Sorted By Test Name - Mayo Medical Laboratories

60506
CIFS
8052
Cutaneous Anaplastic Large Cell Lymphoma, 6p25.3 (IRF4)
Rearrangement, FISH, Tissue
Clinical Information: Primary cutaneous anaplastic large cell lymphoma (ALCL) is a CD30-positive
T-cell lymphoproliferative disorder presenting in the skin and affecting predominantly adults with a male
to female ratio of about 2:1 to 3:1. Most patients have solitary or localized tumor nodules, often with
ulceration. About 20% of cases are multifocal. Regional lymph nodes may be secondarily involved. The
differential diagnosis in skin biopsies includes lymphomatoid papulosis (LyP), transformed mycosis
fungoides (MF), and secondary skin involvement by systemic ALCL. All these disorders have
overlapping morphologic and immunophenotypic features, making collection of a comprehensive clinical
history and staging paramount. LyP typically demonstrates a chronic course with a history of waxing and
waning, papular skin lesions. Transformed MF requires an established diagnosis of MF. Diagnosis of
systemic ALCL is based on presence of systemic disease, timing of skin versus nodal disease, with or
without the presence of anaplastic lymphoma kinase (ALK) protein or ALK gene rearrangements, both of
which are absent in cutaneous ALCL based on World Health Organization (WHO) criteria. Recurrent
translocations in or near the IRF4 (interferon regulatory factor 4) gene locus on 6p25.3 have been
described in cutaneous ALCLs. IRF4 translocations occur in 20% to 57% of cutaneous ALCLs, and recent
studies have shown high specificity for this disorder when present in skin biopsies involved by T-cell
lymphoproliferative disorders. Most CD30-positive T-cell lymphoproliferative disorders are positive for
the IRF4/MUM1 protein by immunohistochemistry, regardless of translocation status; thus, unlike ALK,
IRF4/MUM1 immunohistochemistry is not a surrogate for testing for IRF4 translocations. There currently
are insufficient data to suggest presence of an IRF4 translocation has prognostic value in T-cell
lymphoproliferative disorders. Absence of an IRF4 translocation does not exclude cutaneous ALCL. Rare
instances of IRF4 translocations have been reported in LyP, transformed MF, systemic ALK-negative
ALCL, and CD30-negative systemic T-cell lymphoma; therefore, testing for IRF4 translocations does not
eliminate the need for, or take precedence over, collecting a thorough clinical history and staging. IRF4
translocations are also seen in a subset of multiple myelomas and occasional B-cell lymphomas of various
subtypes; however, clinical utility for demonstrating their presence in B-lineage neoplasms has not been
established.
Useful For: Supporting the diagnosis of cutaneous anaplastic large cell lymphoma when coordinated
with a consultation by anatomic pathology
Interpretation: Among cutaneous CD30-positive T-cell lymphoproliferative disorders, rearrangement
of the IRF4 (interferon regulatory factor 4) gene at 6p25.3 is most closely associated with a diagnosis of
cutaneous anaplastic large cell lymphoma (ALCL). However, systemic ALCL, lymphomatoid papulosis,
and transformed mycosis fungoides are not excluded by this result. Furthermore, other T- and B-lineage
neoplasms can demonstrate this finding. Clinical and pathologic correlation is recommended.
Reference Values:
An interpretative report will be provided.
Clinical References: 1. Feldman AL, Law M, Remstein ED, et al: Recurrent translocations
involving the IRF4 oncogene locus in peripheral T-cell lymphomas. Leukemia 2009;23:574-580 2.
Pham-Ledard A, Prochazkova-Carlotti M, Laharanne E, et al: IRF4 gene rearrangements define a
subgroup of CD30-positive cutaneous T-cell lymphoma: a study of 54 cases. J Invest Dermatol
2010;130:816-825 3. Wada D, Law M, de Souza A, et al: IRF4 Translocations are specific for cutaneous
anaplastic large cell lymphoma in skin biopsies involved by T-cell lymphoproliferative disorders. Mod
Pathol 2009;22(suppl 1):289A (abstract 1308)
Cutaneous Immunofluorescence Antibodies (IgG), Serum
Clinical Information: IgG anti-basement zone (BMZ) antibodies are produced by patients with
pemphigoid. In most patients with bullous pemphigoid, serum contains IgG anti-BMZ antibodies, while in
cicatricial pemphigoid circulating IgG anti-BMZ antibodies are found in a minority of cases. Sensitivity
of detection of anti-BMZ antibodies is increased when serum is tested using sodium chloride (NaCl)-split
human skin as substrate. Circulating IgG anti-BMZ antibodies are also detected in patients with
epidermolysis bullosa acquisita (EBA) and bullous eruption of lupus erythematosus (LE). IgG anti-cell
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