We present case of oral and skin anaplastic T-cell lymphoma in a 68-year-old woman. The patient presented with extensive ulcerations and necrotic tissue on the left mandibular gingiva. Orthopantomogram finding showed extensive necrolytic lesions of the adjacent mandible. Biopsy finding of oral lesions and subsequently of the skin confirmed the diagnosis of anaplastic T-cell lymphoma. The bridge on the teeth 35-37 was taken out. After three cycles of chemotherapy, oral lesions subsided, unlike skin lesions. Dentists should be aware that differential diagnosis when dealing with oral ulcerations might be the result of certain malignant hematologic diseases.U radu se prikazuje slučaj oralnog i kožnog anaplastičnog limfoma velikih T stanica u 68-godišnje osobe. U bolesnice su na prvom pregledu uočene opsežne ulceracije i nekrotično tkivo u području gingive na mandibuli lijeve strane lica. Na ortopantomogramu su se vidjele opsežne nekrolitične lezije na kosti mandibule toga dijela. Patohistološki nalaz sluznice usne šupljine, a poslije i kože potvrdio je dijagnozu anaplastičnog limfoma velikih T stanica. Most na zubima 35-37 je izvađen. Nakon tri ciklusa kemoterapije oralne lezije su se povukle, za razliku od kožnih lezija. Stomatolozi pri diferencijalnoj dijagnostici oralnih ulceracija moraju imati na umu i moguću povezanost tih lezija s malignim hematološkim bolestima

Aleksandar Milenović

Igor Aurer

Ivana Ilić

Ivana Škrinjar

Miroslav Mayer

Mirta Mikulić

Sandra Bašić Kinda

Snježana Dotlić

Vanja Vučićević Boras

Čedna Tomasović-Lončarić

English

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246 Acta Clin Croat,  Vol. 53,   No. 2,  2014Acta Clin Croat 2014; 53:246-251 Case Report SimultAneouS pReSentAtion of oRAl And Skin AnAplAStiC lARge t-Cell lymphomAAleksandar milenović1, Vanja Vučićević Boras2, ivana ilić3, Snježana dotlić3, igor Aurer4, Sandra Bašić kinda4, miroslav mayer5, mirta mikulić6, Čedna tomasović-lončarić7 and ivana Škrinjar21Clinical department of maxillofacial Surgery, dubrava university hospital Center; 2department of oral medicine, School of dentistry, university of Zagreb and Zagreb university hospital Center; 3department of pathology and Cytology, 4department of hematology, 5Clinical department of internal medicine, Zagreb university hospital Center, 6Croatian Bone marrow donor Registry, Zagreb university hospital Center; 7department of pathology and Cytology, dubrava university hospital Center, Zagreb, CroatiaSummARy – We present case of oral and skin anaplastic t-cell lymphoma in a 68-year-old woman. The patient presented with extensive ulcerations and necrotic tissue on the left mandibular gingiva. orthopantomogram finding showed extensive necrolytic lesions of the adjacent mandible. Biopsy finding of oral lesions and subsequently of the skin confirmed the diagnosis of anaplastic t-cell lymphoma. The bridge on the teeth 35-37 was taken out. After three cycles of chemotherapy, oral lesions subsided, unlike skin lesions. dentists should be aware that differential diagnosis when dealing with oral ulcerations might be the result of certain malignant hematologic diseases.key words: Lymphoma; T cell, cutaneous; Oral ulcer; Case reportCorrespondence to: Vanja Vučićević Boras, MD, Department of Oral Medicine, School of Dental Medicine, University of Zagreb, Gundulićeva 5, HR-10000 Zagreb, CroatiaE-mail: boras@sfzg.hrReceived April 18, 2013, accepted February 13, 2014IntroductionAccording to the World health organization (Who) definition, lymphomas are classified as non-hodgkin’s lymphomas (nhl) and hodgkin’s lymphomas (hl). The majority of malignant lym-phomas, of which more prevalent are B-cell nhl, arise in lymphoid tissue, especially in cervical lymph nodes and Waldeyer’s ring, followed by the vestibule and gingiva, mandible, palatal soft tissue, maxilla and tongue1. extranodal sites affected with nhl frequently in-clude skin (21%), bone (17%), soft tissues (17%), lungs (11%) and liver (8%). in general, oral manifestations of nhl occur secondary to a more widespread dis-tribution throughout the body. Clinical presentation is variable. Additionally, simultaneous existence of oral and skin t-cell lymphoma has been described in about thirty case reports so far1.head and neck involvement accounts for 8%-13% of all extranodal lymphomas. oral manifestations of nhl are present in 2%-5% of all lymphomas and are the third most common malignancy in the oral cav-ity2. Case ReportA 68-year-old female patient was referred to de-partment of oral medicine for evaluation of the ex-tensive ulceration on the gingiva extending from 35-38 in the left mandible (fig. 1). no lymphadenopathy was noted. The orthopantomogram finding showed extensive mandibular bone loss in the region 34-38 (fig. 2). She was also suffering from intense pain. At the same time, the patient had skin nodules all over the body. most of them were firm, some of them pru-ritic and some painful, while others had erythematous Acta Clin Croat,  Vol. 53,   No. 2,  2014 247A. milenović et al. oral and skin t-cell lymphomaand ulcerative surface (figs. 3 and 4). detailed medi-cal history showed to have suffered the patient to from gastritis and osteopenia 15 years before, however, she was not treated with bisphosphonates. furthermore, several years before, she had undergone uterine and bile duct operation. Three months before eruptions on the skin and oral lesions, she had undergone surgi-cal operation for para-aortic paraganglioma (supra-renal adenoma which was hormonally inactive) as a coincidental finding. The patient was non drinker and non smoker. Biopsy specimens of the oral mucosa and skin nodules were taken. histologic examination of oral lesions showed medium sized atypical lympho-cytes, some with kidney shaped nuclei, together with Fig. 1. Extensive ulceration in the region 35-37.Fig. 2. Orthopantomogram showing extensive bone re-sorption.Fig. 3. Skin lesions on the patient’s left arm.Fig. 4. Leg lesions in our patient.Fig. 5. Infiltration of the mucosa by atypical lymphoid cells (HE, original magnification X40).248 Acta Clin Croat,  Vol. 53,   No. 2,  2014A. milenović et al. oral and skin t-cell lymphomaeosinophils and neutrophils, primarily in the area of necrosis. Atypical lymphocytes expressed Cd30 in a membrane and golgi pattern, Cd2, Cd3, Cd45Ro, granzyme B and emA antigens. The cells were Alk, Cd15, BCl6, Cd56, Cd21, Cd10 and Cd20 nega-tive, with partial loss of Cd8, Cd7, Cd5 and Cd4 antigens. proliferative antigen ki67 was positive in 40%-50% of described atypical lymphocytes (figs. 5-10).histologic examination of the skin showed large, atypical lymphatic cells, which were immunohis-tochemically positive for Cd30, emA, Cd8, gran-zyme B, and negative for Cd56 tiA, Cd4, Cd20 Fig. 6. Atypical lymphoid cells (HE, original magnifica-tion X400).Fig. 7. CD3 positivity (original magnification X100).Fig. 8. CD2 positivity (original magnification X100).Fig. 9. Scattered membrane and perinuclear dot-like posi-tivity for CD30 (original magnification X400).Fig. 10. Nuclear positivity for proliferation antigen Ki67 (original magnification X100).Acta Clin Croat,  Vol. 53,   No. 2,  2014 249A. milenović et al. oral and skin t-cell lymphomaand Alk1.Routine blood tests were normal except for eryth-rocyte sedimentation rate, which was slightly elevat-ed. Viral markers to hiV, hCV and hCB were nega-tive. Scintigraphy of the whole body and SpeCt/low dose computed tomography of the head showed only pathologic activity in the mandible, however, the rest of the body showed no pathologic changes. Bone marrow biopsy specimen revealed no signs of tumor process within it.The patient was referred to hematology oncolo-gist and was treated with cyclophosphamide, oncovin (vincristine), etoposide, prednisone (Coep regimen), which consists of cyclophosphamide 750 mg/2 i.v., etoposide 100 mg/m2 on the first day, vincristine 1.4 mg/m2 on the first, second and third day and pred-nisone 60 mg/m2 orally from the first to fifth day. Therapeutic cycles were repeated every three weeks3. The patient’s staging was t3b, n0, m1 according to the international Society for Cutaneous lympho-mas (iSCl) and the Cutaneous lymphoma task force of the european organization of Research and treatment of Cancer (eoRtC) proposal on tumor, lymph nodes and metastases (tnm) classification of cutaneous lymphoma other than mycosis fungoides (mf) and Sézary syndrome (SS)4.As mandibular bone beneath the bridge 35-38 be-came very necrotic, the bridge was taken out and se-questrectomy of the adjacent mandible was performed. mandibular necrosis started before chemotherapy.After three cycles of chemotherapy, complete re-gression of the symptoms in the oral cavity occurred, however, some skin lesions subsided while other de-veloped.Discussionmatsumoto et al.5 report that the mean age of pa-tients with oral nhl was 54.6 (range 12-77) years and that the gender distribution was equal. one half of the cases occurred in the gingiva (44.4%), followed by the lip (22.2%), palate (11.1%) and tongue (11.1%), and 44% were not accompanied with lymphade-nopathies. furthermore, all of the reported patients complained of swelling occasionally, combined with ulceration and pain as the first symptom. oral le-sions may appear as painless enlargement, often with surface ulceration secondary to trauma. if bone is the primary site, tooth and alveolar bone loss is often seen. pain, swelling, numbness of the lip and patho-logic fractures may be associated with bone lesions6. Anaplastic large cell lymphoma (AlCl) accounts for 2%-7% of all nhls. AlCl has also been reported in immunosuppressed individuals (hiV+ and iatro-genically immunosuppressed). Clinical presentation of AlCl is variable, extranodal presentation is com-mon, especially in the skin. may et al.7 report on two cases of oral-cutaneous Cd4 positive t-cell lympho-ma having manifestations as tongue and skin nodules. matsumoto et al.5 report on an AlCl characterized by Cd30+positive findings and large epitheloid cell proliferation with a highly anaplastic t-cell pheno-type, which also expresses Cd45Ro, granzyme B, tiA-1 (t-cell intracytoplasmic antigen 1), perforin and p80npm/Alk.immunocytochemical analysis is an imperative in the diagnosis of Cd30-positive or ki-1 positive AlCl. The cells are also positive for Cd30, others may be such as lCA, emA, pan t-cell markers such as uChl-1 and pan-B-cell markers such as l26, al-though almost 25% of cases will not stain for B-cell or t-cell markers at all8,9. Rarely, nhl can be diag-nosed solely on the basis of cytologic examination10; biopsy finding is almost always needed. differential diagnosis when encountering oral ulcerations might be mechanical trauma, histiocytosis, vesiculobullous disease, mycosis fungoides, extranodal nk/t-cell lymphoma, Cd8+ epidermotropic cytotoxic primary cutaneous t-cell lymphoma, benign lymphoid hy-perplasia, lymphomatoid papulosis, Cd30 positive t-cell lymphoproliferative disorder, poorly differen-tiated carcinoma, adult t-cell leukemia/lymphoma, low grade mAlt lymphoma, hl, amelanotic mel-anoma, malignant melanoma, leukemic infiltrates, sarcoidosis, chronic bacterial infections (tuberculosis, syphilis), chronic fungal infections, traumatic eosino-philic granuloma and vasculitis11,12.unfortunately, the patient died, so follow up bi-opsy and pet/Ct scans were not performed.So far, only around twenty cases of oral AlCl have been reported in the literature. Currently, Who considers two AlCl types, Alk-negative and Alk-positive, and those who are Alk-negative show an inaccurate behavior with a relatively unfavorable 250 Acta Clin Croat,  Vol. 53,   No. 2,  2014A. milenović et al. oral and skin t-cell lymphomaprognosis, as was also seen in our case13. Based on the review of the existing literature, Rozza-de-menezes et al.14 report that there is a slight male predilection for AlCl, which could not be confirmed in our case report. however, in accordance with these authors14, gingiva was the most frequent site of AlCl appear-ance together with bone resorption, as also seen in our patient.Conclusiondentists should be aware that differential diag-nosis when dealing with oral ulcerations and/or iso-lated gingival/periodontal lesions might be the result of certain malignant blood diseases, especially when bone necrosis underneath is seen.References1. SAVARRio l, giBSon J, dunlop dJ, o’RouRke n, fitZSimonS eJ. Spontaneous regression of an anaplastic large cell lymphoma in the oral cavity: first reported case and review of the literature. oral oncol 1999;35(6):609-13. 2. mAdAnA J, yolmo d, SAxenA Sk, gopAlAkRiSh-nAn S. primary extranodal t-cell non-hodgkin lymphoma of the tongue. ear nose Throat J 2012;91:1-3.3. moCCiA AA, SChAff k, hoSkinS p, et al. R-Chop with etoposide substituted for doxorubicin (R-Ceop): excel-lent outcome in diffuse large B cell lymphoma for patients with a contraindication for anthracyclines. Blood 2009;114:170a (abstract 408).4. kim yh, WillemZe R, pimpinelli n, WhittAk-eR S, olSen  eA, RAnki A, dummeR R, hoppe Rt, iSCl and eoRtC. tnm classification system for pri-mary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome: a proposal of the international Society for Cutaneous lymphomas (iSCl) and the Cutaneous lym-phoma task force of the european organization of Research and treatment of Cancer (eoRtC). Blood 2007;110(2):479-84.  5. mAtSumoto n, ohki h, mukAe S, AmAno y, hARAdA d, niShimuRA S, komiyAmA k. Ana-plastic large cell lymphoma in gingivitis: case report and lit-erature review. oral Surg oral med oral pathol oral Radiol endod 2008;106:e29-e34.  6. VillA A, mARiAni u, VillA f. t-cell lymphoma of the oral cavity: a case report. Aust dent J 2010;55(2):203-6.  7. mAy SA, JoneS d, medeiRoS lJ, duViC m, pRi-eto Vg, lAZAR AJ. oral-cutaneous Cd4 positive t cell lymphoma: a study of two patients. Am J dermatopathol 2007;29:62-7.  8. hiCkS mJ, flAitZ Cm, niCholS Cm, lunA mA, gReSik mV. intraoral presentation of anaplastic large cell ki-1 lymphoma in association with hiV infection. oral Surg oral med oral pathol 1993;76:73-81.  9. koBAyAShi t, nAgASAWA t, mitSuhAShi S, et al. Clinicopathological characteristics of primary ki-1 anaplastic large cell lymphoma. int J hematol 1996;63:41-50.10. gVeRoViĆ-AntuniCA A, mARkoViĆ i, ĆoRoViĆ-ARneRi e, iVAniŠin-BARAČ A, kARAmAn k. pri-mary orbital non-hodgkin’s lymphoma: case report. Acta Clin Croat 2007;46:113-6.11. geddeS A, SAVin J, White SJ, giBSon J. primary cutaneous Cd8-positive t-cell lymphoma: a case report of a rare and aggressive disease with oral presentation. dent up-date 2011;38(7):472-4, 476.12. iShidA m, hottA m, tAkikitA-SuZuki m, koJi-mA f, okABe h. Cd8-positive granulomatous mycosis fungoides: a case report with review of the literature. J Cutan pathol 2010;37(10):1072-6. 13. ten BeRge Rl, oudeJAnS gJ, oSSenkoppele gJ, meiJeR CJl. Alk-negative systemic anaplastic large cell lymphoma: differential diagnostic and prognostic aspects – a review: J pathol 2003;200:4-15.14. RoZZA-de-meneZeS Re, JeRonimo feRReiRA S, lenZi CApellA d, SChWARtZ S, WillRiCh Ah, de noRonhA l, BAtiStA RodRigueS JohAnn AC, Couto SouZA ph. gingival anaplastic large-cell lymphoma mimicking hyperplastic benignancy as the first clinical manifestation of AidS: a case report and review of the literature. Case Rep dent 2013;2013:852932. Acta Clin Croat,  Vol. 53,   No. 2,  2014 251A. milenović et al. oral and skin t-cell lymphomaSažetakSimultAnA poJAVA oRAlnog i kožnog AnAplAStiČnog limfomA Velikih t StAniCAA. Milenović, V. Vučićević Boras, I. Ilić, S. Dotlić, I. Aurer, S. Bašić Kinda, M. Mayer, M. Mikulić, Č. Tomasović-Lončarić i I. Škrinjaru radu se prikazuje slučaj oralnog i kožnog anaplastičnog limfoma velikih t stanica u 68-godišnje osobe. u bolesnice su na prvom pregledu uočene opsežne ulceracije i nekrotično tkivo u području gingive na mandibuli lijeve strane lica. na ortopantomogramu su se vidjele opsežne nekrolitične lezije na kosti mandibule toga dijela. patohistološki nalaz sluznice usne šupljine, a poslije i kože potvrdio je dijagnozu anaplastičnog limfoma velikih t stanica. most na zubima 35-37 je izvađen. nakon tri ciklusa kemoterapije oralne lezije su se povukle, za razliku od kožnih lezija. Stomatolozi pri diferen-cijalnoj dijagnostici oralnih ulceracija moraju imati na umu i moguću povezanost tih lezija s malignim hematološkim bolestima.ključne riječi: Limfom, T stanični, kožni; Oralni ulkus; Prikaz slučaja

Simultana pojava oralnog i kožnog anaplastičnog limfoma velikih T stanica

Simultana pojava oralnog i kožnog anaplastičnog limfoma velikih T stanica

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