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Cutaneous CD8+ T-cell lymphoma. Regression after HIV antiviral triple therapy
Med Clin (Barc). 2015;145(11):e33–e34
www.elsevier.es/medicinaclinica
Letter to the Editor Cutaneous CD8+ T-cell lymphoma. Regression after HIV antiviral triple therapy夽 Linfoma cutáneo CD8+ en paciente con infección por el VIH, con resolución tras la instauración de tratamiento antirretroviral de gran actividad Dear Editor, HIV, especially in patients with severe immunosuppression, is associated with aggressive lymphomas, especially extranodal.1–3 Although most lymphomas in HIV patients are B cell, the most common primary cutaneous lymphomas are T cell.1,4 We report the case of a 52-year-old man with no history of interest who consulted for cutaneous lesions among which a mild erythroderma stood out, together with alopecia universalis. There were no other associated symptoms, no lymphadenopathy or organomegaly. 2 skin biopsies were performed, showing a dermal infiltrate consisting of atypical lymphocytes with epidermotropism, which formed microabscesses, infecting hair follicles. Immunohistochemistry showed that the cells were CD3+, CD8+ preferably; a small percentage expressing CD4+. The study of monoclonal TCR gamma gene rearrangement analysis by CRP in both samples was monoclonal positive in the same peak, made with Biomed-2 protocols with capillary electrophoresis reading and analysis in duplicate. Lymphocyte subpopulations were visible in flow cytometry with a slight increase of NK cells, with emphasis in a CD4/CD8 ratio inversion (0.57), no other abnormalities. HIV serology was positive, with an HIV viral load of 19,600 copies/ml and absolute CD4 of 280/l, with the remaining serology being negative (HBV, HCV, syphilis). The extension study with pan-CT was negative. With these data the diagnosis of cutaneous CD8+ T-cell lymphoma associated with HIV infection was made. The patient started highly active antiretroviral therapy (HAART) with abacavir, 3TC, azatanavir and ritonavir, with disappearance of erythema and complete repopulation of hair after 4 months of starting HAART and undetectable viral load 10 months after the start of the said medication. Lymphoproliferative processes have been published with an apparent reactive nature in patients with HIV infection, as well as inflammatory dermatoses, which can mimic cutaneous T-cell lymphoma, both clinically and histologically,1,2,5,6 however, the description of real CD8+ T lymphomas in these patients is extremely rare in medical literature. To make this diagnosis, there must be a clinical, histopathological and molecular agreement. A double analysis of monoclonal TCR gamma gene rearrangement analysis with Biomed-2 protocols is performed in 2 skin biopsies from different
夽 Please cite this article as: Santesteban Muruzábal R, Mitxelena Ezeiza J, Córdoba Iturriagagoitia A, Yanguas Bayona I. Linfoma cutáneo CD8+ en paciente con infección por el VIH, con resolución tras la instauración de tratamiento antirretroviral de gran actividad. Med Clin (Barc). 2015;145:e33–e34. ˜ S.L.U. All rights reserved. 2387-0206/© 2015 Elsevier Espana,
anatomical areas has been described to increase the diagnostic accuracy of these processes. If an identical clone is identified in both skin biopsies, this result allows high specificity in distinguishing between cutaneous lymphoma and inflammatory dermatoses.7 In our case, the clinical symptoms and features of erythroderma and alopecia, atypical CD8 infiltrate with microabscess formation and monoclonal TCR gamma gene rearrangement analysis by positive CRP, with identical clone in 2 skin biopsies from different anatomical areas, allow the diagnosis of cutaneous CD8+ T lymphoma. The cases described in medical literature of patients with HIV and atypical cutaneous T cell infiltrates usually had a poor response to most local or systemic therapies, except to systemic glucocorticoids, which, before the use of HAART, were considered treatment of choice for these diseases.8,9 In general, atypical cutaneous T cell infiltrates in HIV patients had a poor prognosis,8 but later, after the introduction of HAART, several cases of very good response have been described for these skin diseases using only this treatment due to HIV infection.8–10 The differential diagnosis of a patient infected with HIV who presents with infiltrated skin lesions, alopecia universalis, eosinophilia or weight loss should include cutaneous CD8+ T lymphoma, CD8+ T pseudolymphoma, primary hypereosinophilic syndrome, toxicoderma, atopic or contact dermatitis, papuloerythroderma of Ofuji and parasitic infestations.2 Also, a patient with erythema, alopecia and skin infiltrates with predominance of CD8+ atypical lymphocytes, histologically diagnosed, should have HIV serology.8 We present a new case of cutaneous CD8+ T cell lymphoma associated with HIV, a very rare entity of which we have only found one case like ours described in medical literature. In our patient, we highlight the monoclonal TCR gamma gene rearrangement analysis by CRP with the same monoclonal result in 2 separate biopsies taken from different anatomical regions and rapid resolution of skin lesions, with complete repopulation of alopecia universalis after initiating antiretroviral therapy, a fact that is consistent with other published cases of both CD8+ T lymphoma as well as pseudolymphoma associated with HIV, placing HAART as first-line treatment for these skin diseases in HIV-infected patients. References 1. Guitart J, Variakojis D, Kuzel T, Rosen S. Cutaneous CD8+ T cell infiltrates in advanced HIV infection. J Am Acad Dermatol. 1999;41:722–7. 2. Fernández-Morano T, Aguilar-Bernier M, del Boz J, Fúnez-Liébana R. Cutaneous CD8+ T-cell infiltrates associated with human immunodeficiency virus. Actas Dermosifiliogr. 2012;103:638–40. 3. Burns MK, Cooper KD. Cutaneous T-cell lymphoma associated with HIV infection. J Am Acad Dermatol. 1993;29:394–9. 4. Kerschmann RL, Berger TG, Weiss LM, Herndier BG, Abrahms KM, Heon V, et al. Cutaneous presentations of lymphoma in human immunodeficiency virus disease. Predominance of T cell lineage. Arch Dermatol. 1995;131:1281–8. 5. Bachelez H, Hadida F, Parizot C, Flageul B, Kemula M, Dubertret L, et al. Oligoclonal expansion of HIV-specific cytotoxic CD8 T lymphocytes in the skin of HIV-1-infected patients with cutaneous pseudolymphoma. J Clin Invest. 1998;101:2506–16.
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Letter to the Editor / Med Clin (Barc). 2015;145(11):e33–e34
6. Bergman R. Pseudolymphoma and cutaneous lymphoma: facts and controversies. Clin Dermatol. 2010;28:568–74. 7. Thurber SE, Zhang B, Kim YH, Schrijver I, Zehnder J, Kohler S. T-cell clonality analysis in biopsy specimens from two different skin sites shows high specificity in the diagnosis of patients with suggested mycosis fungoides. J Am Acad Dermatol. 2007;57:782–90. 8. Hivnor CM, Nguyen V, Rook AH, Junkins-Hopkins J, Gelfand JM, Nasta S, et al. CD8+ lymphoma in a patient with human immunodeficiency virus. Arch Dermatol. 2005;141:1321–2. 9. Schartz NE, de la Blanchardiére A, Alaoui S, Morel P, Sigaux F, Vignon-Pennamen MD, et al. Regression of CD8+ pseudolymphoma after HIV antiviral triple therapy. J Am Acad Dermatol. 2003;49:139–41. 10. Nasta SD, Carrum GM, Shahab I, Hanania NA, Udden MM. Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy. Leuk Lymphoma. 2002;43:423–6.
Raquel Santesteban Muruzábal ∗ , Josune Mitxelena Ezeiza, Alicia Córdoba Iturriagagoitia, Ignacio Yanguas Bayona Servicio de Dermatología, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain ∗ Corresponding
author. E-mail address: [email protected] (R. Santesteban Muruzábal).
www.elsevier.es/medicinaclinica
Letter to the Editor Cutaneous CD8+ T-cell lymphoma. Regression after HIV antiviral triple therapy夽 Linfoma cutáneo CD8+ en paciente con infección por el VIH, con resolución tras la instauración de tratamiento antirretroviral de gran actividad Dear Editor, HIV, especially in patients with severe immunosuppression, is associated with aggressive lymphomas, especially extranodal.1–3 Although most lymphomas in HIV patients are B cell, the most common primary cutaneous lymphomas are T cell.1,4 We report the case of a 52-year-old man with no history of interest who consulted for cutaneous lesions among which a mild erythroderma stood out, together with alopecia universalis. There were no other associated symptoms, no lymphadenopathy or organomegaly. 2 skin biopsies were performed, showing a dermal infiltrate consisting of atypical lymphocytes with epidermotropism, which formed microabscesses, infecting hair follicles. Immunohistochemistry showed that the cells were CD3+, CD8+ preferably; a small percentage expressing CD4+. The study of monoclonal TCR gamma gene rearrangement analysis by CRP in both samples was monoclonal positive in the same peak, made with Biomed-2 protocols with capillary electrophoresis reading and analysis in duplicate. Lymphocyte subpopulations were visible in flow cytometry with a slight increase of NK cells, with emphasis in a CD4/CD8 ratio inversion (0.57), no other abnormalities. HIV serology was positive, with an HIV viral load of 19,600 copies/ml and absolute CD4 of 280/l, with the remaining serology being negative (HBV, HCV, syphilis). The extension study with pan-CT was negative. With these data the diagnosis of cutaneous CD8+ T-cell lymphoma associated with HIV infection was made. The patient started highly active antiretroviral therapy (HAART) with abacavir, 3TC, azatanavir and ritonavir, with disappearance of erythema and complete repopulation of hair after 4 months of starting HAART and undetectable viral load 10 months after the start of the said medication. Lymphoproliferative processes have been published with an apparent reactive nature in patients with HIV infection, as well as inflammatory dermatoses, which can mimic cutaneous T-cell lymphoma, both clinically and histologically,1,2,5,6 however, the description of real CD8+ T lymphomas in these patients is extremely rare in medical literature. To make this diagnosis, there must be a clinical, histopathological and molecular agreement. A double analysis of monoclonal TCR gamma gene rearrangement analysis with Biomed-2 protocols is performed in 2 skin biopsies from different
夽 Please cite this article as: Santesteban Muruzábal R, Mitxelena Ezeiza J, Córdoba Iturriagagoitia A, Yanguas Bayona I. Linfoma cutáneo CD8+ en paciente con infección por el VIH, con resolución tras la instauración de tratamiento antirretroviral de gran actividad. Med Clin (Barc). 2015;145:e33–e34. ˜ S.L.U. All rights reserved. 2387-0206/© 2015 Elsevier Espana,
anatomical areas has been described to increase the diagnostic accuracy of these processes. If an identical clone is identified in both skin biopsies, this result allows high specificity in distinguishing between cutaneous lymphoma and inflammatory dermatoses.7 In our case, the clinical symptoms and features of erythroderma and alopecia, atypical CD8 infiltrate with microabscess formation and monoclonal TCR gamma gene rearrangement analysis by positive CRP, with identical clone in 2 skin biopsies from different anatomical areas, allow the diagnosis of cutaneous CD8+ T lymphoma. The cases described in medical literature of patients with HIV and atypical cutaneous T cell infiltrates usually had a poor response to most local or systemic therapies, except to systemic glucocorticoids, which, before the use of HAART, were considered treatment of choice for these diseases.8,9 In general, atypical cutaneous T cell infiltrates in HIV patients had a poor prognosis,8 but later, after the introduction of HAART, several cases of very good response have been described for these skin diseases using only this treatment due to HIV infection.8–10 The differential diagnosis of a patient infected with HIV who presents with infiltrated skin lesions, alopecia universalis, eosinophilia or weight loss should include cutaneous CD8+ T lymphoma, CD8+ T pseudolymphoma, primary hypereosinophilic syndrome, toxicoderma, atopic or contact dermatitis, papuloerythroderma of Ofuji and parasitic infestations.2 Also, a patient with erythema, alopecia and skin infiltrates with predominance of CD8+ atypical lymphocytes, histologically diagnosed, should have HIV serology.8 We present a new case of cutaneous CD8+ T cell lymphoma associated with HIV, a very rare entity of which we have only found one case like ours described in medical literature. In our patient, we highlight the monoclonal TCR gamma gene rearrangement analysis by CRP with the same monoclonal result in 2 separate biopsies taken from different anatomical regions and rapid resolution of skin lesions, with complete repopulation of alopecia universalis after initiating antiretroviral therapy, a fact that is consistent with other published cases of both CD8+ T lymphoma as well as pseudolymphoma associated with HIV, placing HAART as first-line treatment for these skin diseases in HIV-infected patients. References 1. Guitart J, Variakojis D, Kuzel T, Rosen S. Cutaneous CD8+ T cell infiltrates in advanced HIV infection. J Am Acad Dermatol. 1999;41:722–7. 2. Fernández-Morano T, Aguilar-Bernier M, del Boz J, Fúnez-Liébana R. Cutaneous CD8+ T-cell infiltrates associated with human immunodeficiency virus. Actas Dermosifiliogr. 2012;103:638–40. 3. Burns MK, Cooper KD. Cutaneous T-cell lymphoma associated with HIV infection. J Am Acad Dermatol. 1993;29:394–9. 4. Kerschmann RL, Berger TG, Weiss LM, Herndier BG, Abrahms KM, Heon V, et al. Cutaneous presentations of lymphoma in human immunodeficiency virus disease. Predominance of T cell lineage. Arch Dermatol. 1995;131:1281–8. 5. Bachelez H, Hadida F, Parizot C, Flageul B, Kemula M, Dubertret L, et al. Oligoclonal expansion of HIV-specific cytotoxic CD8 T lymphocytes in the skin of HIV-1-infected patients with cutaneous pseudolymphoma. J Clin Invest. 1998;101:2506–16.
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Letter to the Editor / Med Clin (Barc). 2015;145(11):e33–e34
6. Bergman R. Pseudolymphoma and cutaneous lymphoma: facts and controversies. Clin Dermatol. 2010;28:568–74. 7. Thurber SE, Zhang B, Kim YH, Schrijver I, Zehnder J, Kohler S. T-cell clonality analysis in biopsy specimens from two different skin sites shows high specificity in the diagnosis of patients with suggested mycosis fungoides. J Am Acad Dermatol. 2007;57:782–90. 8. Hivnor CM, Nguyen V, Rook AH, Junkins-Hopkins J, Gelfand JM, Nasta S, et al. CD8+ lymphoma in a patient with human immunodeficiency virus. Arch Dermatol. 2005;141:1321–2. 9. Schartz NE, de la Blanchardiére A, Alaoui S, Morel P, Sigaux F, Vignon-Pennamen MD, et al. Regression of CD8+ pseudolymphoma after HIV antiviral triple therapy. J Am Acad Dermatol. 2003;49:139–41. 10. Nasta SD, Carrum GM, Shahab I, Hanania NA, Udden MM. Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy. Leuk Lymphoma. 2002;43:423–6.
Raquel Santesteban Muruzábal ∗ , Josune Mitxelena Ezeiza, Alicia Córdoba Iturriagagoitia, Ignacio Yanguas Bayona Servicio de Dermatología, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain ∗ Corresponding
author. E-mail address: [email protected] (R. Santesteban Muruzábal).