Dermatology Online Journal

Benign lymphoepithelial tumor of the skin ("cutaneous lymphadenoma")
Ramon M. Pujol, M.D., Xavier Matias-Guiu, M.D., Rosa Taberner, M.D., Agustín Alomar M.D.
Dermatology Online Journal 5(1): 5

Abstract

"Benign lymphoepithelial tumor of the skin" or "cutaneous lymphadenoma" is a distinctive benign adnexal tumor presenting a characteristic combination of lobules of epithelial basaloid cells with a peculiar histopathological pattern and a dense intraepithelial T-cell lymphoid and histiocytic population.

We report an additional example of this peculiar neoplasm. In addition to the characteristic histopathological features, focal areas showing unequivocal follicular differentiation were observed at the periphery of the tumor. In agreement with other authors we consider that this neoplasm should be included within the spectrum of neoplasms of pilosebaceous origin. Nevertheless, we consider that the original and simple concept of "benign lymphoepithelial tumor of the skin" seems more suitable and illustrative than the more widely used term of "cutaneous lymphadenoma" to define this rare benign adnexal neoplasm.

Introduction

"Benign cutaneous lymphoepithelial tumor of the skin"[1] or "cutaneous lymphadenoma"[2] is a rare benign adnexal tumor characterized by a peculiar pattern of lobules of epithelial basaloid cells admixed with a dense lymphocytic and histiocytic intraepithelial cell population.

Since the original description, the histogenesis of this benign cutaneous adnexal tumor has been a matter of debate.[1-14] Some studies have related "cutaneous lymphadenoma" to basal cell carcinoma[9] or desmoplastic trichoepithelioma. Other authors stated that this neoplasm is a trichoblastoma with adamantinoid features.[11-13] Additional studies have considered cutaneous lymphadenoma as a neoplasm related to an immature sweat tumor that could correspond to a peculiar "lymphotropic solid syringoma".[4]

Case Report

A 34 year-old woman was referred to our Department with a 3 year history of a solitary slowly growing papule on the frontal area.

Physical examination revealed an apparently healthy women with a solitary, firm, skin-colored, dome-shaped papule, 0.6 x 0.6 cm in diameter on the right frontal area. Several telangiectatic vessels were noted overlying the tumor. The rest of the physical examination revealed no abnormalities. The family history and past medical history were non-contributory.

The clinical diagnosis was basal cell carcinoma or "adnexal tumor" and a complete surgical excision was performed.

Results

Figure 1	Figure 2
Tumor composed of irregular epithelial lobules and nests of varying sizes and shapes (H-E x 40).	Epithelial lobules bounded by peripheral rows of palisaded basaloid cells and a central core with a pseudo-cystic appearance (H-E x100).

Histological examination disclosed an unencapsulated tumor composed of irregular epithelial lobules and nests of varying sizes and shapes within a fibrous stroma involving the reticular dermis. These lobules were bounded by one to three peripheral rows of palisaded basaloid cells around a central core where the cells adopted a loosely arranged pseudocystic pattern. Within these lobules, two different cell types were noted: large cells and small lymphoid cells. The large cells exhibited clear cytoplasm and large vesicular nucleoli. No cellular atypia was observed. The tumor lobules were surrounded by a dense fibrous stroma containing numerous lymphoid cells.

Figure 3	Figure 4
Follicular differentiation (papillary induction) at the periphery of the tumor (H-E x100).	Keratin expression by the epithelial component of the tumor (AE1-AE3 x 100).

At the periphery of the tumor some solid basaloid nodules were noted. Follicular germ formation and papillary induction were occasionally noted. No sweat gland ducts were noted within the tumor.

Figure 5	Figure 6
Intraepithelial lymphoid cells express T-cell markers (CD3 x 100).	Scattered S-100+ dendritic cells in the stroma and within the epithelial islands (S-100 x 100).

Figure 7
Positive CD34 staining in the surrounding stroma of the tumor. No expression in the perilobular mesenchymal cells (CD34 x 40).

Immunohistochemical studies revealed that tumor cells stained positively for epithelial markers AE1/AE3. The intraepithelial lymphoid component was highlighted with anti-common leukocyte antigen (CLA) and CD3 monoclonal antibodies. Lymphoid cells were CD20 negative. Isolated CD30+ large cells were rarely observed within the lobules. S-100 protein staining revealed several large dendritic cells in the stroma and within the epithelial islands. Carcinoembryonic antigen (CEA) and low-molecular-weight cytokeratin (CAM 5.2) were negative. Positive CD34 staining was observed in the normal surrounding stroma of the tumor, but no expression was detected in the perilobular mesenchymal cells.

Comment

Lymphoepithelial tumor of the skin[1] was originally described in 1987 by Santa Cruz and Barr as a new adnexal tumor characterized by a dual cellular component of epithelial and lymphoid cells. Subsequently, the tumor was given the designation "cutaneous lymphadenoma." [2,8]

This tumor is manifested clinically by a single, small, non-ulcerated, slowly enlarging nodule, mainly located on the head. The age of the diagnosis ranges between 21 and 75 years without a sex predominance. It is a benign tumor that does not tend to recur after surgical excission.[8]

Histologically, it is characterized by a well-defined, non-encapsulated intradermal nodule, formed by oval or round-shaped lobules and nests with a pseudocystic or bag-like appearance.[2,3] In some cases, a connection to the underlying epidermis[7] or to pilosebaceous units has been observed.[2]

Most of the lobules were limited by one to three layers of basaloid cells with a tendency to peripheral palisading and a central area with loosely attached cells. Within the lobules, two populations of cells could be distinguished: large cells intermingled with small lymphoid cells. The large cells were distinguished by clear cytoplasm and large vesicular nuclei. A dense fibrous stroma composed of dense collagen fibers, fibroblasts, lymphocytes and a few of large clear epithelial cells is also a characteristic feature. Focal mucinosis,[5] osteoma formation,[6] or a prominent sweat gland duct component[7] entrapped by the tumor have occasionally been noted.

Immunohistochemical studies support the presence two distinct cellular patterns. Cytokeratin markers label the clear epithelial cells in the lobules and the basaloid peripheral cells, whereas the lymphoid component reacted with common leukocyte antigen ( CLA) and T-cell markers (UCHL-1, CD3). Recently, some intralobular CD30+ large clear cells have been detected, probably corresponding to activated lymphoid cells.[14] Many large epithelial cells in the lobules and some dendritic cells in the stroma are S-100 positive. In our case, CD34 expression was negati ve in the immediate perilobular tumoral stroma with a pattern similar to that reported in basal cell carcinoma and trichoblastoma.[15]

The histogenesis of this neoplasm is still controversial. In spite of some authors having postulated that it corresponds to a rare form of basal cell carcinoma[9] or even a neoplasm with sudoriparous ductal differentiation,[4,7] most reports favor a differentiation towards pilosebaceous structures.[1-3,5,6,8-14] The presence of central keratinization in some lobules, characteristic centrolobular whorled cellular aggregates simulating squamous eddies, the rare presence of sebaceous cells within the tumor, the occasional obse rvation of follicular germs and abortive attempts to form papillary mesenchyme are features that support this latter opinion.[2,6,10] In addition, the dermal perilobular stroma shares histological features with perifollicular sheath connective tissue.

Ackerman et al[11] considered that cutaneous lymphadenoma is a variant of trichoblastoma ("adamantinoid trichoblastoma"). Some authors used this denomination[12] or "trichoblastoma with adamantinoid features"[13] to designate this neoplasm. Other authors pointed out the histologic resemblance between this tumor and desmoplastic trichoepithelioma.In our case we have observed unequivocal areas of follicular differentiation and an immunohistochemical CD34 expression pattern identical to that observed in basal cell carcinoma[17] but not in trichoepithelioma.

Therefore we recommend that this entity should be included within the spectrum of immature follicular tumors. In our opinion cutaneous lymphadenoma can not be considered as a merely "adamantinoid trichoblastoma" as this would overlook a relevant and characteristic feature: the intratumoral lymphoid component. This lymphoid component is usually not observed in adamantinoid variants of other adnexal neoplasms (i.e. adamantinoid basal cell carcinoma[16]) and is a unique feature of this neoplasm. In addition, we consider the original and simple concept of "benign lymphoepithelial tumor of the skin"[1] to be more suitable and illustrative than the more widely used term "cutaneous lymphadenoma"[2] (which implies an unproven glandular differentiation) to define this benign adnexal neoplasm.

References

1, Santa Cruz DJ, Barr RJ. Lymphoepithelial tumor of the skin (abstr.). J Cutan Pathol 1987; 14: 345.

2. Santa Cruz DJ, Barr RJ, Headington JT. Cutaneous lymphadenoma. Am J Surg Pathol 1991; 15: 101-110.

3. Civatte J, Moulonguet-Michau I, Marinho E, Cavelier-Balloy B, Verola O. Tumeur Épithélio-lympho-histiocytaire. Ann Dermatol Venereol 1990; 117: 441-4.

4. Tsang WYW, Chan JKC. So-called cutaneous lymphadenoma: a lymphotropic solid syringoma. Histopathology 1991; 19: 382-5.

5. Wechsler J, Fromont G, AndrJ JM, Zafrani ES. Cutaneous lymphadenoma with focal mucinosis. J Cutan Pathol 1992; 19: 142-4.

6. Massouyé I. Cutaneous lymphadenoma: report of 2 cases. Dermatology 1992; 185: 62-5.

7. Requena L, Sanchez Yus E. Cutaneous lymphadenoma with ductal differentiation. J Cutan Pathol 1992; 19: 429-33.

8. Botella R, Mackie RM. Cutaneous lymphadenoma: a case report and review of the literature. Br J Dermatol 1993; 128: 339-41.

9. Aloi F, Tomasini C, Pippione M. Cutaneous lymphadenoma. A basal cell carcinoma with unusual inflammatory pattern ?. Am J Dermatopathol 1993; 15: 353-7.

10. Filosa G, Bugati L, Ciattagia G. Epithelio-lympho-hystiocytic tumor: a controversial entity. Eur J Dermatol 1994; 4: 376-8.

11. Ackerman AB, de Viragh PA., Chongchitnant N. Neoplasms with follicular differentiation. Philadelphia: Lea & Febiger, 1993: 400-3.

12. Diaz-Cascajo C, Borghi S, Rey-Lopez A, Carretero-Hernández G. Cutaneous lymphadenoma. A peculiar variant of nodular trichoblastoma. Am J Dermatopathol 1996; 18: 186-91.

13. Betti R, Alessi E. Nodular trichoblastoma with adamantinoid features. Am J Dermatopathol 1996; 18: 192-5.

14. Rodriguez-Diaz E, Roman C, Yuste M, Morán AG, Aramendi T. Cutaneous lymphadenoma. An adnexal neoplasm with intralobular activated lymphoid cells. Am J Dermatopathol 1998; 20: 74-8.

15. Schirren CG, Rutten A, Kaudewitz P, Diaz C, McClain S, Burgdorf WH. Trichoblastoma and basal cell carcinoma are neoplasms with follicular differentiation sharing the same profile of cytokeratin intermediate filaments. Am J Dermatopathol 1997; 19: 341-50.

16. Kirchmann TT, Prieto VG, Smoller BR. CD34 staining pattern distinguishes basal cell carcinoma from trichoepithelioma. Arch Dermatol 1994; 130:589-92.

17. Lerchin E, Rahbari H. Adamantinoid basal cell epithelioma. Arch Dermatol 1975; 111: 586-8.