A clonal cutaneous CD30+ lymphoproliferative eruption in a patient with evidence of past exposure to hepatitis E
Authors: Lemons‐Estes Freddye M. , Capt Hon Pak , Skelton Henry , Smith Kathleen J. 
Published: March 2003

The patient was a 52‐year‐old white man who had worked in remote areas of the world during the past 2 years, including an extended period in rural areas of Central Africa and in Central and South America. He had no acute illnesses during the 2‐year period except for rare, mild, upper respiratory tract infections. For approximately 1 year, however, he had developed recurrent, papular‐vesicular, slightly painful lesions on the fingers and palms, that spontaneously healed over weeks to months ( Fig. 1). The patient had no other concurrent illnesses and no abnormal laboratory findings, except for positive enzyme‐linked immunoabsorbent assay (ELISA) for immunoglobulin G (IgG) antibodies for hepatitis E virus (HEV) using a recombinant expressed HEV antigen (Genelabs Technologies, Inc., San Antonio). Prolonged treatment with minocycline did not appear to moderate the lesions. At approximately 2.5 years after the development of his first cutaneous lesion, however, the patient reported that he had had no new lesions for over 3 months.

 Vesicular  lesion on the finger which regressed over a period of weeks

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A biopsy specimen showed an intraepidermal vesicle with prominent epidermal necrosis and reticular degeneration ( Fig. 2). Within the epidermis, there was a dense infiltrate of lymphoid cells. The majority of these cells were pleomorphic with prominent nucleoli and frequent mitotic figures (
Fig. 3). Sheets of atypical cells were found in the subjacent dermis. The infiltrate extended down into the reticular dermis. With extension into the dermis, the infiltrate became more polymorphous with more small lymphoid cells, large numbers of eosinophils, and some plasma cells located more deeply.

Intraepidermal  blister showing reticular degeneration and marked epidermotrophism of large atypical cells with extension into the dermis with a mixed infiltrate containing eosinophils and plasma cells (30×)

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Intraepidermal  infiltrate of large atypical cells with extension into the dermis with a mixed infiltrate containing eosinophils and plasma cells (400×)

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Immunohistochemical stains for CD3 (DAKO), CD4 (Becton Dickinson), CD8 (Becton Dickinson), CD15 (LeuM1, Becton Dickinson), CD20 (L‐26, DAKO), CD30 (Ber‐H2, DAKO), CD45RO (UCHL1, DAKO), S‐100 protein (DAKO), T‐cell intracellular antigen (TIA) (Coulter), epithelial membrane antigen (EMA) (DAKO), KP‐1 (CD68, DAKO), MAC‐387 (DAKO), Epstein–Barr virus (EBV) latent membrane antigen‐1 (LMP‐1, DAKO), and EBV‐encoded nuclear antigen 2 (EBNA2, DAKO) were performed on formalin‐fixed tissue using the ABC method with DABA as the chromagen.

CD3 showed diffuse membrane staining of the large atypical lymphoid cells, as well as the majority of the small lymphoid cells ( Fig. 4). CD4 showed positive membrane staining of the large atypical lymphoid cells and the majority of the small lymphoid cells. CD8 showed only scattered light membrane staining of small lymphoid cells. CD15 was negative, and CD20 showed foci of groups of small lymphoid cells mainly within the reticular dermis. CD30 showed positive membrane and paranuclear staining of the large atypical cells, most abundant within the epidermis and papillary dermis (
Fig. 5). CD45RO showed positive membrane staining of the large atypical cells and the majority of the small lymphoid cells. S‐100 protein showed increased dendritic cells within the surrounding viable epidermis and the subjacent papillary dermis (
Fig. 6). TIA showed granular staining in the large atypical lymphoid cells and only rare staining in small lymphoid cells (
Fig. 7). EMA staining was essentially negative. KP‐1 showed only scattered positive cells mainly in the lower papillary and the reticular dermis. MAC‐387 showed membrane staining in the viable epidermis (
Fig. 8). LMP‐1 and EBNA2 for EBV were negative within the lymphoid cells as well as within the overlying epidermis.

Immunohistochemical  staining for CD3 showing diffuse staining of lymphoid cells within the epidermis and dermis (150×)

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Immunohistochemical  staining for CD30 showing membrane and paranuclear staining of large atypical lymphoid cells within the epidermis and papillary dermis (a, 150× b, 400×)

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Immunohistochemical  staining for S‐100 protein within the epidermis and in the papillary dermis (a, 150× b, 300×)

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Immunohistochemical  granular staining of large atypical lymphoid cells for TIA (200×)

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Immunohistochemical  staining for MAC‐387 showing epidermal staining (100×)

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Gene rearrangement studies showed a β‐T‐cell receptor gene rearrangement. The monoclonal band was detected with VJ1, VJ2, and D1J2 primer sets. The T‐cell receptor β rearrangement assay has a sensitivity of 61% and a specificity of 94% for the detection of a monoclonal rearrangement in T‐cell lymphomas for which amplifiable DNA can be recovered.

Electron microscopy was performed on formalin‐fixed material, positive‐fixed with 2.5% phosphate‐buffered glutaraldehyde and further with 1% osmium tetroxide by standard techniques. Intracellular, 50–60‐nm, cytoplasmic, spherical, viral‐like particles were identified ( Fig. 9).

Electron  microscopy showing 50–60‐nm diameter, intracellular, viral‐like particles (arrows) (70,000×)

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