Dermatology Online Journal

Diffuse large cell non-Hodgkin's lymphoma, CD30+, T-cell phenotype
Lisa Moed Gruson MD and Jo-Ann Latkowski MD
Dermatology Online Journal 11 (4): 17

Department of Dermatology, New York University School of Medicine

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Abstract

A 63-year-old Chinese man presented with an eczematous dermatitis that progressed into a multifocal nodular eruption. Histopathologic examination demonstrated a nodular and diffuse infiltrate in the reticular dermis, which was composed of lymphocytes, macrophages with granulomatous inflammation, and numerous eosinophils. Reactive lymphoid follicles with germinal centers also were present. Immunohistochemistry showed CD30 and LCA. ALK-1 and CD20 were negative. A diagnosis of CD30+ cutaneous T-cell lymphoma was made, and the patient is currently undergoing staging of his disease. Treatment options include excision of nodules, radiation therapy, and systemic chemotherapy.

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A 63-year-old Chinese man was referred to the Dermatology Clinic at Bellevue Hospital Center for an eruption on his trunk and intertriginous areas that he had noticed approximately 2 years ago. The patient stated that the eruption was pruritic and that attempts to control it with over-the-counter hydrocortisone and Chinese herbal creams had been unsuccessful. At that time, a biopsy was taken, and the patient was treated with tacrolimus ointment and triamcinolone ointment. The first biopsy specimen showed a psoriasiform, spongiotic dermatitis with a superficial and deep mixed-cell infiltrate.

Over the next several months, the eruption continued to progress with the development of a large tumor in his right groin despite the use of topical therapy. The patient was referred to the lymphoma clinic. Multiple biopsy specimens of the tumor and the eruption showed a nodular and interstitial granulomatous infiltrate with eosinophils and a mixed lymphoid population. A systemic evaluation, which included gene rearrangement studies, did not yield a specific diagnosis. However, mycosis fungoides remained a concern. The patient was treated with narrow-band ultraviolet-B phototherapy. He remained stable with improvement of his eruption and pruritus until July 2004, when he returned with multiple, erythematous nodules in his groin and lower abdomen.

Medical history includes vertigo, hypertension, peripheral vascular disease, coronary artery disease, and a history of a cerebrovascular accident. Medications include fosinopril, ranitidine, simvastatin, isosorbide, amlodipine, and atenolol.

Elevated, erythematous plaques with minimal scale were present on the lateral neck, upper back, axillae, and inguinal area. There were multiple 1-3-cm, firm, non-tender nodules within the plaques in the groin area and lower abdomen. There was an eythematous tumor in the right groin.

Figure 1	Figure 2

A complete blood count, comprehensive metabolic panel, lactate dehydrogenase, and uric acid levels were normal. Computed tomography scans of the chest, abdomen, and pelvis were normal

Histopathology reveals a diffuse infiltrate of atypical lymphoid cells, which occupies the entire dermis and subcutis. No epidermotropism is present. Atypical lymphocytes have enlarged nuclei with prominent nucleoli. Many cells have irregular horseshoe-shaped nuclei with multiple eosinophilic nuclei and abundant eosinophilic cytoplasm (so-called hallmark cells). Numerous mitotic figures, which include atypical forms, are present. Immunohistochemical stains showed that the atypical lymphocytes express T-cell associated antigens (CD3 and UCHL1, which is an antibody for the 180 kD low-molecular weight isoform of CD 45 or leukocyte common antigen) and CD 30.

Comment

The term cutaneous T-cell lymphomas (CTCL) includes a diverse group of malignant conditions derived from skin-homing T-cells. Mycosis fungoides is the most common form, and primary cutaneous CD30+ lymphoma comprises 25 percent of the cases of CTCL[1]. The CD30 antigen, which is a type-1 transmembrane glycoprotein, is a member of the tumor necrosis factor receptor family and may be expressed on activated B and T cells [2]. A spectrum of CD30+ disorders is described and ranges from the more benign lymphomatoid papulosis to borderline CD30 lesions to anaplastic large-cell lymphoma. CD30+ CTCL usually presents in the sixth decade of life [1]. Its etiology remains unclear; however, one hypothesis is that chronic antigenic stimulation of the skin may lead to a malignant clone of T-cells [3]. Recently, four cases of CD30+ lymphoma arising from a background of atopic dermatitis were described [4].

Classically, CD30+ CTCL presents as a single ulcerated tumor. However, patients may also have multiple nodules in one skin area, and, less frequently, multifocal skin involvement. Spontaneous and complete regression of cutaneous lesions is not uncommon. It has been noted that patients with multifocal lesions may have an increased risk of extracutaneous involvement [1]. On histopathologic examination, there are nodular, dermal and subcutaneous infiltrates of atypical lymphocytes. Immunostains are necessary to further characterize the process [5].

Staging is recommended to evaluate the extent of disease in patients with CD30+ lymphoma. This includes a complete history; physical examination; routine blood tests; computerized tomography scans of the chest, abdomen, and pelvis; and a bone marrow biopsy. Long-term follow-up evaluation is necessary as patients may have a relapsing course [1].

Treatment for patients with CD30+ lymphoma is directed by the extent of skin involvement and the presence of extracutaneous disease. For localized disease, excision of the tumor or radiation is preferred. For mulifocal disease, radiation therapy and systemic chemotherapy should be considered. The standard chemotherapy regimen consists of a doxorubicin-based multiagent protocol, such as CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone). In cases of extracutaneous disease, systemic therapy is the standard of care [1, 2]. A new anti-CD30 monoclonal antibody has also been described [6]. In general, prognosis for cutaneous disease is excellent with a five-year-survival rate of 90 percent [7].

References

1. Bekkenk MW, et al. Primary and secondary cutaneous CD30+ lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment. Blood 2000; 95: 3653

2. Liu HL, et al. CD30+ cutaneous lymphoproliferative disorders: the Stanford experience in lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. J Am Acad Dermatol 2003; 49:1049

3. Latkowski J, Heald P. Cutaneous T-cell lymphomas. In: Freedberg IM, et al., eds. Fitzpatrick's Dermatology in General Medicine, 6th edition. New York, McGraw- Hill, 2003:1537

4. Fletcher CL, et al. CD30+ cutaneous lymphoma in association with atopic eczema. Arch Dermatol 2004;140:449

5. LeBoit PE, McCalmont TH. Cutaneous lymphomas and leukemias. In: Elder D, et al., eds. Lever's Histopathology of the Skin. 8th edition. Philadelphia: Lippincott, Williams and Wilkins,1997:805

6. Shehan JM, et al. Management of multifocal primary cutaneous CD30+anaplastic large cell lymphoma. J Am Acad Dermatol 2004;51:103

7. Fung MA, et al. Practical evaluation and management of cutaneous lymphoma. J Am Acad Dermatol 2002;46:325

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