Mucocutaneous Angiomyolipoma: A Report of 2 Cases Arising in the Nasal Cavity Open Access

Angiomyolipoma (AML) is a distinctive tumor that usually occurs in the kidney with or without tuberous sclerosis (TS).1,2 The same tumor can arise in the liver.3,4 Angiomyolipoma in tissues other than the kidney and liver is extremely rare, and only a few cases in the mediastinum,5 heart,6 spermatic cord,7 vaginal wall,8 fallopian tube,9 oral cavity,10 pharynx,11 nasal cavity,12,13 and skin14–19 have been reported. Among them, cutaneous AML, including angiolipoleiomyoma,15 has been most systematically described, and the differences from renal AML have been pointed out.15,19 We present 2 additional cases of AML in the nasal cavity and discuss their differences from renal AML with respect to clinicopathologic features.

A 66-year-old man who had been receiving chemotherapy for non-Hodgkin lymphoma noticed a mass in his right nasal cavity. The otorhinologic examination revealed a mesorrhine, polypoid, dome-shaped tumor. Polypectomy was performed. The tumor was 20 mm with a brown-to-grayish cut surface and was well circumscribed. The postoperative course has been uneventful for 2 years.

An 88-year-old woman was admitted to a hospital complaining of a nasal polyp. Rhinoscopic examination revealed a 20-mm polypoid tumor with a stalk in the left nasal vestibule to inferior concha. The tumor, which was extirpated by polypectomy, had a firm whitish cut surface. This is a recent case and recurrence has not been observed for 6 months.

Both tumors were fixed in 20% formaldehyde and embedded in paraffin wax. The sections were cut at 3 to 4 mm and prepared for light microscopy and immunohistochemical study. Immunohistochemistry was performed using streptavidin-biotin-peroxidase complex methods (SABC kit, Dako Japan, Kyoto, Japan). The antibodies and their working dilutions were as follows: α–smooth muscle actin (1A4, Dako Japan, 1:50), muscle actin (HHF35, Enzo Diagnostics, New York, NY, 1:8000), desmin (D33, Dako Japan, 1:50), S100 protein (polyclonal, Dako Japan, 1:1000), and HMB45 (Dako Japan, 1:50).

Both tumors were well demarcated from the surrounding mucosa and stroma but were not encapsulated (Figure 1). Their histologic features were similar, and the tumors were composed of mixtures of smooth muscle cells (SMC), blood vessels, and fat tissue in various proportions (Figures 2 and 3). The SMC had fibrillary spindle cytoplasm and transited to the vascular wall. The vessels varied in shape; some had thick walls and others were slitlike. In part, vessels with hyalinized thick walls were seen. The foci of mature fat cells, which had a little variation in cellular size, were irregularly scattered over the tumors. The areas that contained numerous fat cells were lipoma-like, whereas other areas with only scarce fat cells mimicked angioleiomyoma (Figure 4). No epithelioid SMC were seen. Aggregated small lymphocytes were frequently noted in both tumors (Figures 2 and 3).

The SMC of both tumors stained diffusely and intensely for α–smooth muscle actin and muscle actin. Interspersed SMC were positive for desmin, but the vascular wall was occasionally negative. S100 protein only labeled the mature fat cells. HMB45 was completely negative in both cases.

Angiomyolipoma of the kidney is a distinctive tumor composed of SMC, vessels, and mature fat cells, with the proportion of each component varying in individual tumors.1 It is intimately related to TS, and approximately 80% of TS is associated with AML. In addition, half of the cases with renal AML are thought to be complicated with TS.2 Although AML occasionally occurs in the liver, it does not seem to be related to TS.3,4 Recently, the histogenesis of so-called epithelioid SMC in AML has become controversial, since it was demonstrated that in most cases these cells exhibit HMB45 immunoreactivity.20–24 These epithelioid SMC frequently show characteristic features by light microscopy, such as abundant clear cytoplasm and atypical nuclei, which may be confused with those of renal cell carcinoma.24 Moreover, SMC frequently lack immunoreactivity for actin and desmin.21,24 Ultrastructurally, these epithelioid SMC commonly have melanosome-like dense granules in their cytoplasm21 and sometimes have crystalloids mimicking those seen in alveolar soft-part sarcoma,22 whereas the bundles of myofilaments are not seen.21 These findings suggest that epithelioid SMC are distinctive and may be intrinsic for AML and that they may not be true SMC. Zamboni et al25 described an intimate relation between epithelioid SMC of AML and so-called sugar tumor of the lung and pancreas and proposed to call them perivascular epithelial cells.

Among all the types of AML arising in the sites other than the kidney and liver, AML of the skin (cutaneous AML) has been most systematically described. To our knowledge, at least 13 cases have been described in the literature (Table).14–19 In the nasal cavity only 4 cases, including the present ones, have been reported (Table).12,13 Angiomyolipoma of the skin and nasal cavity is commonly composed of various-sized vessels, mature SMC, and fat cells, and, as pointed out previously, these types of AML are apparently distinct from renal and hepatic AML in several clinicopathologic features.12–19 First, they preferentially occur in older men and are never associated with TS. Second, the tumors are small, seldom larger than 40 mm, whereas renal and hepatic AML can reach much larger sizes and are frequently huge.1 Third, the most distinctive point is that AML of the skin and nasal cavity include only mature SMC and do not contain HMB45-positive epithelioid SMC. In addition, lymphocytic aggregation in the tumor, which is uncommon in renal AML, is not infrequent in AML of the skin19 and nasal cavity, including the present cases. Thus, AML of the skin and nasal cavity is considered to be distinct from renal and hepatic AML. In addition, AML of the oral cavity10 and pharynx11 seems to have identical histologic features with those of the skin and nasal cavity. Accordingly, we propose to distinguish these tumors in the skin and nasopharyngeal mucosa as mucocutaneous angiomyolipoma (MCAML) from AML of the kidney and liver.

There is controversy as to whether MCAML may be a variant of angioleiomyoma (AL). Indeed, the histologic features of MCAML mimic AL except for the fatty element, and both tumors occur in either dermis or subcutis. Moreover, AL is known to rarely contain a small amount of fat cells.26,27 However, several differences are also present. First, MCAML exhibits conspicuous predilection in older men (17 of 19 cases: Table), whereas AL tends to occur in women.26 Second, although AL preferentially arises in the lower extremities, MCAML affects the acral regions of the body and the head, including the elbow, ear, and nose. Interestingly, 16 ALs with fat cells described by Hachisuga et al26 all arose in the head, and, in addition, paroxysmal pain characteristic of AL was not seen. Those ALs with fat cells may be identical to the tumors reported as cutaneous angiomyolipoma. Thus, although it is likely that MCAML is intimately related to AL, MCAML should probably be distinguished from AL because of the characteristic clinicopathologic features of MCAML.

Finally, it is not clear whether solitary AML arising in the mediastinum,5 heart,6 spermatic cord,7 and fallopian tube9 are identical with renal AML, since these tumors seem not to include epithelioid SMC and HMB45 positivity has not been described.

In summary, 2 cases of AML arising in the nasal cavity are presented. They were composed of mature SMC, vessel cells, and fat cells mimicking cutaneous AML and were thought to be different from renal and hepatic AML. The term MCAML is thought to be appropriate to express these rare distinctive tumors.