arquivos em odontologia volume 46 nº 03 l l julho/setembro...

Arquivos em Odontologia Volume 46 Nº 03Julho/Setembro de 2010

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Interdisciplinary approach to treating patients withEpithelioid Angiosarcoma: a case report

Conduta Interdisciplinar para tratar paciente comAngiossarcoma Epitelióide: relato de um caso-clínico

Raquel Teodoro Santos Teixeira1, Henrique Zanoni Fernandes1, Haglay Palandi de Oliveira Belloti1, Mariadas Graças Vilela Goulart1, Mônica Fernandes Gomes1

1Bioscience Center for Special Health Care Needs, Dental School, São Paulo State University (UNESP), São José dosCampos, SP, BrazilContato: [email protected]

ABSTRACTEpithelioid angiosarcoma is a rare malignant neoplasm found in vascular endothelial cells. The present

study aims to describe the radiological, clinicopathological, and immunohistochemical findings of a case ofepithelioid angiosarcoma located in the posterior mediastinum of a 65-year-old male patient who underwentsurgery and clinical treatment (Doxorubicin-based chemoterapy). It could be observed that the patient presentedpoor oral hygiene, severe cervical erosions in his teeth, chronic caries, periodontal disease, and periapicalabscess. For this reason, the participation of a dentist in an interdisciplinary team is of utmost importance.Oral support treatment also becomes essential in an attempt to eliminate all foci of oral infections, as well asminimize morbidity and improve the general condition of the patient before, during, and after oncologicaltreatment. In addition, the dentist will work toward the education and motivation of the patient to take on anappropriate oral hygiene so as to minimize the oral complications of chemotherapy, in turn providing betterconditions for the patient to eat, speak, socialize, and maintain a high quality of life.Uniterms: Epithelioid angiosarcoma. Drug therapy. Oral health.

INTRODUCTIONAngiosarcoma is a rare malignant

vascular neoplasm which constitutes less than 1%of all sarcomas. Epithelioid angiosarcoma (EA) isa rare variant of angiosarcoma, which ischaracterized by a high-grade malignant neoplasm,which consists of an atypical, multilayered, or solidendothelial proliferation and vasoformativearchitecture, presenting necrosis and an area ofhemorrhage1-5. The histologic hallmark of AE isrepresented by the presence of sheets and groupsof atypical endothelial cells with prominentepithelioid morphologies. The cells are usuallylarge and polygonal, containing abundanteosinophilic cytoplasm, a large nucleus with openchromatin, a prominent eosinophilic nucleolus, andan occasional intracellular lumina containing redblood cells1,4-7. Immunohistochemical analysis thatdemonstrates the endothelial nature of theneoplasm is frequently positive for specificvascular markers (CD31, CD34, factor VIII), and

keratin1,2,5,6. This neoplasm has been described ina wide range of sites, such as in deep soft tissues,the uterus, the thyroid, adrenals, the breast, thepleura, the lung, the pharynx, the skin, the prostate,seminal vesicles, and bones2,4-7. Prior literaturereports that this neoplasm takes on an aggressivecourse and has a strong tendency to recur locallyand to metastasize. Therefore, the recommendedtreatment which offers the best chance of survivalto the patient is surgery, together with radiotherapyand chemotherapy 3,4,7,8.

The patients receiving chemotherapy aresusceptible to oral complications which can beassociated with significant morbidity and evenmortality. The myelosuppression andimmunosuppression which accompany currenttherapies may lead to severe stomatitis, oralinfections, hemorrhage, xerostomia, among otheroral complications9-16.

Therefore, the present study aimed toreport a case of epithelioid angiosarcoma; discuss

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i ts radiographic, clinicopathological, andimmunohistochemical findings; and correlate thesefindings with the characteristics found in theliterature. The study will also describe the oralconditions of the patient and guide theinterdisciplinary team toward the necessarypreventive and therapeutic dental care to beimplemented before and during chemotherapeutictreatment. The dentist, as a member of theinterdisciplinary team, must prepare the patient forchemotherapy, given that the dental proceduresare important in eliminating all the foci of oralinfections as well as improving the patients’ qualityof life before, during, and after oncologicaltreatment.

CASE REPORTA 65-year-old, leucoderm, male patient

was referred to the Special Health Care NeedsAssociation (ASPE, São José dos Campos, Brazil)for oral evaluation (Figure 1).

Figure 1- 65-year-old male with EpithelioidAngiosarcoma

Upon examining the patient’s medicalrecords, the patient reported to be a user of alcoholand a smoker for 52 years and complained of anintense pain in the thoracic region (Figure 2).

Figure 2 - Computed tomography of the thoracicregion showing an expansive lesion with ahypoattenuating area in the right paravertebralmediastinum region (arrow), before the surgicalprocedure

Computed tomography showed a lesionlocated in the right paravertebral (T6 level) posteriormediastinum region, with a size of 3.9 x 3.0 cm, inaddition to pulmonary interstitial infiltration in the rightbase of the organ and two homogeneoushypoattenuating nodular images, of 1.0 cm in size, inthe liver (Figure 3a-b).

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Figure 3 - Computed tomography showing (a andb) two homogenous hypoattenuating nodular lesions(white arrows)

Upon being submitted to a surgicalresectioning of the mass of posterior mediastinum,the histological examination showed a malignantneoplasm consisting of well-formed irregular vascularspaces lined with atypical epithelioid cells and solidnests and cords of atypical epithelioid cells withmoderate mitotic activity. Necrosis areas (less of50%) and interstitial hemorrhages could also beobserved (Figure 4a-c).

Figure 4a

Figure 4b

Figure 4c

Figure 4 – Photomicrographies showing amalignant neoplasm, consisting of well-formedirregular vascular spaces lined with atypicalepithelioid cells and solid nests and cords of atypicalepithelioid cells with moderate mitotic activity, andpositive for antibody CD 34 (c). (H.E.: 100X and200X, and immunohistochemical staining: 50x)

Upon immunohistochemical examination,neoplasm cells proved to be positive for CD31, CD34,and fascin. The diagnosis was epithelioidangiosarcoma, which was partially excised. Twomonths after surgery, postoperative treatment beganwith chemotherapy, which consisted of six cycles ofdoxorubicin (Adriblastina® RD, Pharmacia ItaliaS.p.A, Milan, Italy), at intervals of 21 days betweeneach cycle. The support medications used includedondansetron HCl dihydrate (antiemetic, Zofran®Glaxo Operations UK Limited, Ware, England), anddexamethasone (Decadron®, Aché LaboratóriosFarmacêuticos S.A., Guarulhos, SP, Brazil).

Upon extra and intraoral examination, afterthe first chemotherapy session, icteric face; pale lips;atrophic oral mucosa; tongue coating; poor oralhygiene with an intense quantity of bacterial plaquein all dental elements; dental calculus; and gingivalbleeding associated with periodontal pockets couldbe observed. The patient did not have maxillary rightand left first molars, a left second premolar, nor the

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mandibular right and left first molars. The residualroots stemmed from the maxillary right second molarand canine, the maxillary left first premolar, and themandibular right and left second molars. In addition,the patient presented a poorly adapted dentalprothesis, chronic caries, and severe cervical teetherosions (Figure 5a-b).

Figure 5a

Figure 5b

Figure 5- Intraoral evaluation, before chemotherapy,showing poor oral hygiene with an intense quantityof bacterial plaque, salivary calculus, residual roots,chronic caries and severe cervical teeth erosions

The panoramic radiography revealed a raredental anomaly characterized by an intrabonymigration of the impacted mandibular right canineand a diffuse periapical bone resorption, suggestinga periapical abscess in the mandibular right firstpremolar (Figure 6).

Figure 6 – Panoramic radiography, beforeodontological treatment, showing a rare dental anomalycharacterized by an intrabony migration of theimpacted mandibular right canine (arrow) and adiffuse periapical bone resorption, suggesting aperiapical abscess in the mandibular right first premolar.

The supporting dental treatment wascarried out two weeks before and duringchemotherapy. First, all the extra and intraosseousinfection foci were eliminated. The patient thenunderwent periodontal treatment and educationconcerning oral hygiene, including the performanceof scaling, planning, and coronary and radicularpolishing procedures, and the application of fluor.After antibiotic prophylaxis, the extractions of theresidual roots, endodontic treatment due topresence of periapical abscess, and deep cariestreatment were performed (Figure 7a-b).

Figure 7a

Figure 7 - Clinical aspect. Immediate oral supporttreatment, before and during chemotherapy,eliminating all the oral infection foci.

Figure 7b

During chemotherapy, the oral mucosaremained dry and erithematous, and a significantreduction in salivary flow occurred. In this phase oftreatment, the patient was advised on tooth brushingtechniques, used an artificial saliva solution(Salivan®, APSEN Farmacêutica S/A, São Paulo,SP, Brazil) six times daily to treat the reduction insalivary flow, and underwent oral mucosaevaluations weekly.


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DISCUSSIONEpithelioid Angiosarcoma is a rare

malignant neoplasm found in vascular endothelialcells which affects a wide age range, with a higherincidence among elderly patients4,7. The peakincidence in the seventh decade of life related byTeltzrow et al.17 was also found in this report.

This neoplasm has been reported to appearin diverse sites, such as deep soft tissues, theuterus, the thyroid, adrenals, the breast, the pleura,the lung, the pharynx, the skin, the prostate, seminalvesicles, the bone, the maxillary sinus, and thegingiva2-7, however, to our knowledge, this has notbeen previously reported in the paravertebral (T6level) posterior mediastinum region, described inthis case.

A variety of conditions are known to beassociated with the development of angiosarcoma;these include chronic edematous states, sunexposure, prior irradiation, and, in more rare cases,chronic exposure to foreign material7. Althoughreports show no alcohol and tobacco consumptionassociated with epithelioid angiosarcoma, thesefactors may well increase the risk for furthermalignancy and may even compromise thechemotherapy treatment18,19. The patient in thiscase report had a previous history of 52 years ofcigarette smoking and alcohol consumption.

Pathologic diagnosis is characterized bypolygonal or oval cells with atypical irregular nucleiand vascular spaces lined with such cells andsurrounded by hemorrhagic phenomena.Immunohistochemical findings that demonstratethe endothelial nature of the tumor proved to bepositive for CD31, CD34, factor VIII, and keratin,whose coexpression is frequently seen inepithelioid angiosarcoma1,4-7. In this study, it waspositive only for CD31, CD 34, and fascin. Poorlydifferentiated angiosarcomas are bestdistinguished from other spindle cell sarcomas withimmunohistochemistry to help diagnosis, especiallywhen the CD31 antigen is present, the mostsensitive endothelial markers3,4. Fascin is a globularactin cross-linking protein that plays a key role informing parallel actin bundles in cell protrusions,which are key specializations of the plasmamembrane for environmental guidance and cellmigration. Fascin is widely expressed inmesenchymal tissues and the nervous system,while it is low or absent in adult epithelia. Recentdata from a number of laboratories havehighlighted that fascin is up-regulated in manyhuman carcinomas and correlated with the clinicalaggressiveness of tumors and poor patientsurvival20,21. In this study, the neoplasm proved to

be positive for fascin, which could confirm thecommon trend of this tumor to metastasize andreduce the patient’s life expectation.

Since angiosarcoma is characteristically ametastasizing tumor, it is always described in theliterature as simultaneously involving 2 to 3 organs.In many cases, the primary focus cannot beidentified, and cardiopulmonary involvement iscommon5,7. Lopez et al.5 found a widespreadinvolvement of the lungs, digestive tract, spleen,liver, and kidney. In this case, the primary focuswas in the right paravertebral (T6 level) posteriormediastinum region. Pulmonary interstitialinfiltration and hepatic nodules could also beobserved. After the diagnosis, the patient wassubmitted to surgical and chemotherapy treatment.

For chemotherapy, anti-neoplasm drugspresenting cytotoxic properties were used inneoplasic cells, as well as in tissues of fastproliferation, such as bone marrow, pilous follicles,oral and gastrointestinal mucosa, which are mostsensible to the anti-proliferative effects of thesedrugs12,22. Doxorubicin is an anti-neoplasm drugwhich is widely used in the treatment of neoplasms,such as carcinoma of the breast, lung, bladder,thyroid and ovary; sarcomas of bone and softtissues; Hodgkin and non-Hodgkin lymphomas;neuroblastoma; Wilms Tumor; acute lymphoblasticleukemia; and acute myeloid leukemia. This drugis obtained from the bacterium Streptomyces

peuceticus. Its mechanism of action consists ofconnecting itself to the DNA and inhibiting thesynthesis of nucleic acid. Its dose limit isdetermined when the patient presentsmyelosuppression and cardiotoxicity. Its effectsinclude hair loss, nausea, vomiting, low number ofwhite and red blood cells and platelets, heartarrhythmias, mucositis, xerostomia, sore mouth andtaste change, discolored urine, and skinchanges23,24. In this case report, the drug used wasdoxorubicin, whose side effects included hair loss,nausea, vomiting, myelosuppression, fever,depression, as well as saliva flow reduction andits subsequent consequences.

The most common oral complicationsduring the chemotherapy include oral mucositis,xerostomia, hemorrhage, and an increase in theindex of caries and opportunistic infections9-16,25.IN an attempt to minimize the oral complicationsduring chemotherapy, the patient must beevaluated by the dentist prior to beginningchemotherapy to identify possible situations of oralinfections, such as caries, gingivitis, periodontitis,and periapical lesions that can cause generalizedinfections. In addition, myelosuppression can


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increase a pre-existing periodontal disease. Oncethe oral lesions have been detected, the dentistthen applies the most appropriate dental treatmentto eliminate all foci of infection. The clinicalprocedures at this stage include oral prophylaxis,roots extractions, draining of abscesses,endodontic and surgical treatment of the periapicallesions, scaling and planning of the crown anddental roots, instructions on hygiene and topicfluoride application9-16,25,26. Our patient presentedsome foci of oral infections, such as severeperiodontitis, extensive chronic caries, andperiapical abscess. These lesions were associatedwith a large amount of bacterial plaque and dentalcalculus. Therefore, all the foci of infections hadbeen completely removed, promoting a reductionin the gingival inflammation and bleeding andavoiding the sprouting of oral mucositis andcandidiasis. In this light, oral care becomesessential in minimizing morbidity and improving thegeneral conditions of the patient before and duringoncological treatment and conditions regardingpatient nutrition.

During chemotherapy, the patient alsocomplained about dry mouth. According toColeman27, the salivary glands are directlyaffected, thus resulting in a reduced salivary flow.This condition has significant consequences on boththe hard and soft components of the oral cavityand can subsequently compromise its functionality.This can lead to swallowing difficulties, which alsocontribute to bacteria colonization and bacterialplaque formation, which in turn lead to dentalcaries and periodontal diseases28,29. In the presentcase, a severe reduction in salivary flow could beobserved. Therefore, an artificial saliva solutionto maintain oral health of our patient wasrecommended.

Furthermore, our patient presented no oralmucositis. According to Coleman28, Sonis11, andGomes et al.16, the younger the patient, the greaterthe possibility of chemotherapy affecting themouth. In the present case, the patient’s age, oralhygiene, and the use of the artificial saliva haveprevented the sprouting of oral mucositis.

CONCLUSIONThe participation of a dentist in an

interdisciplinary team is of utmost importance. Theoral support treatment is essential in eliminatingall foci of oral infections as well as in minimizingmorbidity and improving the general conditions ofthe patients before, during, and after oncologicaltreatment. Moreover, the dentist will work on theeducation and motivation of the patient to take on

an appropriate oral hygiene in an attempt tominimize the oral complications of chemotherapy,in turn providing better conditions for the patientto eat, speak, socialize, and maintain a high qualityof life.

RESUMOAngiossarcoma epitelióide é uma neoplasia

maligna rara das células vasculares endoteliais.Neste estudo, foram descritos os achadosradiológicos, clinicopatológicos eimunohistoquímicos de um caso de angiossarcomaepitelióide no mediastino posterior, em um pacientede 65 anos de idade, submetido à cirurgia etratamento clínico (quimioterapia comDoxorubicina). Observou-se que o pacienteapresentava higiene bucal precária, erosõescervicais severas, lesões de cárie crônicas, doençaperiodontal e abscesso periapical. A participaçãodo dentista em uma equipe multidisciplinar é muitoimportante. O tratamento de suporte é essencialpara eliminar todos os focos de infecção oral,minimizar a morbidade e melhorar as condiçõesgerais do paciente antes, durante e após otratamento oncológico. Além disso, é importanteque o dentista trabalhe na educação e motivaçãodo paciente para conseguir uma adequadahigienização bucal e para tentar minimizar ascomplicações orais da quimioterapia, melhorandoas condições para que o paciente se alimente, falee socialize-se, tendo uma melhor qualidade devida.Descritores: Angiossarcoma epitelióide.Quimioterapia. Saúde bucal.

ACKNOWLEDGEDMENTSWe are grateful to Doctor Venâncio

Avancini Ferreira Alves from the Cytophatological,Pathological, Anatomy, Cytophatological, andImuno-histochemical Center (São Paulo, Brazil);to Doctor Carlos Eduardo de Godoy from theCytophatological, Pathological, and AnatomyLaboratory; to Maria Alcionéia Carvalho deOliveira from the Bioscience Center for SpecialHealth Care Needs; and to the Quaglia Laboratory(São José dos Campos, São Paulo, Brazil).

REFERENCES1. Mentzel T, Katenkamp D. Intraneural

angiosarcoma and angiorsarcoma arising inbenign and malignant peripheral nerve sheathtumours: cl inicopathological andimmunohistochemical analysis of four cases.Histopathology. 1999; 35:114-20.


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2. Roh MS, Seo JY, Hong SH. Epithelioidangiosarcoma of the pleura: a case report. JKorean Med Sci. 2001; 16:792-5.

3. Triantafillidou K, Lazaridis N, ZaramboukasT. Epithelioid angiosarcoma of the maxillarysinus and the maxilla: a case report andreview of the literature. Oral Surg Oral MedOral Pathol Oral Radiol Endod. 2002;94:333-7.

4. Deshpande V, Rosenberg AE, O’Connell JX,Nielsen GP. Epithelioid angiosarcoma of thebone: a series of 10 cases. Am J Surg Pathol.2003; 27:709-16.

5. López L, Iriberri M, Cancelo L, Gómez A,Uresandi F, Atxotegui V. Persistenthemoptysis secondary to extensive epithelioidangiosarcoma. Arch Bronconeumol. 2004,40:188-90.

6. Macías-Martínez V, Murrieta-Tiburcio L,Molina-Cárdenas H, Domínquez-Malagón H.Epithelioid angiosarcoma of the breast:clinicopathological, immunohistochemical, andultrastructural study of a case. Am J SurgPathol. 1997; 21:599-604.

7. Wehrli BM, Janzen DL, Shokeir O, Masri BA,Byrne SK, O’Connell JX. Epithelioidangiosarcoma arising in a surgicallyconstructed arteriovenous fistula: a rarecomplication of chronic immunosuppressionin the setting of renal transplantation. Am JSurg Pathol. 1998; 22:1154-9.

8. Refre GR, Buenconcejo LS, Aleta KNR, Tan-Liu NS, Wang AD. Breast mass in a malepatient: a case of primary thoracic epithelioidangiosarcoma. Philipp J Intern Med. 2006;44:197-203.

9. Rosemberg SW. Oral complications of cancerchemotherapy: a review of 398 patients. JOral Med. 1986; 41:93-7.

10. Massler Jr CF. Preventing and treating oralcomplications of cancer therapy. Gen Dent.2000; 48:652-5.

11. Sonis ST, Fey EG. Oral complications ofcancer therapy. Oncology. 2002; 16:680-95.

12. Barasch A, Peterson DE. Risk factors forulcerative oral mucositis in cancer patients:unanswered questions. Oral Oncol. 2003;39:91-100.

13. McGuire DB. Barriers and strategies inimplementation of oral care standards forcancer patients. Support Care Cancer. 2003;11:435-41.

14. Redding SW. Oral complications of cancertherapy. Tex Med. 2003; 99:54-7.

15. Sadler GR, Stoudt A, Fullerton JT, Oberle-Edwards LK, Nguyen Q, Epstein JB.Managing the oral sequelae of cancer therapy.Medsurg Nurs. 2003; 12:28-36.

16. Gomes MF, Kohlemann KR, Plens G, SilvaMM, Pontes EM, Rocha JC. Oralmanifestations during chemotherapy for acutelymphoblastic leukemia: a case report.Quintessence Int. 2005; 36:307-13.

17. Teltzrow T, Hallermann C, Muller S,Schwipper V. Foreign body-inducedangiosarcoma 60 years after a shell splinterinjury. Mund Kiefer Gesichtschir. 2006;10:415-8.

18. El-Bayoumy K, Chung FL, Richie J, et al.Dietary control of cancer. Proc Soc Exp BiolMed. 1997; 216:211-23.

19. Pinto BM, Trunzo JJ. Health behaviors duringand after a cancer diagnosis. Cancer. 2005;104:2614-23. Errata em: Cancer. 2006;106:1641.

20. Hashimoto Y, Skacel M, Adams JC. Roles offascin in human carcinoma motility andsignaling: prospects for a novel biomarker?Int J Biochem Cell Biol. 2005; 37:1787-804.

21. Yoder BJ, Tso E, Skacel M, et al. Theexpression of fascin, an actin-bundling motilityprotein, correlates with hormone receptor-negative breast cancer and a more aggressiveclinical course. Clin Cancer Res. 2005; 11:186-92.

22. Silverman S. Oral cancer: complications oftherapy. Oral Surg Oral Med Oral Pathol OralRadiol Endod. 1999; 88:122-6.

23. Martindale. The complete drug reference.33nded. London: The Pharmaceutical Press;2002.

24. Kilickap S, Barista I, Akgul E, Aytemir K,Aksoy A, Tekuzman G. Early and latearrhythmogenic effects of doxorubicin. SouthMed J. 2007; 100:262-5.

25. Sonis ST. Oral mucositis in cancer therapy. JSupport Oncol. 2004; 2:3-8.

26. Raut A, Huryn JM, Hwang, FR, Zlotolow, IM.Sequelae and complications related to dentalextractions in patients with hematologicmalignancies and the impact on medicaloutcome. Oral Surg Oral Med Oral Pathol OralRadiol Endod. 2001; 92:49-55.

27. Coleman S. An overview of oral complicationsof adult patients with malignanthaematological conditions who haveundergone radiotherapy or chemotherapy. JAdv Nurs. 1995; 22:1085-91.


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28. Branchi R, Fancelli V, Durval E, De SalvadorA. The patient with xerostomia: medicaltherapy, prosthetic therapy. Minerva Stomatol.2003; 52:455-63.

29. Friedlander AH, Friedlander IK, Gallas M,Velasco E. Late-life depression: its oral healthsignificance. Int Dent J. 2003; 53:41-50.

Received on 02/02/2008 – Accepted on 25/05/2008

Autor correspondente:Profª Adja Mônica Fernandes GomesAvenida Engenheiro José Longo, 777CEP: 12245-000 - São José dos Campos – SP - Brazile-mail: [email protected]

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