PATHOLOGY OF VASCULAR SKIN LESIONS - PART 3 pps

Other cutaneous lesions described in patients with Maffucci’s syndrome include café-au-lait macules 22 and cystic lymphatic malformations 23.. Other rare miscellaneous syndromes that may

The bone lesions are radiologically translucent and histopathologically consist of dromas Of prime importance is the risk of malignant transformation of the enchondromas

enchon-into chondrosarcomas, which occur in approximately 15% of the patients (21).

Other cutaneous lesions described in patients with Maffucci’s syndrome include

café-au-lait macules (22) and cystic lymphatic malformations (23) In addition to

chondro-Fig 16 (A) Dramatic upper limb deformity with large venous malformations involving the entire right upper extremity in a patient with Maffuci’s syndrome (B) Close-up view of the lesions of

the forearm.

sarcoma, other malignant neoplasms have been reported in patients with Maffucci’s

syndrome including fibrosarcoma (24), angiosarcoma (21), lymphangiosarcoma (25), osteosarcoma (22), malignant ovarian neoplasms (21), gliomas (21), adenocarcinoma of pancreas (24), and other multiple primary malignancies (21,22,24).The differential

diagnosis of Maffucci’s syndrome has to be established with Ollier disease’s, in which

there is dyschondroplasia without cutaneous vascular lesions (25).

Venous malformations are also prominent in and are the main cutaneous tion of Klippel-Trenaunay syndrome The dominant features of this syndrome includecutaneous capillary and venous malformations, congenital varicose veins, and hypertro-

manifesta-phy of the involved limb (26) (Fig 17) When, in addition to the aforementioned features, there is an arteriovenous fistula, the disorder is termed Parkes Weber syndrome (27).

Klippel-Trenaunay syndrome affects males and females equally Most commonly themalformation is unilateral, and the lower limb is the most commonly involved area.However, in rare cases the upper and lower limbs or the upper limb alone are affected;bilateral involvement has also been reported, and occasionally the disease affects theentire trunk Regardless of the location, the malformation is present at birth, although itmay not be clinically apparent at that time Almost all reported cases are sporadic, although

a few cases with a familial tendency have been described (28).

Cutaneous lesions of Klippel-Trenaunay syndrome may consist of one or several port

wine stains over the affected limb (26,27,29–35), but in addition, it is common to find

Fig 17 (A) Venous malformation involving the entire lower right extremity in a patient with Klippel-Trenaunay syndrome (B) Close-up view of the lesions involving the leg.

large venous ectatic vessels and vesicular lymphatic lesions (36) These vascular

malfor-mations do not blanch significantly under pressure In many cases varicosities are ciated with the venous malformations The varicosities start from a plexus of veins of thedorsum and lateral side of the foot and extend up a variable distance on the leg Incom-petent perforating veins and deep vein abnormalities, which consist of occlusion by afibrous band, agenesis, or atresia, are also seen in these patients The involved limb isusually hypertrophic, and this enlargement is mostly caused by muscle hypertrophy,thickened skin, excessive subcutaneous fat, the bulkiness of the abnormal vascular tissue,and sometimes concomitant lymphedema Usually there is little increase in bone diam-eter in the hypertrophic limb Patients with this syndrome occasionally complain ofprofuse sweating of the skin involved in the vascular malformation, and the affected areasmay also feel warmer than normal

asso-Other systems and organs may show abnormalities in patients with Klippel-Trenaunay

syndrome (37); these anomalies usually occur within or adjacent to the area involved by

the vascular malformation They can affect any mesodermal and ectodermal structure,suggesting a more generalized dysplasia of the structures subject to a common teratoge-nic influence Venous thrombosis is common in patients with Klippel-Trenaunay syn-drome, and therefore these patients have frequent episodes of pulmonary embolism Thesimultaneous occurrence of Klippel-Trenaunay syndrome and Fabry’s disease has been

described in the same patient (38).

Gorham’s syndrome (39) is a rare, nonfamilial disorder, that affects both sexes equally.

It is characterized by the development of venous and lymphatic malformations in the

skin, mediastinum, and bones (40,41) The osseous lesions cause osteolysis with fibrosis

and may lead to the disappearance of entire bones Roentgenograms demonstrate lyticlesions on the involved bones with little or no sclerosis Cutaneous lesions usually develop

in the areas adjacent to the involved bones and may be accompanied by local muscular

atrophy Usually, Gorham’s syndrome is self-limited (42), although an aggressive ant with a poor prognosis has been described (43).

vari-Bannayan-Zonana syndrome is a rare autosomal dominant disorder characterized by

benign macrocephaly, lipomas, and cutaneous and visceral vascular malformations (44) The cutaneous lesions are usually deeply situated, bluish nodules (45–47), but lesions

resembling superficial lymphatic malformations and angiokeratomas have also been

de-scribed (48) Visceral involvement may be massive, resulting in life-threatening obstruction

of vital organs, including the gastrointestinal tract and the central nervous system (48) The

macrocephaly is not associated with hydrocephalus, and most patients remain intellectually

normal, although mental retardation has been described in some cases (49).

Riley-Smith syndrome is an autosomal dominant condition described in five members

of the same family It consists of macrocephaly without hydrocephalus,

pseudo-papilledema, and cutaneous capillary, venous, and lymphatic malformations (50).

Cutaneous vascular lesions may be present either at birth or appear shortly thereafter Theabdominal wall, hands, feet, and thighs are the most commonly involved sites The patientsremain intellectually and neurologically normal This syndrome is similar to theBannayan-Zonana syndrome, except that patients with the Riley-Smith syndrome havepseudopapilledema and do not have systemic lipomatous lesions

In 1980, Ruvalcaba et al (51) described two male patients thought to be affected with

hamartomatous intestinal polyps and spotted pigmentation of the penis Based on the

description of these two patients and other cases from the literature (52,53); Cohen (54)

suggested that the condition described by Ruvalcaba et al (51) was a distinctive entity

and coined the name Ruvalcaba-Myhre syndrome Since then, additional cases have been

reported under the name of Ruvalcaba-Myhre-Smith syndrome (55–57) In 1988, Dvir

et al (58) described a boy with macrocephaly, pseudopapilledema, lipoangiomatosis,

and spotted pigmentation of the penis Because the patient had clinical features of threesyndromes (Bannayan-Zonana, Riley-Smith, and Ruvalcaba-Myhre-Smith), the authorsproposed that the three conditions were simply different expressions of a single

heredofamilial disorder Cohen (59) supported this unifying theory and suggested that the

“new” syndrome be named after the first authors of the three original reports, i.e.,Bannayan-Riley-Ruvalcaba syndrome Subsequently, additional reports of Bannayan-Riley-Ruvalcaba syndrome have appeared in the literature, lending further support to the

unifying concept (60–62) Recently, patients with Bannayan-Riley-Ruvalcaba syndrome

and facial tricholemmomas have been described, raising the possibility that Riley-Ruvalcaba syndrome and Cowden disease may represent different alleles at the

Bannayan-same genetic locus or mutations of two genes in a common pathway (62).

Other rare miscellaneous syndromes that may show cutaneous venous malformationsinclude zosteriform venous malformations grouped in a unilateral dermatomal distribu-

tion (63,64); hereditary neurocutaneous vascular malformations syndrome (65), which

is transmitted as an autosomal dominant trait and it is characterized by the presence ofmultiple cutaneous vascular malformations associated with intracranial arteriovenousmalformations; venous malformations on the face and anterior trunk associated with

sternal cleft and atrophic scar on the median abdominal raphe (66); retroauricular

hemangiomatous branchial clefts associated with several facial and neurosensorial

anomalies (67); sacral vascular malformations associated with renal, genital, osseous, and neurologic malformations (68); cutaneous vascular malformations associated with vascular anomalies of the retina and optic nerve (69); and several members of a family

affected by venous malformations involving the mouth, skin, and soft tissues, inherited

as an autosomal dominant trait and with no other associated anomalies (70).

H ISTOPATHOLOGIC F EATURES

Histopathologically, venous malformations generally consist of ectatic blood vessels

of irregular size and shape involving the deep dermis and subcutaneous fat (Fig 18).Some of the involved blood vessels show thin walls, whereas others exhibit a thick layer

of smooth muscle in their walls Thrombosis and phleboliths are common, and areas ofextravasated erythrocytes, deposits of hemosiderin, and extravascular calcifications arealso frequent findings

Some of the cutaneous lesions of the aforementioned complex syndromes associatedwith venous malformations may show specific histopathologic features Large blue fa-cial lesions with the clinical appearance of venous malformations showing glomus cells

surrounding the vascular structures are better interpreted as glomangiomas (2) In some

patients with blue rubber bleb nevus, the cutaneous lesions may also show multiple

glomangiomas (18,71–73) The gastrointestinal lesions of patients with blue rubber bleb

nevus show similar histopathologic features to those of the cutaneous lesions The casedescribed as “blue rubber bleb nevus with vascular lesions suggesting a link to the Osler-

Rendu-Weber syndrome” (74) is better interpreted as an example of blue rubber bleb

nevus with telangiectatic cutaneous lesions but not related to the Osler-Rendu-Webersyndrome

Histopathologically, the cutaneous lesions of Maffucci’s syndrome consist of large,blood-filled vascular channels lined with flat endothelial cells The walls of the vascularspaces vary from thin, delicate, irregularly outlined walls to thick, fibrous, and smooth

Fig 18 Histopathologic features of a venous malformation (A) Scanning power view showing

dilated vascular spaces in both superficial and deep dermis The deeper component shows

conges-tive blood vessels (B) Higher magnification of the deeper component shows congesconges-tive dilated blood vessels (C) Still higher magnification shows thin-walled blood vessels and hemosiderin

deposition on adjacent dermis.

muscle-containing walls Several cases of spindle cell hemangiomas in patients with

Maffuci’s syndrome have been described (75–83) Spindle cell hemangioma consists of

well-circumscribed but not encapsulated nodules that combine features of hemangiomaand Kaposi’s sarcoma Dilated blood vessels appear as thin veins that sometimes containorganized thrombi and phleboliths within their lumina Interspersed among the dilatedblood vessels there are fascicles of spindle cells mimicking Kaposi’s sarcoma, but withinthe fascicles there are also round cells with prominent vacuolated cytoplasm Sometimesvacuolization of the cytoplasm of round cells is so marked that they may be mistaken forentrapped fatty tissue

Histopathologically, the cutaneous vascular lesions of patients with Ruvalcaba syndrome show different combinations of capillary, venous, and lymphatic

Bannayan-Riley-malformations (51).

T REATMENT

Small venous cutaneous malformations may be treated by simple surgical excision,but in those cases in which the vascular malformation is associated with other internalabnormalities, a careful follow-up of the patient is required It is usually impossible toremove large extensive venous malformations surgically without causing severe scarringand other complications In those cases involving the limbs, elastic stocking use is man-datory and should be started early in infancy

Management of patients with blue rubber bleb nevus depends on the individual case.Resection of the involved bowel segment may be required in patients with recurrentmelena and anemia Painful cutaneous lesions of glomangiomas may be treated by

excision, cryosurgery, or laser therapy (13).

Patients with Maffucci’s syndrome require careful follow-up, with radiologic andhistopathologic examination of any rapidly enlarging bone lesion for early diagnosis ofchondrosarcoma Surgical excision of the cutaneous vascular malformations may beindicated to improve the appearance of the patient Spindle cell hemangioma is a benignlesion and excision is curative

Superficial venous varicosities of patients with the Klippel-Trenaunay syndrome may

be treated by ligation and stripping to relieve the local pain, but recurrences are common

(33) Before excision of the superficial veins, a radiographic exploration should be performed

to demonstrate that there is neither absence nor hypoplasia of the deep venous system.Patients with Klippel-Trenaunay syndrome should receive antithrombotic prophylasis

prior to any surgery owing to the high risk of thromboembolic complications (33).

No effective treatment has been found for patients with Gorham’s syndrome, althoughradiotherapy may be helpful for bone pain Patients with Bannayan-Riley-Ruvalcabasyndrome should be explored for detection of neurologic or any other associated internalmalformation, and genetic counseling should be given to the family

(“gloman-4 Kern S, Niemeyer C, Darge K, Merz C, Laubenberger J, Uhl M Differential of vascular birthmarks by MR imaging.

An investigation of hemangiomas, venous and lymphatic malformations Acta Radiol 2000;41:453–7.

5 Boyd JB, Mulliken JB, Kaban LB, Upton J III, Murray JE Skeletal changes associated with vascular malformations Plast Reconstr Surg 1984;74:789–97.

6 Enjolras O, Ciabrini D, Mazoyer E, Laurian C, Herbreteau D Extensive pure venous malformations in the upper or lower limb: a review of 27 cases J Am Acad Dermatol 1997;36:219–25.

7 Bean WB Blue rubber bleb nevi of the skin and gastrointestinal tract In: Vascular Spiders and Related Lesions of the Skin Springfield, MO, CC Thomas, 1958:178–85.

8 Berlyne GM, Berlyne N Anaemia due to “blue rubber bleb” naevus disease Lancet 1960;2:1275–7.

9 Munkvad M Blue rubber bleb nevus syndrome Dermatologica 1983;167;307–9.

10 Walshe MM, Evans CD, Warin RP Blue rubber bleb naevus BMJ 1966; 2:931–2.

11 Baker AL, Kahn PC, Binder SC, et al Gastrointestinal bleeding due to blue rubber bleb nevus syndrome Gastroenterology 1971;61:530–4.

12 McCauley RGK, Leonidas JC, Bartoshesky LE Blue rubber bleb nevus syndrome Radiology 1979;133:375–7.

13 Olsen TG, Milroy SK, Goldman L, et al Laser surgery for blue rubber bleb nevus Arch Dermatol 1979;115:81–2.

14 Baiocco FA, Gamoletti R, Negri A, et al Blue rubber bleb nevus syndrome: a case with predominant ENT localization J Laryngol Otol 1984;98:317–9.

15 McCarthy JC, Goldberg MJ, Zimbler S Orthopedic dysfunction in the blue rubber bleb nevus syndrome.

J Bone Joint Surg 1982;64A:280–3.

16 Rennie JG, Shortland JR, Mahood JM, et al Periodic exophthalmos associated with blue rubber bleb nevus syndrome Br J Ophthalmol 1982;66:594–8.

17 Satya-Murti S, Navada S, Eames F Central nervous system involvement in blue rubber bleb nevus syndrome Arch Neurol 1986;43:1184–6.

18 Sakurane HF, Sugai T, Saito T The association of blue rubber bleb nevus and Maffucci’s syndrome Arch Dermatol 1967;95:28–36.

19 Maffucci A Di un caso di encondroma ed angioma multiple: contribuzione alla genesi embrionale dei tumori Mov Med Chir Nap 1891;13:399–412.

20 Tilsley DA, Burden PW A case of Maffucci’s syndrome Br J Dermatol 1981;105:331–6.

21 Lewis RJ, Ketcham AS Maffucci’s syndrome: functional and neoplastic significance: case report and review of the literature J Bone Joint Surg 1973; 55A:1465–79.

22 Bean WB Dyschondroplasia and hemangiomata (Maffucci’s syndrome) II Arch Intern Med 1958;102:544–50.

23 Suringa DWR, Ackerman AB Cutaneous lymphangiomas with dyschondroplasia (Maffucci’s drome): a unique variant of an unusual syndrome Arch Dermatol 1970;191:472–4.

syn-24 Johnson JL, Webster Jr, Sippy HI Maffucci’s syndrome (dyschondroplasia with hemangiomas) Am J Med 1960;28:864–6.

25 Nardell SG Ollier’s disease: dyschondroplasia BMJ 1950;2:555–7.

26 Klippel M, Trenaunay P Du noevus variqueux osteohypertophique Arch Gen Med 1900;3:641–72.

27 Parkes Weber F Angioma formation in connection with hypertrophy of limbs and hemi-hypertrophy.

Br J Dermatol 1907;19:231–5.

28 Lindenauer SM Klippel-Trenaunay syndrome Ann Surg 1965;162:303–10.

29 Cosman B Clinical experience in the laser therapy of port-wine stains Lasers Surg Med 1980;1:133–52.

30 Harper PS Sturge-Weber syndrome with Klippel-Tranaunay syndrome Birth Defects 1971;7:314.

31 Schofield D, Zaatari GS, Gay BB Klippel-Trenaunay and Sturge-Weber syndromes with renal gioma and double inferior vena cava J Urol 1986;136:442–5.

heman-32 Adam JS, Cunliffe WJ The Klippel-Trenaunay-Weber syndrome presenting with cutaneous bleeding Acta Derm Venereol 1981;62:176–7.

33 Baskerville PA, Ackroyd JS, Thomas ML, et al The Klippel-Trenaunay syndrome: clinical, radiological and haemodynamic features and management Br J Surg 1985;72:232–6.

34 Phillips GN, Gordon DH, Mortin EC, et al The Klippel-Trenaunay syndrome: clinical and radiological aspects Radiology 1978;128:429–34.

35 Viljoen D, Saxe N, Peran J, et al The cutaneous manifestations of the Klippel-Trenaunay-Weber drome Clin Exp Dermatol 1987;12:12–7.

syn-36 Servelle M Klippel-Trenaunay syndrome Ann Surg 1985;201:365–76.

37 Young AE, Ackroyd J, Baskerville P Combined vascular malformations In: Mulliken JB, Young AE, eds Vascular Birthmarks Hemangiomas and malformations Philadelphia, WB Saunders, 1988:247–74.

38 Germain DP Co-occurrence and contribution of Fabry disease and Klippel-Trenaunay-Weber drome to a patient with atypical skin lesions Clin Genet 2001;60:63–7.

syn-39 Gorham LW, Wright AW, Shultz HH, et al Disappearing bones: a rare form of massive osteolysis Am

49 Saul RA, Stevenson RE, Bley R Mental retardation in the Bannayan syndrome Pediatrics 1982;69:642–4.

50 Riley HD, Smith WR Macrocephaly, pseudopapilloedema and multiple hemangiomata: a previously undescribed heredofamilial syndrome Pediatrics 1960;26:293–300.

51 Ruvalcaba RHA, Myhre S, Smith DW Sotos syndrome with intestinal polyposis and pigmentary changes

of the genitalia Clin Genet 1980;18:413–6.

52 Halal F Male to male transmission of cerebral gigantism Am J Med Genet 1982;12:411–9.

53 Halal F Cerebral gigantism, intestinal polyposis, and pigmentary spotting of the genitalia Am J Med Genet 1983;15:161.

54 Cohen MM Jr The large-for-gestational-age (LGA) infant in dysmorphic perspective In: Willey AM, Carter TP, Kelly S, Porter IH, eds Clinical Genetics: Problems in Diagnosis and Counseling New York, Academic,1982:153–69.

55 DiLiberti JH, Weleber RG, Budden S Ruvalcaba-Myhre-Smith syndrome: a case with probable somal-dominant inheritance and additional manifestations Am J Med Genet 1983;15:491–5.

auto-56 DiLiberti JH, D’Agostino AN, Ruvalcaba RHA, Schimschock KR A new lipid storage myopathy observed in individuals with the Ruvalcaba-Myhre-Smith syndrome Am J Med Genet 1984;18:163–7.

57 Gretzula JC, Hevia O, Schachner LS, et al Ruvalcaba-Myhre-Smith syndrome Pediatr Dermatol 1988;5:28–32.

58 Dvir M, Beer S, Aladjem M Heredofamilial syndrome of mesodermal hamartomas, macrocephaly, and pseudopapilledema Pediatrics 1988;81:287–90.

59 Cohen MM Jr Bannayan-Riley-Ruvalcaba syndrome: renaming three formerly recognized syndromes

as one etiologic entity Am J Med Genet 1990;35:291.

60 Gorlin RS, Cohen MM, Leven LS Bannayan-Riley-Ruvalcaba syndrome (Bannayan-Zonana syndrome, Ruvalcaba-Myhre, Riley-Smith syndrome) In: Gorlin RS, Cohen MM, Leven LS, eds Syndromes of the Head and Neck New York, Oxford University Press, 1990:336–8.

61 Gorlin RJ, Cohen MM Jr, Condon LM, Burke BA Bannayan-Riley-Ruvalcaba syndrome Am J Med Genet 1992;44:307–14.

62 Fargnoli MC, Orlow SJ, Semel-Concepcion J, Bolognia JL Clinicopathologic findings in the Riley-Ruvalcaba syndrome Arch Dermatol 1996;132:1214–8.

Bannayan-63 Steinway DM, Fretzin DF Acquired zosteriform cavernous hemangiomas: brief clinical observations Arch Dermatol 1977;113:848–9.

64 Wilkin JK Unilateral dermatomal cavernous hemangiomatosis Dermatologica 1980;161:347–54.

65 Hurst J, Baraitser M Hereditary neurocutaneous angiomatous malformations: autosomal dominant transmission in two families Clin Genet 1988;33:44–8.

66 Hersh JH, Waterfill D, Rutledge J, et al Sternal malformation/vascular dysplasia association Am J Hum Genet 1985;21:177–84.

67 Hall BD, deLorimier A, Foster LH Brief clinical report: a new syndrome of hemangiomatous branchial clefts, lip pseudoclefts and unusual facial appearance Am J Med Genet 1983;14:135–8.

68 Goldberg NS, Hebert AA, Esterly NB Sacral hemangiomas and multiple congenital anomalies Arch Dermatol 1986;122:684–7.

69 Goldberg RE, Pheasant TR, Shields JA Cavernous hemangioma of the retina: a four generation pedigree with neurocutaneous manifestations and an example of bilateral retinal involvement Arch Ophthalmol 1979;97:2321–4.

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71 Rice J, Fisher D Blue rubber-bleb nevus syndrome Generalized cavernous hemangiomas or venous hamartoma with medulloblastoma of the cerebellum Case report and review of the literature Arch Dermatol 1962;86:503–11.

72 Fretzin DF, Potter B Blue rubber bleb nevus Arch Intern Med 1965;116:924–9.

73 Hagood MF, Gathright JB Jr Hemangiomatosis of the skin and gastrointestinal tract: report of a case Dis Colon Rectum 1975;18:141–6.

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in the “blue rubber bleb naevus” syndrome A case with aneurysm of vein of Galen and vascular lesions suggesting a link to the Weber-Osler-Rendu syndrome Histopathology 1978;2:301–11.

75 Weiss SW, Enzinger FM Spindle cell hemangioendothelioma: a low-grade angiosarcoma resembling

a cavernous hemangioma and Kaposi’s sarcoma Am J Surg Pathol 1986;10:521–30.

76 Scott GA, Rosai J Spindle cell hemangioendothelioma Report of seven additional cases of a recently described vascular neoplasm Am J Dermatopathol 1988;10:281–8.

77 Lawson JP, Scott G Case report 602 Skeletal Radiol 1990;19:158–62.

78 Murakami J, Sarker AB, Teramoto N, Horie Y, Tagucmi K, Akagi T Spindle cell lioma: a report of two cases Acta Pathol Jpn 1993;43:529–34.

hemangioendothe-79 Pellegrini AE, Drake RD, Qualman SJ Spindle cell hemangioendothelioma: a neoplasm associated with Maffucci’s syndrome J Cutan Pathol 1995;22:176–6.

80 Fukunaga M, Ushigome S, Nikaido T, Ishikawa E, Nakamori K Spindle cell hemangioendothelioma:

an immunohistochemical and flow cytometric study of six cases Pathol Int 1995;45:589–95.

81 Hisaoka M, Koumo H, Aoki T, Hashimoto H DNA flow cytometric and immunohistochemical analysis

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83 Niechajev IA, Hansson LI Maffucci’s syndrome Scand J Plast Reconst Surg 1982;16:215–9.

Fig 19 Superficial lymphatic malformation involving the posterior aspect of the thigh.

Fig 20 Superficial lymphatic malformation involving the anterior aspect of the right forearm.

Numerous small vesicle-like lesions grouped in a plaque.

6 SUPERFICIAL CUTANEOUS LYMPHATIC MALFORMATIONS

C LINICAL F EATURES

Superficial cutaneous lymphatic malformations are localized lesions of the cutaneous,subcutaneous, or submucosal lymphatic vessels These lesions have been referred to inthe past as “lymphangiomas,” which is an inaccurate term

The lesions are usually present at birth or appear shortly thereafter; they can be located

in any anatomic site but have a predilection for the axillary folds, shoulders, neck,

proxi-mal parts of the extremities (Figs 19 and 20), and tongue (1–3) Superficial lymphatic

malformations (inaccurately termed “lymphangioma circunscriptum”) are the est variant of cutaneous lymphatic malformation Clinically, the lesion consists ofnumerous small vesicle-like lesions, often with a verrucous surface, grouped in a plaque.Sometimes, owing to the presence of blood vessels, purplish areas can be seen within thelesion The stereotypical superficial lymphatic malformation is accompanied by dilatedlymphatic cisterns located in the subcutaneous fat, which results in swelling of the tissue

common-beneath the superficial vesicles (4,5) It is believed that the superficial vesicles are

sac-cular dilations of the superficial lymphatics secondary to the increased pressure from the

pulsating cisterns localized underneath (1) MRI is useful in demonstrating the size and invasiveness of these lesions (6) In rare instances, superficial lymphatic malformations

extend deeply and can be associated with visceral lymphatic malformations involving the

mediastinum (7) or the bladder wall (8) Superficial lymphatic malformations may be associated with Becker’s nevus (9), and have been described in patients with Maffucci’s (10) and Cobb’s syndrome (11).

H ISTOPATHOLOGIC F EATURES

Histopathologically, superficial lymphatic malformations are situated immediatelybeneath the epidermis, but they may also involve areas of the reticular dermis (Fig 21).They consist of dilated lymph vessels, lined by a discontinuous layer of flat endothelial

cells (2,12) Sometimes the lymphatic vessels form clusters in the papillary dermis,

which gives a papillated or verrucous appearance to the skin surface

Superficial lymphatic malformations are sometimes difficult to distinguish logically from angiokeratomas, especially when the lesions have been traumatized, whichresults in the presence of erythrocytes within the ectatic lumina The usual immunohis-

histopatho-tochemical markers for endothelial cells, such as factor VIII-related antigen, Ulex europaeus, and CD31 do not differentiate between blood and lymphatic vessels (13) In

these cases, the use of the new endothelial marker vascular endothelial growth factorreceptor-3 can be helpful This marker is expressed by the lymphatic endothelium but not

by the endothelial cells lining blood vessels or neoplasms with blood endothelial

differ-entiation (14,15).

Ultrastructural studies of superficial lymphatic malformations demonstrate the

pres-ence of a fragmented basal lamina and anchoring filaments (13).

T REATMENT

Most of the time, superficial cutaneous lymphatic malformations do not require ment, and it is probably best to leave them untreated Surgical removal of the superficialvesicles tends to be disappointing, especially if there is a deep component, since removal

treat-is followed by local recurrence Some lesions have been effectively treated with

radio-therapy (16), but there is a report of a lymphangiosarcoma arising in a preexisting cial lymphatic malformation following X-ray therapy (17), and radiotherapy is not currently recommended The best cosmetic results have been achieved with argon laser (18)

superfi-or carbon dioxide laser (19–21) Combined therapy, which consists of carbon dioxide

laser vaporization for the superficial component of the lesion and transcutaneous

sclero-therapy with doxycycline for the deeper cisterns, has also been applied with good results (22).

References

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super-17 King DT, Duffy DM, Hirose FM, Gurevitch AW Lymphangiosarcoma arising from lymphangioma circumscriptum Arch Dermatol 1979;115:969–72.

18 Landthaler M, Haina D, Waidelich W, Braun-Falco O Behandlung zirkumskripter lymphangiome mit dem Argonlaser Hautarzt 1982;33:266–70.

19 Bailin PL, Kantor GR, Wheeland RG Carbon dioxide laser vaporization of lymphangioma circumscriptum J Am Acad Dermatol 1986;14:257–62.

20 Eliezri YD, Sklar JA Lymphangioma circumscriptum: review and evaluation of carbon dioxide laser vaporization J Dermatol Surg Oncol 1988;14:357–64.

21 Haas AF, Narurkar VA Recalcitrant breast lymphangioma circumscriptum treated by ultrapulse carbon dioxide laser Dermatol Surg 1998;24:893–5.

22 Wimmershoff MB, Schreyer AG, Glaessl A, et al Mixed capillary/lymphatic malformation with isting port-wine stain: treatment utilizing 3D MRI and CT-guided sclerotherapy Dermatol Surg 2000;26:584–7.

coex-7 CYSTIC LYMPHATIC MALFORMATIONS (CYSTIC HYGROMAS)

Cystic lymphatic malformations are contrasted with superficial lymphatic tions, in being deeply located and consisting of subcutaneous painless nodules covered

malforma-by normal skin (1–3) The lesion may be painful, especially when the tumor is subject to

pressure or is bumped Cases of cystic lymphatic malformations have been described in

patients with Maffucci’s syndrome (4).

C LINICAL F EATURES

Cystic hygroma is a variant of subcutaneous lymphatic malformation whose shape andcharacter are determined by its anatomic location These lesions most commonly occur

in the neck, axilla (Fig 22), and groin, areas where the presence of loose connective tissue

allows for the expansion of the lymphatic channels (5) Cystic hygroma is usually present

at birth or appears in early infancy They present as a large fluid-filled cystic mass thatmay be diagnosed by transillumination Cystic hygromas of the posterior triangle of theneck have been associated with hydrops fetalis, Turner’s syndrome (45X0 karyotype),congenital malformations, several varieties of chromosomal aneuploidy, and fetal death

(6) Since aneuploidic conditions may recur in subsequent pregnancies, cytogenetic

analysis of fetuses born with cystic hygroma is mandatory

H ISTOPATHOLOGIC F EATURES

Histopathologically, cystic lymphatic malformations are made up of irregular, dilated,and interconnected lymphatic vessels localized in the subcutaneous fat (Fig 23) Some

of these vessels contain bundles of smooth muscle in their walls (7) Nodular collections

of lymphocytes, sometimes with germinal centers, may be present within the surroundingconnective tissue

Cystic hygroma lesions consist of large uni- or multilocular cystic cavities surrounded

by a loose connective tissue stroma In some areas the stroma may be denser and evensclerotic as a result of compression by the lymphatic cysts

Fig 22 Clinical appearance of a lymphatic malformation on the axilla, with a deep component of

subcutaneous nodules and a superficial component of an angiomatous appearance.

T REATMENT

The small superficial lymphatic malformations may be adequately managed by

sur-gery (8,9), cryotherapy (10), radiotherapy (11), and laser phototherapy (12) Larger and

subcutaneous lesions of cystic hygroma show a high rate of recurrence after surgery, andunless the lesion causes severe signs or symptoms, such lesions are best left untreated.Complete regression of cystic hygromas has also been reported with intracystic injec-

tions of sclerosing substances with no sequels (13).

References

1 Flanagan BP, Helwig EB Cutaneous lymphangioma Arch Dermatol 1977;113:24–30.

2 Peachey RDG, Lim CC, Whimster JW Lymphangioma of the skin: a review of 65 cases Br J Dermatol 1970;83:519–27.

3 Harkins GA, Sabiston DC Lymphangioma in infancy and childhood Surgery 1960;47:811–22.

4 Suringa DWR, Ackerman AB Cutaneous lymphangiomas with dyschondroplasia (Maffucci’s drome): a unique variant of an unusual syndrome Arch Dermatol 1970;191:472–4.

syn-5 Bill AH, Sumner DS A unified concept of lymphangioma and cystic hygroma Surg Gynecol Obstet 1965;120:79–86.

6 Chervenak FA, Isaacson G, Blakemore KJ, et al Fetal cystic hygroma cause and natural history N Engl

homoge-8 Edwards JM, Peachey RDG, Kinmonth JB Lymphangiography and surgery in lymphangioma of the skin Br J Surg 1972;59:36–41.

9 Jordan PR, Sanderson KV, Wilson JSP Surgical treatment of lymphangioma circumscriptum: a case report Br J Plast Surg 1977;30:306–7.

10 Nanda Kumar H, Bhaskar Roa C, Kukreja R Management of lymphangioma by cryoprobe: a case report.

J Indian Dent Assoc 1982;54:25–7.

11 O’Cathial S, Rostom AY, Johnson ML Successful control of lymphangioma circumscriptum by ficial x-rays Br J Dermatol 1985;113:611–5.

super-12 Bailin PL, Kantor GR, Wheeland RG Carbon dioxide laser vaporization of lymphangioma circumscriptum J Am Acad Dermatol 1986;14:257–62.

13 Ogita S, Tsuto T, Tokiwa K, Takahashi T Intracystic injection of OK-432 A new sclerosing therapy for cystic hygroma in children Br J Surg 1987;74:690–1.

Fig 24 Lymphangiomatosis resulting in deformity of the right leg of a young woman.

8 LYMPHANGIOMATOSIS

This is a rare disorder characterized by the presence of abnormal lymphatic channels

in a diffuse or multifocal arrangement These lesions usually involve both soft tissue andparenchymal organs Most cases of lymphangiomatosis with both bone and visceral

involvement are associated with a poor prognosis and high mortality rate (1) In contrast,

patients with involvement solely of soft tissues and bones of the extremities, show slow

clinical progression and have a good prognosis (2), although there is a report of a patient

with disseminated lymphangiomatosis of the skin and bone who developed disseminated

intravascular coagulation (3) The lesions appear either at birth or in early infancy.

C LINICAL F EATURES

Clinically, the lesions are fluctuant and sponge-like, with progressive swelling of theaffected limb (Fig 24) The overlying skin is usually normal, but it may become second-arily involved and develop a verrucous surface, areas of pigmentation, or vesicle forma-tion Examples of lymphangiomatosis have been described in patients with kaposiform

hemangioendothelioma (4,5).

H ISTOPATHOLOGIC F EATURES

Histopathologically, the lesions of lymphangiomatosis consist of lobules of necting widely dilated lymphatic channels lined by a single, attenuated layer of endothe-