Journal of the American Academy of Dermatology Volume 40, Number 6, Part 1
Cutaneous benign lymphoid hyperplasia is a B- cell pseudolymphoma of unknown origin.1 The most favored sites of involvement include the face.
We report two cases involving the nose that showed complete and stable regression after a 2- month treatment course with thalidomide.
CASE REPORTS
Case 1. A 17-year-old boy had an erythematous infiltrated plaque on the nose of 4 months’ duration (Fig 1). The patient’s physical examination showed no other abnormalities, and chest roentgenogram did not show any abnormality. Complete blood cell count was nor- mal. Borreliosis serology was negative. Histopathologic examination of a skin biopsy specimen showed a dense diffuse dermal infiltrate composed of small lympho- cytes without atypia. Immunophenotypic studies revealed a mixed T- and B-lymphocyte infiltrate expressing both κand λchains. The polymerase chain reaction (PCR) technique was performed to study immunoglobulin and T-cell receptor gene arrangement in the lesions and did not detect a dominant B- or T-cell clone. Antibiotics, topical steroids, and hydroxychloro- quine were used and failed to clear the lesions.
Treatment with oral thalidomide (100 mg/day) was ini- tiated after nerve conduction studies showed normal findings. Complete disappearance of the lesion was observed after 2 months. Thalidomide treatment was continued at a decreased dose (50 mg/day) for one addi-
tional month and then stopped. No adverse effects were observed. The lesion had not recurred after 36 months of follow-up.
Case 2. A 25-year-old woman had an erythematous infiltrated plaque on the nose of 8 months’ duration (Fig 2). Physical examination did not indicate any abnormal- ity. Findings from complete blood cell count, borreliosis serology, and chest roentgenography were normal.
Histopathologic examination of a skin biopsy specimen showed a dense diffuse dermal infiltrate composed of small lymphocytes without atypia. Immunophenotypic studies revealed a mixed T- and B-lymphocyte infiltrate with polytypic B cells. No dominant B- or T-cell clone Brief communications 1005
Treatment of cutaneous lymphoid hyperplasia with thalidomide: Report of two cases
Hakima Benchikhi, MD, Christine Bodemer, MD, PhD, Sylvie Fraitag, MD,
Janine Wechsler, MD, Marie-Hélène Delfau-Larue, MD, PhD, Nicolas Gounod, MD, Yves de Prost, MD, Jean Revuz, MD, and Martine Bagot, MD, PhD Créteil, France
Cutaneous benign lymphoid hyperplasia is a B-cell pseudolymphoma of unknown origin.
The most favored sites of involvement include the face. We report two cases involving the nose that showed complete and stable regression after a 2-month treatment course with thalidomide. (J Am Acad Dermatol 1999;40:1005-7.)
From the Departments of Dermatology, Pathology, and Immunology, Hôpital Henri Mondor, Créteil, Hôpital Necker, Paris, and the French Study Group for Cutaneous Lymphomas.
Reprint requests: Martine Bagot, MD, PhD, Department of Dermatology, Hôpital Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil, France.
Copyright © 1999 by the American Academy of Dermatology, Inc.
0190-9622/99/$8.00 + 0 16/54/97911
Fig 1. Case 1. A 17-year-old boy with cutaneous lymphoid hyperplasia lesion on the nose of 4 months’
duration.
Journal of the American Academy of Dermatology June 1999
radiation, and surgical excision have been reported successful in some cases.1
Thalidomide was first used as a sedative and then withdrawn after discovery of its teratogenic effects. During past decades, thalidomide has been found effective in various dermatologic disorders thought to have an autoimmune or inflammatory basis, such as erythema nodosum leprosum, pruri- go nodularis, actinic prurigo, discoid lupus erythe- matosus, aphthous stomatitis, Behçet’s syndrome, graft-versus-host disease, and Langerhans cell his- tiocytosis.4-6The relevant mechanism of action of thalidomide in these diseases remains unclear.
Thalidomide has been shown to inhibit the tumor necrosis factor–α production by human mono- cytes7 and to decrease the production of granulo- cyte-macrophage colony-stimulating factor and tumor necrosis factor–α in mixed epidermal cell–lymphocyte reactions.8 In addition, it has recently been shown that thalidomide potently suppresses the production of interleukin-12 from human peripheral blood mononuclear cells in a concentration-dependent manner.9 These results suggest that thalidomide may have therapeutic utility in disorders characterized by inappropriate cellular responses.
The efficacy of thalidomide in Jessner’s lym- phocytic infiltration of the skin has been demon- strated in a controlled study.10The dramatic effect of thalidomide in our two cases and in several other patients presenting with identical lesions of other locations (unreported observations) suggest that thalidomide may also be an efficient treatment of cutaneous lymphoid hyperplasia. Our observa- tions suggest that complete and definitive healing of the lesions is achievable after only a few weeks.
Because the teratogenic effects of thalidomide can be controlled, the neurotoxic effects of this drug are the most important limitation of its use.11As treatment of cutaneous lymphoid hyperplasia by thalidomide requires only a short period and no maintenance therapy, neurotoxic effects are not likely to be a limitation to the use of thalidomide in this indication.
REFERENCES
1. Ploysangam T, Breneman DL, Mutasim DF. Cutaneous pseudolymphomas. J Am Acad Dermatol 1998;38:877- 905.
2. Rijlaarsdam JU, Willemze R. Cutaneous pseudolym- phomas: classification and differential diagnosis. Semin Dermatol 1994;13:187-96.
3. Wood GS, Ngan BY, Tung R, Hoffman TE, Abel EA, was detected by PCR in the lesion. Antibiotics, topical
steroids, and hydroxychloroquine had no effect. The lesion had been excised, but had recurred. Treatment with oral thalidomide (100 mg/day) was initiated after verification of normal nerve conduction and absence of pregnancy. The patient previously received a combina- tion of ethinylestradiol and levonorgestrel birth control pills. Complete disappearance of the lesion was observed after 2 months. Thalidomide treatment was continued at a decreased dose (50 mg/day) for one addi- tional month and then stopped. No adverse effects were observed. The lesion had not recurred after 31 months of follow-up.
DISCUSSION
Cutaneous lymphoid hyperplasia clinically and histologically mimics cutaneous B-cell lym- phoma. In our two cases, the demonstration of polytypic B cells by immunophenotypical studies and the absence of a dominant clonal population by PCR favored the diagnosis of pseudo B-cell lymphoma.2 Cutaneous lymphoid hyperplasia most often runs a benign clinical course. However, the transition of pseudo B-cell lymphoma into malignant B-cell lymphoma has been reported, suggesting that some cases could represent an ini- tial step in tumor progression.3Topical or intrale- sional steroids, cryosurgery, interferon alfa, local 1006 Brief communications
Fig 2. Case 2. A 25-year-old woman with cutaneous lymphoid hyperplasia lesion on the nose of 8 months’
duration.
Journal of the American Academy of Dermatology Volume 40, Number 6, Part 1
Hoppe RT, et al. Clonal rearrangements of immunoglob- ulin genes and progression to B cell lymphoma in cuta- neous lymphoid hyperplasia. Am J Pathol 1989;135:13- 9.
4. Tseng S, Pak G, Washenik K, Pomeranz MK, Shupack JL. Rediscovering thalidomide: a review of its mecha- nisms of action, side effects, and potential uses. J Am Acad Dermatol 1996;35:969-79.
5. Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson JB, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunode- ficiency virus infection. N Engl J Med 1997;336:1487- 93.
6. Stevens RJ, Andujar C, Edwards CJ, Ames PR, Barwick AR, Khamashta MA, et al. Thalidomide in the treatment of the cutaneous manifestations of lupus erythematosus:
experience in sixteen consecutive patients. Br J Rheumatol 1997;36:353-9.
7. Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G.
Thalidomide selectively inhibits tumor necrosis factor
alpha production by stimulated human monocytes. J Exp Med 1991;173:699-703.
8. Charue D, Chauvin E, Duguet C, Revuz J, Bagot M.
Thalidomide decreases the production of GM-CSF and TNF-alpha in the mixed epidermal cell-lymphocyte reac- tion. Eur J Dermatol 1996;6:373-6.
9. Moller DR, Wysocka M, Greenlee BM, Ma X, Wahl L, Flockhart DA, et al. Inhibition of IL-12 production by thalidomide. J Immunol 1997;159:5157-61.
10. Guillaume JC, Moulin G, Dieng MT, Poli F, Morel P, Souteyrand P, et al. Crossover study of thalidomide vs placebo in Jessner’s lymphocytic infiltration of the skin.
Arch Dermatol 1995;131:1032-5.
11. Ochonisky S, Verroust J, Bastuji-Garin S, Gherardi R, Revuz J. Thalidomide neuropathy incidence and clinicoelectrophysiologic findings in 42 patients. Arch Dermatol 1994;130:66-9.
Brief communications 1007
