Cutaneous lymphoid hyperplasia

ARTICLE

A 37-year-old man presented with a 2-year history of a slowly enlarging asymptomatic plaque on the right shoulder. He reported that the lesion had begun with a small papule gradually spreading to involve most of the scapular site with central regression. His medical background was unremarkable. Physical examination revealed a 11 x 8 cm plaque on the right shoulder with erythematous follicular papules and raspberry-like nodules. Besides, a keratosis follicularis was observed (Fig. 1). No adenopathy or organomegaly was detected. Laboratory evaluation, including routine parameters, lymphocytes differentiation, serology for HIV and Borrelia Burgdorferi, all were within normal limits. Three nodules were excised and histopathologically examined (Figs. 2 and 3).

Cutaneous lymphoid hyperplasia

The microscopic examinations revealed dense and diffuse infiltrates of cytologically benign-appearing lymphocytes and scattered histiocytes in the upper and mid dermis (Fig. 2). Sporadically, germinal formation was noted in the deep dermis. The epidermis and pilosebaceous units were not involved by the infiltrative process. Immunohistochemical analyses showed a mixture of CD20 (B-cell marker) and CD3 (T cell marker) positive lymphocytes (Fig. 3). MIB-1 proliferation marker was not expressed. PCR of lesional skin for Borrelia Burgdorferi was unremarkable. There was no monoclonal rearrangement of the T cell receptor gene. The follicular papules completely cleared after cream PUVA therapy (cumulative UVA dose 59 J/cm²).

Depending on the predominant cell type in the infiltrate, cutaneous pseudolymphomas are divided into B-cell and T cell pseudolymphomas. Cutaneous lymphomatoid hyperplasia (CLH) falls into the spectrum of B-cell pseudolymphomas, including other lymphoid proliferations such as borrelial lymphocytoma cutis, tattoo-induced lymphozytoma cutis and post-zoster scar lymphozytoma. T cell pseudolymphomas include for example idiopathic cutaneous T cell pseudolymphoma, lymphomatoid drug reaction, lymphomatoid contact dermatitis and persistent nodular arthropod-bite reactions. Correspondingly, apart from idiopathic forms of pseudolymphoma, various stimuli have been implicated including insect bites (i.e. borreliosis), trauma, tattoo reactions and injected drugs. However, the cause of the disease frequently remains obscure. CLH is a benign infiltrative process which is clinically characterized by isolated or few erythematous nodules or plaques favoring the face and extremities. Generally, the patients are in good health without evidence of systemic involvement and the clinical course is characterized by spontaneous remission.

Pseudolymphoma has to be distinguished from cutaneous lymphomas by the combination of clinicopathological correlation, histochemical studies, and, in selected cases, gene rearrangement studies [1, 2]. In contrast to B-cell and T cell pseudolymphomas, cutaneous lymphomas generally present with large or generalized lesions and a progressive clinical course. The lack of acanthosis, "bottom-heavy" infiltrates, light-chain expression of monotypical B-cells, and immunoglobulin gene rearrangements (75%) provide strong evidence for the diagnosis of B-cell lymphoma. T cell lymhoma can be usually distinguished from T cell pseudolymphoma by the presence of prominent epidermotropism, large and atypical lymphocytes, and T cell gene rearrangements up to 90%. As lymphomatous transformation has been noted in a few cases of pseudolymphoma, in selected patients in whom the benign nature of the lesions is not clear-cut, it may be prudent to establish that there is no concurrent extracutaneous involvement. A careful monitoring of these patients for the development of lymphoma is necessary [1, 2].

Our case illustrates a clinically unusual appearing CLH with a predominant follicular pattern which is also found in follicular T cell lymphoma [3]. This variant of T cell lymphoma frequently presents plaques with keratosis pilaris-like lesions. The histological examination usually reveals perifollicular and intrafollicular infiltrates composed of lymphocytes. Besides, the follicular lesions in our patient can be differentiated from pseudolymphomatous folliculitis showing histologically perifollicular clustering of T cell-associated dentritic cells with activation of pilosebaceous units [4]. Histologically, CLH shows diffuse dermal "top heavy" infiltrates of lymphocytes without atypia admixed with a variable number of histiocytes and plasma cells. Germinal center formation occurs frequently. Immunophenotypic studies in CLH usually reveal mixed T and B-cell infiltrates with the presence of at least a few clusters of B cells and polytopic B-cells [1, 2]. The proliferation indexes (i.e. MIB-1) in CLH are lower than the indexes of lymphoma [5]. A DNA analysis (PCR) for gene rearrangements in lymphoid proliferations can serve not only to recognize clonal populations in lymphomas but also to identify a subset of CLH patients with small clones [1, 2]. In the present case, comprehensive investigations could largely exclude a malignant lymphoid proliferation.

The treatment options for localized persistent pseudolymphomas are topical or intralesional corticosteroids, cryosurgery, interferon alfa, local radiation and surgical excision. For widespread lesions, PUVA, antimalarials, and cytotoxic agents have occasionally been used. However, in cases in which the cause of pseudolymphoma can be identified, removal of the causative agent usually leads to resolution [1].

Article accepted on 19/6/00

References

1. Ploysangam T, Breneman DL, Mutasim DF. Cutaneous pseudolymphoma. J Am Acad Dermatol 1998; 38: 877-905.

2. Bouloc A, Delfau-Larue MH, Lenormand B, Meunier F, Wechsler J, Thomine E, et al. Polymerase chain reaction analysis of immunoglobulin gene rearrangement in cutaneous lymphoid hyperplasias. Arch Dermatol 1999; 135: 168-72.

3. Hodak E, Feinmesser M, Segal T, Yosipovitch G, Lapidoth M, Maron L, et al. Follicular cutaneous T cell lymphoma: a clinicopathological study of nine cases. Br J Dermatol 1999; 141: 315-22.

4. Arai E, Okubo H, Tsuchida T, Kitamura K, Katayama I. Pseudolymphomatous Folliculitis. Am J Surg Pathol 1999; 23: 1313-9.

5. Kikuchi A, Nishikawa T. Apoptic and proliferating cells in cutaneous lymphoproliferative diseases. Arch Dermatol 1997; 133: 829-33.