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Ahead of print publication
Lymphomatoid papulosis with DUSP22-IRF4 rearrangement on 6p25.3: A case report


1 Department of Dermatology, MacKay Memorial Hospital, Taipei, Taiwan
2 Department of Pathology, MacKay Memorial Hospital, Taipei, Taiwan
3 Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
4 Department of Dermatology, MacKay Memorial Hospital, Taipei; Department of Medicine, MacKay Medical College, New Taipei City, Taiwan

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Date of Submission09-Aug-2021
Date of Decision19-Sep-2021
Date of Acceptance26-Sep-2021
Date of Web Publication29-Oct-2021
 


How to cite this URL:
Mao YN, Jhuang JY, Chen BJ, Wu YH. Lymphomatoid papulosis with DUSP22-IRF4 rearrangement on 6p25.3: A case report. Dermatol Sin [Epub ahead of print] [cited 2021 Dec 5]. Available from: https://www.dermsinica.org/preprintarticle.asp?id=329636




Dear Editor,

Lymphomatoid papulosis (LyP) is an uncommon relapsing cutaneous lymphoproliferative disorder with histological features mimicking T-cell lymphoma. The median age of the affected patients is 45 years,[1] and this disorder has a slight male predominance. The typical clinical feature is the appearance of several scattered papulonodular or papulonecrotic skin lesions. We report the case of a 69-year-old man with no significant past medical history presenting with asymptomatic skin lesions involving the head-and-neck area for 2–3 months. Lesions appeared intermittently and resolved without scarring. A previous pathological report of skin biopsy performed at a local clinic showed chronic granulomatous inflammation. He then visited our dermatology clinic for a second opinion. Physical examination revealed four 0.5–1 cm-in-diameter nontender erythematous nodules on the forehead, right neck, and chin [Figure 1]. He denied fatigue, fever, or lymphadenopathy. There was no history of skin disease, malignancy, or immunocompromised status.
Figure 1: Clinical presentation. Several 0.5–1 cm-in-diameter nontender elastic erythematous nodules on (a) forehead and (b) right side of the neck.

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Histopathological examination revealed diffuse lymphoid cell infiltration in the entire reticular dermis [Figure 2]a. The epidermis exhibited exocytosis of a few small lymphocytes. The main infiltrating cells in the dermis were medium to large lymphoid cells [Figure 2]b that were strongly positive for cluster of differentiation (CD) 3 [Figure 2]c and CD30 [Figure 2]d but negative for CD4 [Figure 2]e, CD8 [Figure 2]f, CD20, CD56, anaplastic lymphoma kinase, T-cell intracytoplasmic antigen 1, and Epstein–Barr virus-encoded RNA. Due to the unusual immunophenotype of the tumor cells, the specimen was sent for fluorescence in situ hybridization analysis that demonstrated the rearrangement of DUSP22-IRF4 gene, indicating a translocation of chromosome 6p25.3 [Figure 2]g. A diagnosis of CD30-positive lymphoproliferative disorder, LyP with DUSP22-IRF4 rearrangement, was made by correlating clinical, histologic, immunophenotypic, and genetic findings.
Figure 2: Histopathological findings. (a) Diffuse lymphoid cell infiltration in the dermis (H and E, ×40). (b) The tumor cells were medium to large lymphoid cells (H and E, ×400). Immunohistochemically, the tumor cells showed diffuse and strong expression of (c) CD3, and (d) CD30 and were negative for (e) CD4 and (f) CD8 (× 200). (g) Fluorescent in situ hybridization analysis of the DUSP22-IRF4 gene (ZytoLight SPEC IRF4, DUSP22 Dual Color Break Apart Probe) demonstrated separate green and orange signals indicating rearrangement of DUSP22-IRF4 gene.

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Laboratory data showed normal complete blood count, erythrocyte sedimentation rate, and lactate dehydrogenase and beta-2-microglobulin levels. Chest X-ray was unremarkable. Watchful waiting was considered the appropriate management option for the patient according to previous report.[2] All lesions resolved with residual postinflammatory hyperpigmentation within 1 month. No progression to generalized skin involvement or systemic disease was noted. He reported complete resolution without the appearance of new lesions at the last follow-up, 20 months after presentation.

In 2013, a new LyP subtype characterized by chromosomal rearrangement involving the DUSP22-IRF4 locus on 6p25.3 was identified.[2] In addition to LyP Types A, B, and C, the 2018 update of the World Health Organization (WHO)–European Organization for Research and Treatment of Cancer classification in the fourth edition of the WHO Classification of Skin Tumors also included Types D, E, and LyP with DUSP22-IRF4 rearrangement.[3] One more Caucasian case was further reported in 2019.[4] DUSP22, encoding dual-specificity phosphatase-22, may serve as a tumor suppressor gene by inhibiting T-cell signaling. Rearrangement of DUSP22-IRF4 downregulates the expression of DUSP22 and may consequently contribute to tumor expansion.[2]

The previous reported cases of LyP with DUSP22-IRF4 rearrangement had a distinct clinical presentation constituting localized papular lesions without ulceration in the elderly (mean age, 75 years).[2] Treatment included local excision or radiotherapy, and all untreated lesions regressed spontaneously within 2 months.[2] In the current limited experience, LyP with this rearrangement was not associated with worse prognosis than other subtypes, with follow-up ranging from 7 to 150 months (median, 21 months).[2],[4] Our patient also presented with nonulcerated papulonodular lesions localized to the head-and-neck region and rapid resolution without recurrence during the 20-month follow-up. Findings of our case strengthen the evidence regarding the favorable clinical course of this rare subtype.

Nevertheless, the DUSP22-IRF4 rearrangement has been found in approximately 25% of cutaneous anaplastic large-cell lymphoma (ALCL).[2],[4] Therefore, LyP and cutaneous ALCL share the similar pathology of presence of large anaplastic lymphoid cells' infiltration in the skin, and both may have DUSP22-IRF4 rearrangement. The clinical history of wax and wane features, distribution and number of lesions, and staging of systemic involvement are essential to distinguish these two entities.[4]

In conclusion, the role of genetic testing is growing in the diagnosis of cutaneous lymphoproliferative disorders. The result may become a biological marker to predict the clinical outcome and provides possible target to develop a new therapy. The clinicians and pathologists should recognize this uncommon subtype. It can help to collect information to understand the prognosis and deliver proper management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

Dr. Yu-Hung Wu, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.



 
  References Top

1.
Elder DE, Massi D, Scolyer RA, Willemze R, editors. WHO Classification of Skin Tumours. 4th ed. Lyon, France: International Agency for Research on Cancer; 2018.  Back to cited text no. 1
    
2.
Karai LJ, Kadin ME, Hsi ED, Sluzevich JC, Ketterling RP, Knudson RA, et al. Chromosomal rearrangements of 6p25.3 define a new subtype of lymphomatoid papulosis. Am J Surg Pathol 2013;37:1173-81.  Back to cited text no. 2
    
3.
Willemze R, Cerroni L, Kempf W, Berti E, Facchetti F, Swerdlow SH, et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood 2019;133:1703-14.  Back to cited text no. 3
    
4.
Kluk J, Child F, Robson A. Lymphomatoid papulosis with 6p25.3 rearrangement: A further case of the newly described variant. Br J Dermatol 2014;171:1590-2.  Back to cited text no. 4
    

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Correspondence Address:
Yu-Hung Wu,
Department of Dermatology, Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan North Road, Taipei 10449
Taiwan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ds.ds_41_21



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