VOLUME

28

NUMBER

FEBRUARY

20

2010

JOURNAL OF CLINICAL ONCOLOGY

D I A G N O S I S

I N

O N C O L O G Y

Presentation of Extranodal Natural Killer T-Cell Lymphoma, Nasal Type, With Poorly Circumscribed Erythematous Patches
A 54-year-old white man with a past medical history signicant only for mild hypercholesterolemia developed a poorly circumscribed 3 cm erythematous patch on his left upper thigh (Fig 1A). The patient was concerned about the skin lesion and showed it to his primary care physician, who attributed it to a change in the brand of the HMG-CoA reductase inhibitor taken by the patient. However, the lesion persisted despite discontinuation of the medication. Four months later, the patient developed severe nasal congestion, initially diagnosed as allergic rhinitis, and later by an otolaryngologist as nasal polyposis after an intranasal exam revealed a small nasal mass. Glucocorticoids led to a limited response. A repeat intranasal exam 4 months later (8 months after the initial appearance of his thigh lesion) revealed that the nasal mass had increased in size. A magnetic resonance imaging scan showed a left nasal cavity mass measuring 3.7 cm 3.6 cm 0.8 cm, which on biopsy revealed a dense proliferation of lymphoid cells inltrating into the mucosa with an immunophenotype of CD3/CD56/TIA-1/CD30/CD20 and positive in situ hybridization (ISH) for Epstein-Barr virus (EBV), ndings diagnostic of extranodal natural killer (NK)/T-cell lymphoma. A staging evaluation indicated involvement only of the cervical lymph nodes. Although the patient showed the erythematous patch on his thigh to both his community oncologist and radiation oncologist during the staging evaluation, it was dismissed as a minor skin rash unrelated to the lymphoma. A skin biopsy was not performed at that time. He was therefore diagnosed with stage II nasal extranodal NK/T-cell lymphoma, and treated with radiation therapy to the nasopharynx and the cervical nodes. Two weeks after initiating radiation therapy, the patient abruptly developed numerous cutaneous lesions on his trunk and extremities, including additional poorly circumscribed erythematous patches (Fig 1B) and multiple erythematous to violaceous well-demarcated plaques and nodules (Fig 1C). A biopsy from a new nodule revealed a monomorphous inltrate of lymphocytes (Fig 2A) with a CD56 (Fig 2B)/CD3/ TIA/CD7/CD4/CD20 immunophenotype. ISH for EBV showed diffuse nuclear positivity (Fig 2C). A biopsy from the initial erythematous patch was also performed and showed the same histopathology, immunophenotype, and diffuse EBV positivity via ISH as seen in Figure 2. Genotypic analysis via polymerase chain reaction did not show a clonal rearrangement of T-cell receptor genes. The patient was then diagnosed with cutaneous involvement of extranodal NK/T-cell lymphoma, and referred to the university oncology division for treatment. Since the cutaneous lesion on left thigh lesion was the initial presentation of disease, the patient was restaged to stage IV disease. He was recognized to have
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2009 by American Society of Clinical Oncology

Fig 1.

extranodal NK/T-cell lymphoma, nasal type, presenting in skin with subsequent development of symptoms in the aerodigestive tract, rather than nasal extranodal NK/T-cell lymphoma, which had been his original diagnosis.
Journal of Clinical Oncology, Vol 28, No 6 (February 20), 2010: pp e94-e95

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Diagnosis in Oncology

Fig 2.

Most descriptions of the cutaneous manifestations of extranodal NK/T-cell lymphoma, nasal-type, are of well-circumscribed lesions such as nodules/tumors1-7 and/or plaques.4-7 Other clinical morphologies, also all well-circumscribed, have been reported, including papules,1 cysts,1 ulcers,5 and cellulitis.5 Although one older report described the cutaneous presentation of extranodal NK/T-cell lymphoma as poorly circumscribed erythematous patches,8 more recent reports have not recognized this clinical presentation.1-7 The patient described in this report clearly demonstrates that extranodal NK/Tcell lymphoma, nasal type, may present with poorly circumscribed erythematous patches. Unfortunately, this presentation was not recognized by the patients oncologist or the radiation oncology, largely because it did not t the classic descriptions in the literature of wellcircumscribed lesions. It was only when the patient developed typical well-circumscribed plaques and nodules that skin biopsies were done from both a nodule and from the initial poorly circumscribed left thigh erythematous patch. Both biopsies showed lymphoma, demonstrating that the patch that initially appeared in January 2008 was composed of lymphoma cells. Since patches are subtle and not as easily appreciated on physical examination as plaques and nodules, it is important to raise awareness of this inconspicuous presentation of disease. Therefore, in a patient with extranodal NK/T-cell lymphoma, a skin biopsy should be obtained from any suspicious clinical lesion, including poorly circumscribed erythematous patches, to assess for possible cutaneous involvement of lymphoma. Furthermore, in some cases, patch morphology may be the presenting manifestation of the disease, as it was in the patient discussed here. In addition, the differential diagnosis of cutaneous erythematous patches should include extranodal NK/T-cell lymphoma, nasal type.

Isaac M. Neuhaus
Department of Dermatology, University of California, San Francisco, San Francisco, CA

Charalambos Andreadis
Department of Medicine, Division of Hematology/Oncology, University of San Francisco, San Francisco, CA

Timothy H. McCalmont
Departments of Dermatology and Pathology, University of California, San Francisco, San Francisco, CA

AUTHORS DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conicts of interest.

REFERENCES
1. Natkunam Y, Smoller BR, Zehnder JL, et al: Aggressive cutaneous NK and NK-like T-cell lymphomas: Clinicopathologic, immunohistochemical, and molecular analyses of 12 cases. Am J Surg Pathol 23:571-581, 1999 2. Child FJ, Mitchell TJ, Whittaker SJ, et al: Blastic natural killer cell and extranodal natural killer cell-like T-cell lymphoma presenting in the skin: Report of six cases from the UK. Br J Dermatol 148:507-515, 2003 3. Watabe D, Kanno H, Inoue-Narita T, et al: A case of primary cutaneous natural killer/T-cell lymphoma, nasal type, with indolent clinical course: Monoclonal expansion of Epstein-Barr virus genome correlating with the terminal aggressive behaviour. Br J Dermatol 160:205-207, 2009 4. Gniadecki R, Rossen K, Ralfkier E, et al: CD56 lymphoma with skin involvement: Clinicopathologic features and classication. Arch Dermatol 140: 427-436, 2004 5. Choi YL, Park JH, Namkung JH, et al: Extranodal NK/T-cell lymphoma with cutaneous involvement: Nasal vs. nasal-type subgroupsa retrospective study of 18 patients. Br J Dermatol 160:333-337, 2009 6. Cerroni L, Gatter K, Kerl H: An Illustrated Guide to Skin Lymphoma (ed 2). Malden, MA, Blackwell, 2004 7. Bolognia J, Jorizzo JL, Rapini RP: Dermatology. Edinburgh, United Kingdom, Mosby, 2003 8. Miyamoto T, Yoshino T, Takehisa T, et al: Cutaneous presentation of nasal/nasal type T/NK cell lymphoma: Clinicopathological ndings of four cases. Br J Dermatol 139:481-487, 1998

Laura B. Pincus
Department of Dermatology, University of California, San Francisco, San Francisco, CA

James L. Zehnder
Department of Pathology, Stanford University, Stanford, CA

DOI: 10.1200/JCO.2009.24.3428; published online ahead of print at www.jco.org on November 23, 2009

www.jco.org

2009 by American Society of Clinical Oncology

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