Hydroa vacciniforme-like cutaneous T-cell lymphoma.

A 14-year-old Chinese girl had a 6-year history of recurrent lesions on her head, face, and limbs. Epstein-Barr virus (EBV)-IgM was positive. Histopathological findings revealed focal lymphocyte invasion in subcutaneous panniculus adiposus, mainly surrounding the blood vessels. Immunohistochemistry showed CD3+, CD4+, CD5+, CD8+, TIA-1+, GrB+, CD56-, and L26-. In situ hybridization staining for EBV-encoded small nonpolyadenylated RNA (EBER)-1 was positive. The patient showed significant improvement in clinical symptoms after being treated with acyclovir and IFN-α in this patient.

What was known?

EBV has been demonstrated to be associated with cutaneous T-cell lymphoma.

Introduction

Hydroa vacciniforme-like cutaneous T-cell lymphoma is a rare variant of cutaneous T-cell lymphoma. It belongs to the spectrum of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders. We describe a case with erythematous papules, vesicles, and papules with a necrotic center on the face, hands, and ankles resembling hydroa vacciniforme (HV).

Case History

A 14-year-old Chinese girl had a 6-year history of recurrent lesions on her head, face and limbs. Six years ago, the patient had scattered small erythematous papules, vesicles, and papules with a necrotic center on the face, hands, and ankles. The lesions progressed through a large ulcerated eschar stage before healing with an atrophic scars ranging from 5 to 9 mm in size. Although each eruption resolved within 2 to 8 weeks after treatment at a local hospital, new papules and vesicles continued to appear. The lesions were not being induced by repeated exposure of her skin to the sun. The patient was brought to our clinic because of a recurrent erythematous papules and ulcer with fever. On physical examination, variously sized edemas, erythematous papules, vesicles, and crusts along with some pitting scars on the face and extremities were observed. There were some tender edematous infiltrated plaques with a necrotic center and ulcers on the legs and arms [Figure 1a–c].

Figure 1

(a-c) Variously sized edemas, erythematous papules, vesicles, and crusts were along with some pitting scars on the face and extremities. There were some tender edematous infiltrated plaques with a necrotic center and ulcers on the legs and arms. (d) A marked improvement was noted after 3 weeks treatment

Serological examinations for HIV and syphilis were negative. The liver function and renal function tests were negative. Serology study of EBV showed anti-EBV nuclear antigen (EBNA)-IgM antibody 22.8 U/ml (+). Peripheral blood cell counts of T- and B-lymphocytes, levels of serum immunoglobulins (IgG, IgA and IgM) as well as complements (C3 and C4) were also within normal limits. No atypical lymphocyte was found in the peripheral blood. Ultrasonic examination revealed slight enlargement of the liver and spleen. Chest X-ray was unremarkable.

A histologic section of the biopsy material stained with hematoxylin and eosin (H and E), revealed a necrotic epidermis and dense infiltration of numerous lymphoid cells throughout the dermis [Figure 2a], involving subcutaneous fat lobules [Figure 2b]. A few neutrophils and eosinophils were scattered among the lymphoid cells. Among the infiltrate, many large atypical lymphocytes were present, but cerebriform mononuclear cells were absent [Figure 2b]. Neither an angiocentric nor angiodestructive picture was seen.

Figure 2

(a) Necrotic epidermis and dense infiltration of numerous lymphoid cells throughout the dermis (H and E, ×100). (b) Among the infiltrate, many large atypical lymphocytes were present, but cerebriform mononuclear cells were absent (H and E, ×200)

Immunohistochemical stain showed that most of the infiltrating large lymphoid cells were positive for CD3 [Figure 3a], CD4 [Figure 3b], CD5 [Figure 3c], CD8 [Figure 3d], TIA-1, and GrB; and negative for CD20 and L26. Only a few cells, which were small reactive lymphocytes, expressed CD56. In situ hybridization staining for EBV-encoded small nonpolyadenylated RNA (EBER)-1 was positive.

Figure 3

Immunohistochemical stain showing that most of the infiltrating large lymphoid cells are positive for (a) CD3 (ABC ×100), (b) CD4 (ABC ×100), (c) CD5 (ABC ×100), (d) CD8 (ABC ×100)

The patient was treated with intravenous acyclovir 200 mg twice daily and subcutaneous injections of IFN-α 50 μg every other day. A marked improvement was noted after 3 weeks of treatment [Figure 1d]. The treatment was continued with subcutaneous injections of IFN-α 50 μg every other day for 2 months. After 8 months of follow up, no obvious eruptions continued.

Discussion

HV is a rare chronic photodermatitis of childhood characterized by recurrent vacciniforme vesicles, necrotic ulcers, and scars on sun-exposed areas.[123] Typical HV fulfills the following criteria proposed by Iwatsuki et al.:[4] (i) a self-limited, vesiculopapular eruption on the exposed areas; (ii) no systemic involvement is present and the disorder improves with rigorous protection from the sun; (iii) histological features of reticulated epidermal necrosis or blister formation associated with dense lymphocytic infiltration; and (iv) normal porphyrin concentrations in the blood and urine. The atypical cases of HV were reported to have a high-grade fever, liver damage, edematous swelling of the cheeks, eyelids, and lips, and unusual skin lesions on the sun-protected areas.[45] Some of the cases were found to progress to lymphoma.[3467] Patients with EBV-associated cutaneous T/NK-cell proliferative disorders are characterized by similar clinicopathologic features, including subcutaneous lymphoma associated with hemophagocytosis, hydroa vacciniforme-like vesiculopapular eruptions, and angiocentric lymphoma.[8] These clinicopathologic features may overlap during the course of the illness.[8]

Our patient was unusual, both in the age of onset of her disease and the exclusive facial distribution of her skin lesions. Clinically her lesions resembled HV, but histologically they revealed a necrotic epidermis and dense infiltration of numerous CD3+, CD4+, CD5+, CD8+, CD56- lymphocytes throughout the dermis, and many large atypical lymphocytes. EBV-encoded RNA (EBER-1)-positive lymphocytes were detected. Most EBV-associated cutaneous T-cell lymphomas are of a T-cell lineage, for example, CD8+, natural-killer (NK), or T/NK cells.[34910] Interestingly, the angiocentric- and angiodestructive lymphoid cells in the skin biopsies of this patient showed phenotypic features of cytotoxic T-cells with CD4 expression instead of CD8.[3910] The immunohistochemical study of our patient showed CD4+ cells and CD8+ cells in the infiltrate. The finding has rarely been reported in EBV-associated peripheral T-cell lymphoma.

Based on the clinical, pathologic, and serologic findings, a diagnosis of HV-like cutaneous T-cell lymphoma was made. Treatment for patients with EBV-associated HV is not satisfactory. Photoprotection may not prevent the skin lesions or systemic symptoms.[49] Immunosuppressive therapy, such as systemic corticosteroids or cyclosporine A has been used, but the disease usually flares after decreasing the dose, as occurred in this reported patient.[10] Severe chronic, active EBV infection may require bone marrow transplantation.[78]

Our patient was successfully treated with acyclovir and IFN-α. After 8 months of follow up, no obvious eruptions continued. This evidence highlights the therapeutic potential of antivirus treatment for EBV-associated HV. We hope that the investigation may provide some valuable data and experience in this special field.

What is new?

The immunohistochemical study of this case showed CD4+ cells and CD8+ cells in the infiltrate. This case was successfully treated with acyclovir and IFN-α.