Customize your JAMA Network experience by selecting one or more topics from the list below.
Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
Primary cutaneous gamma-delta T-cell lymphoma (GD-TCL) is a rare skin lymphoma with numerous clinical presentations. Cytotoxic features on histologic analysis and the T-cell receptor (TCR)-gamma expression on immunohistochemical analysis are clues that should raise suspicion for the diagnosis. Expression of CD30 can also be seen in some cases and should be evaluated because it allows for patients to be treated with brentuximab, as in the present case.
A man in his 40s presented with numerous partially ulcerated papules and small plaques on the trunk (Figure 1A) and extremities covering 35% of the total body surface area without peripheral lymphadenopathy. He also reported severe pruritus and weight loss of 10 pounds over the previous 6 months.
A, Multiple necrotic papules and small scaly plaques on the anterior trunk. B, Partial clearing of skin lesions after 4 cycles of brentuximab vedotin treatment.
In 2011, he had been diagnosed with presumed mycosis fungoides (MF) for which he was initially treated with weekly oral methotrexate combined with daily topical applications of bexarotene, 1%, gel; then he was switched to extracorporeal photopheresis once a week and application of clobetasol ointment, 0.05%, daily. Two years after his original diagnosis, he underwent a female sibling–matched donor transplantation to treat cutaneous tumors that showed large-cell transformation on histologic analysis. At that time, positron emission tomography/computed tomography and peripheral flow cytometry did not reveal systemic involvement. After transplantation, he showed 100% donor chimerism in the bone marrow and peripheral blood and was in complete remission for 2 years.
The patient subsequently relapsed, developing disseminated ulcerated plaques on the trunk and extremities, and he was treated with denileukin diftitox, vorinostat, and narrowband UV-B phototherapy twice weekly.
Nine months after relapse, he presented with worsening skin lesions. Skin biopsy specimens from lesions on the left thigh and left buttock revealed a cytotoxic intraepidermal infiltration of atypical large lymphocytes with clumped chromatin, numerous dyskeratotic keratinocytes, overlying ulceration, and scarce superficial perivascular infiltrate (Figure 2A and B). No Pautrier microabscesses were seen.
A, Epidermal infiltration of atypical large pleomorphic lymphocytes with associated dyskeratotic and apoptotic keratinocytes and partial ulceration; the underlying superficial dermis shows a bandlike lymphohistiocytic infiltrate. B, Detail of the large cells with clumped chromatin. C, Most of the large cells show T-cell receptor (TCR)-gamma expression by immunohistochemical analysis. D, The results of FISH analysis using X and Y probes (green and red spots, respectively) revealed that the atypical lymphoid cells in epidermis (above the curved line) showed a male (XY) host pattern, while dermal cells (below the curved line) showed a predominant female (XX) donor pattern with scattered male (XY) positive cells.
The neoplastic cells tested negative for CD4, CD5, CD8, and BF-1 and positive for CD2, CD3, CD7, CD30, CD56, TIA-1, granzyme B, and TCR-gamma (Figure 2C). Findings of in situ hybridization for Epstein-Barr virus were negative, and molecular analysis revealed a clonal rearrangement of the TCR-gamma–chain gene. Fluorescence in situ hybridization was performed on formalin-fixed, paraffin-embedded tissue, which revealed that 60% of atypical lymphoid cells contained a male (XY) pattern, consistent with the host (Figure 2D). Almost all previous biopsy specimens were reviewed and, unlike MF specimens, showed pleomorphic tumor cells with clumped chromatin, a CD4-CD8 phenotype with loss of CD5, but preserved CD7 expression and various degrees of dyskeratotic keratinocytes. Findings of molecular analysis and TCR-gamma immunostaining were positive in all available specimens, revealing identical clones for TCR-gamma–chain genes.
Restaging workup found no systemic disease, and in light of the CD30 expression, the patient was started on intravenous brentuximab vedotin therapy, 1.8 mg/kg, every 3 weeks. At last follow-up, 7 months after beginning treatment, his condition was improved, and he had no progressing lesions.
Primary cutaneous GD-TCL represents less than 1% of all primary cutaneous T-cell lymphomas.1 In the largest published patient series to our knowledge, Guitart et al2 defined clinical and pathological features and correlated them with outcomes. The condition generally manifests with necrotizing plaques and tumors, but cases have presented with chronic and scaly plaques mimicking MF,2,3 as seen in the present case. Cytotoxic features of dyskeratotic and/or necrotic keratinocytes with ulceration and epidermotropic, atypical lymphoid cells, morphologically distinct from MF, provide important clues toward the diagnosis. Graft-vs-host disease was ruled out in the present case, based on lymphoid atypia and fluorescence in situ hybridization results. The strong expression of TCR-gamma helped to support the diagnosis of primary cutaneous GD-TCL.
The present patient was treated with brentuximab vedotin, and after 7 months of treatment, his skin lesions had partially cleared (Figure 1B). At least 4 other primary cutaneous GD-TCL cases have also shown clinical response to brentuximab.4 Overexpression of CD30 may be present in some cases of primary cutaneous GD-TCL, and these patients should be assessed for evaluation of potential therapeutic options.
Corresponding Author: Christiane Querfeld, MD, PhD, Department of Pathology, City of Hope, 1500 E Duarte Rd, Duarte, CA 91010 (email@example.com).
Published Online: September 21, 2016. doi:10.1001/jamadermatol.2016.3117
Conflict of Interest Disclosures: None reported.
Rubio-Gonzalez B, Zain J, Garcia L, Rosen ST, Querfeld C. Cutaneous Gamma-Delta T-Cell Lymphoma Successfully Treated With Brentuximab Vedotin. JAMA Dermatol. 2016;152(12):1388–1390. doi:10.1001/jamadermatol.2016.3117