Lymphangioma Circumscriptum of the Vulva in a Patient With Noonan Syndrome Llana Pootrakul, MD, PhD; Michael R. Nazareth, MD, PhD; Richard T. Cheney, MD; Marcelle A. Grassi, MD Practice Points Lymphatic malformations such as lymphedema and cystic hygroma are not uncommonly observed in patients with Noonan syndrome; there are rare reports of cutaneous lymphangioma in this population. Lymphangioma circumscriptum of the vulva should be considered when patients with Noonan syndrome present with grouped vesicular lesions in the vulvar region characterized by erythema, swelling, and/or drainage. The mainstay of treatment of lymphangioma circumscriptum of the vulva includes complete surgical resection of superficial CUTISlesions and deep communicating lymphatics. Lymphangioma circumscriptum (LC) results from he clinical manifestations of Noonan syn- the development of abnormal lymphatic vas- drome (NS) are seen in multiple organ culature and is characterized by the presence Tsystems and include cardiovascular, muscu- of grouped vesicles filled with clear or colored loskeletal, genitourinary, dermatologic, and gastro- fluid. Vulvar localization is uncommon. Abnor- intestinal findings. Patients with NS may present malitiesDo of the lymphatic system,Not such as lymph- with a wideCopy range of features including ptosis of the edema and cystic hygroma, are well-known eyelids, ocular hypertelorism, epicanthus, pterygium features of genetic disorders such as Noonan syn- colli, undescended testicles in men, short stature, drome (NS) and Turner syndrome. We report the pectus excavatum or pectus carinatum, congenital case of a patient with NS who presented with heart defects, cubitus valgus, low-set ears, mental LC of the vulva. We also discuss the expanding retardation, micrognathia, lymphedema, and cystic spectrum of clinical anomalies associated with hygroma.1,2 Lymphatic dysplasia has been reported in the presentation of NS. up to 20% of patients with NS, with the most com- Cutis. 2014;93:297-300. mon presentation being lymphedema.1 Although the association of NS with lymphedema and cystic hygroma have been well described, the finding of cutaneous lymphangioma in NS is rare. We present a patient with NS who developed the Dr. Pootrakul was from and Dr. Nazareth is from the Department of uncommon finding of classic lymphangioma circum- Dermatology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo. Dr. Pootrakul currently is from the scriptum (LC) of the vulva. Due to the extensive Division of Dermatology, Ohio State University Medical Center, nature of the vascular abnormalities in this case, the Columbus. Drs. Cheney and Grassi are from Roswell Park Cancer patient underwent surgical resection of the lesions. Institute, Buffalo. Dr. Cheney is from the Department of Pathology and Dr. Grassi is from the Department of Dermatology. Case Report The authors report no conflict of interest. Correspondence: Llana Pootrakul, MD, PhD, Division of Dermatology, A 30-year-old woman presented to the derma- Ohio State University Medical Center, 2012 Kenny Rd, Columbus, tology clinic with vascular lesions on the vulva OH 43221 ([email protected]). that had been present for several years. Although WWW.CUTIS.COM VOLUME 93, JUNE 2014 297 Copyright Cutis 2014. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Lymphangioma Circumscriptum the lesions remained unchanged in size, they had other concerns aside from cutaneous findings were become increasingly bothersome due to persistent elicited during a review of systems. Physical exami- oozing and subsequently had negative effects on the nation revealed erythema and swelling with a pink patient’s quality of life. Her primary concerns were mammillated surface on the bilateral labia majora the appearance of the lesions, pruritus, and weep- accompanied by a clear, yellow, lymphlike discharge. ing discharge from the affected area. The patient The lesions did not extend to the introitus but dem- previously was referred to the urology department onstrated substantial involvement of the bilateral and then laser therapy for the lesion was attempted vulvar tissue. with minimal benefit. She also had been evaluated The patient was referred to the gynecology by a gynecologist who proposed an initial diagno- department for diagnostic hysteroscopy, dilation and sis of vulvar angiokeratoma and suggested surgi- curettage, vaginoscopy, and bilateral vulvectomy. cal treatment. Two weeks following surgery, dramatic improvement The patient’s medical history included NS, a of the vulvar lesions was noted, with some edema heart murmur, and narrow-angle glaucoma. No of the genital region as well as residual scattered red and clear vesicular lesions of LC (Figure 1). A microscopic analysis of surgical specimens performed by a board-certified pathologist (R.T.C.) revealed superficial and deep infiltrative growth of irregularly outlined lymphatic channels that did not closely border the overlying epithelial basement membrane, resulting in the presence of a prominent grenz zone (Figure 2). On immunohistochemical evaluation of sections of the left labium majus, lymphatic channels and endothelial vasculature stained positive with CD31 (platelet-endothelial cell adhesion molecule), which stained both lymphatic and blood vessel CUTISendothelium as well as a subset of tissue macrophages Figure 1. Edema and scattered red and clear vesicular lesions 2 weeks following bilateral vulvectomy for treat- (Figure 3A). A number of vascular channels stained mentDo of lymphangioma circumscriptum Not of the vulva. positive Copy with D2-40, a marker that is relatively A B C Figure 2. A tissue section from the left labium majus revealed superficial and deep dilated vascular channels with increased density in the superficial dermis beneath a mildly papillomatous epidermis (A)(H&E, original magnifica- tion 2); ectatically dilated, endothelial-lined vascular spaces separated from an overlying basement membrane zone by an intervening grenz zone (B)(H&E, original magnification 10); and dilated endothelial-lined vascular channels with intraluminal eosinophilic lymph in the lumen. Intraluminal valves were seen in the centrally located lymphatic vessel (C)(H&E, original magnification 20). 298 CUTIS® WWW.CUTIS.COM Copyright Cutis 2014. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Lymphangioma Circumscriptum specific for lymphatic endothelium. The endothelial an uncommon finding. Vlastos et al5 reported only lining of adjacent capillaries demonstrated negative 11 cases of congenital LC of the vulva and staining for D2-40 (Figure 3B). Histopathologically, 22 acquired cases. There have been additional these results were consistent with the diagnosis of reports of acquired LC of the vulva.6-13 LC of the vulva. Prior reports of lymphatic dysplasia associated with NS include the presence of cystic hygroma, Comment lymphedema, intestinal lymphangiectasia, pulmo- Lymphangiomas previously have been classified as nary lymphangiectasia, and facial cutaneous lym- superficial and deep lesions, with LC comprising phangioma in NS.14-16 Our case provides additional the superficial group and cavernous lymphangiomas evidence that the characteristic phenotypes involv- and cystic hygromas classified in the deep group. ing lymphatic dysplasia in NS may be broadened Lymphangioma circumscriptum generally presents to include cutaneous lymphangioma in addition to as cutaneous vesicles ranging in color from pink to generalized lymphedema and cystic hygroma. black depending on the amount of blood intermixed Management considerations for LC involve cos- with the clear lymph fluid.3 In 1970, Peachey et al4 metic effects, pain, swelling, persistent lymph fluid reviewed and characterized lesions in 65 patients and blood leakage, and continued recurrence of with cutaneous LC. The 2 most commonly described infections.17 The mainstay of treatment of LC is sur- variants of cutaneous LC are classic and localized gical resection of the lesion with radical vulvectomy LC. Classic LC generally is characterized by exten- demonstrating the lowest recurrence rate following sive lesions with affected areas of skin greater than treatment of LC of the vulva.18 Complete surgi- 1 cm². The lesions tend to be concentrated over cal resection also should include excision of deep the proximal regions of limbs and adjacent to limb communicating lymphatics. Additional therapeutic girdles; however, they can be found on almost any options include abrasive therapy, sclerotherapy, and area of the body.4 Localized LC presents as single electrocoagulation; however, these methods com- discrete lesions of vesicles comprising an area of less monly result in recurrence if the entire lesion and than 1 cm². Lesions do not consistently present in deep communicating system have not been destroyed any particular areas of the bodyCUTIS but tend to be absent by the treatment.18-20 from regions where classic LC is seen.4 The differential diagnosis of LC of the vulva Conclusion should include condyloma acuminatum, herpes zos- It is not uncommon for patients with NS to dem- ter, molluscum contagiosum, angiomyofibroblastoma, onstrate features of lymphatic abnormalities, and angiomyxoma. Lymphangioma circumscriptum with lymphedema and cystic hygroma most often of theDo vulva may be congenital Not or acquired and is observed. Copy1 As demonstrated