PATHOLOGY OF VASCULAR SKIN LESIONS - PART 6 doc

Christenson and Seabury Stone 19 described a patient with lesions showing histopathologic features of hobnail hemangioma, which developedafter trauma of an inflammatory cutaneous lesion.

1 Biberstein HH, Jessner M A cirsoid aneurysm of the skin Dermatologica 1956;113:129–41.

2 Girard C, Graham JH, Johnson WC Arteriovenous hemangioma (arteriovenous shunt) J Cutan Pathol 1974;1:73–87.

3 Rosen T Arteriovenous hemangioma Cutis 1979;24:57–9.

4 Carapeto FJ, Garcia-Pérez A, Winkelmann RK Acral arteriovenous tumor Acta Derm Venereol 1977;57:155–8.

5 Carapeto FJ, Armijo M Tumeur acrale arterio-veineuse Ann Dermatol Venereol 1978;105:977–9.

6 Persson JR Acral arteriovenous tumor Acta Derm Venereol 1978;58:95.

7 Connelly MG, Winkelmann RK Acral arteriovenous tumor: a clinicopathologic review Am J Surg Pathol 1985;9:15–21.

8 Neumann RA, Knobler M, Schuller Petrovic S, et al Giant arteriovenous hemangioma (cirsoid rysm) of the nose J Dermatol Surg Oncol 1989;15:739–42.

aneu-9 Koutlas IG, Jessurum J Arteriovenous hemangioma: a clinicopathological and immunohistochemical study J Cutan Pathol 1994;21:343–9.

10 Lazarou G, Goldberg MI Vulvar arteriovenous hemangioma A case report J Reprod Med 2000;45:439–41.

11 Calzavara Pinton P, Carlino A, Manganoni AM, Donzelli C, Faccheti F Sindrome del nevo epidermico con malformazioni e amartomi vascolari multipli G Ital Dermatol Venereol 1990;125:251–4.

12 Akiyama M, Inamoto N Arteriovenous hemangiomas on the foreheads of patients with chronic liver disease Arch Intern Med 1998;158:1469.

13 Satomi H, Imakado S, Ichikawa E, Fujisawa H, Otsuka F A case of arteriovenous hemangioma ciated with liver cirrhosis Dermatology 1999;199:278.

asso-14 Akiyama M, Inamoto N Arteriovenous haemangioma in chronic liver disease: clinical and logic features of four cases Br J Dermatol 2001;144:604–9.

histopatho-15 Kutzner H, Winzer M, Mentzel T Symplastisches Hamangiom Hautarzt 2000;51:327–31.

16 Kishimoto S, Takenaka H, Shibagaki R, Nagata M, Katoh N, Yasuno H Verruciform xanthoma arising

in an arteriovenous haemangioma Br J Dermatol 1998;139:546–8.

Fig 19 Clinical features of hobnail hemangioma Some lesions, such as the one shown in this

figure, have a targetoid appearance, with a central angiomatous papule surrounded by an motic halo.

ecchy-5 HOBNAIL HEMANGIOMA (TARGETOID HEMOSIDEROTIC HEMANGIOMA)

Santa Cruz and Aronberg (1) first described this lesion under the term targetoid

hemo-siderotic hemangioma After the original description, a few cases of mostly single lesions

were reported in the literature (2–14) Recently, Guillou et al (15) revisited the lesion and

coined the term hobnail hemangioma, which is currently the preferred term

C LINICAL F EATURES

Most lesions are characterized by a brown to violaceous central papule, surrounded by

a thin, pale area and a peripheral ecchymotic ring (Fig 19) The ecchymotic halo mately disappears, in contrast to the central papule which persists However, there arehemangiomas with histopathologic features identical to those of targetoid hemosiderotichemangioma that do not have the targetoid appearance Thus the term hobnail heman-

ulti-gioma appears to be a more appropriate name (1,16–17).

H ISTOPATHOLOGIC F EATURES

Histopathologically, hobnail hemangioma has a distinctive biphasic appearance Thecenter of the lesion is composed of dilated, irregular, thin-walled ectatic vascular spacespositioned in the superficial dermis (Fig 20) These vascular spaces sometimes exhibitintraluminal papillary projections and fibrin thrombi at different stages of organization.Prominent, plump, endothelial cells with a hobnail appearance line the papillary projec-tions The deep areas are distinct from the peripheral areas of the lesion because they showirregular, angulated, thin-walled, slit-shaped vascular channels that dissect collagenbundles of the dermis In these areas, dermal fibrosis, hemosiderin deposits, extravasatedred blood cells, and a sparse mononuclear inflammatory infiltrate are frequent findings.Hobnail hemangioma focally exhibits features reminiscent of retiform hemangioendot-helioma, Kaposi’s sarcoma, benign lymphangioendothelioma, and Dabska’s tumor

(1,17,18).

Fig 20 Histopathologic features of hobnail hemangioma (A) Scanning power shows a vascular

proliferation involving the upper half of the dermis (B) Higher magnification shows irregular vascular spaces between collagen bundles of the dermis (C) Still higher magnification demon-

strates that the irregular slit-like spaces are lined by endothelial cells that seem to dissect between collagen bundles of the dermis Note also the abundant extravasation of erythrocytes.

Immunohistochemical studies have demonstrated that the endothelial cells lining thevascular spaces of hobnail hemangioma stain weakly for factor VIII-related antigen and

strongly with Ulex europaeus I lectin, CD 34, and CD31 (1–3,16) Smooth muscle positive pericytes are observed focally around some of the abnormal vascular spaces (1).

actin-Four out of eight cases studied stained positive for vascular endothelial growth factorreceptor-3 (VEGFR-3), which suggests a lymphatic line of differentiation for this distinc-

tive vascular neoplasm(17).

The histopathologic differential diagnosis with the patch stage of Kaposi’s sarcomacan be difficult Hobnail hemangioma shows dilated vessels with intraluminal papillaryprojections lined by prominent endothelial cells, a feature that is absent in Kaposi’ssarcoma The vascular channels at the periphery of the lesion do not surround preexistingvascular and adnexal structures in the dermis, as is the case in the patch stage of Kaposi’ssarcoma Furthermore, in contrast to patch lesions of Kaposi’s sarcoma, there is abundanthemosiderin and absence of plasma cells in the inflammatory infiltrate

Evidence seems to support the fact that hobnail hemangioma with a targetoid ance results from trauma to a preexisting hemangioma or angiokeratoma, with subse-quent development of thrombi and recanalization The central and superficial areas of thelesion show intraluminal projections and thrombi, closely resembling the intravascularpapillary endothelial hyperplasia of Masson, lending further support to the view thathobnail hemangiomas are traumatized hemangiomas or angiokeratomas Once thrombo-sis and canalization occur, the preexisting vessels at the center of the lesion persist,whereas the peripheral ecchymotic halo disappears Support for this sequence is shared

appear-by other authors (14,19) Carlson et al (14) compared the clinicopathologic features of

33 cases of hobnail hemangioma with those of 20 cases of solitary angiokeratoma andfound an overlap of the clinical and histopathologic features in both groups The authorsconcluded that the histopathologic findings of extravasated red blood cells, hemosiderin,telangiectases, lymphangiectases, and fibrosis implicate trauma as the cause of these

acquired vascular proliferations Christenson and Seabury Stone (19) described a patient

with lesions showing histopathologic features of hobnail hemangioma, which developedafter trauma of an inflammatory cutaneous lesion

T REATMENT

Surgical excision is curative, and recurrences have been not reported

References

1 Santa Cruz DJ, Aronberg J Targetoid hemosiderotic hemangioma J Am Acad Dermatol 1988;19:550–8.

2 Rapini RP, Golitz LE Targetoid hemosiderotic hemangioma J Cutan Pathol 1990;17:233–5.

3 Vion B, Frenk E Targetoid hemosiderotic hemangioma Dermatology 1992;184:300–2.

4 Benes P, Douglass M, Lowe L Targetoid hemosiderotic hemangioma; a series of four cases [Abstract].

J Cutan Pathol 1993;20:533.

5 Krahl D, Petzoldt D Targetoides hamosiderotisches Hamangiom Eine weitere Differentialdiagnose des Kaposi-Sarkoms Hautarzt 1994;45:34–7.

6 Lowe L Self assessment—1993 Targetoid hemosiderotic hemangioma J Cutan Pathol 1994;21:568–9.

7 Perrin C, Rodot S, Ortonne JP, Michiels JF L’hémangiome en cible hémosidériniqué Ann Dermatol Venereol 1995;122:111–4.

8 Margaroth GS, Tigelaar RE, Longley J, Luck LE, Leffell DJ Targetoid hemangioma associated with pregnancy and the menstrual cycle J Am Acad Dermatol 1995;32:282–4.

9 Held JL, Malhotra R Targetoid hemosiderotic hemangioma Fitzpatrick’s J Clin Dermatol 1995;3:70.

10 Fariña MC, Montalvo N, Piqué E, et al Hemangioma hemosiderótico en diana: un nuevo caso y revisión

de la literatura Actas Dermosifiliogr 1995;86:383–7.

11 Ho C, McCalmont TH Targetoid hemosiderotic hemangioma: report of 24 cases, with emphasis on unusual features and comparison to early Kaposi’s sarcoma [Abstract] J Cutan Pathol 1995;22:67.

12 Ly S, Versapuech J, Vergier B, Beylot-Barry M, Beylot C Guess what? Targetoid hemosiderotic hemangioma Eur J Dermatol 1998;8:583–5.

13 Avci O, Soyal MC, Sagol O, Gunes AT Targetoid hemosiderotic hemangioma [Letter] J Eur Acad Derm Venereol 1998;11:186–7.

14 Carlson JA, Daulat S, Goodheart HP Targetoid hemosiderotic hemangioma—a dynamic vascular tumor: report of 3 cases with episodic and cyclic changes and comparison with solitary angiokeratomas J Am Acad Dermatol 1999;41:215–24.

15 Guillou L, Calonje E, Speight P, Rosai J, Fletcher CD Hobnail hemangioma: a pseudomalignant vascular lesion with a reappraisal of targetoid hemosiderotic hemangioma Am J Surg Pathol 1999;23:97–105.

16 Santoja C, Torrelo A Hobnail hemangioma Dermatology 1995;191:154–6.

17 Mentzel T, Partanen TA, Kutzner H Hobnail hemangioma (“targetoid hemosiderotic hemangioma”): clinicopathologic and immunohistochemical analysis of 62 cases J Cutan Pathol 1999;26:279–86.

18 Requena L, Sangueza OP Cutaneous vascular proliferations Part II Hyperplasias and benign neoplasms.

J Am Acad Dermatol 1997;37:887–919.

19 Christenson LJ, Seabury Stone M Trauma-induced simulator of targetoid hemosiderotic hemangioma.

Am J Dermatopathol 2001;23:221–3.

Fig 21 Microvenular hemangioma Angiomatous plaque on the anterior chest of a girl.

6 MICROVENULAR HEMANGIOMA

Microvenular hemangioma is a recently described benign vascular neoplasm Hunt

et al (1) coined this name in 1991, but the lesions described in 1989 by Bantel et al (2)

as microcapillary hemangiomas probably represent the same entity So far, 25 cases have

been reported in the literature (1–9).

C LINICAL F EATURES

Microvenular hemangioma is an acquired, slowly growing asymptomatic lesion withangiomatous appearance It is usually solitary, varying in size from 0.5 to 2 cm It mostcommonly affects the upper limbs, particularly the forearms However, lesions on the

trunk (Fig 21), face, and lower limbs have also been recorded (3,4,9) In some patients,

a histogenetic relationship between microvenular hemangioma and hormonal factors

such as pregnancy and hormonal contraceptives has been postulated (2,4), but this feature

has not been corroborated by other authors An example of microvenular hemangioma

developed in a patient with Wiskott-Aldrich syndrome (9) Hemangiomas identical to microvenular hemangiomas can be seen in patients with POEMS syndrome (10).

H ISTOPATHOLOGIC F EATURES

Histopathologically, microvenular hemangioma appears as a poorly circumscribedproliferation of irregularly branched, round to oval, thin-walled blood vessels lined by asingle layer of endothelial cells They involve the entire reticular dermis, and a variabledegree of dermal sclerosis is present in the stroma (Fig 22) The lumina of the neoplasticblood vessels are inconspicuous and often collapse with only a few erythrocytes in them.Immunohistochemically, the cells lining the lumina show positivity for factor VIII-

related antigen and Ulex europaeus I lectin (1–3), which qualifies them as endothelial

cells Some smooth muscle actin, positive perithelial cells have also been described

surrounding these vascular spaces (3,5).

The main differential diagnosis of microvenular hemangioma is with Kaposi’s sarcoma

in the patch stage Kaposi’s sarcoma shows irregular anastomosing vascular spaces,newly formed ectatic vascular channels surrounding preexisting normal blood vesselsand adnexa (promontory sign), plasma cells, hyaline (eosinophilic) globules, and small

interstitial fascicles of spindle cells All these features are absent in microvenularhemangioma.

Characteristic of microvenular hemangioma is the presence of monomorphous small,elongated blood vessels with inconspicuous lumina involving the full thickness of thereticular dermis

T REATMENT

Lesions of microvenular hemangioma are cured by simple excision

References

1 Hunt SJ, Santa Cruz DJ, Barr RJ Microvenular hemangioma J Cutan Pathol 1991;18:235–40.

2 Bantel E, Grosshans E, Ortonne JP Zuz Kenntnis mickrokapillärer angiome, beobachtungen bei schwangeren bzw unter hormoneller antikonzeption stehenden Frauen Z Hautkr 1989;64:1071–4.

3 Aloi F, Tomasini C, Pippione M Microvenular hemangioma Am J Dermatopathol 1993;15:534–8.

4 Satge D, Grande-Goburdhun J, Grosshans E Hémangiome microcapillaire Ann Dermatol Venereol 1993;120:297–8.

Fig 22 Histopathologic features of microvenular hemangioma (A) Scanning power shows a

proliferation of irregular blood vessels with inconspicuous lumina involving the dermis (B) Higher magnification demonstrates irregular vascular spaces lined by endothelial cells (C) Still

higher magnification shows plump endothelial cells lining the inconspicuous lumina.

5 Horn MS, Stern JB Small red nodule on the leg of a young woman Microvenular hemangioma Arch Dermatol 1995;131:483.

6 Black RJ, McCusker GM, Eedy DJ Microvenular haemangioma Clin Exp Dermatol 1995;20:260–2.

7 Sanz Trelles A, Ojeda Martos A, Jiménez Fernández A, Vera Castaño A Microvenular hemangioma:

a new case in a child Histopathology 1998;32:89–90.

8 Fukunaga M, Ushigome S Microvenular hemangioma Pathol Int 1998;48:237–9.

9 Rikihisa W, Yamamoto O, Kohda F, et al Microvenular hemangioma in a patient with Wiskott-Aldrich syndrome Br J Dermatol 1999;141:752–4.

10 Ackerman AB, Guo Y, Vitale P Clues to Diagnosis in Dermatopathology II Chicago, ASCP Press, 1992:285–8.

7 TUFTED ANGIOMA

Tufted angioma is an unusual, acquired vascular neoplasm first described by Wilson

Jones in 1976 (1) A similar lesion was previously described by MacMillan and pion (2) in 1971 under the name progressive capillary hemangioma The neoplasm

Cham-described by Nakagawa as angioblastoma also appears to be identical to acquired tufted

angioma (3–5), although not all authors agree on this point (6).

C LINICAL F EATURES

Clinically, lesions of tufted angioma most commonly affect children and young adults,

but both congenital and very late onset cases have been described (7–11) Most cases are

sporadic, although a family with several members affected by tufted angioma has been

reported (12) In this particular family, the mode of transmission was in an autosomal

dominant fashion The lesions have a predilection for the neck, upper chest, back, and

shoulders (4,13,14), although examples of tufted angioma have also been reported on the head, extremities (Fig 23), and oral mucosa (15–18) Tufted angioma grows slowly and

insidiously and may eventually come to cover a large area of the trunk or neck In mostcases the growth is halted after some years, but there is a slight tendency toward spon-

taneous regression (19).

The clinical appearance of the lesions is variable Some of them are characterized byenlarging erythematous or brown macules or plaques with an angiomatous appearance;other lesions may resemble granulomas or a connective tissue abnormality In some cases

the lesions are tender (20,21) whereas in other cases, there is hyperhidrosis on the surface

(21,22) Raised papules resembling pyogenic granulomas are sometimes seen within the

area of the lesion (23), and occasionally the lesions may show a linear arrangement

(24).Tufted angiomas have been associated with nevus flammeus (25,26) and other

vascular malformations (27), pregnancy (28), and nonregressing lipodystrophy centrifugalis abdominalis (29) There is also a single example of tufted angioma described

in a liver transplant recipient (30) In some cases the lesions spread by infiltration, leading

to sclerosing plaques (31) Many cases of Kasabach-Merritt syndrome are associated with tufted angioma (32–38) It has been demonstrated that in most cases of Kasabach-

Fig 23 Clinical features of tufted hemangioma An angiomatous plaque involving the inner

aspect of the arm.

Fig 24 Histopathologic features of tufted hemangioma (A) Low power shows multiple cellular

lobules at different levels of the dermis separated by connective tissue (B) Higher magnification

demonstrates that each lobule is composed of aggregates of endothelial cells with some small

vascular lumina (C) Still higher magnification showing aggregations of endothelial cells with

small capillary lumina containing erythrocytes.

Merritt syndrome the underlying lesion is not an infantile hemangioma, as was originallythought, but is either a tufted angioma or a kaposiform hemangioendothelioma.

H ISTOPATHOLOGIC F EATURES

Histopathologically, tufted angioma is quite characteristic There are multiple vidual vascular lobules within the dermis and subcutaneous fat (Fig 24) These aggre-gations are more prominent in the middle and lower part of the dermis Each lobule iscomposed of aggregates of endothelial cells that whorl concentrically around a preexistingvascular plexus Some lobules bulge into the walls of dilated thin-walled vascular

indi-structures, giving these vessels a slit-like or semilunar appearance(23,28,39) This

peculiar shape in addition to the angiocentricity of the vascular structures prompted thename tufted angioma Small capillary lumina are identified within the aggregations ofendothelial cells Unusual histopathologic findings in tufted angioma include a mucinous

stroma (22), abundant eccrine sweat glands (40), and an intravenous location of the lesion (41).

Immunohistochemically, the cells in the capillary tufts are weakly positive or negative

for factor VIII related antigen They exhibit strong positivity for Ulex europaeus I lectin,

EN4, CD31, CD34, and α-smooth muscle actin, which is related to the immature nature

of the endothelial cells (4,42) The cells that show reactivity for smooth muscle actin most likely represent pericytes (23) Ultrastructural studies have shown characteristic crystal- loid inclusions within endothelial cells in addition to Weibel-Palade bodies (13).

The differential diagnosis of tufted angioma includes Kaposi’s sarcoma and ally infantile hemangiomas The “cannonball” pattern is characteristic of tufted angioma.Nodular lesions of Kaposi’s sarcoma are composed of interlacing fascicles of spindlecells lining slit-like vessels, and an inflammatory infiltrate of plasma cells is usually

occasion-present (43) Infantile hemangiomas occasionally occasion-present with a lobular pattern, but these

collections are present only focally In addition, tufted angiomas are rare in infants

T REATMENT

Tufted angioma showing spontaneous regression is a rare event (24,40,44–46) For the treatment of these lesions, soft radiation has been recommended (13) Satisfactory results have been also reported with surgery (47), pulse dye laser (11,48), high-dose systemic steroids (49), and interferon- α, (50–54) although there is a report of one case that failed

to respond to intralesional injections of interferon-α (55)

References

1 Wilson Jones E Malignant vascular tumors Clin Exp Dermatol 1976;1:287–312.

2 MacMillan A, Champion RH Progressive capillary haemangioma Br J Dermatol 1971;85:492–3.

3 Nakagawa K Case report of angioblastoma of the skin Nippon Hifuka Gakkai Zasshi 1949;59:92–4.

4 Wilson Jones E, Orkin M Tufted angioma (angioblastoma) A benign progressive angioma not to be confused with Kaposi’s sarcoma or low-grade angiosarcoma J Am Acad Dermatol 1989;20:214–25.

5 Igarashi M, Oh-i T, Koga M The relationship between angioblastoma (Nakagawa) and tufted angioma: report of four cases with angioblastoma and a literature-based comparison of the two conditions.

J Dermatol 2000;27:537–42.

6 Cho KH Tufted angioma: is it the same as angioblastoma (Nakagawa)? Arch Dermatol 1997;133:789.

7 Satomi I, Tanaka Y, Murata J, Fujisawa R A case of angioblastoma (Nakagawa) Rinsho Dermatol (Tokyo) 1981;23:703–9.

8 Kim KJ, Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK A case of congenital tufted angioma mimicking cavernous hemangioma J Dermatol 2001;28:514–5.

9 Hebeda CL, Scheffer E, Starink TM Tufted angioma of late onset Histopathology 1993;23:191–3.

10 Descours H, Grezard P, Chouvet B, Labeille B Angiome en touffes acquis de l’adulte Ann Dermatol Venereol 1998;125:44–6.

11 Dewerdt S, Callens A, Machet L, Grangeponte MC, Vaillant L, Lorette G Angiome en touffes acquis

de l’adulte: échec du traitement par laser à colorant pulse Ann Dermatol Venereol 1998;125:47–9.

12 Heagerty AHM, Rubin A, Robinson TWE Familial tufted angioma Clin Exp Dermatol 1992;17:344–5.

13 Kumakiri M, Muramoto F, Tsukinaga I, Yoshida T, Ohura T, Miura Y Crystalline lamellae in the endothelial cells of a type of hemangioma characterized by the proliferation of immature endothelial cells and pericytes-angioblastoma (Nakagawa) J Am Acad Dermatol 1983;8:68–75.

14 Okada E, Tamura A, Ishikawa O, Miyachi Y Tufted angioma (angioblastoma): case report and review

of 41 cases in the Japanese literature Clin Exp Dermatol 2000;25:627–30.

15 Ward KA, Kennedy CT, Ashworth MT Acquired tufted angioma frequently develops at sites other than the neck and upper trunk Clin Exp Dermatol 1996;21:80.

16 Kleinegger CL, Hammond HL, Vincent SD, Finkelstein MW Acquired tufted angioma: a unique cular lesion not previously reported in the oral mucosa Br J Dermatol 2000;142:794–9.

vas-17 Daley T Acquired tufted angioma of the lower lip mucosa J Can Dent Assoc 2000;66:137.

18 Michel S, Hohenleutner U, Stolz W, Knuchel-Clarke R, Helmig M, Landthaler M Buschelartiges angiom (“tufted angioma”) Klin Padiatr 2001;213:39–42.

19 Allen PW Three new vascular tumors—tufted angioma, kaposiform infantile hemangioendothelioma, and proliferative cutaneous angiomatosis Int J Surg Pathol 1994;2:63–72.

20 Sumitra S, Yesudian P Painful tufted angioma precipitated by trauma Int J Dermatol 1994;33:675–6.

21 Bernstein EF, Kantor G, Howe N, Savit RM, Koblenzer P, Uitto J Tufted angioma of the thigh J Am Acad Dermatol 1994;31:307–11.

22 Cho KH, Kim SH, Park KC, et al Angioblastoma (Nakagawa)— is it the same as tufted angioma? Clin Exp Dermatol 1991;16:110–3.

23 Padilla RS, Orkin M, Rosai J Acquired “tufted” angioma (progressive capillary hemangioma) A distinctive clinicopathologic entity related to lobular capillary hemangioma Am J Dermatopathol 1987;9:292–300.

24 Jang KA, Choi JH, Sung KJ, Moon KC, Koh JK Congenital linear tufed angioma with spontaneous regression Br J Dermatol 1998;138:912–3.

25 Alessi E, Bertani E, Sala F Acquired tufted angioma Am J Dermatopathol 1986;8:426–9.

26 Kim TH, Choi EH, Ahn SK, Lee SH Vascular tumors arising in port-wine stains: two cases of pyogenic granuloma and a case of acquired tufted angioma J Dermatol 1999;26:813–6.

27 Michel S, Hohenleutner U, Stolz W, Landthaler M Acquired tufted angioma in association with a complex cutaneous vascular malformation Br J Dermatol 1999;141:1142–4.

28 Kim YK, Kim HJ, Lee KG Acquired tufted angioma associated with pregnancy Clin Exp Dermatol 1992;7:458–9.

29 Hiraiwa A, Takai K, Fukui Y, Adachi A, Fujii H Non-regressing lipodystrophia centrifugalis abdominalis with angioblastoma (Nakagawa) Arch Dermatol 1990;126:206–9.

30 Chu P, LeBoit PE An eruptive vascular proliferation resembling acquired tufted angioma in the ent of a liver transplant J Am Acad Dermatol 1992;26:322–5.

recipi-31 Catteau B, Enjolras O, Delaporte E, Friedel J, Breviere G, Wassef M Angiome en touffes sclérosant.

A propos de 4 observations aux membres inférieurs Ann Dermatol Venereol 1998;125:682–7.

32 Enjolras O, Wassef M, Mazoyer E, et al Infants with Kasabach-Merritt syndrome do not have “true” hemangiomas J Pediatr 1997;130:631–40.

33 Leaute-Labreze C, Bioulac-Sage P, Labbe L, Meraud JP, Taieb A Tufted angioma asssociated with platelet trapping syndrome: response to aspirin Arch Dermatol 1997;133:1077–9.

34 Enjolras O, Wassef M, Dosquet C, et al Syndrome de Kasabach-Merritt sur angiome en touffes congénital Ann Dermatol Venereol 1998;125:257–60.

35 Nakamura E, Ohnishi T, Watanabe S, Takahashi H Kasabach-Merritt syndrome associated with blastoma Br J Dermatol 1998;139:164–6.

angio-36 Seo SK, Suh JC, Na GY, Kim IS, Sohn KR Kasabach-Merritt syndrome: identification of platelet trapping in a tufted angioma by immunohistochemistry technique using monoclonal antibody to CD61 Pediatr Dermatol 1999;16:392–4.

37 Enjolras O, Mulliken JB, Wassef M, et al Residual lesions after Kasabach-Merritt phenomenon in 41 patients J Am Acad Dermatol 2000;42:225–35.

38 Alvarez-Mendoza A, Lourdes TS, Ridaura-Sanz C, Ruiz-Maldonado R Histopathology of vascular lesions found in Kasabach-Merritt syndrome: review based on 13 cases Pediatr Dev Pathol 2000;3: 556–60.

39 Croue A, Habersetzer M, Leclech C, Forest JL, Saint-Andre JP, Verret JL Le “tufted angioma” (angiome

en touffes) Une tumeur vasculaire benigne à différencier du sarcoma de Kaposi Arch Anat Cytol Pathol 1993;41:159–63.

40 Ban M, Kamiya H, Kitajima Y Tufted angioma of adult onset, revealing abundant eccrine glands and central regression Dermatology 2000;201:68–70.

41 Fukunaga M Intravenous tufted angioma APMIS 2000;108:287–92.

42 Mentzel T, Wollina U, Castelli E, Kutzner H Buschelartiges Hamangiom (“tufted angioma”) pathologische und immunohistologische Analyse von funf Fallen einer distinkten Entitat im Spektrum der kapillaren Hamangiome Hautarzt 1996;47:369–75.

Klinisch-43 Nielsen H, Nielsen PL Cutaneous tufted angioma as differential diagnosis to Kaposi’s sarcoma in HIV infection AIDS 1994;8:707–8.

44 Miyamoto T, Mihara M, Mishima, E, et al Acquired tufted angioma showing spontaneous regression.

48 Frenk E, Vion B, Merot Y, Ruffieux C Tufted angioma Dermatologica 1990;181:242–3.

49 Munn SE, Jackson JE, Russell Jones R Tufted haemangioma responding to high-dose systemic steroids:

a case report and review of the literature Clin Exp Dermatol 1994;19:511–4.

50 Suarez SM, Pensler JM, Paller AS Response of deep tufted angioma to interferon alpha J Am Acad Dermatol 1995;33:124–6.

51 Park KC, Ahn PS, Lee YS, Kim KH, Cho KH Treatment of angioblastoma with recombinant alpha 2 Pediatr Dermatol 1995;12:184–6.

interferon-52 Robenzadeh A, Don PC, Weinberg JM Treatment of tufted angioma with interferon alfa: role of bFDG Pediatr Dermatol 1998;15:482.

53 Wilmer A, Kaatz M, Bocker T, Wollina U Tufted angioma Eur J Dermatol 1999;9:51–3.

54 Wollina U Interferon for tufted angioma Pediatr Dermatol 1999;16:338.

55 Fariña MC, Torrelo A, Mediero IG, Zambrano A Angioma en penacho Actas Dermosifiliogr 1996;87:563–7.

8 GLOMERULOID HEMANGIOMA

The term glomeruloid hemangiomas was coined by Chan et al (1) in 1990 to describe

a distinctive vascular proliferation that occurs in patients affected with the POEMSsyndrome POEMS is an acronym for this syndrome, which includes: polyneuropathy,organomegaly, endocrinopathy, monoclonal gammopathy (M protein), and skin lesions.Other terms for the POEMS syndrome include Takatsuki’s syndrome, Crow-Fukasesyndrome, plasma cell dyscrasia with polyneuropathy and endocrine disorders POEMSsyndrome and multicentric Castleman’s disease are closely related, and some authors

consider them to be overlapping entities (2).

C LINICAL F EATURES

There are several cutaneous manifestations in POEMS syndrome, including mentation, hypertrichosis, scleroderma-like skin thickening, digital clubbing, edema,nail changes, acquired ichthyosis, multiple seborrheic keratosis, livedo reticularis,

hyperpig-purpura, ulcers, flushing, Raynaud’s phenomenon, and angiomas (3–7) The exact

frequency of angiomas in patients with POEMS syndrome is difficult to judge, but the

incidence ranges from 26 to 44% (5,6) When present, the angiomas are small, firm, red

to violaceous, dome-shaped papules that measure a few millimeters in diameter (Fig 25)

and are usually located on the trunk and proximal parts of the extremities (1,7–12) In some cases the angiomatous lesions resemble eruptive histiocytomas (13).

H ISTOPATHOLOGIC F EATURES

Histopathologically, the vascular lesion in patients with POEMS syndrome fall into

four categories, namely, microvenular hemangiomas (14), cherry hemangiomas (9,10), multinucleate cell angiohistiocytomas (13), and glomeruloid hemangiomas (1,11,12,15–17).

Glomeruloid hemangiomas seem to be fairly specific for POEMS syndrome, becausethey have not been reported in other settings Furthermore, POEMS syndrome patientsaffected with cherry hemangiomas occasionally show miniature foci with glomeruloid

features(1) Microscopically, glomeruloid hemangioma consists of multiple ectatic

vascu-lar structures containing aggregates of capilvascu-lary loops resembling renal glomeruli (Fig 26).The capillaries are lined with either flat or plump endothelial cells with vacuoles andsurrounded by pericytes The vacuoles in the cytoplasm of the endothelial cells containeosinophilic PAS positive globules that represent deposits of immunoglobulins absorbed

through circulation (1,12).

The endothelial nature of the cells is further confirmed by immunohistochemistry The

neoplastic cells are positive for factor VIII-related antigen, Ulex europaeus I lectin, and vimentin, whereas muscle-specific actin is negative (15) Two different types of endot- helial cells have been described in glomeruloid hemangioma (18) The first type consists

of endothelial cells that have large vesicular nuclei with open chromatin and large amounts

of cytoplasm These cells are positive for CD31, CD34, and Ulex europaeus I lectin, but

not for CD68 The second type of endothelial cells consists of cells with small nucleicontaining a dense chromatin and scant cytoplasm This second type of cells is positive

for CD31 and CD68, whereas CD34 and Ulex europaeus I lectin are negative.

Speculation remains as to the histogenesis of glomeruloid hemangioma Chan et al (1)

postulated that the deposition of immunoglobulins within the endothelial cells stimulatesthe proliferation of these cells in a glomeruloid fashion The description of cases ofreactive angioendotheliomatosis with a glomeruloid pattern in patients with cryoglobu-

linemia (19), cold agglutinins syndrome (20), and local intravascular immunoglobulin deposits associated with monoclonal gammopathy (21); lends further support to this

hypothesis Additional possible explanations for the development of vascular tions in patients with POEMS syndrome include the production of angiogenic factors by

prolifera-proliferating plasma cells or an increased level of serum estrogens (9).

Fig 25 Patient with POEMS syndrome and multiple angiomatous papules all over the skin (A)

Small angiomatous papules scattered on the buttocks and trunk (B) Similar lesions on the dorsum

of the foot.

The differential diagnosis of glomeruloid hemangioma includes other lesions showing

a predominant intravascular growth Intravascular pyogenic granuloma is characterized

by lobules of capillaries embedded in a fibromyxoid stroma, forming a polypoid massthat protrudes into a vein, but these lesions lack a glomeruloid arrangement In intravas-cular papillary endothelial hyperplasia or Masson’s tumor, fibrinoid or fibrous cores

Fig 26 Histopathologic features of glomeruloid hemangioma (A) Scanning power showing an

exophytic and pedunculated lesion (B) Higher magnification demonstrates dilated vascular tures with their lumina filled by a lobular capillary proliferation (C) Still higher magnification

struc-shows aggregates of capillary loops within dilated lumina closely resembling a renal glomerulus.

form the intravascular papillary projections, but well-formed capillaries are absent.Acquired tufted angioma is composed of solid aggregates of endothelial cells forminglobules They lack a glomeruloid arrangement, and there is no evidence of eosinophilicPAS-positive deposits within the endothelial cells Malignant endovascular papillaryangioendothelioma (Dabska’s tumor) is also characterized by intravascular papillaryendothelial tufts, but the endothelial cells are atypical and the vascular channels are lesswell formed when compared to glomeruloid hemangioma.

T REATMENT

Most patients with POEMS syndrome have a progressive, disabling clinical coursewith a poor prognosis, in spite of any therapy Combination chemotherapy can be usefulfor treatment of the plasma cell dyscrasia, but there is only partial response to alkylating

agents and prednisone Plasmapheresis has been found to be ineffective (5) The 5-year

survival rate in patients with POEMS syndrome is higher than that in patients withmultiple myeloma In a series of 38 patients with POEMS syndrome, 60% of patients had

a 5-year survival rate (5).

References

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