Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Reversible rituximab-induced rectal Kaposi’s sarcoma misdiagnosed as ulcerative colitis in a patient with HIV-negative follicular lymphoma

Reversible rituximab-induced rectal Kaposi’s sarcoma misdiagnosed as ulcerative colitis in a... Background: Kaposi’s sarcoma is a low‑ grade mesenchymal angioproliferative tumor, most commonly observed in immunocompromised individuals, such as HIV‑ infected patients. Iatrogenic Kaposi’s sarcoma occurs in patients undergoing immunosuppressive therapies. Rituximab is a chimeric monoclonal antibody targeted against the pan B cell marker CD20. Because of its immunosuppressive effects through reduction of mature B ‑ cells, it may exacerbate Kaposi’s sarcoma in HIV‑ positive patients. Rituximab‑ related Kaposi’s sarcomas have been previously reported in only two HIV‑ negative patients and were treated surgically. Case presentation: Here, we report on a Kaposi’s sarcoma that developed under rituximab treatment in a HIV‑ negative 55‑ year‑ old patient treated for follicular lymphoma. The lesion developed during the maintenance rituximab therapy at the rectal level with an aspect of apparent ulcerative colitis, without any cutaneous lesion. The premature stop of rituximab led to the complete regression of Kaposi’s sarcoma, without any additional specific treatment. Conclusions: To our knowledge, this is the third case of Kaposi’s sarcoma diagnosed under rituximab in a HIV‑ nega‑ tive patient, the first one at the rectal level and the first one that completely regresses after stop of rituximab. This case raises awareness of iatrogenic Kaposi’s sarcoma in HIV‑ negative patients treated with rituximab, and further highlights the importance of immunosuppression in the pathophysiology of disease. Keywords: Follicular lymphoma, Immune suppression, Kaposi sarcoma, Rituximab Kaposi’s sarcoma occurs in patients undergoing immuno- Background suppressive therapies for autoimmune disorders or after Kaposi’s sarcoma is a low-grade mesenchymal angiopro- organ transplantation [1]. liferative tumor caused by the lytic replication of human Rituximab is a chimeric murine/human monoclo- herpesvirus type 8 (HHV8), identified with Polymerase nal antibody (mAb) targeted against the pan B-cell Chain Reaction (PCR) in 95% of cases. The lesions pre - marker CD20. It was the first mAb to receive approval dominantly present at muco-cutaneous sites, but may by the Food and Drug Administration for use in can- involve all organs and anatomic locations. Kaposi’s sar- cer treatment. Since its approval for relapsed/refractory coma occurs most commonly in immunocompromised non-Hodgkin’s lymphoma in 1997, rituximab has been individuals such as HIV-infected patients. Iatrogenic licensed for use in the treatment of numerous other B-cell malignancies, including the follicular lymphoma *Correspondence: bertuccif@ipc.unicancer.fr 1 [2], as well as autoimmune conditions, including rheuma- INSERM UMR1068, CNRS UMR725, Department of Medical Oncology, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli‑ toid arthritis. Because of its immunosuppressive effects Calmettes, 232 Bd de Sainte‑Marguerite, 13009 Marseille, France through action on CD20 and reduction of mature B-cells, Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Billon et al. Clin Sarcoma Res (2018) 8:11 Page 2 of 8 rituximab therapy may exacerbate Kaposi’s sarcoma in our institution (Fig. 1A, B). There was no clinical general HIV-positive patients [3]. Rituximab-related Kaposi’s sar- symptom, and the disease stage was II. He had no specific comas have been previously reported in two HIV-nega- personal or familial medical history. Because of the low tive patients, without multicentric Castelman’s disease [4, malignancy grade and the low tumor mass, no treatment 5], and were treated surgically. was introduced, and a monitoring was set up. In June We herein report a rectal Kaposi’s sarcoma that devel- 2015, because of increase in size of cervical adenopathies, oped under rituximab treatment in a HIV-negative therapy combining rituximab (375  mg/m ) and benda- patient treated for follicular lymphoma, and that com- mustine (90  mg/m ) was initiated. Six monthly cycles pletely regressed upon cessation of rituximab, without were delivered, with good tolerance and complete met- any additional specific treatment. abolic response (PET-scan of October 2015), then fol- lowed by maintenance rituximab (375 mg/m , 1 injection Case presentation every 2  months) started in December 2015 and planned In July 2014, a 55-year-old Caucasian man with cervical for 2 years (Fig. 2) [6]. and mediastinal polyadenopathies was diagnosed with In June 2016, before the fourth maintenance injec- a non-Hodgkin follicular lymphoma (WHO grade 2) in tion, the patient developed diarrhea alternating with Fig. 1 PET‑scan imaging. A, B PET ‑scan of July 2014 at time of diagnosis, showing hypermetabolic cervical, mediastinal and hilar lymphadenopa‑ thies (red arrows). There was no digestive localization. C, D PET‑scan of October 2016, showing pulmonary FDG uptake compatible with lung infec‑ tion. No suspect FDG uptake of lymphoma recurrence or digestive uptake was found Billon et al. Clin Sarcoma Res (2018) 8:11 Page 3 of 8 constipation, nausea, associated with weight loss. Colo- noscopy showed sigmoiditis, with a 4-mm-depth rectal ulceration at 20 cm of the anal canal (Fig.  3), compatible with ulcerative colitis. Multiple biopsies were performed, and the provisional diagnosis of ulcerative colitis was retained before availability of pathological results. No fecal calprotectin measurement was done. Mesalazine therapy (2  g/day) was introduced in September 2016. Pathological analysis of the colic biopsies showed aspects of non-specific subacute colitis. However, the rectal biopsy showed a spindle-cell proliferation with high cell density. Cell atypia were moderate, the cytoplasm was scarce, and the nuclei were slightly dyscaryotic, with rare mitoses. There was no necrosis. Immunohistochemis - try (IHC) revealed positive staining of cancer cells for CD34 and negative for CD117. The diagnosis of Kaposi’s sarcoma was suspected, and the samples were sent to 1 cm our Department of Pathology for reviewing by expert pathologist within the French Sarcoma Network (Réseau Fig. 3 Colonoscopy imaging. Colonoscopy of June 2016 showing de Référence en Pathologie des Sarcomes, RRePS). The sigmoiditis, with a 4‑mm‑ depth rectal ulceration (black arrow) at diagnosis of rectal Kaposi’s sarcoma was confirmed in 20 cm of the anal canal, compatible with ulcerative colitis October 2016: there was an ill-defined, fasciculated to diffuse proliferation of spindle cells with little to mod - erate nuclear atypia and few mitoses, outlining vascular Given the description in the literature of rituximab- slots; IHC showed positive staining of tumor cells for induced Kaposi’s sarcoma in HIV-positive patients, CD31 and ERG endothelial markers and for HHV8, and rituximab was prematurely discontinued in October 2016 negative staining for CD117, DOG1, and STAT6 (Fig. 4). after the sixth maintenance injection. At this time, PET- No cutaneous lesion was present. The patient stopped scan showed neither suspect hypermetabolism of lym- mesalazine after 1  month treatment because of relief phomatous recurrence, nor digestive FDG uptake likely of digestive symptoms and the diagnosis of ulcerative because of the disappearance of colitis after mesalazine colitis was not finally retained because of pathological treatment and the low proliferation rate of sarcoma. We results Blood tests did not detect HHV-8 viremia, and the noted only the appearance of lung lesions of infectious patient was serologically negative for HIV-1 and HIV-2, appearance without concomitant respiratory and infec- hepatitis B and C, and HTLV1 viruses. The circulating tious clinical symptoms (Fig.  1C, D). In December 2016, CD4+ T-cell count was 387/mm . after complete disappearance of digestive symptoms, the patient underwent a colonoscopy, which was strictly Kaposi’s sarcomadiagnosis Treatment NHL diagnosis Rituximabdiscontinuation introduction Therapeutic Rituximab + Rituximabmaintenance treatment: x 6 Active monitoring abstention bendamustine: x 6 July 2014 June 2015 Oct. 2015 Dec. 2015 // June 2016 Sept. 2016 Oct. 2016 Dec. 2016 // Oct. 2017 Digestive symptoms Mesalazine Positive colonoscopy Negative colonoscopy Fig. 2 Timeline of patient’s care Billon et al. Clin Sarcoma Res (2018) 8:11 Page 4 of 8 a b 500 µm 100 µm 100 µm 100 µm Fig. 4 Pathological aspect of the rectal Kaposi’s sarcoma. a Microscopic aspect of the biopsy of rectal ulceration: the rectal mucosa is infiltrated by an ill‑ defined cellular fasciculated to diffuse proliferation (HES ×10). b Microscopic aspect showing spindle cells with little to moderate nuclear atypia surround vascular clefts. Few mitoses are noted. Lymphocytes and plasma cells are admixed (HES ×40). c IHC with ERG antibody: the lining cells of vascular structures and spindle cells express the ERG endothelial marker (×20). d IHC with HHV8 antibody: see the nuclear positive immu‑ nostaining of spindle tumor cells (×40) normal without any sign of rectal Kaposi’s sarcoma or to prematurely stop the treatment. Interestingly, stopping colitis. Because of the infectious images on the PET-scan, rituximab allowed the complete regression of Kaposi’s explorations were carried out with pneumocystis PCR, sarcoma. To our knowledge, this is the first description of and CMV, HSV, and HTLV1 serologies. All these explo- such case in the literature. rations remained negative, as well as a bronchoscopy. Of Two other cases of rituximab-induced Kaposi’s sar- note, in July 2017, the colonoscopy was normal, notably coma in HIV-negative patients have been reported in the at the rectal level. In October 2017, 12  months after the literature. One case of cutaneous Kaposi’s sarcoma was last dose of rituximab maintenance, our patient was still described in a patient treated with rituximab for throm- in complete remission of his lymphoma. botic thrombocytopenic purpura. The lesion was treated with cryodestruction [4]. Another case was reported in Discussion and conclusions an 84-year-old patient after undergoing rituximab-con- We report a case of rectal Kaposi’s sarcoma likely taining chemotherapy (R-CHOP regimen) for the treat- induced by rituximab therapy in a HIV-negative patient ment of a diffuse large B-cell lymphoma (DLBCL); after treated for a follicular lymphoma. The lesion developed the seventh cycle, the patient developed a severe bacterial while being treated with maintenance rituximab, leading pneumonia and subsequent CMV viremia. The cutaneous Billon et al. Clin Sarcoma Res (2018) 8:11 Page 5 of 8 Kaposi’s sarcoma developed after the complete resolution of Kaposi’s sarcoma in these patients. As B-cells are the of pneumonia and was treated with surgical resection HHV8’s main human reservoir, another hypothesis may [5]. Our case is the first rituximab-induced Kaposi’s sar - be that B-cell depletion induced by rituximab can expose coma that developed at the mucosa level. The diagnosis endothelial cells to high HHV8 level, causing latent viral of Kaposi’s sarcoma of the bowel was difficult to estab - infection, and promoting Kaposi’s sarcoma development lish immediately in the absence of skin and oral lesions, [23]. In HIV-positive patients, lower B-cell counts are and a provisional diagnosis of ulcerative colitis was made associated with the risk of Kaposi’s sarcoma development before availability of pathological results. We suppose [27], suggesting a role of humoral immune system in that the inflammation present in the mucosa was sec - disease etiopathogenesis. One study, which investigated ondary to the underlying submucosal Kaposi’s sarcoma the pathological findings in a HIV-positive patient with ulceration. Kaposi’s sarcoma of the bowel presenting as rituximab-related Kaposi’s sarcoma who was treated for apparent ulcerative colitis has already been reported in multicentric Castleman’s disease, showed depletion of HIV-positive patients several years ago, when the patho- intralesional B-lymphocytes accompanied with an upreg- logical diagnosis used antibodies for IHC less sensitive ulation of the HHV8 gene product K5 [28]. These authors and specific than now [7, 8]. But, intestinal Kaposi’s sar- also postulated that the diminished B-lymphocyte count coma has also been reported during the last decades in interfered with the normal immune response to HHV8, HIV-negative patients treated with immunosuppressive allowing for viral activation. Unfortunately, the circulat- drugs for ulcerative colitis or Crohn disease, mimick- ing CD20+ cell count and the Ig levels were not avail- ing acute flare of colitis. Table  1 summarizes the cases able for our patient, but they were low in the Ureshino’s reported since 2000 [9–22], as well as the other cases case [5]. Despite the widespread use of rituximab, there diagnosed in HIV-negative patients treated with immu- has been only one case of rituximab-related Kaposi’s nosuppressive drugs after organ transplantation or for sarcoma in HIV-negative patients with DLBCL [5], and another inflammatory disease. In our case, we observed it was suggested that additional factors causing systemic the complete resolution of Kaposi’s sarcoma 2  months inflammation, such as an infection, might contribute to after rituximab discontinuation without the use of any the development of Kaposi’s sarcoma in addition to ritux- specific treatment. To our knowledge, this is the first case imab. In our patient, lung infection may have triggered of reversible rituximab-induced KS described in the lit- Kaposi’s sarcoma progression. erature. In their review, Antman and Chang [23] reported In conclusion, we report the case of Kaposi’s sarcoma several examples of Kaposi’s sarcoma regressions in diagnosed under rituximab in a HIV-negative patient, renal transplant recipients after cessation, reduction or the first one at the rectal level, and the first one that modification of immunosuppressive therapy. However, completely regressed after cessation of rituximab. This such modification led to graft rejection in approximately case further highlights the importance of immunosup- half of the patients. Similarly, in a HIV-negative patient pression in the pathophysiology of Kaposi’s sarcoma and treated with corticosteroid for idiopathic thrombocyto- how immune restitution takes part in its management. It penic purpura, the skin Kaposi’ tumors regressed soon also suggests awareness of iatrogenic Kaposi’s sarcoma after discontinuation of corticosteroid therapy, and no in patients treated with rituximab. Even if the occur- recurrence was observed during the 30-month follow-up rence of Kaposi’s sarcoma is a very rare event, vigilance period [24]. In our case, we suppose that the rituximab is needed, particularly for cancer patients often immu- cessation permitted immune restitution and regression of nocompromised by disease and treatments. Patients at Kaposi’s sarcoma. risk of HHV8 infection (ethnicity with high Fitzpatrick The role of CD4 T-cells in the Kaposi’s sarcoma patho - skin phototype, Mediterranean or equatorial African physiology is suspected [25], especially in HIV-positive geographic origin, male gender, homosexuality or multi- patients who usually present Kaposi’s sarcoma when ple sexual partners, immune deficiency) should be care - circulating CD4+ T-cell count is under 350/mm under fully screened for HHV8 before rituximab and closely highly active antiretroviral therapy [26]. In our case as monitored during treatment. Even if efforts to develop a well as in Ureshino’s case, the CD4+ T-cell count was HHV8 vaccine are ongoing [29], no prophylaxis for Kapo- higher than 350/mm [5], suggesting that cellular immu- si’s sarcoma is available today. Finally, given the risk of nodeficiency played only a minor role in the development lymphoma progression after rituximab cessation, further Billon et al. Clin Sarcoma Res (2018) 8:11 Page 6 of 8 ‑ ‑ ‑ ‑ ‑ ‑ ‑ Table 1 Published cases of intestinal Kaposi’s sarcoma in HIV-negative patients after 2000 First author Year Sex Age at diagnosis Clinical conditions Visceral KS localiza- Immunosuppres- Tumor HHV8 status Blood HHV8 status KS management (years) tions sion therapy Cohen 2001 F 67 Crohn disease Ileum Prednisone ND ND Discontinuation of immunosuppressive therapy Kang 2004 F 60 Ulcerative colitis Colon Prednisone + ND ND Nepomniashchaia 2004 M 41 Allogenic kidney Stomach, intestinal ND ND ND ND transplantation mesentery, cerebral Bursics 2005 M 49 Ulcerative colitis Colon Methylprednisolone − − Discontinuation of immunosuppressive therapy and colopro tectomy Svrcek 2009 M 62 Ulcerative colitis Rectum Steroid, azathioprine + + Discontinuation of immunosuppressive therapy and colopro tectomy Girelli 2009 M 43 Ulcerative colitis Descending colon Prednisone, mesala + − Discontinuation of zine, ciclosporin immunosuppressive therapy and colopro tectomy Rodriguez 2010 M 65 Ulcerative colitis Colon Prednisone, metho + + Discontinuation of trexate immunosuppressive therapy and colopro tectomy Tas 2012 F 77 Chronic anemia Colon, lymph nodes None + ND Etoposide Pioche 2013 M 49 Ulcerative colitis Colon Corticosteroids, + + Coloprotectomy azathioprine, ciclo sporin, infliximab Hamzaoui 2013 M 30 Ulcerative colitis Colorectal Prednisone, mesala + ND Subtotal colectomy zine, azathioprine, infliximab Herculano 2014 M 63 Ulcerative colitis Sigmoid colon Prednisolone, mesala + − Discontinuation of zine immunosuppressive therapy Windon 2017 M 21 Crohn disease Colon Prednisone, infliximab − − Discontinuation of immunosuppressive therapy Duh 2017 M 48 Ulcerative colitis Rectum Prednisone + ND Discontinuation of immunosuppressive therapy followed by subtotal colectomy Kumar 2017 M 70 Ulcerative colitis Ascending colon None + ND ND KS Kaposi’s sarcoma, F female, M male, ND not determined Billon et al. Clin Sarcoma Res (2018) 8:11 Page 7 of 8 4. Jerdan K, Brownell J, Singh M, Braniecki M, Chan L. A case report of studies are needed to better understand the immunologi- iatrogenic cutaneous Kaposi sarcoma due to rituximab therapy for cal mechanisms involved in rituximab-induced Kaposi’s thrombotic thrombocytopenic purpura. Acta Oncol. 2017;56:111–3. sarcoma and to define optimal treatment. 5. Ureshino H, Ando T, Kojima K, Itamura H, Jinnai S, Doi K, et al. Rituximab‑ containing chemotherapy (R‑ CHOP)‑induced Kaposi’s sarcoma in an HIV‑negative patient with diffuse large B cell lymphoma. Intern Med. 2015;54:3205–8. Abbreviations 6. Salles G, Seymour JF, Offner F, López‑ Guillermo A, Belada D, Xerri L, CMV: cytomegalovirus; DLBCL: diffuse large B‑ cell lymphoma; HHV8: human et al. Rituximab maintenance for 2 years in patients with high tumour herpes virus type 8; HIV: human immunodeficiency virus; HSV: herpes simplex burden follicular lymphoma responding to rituximab plus chemotherapy virus; HTLV1: human T‑ cell lymphotropic virus de type I; IHC: immunohis‑ (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011;377:42–51. tochemistry; mAb: monoclonal antibody; PCR: polymerase chain reaction; 7. Biggs BA, Crowe SM, Lucas CR, Ralston M, Thompson IL, Hardy KJ. AIDS PET‑scan: positron emission tomography scan; RRePS: Réseau de Référence en related Kaposi’s sarcoma presenting as ulcerative colitis and complicated Pathologie des Sarcomes; WHO: World Health Organization. by toxic megacolon. Gut. 1987;28:1302–6. 8. Weber JN, Carmichael DJ, Boylston A, Munro A, Whitear WP, Pinching AJ. Authors’ contributions Kaposi’s sarcoma of the bowel‑presenting as apparent ulcerative colitis. Conception and design: FB; Manuscript writing: FB and EB; Final approval: FB, Gut. 1985;26:295–300. EB, AMS, LM, MB, AM, DP; Pathological explorations: LM; Patient’s manage‑ 9. Cohen RL, Tepper RE, Urmacher C, Katz S. Kaposi’s sarcoma and cyto‑ ment: AMS, MB, LM, FB. All authors read and approved the final manuscript. megaloviral ileocolitis complicating long‑standing Crohn’s disease in an HIV‑negative patient. Am J Gastroenterol. 2001;96:3028–31. Author details 10. Kang MJ, Namgung KY, Kim MS, Ko BS, Han CS, Ahn HT, et al. A case of INSERM UMR1068, CNRS UMR725, Department of Medical Oncology, Centre Kaposi’s sarcoma associated with ulcerative colitis. Korean J Gastroenterol de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli‑ Calmettes, Taehan Sohwagi Hakhoe Chi. 2004;43:316–9. 232 Bd de Sainte‑Marguerite, 13009 Marseille, France. Department of Hema‑ 11. Nepomniashchaia EM, Gusarev SA, Kirichenko IG. Generalized Kaposi’s tology, Institut Paoli‑ Calmettes, Marseille, France. Department of Pathol‑ sarcoma after allogenic transplantation of cadaver kidney. Arkh Patol. ogy, Institut Paoli‑ Calmettes, Marseille, France. Department of Digestive 2004;66:55–7. Endoscopy Centre Hospitalier Edmond Garcin, Aubagne, France. Faculty 12. Bursics A. HHV‑8 positive, HIV negative disseminated Kaposi’s sarcoma of Medicine, Aix‑Marseille University, Marseille, France. French Sarcoma complicating steroid dependent ulcerative colitis: a successfully treated Group, Paris, France. case. Gut. 2005;54:1049–50. 13. Svrcek M, Tiret E, Bennis M, Guyot P, Fléjou J‑F. KSHV/HHV8‑associated Acknowledgements intestinal Kaposi’s sarcoma in patient with ulcerative colitis receiv‑ Our work is supported by Institut Paoli‑ Calmettes. ing immunosuppressive drugs: report of a case. Dis Colon Rectum. 2009;52:154–8. Competing interests 14. Girelli CM, Serio G, Rocca E, Rocca F. Refractory ulcerative colitis and The authors declare that they have no competing interests. iatrogenic colorectal Kaposi’s sarcoma. Dig Liver Dis. 2009;41:170–4. 15. Rodríguez‑Peláez M, Fernández‑ García MS, Gutiérrez‑ Corral N, de Fran‑ Availability of data and materials cisco R, Riestra S, García‑Pravia C, et al. Kaposi’s sarcoma: an opportunistic Not applicable. infection by human herpesvirus‑8 in ulcerative colitis. J Crohns Colitis. 2010;4:586–90. Consent for publication 16. Tas F, Yegen G, Keskin S, Gozubuyukoglu N. Classic Kaposi’s sarcoma with Written informed consent was obtained from the patient for publication of colonic involvement: a rare presentation with successful treatment with this Case report and any accompanying images. oral etoposide. J Cancer Res Ther. 2012;8:112. 17. Pioche M, Boschetti G, Cotte E, Graber I, Moussata D, François Y, et al. Ethics approval and consent to participate Human herpesvirus 8‑associated colorectal Kaposi’s sarcoma occurring in Not applicable. a drug‑induced immunocompromised patient with refractory ulcerative colitis: report of a new case and review of the literature. Inflamm Bowel Funding Dis. 2013;19:E12–5. Not applicable. 18. Hamzaoui L, Kilani H, Bouassida M, Mahmoudi M, Chalbi E, Siai K, et al. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative Publisher’s Note colitis in a human immunodeficiency negative ‑ virus patient. Pan Afr Med Springer Nature remains neutral with regard to jurisdictional claims in pub‑ J. 2013;15. https://doi.org/10.11604/pamj.2013.15.154.2988. lished maps and institutional affiliations. 19. Herculano R, Barreiro P, Hann A, Chapim I, Bispo M, Santos S, et al. Drug‑ induced colonic Kaposi’s sarcoma in a HIV‑negative patient with ulcera‑ Received: 10 November 2017 Accepted: 13 March 2018 tive colitis: a case report and review of the literature. Int J Colorectal Dis. 2014;29:1441–2. 20. Windon AL, Shroff SG. Iatrogenic Kaposi’s sarcoma in an HIV ‑negative young male with Crohn’s disease and IgA nephropathy: a case report and brief review of the literature. Int J Surg Pathol. 2017. https://doi. org/10.1177/1066896917736610. References 21. Duh E, Fine S. Human herpesvirus‑8 positive iatrogenic Kaposi’s sar ‑ 1. Geraminejad P, Memar O, Aronson I, Rady PL, Hengge U, Tyring SK. coma in the setting of refractory ulcerative colitis. World J Clin Cases. Kaposi’s sarcoma and other manifestations of human herpesvirus 8. J Am 2017;5:423–7. Acad Dermatol. 2002;47:641–55. 22. Kumar V, Soni P, Garg M, Abduraimova M, Harris J. Kaposi sarcoma mim‑ 2. Fisher RI, LeBlanc M, Press OW, Maloney DG, Unger JM, Miller TP. New icking acute flare of ulcerative colitis. J Investig Med High Impact Case treatment options have changed the survival of patients with follicular Rep. 2017;5:232470961771351. lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23:8447–52. 23. Antman K, Chang Y. Kaposi’s sarcoma. N Engl J Med. 2000;342:1027–38. 3. Gérard L, Michot J‑M, Burcheri S, Fieschi C, Longuet P, Delcey V, et al. 24. Toyohama T, Nagasaki A, Miyagi J, Takamine W, Sunagawa K, Uezato H, Rituximab decreases the risk of lymphoma in patients with HIV‑associ‑ et al. Kaposi’s sarcoma in a human immunodeficiency virus‑negative ated multicentric Castleman disease. Blood. 2012;119:2228–33. patient treated with corticosteroid for idiopathic thrombocytopenic purpura. Intern Med Tokyo Jpn. 2003;42:448–9. Billon et al. Clin Sarcoma Res (2018) 8:11 Page 8 of 8 25. Robey RC, Mletzko S, Gotch FM. The T‑ cell immune response against 28. Pantanowitz L, Früh K, Marconi S, Moses AV, Dezube BJ. Pathology of Kaposi’s sarcoma‑associated herpesvirus. Adv Virol. 2010;2010:1–9. rituximab‑induced Kaposi sarcoma flare. BMC Clin Pathol. 2008;8:7. 26. Lupia R, Wabuyia PB, Otiato P, Fang C‑ T, Tsai F‑ J. Risk factors for Kaposi’s 29. Wu TT, Qian J, Ang J, Sun R. Vaccine prospect of Kaposi sarcoma‑associ‑ sarcoma in human immunodeficiency virus patients after initiation of ated herpesvirus. Curr Opin Virol. 2012;2:482–8. antiretroviral therapy: A nested case–control study in Kenya. J Microbiol Immunol Infect. 2017;50:781–8. 27. Stebbing J, Gazzard B, Newsom‑Davis T, Nelson M, Patterson S, Gotch F, et al. Nadir B cell counts are significantly correlated with the risk of Kaposi’s sarcoma. Int J Cancer. 2004;108:473–4. Submit your next manuscript to BioMed Central and we will help you at every step: • We accept pre-submission inquiries • Our selector tool helps you to find the most relevant journal • We provide round the clock customer support • Convenient online submission • Thorough peer review • Inclusion in PubMed and all major indexing services • Maximum visibility for your research Submit your manuscript at www.biomedcentral.com/submit http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Sarcoma Research Springer Journals

Reversible rituximab-induced rectal Kaposi’s sarcoma misdiagnosed as ulcerative colitis in a patient with HIV-negative follicular lymphoma

Download PDF
8 pages

Loading next page...
 
/lp/springer-journals/reversible-rituximab-induced-rectal-kaposi-s-sarcoma-misdiagnosed-as-fqPvxMfRY2

References (30)

Publisher
Springer Journals
Copyright
Copyright © 2018 by The Author(s)
Subject
Biomedicine; Cancer Research; Oncology; Surgical Oncology
eISSN
2045-3329
DOI
10.1186/s13569-018-0097-7
Publisher site
See Article on Publisher Site

Abstract

Background: Kaposi’s sarcoma is a low‑ grade mesenchymal angioproliferative tumor, most commonly observed in immunocompromised individuals, such as HIV‑ infected patients. Iatrogenic Kaposi’s sarcoma occurs in patients undergoing immunosuppressive therapies. Rituximab is a chimeric monoclonal antibody targeted against the pan B cell marker CD20. Because of its immunosuppressive effects through reduction of mature B ‑ cells, it may exacerbate Kaposi’s sarcoma in HIV‑ positive patients. Rituximab‑ related Kaposi’s sarcomas have been previously reported in only two HIV‑ negative patients and were treated surgically. Case presentation: Here, we report on a Kaposi’s sarcoma that developed under rituximab treatment in a HIV‑ negative 55‑ year‑ old patient treated for follicular lymphoma. The lesion developed during the maintenance rituximab therapy at the rectal level with an aspect of apparent ulcerative colitis, without any cutaneous lesion. The premature stop of rituximab led to the complete regression of Kaposi’s sarcoma, without any additional specific treatment. Conclusions: To our knowledge, this is the third case of Kaposi’s sarcoma diagnosed under rituximab in a HIV‑ nega‑ tive patient, the first one at the rectal level and the first one that completely regresses after stop of rituximab. This case raises awareness of iatrogenic Kaposi’s sarcoma in HIV‑ negative patients treated with rituximab, and further highlights the importance of immunosuppression in the pathophysiology of disease. Keywords: Follicular lymphoma, Immune suppression, Kaposi sarcoma, Rituximab Kaposi’s sarcoma occurs in patients undergoing immuno- Background suppressive therapies for autoimmune disorders or after Kaposi’s sarcoma is a low-grade mesenchymal angiopro- organ transplantation [1]. liferative tumor caused by the lytic replication of human Rituximab is a chimeric murine/human monoclo- herpesvirus type 8 (HHV8), identified with Polymerase nal antibody (mAb) targeted against the pan B-cell Chain Reaction (PCR) in 95% of cases. The lesions pre - marker CD20. It was the first mAb to receive approval dominantly present at muco-cutaneous sites, but may by the Food and Drug Administration for use in can- involve all organs and anatomic locations. Kaposi’s sar- cer treatment. Since its approval for relapsed/refractory coma occurs most commonly in immunocompromised non-Hodgkin’s lymphoma in 1997, rituximab has been individuals such as HIV-infected patients. Iatrogenic licensed for use in the treatment of numerous other B-cell malignancies, including the follicular lymphoma *Correspondence: bertuccif@ipc.unicancer.fr 1 [2], as well as autoimmune conditions, including rheuma- INSERM UMR1068, CNRS UMR725, Department of Medical Oncology, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli‑ toid arthritis. Because of its immunosuppressive effects Calmettes, 232 Bd de Sainte‑Marguerite, 13009 Marseille, France through action on CD20 and reduction of mature B-cells, Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Billon et al. Clin Sarcoma Res (2018) 8:11 Page 2 of 8 rituximab therapy may exacerbate Kaposi’s sarcoma in our institution (Fig. 1A, B). There was no clinical general HIV-positive patients [3]. Rituximab-related Kaposi’s sar- symptom, and the disease stage was II. He had no specific comas have been previously reported in two HIV-nega- personal or familial medical history. Because of the low tive patients, without multicentric Castelman’s disease [4, malignancy grade and the low tumor mass, no treatment 5], and were treated surgically. was introduced, and a monitoring was set up. In June We herein report a rectal Kaposi’s sarcoma that devel- 2015, because of increase in size of cervical adenopathies, oped under rituximab treatment in a HIV-negative therapy combining rituximab (375  mg/m ) and benda- patient treated for follicular lymphoma, and that com- mustine (90  mg/m ) was initiated. Six monthly cycles pletely regressed upon cessation of rituximab, without were delivered, with good tolerance and complete met- any additional specific treatment. abolic response (PET-scan of October 2015), then fol- lowed by maintenance rituximab (375 mg/m , 1 injection Case presentation every 2  months) started in December 2015 and planned In July 2014, a 55-year-old Caucasian man with cervical for 2 years (Fig. 2) [6]. and mediastinal polyadenopathies was diagnosed with In June 2016, before the fourth maintenance injec- a non-Hodgkin follicular lymphoma (WHO grade 2) in tion, the patient developed diarrhea alternating with Fig. 1 PET‑scan imaging. A, B PET ‑scan of July 2014 at time of diagnosis, showing hypermetabolic cervical, mediastinal and hilar lymphadenopa‑ thies (red arrows). There was no digestive localization. C, D PET‑scan of October 2016, showing pulmonary FDG uptake compatible with lung infec‑ tion. No suspect FDG uptake of lymphoma recurrence or digestive uptake was found Billon et al. Clin Sarcoma Res (2018) 8:11 Page 3 of 8 constipation, nausea, associated with weight loss. Colo- noscopy showed sigmoiditis, with a 4-mm-depth rectal ulceration at 20 cm of the anal canal (Fig.  3), compatible with ulcerative colitis. Multiple biopsies were performed, and the provisional diagnosis of ulcerative colitis was retained before availability of pathological results. No fecal calprotectin measurement was done. Mesalazine therapy (2  g/day) was introduced in September 2016. Pathological analysis of the colic biopsies showed aspects of non-specific subacute colitis. However, the rectal biopsy showed a spindle-cell proliferation with high cell density. Cell atypia were moderate, the cytoplasm was scarce, and the nuclei were slightly dyscaryotic, with rare mitoses. There was no necrosis. Immunohistochemis - try (IHC) revealed positive staining of cancer cells for CD34 and negative for CD117. The diagnosis of Kaposi’s sarcoma was suspected, and the samples were sent to 1 cm our Department of Pathology for reviewing by expert pathologist within the French Sarcoma Network (Réseau Fig. 3 Colonoscopy imaging. Colonoscopy of June 2016 showing de Référence en Pathologie des Sarcomes, RRePS). The sigmoiditis, with a 4‑mm‑ depth rectal ulceration (black arrow) at diagnosis of rectal Kaposi’s sarcoma was confirmed in 20 cm of the anal canal, compatible with ulcerative colitis October 2016: there was an ill-defined, fasciculated to diffuse proliferation of spindle cells with little to mod - erate nuclear atypia and few mitoses, outlining vascular Given the description in the literature of rituximab- slots; IHC showed positive staining of tumor cells for induced Kaposi’s sarcoma in HIV-positive patients, CD31 and ERG endothelial markers and for HHV8, and rituximab was prematurely discontinued in October 2016 negative staining for CD117, DOG1, and STAT6 (Fig. 4). after the sixth maintenance injection. At this time, PET- No cutaneous lesion was present. The patient stopped scan showed neither suspect hypermetabolism of lym- mesalazine after 1  month treatment because of relief phomatous recurrence, nor digestive FDG uptake likely of digestive symptoms and the diagnosis of ulcerative because of the disappearance of colitis after mesalazine colitis was not finally retained because of pathological treatment and the low proliferation rate of sarcoma. We results Blood tests did not detect HHV-8 viremia, and the noted only the appearance of lung lesions of infectious patient was serologically negative for HIV-1 and HIV-2, appearance without concomitant respiratory and infec- hepatitis B and C, and HTLV1 viruses. The circulating tious clinical symptoms (Fig.  1C, D). In December 2016, CD4+ T-cell count was 387/mm . after complete disappearance of digestive symptoms, the patient underwent a colonoscopy, which was strictly Kaposi’s sarcomadiagnosis Treatment NHL diagnosis Rituximabdiscontinuation introduction Therapeutic Rituximab + Rituximabmaintenance treatment: x 6 Active monitoring abstention bendamustine: x 6 July 2014 June 2015 Oct. 2015 Dec. 2015 // June 2016 Sept. 2016 Oct. 2016 Dec. 2016 // Oct. 2017 Digestive symptoms Mesalazine Positive colonoscopy Negative colonoscopy Fig. 2 Timeline of patient’s care Billon et al. Clin Sarcoma Res (2018) 8:11 Page 4 of 8 a b 500 µm 100 µm 100 µm 100 µm Fig. 4 Pathological aspect of the rectal Kaposi’s sarcoma. a Microscopic aspect of the biopsy of rectal ulceration: the rectal mucosa is infiltrated by an ill‑ defined cellular fasciculated to diffuse proliferation (HES ×10). b Microscopic aspect showing spindle cells with little to moderate nuclear atypia surround vascular clefts. Few mitoses are noted. Lymphocytes and plasma cells are admixed (HES ×40). c IHC with ERG antibody: the lining cells of vascular structures and spindle cells express the ERG endothelial marker (×20). d IHC with HHV8 antibody: see the nuclear positive immu‑ nostaining of spindle tumor cells (×40) normal without any sign of rectal Kaposi’s sarcoma or to prematurely stop the treatment. Interestingly, stopping colitis. Because of the infectious images on the PET-scan, rituximab allowed the complete regression of Kaposi’s explorations were carried out with pneumocystis PCR, sarcoma. To our knowledge, this is the first description of and CMV, HSV, and HTLV1 serologies. All these explo- such case in the literature. rations remained negative, as well as a bronchoscopy. Of Two other cases of rituximab-induced Kaposi’s sar- note, in July 2017, the colonoscopy was normal, notably coma in HIV-negative patients have been reported in the at the rectal level. In October 2017, 12  months after the literature. One case of cutaneous Kaposi’s sarcoma was last dose of rituximab maintenance, our patient was still described in a patient treated with rituximab for throm- in complete remission of his lymphoma. botic thrombocytopenic purpura. The lesion was treated with cryodestruction [4]. Another case was reported in Discussion and conclusions an 84-year-old patient after undergoing rituximab-con- We report a case of rectal Kaposi’s sarcoma likely taining chemotherapy (R-CHOP regimen) for the treat- induced by rituximab therapy in a HIV-negative patient ment of a diffuse large B-cell lymphoma (DLBCL); after treated for a follicular lymphoma. The lesion developed the seventh cycle, the patient developed a severe bacterial while being treated with maintenance rituximab, leading pneumonia and subsequent CMV viremia. The cutaneous Billon et al. Clin Sarcoma Res (2018) 8:11 Page 5 of 8 Kaposi’s sarcoma developed after the complete resolution of Kaposi’s sarcoma in these patients. As B-cells are the of pneumonia and was treated with surgical resection HHV8’s main human reservoir, another hypothesis may [5]. Our case is the first rituximab-induced Kaposi’s sar - be that B-cell depletion induced by rituximab can expose coma that developed at the mucosa level. The diagnosis endothelial cells to high HHV8 level, causing latent viral of Kaposi’s sarcoma of the bowel was difficult to estab - infection, and promoting Kaposi’s sarcoma development lish immediately in the absence of skin and oral lesions, [23]. In HIV-positive patients, lower B-cell counts are and a provisional diagnosis of ulcerative colitis was made associated with the risk of Kaposi’s sarcoma development before availability of pathological results. We suppose [27], suggesting a role of humoral immune system in that the inflammation present in the mucosa was sec - disease etiopathogenesis. One study, which investigated ondary to the underlying submucosal Kaposi’s sarcoma the pathological findings in a HIV-positive patient with ulceration. Kaposi’s sarcoma of the bowel presenting as rituximab-related Kaposi’s sarcoma who was treated for apparent ulcerative colitis has already been reported in multicentric Castleman’s disease, showed depletion of HIV-positive patients several years ago, when the patho- intralesional B-lymphocytes accompanied with an upreg- logical diagnosis used antibodies for IHC less sensitive ulation of the HHV8 gene product K5 [28]. These authors and specific than now [7, 8]. But, intestinal Kaposi’s sar- also postulated that the diminished B-lymphocyte count coma has also been reported during the last decades in interfered with the normal immune response to HHV8, HIV-negative patients treated with immunosuppressive allowing for viral activation. Unfortunately, the circulat- drugs for ulcerative colitis or Crohn disease, mimick- ing CD20+ cell count and the Ig levels were not avail- ing acute flare of colitis. Table  1 summarizes the cases able for our patient, but they were low in the Ureshino’s reported since 2000 [9–22], as well as the other cases case [5]. Despite the widespread use of rituximab, there diagnosed in HIV-negative patients treated with immu- has been only one case of rituximab-related Kaposi’s nosuppressive drugs after organ transplantation or for sarcoma in HIV-negative patients with DLBCL [5], and another inflammatory disease. In our case, we observed it was suggested that additional factors causing systemic the complete resolution of Kaposi’s sarcoma 2  months inflammation, such as an infection, might contribute to after rituximab discontinuation without the use of any the development of Kaposi’s sarcoma in addition to ritux- specific treatment. To our knowledge, this is the first case imab. In our patient, lung infection may have triggered of reversible rituximab-induced KS described in the lit- Kaposi’s sarcoma progression. erature. In their review, Antman and Chang [23] reported In conclusion, we report the case of Kaposi’s sarcoma several examples of Kaposi’s sarcoma regressions in diagnosed under rituximab in a HIV-negative patient, renal transplant recipients after cessation, reduction or the first one at the rectal level, and the first one that modification of immunosuppressive therapy. However, completely regressed after cessation of rituximab. This such modification led to graft rejection in approximately case further highlights the importance of immunosup- half of the patients. Similarly, in a HIV-negative patient pression in the pathophysiology of Kaposi’s sarcoma and treated with corticosteroid for idiopathic thrombocyto- how immune restitution takes part in its management. It penic purpura, the skin Kaposi’ tumors regressed soon also suggests awareness of iatrogenic Kaposi’s sarcoma after discontinuation of corticosteroid therapy, and no in patients treated with rituximab. Even if the occur- recurrence was observed during the 30-month follow-up rence of Kaposi’s sarcoma is a very rare event, vigilance period [24]. In our case, we suppose that the rituximab is needed, particularly for cancer patients often immu- cessation permitted immune restitution and regression of nocompromised by disease and treatments. Patients at Kaposi’s sarcoma. risk of HHV8 infection (ethnicity with high Fitzpatrick The role of CD4 T-cells in the Kaposi’s sarcoma patho - skin phototype, Mediterranean or equatorial African physiology is suspected [25], especially in HIV-positive geographic origin, male gender, homosexuality or multi- patients who usually present Kaposi’s sarcoma when ple sexual partners, immune deficiency) should be care - circulating CD4+ T-cell count is under 350/mm under fully screened for HHV8 before rituximab and closely highly active antiretroviral therapy [26]. In our case as monitored during treatment. Even if efforts to develop a well as in Ureshino’s case, the CD4+ T-cell count was HHV8 vaccine are ongoing [29], no prophylaxis for Kapo- higher than 350/mm [5], suggesting that cellular immu- si’s sarcoma is available today. Finally, given the risk of nodeficiency played only a minor role in the development lymphoma progression after rituximab cessation, further Billon et al. Clin Sarcoma Res (2018) 8:11 Page 6 of 8 ‑ ‑ ‑ ‑ ‑ ‑ ‑ Table 1 Published cases of intestinal Kaposi’s sarcoma in HIV-negative patients after 2000 First author Year Sex Age at diagnosis Clinical conditions Visceral KS localiza- Immunosuppres- Tumor HHV8 status Blood HHV8 status KS management (years) tions sion therapy Cohen 2001 F 67 Crohn disease Ileum Prednisone ND ND Discontinuation of immunosuppressive therapy Kang 2004 F 60 Ulcerative colitis Colon Prednisone + ND ND Nepomniashchaia 2004 M 41 Allogenic kidney Stomach, intestinal ND ND ND ND transplantation mesentery, cerebral Bursics 2005 M 49 Ulcerative colitis Colon Methylprednisolone − − Discontinuation of immunosuppressive therapy and colopro tectomy Svrcek 2009 M 62 Ulcerative colitis Rectum Steroid, azathioprine + + Discontinuation of immunosuppressive therapy and colopro tectomy Girelli 2009 M 43 Ulcerative colitis Descending colon Prednisone, mesala + − Discontinuation of zine, ciclosporin immunosuppressive therapy and colopro tectomy Rodriguez 2010 M 65 Ulcerative colitis Colon Prednisone, metho + + Discontinuation of trexate immunosuppressive therapy and colopro tectomy Tas 2012 F 77 Chronic anemia Colon, lymph nodes None + ND Etoposide Pioche 2013 M 49 Ulcerative colitis Colon Corticosteroids, + + Coloprotectomy azathioprine, ciclo sporin, infliximab Hamzaoui 2013 M 30 Ulcerative colitis Colorectal Prednisone, mesala + ND Subtotal colectomy zine, azathioprine, infliximab Herculano 2014 M 63 Ulcerative colitis Sigmoid colon Prednisolone, mesala + − Discontinuation of zine immunosuppressive therapy Windon 2017 M 21 Crohn disease Colon Prednisone, infliximab − − Discontinuation of immunosuppressive therapy Duh 2017 M 48 Ulcerative colitis Rectum Prednisone + ND Discontinuation of immunosuppressive therapy followed by subtotal colectomy Kumar 2017 M 70 Ulcerative colitis Ascending colon None + ND ND KS Kaposi’s sarcoma, F female, M male, ND not determined Billon et al. Clin Sarcoma Res (2018) 8:11 Page 7 of 8 4. Jerdan K, Brownell J, Singh M, Braniecki M, Chan L. A case report of studies are needed to better understand the immunologi- iatrogenic cutaneous Kaposi sarcoma due to rituximab therapy for cal mechanisms involved in rituximab-induced Kaposi’s thrombotic thrombocytopenic purpura. Acta Oncol. 2017;56:111–3. sarcoma and to define optimal treatment. 5. Ureshino H, Ando T, Kojima K, Itamura H, Jinnai S, Doi K, et al. Rituximab‑ containing chemotherapy (R‑ CHOP)‑induced Kaposi’s sarcoma in an HIV‑negative patient with diffuse large B cell lymphoma. Intern Med. 2015;54:3205–8. Abbreviations 6. Salles G, Seymour JF, Offner F, López‑ Guillermo A, Belada D, Xerri L, CMV: cytomegalovirus; DLBCL: diffuse large B‑ cell lymphoma; HHV8: human et al. Rituximab maintenance for 2 years in patients with high tumour herpes virus type 8; HIV: human immunodeficiency virus; HSV: herpes simplex burden follicular lymphoma responding to rituximab plus chemotherapy virus; HTLV1: human T‑ cell lymphotropic virus de type I; IHC: immunohis‑ (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011;377:42–51. tochemistry; mAb: monoclonal antibody; PCR: polymerase chain reaction; 7. Biggs BA, Crowe SM, Lucas CR, Ralston M, Thompson IL, Hardy KJ. AIDS PET‑scan: positron emission tomography scan; RRePS: Réseau de Référence en related Kaposi’s sarcoma presenting as ulcerative colitis and complicated Pathologie des Sarcomes; WHO: World Health Organization. by toxic megacolon. Gut. 1987;28:1302–6. 8. Weber JN, Carmichael DJ, Boylston A, Munro A, Whitear WP, Pinching AJ. Authors’ contributions Kaposi’s sarcoma of the bowel‑presenting as apparent ulcerative colitis. Conception and design: FB; Manuscript writing: FB and EB; Final approval: FB, Gut. 1985;26:295–300. EB, AMS, LM, MB, AM, DP; Pathological explorations: LM; Patient’s manage‑ 9. Cohen RL, Tepper RE, Urmacher C, Katz S. Kaposi’s sarcoma and cyto‑ ment: AMS, MB, LM, FB. All authors read and approved the final manuscript. megaloviral ileocolitis complicating long‑standing Crohn’s disease in an HIV‑negative patient. Am J Gastroenterol. 2001;96:3028–31. Author details 10. Kang MJ, Namgung KY, Kim MS, Ko BS, Han CS, Ahn HT, et al. A case of INSERM UMR1068, CNRS UMR725, Department of Medical Oncology, Centre Kaposi’s sarcoma associated with ulcerative colitis. Korean J Gastroenterol de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli‑ Calmettes, Taehan Sohwagi Hakhoe Chi. 2004;43:316–9. 232 Bd de Sainte‑Marguerite, 13009 Marseille, France. Department of Hema‑ 11. Nepomniashchaia EM, Gusarev SA, Kirichenko IG. Generalized Kaposi’s tology, Institut Paoli‑ Calmettes, Marseille, France. Department of Pathol‑ sarcoma after allogenic transplantation of cadaver kidney. Arkh Patol. ogy, Institut Paoli‑ Calmettes, Marseille, France. Department of Digestive 2004;66:55–7. Endoscopy Centre Hospitalier Edmond Garcin, Aubagne, France. Faculty 12. Bursics A. HHV‑8 positive, HIV negative disseminated Kaposi’s sarcoma of Medicine, Aix‑Marseille University, Marseille, France. French Sarcoma complicating steroid dependent ulcerative colitis: a successfully treated Group, Paris, France. case. Gut. 2005;54:1049–50. 13. Svrcek M, Tiret E, Bennis M, Guyot P, Fléjou J‑F. KSHV/HHV8‑associated Acknowledgements intestinal Kaposi’s sarcoma in patient with ulcerative colitis receiv‑ Our work is supported by Institut Paoli‑ Calmettes. ing immunosuppressive drugs: report of a case. Dis Colon Rectum. 2009;52:154–8. Competing interests 14. Girelli CM, Serio G, Rocca E, Rocca F. Refractory ulcerative colitis and The authors declare that they have no competing interests. iatrogenic colorectal Kaposi’s sarcoma. Dig Liver Dis. 2009;41:170–4. 15. Rodríguez‑Peláez M, Fernández‑ García MS, Gutiérrez‑ Corral N, de Fran‑ Availability of data and materials cisco R, Riestra S, García‑Pravia C, et al. Kaposi’s sarcoma: an opportunistic Not applicable. infection by human herpesvirus‑8 in ulcerative colitis. J Crohns Colitis. 2010;4:586–90. Consent for publication 16. Tas F, Yegen G, Keskin S, Gozubuyukoglu N. Classic Kaposi’s sarcoma with Written informed consent was obtained from the patient for publication of colonic involvement: a rare presentation with successful treatment with this Case report and any accompanying images. oral etoposide. J Cancer Res Ther. 2012;8:112. 17. Pioche M, Boschetti G, Cotte E, Graber I, Moussata D, François Y, et al. Ethics approval and consent to participate Human herpesvirus 8‑associated colorectal Kaposi’s sarcoma occurring in Not applicable. a drug‑induced immunocompromised patient with refractory ulcerative colitis: report of a new case and review of the literature. Inflamm Bowel Funding Dis. 2013;19:E12–5. Not applicable. 18. Hamzaoui L, Kilani H, Bouassida M, Mahmoudi M, Chalbi E, Siai K, et al. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative Publisher’s Note colitis in a human immunodeficiency negative ‑ virus patient. Pan Afr Med Springer Nature remains neutral with regard to jurisdictional claims in pub‑ J. 2013;15. https://doi.org/10.11604/pamj.2013.15.154.2988. lished maps and institutional affiliations. 19. Herculano R, Barreiro P, Hann A, Chapim I, Bispo M, Santos S, et al. Drug‑ induced colonic Kaposi’s sarcoma in a HIV‑negative patient with ulcera‑ Received: 10 November 2017 Accepted: 13 March 2018 tive colitis: a case report and review of the literature. Int J Colorectal Dis. 2014;29:1441–2. 20. Windon AL, Shroff SG. Iatrogenic Kaposi’s sarcoma in an HIV ‑negative young male with Crohn’s disease and IgA nephropathy: a case report and brief review of the literature. Int J Surg Pathol. 2017. https://doi. org/10.1177/1066896917736610. References 21. Duh E, Fine S. Human herpesvirus‑8 positive iatrogenic Kaposi’s sar ‑ 1. Geraminejad P, Memar O, Aronson I, Rady PL, Hengge U, Tyring SK. coma in the setting of refractory ulcerative colitis. World J Clin Cases. Kaposi’s sarcoma and other manifestations of human herpesvirus 8. J Am 2017;5:423–7. Acad Dermatol. 2002;47:641–55. 22. Kumar V, Soni P, Garg M, Abduraimova M, Harris J. Kaposi sarcoma mim‑ 2. Fisher RI, LeBlanc M, Press OW, Maloney DG, Unger JM, Miller TP. New icking acute flare of ulcerative colitis. J Investig Med High Impact Case treatment options have changed the survival of patients with follicular Rep. 2017;5:232470961771351. lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23:8447–52. 23. Antman K, Chang Y. Kaposi’s sarcoma. N Engl J Med. 2000;342:1027–38. 3. Gérard L, Michot J‑M, Burcheri S, Fieschi C, Longuet P, Delcey V, et al. 24. Toyohama T, Nagasaki A, Miyagi J, Takamine W, Sunagawa K, Uezato H, Rituximab decreases the risk of lymphoma in patients with HIV‑associ‑ et al. Kaposi’s sarcoma in a human immunodeficiency virus‑negative ated multicentric Castleman disease. Blood. 2012;119:2228–33. patient treated with corticosteroid for idiopathic thrombocytopenic purpura. Intern Med Tokyo Jpn. 2003;42:448–9. Billon et al. Clin Sarcoma Res (2018) 8:11 Page 8 of 8 25. Robey RC, Mletzko S, Gotch FM. The T‑ cell immune response against 28. Pantanowitz L, Früh K, Marconi S, Moses AV, Dezube BJ. Pathology of Kaposi’s sarcoma‑associated herpesvirus. Adv Virol. 2010;2010:1–9. rituximab‑induced Kaposi sarcoma flare. BMC Clin Pathol. 2008;8:7. 26. Lupia R, Wabuyia PB, Otiato P, Fang C‑ T, Tsai F‑ J. Risk factors for Kaposi’s 29. Wu TT, Qian J, Ang J, Sun R. Vaccine prospect of Kaposi sarcoma‑associ‑ sarcoma in human immunodeficiency virus patients after initiation of ated herpesvirus. Curr Opin Virol. 2012;2:482–8. antiretroviral therapy: A nested case–control study in Kenya. J Microbiol Immunol Infect. 2017;50:781–8. 27. Stebbing J, Gazzard B, Newsom‑Davis T, Nelson M, Patterson S, Gotch F, et al. Nadir B cell counts are significantly correlated with the risk of Kaposi’s sarcoma. Int J Cancer. 2004;108:473–4. Submit your next manuscript to BioMed Central and we will help you at every step: • We accept pre-submission inquiries • Our selector tool helps you to find the most relevant journal • We provide round the clock customer support • Convenient online submission • Thorough peer review • Inclusion in PubMed and all major indexing services • Maximum visibility for your research Submit your manuscript at www.biomedcentral.com/submit

Journal

Clinical Sarcoma Research – Springer Journals

Published: Jun 11, 2018

There are no references for this article.