Lymphomatoid papulosis (LyP) with 6p25.3 rearrangement DUSP22 and IRF4/

2013-09-01   Andrew L Feldman , Laszlo J Karai 

1.Aurora, DermDx Miami, 16250 NW 59 Ave., Suite 206, Miami Lakes, FL 33014, USA (LJK); Department of Laboratory Medicine, Pathology, College Of Medicine, Mayo Clinic, 200 First Street SW, Hilton Building, Room 8-00F, Rochester, MN 55905, USA (ALF)

Clinics and Pathology

Disease

Lymphomatoid papulosis (LyP)

Phenotype stem cell origin

Mature (peripheral) T cell.

Etiology

No etiologic factors are known.

Epidemiology

All reported cases occurred in elderly adults (67-88 years, mean 75 years) with strong male predominance (9M:2F) (Karai et al., 2013).

Clinics

The lesions are usually restricted to a single body area. Affected sites included the head and neck, upper torso, and extremities. Lesions ranged in size from 0.3 cm to 1.0 cm in diameter and had variable scale but no ulceration. No patient had disseminated cutaneous disease or clinical evidence of extracutaneous disease.
Atlas Image
Lymphomatoid papulosis with 6p25.3 rearrangement. Low power H&E image shows a prominent lymphoid nodule in the dermis (A) with characteristic pagetoid reticulosis-like epidermal involvement (B) at medium power. Inset in (A) shows high power image of atypical cells with small to medium nuclei and with the presence of frequent apoptotic bodies and mitotic figures. Immunohistochemical stains reveal a CD3 and CD30 positive phenotype with high proliferative ratio depicted by Ki-67 (C, D, and E, respectively).

Pathology

The histological features are remarkably consistent and different from the other types of cutaneous LyPs. Salient features include: prominent dermal nodule with the overlying epidermis showing pagetoid reticulosis-like histological changes. Marked periadnexal involvement is sometimes present. Tumor cells are mostly small to medium-sized with markedly irregular nuclei. Lesions show high mitotic rate and the presence of frequent apoptotic bodies. Necrosis is absent. No significant amount of eosinophils and neutrophils are present.

Treatment

No established treatment. Most of the lesions involute spontaneously and without therapy. Consideration to radiation, injection with kenalog or excision can be made depending on individual presentation.

Evolution

Similar to other types of LyP, recurring-remitting course.

Prognosis

According to the series of 11 patients the prognosis is good (Karai et al., 2013).

Cytogenetics

Cytogenetics morphological

Karyotypic findings have not been reported.
Atlas Image
Breakapart FISH for the DUSP22-IRF4 locus on 6p25.3 demonstrates abnormal separation of the red and green signals in the cell in the lower left (arrows). A cell with a normal signal pattern (two fusion signals, f) is seen in the upper right.

Probes

See Karai et al., 2013.

Additional anomalies

Unknown.

Variants

Unknown.

Genes Involved and Proteins

Note
The breakapart probe used to identify 6p25.3 rearrangements in LyP spans both the DUSP22 and the IRF4 genes. The specific breakpoints have not been reported in LyP. In ALK-negative anaplastic large cell lymphomas (ALCLs), 6p25.3 breakpoints in or near either gene have been reported (Feldman et al., 2011). The partner locus was confirmed to be 7q32.3 in a single case of LyP tested, analogous to the t(6;7)(p25.3;q32.3) reported in ALCLs, but was not investigated in the remaining reported cases.
Gene name
DUSP22 (dual specificity phosphatase 22)
Location
6p25.3
Protein description
DUSP22 encodes a dual-specificity phosphatase that inhibits T-cell antigen-receptor signaling in T cells by inactivating the MAP kinase, ERK2. The expression and function of DUSP22 in cases of LyP with 6p25.3 rearrangements have not been reported.
Gene name
IRF4 (interferon regulatory factor 4)
Location
6p25.3
Protein description
IRF4 encodes a transcription factor, IRF4/MUM1, critical in lymphocyte activation and differentiation. Although IRF4/MUM1 is expressed in most cases of LyP, the expression and function of IRF4/MUM1 in cases of LyP with 6p25.3 rearrangements have not been reported.

Result of the Chromosomal Anomaly

Note

Not known.Not known.

Bibliography

Pubmed IDLast YearTitleAuthors
210305532011Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing.Feldman AL et al
236484612013Chromosomal rearrangements of 6p25.3 define a new subtype of lymphomatoid papulosis.Karai LJ et al

Citation

Andrew L Feldman ; Laszlo J Karai

Lymphomatoid papulosis (LyP) with 6p25.3 rearrangement DUSP22 and IRF4/

Atlas Genet Cytogenet Oncol Haematol. 2013-09-01

Online version: http://atlasgeneticsoncology.org/haematological/1658/lymphomatoid-papulosis-(lyp)-with-6p25-3-rearrangement-dusp22-and-irf4