Angiomyolipoma (AML) is a tumor of uncertain

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1 Case reports 167 Cutaneous angiolipoleiomyoma Eiichi Makino, MD, Jun Yamada, MD, Joji Tada, MD, Jiro Arata, MD, and Keiji Iwatsuki, MD Okayama-shi, Japan We describe a girl with cutaneous angiolipoleiomyoma on the buttock. The 16-year-old girl had a cm subcutaneous tumor on the right buttock, which was slightly tender. The tumor appeared to be vascular and was, therefore, surgically excised. Histologically, the lesion was poorly circumscribed and was composed of differently sized blood vessels, smooth-muscle bundles, and mature adipose tissue. These histologic findings were consistent with those of angiomyolipoma, which commonly occurs in the kidney. Cutaneous angiomyolipoma, which is also known as cutaneous angiolipoleiomyoma, is a rare benign mesenchymal tumor. To our knowledge, only 16 cases have been reported in the Englishlanguage literature. In our report, we review the clinical features of 17 cases, including the current one. We point out the differences between the cutaneous and renal forms of angiomyolipoma, and conclude that the cutaneous lesion is distinct from a renal lesion in several aspects, including tuberous sclerosis complex association and immunoreactivity to both HMB-45 and MART-1. ( J Am Acad Dermatol 2006;54: ) Angiomyolipoma (AML) is a tumor of uncertain histogenesis, and is most commonly associated with the kidney. Extrarenal sites of AML are rare lesions, and include the liver, nasal cavity, oral cavity, heart, colon, lung, and skin. 1 Cutaneous AML, also known as cutaneous angiolipoleiomyoma, is a rare benign tumor and, until now, only 16 cases had been reported in the Englishlanguage literature. 2-9 In this article, we report the case of a girl with cutaneous angiolipoleiomyoma on her buttock. We summarize the clinical features of 17 published cases, including the current one. Moreover, we point out the differences between the cutaneous and renal forms of AML, which can probably justify the term angiolipoleiomyoma for the cutaneous lesion rather than for AML. From the Department of Dermatology, Okayama University, Graduate School of Medicine and Dentistry, Okayama-shi, Japan. Funding sources: None. Conflicts of interest: None identified. Reprint requests: Eiichi Makino, MD, Department of Dermatology, Okayama University, Graduate School of Medicine and Dentistry, Shikatachou, Okayama-shi , Japan. makinoh@cc.okayama-u.ac.jp /$32.00 ª 2006 by the American Academy of Dermatology, Inc. doi: /j.jaad CASE REPORT A 16-year-old girl had a subcutaneous tumor with slight tenderness on the right buttock. The onset of the tumor was not specified. The patient was otherwise in good health except for a history of atopic dermatitis. She had no clinical signs of tuberous sclerosis complex (TSC), including renal AML. The tumor was cm in size, and composed of grouped elastically firm, violaceous nodules, the clinical patterns of which indicated a vascular tumor (Fig 1, A). The nodules had adhered to both the overlying skin and deeper tissues, thereby resulting in immovability. Magnetic resonance imaging revealed a hypointense circumscribed mass in the subcutis of the buttock on T1-weighted images, and a hyperintense granular-like appearance on T2-weighted images (Fig 2). Contrast enhancement of the lesion revealed a hyperintense network of septa that formed a multiloculated appearance (Fig 2, C and D). Although enhancement by contrast material was slight, these magnetic resonance imaging findings suggested the presence of hemangioma. The tumor was surgically excised under local anesthesia. On excision, the tumor was poorly circumscribed and had been penetrated by a few blood vessels and, thus, appropriate steps to ensure minimal bleeding were required. The cut surfaces of the excised tumor revealed an ill-defined, pale white fibrous tissue containing thrombi encapsulated in various sizes and shapes (Fig 1, B). No recurrence has been noted 2 years after operation. Histologically, the tumor was composed of a mixture of vascular spaces, smooth-muscle bundles, and mature adipose tissue. The specimen had illdefined margins with no fibrous capsule (Fig 3). Masson trichrome staining stained the muscular portions of the tumors bright red and the collagen

2 168 Case reports JAM ACAD DERMATOL JANUARY 2006 Fig 2. Magnetic resonance image findings of subcutaneous nodule. T1-weighted (A), T2-weighted (B), and gadolinium-enhanced (C and D) images. Fig 1. A, Clinical appearance of angiolipoleiomyoma. B, Cut surface of excised tumor. blue (Fig 4). Elastica van Gieson staining revealed small arterioles within the lesion (Fig 5). Desmin staining showed focal immunoreactivity in the lesion, and the endothelial cell lining of the vascular spaces was strongly positive for factor VIII (not shown). S100 staining revealed no neural elements within the lesion and immunostaining for HMB-45 and MART-1 was also negative (not shown). No cytologic atypia or mitotic figures were noted, and there were no areas of necrosis or hemorrhage. All these findings were consistent with those of cutaneous angiolipoleiomyoma. DISCUSSION The clinical features of the 17 published cases, including the current one, of cutaneous angiolipoleiomyoma are summarized in Table I. Cutaneous angiolipoleiomyoma has usually occurred as a solitary, asymptomatic subcutaneous nodule, 1 to 4 cm in diameter, commonly located in acral skin or on the ear. Patient age has ranged from 16 to 77 years (mean: 50 years), with a male/female ratio of 13:4. Histologically, the tumors have been composed of a mixture of vascular spaces, smooth-muscle bundles, and mature adipose tissue in variable quantities, and have had a well-defined fibrous capsule. Signs of TSC were absent in all reported cases and recurrence has been noted in only one case after surgical resection. Buyukbabani et al 7 experienced a patient with two previous local recurrences at the same site after operation. They reported that these recurrences seemed to be a result of incomplete surgical excision, and not to local invasion of the tumor. Although neither cytologic atypia nor mitoses have been observed in most cases, one case presented marked pleomorphism in the smoothmuscle component. 5 However, the author considered these changes to be degenerative, excluding the possibility of malignant potential as a result of pseudocapsulation without mitotic activity, no progression of the tumor for 15 years, and no recurrence for 15 months after operation. These previous observations suggest that simple excision is generally adequate treatment for cutaneous angiolipoleiomyoma. Most of the lesions in the previously reported cases were easily shelled-out, however, Lin and Chiu 9 reported a patient in whom massive bleeding occurred during this procedure. They identified a large feeding artery at the base of the tumor. In our case, small arterioles were also revealed on histologic examination. Indeed, during resection of the tumor, appropriate steps to stop bleeding were necessary. Cutaneous angiolipoleiomyoma usually presents as a well-circumscribed subcutaneous nodule. 10,11 An unusual finding in our case was that the lesion was poorly circumscribed, and interlacing fascicles and bundles of smooth muscle extended through the stroma of the tumor and into the septas of the adipose tissue. Moreover, buttock presentation and young-age (16 years) onset is rare, making our case unique (Table I).

3 Case reports 169 Fig 3. Histopatology of cutaneous angiolipoleiomyoma at low- (A) and high- (B) magnification views. (A and B, Hematoxylin-eosin stain; original magnifications: A, 320; B, 3100.) Fig 5. Elastica van Gieson method revealed small arterioles within lesion. (Original magnification 3100.) Fig 4. Masson trichrome method stained muscular portions of tumor bright red and stained collagen blue. (Original magnifications: A, 340; B, 3200.) The clinical and pathologic findings in the cutaneous and renal forms of AML are listed in Table II. Approximately one third of patients with renal AML present with manifestations of TSC. The two genes associated with TSC (TSC1 and chromosome 9q34 12 ; TSC2 and chromosome 16p ) may act as tumor suppressor genes, and loss of hamartin and tuberin expression, the products of the TSC1 and TSC2 genes, respectively, can be detected in AMLs with TSC1 and TSC2 mutations. 14 In cutaneous AML, the smooth muscle is present as sheets and fascicles of spindled cells with cigarshaped nuclei. In contrast, the smooth-muscle cells in renal AML generally appear to be less mature and are often present in a more diffuse pattern without the formation of distinct fascicles. 2,15 The smoothmuscle cells in renal AML are not only immunoreactive for desmin but also, unlike other smooth-muscle tumors, express the melanoma-associated antigen HMB and MART In cutaneous AML, there is no TSC association and no loss of heterozygosity in tumors. Unlike the renal form, immunoreactivity for HMB-45 is not present in the cutaneous form. In our case, immunoreactivity for both HMB-45 and MART-1 was negative. The basic components of these two tumors are the same; however, our results clearly demonstrate that the cutaneous and renal forms of AML have distinct clinical and pathologic findings. Therefore, we propose the term angiolipoleiomyoma for the cutaneous form. Fitzpatrick et al 2 have mentioned this suggestion. We also support the contention of

4 170 Case reports JAM ACAD DERMATOL JANUARY 2006 Table I. Clinical features of the 17 cases of cutaneous angiolipoleiomyoma Reference Age (y)/sex Size (cm) Location Duration Recurrence Unusual findings TSC 2 77/M - - (ÿ) (ÿ) 63/M - 6 mo (ÿ) (ÿ) 50/M - Head 3 - (ÿ) (ÿ) 59/F - Elbow 2 - (ÿ) (ÿ) 52/M - Hand 2 1 y (ÿ) (ÿ) 33/M - Toe 1 3 y (ÿ) (ÿ) 48/M - 2 mo (ÿ) (ÿ) 39/M - - (ÿ) (ÿ) 3 67/M Ear 40 y (ÿ) (ÿ) 4 49/M - Ear - (ÿ) (ÿ) 5 58/M Elbow 15 y (ÿ) With pleomorphic changes (ÿ) 6 49/M Ear 5 y (ÿ) (ÿ) 7 38/M Ear 10 y (1) Two previous recurrences (ÿ) 36/M Nose 3 y (ÿ) (ÿ) 8 54/F - Nose 5 y (ÿ) (ÿ) 9 65/F Preaulicular area 10 y (ÿ) Massive bleeding on excision (ÿ) Current case 16/F Buttock - (ÿ) Ill-defined margins, histologically; buttock presentation; early onset with slight tenderness (ÿ) F, Female; M, male; TSC, tuberous sclerosis complex. Table II. Clinical and pathologic findings in cutaneous and renal angiomyolipoma Cutaneous form Renal form No. of lesions Solitary Often solitary (multiple in TSC-associated tumor) Median age of patients (y) 50 y 46 y TSC association Absent One third LOH in tumors Not detected 9q34 & 16p13 Smooth-muscle cells in tumors Cigar-shaped nuclei, fascicles formation Diffuse, clumped marked cellular pleomorphism Immunoreactivity for HMB-45 & MART-1 Negative Positive Symptoms Asymptomatic Abdominal and flank pain, hematuria, chills, fever LOH, Loss of heterozygosity; TSC, tuberous sclerosis complex. Enzinger and Weiss, 1 who stated that the term angiomyolipoma should be reserved for a specific lesion arising most commonly in one or both kidneys as a solitary or multicentric mass. REFERENCES 1. Enzinger FM, Weiss SW. Soft tissue tumors. 4th ed. St Louis: CV Mosby; pp Fitzpatrick JE, Mellett JR, Hwang RJ, Golitz LE, Zaim T, Clemons D. Cutaneous angiolipoleiomyoma. J Am Acad Dermatol 1990;23: Argenyi ZB, Piette WW, Goeken JA. Cutaneous angiomyolipoma: a light-microscopic, immunohistochemical, and electron-microscopic study. Am J Dermatopathol 1991;13: Mehregan DA, Mehregan DR, Mehregan AH. Angiomyolipoma. J Am Acad Dermatol 1992;27: Rodriguez-Fernandez A, Caro-Mancilla A. Cutaneous angiomyolipoma with pleomorphic changes. J Am Acad Dermatol 1993;29: Val-Bernal FJ, Mira C. Cutaneous angiomyolipoma. J Cutan Pathol 1996;23: Buyukbabani N, Tetikkurt S, Ozturk AS. Cutaneous angiomyolipoma: report of two cases with emphasis on HMB-45 utility. J Eur Acad Dermatol Venereol 1998;11: Obata C, Murakami Y, Furue M, Kiryu H. Cutaneous angiomyolipoma. Dermatology 2001;203: Lin SJ, Chiu HC. An asymptomatic preauricular subcutaneous nodule in a 65-year-old woman. Arch Dermatol 2003;139: Holst VA, Junkins-Hopkins JM, Elenitsas R. Cutaneous smooth muscle neoplasms: clinical features, histologic findings, and treatment options. J Am Acad Dermatol 2002;46: Requena L, Sangueza OP. Cutaneous vascular proliferations. Part III. Malignant neoplasms, other cutaneous neoplasms

5 Case reports 171 with significant vascular component, and disorders erroneously considered as vascular neoplasms. J Am Acad Dermatol 1998;38: van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 1997;277: European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 1993;75: Plank TL, Logginidou H, Klein-Szanto A, Henske EP. The expression of hamartin, the product of the TSC1 gene, in normal human tissues and in TSC1- and TSC2-linked angiomyolipomas. Mod Pathol 1999;12: Mentzel T. Cutaneous lipomatous neoplasms. Semin Diagn Pathol 2001;18: Ashfaq R, Weinberg AG, Albores-Saavedra J. Renal angiomyolipomas and HMB-45 reactivity. Cancer 1993;71: Jungbluth AA, Iversen K, Coplan K, Williamson B, Chen YT, Stockert E, et al. Expression of melanocyte-associated markers gp-100 and Melan-A/MART-1 in angiomyolipomas. An immunohistochemical and rt-pcr analysis. Virchows Arch 1999;434: