Case Report. Sabha Mushtaq 1, Arti Sakral 1, Devraj Dogra 1, Subhash Bhardwaj 2, Arshad Bhat 3 CASE REPORT INTRODUCTION
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1 19.Primry_CR Our Dermtology Online Primry ngiosrcom of chest wll inside out: A rre presenttion Sh Mushtq 1, Arti Skrl 1, Devrj Dogr 1, Suhsh Bhrdwj 2, Arshd Bht 3 1 Deprtment of Dermtology, Venereology & Leprology, SMGS Hospitl, Government Medicl College, University of Jmmu, Jmmu Jmmu & Kshmir, Indi, 2 Deprtment of Pthology, SMGS Hospitl, Government Medicl College, University of Jmmu, Jmmu Jmmu & Kshmir, Indi, 3 Deprtment of Rdio-Dignosis, SMGS Hospitl, Government Medicl College, University of Jmmu, Jmmu Jmmu & Kshmir, Indi Corresponding uthor: Dr. Sh Mushtq, E-mil: smqzi.gmc@gmil.com Cse Report ABSTRACT Angiosrcoms re ggressive, mlignnt tumors of vsculr or lymphtic origin with high potentil to locl nd distnt spred. Cutneous invsion of internl tumors is rrely encountered in clinicl prctice. We report on ptient with vsculr skin lesions over nterior chest which turned out to e incursion from chest wll ngiosrcom. Alongside the cse report, literture on therpeutic rsenl of ngiosrcom is reviewed. Angiosrcom of chest wll invding into the skin hs never een reported in dermtologicl literture. This cse is intriguing s the ptient hd symptomless progression of the mlignncy despite ggressive invsion to overlying skin nd metstsis to lungs nd pleur. This impresses upon the crucil role of dermtologists in suspecting cutneous lesions which my pper skin deep ut re otherwise silent sign of grve internl disese so tht serch of underlying condition is sought s soon s possile to chieve etter ptient outcome. So the dictum is erlier the dignosis, etter the prognosis. Key words: Primry ngiosrcom; Cutneous; Chest wll; Invsion; Pulmonry INTRODUCTION Angiosrcoms re sutype of soft-tissue srcoms nd re ggressive, mlignnt endothelil tumors of vsculr or lymphtic origin [1]. The clinicl presenttion of ngiosrcom vries depending upon the ntomic site involved. Angiosrcoms my occur in ny region of the ody ut re more frequent in skin nd soft tissue. They cn lso originte in the liver, rest, spleen, one, or hert [2]. Angiosrcoms hve high propensity to metstsize or infiltrte to other sites with sustntil mortlity rte [3]. Herein, we present the cse of 50 yer old mn with primry ngiosrcom of chest wll (PACW) infiltrting nd colonising the skin. The interesting nture nd pucity of documenttion of this rre presenttion in the world literture encourged us to report the cse. CASE REPORT A 50 yer old mn presented with 3 months history of pinless vsculr lesions over left nterior chest wll. There ws preceding history of skin coloured deep seted nodulr swelling in the mmmry re which over period of 1 month developed overlying erythemtous exuernt growth. This ws followed y the ppernce of similr lesion ner the vicinity long with smll stellite lesions. Ptient gve history of ulcertion nd leeding from oth the lrger lesions with no history of ny penetrting injury, rest mlignncy or irrdition in the pst. Rest of the medicl history ws not significnt. On exmintion, n indurted, erythemto-voilceous fungting growth with ulcertion ws present over the left nterior chest wll deforming the nipple. Similr How to cite this rticle: Mushtq S, Skrl A, Dogr D, Bhrdwj S, Bht A. Primry ngiosrcom of chest wll inside out: A rre presenttion. Our Dermtol Online. 2017;8(3): Sumission: ; Acceptnce: DOI: /ourd Our Dermtol Online
2 smller sized lesion ws present over supero-medil spect of the min lesion. The surrounding norml skin showed multiple smll discrete s well s colscing ppulr lesions (Fig. 1). The lesion ws non-tender, led on gentle mnipultion nd ws fixed to underlying structures. Regionl lymph nodes were not enlrged. Generl physicl nd systemic exmintion ws unremrkle. All routine investigtions were within norml limits. For histologicl chrcteristion, n incisionl iopsy ws otined with differentil dignosis of cutneous ngiosrcom, Kposi s srcom, dermtofirosrcom protuerns nd cutneous lymphom. Histopthology demonstrted highly vsculr lesion in the dermis composed of mny vrile sized vsculr spces contining ppillry configurtions hving RBCs nd lined y pleomorphic cells with vesiculr nuclei nd prominent nucleoli. Anorml mitotic figures were lso seen (Fig. 2). The histologicl fetures were consistent with mlignnt vsculr tumor suggestive of ngiosrcom. Immunohistochemistry (IHC) could not e done due to limittion of resources. Chest X-ry showed n re of hziness in left lower lung zone (Fig. 3), which on lterl view ppered to e extrpulmonic chest wll mss. Ultrsound of the domen & pelvis ws significnt for pleurl effusion. Contrst enhnced computerized tomogrphy (CECT) of the chest reveled heterogeneous enhncing lesion mesuring cm with non-enhncing centrl re of necrosis in left nterior chest wll with musculr invsion. The lesion ws lso seen to infiltrte the overlying skin. An ill defined enhncing nodule ws seen medil to the min lesion in prsternl re. Bilterl pleurl sed soft tissue densities long with secondries in oth lung fields were lso visulized (Fig. 4). CT ws lso significnt for ilterl pleurl effusion nd sucentimetric medistinl lymph nodes. Bsed on histopthology nd imging, dignosis of primry ngiosrcom of chest wll with pulmonry metstsis ws reched. The ptient ws referred to surgery deprtment for further mngement. As the ptient presented t very dvnced stge (stge IV), surgery ws not n option. He ws strted on chemotherpy in the oncology deprtment ut died within 3 months of strting tretment. DISCUSSION Angiosrcom is very rre mesenchyml tumor ccounting for 1-2% of ll soft-tissue srcoms [4]. Figure 1: () Two fungting growths over left nterior chest wll (rrows); () Ulcer on the surfce of lrger plque long with discrete ppulr lesions in the vicinity (rrows). Figure 2: Photomicrogrph showing: () Mild cnthosis of the epidermis, dermis contins vsculr tumor with slit-like spces (100 H&E); () Slit-like vsculr chnnels lined y lrge pleomorphic cells hving vesiculr nuclei nd prominent nucleoli (400 H&E). Figure 3: Chest X-ry showing re of hziness in left lower lung zone (rrow). Figure 4: CECT chest showing: () A heterogeneous enhncing lesion with non- enhncing centrl re of necrosis in left chest wll with musculr invsion, infi ltrtion into the overlying skin & two smll well defi ned enhncing nodules medil to the min lesion (rrows); () Bilterl pleurl sed soft tissue densities long with multiple secondries in oth lung fi elds & ilterl pleurl effusion (rrows). Our Dermtol Online
3 It cn e primry i.e rising de novo or secondry to irrdition, trum, lymphedem [5]. The common sites ffected re skin, soft tissue, liver, spleen, hert nd rest [6]. Primry ngiosrcom of chest wll cn originte from one, soft tissue or crtilge of chest wll nd ccount for 5% of ll thorcic neoplsms [7]. Chronic lymphedem, irrdition nd exposure to vinyl chloride, thorostt, rsenic, nolic steroid or foreign odies re considered s min culprits [8]. None of these fctors were present in our ptient who ws dignosed s de novo cse of primry ngiosrcom of chest wll. The clinicl presenttion of PACW cn vry from chest pin, dyspnoe, hemothrx, chest wll mss or cn e totlly symptomtic [9] (s in our cse). In our ptient, the first impression ws of primry cutneous ngiosrcom (PCA) ut s chest is not common site for PCA, we considered other possiilities nd further evluted the ptient. Histopthology ws consistent with ngiosrcom. To rule out ny metstsis to internl orgns, chest x-ry, CECT nd USG domen nd pelvis were requested. CECT reveled heterogeneous enhncing mss in the left nterior chest wll with invsion into su-cutneous ft plnes nd infiltrting the overlying skin. Therefore, dignosis of chest wll ngiosrcom ws reched y co-relting clinicl, rdiologicl nd pthologicl findings. We did not come cross ny such presenttion in dermtologicl literture. Such rre clinicl presenttions my often confront dermtologists nd dermtosurgeons. This emphsizes their role in keeping high index of suspicion in such cses nd lso the importnce of referring the ptient to other specilities relevnt to the condition to expedite the dignosis. This would led to timely intervention nd increment survivl s these tumors hve d prognosis owing to their ggressive nture nd ssocited mortlity. Gold Stndrd nd Advnces in the Tretment of Angiosrcoms Angiosrcoms re very ggressive tumors, so tretment should e strted erly once dignosis is estlished. As regrds the therpy, it is importnt to underline tht Angiosrcom tretment hs to e plnned y multidisciplinry tem of medicl experts drwn from ll the involved disciplines [10]. Surgicl Intervention In operle ptients with loclised disese, surgicl resection (en loc) with the im of otining negtive surgicl mrgins is the primry mode of tretment [11]. Chemotherpy Cytotoxic chemotherpy forms the cornerstone of tretment for loclly dvnced inoperle or metsttic ngiosrcom. The therpeutic gols re to chieve control over the disese, to stop or postpone disese progression nd to chieve or mintin symptom control for prolonged periods of time [12]. Doxoruicin The first-line chemotherpy for dvnced, metsttic or non-resectle soft tissue srcom is sed on nthrcyclines, nd the most frequently used compound is doxoruicin [13]. The response rte to doxoruicin s single gent or in comintion is reported to rnge etween 40% nd 65% [14,15]. The mjor dverse effect ssocited with doxoruicin is crdiomyopthy [12]. Ifosfmide Ifosfmide, cytotoxic lklizing gent is used s second line drug when doxoruicin hs filed or is contrindicted. Ifosmide is usully given t dose of 8-12 g/m 2 per cycle eqully frctioned s single doses over 3-5 dys. It chieves results comprle to doxoruicin ut it is ccocited with numer of severe dverse effects including leucopeni, neutopeni, renl toxicity nd encephlopthy [12]. Pclitxel Pclitxel hs specific exquisite efficcy in ngiosrcom [12]. The ctivity of pclitxel in ngiosrcom hd een confirmed y phse II tril ssessing the efficcy of the weekly pclitxel regimen (80 mg/m 2 d1, d8, d15, 21-dy-cycle) [16]. Gemcitine Only few necdotl responses to gemcitine monotherpy hve een reported in ngiosrcom previously treted with nthrcyclines nd pclitxel. Tolerility of gemcitine plus docetxel is fir, with less crdic toxicity compred with nthrcyclines [17,18]. Bevcizum Bevcizum, recomined humnized monoclonl ntiody ginst vsculr endothelil growth fctor Our Dermtol Online
4 (VEGF), hs emerged s potentil therpeutic option for ngiosrcom mngement [19-21]. In phse 2 tril (N = 26), evcizum produced 12% PR rte in ptients with ngiosrcom nd epithelioid hemngioendotheliom [22]. Pzopni Pzopni, tyrosine kinse inhiitor is the first non-chemotherpeutic nticncer gent pproved y regultory uthorities for soft tissue srcom. Pzopni cts y interfering with the vsculr endothelil growth fctor nd pltelet-derived growth fctor pthwys. The pprovl of this orl nti-ngiogenic gent is sed on the EORTC tril (PALETTE) [23,24]. Other Chemotherpeutic Drugs Other non-pproved tretment options for ngiosrcoms include multikinse inhiitors (eg, sorfeni nd sunitini). In phse 2 trils, sorfeni produced 14% PR rte nd medin OS of 14.3 months in n ngiosrcom tril (n = 37), [25] wheres sunitini did not produce response rte in ptients with ngiosrcom (n = 2) or firous tumor/ hemngiopericytom (n = 3) [26]. Rdition Therpy Preopertive rdition followed y resection is dvised in orderline resectle cses. The dose recommendtions include 45 to 50 Gy for undissected suclinicl disese, 60 to 65 Gy for postopertive tumor ed with positive microscopic mrgins, nd 70 to 75 Gy for gross disese [27]. Adjuvnt rdition with or without chemotherpy is indicted for ptients with high-grde STS [stge II-III; Americn Joint Committee on Cncer, Cncer Stging Mnul, Seventh Edition (2010)]. Alterntively, these modlities my e delivered preopertively to reduce tumor size or improve resectility, prticulrly in potentilly resectle cses or when there re concerns for dverse functionl outcomes fter surgery [28]. Interntionl Therpeutics Guidelines A numer of cdemic orgnistions hve pulished guidelines for the tretment of inoperle, dvnced, metsttic srcom. Europen society for medicl oncology (ESMO) ESMO guidelines recommend s first-line tretment nthrcyclines s single gent or in comintion with ifosfmide or single-gent ifosfmide if there re specific contr-indictions. Second-line tretments include ifosfmide t stndrd doses if ptients hve not een previously treted with this gent during first-line tretment. A high-dose ifosfmide schedule is recommended y ESMO if the drug hd een previously used t lower dose [29]. British srcom group (BSG) BSG recommends single-gent doxoruicin or ifosfmide or doxoruicin nd ifosfmide in the firstline setting. It recommends second-line tretments with either ifosfmide, trectedin, gemcitine nd docetxel or the older drug dcrzine [13]. Ntionl comprehensive cncer network (NCCN) NCCN guidelines recommend pclitxel nd evcizum s tretment options for ptients with ngiosrcom [28]. There hve een some promising developments in the res of immunotherpy, vccine therpy, doptive immunotherpy, immune synpse lockde nd ntiody therpy in soft tissue srcoms ut mostly remins experimentl. Current clinicl experience with these gents/regimen is too, limited to drw ny conclusions [30]. The mjor drwck is the pucity of rndomised trils with only few retrospective cse series or cse reports, ll suggesting tht mong soft tissue srcoms, ngiosrcom ppers to e more sensitive to cytotoxic chemotherpy. The rrity of ngiosrcom represents mjor limittion to the rndomized trils [1,10]. Despite ll therpeutic efforts, the ptients prognosis is still unfvourle [31,32]. As our ptient presented t very dvnced stge, surgery ws not n option. He ws strted on chemotherpy with cytotoxic drugs ut unfortuntely he succumed to the disese within three months of strting the tretment. CONCLUSION Primry ngiosrcom of chest wll remins rre medicl condition nd its invsion to skin is n exceptionlly rre phenomenon. Our cse illustrtes the insidious nture nd cutneous invsive potentil of ngiosrcom with dignosis only in lte stges which hrours worst prognosis with deth coming within few months. Medicl prctitioners in generl nd dermtologists in prticulr re likely to encounter Our Dermtol Online
5 such presenttion of internl diseses mnifesting in the skin which therefore serves s window to systemic diseses. REFERENCES 1. Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. Angiosrcom. Lncet Oncol. 2010;11: Khodyri A, Khojsteh A. Mndiulr pthologic frcture s first sign of disseminted ngiosrcom: A cse report nd review of litertures. Orl Oncol Extr. 2005;41: Bocklge T, Leslie K, Yousem S, Coly T. Clinicl nd Pthologic Fetures of Twenty-One Cses. Mod Pthol. 2001;14: Andersen NJ, Fromn RE, Kitchell BE, Duesery NS. Clinicl nd Moleculr Biology of Angiosrcom. In: Derl F, ed. Soft Tissue Tumours. InTech. 2011; Weiss SW, Goldlum JR. Mlignnt vsculr tumors. In: Weiss SW, Goldlum JR, ed. Enzinger nd Weiss s soft tissue tumors. St. Louis: Mosy; 2001; Ptel AM, Ryu JH. Angiosrcom in the lung. Chest. 1993;103: Hsu PK, Lee HC, Hsieh CC, Wu YC, Wng LS, Hung BS, et l. Mngement of primry chest wll tumors: 14 yers clinicl experience. J Chin Med Assoc. 2006;69: Kim DW, Lee KN, Lee SY, Roh MS. 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A 14-yer retrospective review of ngiosrcom: clinicl chrcteristics, prognostic fctors, nd tretment outcomes with surgery nd chemotherpy. Cncer J. 2005;11: Penel N, Binh NB, By JO, Cupissol D, Ry-Coqurd I, Piperno-Neumnn S, et l. Phse II tril of weekly pclitxel for unresectle ngiosrcom: the AngioTx study. J Clin Oncol. 2008;26: Hensley ML, Mki R, Venktrmn E. Gemcitine nd docetxel in ptients with unresectle leiomyosrcom: results of phse II tril. J Clin Oncol. 2002;20: Mki RG, Wthen JK, Ptel SR. For SARC, the Srcom Allince for Reserch through Collortion Rndomized phse II study of gemcitine nd docetxel versus gemcitine lone in ptients with metsttic soft-tissue srcoms: results of srcom llince for reserch through collortion study 002. J Clin Oncol. 2007;25: Koontz BF, Miles EF, Ruio MA, et l. Preopertive rdiotherpy nd evcizum for ngiosrcom of the hed nd neck: two cse studies. Hed Neck 2008;30: Fuller CK, Chrlson JA, Dnkle SK, Russell TJ. Drmtic improvement of inoperle ngiosrcom with comintion pclitxel nd evcizum chemotherpy. J Am Acd Dermtol. 2010;63:e De Yo JT, Sun D, Powell AT, Rehmus EH. Sclp ngiosrcom remission with evcizum nd rdiotherpy without surgery: A cse report nd review of the literture. Srcom. 2011;2011: Agulnik M, Okuno SH, Von Mehren M, von Mehren M, Jovnovic BD, Brockstein BE, et l. An open-lel multicenter phse II study of evcizum for the tretment of ngiosrcom. Ann Oncol. 2013;24: Hurwitz HI, Dowlti A, Sini S, Svge S, Suttle AB, Gison DM, et l. Phse I tril of pzopni in ptients with dvnced cncer. Clin Cncer Res. 2009;15: Sleijfer S, Ry-Coqurd I, Ppi Z, Le Cesne A, Scurr M, Schöffski P, et l. Pzopni, multikinse ngiogenesis inhiitor, in ptients with relpsed or refrctory dvnced soft tissue srcom: A phse II study from the Europen Orgnistion for Reserch nd Tretment of Cncer Soft Tissue nd Bone Srcom Group (EORTC study 62043). J Clin Oncol. 2009;27: Mki RG, D Admo DR, Keohn ML, Sulle M, Schuetze SM, Undevi SD, et l. Phse II study of sorfeni in ptients with metsttic or recurrent srcoms. J Clin Oncol. 2009;27: George S, Merrim P, Mki RG, Vn den Aeele AD, Yp JT, Akhurst T, et l. Multicenter phse II tril of sunitini in the tretment of nongstrointestinl stroml tumor srcoms. J Clin Oncol. 2009;27: Scott MT, Portnow LH, Morris CG, Mrcus Jr RB, Mendenhll NP, Mendenhll WM, Indelicto DJ. Rdition therpy for ngiosrcom: the 35-yer University of Florid experience. Am J clin Oncol. 2013;36: Ntionl Comprehensive Cncer Network. NCCN Clinicl Prctice Guidelines in Oncology. Soft Tissue Srcom, Vol. 1, Aville t Accessed July 26, The ESMO/Europen Srcom Network Working Group. Soft tissue nd viscerl srcoms: ESMO Clinicl Prctice Guidelines for dignosis, tretment nd follow-up. Ann Oncol. 2012;23(Suppl 7):vii Linch M, Mih AB, Thwy K, Judson IR, Benson C. Systemic tretment of soft-tissue srcom- gold stndrd nd novel therpies. Nt Rev Clin Oncol. 2014;11: Buehler D, Rice SR, Moody JS, Rush P, Hfez GR, Atti S, et l. Angiosrcom outcomes nd prognostic fctors: 25-yer single institution experience. Am J Clin Oncol. 2014;37: Lht G, Dhuk AR, Hllevi H, Xio L, Zou C, Smith KD et l. Angiosrcom: clinicl nd moleculr insights. Ann Surg. 2010;251: Copyright y Sh Mushtq, et l. This is n open-ccess rticle distriuted under the terms of the Cretive Commons Attriution License, which permits unrestricted use, distriution, nd reproduction in ny medium, provided the originl uthor nd source re credited. Source of Support: Nil, Conflict of Interest: None declred. Our Dermtol Online
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