[16] Gamberini MR, Fortini M, De Sanctis V. Paraplegia due to spinal cord ion

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compression by extramedullary erythropoietic tissue in a thalassemiaintermedia patient with gynecomastia secondary to cirrhosis: successfultreatment with hydroxyurea. Pediatr Endocrinol Rev 2004;2:316-8.

[17] Martinez-Rodrigo MA, Sanjuanbenito L, Rodriguez del Barrio E, Martinez-San Milan J, Saldana D. Spinal cord compression secondary to epiduralextramedullary hematopoiesis in thalassemia: a clinical case and review

tre

sà

laré

da

ct

Conclusion

L’hématopoïèse extramédullaire forme des îlots tissulairesconstitués de cellules hématopoïétiques actives, intéressantprincipalement le foie, la rate et les ganglions lymphatiques,alors que la localisation thoracique demeure exceptionnelle.Les thalassémies en constituent le facteur étiologique le plusfréquent. La TDM et l’IRM sont les deux examens les plusfiables, permettant à la fois le diagnostic positif et l’évaluation

s. Le recours à et

du retentissement sur les structures avoisinante

L

la biopsie est exceptionnel en raison du risque hémorragique

de ce geste. Cette entité rare doit être incluse dans le diagnostic

Correspondance : Jihen Ben Amar,Charles Nicolle hospital, pulmonary department,

boulevard 9-Avril, 1009 Tunis, Tunisie.jihenbenamar@gmail.com

Reçu le 28 août 2013Accepté le 17 mars 2014

Disponible sur internet le 27 juin 2014

http://dx.doi.org/10.1016/j.lpm.2014.03.023� 2014 Elsevier Masson SAS Tous droits réservés.

Rectal perforation aftertwo years of treatmentwith sunitinib formetastatic kidney cancerPerforation rectale après deux ans detraitement par sunitinib pour un cancer du reinmétastatique

Case report

A 63-year-old man was admitted to our hospital at the beginn-ing of November 2012. This patient is affected by a renal-cellcarcinoma, clear-cell type, metastatic with thoracic lymph

différentiel des tumeurs du médiastin postérieur, surtout chezles porteurs d’une hémopathie chronique.

Déclaration d’intérêts : les auteurs déclarent ne pas avoir de conflitsd’intérêts en relation avec cet article.

Références[1] Ohta Y, Shichinihe H, Nagashima K. Spinal cord compression due to

extramedullary hematopoiesis associated with polycytemia vera. NeurolMed Chir 2002;42:40-3.

[2] Ketata W, Msaad S, Kwass H. Thoracic extramedullary hematopoiesis: adiagnosis to not forget in a patient with posterior mediastinal mass withanemia. Respir Med CME 2009;2:118-20.

[3] Yusen RD, Kollef MH. Acute respiratory failure due to extramedullaryhematopoiesis. Chest 1995;108:1170-2.

[4] Koch CA, Li CY, Mesa RA, Tefferi A. Non-hepatosplenic extramedullaryhematopoiesis: associated diseases, pathology, clinical course andtreatment. Mayo Clin Proc 2003;78:1223-33.

[5] Cario H, Wegener M, Debatin KM, Kohne E. Treatment with hydroxyureain thalassemia intermedia with paravertebral pseudotumors of extra-medullary hematopoiesis. Ann Hematol 2002;81:478-82.

[6] Nasr Ben Ammar C, Belaïd A, Kochbati L, Maalej M. Hématopoïèseextramédullaire : à propos de deux cas. Cancer Radiother 2007;11:490-4.

[7] Wong Y, Chen F, Tai KS, Yip LK, Tsang KW, Chan FL. Case report: imagingfeatures of focal intrahepatic extramedullary hematopoiesis. Br J Radiol1999;72:906-10.

[8] Babazadeh S, Broadhead ML, Slavin JL, Choong PF. An interestingdiagnosis for a presacral mass: case report. Int Semin Surg Oncol2009;6:18.

[9] Haidar S, Ortiz-Neira C, Shroff M, Gilday D, Blaser S. Intracranialinvolvement in extramedullary hematopoiesis: case report and reviewof literature. Pediatr Radiol 2005;35:630-4.

[10] Maliszewski M, Majchrzak H, Ladzinski P, Bierzynska-Macyszyn G, LechA. Extramedullary hematopoiesis in cerebellar hemangioblastoma.Neurosurgery 1991;29:34-7.

[11] Galperin-Aizenberg M, Volchek Y, Even Sapir E, Vasserman M, Maizlin ZV,Cohenpour M. Renal extramedullary haematopoiesis mimicking renallymphoma on computed tomography. Clin Radiol 2006;61:896-8.

[12] Isasi CR, Lu P, Blaufox MD. A meta-analysis of 18 F-2-deoxy-2-fluoro-D-glucose positron emission tomography in the staging and restaging ofpatients with lymphoma. Cancer 2005;104:1066-74.

[13] Chadli-Debbiche A, Koubâa-Mahjoub W, Khayat O. Heterotopic hemato-poiesis presenting as a mediastinal tumor: report of case in a malarialpatient. Rev Tunis Sante Mil 2004;6:150-2.

[14] Kchir N, Dellagi K, Mezni F, Boubaker S, Ouertani L, Zitouna MM.Mediastinal hematopoietic pseudotumors. Study of clinical and patho-logical features. Report of a case. Arch Anat Cytol Path 1985;33:214-7.

[15] Boyacigil S, Ali A, Ardic S, Yuksel E. Epidural extramedullaryhaemopoeisis in thalassemia. Australas Radiol 2002;46:180.

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of literature. Rev Neurol 1998;27:998-1004.[18] Munn RK, Kramer CA, Arnold SM. Spinal cord compression due to

extramedullary hematopoiesis in beta-thalassemia intermedia. Int JRadiat Oncol Biol Phys 1998;42:607-9.

[19] Rey J, Gagliano R, Christides C, Pillard E, Magnan F, Tourniaire P. Spinalcord compression caused by extramedullary hematopoeisis foci in thecourse of thalassemia. Presse Med 2001;29:1351-3.

[20] Luo Y, Zhang Y, Lou SF. Bilateral pleural effusion in a patient with anextensive extramedullary hematopoietic mass. Case Rep Hematol2013;2013:857610.

[21] Meo A, Cassinerio E, Castelli R, Bignamini D, Perego L, Cappellini MD.Effect of hydroxyurea on extramedullary haematopoiesis in thalassemiaintermedia: case reports and literature review. Int J Lab Hematol2008;30:425-31.

[22] Soman S, Rosenfeld DL, Roychowdhury S, Drachtman RA, Cohler A. Cordcompression due to extramedullary hematopoiesis in an adolescentwith known beta-thalassemia major. Radiol Case 2009;3:17-22.

Jihen Ben Amar, Mouna Berrais, Leila El Gharbi, Besma Dhahri,Hichem Aouina, Hend Bouacha

Charles Nicolle hospital, pulmonary department,boulevard 9-Avril, 1009 Tunis, Tunisie

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nodes and parenchymal pulmonary metastasis from mid-2010.The diagnosis of kidney cancer dated back to 2008 when heunderwent a radical nephrectomy. The medical treatment wasbegun in October 2010 with sunitinib at the classical 50 mg/day on a 4-weeks-on/2-weeks-off schedule. The tolerance wasgood. At the beginning of October 2012, the patient was seenafter the 17th cycle of sunitinib. He told us at that time that hesuffered mid-September 2012 from febrile diarrhoea withrectal syndrome; this event was finishing at that time. Weprescribed an antibiotherapy with ciprofloxacine and metroni-dazole and postponed the beginning of the 18th sunitinib cycleby one week, which thus began on the 15th of October. Thepatient was admitted on the 8th of November for acute urinaryretention. He had fever and biological acute-phase inflamma-tion. The computed tomography (CT) scan revealed a pneumo-retroperitoneum (figure 1). Antibiotherapy with piperacilline/

tazobactam and metronidazole was begun. Coelioscopic sur-gery was performed on the 11th of November with first adiverting loop colostomy and secondly a rectal explorationwhich discovered a small perforation at the recto-sigmoidjunction, permitting insertion of a drain. The postoperativecourse was uneventful and the patient was discharged tohome. The colostomy reversal was performed in March2013. We began from the end of December 2012 a new medicaltreatment with everolimus but tolerance was particularly poorand we stopped all treatment in March 2013. In fact, there wereno more tumoral targets on CT-scans from the spring of 2012.The patient is currently (December 2013) well without anyevidence of progression of the malignancy.

Discussion

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Figure 1

Computed tomography (CT) scan showing a pneumo-retroperitoneum

Table I

Summarized data of patients with bowel perforation during sunitinib treatment

Reference Gender Age Tumour Time to perforation Perforation location Surgical treatment Outcome

Hur et al. [1] Female 70 GIST 6 weeks Transverse colon Percutaneous drainage Favourable

Flaig et al. [2] Female Unknown MRCC 13 months Right colon Right hemicolectomy Unknown

Flaig et al. [2] Female Unknown MRCC 5 months Right colon None Favourable

Walraven et al. [3] Female 62 MRCC Second cycle Anal None Death

Hoshino et al. [4] Male 50 MRCC 6 months (four cycles) Right colon Right hemicolectomy Favourable

Jejunum Jejunostomy Death

Recto-sigmoid junction Diverting loop colostomy, drainage Favourable

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Hoshino et al. [4] Female 60 MRCC 11 days

Our case Male 63 MRCC 24 months18 cycles

GIST: gastro-intestinal stromal tumours; MRCC: metastatic renal-cell carcinoma.

Sunitinib is a multitargeted and antiangiogenic tyrosine kinaseinhibitor (TKI) well established in the treatment of metastaticrenal-cell carcinoma (MRCC) and gastro-intestinal stromaltumours (GIST). Bowel perforation is a very rare adverseevent related to this drug with so far barely six case reportsin the English-language literature (data summarized in table I)[1–4]. No cases of bowel perforation have been reported in thepivotal study establishing sunitinib for the treatment of MRCC[5]. Four cases of bowel perforation are also reported withsorafenib, another antiangiogenic TKI with very similar issues[3,5,6]. All these cases apart from one [1] are described inpatients affected by MRCC. Bowel perforation is much moreknown with bevacizumab, a monoclonal antibody directedagainst vascular endothelial growth factor. Two differentkinds of bowel perforations related to sunitinib can be des-cribed: by antitumoral efficacy against tumoral localisations inthe gastro-intestinal wall (for instance in case of a gastro-intestinal stromal tumor treated by sunitinib [1], or even in acase of gastro-intestinal metastasis of renal-cell carcinoma [4]);or, as in our case, by still unclear mechanisms involving

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http://dx.doi.org� 2014 Elsevier

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microvascular toxicity and therefore mucosal fragility. Bowelperforation under antiangiogenic TKI treatment is in most casesof early occurrence, in the first months (up to five months) if notthe first weeks of treatment. Late event, as in our case, has justbeen reported in one case (thirteen months) [2]. Our case ispeculiar in that the bowel perforation has been preceded byfebrile diarrhoea, probably infectious, may be acting as a firsthit on the mucosae paving the way to the subsequent per-foration. Risk factors of bowel perforation under antiangiogenicTKI treatments are not known. However, in three cases linkedwith radiotherapy, all three with sorafenib, a possible radio-sensitization is underlined [6,7]. At last, our case illustrates theissue of long-lasting antiangiogenic TKI treatments and therisk of late toxicity. It also illustrates the need of havingguidelines concerning this small but existing subset ofpatients with MRCC in complete response under TKI treat-ments; a French group has already given clues: the interrup-tion of TKI is possible with more than 60% of patientsremaining in complete response with a median follow-upof about nine months [8].

Disclosure of interest : the authors declare that they have no conflicts ofinterest concerning this article.

References[1] Hur H, Park AR, Jee SB, Jung SE, Kim W, Jeon HM. Perforation of the colon

by invading recurrent gastro-intestinal stromal tumors during sunitinibtreatment. World J Gastroenterol 2008;14:6096-9.

[2] Flaig TW, Kim FJ, La Rosa FG, Breaker K, Schoen J, Russ PD. Colonicpneumatosis and intestinal perforations with sunitinib treatment forrenal cell carcinoma. Invest New Drugs 2009;27:83-7.

[3] Walraven M, Witteveen PO, Lolkema MP, van Hillegersberg R, Voest EE,Verheul HM. Antiangiogenic tyrosine kinase inhibition related gastro-

[4]

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intestinal perforations: a case report and literature review. Angiogenesis2011;14:135-41.Hoshino Y, Hasegawa H, Ishii Y, Endo T, Ochiai H, Okabayashi K et al. Two

cases of bowel perforation associated with sunitinib treatment for renalcell carcinoma. Int J Clin Oncol 2012;17:412-6.

[5] Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe Oet al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.N Engl J Med 2007;356:115-24.

[6] Peters NA, Richel DJ, Verhoeff JJ, Stalpers LJ. Bowel perforation afterradiotherapy in a patient receiving sorafenib. J Clin Oncol 2008;26:2405-6.

[7] Inoue T, Kinoshita H, Komai Y, Kawabata T, Kawa G, Uemura Y et al. Twocases of gastro-intestinal perforation after radiotherapy in patientsreceiving tyrosine kinase inhibitor for advanced renal cell carcinoma.World J Surg Oncol 2012;10:167.

[8] Albiges L, Oudard S, Negrier S, Caty A, Gravis G, Joly F et al. Completeremission with tyrosine kinase inhibitors in renal cell carcinoma. J ClinOncol 2012;30:482-7.

Jean-Sébastien Bladé1, Stéphane Bourgouin2, Émilie Romeo1,Laurys Boudin1, Jean-Pierre de Jauréguiberry1

1HIA Sainte-Anne, service de médecine interne-oncologie,BP no 600, 83800 Toulon cedex 9, France

2HIA Sainte-Anne, service de chirurgie viscérale et vasculaire,BP no 600, 83800 Toulon cedex 9, France

43 > n811 > novembre 2014

Correspondence: Jean-Sébastien Bladé,

HIA Sainte-Anne, service de médecine interne-oncologie,

BP no 600, 83800 Toulon cedex 9, France.jsblade@wanadoo.fr

Received 26 January 2014Accepted 17 March 2014

Available online 3 July 2014

/10.1016/j.lpm.2014.03.021Masson SAS Tous droits réservés.

Splenomegaly in

haematologicalmalignancies and portalhypertension Splénomégalie dans les hémopathiesmalignes et hypertension portale

It is usually accepted that the sole condition of portal hyper-afflux cannot explain the development of portal hypertension,in absence of other factors, as an intrinsic pathology of the liveror of the portal venous system, with consequently increasedvascular resistances. The clinical condition of a homogeneoussplenomegaly secondary to haematological malignancies canbe considered an interesting model to study this problem.

Observation

We retrospectively examined clinical and radiological data of20 patients, 15 males and 5 females, with a median age of63 years (range 18–85 years), with a homogeneous spleno-megaly secondary to haematological malignancy: chronic lym-phocytic leukemia (7 cases), acute lymphoblastic leukemia(1 case), chronic myeloid leukemia (1 case), hairy cell leukemia(3 cases), splenic marginal zone lymphoma (4 cases), diffuselarge B cell lymphoma (3 cases) and cutaneous follicularlymphoma (1 case). The liver function tests were normal inall the cases, and no signs of extramedullary haematopoiesiswere demonstrated by haematological investigations.Our study has been chiefly based on the findings of contrast-enhanced computed tomography and of ultrasonography, per-formed in every case before any treatment. The mean splenicvolume calculated volumetrically with a software automaticallycontouring the spleen was 1610.22 cm3, ranging from 417.50to 4728 cm3, being the mean normal value 214.6 cm3 [1]. Thesplenic artery and especially the splenic vein, at the hilum,appeared enlarged and tortuous, especially in cases ofbigger splenomegaly. No signs of general or left-sided portal

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