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Granulomatous Slack Skin S.J.C View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Erasmus University Digital Repository Clinical and Laboratory Investigations Dermatology 1998;196:382–391 Received: September 5, 1997 Accepted: November 29, 1997 C.W. van Haselen a J. Toonstra a Granulomatous Slack Skin S.J.C. van der Putte b Report of Three Patients with an Updated Review of the Literature J.J.M. van Dongen d C.L.M. van Hees c W.A. van Vloten a ooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo Abstract Departments of Purpose: Granulomatous slack skin (GSS) is a rare cutaneous disorder char- a Dermatology and b Pathology, University Hospital of Utrecht, acterized clinically by the evolution of circumscribed erythematous lax skin c Department of Dermatology, masses, especially in the body folds, and histologically by a granulomatous University Hospital of Leiden, and T-cell infiltrate and loss of elastic fibers. GSS is often associated with preceding d Department of Immunology, or subsequent lymphoproliferative malignancies, especially mycosis fungoides Erasmus University Rotterdam, (MF) and Hodgkin’s disease (HD). No effective treatment is known yet. Wheth- The Netherlands er this entity is a benign disorder, a peculiar host reaction to a malignant lym- phoma, a precursor of malignant lymphoma or an indolent cutaneous T-cell lym- phoma (CTCL) in itself is still a matter of debate. Patients and Methods: The results of the patients with GSS from the Netherlands are compared with the cases reported in the world literature. Results: A female patient had had GSS for 8 years without developing a secondary malignancy. In a second female patient with a histologically confirmed diagnosis of MF, GSS developed 18 years later in the axillary and inguinal folds which had previously been affected by plaque- stage MF lesions. A third male patient with a 6-year history of erythematosqua- mous skin disease diagnosed as CTCL developed GSS. Moreover, granuloma formation was also found in a facial basal cell carcinoma, in a cervical lymph node and the spleen. Clonal rearrangements of the T-cell receptor β genes were found in the 2 female patients; the male patient could not be tested. Conclusion: GSS is a rare clinicopathological entity. Only 34 patients have been described so far. The development of GSS within plaque MF lesions has not been reported before. Our third case developed very extensive skin lesions and showed a strong propensity to develop granulomas as compared to cases reported before. The presence of a clonal T-cell population was demonstrated in all cases tested. Our cases support the idea that GSS is a very rare and rather indolent type of oooooooooooooooooooooooooooooooooooooooooooo CTCL. Apparently, the disease is associated with a peculiar immune response, Key Words characterized by granuloma formation and disappearance of elastic fibers result- Granulomatous slack skin ing in the lax skin. The relationship between GSS and other preexisting or sub- Mycosis fungoides sequent lymphoproliferative diseases (diagnosed in approximately 50% of the Hodgkin’s disease cases) warrants a life-long follow-up. oooooooooooooooooooo Introduction folds, predominantly in the flexural areas and especially in the inguinal and axillary region. In long-standing disease, Granulomatous slack skin (GSS) is a rare cutaneous other skin areas can also become involved. Histological ex- disorder, characterized by slowly progressive indurated amination of early lesions shows a dense dermal infiltrate plaques which evolve into erythematous pendulous skin consisting of small- to medium-sized normochromatic © 1998 S. KargerAG, Basel C.W. van Haselen, MD 1018–8665/98/1964–0382$15.00/0 Department of Dermatology Fax+41 61 306 12 34 University Hospital Utrecht E-Mail [email protected] This article is also accessible online at: PO Box 85500 www.karger.com http://BioMedNet.com/karger NL–3508 GA Utrecht (The Netherlands) Downloaded by: Erasmus Univ.of Rotterdam Medical Library 149.126.75.33 - 8/11/2015 8:49:33 AM T lymphocytes and monocyte-derived nonneoplastic macro- A chest X-ray and a CT scan of the abdomen revealed no signs of phages intermingled with eosinophils, and sometimes plas- lymphoproliferative disease. Laboratory investigations were within ma cells and B lymphocytes. Fully developed lesions also normal limits. A diagnosis of GSS was made, based on the clinical and histolog- show cells with larger hyperchromatic cerebriform nuclei ical data. The diseased skin in the groin was excised, but the skin le- among tumor-infiltrating lymphocytes. As the most con- sions recurred. Lesions were treated topically with steroids of differ- spicuous feature, numerous epithelioid and giant cell gran- ent strengths and topical nitrogen mustard without success. ulomas occur in which phagocytized elastic fibers can be Treatment with psoralen-ultraviolet A resulted in partial remission found [1–3]. The disappearance of elastic fibers results in of early lesions on the buttocks and hips but had no effect on the le- sions in the groins. During the 8-year follow-up period after the initial lax skin. Follow-up data from all reported patients with GSS diagnosis the lesions slowly progressed. Duing the last half year GSS reveal a relationship between GSS and a preexistent or she was treated with intralesional interferon α which was not effec- subsequent lymphoproliferative malignancy in about half tive. However, no clinical or histological signs for the development of of the cases [3–11]. a malignant lymphoproliferative disease were observed, in spite of the Molecular clonality studies of skin samples have been clonal T cells in the skin infiltrate. reported in 8 patients [3, 8–13]. These studies revealed Case II clonal rearrangement of the T-cell receptor TCRβ or TCRγ A 22-year-old Caucasian female patient with a history of psoriasis gene. Genotypic studies in 2 cases revealed trisomy 8 in vulgaris presented in 1975 with several red infiltrated well-demar- both of them [13, 14]. Therefore most authors suggest that cated scaling skin lesions which were diagnosed as mycosis fungoides GSS in fact is an indolent cutaneous T-cell lymphoma (MF). No enlarged lymph nodes were found. The patient was treated with total skin electron beam irradiation (CTCL) [3, 8–15]. (4 MeV, 3,500 rad). This resulted in remission of all lesions except for We present 3 patients with GSS in the context of an up- a lesion on the dorsum of the left foot. dated review of the literature. The purpose of this study is From 1983, recurrences were treated with topical application of ni- to define a place for GSS among the known lymphoprolif- trogen mustard which resulted in partial remission. erative disorders and to contribute to the discussion on the In 1993, MF lesions involved the axillary and inguinal folds, the lower quadrants of the abdomen, the mammae and flexural areas pathobiology of GSS. (fig.1b). Sometimes papules and nodi were noticed within the lesions during an exacerbation. Hanging laxy skin folds developed in the right axilla and both inguinal folds within the preexisting MF lesions. A Case Reports skin biopsy specimen showed a granulomatous infiltrate (fig.3) with small lymphocytes revealing epidermotropism and a dermal infiltrate Case I of lymphocytes with medium-sized irregular and hyperchromatic nu- A 35-year-old Caucasian female patient presented in 1988 with clei, histiocytes and scattered multinucleated giant cells, some of circumscribed nonitching, slightly scaling, slowly progressive skin which contained fragments of elastic fibers. The size of the lympho- lesions in the right inguinal fold and on the right medial thigh. The cytes was invariably much smaller than the MF cells found in earlier lesions had been present for 7 years and the skin showed a tendency biopsies (fig.4). Absence of elastin was confirmed by Verhoeff-Van to hang in loose folds (fig.1a). Further physical examination revealed Gieson staining. Occasional eosinophils were seen. no abnormalities. A skin biopsy specimen showed acanthosis, slight All lesional lymphocytic cells had the T-cell phenotype (CD2+, parakeratosis and a dense dermal lymphocytic infiltrate with scattered 3+) with CD4+ cells predominating over CD8+ cells. The atypical multinucleated giant cells. The lymphocytes had normal-sized, nor- lymphocytes were CD5–. mochromatic, slightly irregular nuclei. Occasionally scattered eosin- Molecular clonality studies of a representative skin specimen from ophils were seen. Almost complete absence of elastic fibers was con- the axilla revealed that approximately 20% of the nucleated cells in firmed by Verhoeff-Van Gieson staining. Some giant cells contained the biopsy specimen contained a clonal TCRβ gene rearrangement fragments of elastic fibers (fig.2). which is consistent with the presence of 20–30% of atypical T lym- The lymphocytes had the T-cell phenotype without loss of T-cell phocytes. A diagnosis of GSS was made. For cosmetic reasons, a le- markers [CD2 (TII)+, CD3 (leu-4)+ and CD5 (leu-1)+]. T cells with the sion of 3×5 cm was excised from the right axilla. The lesions in the helper phenotype, CD4 (leu-3a), predominated over cells with the sup- axillae have continued to progress, and on the abdomen GSS lesions pressor phenotype, CD8 (leu-2a; CD2, Central Laboratory of the Nether- have appeared in areas which had previously been affected by MF. lands Blood Transfusion Service, Amsterdam, the Netherlands, all other Treatment with topical carmustine resulted in partial remission. antibodies
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