloid haemangioma without POEMS syndrome.
Glomeruloid hemangioma in POEMS syndrome shows two different immunophenotypic endothelial cells
Saburo Kishimoto, Hideya Takenaka, Ryo Shibagaki, Yosuke Noda, Mari Yamamoto and Hirokazu Yasuno
Department of Dermatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
J Cutan Pathol 2000;27 (2), 87-92 Abstract quote
The case of a Japanese woman with glomeruloid hemangioma, an initial marker for POEMS syndrome, is reported. Her cutaneous lesions were multiple and consisted of glomeruloid hemangiomas, cherry-type capillary hemangiomas, and a mixture of both. The specimens of glomeruloid hemangiomas were studied by paraffin section immunohistochemistry with a large panel of antibodies and electron microscopy, respectively.
The lesions, whose size ranged from minute foci to large nodules, were composed of anastomosing vascular channels resembling renal glomeruli and had irregular lumina, often featuring capillaries and sinusoid-like spaces. The vascular channels were lined by a single layer of endothelial cells, which showed two types of cells. The capillary-type endothelium possessed large vesicular nuclei with open chromatin and large amount of cytoplasm. The sinusoidal endothelium possessed small basal nuclei with dense chromatin as well as scant amount of cytoplasm. The former cells had a characteristic CD31+/CD34+/UEA I +/CD68- phenotype. Some of these cells ultrastructurally showed intracytoplasmic lumen formation. The latter cells had a characteristic CD31+/CD34-/UEA I-/CD68+ phenotype.
The present study shows that glomeruloid hemangioma has unique morphologic and immunologic features that differ from the traditional hemangiomas as well as littoral cell angioma of the spleen.
TARGETOID HEMOSIDEROTIC HEMANGIOMA
Hobnail hemangiomas (targetoid hemosiderotic hemangiomas) are true lymphangiomas.
Franke FE, Steger K, Marks A, Kutzner H, Mentzel T.
Department of Pathology, Justus-Liebig University, Giessen, Germany.
J Cutan Pathol. 2004 May;31(5):362-7. Abstract quote
Background: Hobnail hemangioma (targetoid hemosiderotic hemangioma) is a small benign vascular tumor of the superficial and mid-dermis. In contrast to its well-characterized histology, it has been unclear whether this tumor arises from blood vessel endothelial cells (BECs) or lymphatic vessel endothelial cells (LECs).
Methods: We analyzed 10 hobnail hemangiomas by immunohistochemistry, using the recently described lymphatic endothelial cell marker, D2-40. For comparison, CD31, CD34, and alpha-smooth muscle actin expression were studied in consecutive sections of the paraffin-embedded tissues.
Results: In all analyzed vessels, D2-40 labeled exclusively LECs, whereas BECs were consistently negative. In contrast to capillary BECs, either neighboring the tumors or intermingled, neoplastic endothelial cells of all 10 hobnail hemangiomas were strongly labeled by D2-40.
Conclusions: The results suggest a lymphatic origin for hobnail hemangiomas. This view is further supported by the CD34 negativity of endothelial cells and the lack of actin-labeled pericytes in hobnail hemangiomas, both characteristic of lymphatic vessels. Moreover, our analysis revealed that microshunts between neoplastic lymphatic vascular channels and small blood vessels occur, explaining some features of hobnail hemangiomas, such as aneurysmatic microstructures, erythrocytes within and beneath neoplastic vascular spaces, inflammatory changes, scarring, and interstitial hemosiderin deposits.
Hobnail hemangioma ("targetoid hemosiderotic hemangioma"): clinicopathologic and immunohistochemical analysis of 62 cases.
Mentzel T, Partanen TA, Kutzner H.
Department of Pathology, University of Jena, Germany.
J Cutan Pathol 1999 Jul;26(6):279-86 Abstract quote
Hobnail hemangioma, also known as "targetoid hemosiderotic hemangioma", represents a distinctive, benign vascular tumor, characterized histologically by a biphasic growth pattern of dilated vascular structures in the superficial dermis lined by prominent hobnail endothelial cells, and collagen dissecting, rather narrow neoplastic vessels in deeper parts of the lesion.
We analyzed the clinicopathologic and immunohistochemical features in a series of 62 cases.
Patient age range was 6-72 years (median: 32 years); 34 patients were male and 25 female. Clinically, a broad variation of diagnoses ranging from hemangioma to dermal melanocytic nevus and fibrous histiocytoma was suggested. Nineteen tumors arose in the lower and 13 in the upper extremities, 12 on the back, 8 in the buttock and hip region, and one case on the chest wall. Follow-up information on 35 patients (range from 1 to 4 years; mean: 1.5 years) revealed no local recurrence nor systemic metastasis. All neoplasms were located in the dermis and showed a broad morphologic spectrum in dependence of the age of the lesions. In addition to lesions resembling cavernous lymphangioma or lymphangioma circumscriptum, neoplasms were seen with morphologic features reminiscent to retiform hemangioendothelioma, progressive lymphangioma and so-called Dabska's tumor. Immunohistochemistry performed in 28 cases showed positive staining of tumor cells for CD31 in all cases tested, whereas only 3 out of 28 cases stained completely positive for CD34. In addition 4 out of 8 cases stained positively for vascular endothelial growth factor receptor-3 (VEGFR-3). Neoplastic endothelial cells were surrounded by actin-positive pericytes in only 7 out of 27 cases tested.
Hobnail hemangioma occurs more frequently in male patients and arises commonly in the extremities and the trunk. Histologic and immunohistochemcial features suggest a lymphatic line of differentiation for this distinctive vascular neoplasm.
Trauma-Induced Simulator of Targetoid Hemosiderotic Hemangioma
Leslie J. Christenson, M.D.; Mary Seabury Stone, M.D.
From the Department of Dermatology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
Am J Dermatopathol 2001;23:221-223 Abstract quote
Reported here is a 15-year-old with lesions demonstrating histologic features of targetoid hemosiderotic hemangioma (THH) developing after trauma to inflammatory lesions. These lesions pose as simulators of THH. Targetoid hemosiderotic hemangioma is a benign vascular lesion first described by Santa Cruz and Aaronburg. It classically presents as a single, small, red/brown, targetoid lesion on the trunk or extremities of a young or middle-aged individual.
Histologically, it is characterized by ectatic vascular lumina in the papillary dermis lined by a single layer of endothelial cells with an epithelioid or ``hobnail'' appearance. In the deeper dermis, vascular spaces become slit-like and angulated, appearing to dissect through collagen bundles. A commonly proposed etiology of THH is trauma to a preexisting hemangioma.
This case is remarkable for its unusual clinical presentation, histologic simulation of THH, and for its support for the theory that trauma can induce the histologic changes seen in THH.
Absence of HHV-8 DNA in hobnail hemangiomas.
Gutzmer R, Kaspari M, Herbst RA, Kapp A, Kiehl P.
Department of Dermatology and Allergology, Hannover Medical University, Hannover, Germany.
J Cutan Pathol 2002 Mar;29(3):154-8 Abstract quote
BACKGROUND: Hobnail hemangioma (HH) is a rare subtype of hemangioma that shares the morphological feature of hobnail endothelia with retiform hemangioendothelioma (RHE) and has to be considered in the differential diagnosis of Kaposi sarcoma. Since DNA of the human herpesvirus type 8 (HHV-8) has been detected in more than 90% of Karposi sarcomas and could recently be demonstrated in RHE, we sought to detect HHV-8 DNA in HH.
METHODS AND RESULTS: DNA from 12 HH was extracted and subjected to polymerase chain reaction analysis for HHV-8 DNA using two independent protocols with a single set of primers and a nested PCR approach, respectively. PCR amplification was performed using the LightCycler as well as using a thermocycler. HHV-8 DNA could not be detected in HH, although each sample contained DNA adaequately preserved for PCR reactions, as determined by amplification of the beta actin gene.
CONCLUSIONS: HHV-8 appears to play no rule in the pathogenesis of HH. Absence of HHV-8 DNA in HH might be important in the differential diagnosis to other vascular tumours, in particular Kaposi sarcoma.
Large, purpuric with irregular borders and firm nodularity
Unifocal and favors the trunk or retroperitoneum
Spindle cell hemangioma.
Tomasini C, Aloi F, Soro E, Elia V.
Department of Dermatology, University of Turin, Italy.
Dermatology 1999;199(3):274-6 Abstract quote
A 27-year-old woman presented with multiple nodules closely grouped on her right upper distal extremity.
The lesions, dating from childhood, increased slowly in time. Microscopic examination of one nodule showed the histologic features of spindle cell hemangioendothelioma (SCH). At the periphery of the nodule there were also some features of the so-called sinusoidal hemangioma. Clinically, SCH can present as a solitary lesion or as multiple lesions in zonal distribution. When the lesions are multiple, the diagnosis of Maffucci's syndrome should be considered. SCH may be interpreted as a reactive process secondary to thrombosis and recanalization occurring in angiomatous lesions with different clinical presentations. Spindle cells are probably mesenchymal cells modified by blood pressure.
For this entity the term hemangioma seems to be preferable to that of hemangioendothelioma.
- J Cutan Pathol. 2006 Nov;33(11):735-740. Abstract quote
Symplastic hemangioma is characterized by degenerative atypia of vascular smooth muscle and interstitial cells within a pre-existing vascular lesion with minimal endothelial cell atypia.
We describe an additional two cases of this distinctive but poorly recognized entity. On histology, both lesions revealed a cirsoid aneurysm-type appearance with thick-walled and variably dilated blood vessels. The vascular endothelial cells showed mild nuclear hyperchromasia with no multilayering or mitoses. The atypical cells, either located within the vascular smooth muscle wall or within the interstitium, were spindle or epithelioid with varying degrees of hyperchromasia, nuclear enlargement, pleomorphism, and multinucleation. Perivascular hemorrhage, vascular thrombosis, and focal papillary endothelial hyperplasia were uniformly present. The variably fibrous to edematous stroma showed hemosiderin deposits and a mononuclear inflammatory infiltrate.
Clusters of adipocytes were present within the superficial dermis. Rare atypical mitoses and occasional bizarre lipoblast-like stromal cells were identified in one tumor. Immunohistochemistry showed focal smooth muscle actin positivity in the pleomorphic cells of the vascular walls. CD68 and CD34 stained occasional stromal cells in the interstitial location. Both the cases showed no recurrence.
The bizarre cytologic changes are interpreted as degenerative in nature and probably akin to that observed in ancient schwannoma and uterine symplastic leiomyoma.
TUFTED ANGIOMA Numerous tufts or lobules of capillaries present within the middle to lower dermis
Capillary tufts composed of benign spindle cells protruding into neighboring vessels
Subcutaneous plaque or nodule, often annular with a palpable border and central depression
Most common on the thorax
The relationship between angioblastoma (Nakagawa) and tufted angioma: report of four cases with angioblastoma and a literature-based comparison of the two conditions.
Igarashi M, Oh-i T, Koga M.
Department of Dermatology, Tokyo Medical University, Japan.
: J Dermatol 2000 Aug;27(8):537-42 Abstract quote
We report four recent cases of angioblastoma (Nakagawa). Histopathologic examinations of all cases revealed dispersed islets of clear marginal lobules of varying sizes in the dermis. Neoplastic endothelioid cells with moderate atypia and enlarged capillaries containing erythrocytes were found in the conglomerates. Recently, the features of this disease have been compared to the tufted angioma that has been reported in Europe and the U.S. Our evaluation suggests that these two diseases are very likely the same.
We suggest that this disease should be called "angioblastoma" in agreement with the first report of this disease by Nakagawa.
Klein JA, Barr RJ
Pediatr Dermatol 1985 Mar;2(3):191-3 Abstract quote
Two patients with verrucous hemangioma, a congenital vascular malformation, were seen. The typical lesion is a unilateral group of hyperkeratotic papules and nodules on a lower extremity.
Unlike the more common capillary or cavernous hemangiomas, verrucous hemangiomas tend to enlarge and spread with time, and to recur after excision.
GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas.
North PE, Waner M, Mizeracki A, Mihm MC Jr.
Department of Pathology, University of Arkansas for Medical Sciences, and Arkansas Children's Hospital, Little Rock 72202, USA.
Hum Pathol 2000 Jan;31(1):11-22 Abstract quote
Juvenile hemangiomas are common, benign vascular tumors of infancy. These lesions enlarge rapidly through cellular hyperplasia during the first year of life and then involute over several years. Distinctive histopathologic features of hemangiomas diminish during this evolution, and differentiation from vascular malformations becomes increasingly difficult. This distinction has important therapeutic implications, as juvenile hemangiomas differ from malformations in natural history and in potential for recurrence.
We report here that high endothelial immunoreactivity for the erythrocyte-type glucose transporter protein GLUT1 is a specific feature of juvenile hemangiomas during all phases of these lesions. In a retrospective study, we found intense endothelial GLUT1 immunoreactivity, involving more than 50% of lesional microvessels, in 97% (139 of 143) of juvenile hemangiomas from patients aged 1 month to 11 years. No endothelial GLUT1 immunoreactivity was found in any of 66 vascular malformations (17 arteriovenous, 33 venous, 11 lymphatic, and 5 port-wine) from patients aged 5 days to 75 years, or in any of 20 pyogenic granulomas or 7 granulation tissue specimens. Abundant Ki-67 positivity in these latter lesions established that GLUT1 expression does not simply reflect mitotically active endothelium. Focal GLUT1 immunoreactivity was found in 3 of 12 angiosarcomas, but not in any of 5 hemangioendotheliomas (epithelioid or infantile kaposiform). These findings establish GLUT1 immunoreactivity as a highly selective and diagnostically useful marker for juvenile hemangiomas.
Because high levels of endothelial GLUT1 expression in normal tissue are restricted to microvessels with blood-tissue barrier function, these findings also have implications for the molecular and developmental pathogenic mechanisms of juvenile hemangiomas
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
Benign cutaneous vascular tumors of infancy: when to worry, what to do.
Metry DW, Hebert AA.
Department of Pediatric Dermatology, Baylor College of Medicine, 6621 Fannin, MC 3-3315, Houston, TX 77039, USA.
Arch Dermatol 2000 Jul;136(7):905-14 Abstract quote
OBJECTIVES: To discuss the current knowledge regarding complicated hemangiomas (cervicofacial, periorbital, lumbosacral, and parotid), including the associated syndromes of diffuse neonatal hemangiomatosis and PHACES (posterior fossa malformations, most commonly of the Dandy-Walker variant; hemangiomas [especially large, plaquelike, facial lesions]; arterial anomalies; cardiac anomalies and coarctation of the aorta; eye abnormalities; and sternal cleft and/or supraumbilical raphe). To discuss 2 newly recognized entities that may be a source of diagnostic confusion with the common hemangioma, the kaposiform hemangioendothelioma and tufted angioma. To discuss the risks and benefits of current treatment options, including the use of systemic corticosteroids and interferon in necessary situations.
DATA SOURCES: The pertinent world literature was reviewed and incorporated into experience from our pediatric dermatology practice at the University of Texas Medical School at Houston.
CONCLUSIONS: The common hemangioma, kaposiform hemangioendothelioma, and tufted angioma, though benign histologically, may cause serious consequences for children. Dermatologists should be able to recognize unique clinical presentations of these lesions and obtain further diagnostic evaluation accordingly. Dermatologists should also be aware of available treatment options, including the use of systemic chemotherapy in life-threatening situations.
- Hemangioma versus vascular malformation: presence of nerve bundle is a diagnostic clue for vascular malformation.
Adegboyega PA, Qiu S.
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0588, USA.
Arch Pathol Lab Med. 2005 Jun;129(6):772-5. Abstract quote
CONTEXT: Arteriovenous vascular malformations and hemangiomas are benign vascular lesions that are difficult to distinguish from one another clinically. Also, they may be confused with each other at histopathology. Therefore, histochemical stains for the presence of an artery are frequently used to distinguish between the two.
OBJECTIVE: Because it is clinically relevant to differentiate between arteriovenous vascular malformations and hemangiomas, this study was carried out to explore additional diagnostic clues that may help in the diagnosis and differentiation of these lesions.
DESIGN: A total of 167 cases of benign extracranial vascular lesions were retrieved from the anatomic pathology file of our institution. These comprised 66 cases diagnosed as arteriovenous vascular malformations and 101 cases previously diagnosed as hemangiomas. The hematoxylin-eosin-stained glass slides were reviewed, Movat pentichrome histochemical stain was used to identify elastic vessels (arteries/arterioles), and S100 immunostain was used to identify nerves within these vascular lesions. For immunohistochemistry, the avidin-biotin detection method was used.
RESULTS: With Movat stain, the presence of thick-walled elastic arteries was detected in 12 of the 101 cases previously diagnosed as hemangiomas, and these cases were therefore reclassified as vascular malformations. Using the same criterion, 2 of the 66 cases originally diagnosed as arteriovenous vascular malformations were reclassified as hemangiomas because they lacked arterial structures. Thus, with this strict criterion, we ended up with 91 cases of hemangiomas and 76 cases of arteriovenous vascular malformations. Intralesional nerves were identified in 91% (69/76) of cases of arteriovenous vascular malformations, including all the 12 arteriovenous vascular malformations previously diagnosed as hemangiomas. In contrast, no intralesional nerve was detected in any of the 91 hemangiomas.
CONCLUSIONS: These results show that nerve bundles are consistently present in vascular malformations and absent in hemangiomas and so can be used as a diagnostic clue to differentiate between these lesions. Also, in addition to describing a previously unreported component of vascular malformations, these data further confirm the hamartomatous nature of these lesions.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS Usually involute over 2-6 years after 18 months of age TREATMENT GENERAL
Ulcerated hemangiomas: Clinical characteristics and response to therapy
Ho Jin Kim, etal.
J Am Acad Dermatol 2001;44:962-72. Abstract quote
Background: Hemangiomas represent the most common benign tumor of infancy, with ulceration its most frequent complication.
Objective: Our purpose was to review our experience with this challenging problem by evaluating the clinical features, management, and therapeutic responses of ulcerated hemangiomas.
Methods: A retrospective analysis of ulcerated hemangiomas at the University of California, San Francisco outpatient pediatric dermatology clinics and Oakland Children's Hospital from 1987 to 1997 was performed.
Results: The medical records of 60 patients were examined. Forty-nine female and 11 male patients were seen with a female/male ratio of 4.5:1. The majority of ulcerated hemangiomas were of the plaque type (n = 50; 83%) and relatively large; 47 (78%) were larger than 6 cm2. The perineum was the single most frequently involved site, affected in 20 cases (33%). Topical antibiotics, barrier creams, and bio-occlusive dressings were used in most cases. Systemic antibiotics were used in 26 cases (43%) for overt or presumed infection. Systemic corticosteroids were used in 21 children (37%), 5 of whom did not show a response. Intralesional triamcinolone was used in 7 cases (12%), with 4 showing definite improvement. The flashlamp pulsed-dye laser was the modality used in 22 children (37%), 11 (50%) of whom showed definite improvement, 4 (18%) who showed no significant response, and 1 (5%) who showed definite worsening. Interferon alfa-2a was required in 5 patients (8%), all of whom showed improvement without appreciable neurologic side effects. Immediate surgical excision was required in only 2 cases (3%). Pain control with oral acetaminophen, acetaminophen with codeine, and topical 2.5% lidocaine ointment was effective in managing the pain of lip and perineal hemangiomas, with no side effects noted.
Conclusion: No one uniformly effective treatment modality was found, and frequently several were used concurrently. The decision to use specific therapies was dependent on the age of the patient, as well as the location, size, and stage of growth or involution of the hemangioma. Our approach to management included 4 major areas: local wound care, management of infection, specific therapeutic modalities (systemic and intralesional corticosteroids, flashlamp pulsed-dye laser, and interferon alfa-2a), and pain management.
High injection pressure during intralesional injection of corticosteroids into capillary hemangiomas
Arch Opthalmol 2001;119:677-683
Injections of head and neck hemangiomas have been associated with ocular embolization and loss of vision secondary to retrograde flow of the steroid into the ophthalmic arteri proximal to the central retinal artery
Amount needed to cause retrograde flow is not known but may be as low as 0.10 mL
4 infants with 5 treatment sessions, combined receiving 71 injections
63 injections had maximum pressure >100 mm Hg
Volumes ranged from 0.9 to 2.1 mL
Adverse effects of systemic glucocorticosteroid therapy in infants with hemangiomas.
George ME, Sharma V, Jacobson J, Simon S, Nopper AJ.
Sections of Dermatology, Endocrinology, and Research and Statistics, Children's Mercy Hospital, Kansas City, Mo.
Arch Dermatol. 2004 Aug;140(8):963-9. Abstract quote
OBJECTIVE: To evaluate the short- and long-term adverse effects of systemic glucocorticosteroid (GS) therapy in infants with hemangiomas.
DESIGN: Retrospective chart review of infants treated with GSs for hemangiomas during a 3-year period.
SETTING: Tertiary care children's hospitalPatients Of 141 patients identified with hemangiomas, 22 were treated with GSs.Interventions Minimum of 1-month GS therapy at a minimum starting dose of 0.5 mg/kg per day.
OUTCOME MEASURES: Demographic and anthropometric measurements, starting dose and duration of GS therapy, subjective parental concerns, complications related to hemangioma, adjunctive treatment, and morning cortisol levels and/or results of corticotropin stimulation tests.
RESULTS: The average starting dose was 2.23 mg/kg per day; average length of therapy was 28.1 weeks. Complaints of irritability, fussiness, or insomnia were identified in 16 patients (73%). Hypertension, defined as 3 or more episodes of systolic blood pressure higher than 105 mm Hg, was observed in 10 patients (45%). Morning cortisol levels were abnormal in 13 (87%) of the 15 patients evaluated. Low-dose corticotropin stimulation test results were abnormal in 2 of the 3 infants tested.
CONCLUSIONS: While GS therapy for infantile hemangiomas was tolerated well overall, changes in behavior, insomnia, and gastrointestinal symptoms were common parental concerns. Hypertension and hypothalamic-pituitary-adrenal axis suppression were observed frequently. Infants undergoing long-term GS treatment of hemangiomas should be monitored carefully for these potential adverse effects.
Oral Corticosteroid Use Is Effective for Cutaneous Hemangiomas An Evidence-Based Evaluation
Michelle L. Bennett, MD; Alan B. Fleischer, Jr, MD; Sarah L. Chamlin, MD; Ilona J. Frieden, MD
Arch Dermatol. 2001;137:1208-1213 Abstract quote
To determine the efficacy of systemic corticosteroid therapy in treating enlarging, problematic cutaneous hemangiomas and to assess the relationship of dose to response and adverse effects.
A quantitative systematic literature review was performed and inclusion and exclusion criteria were applied.
Patients were treated in primary care, referral centers, and institutional practices. Most patients were ambulatory, although some required hospitalization.
Inclusion criteria were original case series with a minimum of 5 patients with enlarging, problematic cutaneous hemangiomas treated with systemic corticosteroids. Exclusion criteria were being older than 2 years, receiving simultaneous other treatments, being lost to follow-up, or having insufficient information. Twenty-four original case series met inclusion criteria; 10 case series remained (184 patients) after exclusion criteria were applied.
Patients were given a mean prednisone equivalent daily dose of 2.9 mg/kg (95% confidence interval [CI], 2.7-3.1 mg/kg) for a mean of 1.8 months (95% CI, 1.5-2.2 months).
Main Outcome Measures
Response and rebound rates and dose-response and adverse effects–response relationships in responders vs nonresponders.
Response was 84% (95% CI, 78%-89%; range, 60%-100%) and rebound was 36% (95% CI, 29%-44%; range, 0%-65%). A significant difference was found between the mean dose administered to responders vs nonresponders (P<.001). No significant difference was observed as to the occurrence of adverse effects (P = .3).
Systemic corticosteroid treatment seems to be effective for problematic cutaneous hemangiomas of infancy.
- J Am Acad Dermatol. 2007 Jan;56(1):63-8. Abstract quote
BACKGROUND: Active nonintervention remains the mainstay of therapy for most uncomplicated infantile hemangiomas (IH) because of their expected involution. Topical imiquimod, with its ability to induce the production of interferon, tumor necrosis factor-alpha, and the antiangiogenesis factor tissue inhibitor of matrix metalloproteinase, has been recently reported to be efficacious in the treatment of IH.
OBJECTIVE: We sought to evaluate the efficacy of imiquimod 5% cream in the treatment of noncomplicated IH and possible side effects.
METHODS: A retrospective chart review analysis was performed in 18 children (16 girls and 2 boys) with a median age of 18 weeks (range: 4-256 weeks). A total of 22 hemangiomas (14 located on head, 3 on genitalia, 2 on trunk, and 3 on extremities) were treated with imiquimod 5% cream. Imiquimod was applied 3 times weekly in 10 patients and 5 times weekly in 8 patients for a mean duration of 17 weeks (7-46 weeks).
RESULTS: All superficial IH improved, and remission was achieved in 4 hemangiomas. There was little improvement in mixed IH with no or minimal change in all deep hemangiomas. One case with ulcerated hemangioma substantially improved with accelerated ulcer healing and hemangioma size reduction. No systemic complication was observed in any of our patients, with irritation and crusting being the most common reactive effects.
LIMITATIONS: The small-sample, retrospective study limits the interpretation of results.
CONCLUSION: Imiquimod 5% cream may be most effective in superficial IH. There was no significant correlation between response and early onset of treatment for any IH in our small sample study. Pharmacokinetic analysis and placebo-controlled study should follow to ascertain the safety and efficacy of imiquimod 5% cream in the pediatric age group.
- Laser treatment of pediatric vascular lesions: Port wine stains and hemangiomas.
Skincare Doctors, Cambridge, Massachusetts, USA.
- J Am Acad Dermatol. 2008 Feb;58(2):261-85. Abstract quote
Pediatric vascular lesions can be medically threatening and psychologically distressing to patients.
This article reviews literature on the laser treatment of two common pediatric vascular lesions, port wine stains and hemangiomas. The purpose of this report was to distinguish the lesions from one another and to present the advantages, disadvantages, complications, and limitations of laser treatment for each lesion type. This review is not a comprehensive inventory but instead highlights the studies that best show promising results or the limitations of laser treatment for the lesions.
Overall, port wine stain laser treatment promoted notable clearing with low side effects, whereas hemangioma laser treatment provided inconsistent benefits and severe side effects occasionally. Laser treatment of port wine stains is safe and effective, but laser treatment of hemangiomas remains controversial and is best for lesions without deeper components.
- Evaluation of the treatment of port-wine stains with the 595-nm long pulsed dye laser: a large prospective study in adult Japanese patients.
Asahina A, Watanabe T, Kishi A, Hattori N, Shirai A, Kagami S, Watanabe R, Le Pavoux A, Maekawa T, Tamaki K, Ohara K.
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
J Am Acad Dermatol. 2006 Mar;54(3):487-93. Abstract quote
BACKGROUND: Treatments of port-wine stains with conventional pulsed dye laser yield inconsistent results.
OBJECTIVE: We evaluated the efficacy and safety of the longer pulse duration 595-nm dye laser.
METHODS: Sixty-six adult Japanese patients were enrolled in this prospective study. The laser treatment with a cooling device was repeated 4 times at 8-week intervals with a consistent setting of 10-ms pulse duration and an energy fluence of 12 J/cm2, using 7-mm spot size.
RESULTS: Improvement of port-wine stains was observed after multiple treatments, and 67% of the patients achieved either good or excellent response after the fourth treatment. Transient purpura, edema, or both were noted immediately after each treatment (76%-79% and 58%-67%, respectively). Hyperpigmentation (8%-17%) and hypopigmentation (6%-14%) were also mild and their occurrence did not increase by repeating treatments.
LIMITATIONS: Eighty five percent of the patients were classified as having Fitzpatrick skin type IV.
CONCLUSION: Our study indicated that the 595-nm dye laser with 10-ms pulse duration may be effective and well tolerated in the treatment of port-wine stains in adult Asians.
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Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
Telangiectasia-These are vascular ectasias characterized histologically by dilated capillaries. Most are probably congenital anomalies and not true neoplasms.
Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation
Commonly Used Terms
This is a glossary of terms often found in a pathology report.
Learn how a pathologist makes a diagnosis using a microscope
Surgical Pathology Report
Examine an actual biopsy report to understand what each section means
Understand the tools the pathologist utilizes to aid in the diagnosis
How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate
Recent teaching cases and lectures presented in conferences
Last Updated December 1, 2008
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