Introduction
Kaposi’s sarcoma is an angioproliferative disease associated with human herpesvirus 8 (HHV8). Iatrogenic Kaposi’s sarcoma typically affects patients who undergo long-term immunosuppressant treatments for solid-organ transplantations and immune-mediated diseases or malignancies.1,2 Immunosuppression is thought to lead to Kaposi’s sarcoma by allowing the reactivation of a preexisting HHV8 infection and by giving rise to the proliferative transformation of infected endothelial cells.2
Here, we report a case of new-onset Kaposi’s sarcoma in a patient with a history of mantle cell lymphoma previously treated with chemotherapy, autologous stem-cell transplantation (SCT), and rituximab.
Case Report
A 52-year-old male patient of Turkish descent presented to our cutaneous lymphoma multidisciplinary clinic with a 2-month history of tender violaceous lesions on the face, neck, and upper chest. Medical history was notable for mantle cell lymphoma in remission after chemotherapy (rituximab, dexamethasone, cytarabine, cisplatin/oxaliplatin), and autologous SCT had been performed 5 months before the onset of the rash. The patient noticed that the cutaneous lesions appeared shortly after receiving the first dose of rituximab, administered to him as maintenance therapy. No other immunosuppressive therapy was used at presentation. Physical examination revealed violaceous papules that were 2 to 5 mm in diameter and grouped on bilateral nasal alae and ear lobes (Figs 1A and 1B). Purple papules were also seen on the patient’s neck and upper chest, as well as on the hard palate. Skin biopsy demonstrated well-defined cellular dermal nodules that were comprised of spindle cells with peripheral slit-like spaces, extravasated erythrocytes, and inflammatory cells (Figs 1C and 1D). Tumor cell nuclei stained positive for HHV8 (Fig 1E). Serologic studies were negative for HIV, and radiology studies demonstrated no visceral involvement. Diagnosis of Kaposi’s sarcoma was made and the rituximab treatment was stopped. On follow-up, Kaposi’s sarcoma lesions have remained stable for 1 year now and the patient continues to be monitored.
Fig 1.
Clinical and histopathologic findings of Kaposi’s sarcoma. (A and B) Clinically, purple papules 2 to 5 mm in diameter are clustered on the (A) ear lobe and (B) nose. (C and D) Histopathology examination showed (C) dermal nodules that were comprised of spindle cells with (D) peripheral slit-like spaces, extravasated erythrocytes, and inflammatory cells. (E) Tumor cell nuclei stained positive for human herpesvirus 8. Original magnification, × 10 (C), × 40 (D and E).
Discussion
Kaposi’s sarcoma has four principal clinical variants: classic, endemic, iatrogenic, and AIDS-associated Kaposi’s sarcoma.1 The presented case could be considered as classic or iatrogenic Kaposi’s sarcoma. Our patient’s demographics are characteristic for classic Kaposi’s sarcoma; however, this variant usually presents as chronic lesions that are confined to the lower extremities.1 As for iatrogenic Kaposi’s sarcoma, our patient was immunosuppressed by autologous SCT, previous chemotherapy, and a conditioning regimen, as well as recent rituximab therapy. Development of Kaposi’s sarcoma after SCT is uncommon and only few cases of autologous SCT–related Kaposi’s sarcoma have been thus far reported.3,4 Recipients of autologous SCT demonstrate a profound and long-lasting impairment of cellular immunity in addition to secondary immune deficiency as a result of previous chemotherapy and conditioning regimen,3 and it was suggested that in the SCT setting, withdrawal of immunosuppression alone or watchful waiting can be effective in Kaposi’s sarcoma that is limited to the skin.4
A retrospective study in a single center studied 143 cases of iatrogenic Kaposi’s sarcoma and confirmed that corticosteroids and cyclosporine are the most frequent immunosuppressive drugs that are associated with Kaposi’s sarcoma, and, of interest, rituximab was described in two cases.2 Rituximab is known to cause or exacerbate Kaposi’s sarcoma in patients with HIV-associated multicentric Castleman’s disease as well as in those with HIV-negative multicentric Castleman’s disease.5 Four patients who received rituximab for different indications and developed Kaposi’s sarcoma have been recently reported.6 A literature review revealed several additional case reports that have described HIV-negative patients who developed Kaposi’s sarcoma in association with rituximab (Table 1). In all of these cases, previous or concurrent immunosuppressive therapies were described, which makes it difficult to appreciate the direct role of rituximab in the development of Kaposi’s sarcoma. Decreased T-cell immunity is thought to be associated with Kaposi’s sarcoma development, and the exact mechanism that links rituximab-mediated CD20+ B-cell depletion with HHV8 activation and the development of Kaposi’s sarcoma is unclear. We cannot rule out that, in our patient, the cumulative immunosuppressive effect of chemotherapy, a conditioning regimen, autologous SCT, and rituximab were, together, related to the onset of Kaposi’s sarcoma.
Table 1.
Rituximab-Associated Kaposi’s Sarcoma Cases Reported in the Literature
ACKNOWLEDGMENT
Funded, in part, by US National Institutes of Health, National Cancer Institute Cancer Center Support Grant No. P30-CA008748. Presented at the 2018 American Academy of Dermatology Annual Meeting, San Diego, CA, February 17, 2018.
AUTHOR CONTRIBUTIONS
Conception and design: All authors
Provision of study materials or patients: Klaus J. Busam, Patricia L. Myskowski
Collection and assembly of data: All authors
Data analysis and interpretation: All authors
Manuscript writing: All authors
Final approval of the manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Kaposi’s Sarcoma After Autologous Stem-Cell Transplantation and Rituximab Treatment
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jop/site/ifc/journal-policies.html.
Shamir Geller
Patents, Royalties, Other Intellectual Property: Royalties for contributions to UpToDate
Mark A. Dickson
Consulting or Advisory Role: Celgene
Research Funding: Eli Lilly
Klaus J. Busam
No relationship to disclose
Patricia L. Myskowski
No relationship to disclose
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