Becker Nevus with an Underlying Desmoid Tumor a Case Report and Review Including Mayo Clinic’S Experience

OBSERVATION Becker Nevus With an Underlying Desmoid Tumor A Case Report and Review Including Mayo Clinic’s Experience

Gabriel F. Sciallis, MD; Andrew P. Sciallis, MD

Background: Becker nevus is a nevoid melanosis, re- yielded 52 patients with Becker nevi, 12 of whom had ferred to as Becker nevus syndrome when it is associ- an associated bone, vascular, neural, congenital, or other ated with other anomalies. Our objectives were to re- soft-tissue abnormality, ranging from liposarcoma to an port the occurrence of a Becker nevus with an underlying accessory areola. desmoid soft-tissue tumor; to review Mayo Clinic’s experience with Becker nevi, concentrating on Becker nevi Conclusions: We add to the literature a unique case of associated with bone, vascular, neural, and other soft- desmoid-type fibromatosis immediately beneath a Becker tissue abnormalities; to inform physicians of the Becker melanosis, which presented as a painful dimple. We hope nevus syndrome; and finally to alert clinicians to evalu- to raise awareness that a Becker nevus may be associ- ate a Becker nevus with its associations in mind. ated with other abnormalities, including an infiltrative soft-tissue tumor. We also emphasize the importance of Observations: A 46-year-old woman had a Becker ne- follow-up, including inspection of not only the surface vus with an underlying desmoid-type fibromatosis (desmoid tumor) presenting clinically as a “painful dimple” but also the deep tissues underlying the Becker nevus. within the nevus. Review of medical records for 1997 through 2006 at Mayo Clinic, Rochester, Minnesota, Arch Dermatol. 2010;146(12):1408-1412

ECKER NEVUS IS A SHARPLY case reports and reviews in the literature marginated and typically have not identified a similar association. unilateral nevoid melano- We reviewed Mayo Clinic’s experience sis commonly arising on the with Becker nevi from 1997 through 2006. upper extremities or thorax.B Although most Becker nevi are iso- lated findings, they have been associated REPORT OF A CASE with various skeletal and other abnormalities included under the designation “Becker nevus syndrome.” Becker nevi do A 46-year-old woman with a known Becker not pursue a malignant course but may be- nevus involving the left upper arm and come cosmetically problematic. During shoulder was referred to the Department adolescence, Becker nevi may become of Dermatology at Mayo Clinic, Roches- more prominent with increased hair ter, Minnesota, in December 2006 when growth. additional associated signs and symp- Desmoid-type fibromatosis (desmoid toms of burning pain developed under- tumor) is a nonmetastasizing but locally neath the nevus. The patient reported the aggressive soft-tissue tumor that occurs existence of her Becker nevus since at least both extra-abdominally and intra- adolescence. The underlying pain was ac- abdominally. There is an increased occur- centuated by pressure, touch, and move- rence of desmoid tumors in patients with ment. The patient otherwise felt well. In- familial adenomatous polyposis (FAP). terestingly, she maintained that the area Author Affiliations: Herein, we describe a 46-year-old pa- had “always felt uncomfortable,” but the Departments of Dermatology (Dr G. F.Sciallis) and tient with a known Becker nevus that be- symptoms amounted to only a mild nui- Laboratory Medicine and came dimpled and painful. Immediately sance. The apparent change in the qual- Pathology (Dr A. P.Sciallis), underneath the Becker nevus was a des- ity and magnitude of her symptoms dur- Mayo Clinic, Rochester, moid tumor that was responsible for the ing the preceding 2 months prompted the Minnesota. cutaneous dimpling. To our knowledge, referral. Her medical and surgical history

(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 12), DEC 2010 WWW.ARCHDERMATOL.COM 1408

©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 included a hysterectomy, arthritis, Hashimoto thyroiditis– induced hypothyroidism, and a lipoma of the right thigh. Interestingly, her family history was contributory for pap- illary thyroid carcinoma in 3 first-degree relatives. Physical examination of her back and left arm re- vealed a tan-to-brown macule with 2 areas of dimpling over the left upper back (Figure 1). There were nei- ther prominent follicles nor an associated hypertrichosis. Palpation of the dimpled areas elicited pain. The deep soft tissue surrounding the dimpled area was firm over an area that measured approximately 12ϫ7 cm. Because of this associated firmness, magnetic reso- nance imaging (MRI) was performed, which identified an ill-defined and infiltrative subcutaneous mass di- rectly underneath the nevus and close to both the teres minor and deltoid muscles. The radiographic differential diagnosis included desmoid-type fibromatosis or a soft-tissue sarcoma, and excision was recommended. Figure 1. Clinical photograph identifying the Becker nevus with areas of Intraoperatively, the mass was noted to involve the fas- dimpling (arrows) with darker ambient light to accentuate the dimpling. cia and subcutis. On gross examination, the mass was poorly circumscribed, with a pale, whorled, and fibrous cut surface, measuring 10.2ϫ7.4ϫ5.3 cm (Figure 2). The borders of the mass were infiltrative with unin- volved surgical margins. The skin overlying the mass was pigmented and with the aforementioned dimpling. Histologically, the overlying skin demonstrated a mildly hyperplastic epidermis with elongated rete ridges and basal layer hyperpigmentation (Figure 3). There was clearly no increase in the number of junctional melanocytes. The superficial dermis demonstrated foci of actin-positive smooth muscle bundles separated by collagen (Figure 3). Moreover, there was no increase in the number of hair follicles. Taken together, these features are consistent with the patient’s clinical diagnosis of a Becker nevus. Figure 2. Gross photograph of the wide local excision specimen, showing a Immediately beneath the Becker nevus was an infil- dimpled and hyperpigmented epidermis with an underlying infiltrative soft-tissue mass. The unit of measure for the ruler is centimeters. trative and moderately cellular mass composed of bland spindle cells arranged in fascicles, with admixed collagen fibrosis and dilated arterioles (Figure 4). All these genital, or other soft-tissue abnormality. These abnor- features support a diagnosis of desmoid-type fibromato- malities, which may be incidental, included malignant sis (desmoid tumor). Immunohistochemical studies of neoplasms (lower extremity liposarcoma) as well as con- the neoplastic cells were negative for estrogen and an- genital anomalies (extra areola; absence of a testicle). One drogen receptors. Because of the desmoid tumor’s po- such neoplasm arose close to the patient’s Becker nevus tential for recurrence, our patient has been followed clini- (dermatofibrosarcoma protuberans). cally and with serial MRIs, the findings of which have In 1949, Becker1 described hyperpigmented, sharply been negative for tumor recurrence for 3 years. marginated, unilateral macules with hypertrichosis lo- After obtaining approval of the Mayo Clinic institu- cated on the shoulders of 2 young men. Today, this is tional review board, we reviewed the Mayo Clinic elec- generally referred to as Becker nevus, but has also been tronic medical records for Becker nevi and desmoid tu- termed Becker melanosis, pigmented hairy epidermal ne- mors. Including the patient described herein, of the 53 vus, and melanosis neviformis of Becker.2,3 Becker nevus patients with Becker nevi, only our patient had a co- usually occurs on the thorax or upper extremities, al- occurring desmoid tumor. though there have been reports of lower extremity mani- festations.4 In 1995, Happle5 defined the pigmented hairy epidermal nevus syndrome to include Becker nevus, ip- COMMENT silateral hypoplasia of the breast, and skeletal defects such as scoliosis and indicated the syndrome may be ex- Our patient, a middle-aged woman, demonstrated the oc- plained by paradominant inheritance. Happle and Koop- currence of a desmoid tumor beneath a Becker nevus. The man6 in 1997 proposed the new term Becker nevus syn- patient’s symptoms, as well as the cutaneous dimpling, drome for a phenotype characterized by the presence of were secondary to the localized infiltration of the under- a particular type of organoid epithelial nevus showing lying desmoid tumor. In our retrospective case review, hyperpigmentation, increased hairiness, and hamarto- a notable percentage of patients (23%) with confirmed matous augmentation of smooth muscle fibers, and other Becker nevi had an associated bone, vascular, neural, con- developmental defects such as ipsilateral hypoplasia of

(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 12), DEC 2010 WWW.ARCHDERMATOL.COM 1409

Figure 3. Becker nevus. A, Photomicrograph of a slightly hyperplastic squamous epithelium with basilar hyperpigmentation and blunted rete ridges (hematoxylin-eosin, original magnification ϫ200). B, The smooth muscle bundles stained positive for smooth muscle actin (hematoxylin-eosin, original magnification ϫ100).

A B

Figure 4. Subcutaneous mass. A, Photomicrograph of a spindle cell lesion arranged in broad fascicles with an infiltrative growth pattern (hematoxylin-eosin, original magnification ϫ20). B, The spindle cells were cytologically bland and without appreciable mitotic activity (hematoxylin-eosin, original magnification ϫ200).

the breast and skeletal anomalies including scoliosis, spina smooth muscle hyperplasia to be the 2 ends— bifida occulta, or ipsilateral hypoplasia of a limb. The as- hyperpigmentation and smooth muscle prolifera- sociated anomalies tend to show a definite regional cor- tion—of a continuum representing the same disor- respondence, suggesting a common origin from an early der.12,13 Thus, not every case of Becker nevus syndrome postzygotic mutation. has to manifest every association that has been re- In 1998, Urbani and Betti7 suggested supernumerary ported, but the presence of an associated manifestation nipple and urogenital anomalies in association with Becker does raise awareness to consider other anomalies that may nevus. In response, Happle and Koopman8 included su- indicate mosaic mutations involving cellular lines other pernumerary nipples and genital anomalies as part of the than epidermal lines. 9(p225) Becker nevus syndrome. In 2007, Sugarman, in re- Histologically, a Becker nevus demonstrates a hyper- viewing the epidermal nevus syndromes, indicated that plastic epidermis with increased pigmentation of the basal Becker nevi have been associated with ipsilateral hypoplasia of keratinocytes. There may be elongation or “clubbing” of the breast, hypoplasia of underlying musculature, lipoatro- the rete ridges. The dermis may also show increased hair phy, and underlying skeletal anomalies, including scoliosis, he- follicles and/or smooth muscle bundles that are unasso- mivertebrae, fused or accessory cervical ribs, pectus excava- ciated with the surrounding adnexa. Although the epi- tum or carinatum, and internal tibial torsion. dermis may appear to show a focal increase in melano- Happle10 in 2004 described 5 pigmentary patterns in- cytes, there are no nests.14 volving mosaic epigenetic and genomic etiologies. Ac- Desmoid-type fibromatoses are synonymous with ag- cording to Happle, the syndrome, which occurs sporadi- gressive fibromatoses and desmoid tumors. These clonal cally, has a greater frequency in females, and they may tumors may arise both intra-abdominally and extra- not have hypertrichosis. Haneke11 described prolifera- abdominally and may be sporadic or associated with FAP, tion of the erector pili muscles in the dermis of a Becker a hereditary tumor syndrome resulting from germline mu- nevus that resembled smooth muscle hamartoma, and this tation in the APC tumor suppressor gene. The APC pro- feature has caused some to consider Becker nevus and tein is involved in the regulation and degradation of ␤-

(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 12), DEC 2010 WWW.ARCHDERMATOL.COM 1410

©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 catenin, and mutations in the APC gene allow for defective are also found. This category would include several cases protein function, resulting in the translocation and ac- in our Mayo Clinic review. cumulation of ␤-catenin within the cell nucleus, which 15,16 in turn leads to cell proliferation. This defect is be- CONCLUSIONS lieved to account for an increased risk of desmoid tumors in patients with FAP. Reassurance and monitoring the patient for both in- Sporadic extra-abdominal desmoid-type fibromato- tranevus and underlying changes are appropriate. ses arise from the connective tissue of muscle and the Given the propensity for a Becker nevus to be associ- overlying fascia, although the actual cell of origin is not 17 ated with other abnormalities, the clinician should al- known. They typically present between puberty and 40 ways inquire if the patient has noticed changes in his or years of age, with women affected more than men. They her Becker nevus and then examine the nevus to detect most often involve the shoulder, chest wall, and back. additional abnormalities, especially if there is either Although these desmoid-type fibromatoses are histologi- pain or restricted motion. cally similar to desmoid tumors occurring in patients with Becker nevus is a nevoid melanosis, and it can be as- FAP, the mechanism of ␤-catenin dysregulation is dif- ␤ sociated with other anomalies for which the term Becker ferent and involves mutations of the -catenin gene rather nevus syndrome is used. We add to the literature the as- 18 than loss of function of APC. The clinicopathologic dif- sociation of desmoid-type fibromatosis beneath a Becker ferential diagnosis of extra-abdominal desmoid-type fi- nevus, which presented as a painful dimple. We hope to bromatoses should include leiomyoma, a low-grade sar- raise clinical and pathologic awareness that a Becker ne- coma, and reactive spindle-cell proliferations (ie, nodular vus may be associated with other abnormalities. fasciitis).19 In our case, a more focused differential diagnosis would include another bland spindle cell neoplasm, such as a leiomyoma. Both tumors can be posi- Accepted for Publication: May 20, 2010. tive for both smooth muscle actin and desmin.20 However, Correspondence: Gabriel F. Sciallis, MD, Department of the lack of tumor circumscription should alert the pa- Dermatology, Mayo Clinic, 200 First St SW, Rochester, thologist to a diagnosis of desmoid-type fibromatosis. In MN 55905 ([email protected]). difficult-to-distinguish cases, desmoid tumors demon- Author Contributions: Both authors had full access to strate nuclear positivity on immunostains for ␤- all the data in the study and take responsibility for the catenin,21 which reflects the importance of ␤-catenin in integrity of the data and the accuracy of the data analy- this tumor’s pathogenesis.22 sis. Study concept and design: G.F. Sciallis. Acquisition of Becker nevi have been reported to have an increased data: G.F. Sciallis and A.P. Sciallis. Analysis and interpre- amount of androgen receptors, which may explain its tation of data: G.F. Sciallis and A.P. Sciallis. Drafting of overall male predominance as well as the phenomenon the manuscript: G.F. Sciallis and A.P. Sciallis. Critical re- of increased hypertrichosis during pubertal years.23,24 Hy- vision of the manuscript for important intellectual content: pertrichosis is evident in 50% of cases and is less evi- G.F. Sciallis and A.P. Sciallis. dent or absent in females. Interestingly, occasional des- Financial Disclosure: None reported. moid tumors have demonstrated immunoreactivity for Additional Contributions: Thomas Flotte, MD, re- androgen receptors; in 1 study, positive immunostain- viewed the manuscript and pathologic findings. ing was limited to the extra-abdominal desmoids rather than the intra-abdominal ones.25 As mentioned, our pa- REFERENCES tient’s desmoid tumor was negative for androgen- receptor staining. 1. Becker SW. Concurrent melanosis and hypertrichosis in distribution of nevus We propose the following for clarification of termi- unius lateris. Arch Derm Syphilol. 1949;60(2):155-160. 2. Hsu S, Chen JY, Subrt P. Becker’s melanosis in a woman. J Am Acad Dermatol. nology pertaining to the Becker disorders: 2001;45(6)(suppl):S195-S196. 1. Becker melanosis: We suggest this designation be 3. McKee PH, Calonje E, Granter SR, eds. Pathology of the Skin: With Clinical Correlations. 3rd ed. Edinburgh, Scotland: Elsevier Mosby; 2005. restricted to pigmentary macular changes. This term 4. Rathi S. Becker’s nevus on the lower extremity: an uncommon site. J Dermatol. would apply to hyperpigmentation in the regions iden- 2002;29(7):461-462. tified by Becker1 and by Happle10 in his discussion of mo- 5. Happle R. Epidermal nevus syndromes. Semin Dermatol. 1995;14(2):111-121. saic patterns. This term would include, but not be lim- 6. Happle R, Koopman RJ. Becker nevus syndrome. Am J Med Genet. 1997;68(3): 357-361. ited to, prepubertal hyperpigmented macules. 7. Urbani CE, Betti R. Supernumerary nipple in association with Becker nevus vs. 2. Becker nevus: We suggest this term be applied to Becker nevus syndrome: a semantic problem only. Am J Med Genet. 1998; cases with clinical macular pigmentation and associated 77(1):76-77. contiguous adnexal changes involving follicular compo- 8. Happle R, Koopman RJ. Becker nevus syndrome and supernumerary nipples. nents (hypertrichosis), smooth muscle hamartomas, des- Am J Med Genet. 1998;77(1):78. 9. Sugarman JL. Epidermal nevus syndromes. Semin Cutan Med Surg. 2007;26(4): moid tumors, dermal and subcutaneous alterations, and 221-230. epidermal tumors. This category would include the case 10. Happle R. Patterns on the skin: new aspects of their embryologic and genetic described in this report. causes [in German]. Hautarzt. 2004;55(10):960-961, 964-968. 3. Becker nevus syndrome: We suggest this term be used 11. Haneke E. The dermal component in melanosis naeviformis Becker. J Cutan Pathol. 1979;6(1):53-58. when, in addition to the above 2 categories (ie, Becker 12. de la Espriella J, Grossin M, Marinho E, Belaïch S. Smooth muscle hamartoma: melanosis and Becker nevus), associated abnormalities anatomoclinical characteristics and nosological limits [in French]. Ann Derma- identified by Happle and Koopman8 and by Sugarman9 tol Venereol. 1993;120(12):879-883.

(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 12), DEC 2010 WWW.ARCHDERMATOL.COM 1411

©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 13. Slifman NR, Harrist TJ, Rhodes AR. Congenital arrector pili hamartoma: a case and Atlas of Lever’s Histopathology of the Skin. Philadelphia, PA: Lippincott Wil- report and review of the spectrum of Becker’s melanosis and pilar smooth- liams & Wilkins; 1999. muscle hamartoma. Arch Dermatol. 1985;121(8):1034-1037. 20. Miettinen M. Antibody specific to muscle actins in the diagnosis and classifica- 14. Elder DE, Murphy GF. Melanocytic Tumors of the Skin. Washington, DC: Armed tion of soft tissue tumors. Am J Pathol. 1988;130(1):205-215. Forces Institute of Pathology; 1991:211. Atlas of Tumor Pathology;3rdser,pt 21. Ferenc T, Wron´ski JW, Kopczyn´ski J, et al. Analysis of APC, alpha-, beta- 2. catenins, and N-cadherin protein expression in aggressive fibromatosis (des- 15. Lips DJ, Barker N, Clevers H, Hennipman A. The role of APC and beta-catenin in moid tumor). Pathol Res Pract. 2009;205(5):311-324. the aetiology of aggressive fibromatosis (desmoid tumors). Eur J Surg Oncol. 22. Lazar AJ, Hajibashi S, Lev D. Desmoid tumor: from surgical extirpation to mo- 2009;35(1):3-10. lecular dissection. Curr Opin Oncol. 2009;21(4):352-359. 16. Cheon SS, Cheah AY, Turley S, et al. Beta-catenin stabilization dysregulates mes- 23. Person JR, Longcope C. Becker’s nevus: an androgen-mediated hyperplasia with enchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. Proc Natl Acad Sci U S A. 2002; increased androgen receptors. J Am Acad Dermatol. 1984;10(2, pt 1):235- 99(10):6973-6978. 238. 17. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors. 5th ed. Phila- 24. Nirde´ P, Dereure O, Belon C, Lumbroso S, Guilhou JJ, Sultan C. The association delphia, PA: Mosby Elsevier; 2008. of Becker nevus with hypersensitivity to androgens. Arch Dermatol. 1999;135 18. Folpe AL, Inwards CY, eds. Bone and Soft Tissue Pathology. Philadelphia, PA: (2):212-214. Saunders/Elsevier; 2010. 25. Leithner A, Gapp M, Radl R, et al. Immunohistochemical analysis of desmoid 19. Elder D, Elenitsas R, Johnson B Jr, Ioffreda M, Miller JJ, Miller OF III. Synopsis tumours. J Clin Pathol. 2005;58(11):1152-1156.

Correction

Errors in Byline, Text, and Data. In the Evidence- Based Dermatology: Review article titled, “Retrospec- tive Analysis of the Association Between Demodex Infes- tation and Rosacea,” by Zhao et al, published in the August issue of the Archives (2010;146[8]:896-902), several errors occurred. In the byline on page 896 and in the correspondence in the right-hand column on page 901, the first author’s name should have read as follows: Ya E Zhao, MPH. On page 897, right-hand column, “Sensitivity Analysis” subsection of the “Methods” section, the sentence should have read as follows: “Four approaches were applied to identify the sensitivity of the studies: we com- pared the pooled effect sizes (1) with different statisti- cal models; (2) of Chinese- and English-language articles; (3) before and after excluding studies of small sample size; and (4) of studies using the cellophane tape method, skin pressurization, and skin surface biopsy.” Beginning with the third sentence of the “Sensitivity Analysis” subsection of the “Results” section, the text should have read as follows: “Twenty-eight of 48 articles included had a sample size smaller than 40 (OR, 6.96; 95% CI, 3.69-13.15). After these articles were ex- cluded, the pooled OR of the remaining ones was 8.42 (95% CI, 5.49-12.90) (Figure 4), which was not signifi- cantly different from that of 7.57 (5.39-10.62) in the pre- exclusion meta-analysis. The ORs of studies using the cellophane tape method13,15-18,20,21,23-26,28,30-32,34-36,39,40,42,49 (OR, 9.29; 95% CI, 5.60-15.40), skin pressurization tech- nique10,22,37,38,43-48,50-56 (5.24; 2.85-9.63), and skin surface biopsy4,7,9,14,19,27,29,33,41 (8.87; 3.28-24.01) were coincident.”

(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 12), DEC 2010 WWW.ARCHDERMATOL.COM 1412