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Inicio Enfermedades Infecciosas y Microbiología Clínica Anaplastic large cell lymphoma as a cause of rapidly appearing subcutaneous nodu...
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Vol. 30. Núm. 9.
Páginas 581-582 (noviembre 2012)
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Vol. 30. Núm. 9.
Páginas 581-582 (noviembre 2012)
Scientific letter
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Anaplastic large cell lymphoma as a cause of rapidly appearing subcutaneous nodules in an HIV-infected patient
Nódulos subcutáneos de rápida aparición como forma de presentación de linfoma Ten paciente con infección por VIH
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Javier Rianchoa,
Autor para correspondencia
jariancho@humv.es

Corresponding author.
, Carmen Gutiérrez-Velab, Raquel Sánchezc, Carmen Valeroc
a Service of Neurology, Hospital U.M. Valdecilla, University of Cantabria, Santander, Spain
b Service of Pathology, Hospital U.M. Valdecilla, University of Cantabria, Santander, Spain
c Service of Internal Medicine, Hospital U.M. Valdecilla, University of Cantabria, Santander, Spain
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To the Editor,

AIDS patients have an increased risk of cancer, and one third of them will eventually develop a tumour. The risk of non-Hodgkin lymphomas (NHL) is much higher than in immunocompetent individuals.1 However, this risk has decreased since highly active antiretroviral treatment (HAART) was introduced, and the frequency has now been reported to be 1–4% in modern series.2 T-cell derived lymphomas are uncommon and represent less than 3% of NHL, and they usually present worse outcomes than B-cell derived ones.3 We report a patient with AIDS who developed a rapidly evolving T-cell type NHL.

A 50 year-old patient was admitted to hospital due to fever, weight loss and malaise for the past 3 weeks. He had a history of intravenous drug use and was diagnosed with HIV infection and hepatitis C virus-associated liver disease 11 years earlier. One year before the current admission he suffered P. jiroveci pneumonia, but refused to take HAART or prophylactic drugs against opportunistic infections. The physical examination was remarkable for low body weight (body mass index 17kg/m2), and enlargement of the liver and spleen. There were no palpable lymph nodes. Blood analyses revealed a normocytic anaemia, a markedly increased ESR, 14 CD4 cells/μl, and 1,480,000 HIV copies/μl. Chest X-ray revealed a slight interstitial pattern. All microbiological tests were negative. A CT scan revealed a 3cm×5cm necrotic mediastinal lymph node, with an inconclusive biopsy. A bone marrow biopsy showed non-specific abnormalities. In the following days subcutaneous painful nodules appeared in the abdomen. They were about 2cm in diameter, but the size changed, enlarging or decreasing over a few days. An excisional biopsy of one of these nodules revealed a dense infiltrate of lymphoid cells with horse-shoe nuclei in the hypodermis, with abundant expression of Ki67 in most cells (a cell proliferation marker) and positive staining for CD3, CD4, CD30, and EMA, being negative for CD8, CD15, CD20, ALK, LMP1, HHV8, consistent with ALK-negative anaplastic large cell lymphoma of T-cell type. Due to the poor patient status, HAART with atazanavir/ritonavir, lamivudine and abacavir was initiated prior to chemotherapy. However, the patient deteriorated rapidly and died 2 weeks later due to a lung infection.

Unlike from lymphomas derived from B-cells, T-cell lymphomas tend to be extranodal, with a higher propensity to affect skin and bone marrow.4,5 Among them the peripheral T-cell lymphoma is the most frequent, while other subtypes, such as angioimmunoblastic and anaplastic large cell lymphoma (ALCL) are less common. Less than 40 cases of ALCL have been reported in HIV-infected patients.6,7

ALCL was first characterised by Stein, who described a new type of lymphoma consisting of large anaplastic lymphoid cells with a strong expression of CD30, and a tendency to grow cohesively and invade lymph node sinuses.8 As in our case the common type is characterised by sheets of large lymphoid cells with horseshoe-shaped nuclei containing multiple nucleoli. Tumour cells have an abundant cytoplasm with vacuoles and an increased Golgi region. Most cases of ALCL express T-cell markers. The CD3 complex (TCR) is one of the most commonly expressed T-cell antigens, whereas unlike that of our patient CD4 or CD8 expression is less common.9 Some ALCLs are associated with a 2;5 chromosomal translocation encoding the tyrosine kinase anaplastic lymphoma kinase (ALK).10 It is assumed that both CD30 and ALK are involved in the growth and replication of the tumour cells.7

ALCL in HIV-infected patients has a distinct course, being much more aggressive than in immunocompetent patients. Although it is usually associated with extranodal involvement and systemic symptoms,5 presentation with rapidly appearing painful subcutaneous nodes, as in our patient, is very rare. Two clinical forms of ALCL have been described, systemic and cutaneous.7 Although the skin may be involved in both forms, in systemic cases the hypodermis is affected, but characteristically the dermis is preserved. This was the pattern in the case reported here. As in this case, ALCL tends to affect patients with severe immunodepression, and contrary to cases in non-infected population, rarely expresses ALK, which is associated with better responses to chemotherapy.4,9 Immune reconstitution by HAART is crucial. Anti-neoplastic regimens are frequently considered, but the prognosis is poor, with a median survival of 5 months.5,10

Although uncommon, clinicians caring for patients with HIV infection should be aware of this tumour, especially in patients presenting with swollen lymph nodes, or subcutaneous nodes. Since it affects patients with severe immunodeficiency, and has an ominous prognosis, good control of HIV infection and subsequent immunodepression is the best preventive strategy.

References
[1]
A.E. Grulich, M.T. van Leeuwen, M.O. Falster, C.M. Vajdic.
Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis.
[2]
J. Stebbing, B. Gazzard, S. Mandalia, A. Teague, A. Waterston, V. Marvin, et al.
Antiretroviral treatment regimens and immune parameters in the prevention of systemic AIDS-related non-Hodgkin's lymphoma.
J Clin Oncol, 22 (2004), pp. 2177-2183
[3]
K.K. Arzoo, X. Bu, B.M. Espina, L. Seneviratne, B. Nathwani, A.M. Levine.
T-cell lymphoma in HIV-infected patients.
J Acquir Immune Defic Syndr, 36 (2004), pp. 1020-1027
[4]
J.J. Castillo, B.E. Beltran, M. Bibas, M. Bower, J.A. Collins, K. Cwynarski, et al.
Prognostic factors in patients with HIV-associated peripheral T-cell lymphoma: a multicenter study.
Am J Hematol, 86 (2011), pp. 256-261
[5]
K. Perez, J. Castillo, B.J. Dezube, L. Pantanowitz.
Human immunodeficiency virus-associated anaplastic large cell lymphoma.
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[6]
H. Stein, D.Y. Mason, J. Gerdes, N. O’Connor, J. Wainscoat, G. Pallesen, et al.
The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed–Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells.
Blood, 66 (1985), pp. 848-858
[7]
H. Stein, H.D. Foss, H. Durkop, T. Marafioti, G. Delsol, K. Pulford, et al.
CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.
Blood, 96 (2000), pp. 3681-3695
[8]
H.M. Amin, R. Lai.
Pathobiology of ALK+ anaplastic large-cell lymphoma.
Blood, 110 (2007), pp. 2259-2267
[9]
K.J. Savage, N.L. Harris, J.M. Vose, F. Ullrich, E.S. Jaffe, J.M. Connors, et al.
ALK-anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project.
Blood, 111 (2008), pp. 5496-5504
[10]
V.E. Nava, P. Cohen, M. Kalan, M. Ozdemirli.
HIV-associated anaplastic large cell lymphoma: a report of three cases.
Copyright © 2012. Elsevier España, S.L.. All rights reserved
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