SHORT COMMUNICATION
855
ActaDV ActaDV
Advances in dermatology and venereology Acta Dermato-Venereologica
Imatinib Treatment of Lymphomatoid Papulosis Associated with Myeloproliferative Hypereosino philic Syndrome Presenting the FIP1L1-PDGFRA Fusion Gene
Pablo GARCÍA-MARTÍNEZ 1, Dolors SITJAS 2, Enric LLISTOSELLA 2, Blanca ESPINET 3, María RODRÍGUEZ-RIVERA 3, Maria I. HERNANDEZ-MUÑOZ 4, Fernando GALLARDO 1 and Ramon M. PUJOL 1 * Departments of 1 Dermatology and 3 Pathology, 4 Institut Mar d’ Investigacions Mèdiques( IMIM), Universitat Autònoma de Barcelona, Hospital del Mar-Parc de Salut Mar, Passeig Marítim 25 – 29, ES-08003 Barcelona, and 2 Department of Dermatology, Hospital Josep Trueta, Girona, Spain. * E-mail: 93329 @ parcdesalutmar. cat Accepted Apr 3, 2017; Epub ahead of print Apr 4, 2017
Peripheral blood eosinophilia has been reported to occur in a wide range of haematological malignancies including primary cutaneous lymphomas. The concurrence of lymphomatoid papulosis( LyP) with peripheral blood eosinophilia seems to be an uncommon phenomenon. Atypical lymphocytes in LyP display the phenotype of activated T-helper cells, consistently express CD30 antigen, have a Th2 cytokine profile, and secrete eosinophilstimulating cytokines. Cases of LyP have been reported in association with myeloproliferative hypereosinophilic syndrome( M-HES) presenting the Fip1-like 1 / plateletderived growth factor receptor-α( FIP1L1-PDGFRA) fusion gene. In such cases, imatinib treatment may lead to a complete and persistent resolution of LyP lesions.
CASE REPORT
A 25-year-old man was referred to our Department in November 2011 for evaluation of a 3-year history of recurrent crops of self-healing erythematous papules and nodules with central ulceration on the lower extremities, oral mucosa and face. Biopsy had established the diagnosis of LyP. The patient reported periodical appearance of lesions that regressed spontaneously leaving residual scars. His past medical history revealed childhood-onset asthma, allergic conjunctivitis and rhinitis. Peripheral eosinophilia of 1,200 / mm 3 had also been detected and was related to the allergic symptoms along with progressive cough and discrete dyspnoea.
Physical examination disclosed a firm, well-demarcated, painless, ulcerated nodule, 1.2 cm in diameter on the right aspect of the chin. Several erythematous papules and residual scars on the lower extremities were also observed. A solitary nodule with a central crust was noted on the left leg( Fig. 1a, b). No enlarged lymph nodes were detected.
Two 4-mm punch biopsies from different lesions disclosed a dense, dermal, wedge-shaped infiltrate with clusters of large atypical lymphoid cells admixed with small lymphocytes, histiocytes, neutrophils and eosinophils( Fig. 1c – f). Neoplastic cells were CD30 + and expressed mature T helper cell markers( CD3, CD2, CD5 and CD7, CD4). No expression of ALK, c-KIT or CD56 was detected. Neoplastic cells were also MUM-1 + and 60 % of cells expressed Ki-67 antigen. In both biopsy specimens, an identical clonal rearrangement of the T-cell receptor( TCR) γ and β chains was detected. No T-cell clonality was detected in peripheral blood samples.
Laboratory tests disclosed massive peripheral eosinophilia( 6,120 / mm 3), normal IgE levels, elevated tryptase( 15.5 ng / ml)( NV < 13.5) and vitamin B12 serum levels(> 2,000 ng / ml)( NVs: 197 – 866). Stools for ova and parasites were negative. Body computed tomography( CT) showed bronchial dilatation with peribronchial thickening and confluent centrolobulillar nodules forming a ground glass pattern. Electrocardiogram, echocardiogram and ophthalmological examination showed no abnormalities.
A bone marrow biopsy was obtained showing hypercellular marked eosinophilia, atypical spindle-shaped mast cells and increased reticulin fibrosis. Interstitial deletion of the 4q12
Fig. 1. Clinical and histochemical characteristics.( a) Ulcerated inflammatory nodule on the right side of the patient’ s chin.( b) Necrotic erythematous infiltrated plaque on the leg.( c) Histopathology revealing a wedge-shaped dense inflammatory infiltrate extending from papillary to reticular dermis( haematoxylin and eosin staining( H & E); original magnification × 40).( d) Atypical, enlarged lymphocytes admixed with smaller lymphocytes, neutrophils and eosinophils( H & E × 400).( e) The infiltrate showed positive CD4 immunoreactivity( CD4 stain; × 40).( f) Atypical, large lymphocytes corresponded with CD30 + cells( CD30 stain; × 400).( g) Detection of the( 4q12) deletion by interphase fluorescence in situ hybridization( FISH) in peripheral blood cells. Loss of red signal indicating fusion of FIP1L1-PDGFRA.( h) FIP1L1-PDGFRA fusion gene was not detected in T cells from cutaneous LyP lesion by FISH.
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2669 Acta Derm Venereol 2017; 97: 855 – 857