Dermatology Online Journal

Anaplastic large-cell T-cell lymphoma
Jennifer A Stein MD PhD, Anthony C Soldano MD, Jo-Ann M Latkowski MD
Dermatology Online Journal 14 (5): 15

Department of Dermatology, New York University

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Abstract

A 64-year-old woman presented with 2 years of pruritic and ulcerated nodules and tumors on the trunk and arms. Histopathologic examination showed a diffuse infiltrate that consisted of predominantly small lymphocytes and scattered large atypical multinucleated cells positive for CD30. These findings were consistent with a diagnosis of anaplastic large-cell T-cell lymphoma, which is a CD30+ cutaneous lymphoma. This case highlights the importance of considering both histopathologic and clinical criteria in diagnosing a patient with a CD30+ cutaneous lymphoma.

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Clinical synopsis

A 64-year-old woman was referred to the Charles C. Harris Skin and Cancer Pavilion from Coney Island Hospital with a 2-year history of waxing and waning, pruritic, ulcerated nodules on the arms and trunk. Her past medical history includes eczema since age 13 and her review of systems was negative. Two biopsy specimens from the left arm had been performed at Coney Island Hospital and disclosed a diagnosis of lymphomatoid papulosis. Additional biopsy specimens from nodules on the right flank and left arm were obtained at the Charles Harris Skin and Cancer Pavilion with similar interpretations. The patient's care was then transferred to the Dermatology Clinic at Bellevue Hospital Center at which time another biopsy was performed. A systemic evaluation was initiated.

Physical examination

Scattered, hyper- and hypo-pigmented papules, nodules, and plaques were present on the trunk and arms. Several tumors were larger than 5 cm, and many were ulcerated. The patient has no cervical, axillary, or inguinal lymphadenopathy or hepatosplenomegaly.

Figure 1	Figure 2

Laboratory data

A complete blood count showed an elevated eosinophil count of 37 percent. Lactate dehydrogenase was elevated at 730 u/L. The alkaline phosphatase was 134 u/L. Basic metabolic panel was normal. Chest computed tomography scan showed enlarged bilateral axillary lymph nodes and multiple sub-centimeter pulmonary nodules. A PET-CT scan showed increased activity within axillary and cervical lymph nodes. Fine needle aspiration of a left cervical lymph node showed multinucleated, atypical cells with numerous eosinophils.

Histopathology

There is a diffuse infiltrate within the papillary and reticular dermis. This mixed-cell infiltrate is composed predominantly of lymphocytes admixed with eosinophils, histiocytes, and plasma cells. Scattered within the infiltrate are large, atypical cells with hyperchromatic nuclei, large single basophilic nucleoli, and irregular nuclear contours. The epidermis shows spongiosis. Immunohistochemical stains were performed on formalin fixed, paraffin-embedded tissue sections. The small lymphocytes are positive for CD2, CD3, CD5, with partial loss of CD7. The CD4 and CD8 ratio is approximately 1.0. The large, atypical cells, which comprise less than 10 percent of the cellular components, stain positive for CD30. No monoclonal T-cell receptor gamma gene rearrangements are identified by molecular studies.

Comment

The CD30+ primary cutaneous T cell lymphomas represent about 30 percent of all primary cutaneous T-cell lymphomas, second only to mycosis fungoides (MF). The CD30+ cutaneous lymphomas are thought to represent a spectrum of disease, with lymphomatoid papulosis (LyP) at the benign end and primary cutaneous anaplastic large cell lymphoma (PCALCL) at the other. Some cases histologically resemble LyP but clinically look like PCALCL or vice versa, and these cases are referred to as borderline CD30+ cutaneous lymphomas [1, 2]. Clinically, PCALCL presents as either single lesions, which range from smaller papules to very large tumors, or multifocal disease. The 5-year-survival rate of PCALCL is 95 percent and about 20 percent of lesions regress spontaneously. Draining lymph nodes are found to be positive in about 25 percent of cases, but this finding does not seem to alter the prognosis [3, 4, 5, 6]. Histopathologically, dense clusters or nodules of large CD30+ tumor cells are observed in PCALCL. Greater than 75 percent of tumor cells should be CD30+ for a diagnosis of PCALCL. The pathologic findings of MF, large cerebriform cells and epidermotropism, are absent in PCALCL. The CD30+ tumor cells are CD4+ and can have loss of T-cell markers, such as CD2, CD3, and CD5. CD30 is an antigen found on activated T- or B-cells. The CD30+ tumor cells can express other activation markers such as CD25, T9, HECA-452 but generally do not express EMA or CD15. Cell surface markers can help in distinguishing PCALCL from its nodal counterpart with secondary cutaneous disease. The PCALCL tumors more commonly express HECA-452 and not EMA; secondary disease is more likely to express EMA and not HECA-452 [1]. Systemic lymphomas are also more likely to contain the t(2;5) translocation, which creates the novel fusion protein NPM-ALK [7]. Distinguishing PCALCL from secondary disease is important, because patients with secondary skin disease generally have a worse prognosis and often need to be treated more aggressively [1, 4]. The distinction between PCACL and LyP is also important. By definition, PCALCL has sheets of CD30+ tumor cells and a scant inflammatory infiltrate, whereas in LyP, the inflammatory infiltrate predominates over the tumor cells. The histopathologic findings in LyP vary and are subdivided into three types. Type A contains scattered CD30+ blast cells and an extensive inflammatory infiltrate, type B shows atypical CD30- T cells with cerebriform nuclei that resemble those seen in MF, and type C lesions demonstrate large clusters of CD30+ cells with few inflammatory cells. Type-C lesions can closely resemble PCALCL histopathologically. Ultimately, both the clinical and histopathologic features must be considered in making a final diagnosis of PCALCL or LyP [1, 2, 8]. Clinically, LyP presents as chronic, recurrent, and self-resolving erythematous-to-brown papules and nodules. The lesions of LyP are more often papules or nodules and occur frequently in a generalized pattern. In distinction, PCALCL is better characterized by fewer but larger nodules and tumors. Although both LyP and PCALCL have favorable prognoses, LyP is thought to almost always undergo spontaneous remission, whereas this occurs in PCALCL only about 20 percent of the time. Extracutaneous disease is extremely rare in LyP but is found in about 25 percent of PCALCL patients [2, 3, 4, 5, 6]. Treatment of PCALCL is determined by the extent of disease. It is crucial to distinguish it from LyP when determining treatment because of its potentially more aggressive course. Although both diseases have an overall favorable prognosis, LyP has a 100 percent survival rate and should not be treated aggressively as PCALCL sometimes requires. The standard treatment of single or localized PCALCL lesions is local excision or radiation [4, 9]. Case reports have described the use of intralesional methotrexate and topical imiquimod [10, 11, 12]. Systemic methotrexate has been used to treat more generalized lesions [4, 9, 13]. Chemotherapy is usually reserved for patients with systemic involvement. The treatment of patients with only skin and nodal disease is controversial, with some practitioners favoring radiation and chemotherapy for these patients [2, 3, 4, 5, 6].

References

1. Willemze R, Beljaards RC. Spectrum of primary cutaneous CD30 (Ki-1)-positive lymphoproliferative disorders: a proposal for classification and guidelines for management and treatment. J Am Acad Dermatol 1993; 28:973

2. Willemze R, et al. WHO-EORTC classification for cutaneous lymphomas. Blood 2005; 105:3768

3. 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

4. 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

5. Vergier B, et al. Statistical evaluation of diagnostic and prognostic features of CD30+ cutaneous lymphoproliferative disorders: a clinicopathologic study of 65 cases. Am J Surg Pathol 1998; 22:1192

6. Paulli M, et al. CD30/Ki-1-positive lymphoproliferative disorders of the skin- clinicopathologic correlation and statistical analysis of 86 cases: a multicentric study from the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group. J Clin Oncol 1995; 13:1343

7. DeCoteau JF, et al. The t(2;5) chromosomal translocation is not a common feature of primary cutaneous CD30+ lymphoproliferative disorders: comparison with anaplastic large-cell lymphoma of nodal origin. Blood 1996; 87:3437

8. El Shabrawi-Caelen L, et al. Lymphomatoid papulosis: reappraisal of clinicopathologic presentation and classification into subtypes A, B, and C. Arch Dermatol 2004; 140:441

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

10. Blume JE, et al. Treatment of primary cutaneous CD30+ anaplastic large cell lymphoma with intralesional methotrexate. J Am Acad Dermatol 2006; 54: S229

11. Coors EA, et al. Topical imiquimod as treatment for different kinds of cutaneous lymphoma. Eur J Dermatol 2006; 16:391

12. Didona B, et al. Primary cutaneous CD30+ T-cell lymphoma responsive to topical imiquimod (Aldara).Br J Dermatol 2004; 150:1198

13. Vonderheid EC, et al. Methotrexate is effective therapy for lymphomatoid papulosis and other primary cutaneous CD30-positive lymphoproliferative disorders. J Am Acad Dermatol 1996; 34:470

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