Basaloid Follicular Hamartoma: a Case Report and Review of the Literature

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provided by Elsevier - Publisher Connector Kaohsiung Journal of Medical Sciences (2012) 28,57e60

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CASE REPORT Basaloid follicular hamartoma: A case report and review of the literature

Shu-Han Huang a, Tien-Fa Hsiao b, Chin-Cheng Lee a,*

a Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan b Department of General Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

Received 2 September 2010; accepted 1 December 2010 Available online 11 December 2011

KEYWORDS Abstract Basaloid follicular hamartoma (BFH) is a rare, benign, skin adnexal tumor. Several Basaloid follicular clinical patterns have been reported, but they all share the same histopathological features. hamartoma; BFH may be hereditary or nonhereditary and can be accompanied by systemic diseases. Micro- Infundibulocystic basal scopic examination of BFH shows branching cords and anastomosing strands of basaloid cells in cell carcinoma; a loose, ﬁbrous stroma. The most important pathological differential diagnosis is infundibulo- Skin adnexal tumor cystic basal cell carcinoma. These two lesions must be differentiated carefully based on clinical presentation and histopathological picture, and even molecular studies may be needed. We present a report of a 78-year-old woman with a solitary, asymptomatic, slow- growing skin tumor on her left scalp. No associated systemic disorders were found. On the basis of an excisional biopsy performed on the tumor, a pathological diagnosis of sporadic BFH was made. Copyright ª 2011, Elsevier Taiwan LLC. All rights reserved.

Introduction and also because the occurrence of BFH is very rare. In this article, we present a case of a solitary BFH on the left scalp Basaloid follicular hamartoma (BFH) is a malformation of in a patient and review the clinical presentation and a hair follicle and is restricted to the superﬁcial dermis histopathological differential diagnosis. [1,2]. BFH can be associated with several systemic diseases, such as myasthenia gravis, systemic lupus erythematosus, Case presentation and alopecia. There is a likelihood that the incidence of BFH may be underestimated because of its benign course A 78-year-old woman had a skin tumor on her left scalp for more than 2 years. The tumor was stable and asymp- * Corresponding author. Department of Pathology and Laboratory tomatic without itching or tenderness. She presented to Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen- the Department of General Surgery at Shin-Kong Wu chang Road, Shilin District, Taipei City 11101, Taiwan. Ho-Su Memorial Hospital for management in December E-mail address: [email protected] (C.-C. Lee). 2009. Physical examination showed a smooth surfaced,

1607-551X/$36 Copyright ª 2011, Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.kjms.2011.06.034 58 S.-H. Huang et al. erythematous papule measuring 0.6 cm in diameter on the temporofrontal area of the left scalp. It was well defined and elastic on palpation. There was no other similar skin lesion. The patient did not have alopecia, ptosis, dysphagia, or diplopia. She had no family history on record for similar lesions. An excisional biopsy of the tumor was done, and the specimen was sent for histopathological examination. Microscopically, the tumor was characterized by branching cords and anastomosing strands of basaloid cells embedded in a loose, fibrous stroma. The tumor was well demarcated and located in the superficial dermis (Fig. 1). The cords and strands were formed by two to four layers of basaloid cells (Fig. 2). Peripheral palisading was not seen. Horn cysts and abortive hair follicleelike structures were present in the tumor (Fig. 3). No mucinous areas were identified. There were no cleft-like spaces between the Figure 2. The cords and strands are composed of a few stroma and the epithelial strands. The epidermis was layers of basaloid cells. The tumor cells are relatively uniform atrophic but intact. The tumor was not associated with the with bland-looking nuclei. The stroma is hypocellular and hair follicles nor was it connected with the epidermis. The myxoid. There is no cleft between epithelial strands and tumor cells were uniform with bland-looking nuclei and stroma (hematoxylin and eosin: 400Â). eosinophilic cytoplasm. No squamoid cell was identified. Mitoses were absent. Immunohistochemical stains for Ki-67 (Cellular marker for proliferation), Bcl-2 (B-cell lymphoma 2), CD34, and CD10 were performed (Fig. 4). Very few tumor cells showed nuclear positivity for Ki-67, and only the peripheral tumor cells showed weak cytoplasmic positivity for Bcl-2. The stromal cells showed positive staining against CD34. CD10 stained weakly for the stromal cells but not the tumor cells. Based on the histopathological features, immunohistochemical studies, and stable clinical presentation, a diagnosis of a solitary BFH was made.

Discussion

BFH is a unique, benign, skin adnexal tumor. In 1969, this tumor was ﬁrst reported under the title “generalized hair follicle hamartoma” with associated alopecia, aminoacid- uria, and myasthenia gravis [3]. Mehregan and Baker [1] ﬁrst used the term “basaloid follicular hamartoma” to

Figure 3. (A) A horn cyst with keratin can be seen in the tumor. The overlying epidermis is intact (hematoxylin and Figure 1. The scalp tumor comprising branching cords and eosin: 100Â). (B) Keratinizing material surrounded by anastomosing strands sitting in the superﬁcial dermis. The tumor cells that form an abortive hair follicleelike structure border is clear (hematoxylin and eosin: 40Â). (hematoxylin and eosin: 400Â). Basaloid follicular hamartoma 59

Figure 4. Immunohistochemical stains. (A) Very few tumor cells show nuclear positivity for Ki-67 (400Â); (B) Low-power view of Bcl-2 shows that only the peripheral tumor cells are weakly positive (Bcl-2: 100Â); (C) The stroma cells showing positive staining for CD34 (400Â); (D) The stromal cells showing weak positive staining for CD10 and the tumor cells that are negative (CD10: 400Â). report of similar skin tumors in 1985. Since then, only a few Solitary BFH was first described in 1992 as a smooth cases have been reported. Morohashi et al. [2], based on plaque or a papule appearing most commonly on the face or ultrastructural and immunohistochemical studies, thought scalp as in our case [5]. The incidence of solitary BFH may that BFH was an abortive growth of secondary hair germs be underestimated because solitary BFH is usually asymp- with a limited differentiation toward the upper follicular tomatic and stable. portion of the hair shaft. Although there are many clinical forms of BFH, they all The pathogenesis of BFH is found to be associated with share the same unique histopathological features as previ- the patched (PTCH: Protein patched homolg) gene muta- ously described in our case. BFH is a folliculocentric tumor tion on chromosome 9q23. The PTCH gene encodes limited to superficial dermis. Deep reticular dermis or soft a receptor involved in the sonic hedgehog-patched-Gli tissue involvement is not typical of this disease. In early (Products of Glioma-associated oncogene) signal pathway lesions, the branching cords of basaloid cells connecting [4]. Mutations in this signal pathway can lead to abnormal the central pilosebaceous structures can be seen. In long- growth and patterning of cells. standing cases, the central pilosebaceous structures may BFH may manifest in multiple clinical presentations, be totally replaced by the tumor [14]. such as multiple lesions with a generalized or localized Histopathological differential diagnosis includes (1) tri- distribution, or as a solitary lesion. Several forms of choepithelioma, (2) fibrofolliculoma, (3) fibroepithelioma generalized BFH have been described: (1) sporadic form: of Pinkus, (4) folliculocentric basaloid proliferation, and (5) multiple BFHs without systemic disease [5]; (2) acquired infundibulocystic basal cell carcinoma (IFBCC). form: female patients with generalized BFHs associated Trichoepitheliomas are usually larger than BFH. The with alopecia and autoimmune diseases, such as myas- tumor islands of basaloid cells may have “swiss cheese” or thenia gravis or systemic lupus erythematosus [6,7]; (3) lace-like pattern with no branching tumor strands. The familial form: an autosomal dominant disease that may or stroma of trichoepithelioma is more cellular than that of may not be associated with hypotrichosis, hypohidrosis, and BFH [5,15]. palmoplantar pitting [8e10]; and (4) congenital form: Fibrofolliculoma is another type of tumor with epithelial generalized BFHs associated with alopecia and cystic strands embedded in a fibrous stroma. Compared with BFH, fibrosis [11]. fibrofolliculoma has much more prominent stroma and less The localized forms of BFH present as linear unilateral amount of epithelial strands [5]. In some areas, no lesions or as plaques with alopecia [1,2,12,13]. The linear epithelial strands can be found [15]. unilateral type of BFH is associated with lines of Blaschko Fibroepithelioma of Pinkus is a variant of basal cell and presents at birth or appears in early childhood carcinoma (BCC), which is characterized by arborizing cords [1,12,13]. of basaloid cells from epidermis and may be identical to 60 S.-H. Huang et al.

BFH microscopically. However, eccrine ducts, which are not References seen in BFH, may be present in some epithelial cords of fibroepithelioma of Pinkus. In addition, fibroepithelioma of [1] Mehregan AH, Baker S. Basaloid follicular hamartoma: three Pinkus is surrounded by more prominent fibrovascular cases with localized and systematized unilateral lesions. stroma [10,15]. J Cutan Pathol 1985;12:55e65. Folliculocentric basaloid proliferation occurs in the skin [2] Morohashi M, Sakamoto F, Takenouchi T, Hashimoto T, Tago O, adjacent to a BCC [16]. It is a reactive lesion characterized Ito M. A case of localized follicular hamartoma: an ultra- by folliculocentric, vertically oriented basaloid aggregates structural and immunohistochemical study. J Cutan Pathol e with histologically unaltered stroma [16]. Most of the 2000;27:191 8. basaloid aggregates are surrounded by a prominent hyaline [3] Brown AC, Crounse RG, Winkelmann RK. Generalized hair- follicle hamartoma, associated with alopecia, aminoacid- basement membrane. The folliculocentric basaloid prolif- uria, and myasthenia gravis. Arch Dermatol 1969;99:478e93. eration has no keratin cysts, which is the most notable [4] Grachtchouk V, Grachtchouk M, Lowe L, Johnson T, Wei L, difference from BFH [16]. Wang A, et al. The magnitude of hedgehog signaling activity The most important histopathological differential diag- defines skin tumor phenotype. Eur Mol Biol Organ 2003;22: nosis of BFH is the IFBCC. IFBCC is formed by cords and 2741e51. strands of basaloid cells embedded in a loose, fibrous [5] Brownstein MH. Basaloid follicular hamartoma: solitary and stroma, as in BFH [15]. Horn cysts can also be found in multiple types. J Am Acad Dermatol 1992;27:237e40. IFBCC. IFBCC is not a folliculocentric tumor like BFH and [6] Ridley CM, Smith N. Generalized hair follicle hamartoma may be located in the interfollicular dermis [10]. Pilose- associated with alopecia and myasthenia gravis: report of e baceous structures are usually destroyed by the tumor cells a second case. Clin Exp Dermatol 1981;6:283 9. [7] Morton S, Stevens A, Powell RJ. Basaloid follicular hamar- and, thus, are not seen in IFBCC. Deep infiltration, toma, total body hair loss and SLE. Lupus 1998;7:207e9. epidermal ulceration, and clinical rapid growth also imply [8] Girardi M, Federman GL, McNiff JM. Familial multiple basaloid a diagnosis of IFBCC [10,15]. Immunohistochemical stains follicular hamartomas: a report of two affected sisters. using proliferative antibodies, such as Ki-67, and prolifer- Pediatr Dermatol 1999;16:281e4. ating cell nuclear antigen have a more intense reaction in [9] Wheeler Jr CE, Carroll MA, Groben PA, Briggaman RA, IFBCC than in BFH [14]. Bcl-2 stains only the outermost Prose NS, Davis DA. Autosomal dominantly inherited general- tumor cells of BFH but is more prominent in BCC [17]. The ized basaloid follicular hamartoma syndrome: report of a new stromal cells of the BFH stain positive for CD34, but the disease in a North Carolina family. J Am Acad Dermatol 2000; e stromal cells of BCC are negative. CD10 stains both the 43:189 206. stromal and tumor cells of BCC, whereas it stains only [10] El-Darouti MA, Marzouk SA, Abdel-Halim MR, Zidan AZ, Fawzy MM. Basaloid follicular hamartoma. Int J Dermatol weakly in the stromal cells of BFH [17]. At the molecular 2005;44:361e5. level, both IFBCC and BFH have abnormal PTCH signaling [11] Mascaro´ JM, Ferrando J, Bombi JA, Lambruschini N, pathways. However, the degree of aberrant overexpression Mascaro´ JM. Congenital generalized follicular hamartoma of PTCH mRNA is higher in IFBCC [14]. associated with alopecia and cystic fibrosis in three siblings. The clinical significance of BFH is that it can be mistaken Arch Dermatol 1995;131:454e8. for BCC clinically and histologically, especially the IFBCC [12] Jimeńez-Acosta FJ, Redondo E, Baez O, Hernandez B. Linear subtype. They must be differentiated carefully because BFH unilateral basaloid follicular hamartoma. J Am Acad Dermatol is a benign tumor, and BCC is malignant. Excisional biopsy 1992;27:316e9. with adequate resection margin is needed for BCC because it [13] Lee MW, Choi JH, Moon KC, Koh JK. Linear basaloid follicular is a locally invasive tumor and rarely can metastasize. hamartoma on the Blaschko’s line of the face. Clin Exp Dermatol 2005;30:30e4. Moreover, about half of the patients who are diagnosed with [14] Jih DM, Shapiro M, James WD, Levin M, Gelfand J, Williams PT, BCC may develop new lesions within 5 years [18]. Avoiding et al. Familial basaloid follicular hamartoma: lesional char- sun exposure and regular skin screening are recommended acterization and review of the literature. Am J Dermatopathol for patients with BCC. On the other hand, BFH is clinically 2003;25:130e7. stable and limited in the superficial dermis. Surgical treat- [15] Elston DM. Malignant tumors of the epidermis, benign pilar ment is not usually needed except for cosmetic reasons or to and sebaceous neoplasms. In: Elston DM, Ferringer T, Ko CJ, exclude other skin tumors. We present a report of this rare Peckham S, High WA, DiCaudo DJ, et al., editors. Dermato- skin tumor to emphasize its unique histopathological picture pathology. 1st ed. Philadelphia, PA: Saunders Elsevier; 2009: e e and benign nature. When multiple BFH lesions are present, 64 5, 71 6. clinicians should be aware that they may be associated with [16] Leshin B, White WL. Folliculocentric basaloid proliferation: the bulge(der Wulst) revisited. Arch Dermatol 1990;126:900e6. systemic diseases. BCC can rarely develop in BFH [19]. [17] Ramos-Ceballos F, Pashaei S, Kincannon J, Morgan M, Biopsy should be done on rapidly growing lesions or lesions Smoller B. Bcl-2, CD34 and CD10 expression in basaloid that exhibit a change in clinical appearance [10]. follicular hamartoma, vellus hair hamartoma and neuro- follicular hamartoma demonstrate full follicular differentia- Acknowledgments tion. J Cutan Pathol 2008;35:477e83. [18] Mc Loone NM, Tolland J, Walsh M, Dolan OM. Follow-up of basal cell carcinomas: an audit of current practice. J Eur Acad The authors thank Dr Shu-Wen How and Dr Cheng-Hsiang Dermatol Venereol 2006;20:698e701. Hsiao, Department of Pathology, National Taiwan University [19] Nelson BR, Johnson TM, Waldinger T, Gillard M, Lowe L. Hospital (NTUH), for their help in the diagnosis of this Basaloid follicular hamartoma: a histologic diagnosis with tumor, and Dr Cecile Logan for her help in the writing and diverse clinical presentations. Arch Dermatol 1993;129: preparation of the English manuscript. 915e7.