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Med Oral Patol Oral Cir Bucal. 2012 May 1;17 (3):e383-8. Primary oral melanoma e383 Journal section: Oral Medicine and Pathology Publication Types: Research Primary oral melanoma: A histopathological and immunohistochemical study of 22 cases of Latin America Bruno-Augusto-Benevenuto de-Andrade 1 , Víctor-Hugo Toral-Rizo 1 , Jorge-Esquiche León 2 , Elisa Contreras 3 , Román Carlos 4 , Wilson Delgado-Azañero 5 , Adalberto Mosqueda-Taylor 6 , Oslei-Paes de-Almeida 2 1 ��� M�c. Oral Pat�olo�y �ection�e�artment o� Oral �ia�no�i�� Piracica�a �ental �c�ool�ni�er�ity o� Cam�ina� (�- ��� M�c. Oral Pat�olo�y �ection�e�artment o� Oral �ia�no�i�� Piracica�a �ental �c�ool�ni�er�ity o� Cam�ina� (�- CAMP)� Piracica�a�ão Paulo� Brazil 2 ��� P�. Oral Pat�olo�y �ection�e�artment o� Oral �ia�no�i�� Piracica�a �ental �c�ool�ni�er�ity o� Cam�ina� (�- ��� P�. Oral Pat�olo�y �ection�e�artment o� Oral �ia�no�i�� Piracica�a �ental �c�ool�ni�er�ity o� Cam�ina� (�- CAMP)� Piracica�a�ão Paulo� Brazil 3 ��� M�c. Centro Clínico de Ca�eza y Cuello� Ciudad de Guatemala� Guatemala 4 ���. Centro Clínico de Ca�eza y Cuello� Ciudad de Guatemala� Guatemala 5 ��� P�. �e�artamento de Patolo�ía� Medicina y Ciru�ía Oral. Facultad de E�tomatolo�ía. �ni�er�idad Peruana Cayetano Heredia� Lima� Perú 6 ��� M�c. �e�artamento de Atención a la �alud. �ni�er�idad Autónoma Metro�olitana Xoc�imilco� México� �.F Correspondence: Oral Pathology, Piracicaba Dental School University of Campinas (UNICAMP) Av. Limeira 901, P.O. Box 52 13414-903, Piracicaba, São Paulo, Brazil [email protected] Recei�ed: 08/03/2011 Acce�ted: 02/05/2011 Abstract O�jecti�e: T�e aim o� t�i� �tudy wa� to analyze t�e �i�to�at�olo�ical and immuno�i�toc�emical c�aracteri�tic� o22 ca�e� o�rimary oral melanoma� (OM). �tudy �e�i�n: Twenty two ca�e� o�rimary oral melanoma were analyzed �y de�cri�tion o� t�eir �i�to�at�olo�i- �e�i�n: Twenty two ca�e� o�rimary oral melanoma were analyzed �y de�cri�tion o� t�eir �i�to�at�olo�i- e�i�n: Twenty two ca�e� o�rimary oral melanoma were analyzed �y de�cri�tion o� t�eir �i�to�at�olo�i- cal �eature� and immuno�i�toc�emical �tudy u�in� t�e anti�odie�-100� HMB-45� Melan-A and Ki-67. Re�ult�: T�e mean a�e wa� 58 year� and 14 ca�e� were �emale. T�e main a��ected �ite� were t�e �ard �alate�ol- lowed �y t�e u��er �in�i�a. Micro�co�ically � 15 ca�e� �re�ented le�el ��� o� in�a�ion� 2 ca�e� were amelanotic and 13 ��owed a mixed e�it�elioid and �la�macytoid or ��indle cell� com�o�ition. �ome ca�e� ��owed necro�i��eri�a�cular and �erineural in�a�ion. �-100 and HMB-45 were �o�iti�e in all ca�e��ut 3 ca�e� were ne�ati�e �or Melan-A. T�e �roli�erati�e index wit� Ki-67 wa�i� wit� la�elin� index ran�in� �rom 15.51% to 63% o� �o�iti�e cell�. Conclu�ion: �-100 and HMB-45 are more �requently ex�re��ed t�an Melan-A in �rimary oral melanoma� and these markers are helpful to confirm the diagnosis. Key words: Oral melanoma, histopathology, immunohistochemistry. de-Andrade BB� Toral-Rizo VH� León JE� Contrera� E� Carlo� R�el- �ado-Azañero W� Mo�queda-Taylor A� de-Almeida OP. Primary oral melanoma: A �i�to�at�olo�ical and immuno�i�toc�emical�tudy o� 22 ca�e� o� Latin America. Med Oral Patol Oral Cir Bucal. 2012 May 1;17 (3):e383-8. �tt �://www.medicinaoral.com/medoral�ree01/�17i3/medoral�17i3�383.�dArticle Number: 17588 http://www.medicinaoral.com/ © Medicina Oral S. L. C.I.F. B 96689336 - pISSN 1698-4447 - eISSN: 1698-6946 eMail: [email protected] Indexed in: �cience Citation �ndex Ex�anded Journal Citation Re�ort�ndex Medicu� ME�L�E� Pu�Med �co�u� Em�a�e and Emcare �ndice Médico E�añol doi:10.4317/medoral.17588 http://dx.doi.org/doi:10.4317/medoral.17588

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Page 1: Melanoma

Med Oral Patol Oral Cir Bucal. 2012 May 1;17 (3):e383-8. Primary oral melanoma

e383

Journal section: Oral Medicine and PathologyPublication Types: Research

Primary oral melanoma: A histopathological and immunohistochemicalstudy of 22 cases of Latin America

Bruno-Augusto-Benevenuto de-Andrade 1, Víctor-Hugo Toral-Rizo 1, Jorge-Esquiche León 2, Elisa Contreras 3, Román Carlos 4, Wilson Delgado-Azañero 5, Adalberto Mosqueda-Taylor 6, Oslei-Paes de-Almeida 2

1 ���� M�c. Oral Pat�olo�y �ection� �e�artment o� Oral �ia�no�i�� Piracica�a �ental �c�ool� �ni�er�ity o� Cam�ina� (���-���� M�c. Oral Pat�olo�y �ection� �e�artment o� Oral �ia�no�i�� Piracica�a �ental �c�ool� �ni�er�ity o� Cam�ina� (���-CAMP)� Piracica�a� �ão Paulo� Brazil2 ���� P��. Oral Pat�olo�y �ection� �e�artment o� Oral �ia�no�i�� Piracica�a �ental �c�ool� �ni�er�ity o� Cam�ina� (���-���� P��. Oral Pat�olo�y �ection� �e�artment o� Oral �ia�no�i�� Piracica�a �ental �c�ool� �ni�er�ity o� Cam�ina� (���-CAMP)� Piracica�a� �ão Paulo� Brazil3 ���� M�c. Centro Clínico de Ca�eza y Cuello� Ciudad de Guatemala� Guatemala4 ���. Centro Clínico de Ca�eza y Cuello� Ciudad de Guatemala� Guatemala5 ���� P��. �e�artamento de Patolo�ía� Medicina y Ciru�ía Oral. Facultad de E�tomatolo�ía. �ni�er�idad Peruana Cayetano Heredia� Lima� Perú6 ���� M�c. �e�artamento de Atención a la �alud. �ni�er�idad Autónoma Metro�olitana Xoc�imilco� México� �.F

Correspondence: Oral Pathology, Piracicaba Dental School University of Campinas (UNICAMP)Av. Limeira 901, P.O. Box 52 13414-903, Piracicaba, São Paulo, [email protected]

Recei�ed: 08/03/2011Acce�ted: 02/05/2011

AbstractO�jecti�e: T�e aim o� t�i� �tudy wa� to analyze t�e �i�to�at�olo�ical and immuno�i�toc�emical c�aracteri�tic� o� 22 ca�e� o� �rimary oral melanoma� (OM). �tudy �e�i�n: Twenty two ca�e� o� �rimary oral melanoma were analyzed �y de�cri�tion o� t�eir �i�to�at�olo�i-�e�i�n: Twenty two ca�e� o� �rimary oral melanoma were analyzed �y de�cri�tion o� t�eir �i�to�at�olo�i-e�i�n: Twenty two ca�e� o� �rimary oral melanoma were analyzed �y de�cri�tion o� t�eir �i�to�at�olo�i-cal �eature� and immuno�i�toc�emical �tudy u�in� t�e anti�odie� �-100� HMB-45� Melan-A and Ki-67. Re�ult�: T�e mean a�e wa� 58 year� and 14 ca�e� were �emale. T�e main a��ected �ite� were t�e �ard �alate� �ol-lowed �y t�e u��er �in�i�a. Micro�co�ically� 15 ca�e� �re�ented le�el ��� o� in�a�ion� 2 ca�e� were amelanotic and 13 ��owed a mixed e�it�elioid and �la�macytoid or ��indle cell� com�o�ition. �ome ca�e� ��owed necro�i�� �eri�a�cular and �erineural in�a�ion. �-100 and HMB-45 were �o�iti�e in all ca�e�� �ut 3 ca�e� were ne�ati�e �or Melan-A. T�e �roli�erati�e index wit� Ki-67 wa� �i��� wit� la�elin� index ran�in� �rom 15.51% to 63% o� �o�iti�e cell�. Conclu�ion: �-100 and HMB-45 are more �requently ex�re��ed t�an Melan-A in �rimary oral melanoma� and these markers are helpful to confirm the diagnosis.

Key words: Oral melanoma, histopathology, immunohistochemistry.

de-Andrade BB� Toral-Rizo VH� León JE� Contrera� E� Carlo� R� �el-�ado-Azañero W� Mo�queda-Taylor A� de-Almeida OP. Primary oral melanoma: A �i�to�at�olo�ical and immuno�i�toc�emical�tudy o� 22 ca�e� o� Latin America. Med Oral Patol Oral Cir Bucal. 2012 May 1;17 (3):e383-8. �tt�://www.medicinaoral.com/medoral�ree01/�17i3/medoral�17i3�383.�d�

Article Number: 17588 http://www.medicinaoral.com/© Medicina Oral S. L. C.I.F. B 96689336 - pISSN 1698-4447 - eISSN: 1698-6946eMail: [email protected] Indexed in:

�cience Citation �ndex Ex�andedJournal Citation Re�ort��ndex Medicu�� ME�L��E� Pu�Med�co�u�� Em�a�e and Emcare �ndice Médico E��añol

doi:10.4317/medoral.17588http://dx.doi.org/doi:10.4317/medoral.17588

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IntroductionMelanoma i� �ormed �y mali�nant melanocyte�� w�ic� are cell� deri�ed �rom t�e neural cre�t t�at �roduce melanin (1). O�er 90% o� melanoma� occur in t�e �kin� �ut t�ey may al�o ari�e �rom muco�al �ur�ace� or at ot�er �ite� w�erein neural cre�t mi�rate (1�2). Primary oral melano-ma� are rare� com�ri�in� 0.4-1.8% o� all melanoma� and 0.5% o� oral mali�nance� (3-5). Primary OM i� more com-mon in t�e �alate and �in�i�a o� adult �atient�� and initially a�ym�tomatic contri�utin� to t�e delay o� dia�no�i� (6-10). Clinical �eature� �ary� �ut t�e mo�t common �re�entation i� an initial dark �lue or �lack irre�ular macule� turnin� later to an ulcerated �lack nodule (4�10-12). A� in ot�er ty�e� o� melanoma�� t�e �i�tolo�y o� OM i� �aria�le. Ba�ically it i� con�idered t�ree �attern�� in �itu� in�a�i�e and mixed� t�e latter i� t�e mo�t common corre��ondin� to a�out 55% o� t�e ca�e� (4�12). T�e tumor i� �ormed �y e�it�elioid� ��indle and �la�macy-toid tumor cell� arran�ed in a ��eet-like� or�anoid� al-veolar, solid or desmoplastic configuration (4,5,12,13). Mo�t �rimary OM are �ea�ily �i�mented� �ut �ome are amelanotic and immuno�i�toc�emi�try can �e �el��ul to confirm the diagnosis of these cases (14-25). T�e aim o� t�i� �tudy i� to de�cri�e t�e �i�tolo�ical c�aracter-i�tic� and ex�re��ion o� �-100� HMB-45� Melan-A and Ki-67 in 22 ca�e� o� �rimary OM o� Latin American �atient�.

Materials and MethodsFormalin-fixed, paraffin-embedded tissue blocks were o�tained �rom 22 �atient� (8 men and 14 women� mean a�e 58 year�� ran�e o� 23-86 year�) wit� �rimary OM. Ele�en ca�e� were �rom Guatemala� 7 �rom Mexico� and 4 �rom Peru. O� t�e 22 OM� �e�en (31.82%) were locat-ed on the hard palate, five (22.73%) on hard palate and u��er �in�i�a� �our (18.18%) only on t�e u��er �in�i�a� and two eac� (9.09%)� on �ard and �o�t �alate� on t�e lower �in�i�a and on t�e �uccal muco�a (Fi�. 1). Diagnosis of primary OM was confirmed by the clinical and �i�tolo�ical c�aracteri�tic�� excludin� t�e �re�ence o�

melanoma at ot�er anatomical �ite� and con�equently t�e �o��i�ility o� oral meta�ta�i�. T�e �arameter� e�aluated included �re�ence or a��ence o� melanin in t�e tumor (melanotic or amelanotic)� le�el o� tumor cell� in�a�ion� cellular mor��olo�y (e�it�elioid� ��indle� �la�macytoid or mixed) and �attern (�olid� al�eolar� or�anoid or �a�et-oid)� necro�i�� �erineural and �eri�a�cular in�a�ion. Cellular in�a�ion wa� con�idered accordin� to Pra�ad et al. (26) a� nonin�a�i�e (in �itu)� microin�a�i�e (le�el �� cell clusters in the superficial lamina propria), invasive (level ��� cell in�a�ion into t�e lamina �ro�ria)� and dee� in�a�i�e (le�el ���� in�a�ion into �keletal mu�cle� �one or cartila�e). For immuno�i�toc�emical �tainin� t�ree-micrometer-thick sections were used. Briefly, after antigen retrieval wit� E�TA/Tri� �u��er (�H 9.0) in a microwa�e o�en� endo�enou� �eroxida�e acti�ity wa� �locked wit� 20% H2O2 �or 5 cycle� o� 5 minute� eac�. Primary anti�odie� (Ta�le 1)� a�ter o�erni��t incu�ation� were detected �y �econdary anti�odie� conju�ated wit� �olymer dextran marked wit� �eroxida�e (�ako EnVi�ion La�elled Poly-mer; �ako� Glo�tru�� �enmark). T�e reaction wa� de-�elo�ed wit� Permanent Red (Permanent Red �u��trate �y�tem� �ako) �or t�e �rimary anti�odie� �-100� HMB-45 and Melan-A� and diamino�enzidine �ydroc�loride (�AB� �ako) wa� u�ed a� c�romo�en �or Ki-67. T�e �re�aration� were li��tly counter�tained wit� Carazzi �ematoxylin� mounted wit� Aquatex (MERCK� Ger-many) and examined �y li��t micro�co�e.

Antibody Clone Dilution Source

HMB-45 HMB-45 1:200 �ako®*

Melan-A A�03 1:800 �ako®*

Ki-67 M�B-1 1:100 �ako®*

�-100 Polyclonal 1:10.000 �ako®*

Table 1. Anti�odie� u�ed �or immuno�i�toc�emical e�alua-tion o� 22 ca�e� o� �rimary oral melanoma�.

*�ako� �ako Cor�oration� Car�interia� Cali�ornia.

Fig. 1. Clinical a��ect� o� �rimary oral melanoma. A. Oral melanoma o� t�e �ard �alate ��owin� a lar�e �lack� irre�ular macula wit� a �mall nodular area. B. Lar�e �i�mented melanoma o� t�e lower �in�i�a cau�in� toot� di��lacement.

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T�e inten�ity o� �tainin� �or �-100� HMB-45 and Me-lan-A wa� �raded a� �ollow�: ne�ati�e (-); weak (+) 1% to 25%; moderate (++) 25% to 50%; and �tron� (+++) 50% to 100% o� t�e neo�la�tic cell�. To calculate t�e la�elin� index (L�) �or Ki-67� 1000 tumor cell� were counted �or eac� ca�e and t�e re�ult� were ex�re��ed in �ercenta�e o� �o�iti�e cell�.

ResultsTwenty out o� 22 �rimary oral melanoma� �tudied were melanotic� and only two were amelanotic. Fi�teen ca�e�

(68.18%) ��owed dee� cellular in�a�ion (le�el ���) w�en dia�no�ed� w�ile 4 and 2 ca�e� �re�ented le�el� �� and � respectively, and only one case was classified as in situ. Cellular mor��olo�y �aried� wit� 8 ca�e� �ormed �y e�i-t�elioid and one �y ��indle cell�� w�ile t�e ot�er 13 ca�e� ��owed a mixed �o�ulation o� e�it�elioid and �la�macytoid or ��indle cell�. Mo�t ca�e� ��owed a �redominant cellu-lar �olid �attern (17 ca�e�-77.27%)� �ollowed �y al�eolar (3 ca�e�)� wit� or�anoid and �a�etoid �attern in only one ca�e eac�. �ecro�i�� �eri�a�cular and �erineural in�a�ion wa� �ound in 6� 7 and 3 ca�e� re��ecti�ely (Fi�. 2).

Fig. 2. Hi�tolo�ical a��ect� o� �rimary oral melanoma (H&E). A. Oral melanoma o� t�e �ard �alate com�o�ed mainly �y amelanotic ��indle cell� (x200). B. Oral melanoma o� t�e u��er �in�i�a �ormed �y e�it�elioid and �la�macytoid neo�la�tic melanocyte� (x400). C. �olid OM ��owin� nodular �attern o� neo�la�tic melanocytic cell� (x25). �. E�it�elioid and �la�ma-cytoid neo�la�tic melanocyte� arran�ed in or�anoid �attern (x100). E. �n �itu le�ion wit� neo�la�tic melanocyte� arran�ed in �a�etoid �attern (x100). F. Oral melanoma o� t�e �ard �alate ��owin� �eri�a�cular in�a�ion (x400).

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�mmuno�tainin� wit� t�ree melanocytic marker� �-100� HMB-45 and Melan-A in melanoma cell� wa� cyto�la�-mic� �ut nuclear �tainin� wa� al�o noted wit� �-100. �-100 and HMB-45 were ex�re��ed in all ca�e�� w�ile Melan-A wa� ne�ati�e in 3 ca�e�. �-100 wa� �o�iti�e in more t�an 50% o� tumor cell� in all ca�e�� and HMB-45 �ad a �tron� �tainin� in 21 ca�e� (95.45%)� and in one it wa� moderate. Melan-A wa� ex�re��ed in 19 out o� 22 ca�e�; in 16� one and 2 ca�e� it wa� �tron�� moderate and weak re��ecti�ely. Cell �roli�eration wit� Ki-67 ran�ed �rom 15.51% to 63% o� �o�iti�e cell� (Fi�. 3).

(13�23�24)� �ut in�ormation o� �i�tolo�ical and immuno-histochemical profile is scarce.Different from the skin there is not a definitive clinico-pathological classification of OM (10,12,23). Classifica-tion and �ta�in� o� cutaneou� melanoma� u�in� Bre�-low and Clark le�el� cannot �e a��lied to oral muco�a tumor� due to �tructural di��erence� �etween �kin and muco�a (13�25). �n �act OM di��er �rom cutaneou� in �e�eral a��ect�� includin� ri�k �actor� a� actinic radia-tion� a �amily �i�tory and a��ociation wit� aty�ical ne�i� �actor� a��lied mainly to cutaneou� melanoma (4). �n

Fig. 3. Ex�re��ion o� �-100 (A)� HMB-45 (B)� Melan-A (C)� and Ki-67 (�) in �rimary oral melanoma o� �ard �alate and u��er �in�i�a (x400).

DiscussionPrimary OM i� a rare neo�la�m accountin� �or only 0.5% o� all oral mali�nance�� wit� an incidence o� 1.2 ca�e� �er 10 million �er year (4�10�13). A� it i� �ery rare� t�ere are �ew re�orted �erie� o� OM. �t i� con�idered t�at in Euro�e and Au�tralia t�e incidence o� OM i� lower t�an in Ja�an and in ot�er nonw�ite �o�ulation� like in ��anda� �ndia and �ort� American �ndian (2� 6-8). �e-rie� o� OM ca�e� in Latin America �a�e �een re�orted

our present study we used the histological classification �ro�o�ed �y Pra�ad et al. (26) �a�ed on t�e le�el o� cel-lular in�a�ion. A� noted �re�iou�ly� in contra�t to cuta-neou� melanoma� w�ere t�e majority are dia�no�ed in t�e radial �rowt� ��a�e� OM are �ound �redominantly in t�e �ertical �rowt� ��a�e (4�12). Mo�t ca�e� in our �tudy were dia�no�ed wit� dee� in�a�ion (le�el ���) and only one a� in �itu. Alt�ou�� le�ion� in t�e mout� u�ually are ea�ily �i�ualized� �articularly i� �i�mented�

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mo�t ca�e� o� OM are in ad�anced �ta�e� w�en dia�-no�ed. �n�ortunately� t�i� i� al�o true �or oral �quamou� cell carcinoma� de��ite exten�i�e e��ort� �or early de-tection o� t�i� relati�ely common neo�la�ia. Our re�ult� were �imilar to t�o�e �ound �y Lourenço et al. (13)� wit� 82.35% o� t�e ca�e� dia�no�ed a� le�el ���� wit� only one ca�e a� le�el �. Oral melanoma� �a�e a �oor �ro�no�i�� and accordin� to Pra�ad et al. (26) t�e mo�t im�ortant �i�to�at�olo�ical �redictor i� tumor �i�tolo�ical le�el.Pre�ence o� melanin wa� o��er�ed in 20 ca�e�� a� 2 were amelanotic. �n �act� it i� known t�at o�er 90% o� oral melanoma� contain melanin t�at can �e ea�ily o�-�er�ed in routine �ematoxilin and eo�in (5�27). Bac�ar et al. (28) �tudied 61 ca�e� o� �ead and neck muco�al melanoma finding 6 amelanotic cases (12.8%), similar to t�e �alue� �ound in our �tudy.�i��erent cell ty�e�� ��owin� e�it�elioid� ��indle and �la�macytoid mor��olo�y �a�e �een de�cri�ed in OM (5�12�13). �n our �erie� e�it�elioid cell� �redominated in mo�t ca�e�� eit�er a� a monomor��ou� or �olymor-phous infiltrate, usually mixed with plasmacytoid or spindle cells. The type of cellular infiltrate seems to �a�e no im�act in �rediction o� tumor �e�a�ior; �ow-e�er� Lourenço et al. (13) o��er�ed in t�eir �erie� t�at �olymor��ou� tumor� �ad a �li��tly �i��er incidence of vascular infiltration and necrosis. Primary OM are com�o�ed o� ne�t� or ��eet� o� mali�nant cell� in �olid� al�eolar or or�anoid �attern�� a� �ound in our �erie� w�ere t�e �olid �attern (77.27%) �redominated. A� �or t�e cell ty�e� t�e cellular �attern al�o doe� not �eem to influence the prognosis (5,12,13).Va�cular and �erineural in�a�ion wa� �een in 7 and 3 ca�e� re��ecti�ely� and �imilar re�ult� were de�cri�ed by Lourenço et al. (13), who identified 45.71%, 60.61% and 25.71% o� ca�e� wit� necro�i�� �eri�a�cular and �erineural in�a�ion re��ecti�ely. �t i� intere�tin� t�at �a�cular in�a�ion i� more common t�an �erineural� di�-�erent �rom ot�er more common oral tumor�� a� carci-noma� and adenocarcinoma� �uc� a� adenoid cy�tic car-cinoma and �olymor��ou� low-�rade adenocarcinoma. Alt�ou�� not commonly o��er�ed� and t�ere�ore not con�idered to �e an inde�endent �actor in mo�t �ro�no�-tic model�� �a�cular in�a�ion w�en �re�ent in cutaneou� melanoma a��ear� to �e a��ociated wit� a wor�e �ro�-no�i� (14). A� �u��e�ted �y Pra�ad et al. (29) �re�ence o� �a�cular in�a�ion �otentially i� an im�ortant indica-tor of poor prognosis in OM, as this is the first step for re�ional and di�tant meta�ta�e�.�t i� im�ortant to determine w�et�er OM i� a �rimary or meta�tatic le�ion. Clinical and micro�co�ical c�ar-acteri�tic� ��ould �e con�idered a� �ite o� in�ol�ement� �re�ence or a��ence o� �i�mentation� o�erlyin� muco�al ulceration� exten�ion alon� �ali�ary �land� duct�� and �a�cular and �erineural in�a�ion (4�6). Pi�mented le-�ion� in�ol�in� t�e �alate and �in�i�a� wit� ulcerated

muco�a and exten�ion alon� minor �ali�ary �land are common findings in primary OM. On the other hand in�ol�ement o� �a�e o� ton�ue wit� intact o�erlyin� muco�a� �alatal and �in�i�al ��arin�� �a�cular and �erineural in�a�ion are more commonly �een in meta-�tatic melanoma (4�6).�t i� well known t�at melanoma �a� a wide ��ectrum o� �i�tolo�ical �eature� w�ic� mimic e�it�elial� �ema-tolo�ical� me�enc�ymal and neural tumor�� and w�en nece��ary immuno�i�toc�emi�try i� t�e �rimary tool to e�ta�li�� t�e correct dia�no�i� (14-16� 30). Yu et al. (17) �tudied t�e ex�re��ion o� melanocytic di��erentiation marker� in 6 �rimary OM. T�ey ��owed t�at HMB-45� �-100 and Melan-A were �o�iti�e in 100%� 83% and 67% o� t�e ca�e� re��ecti�ely� �u��e�tin� t�at �ot� HMB-45 and �-100 are �ood marker� �or immuno�i�toc�emical dia�no�i� o� �rimary OM. �n t�i� �tudy� we �ound t�at �-100 wa� a more �en�iti�e marker t�an HMB-45 and Melan-A, although it is much less specific. On the other �and Pra�ad et al. (16) �ound t�at in �inona�al and OM t�e lea�t �en�iti�e marker wa� HMB-45� markin� 85% o� t�e ca�e�� w�ile �-100 and Melan-A were �o�iti�e in a�out 95% o� t�e ca�e�. �n cutaneou� melanoma�� �-100 i� t�e mo�t �en�iti�e marker wit� ex�re��ion in a�out 98% of cases, but again it is the least specific (14-17). HMB-45 and Melan-A show similar specificity in cu-taneou� melanoma� wit� ex�re��ion �aryin� �rom 77-100% (14-17� 20). Ki-67 �tainin� i� re�orted a� �o�iti�e in 13-30% o� t�e cell� in cutaneou� melanoma� alt�ou�� indi�idual ca�e� can ��ow almo�t 100% o� nuclear �o�i-ti�ity (14�15�31). �n our �tudy Ki-67 ��owed �roli�erat-in� index ran�in� �rom 15.51% to 63% o� �o�iti�e cell�. T�e �re�ent �tudy did not con�ider treatment and �ro�-no�i� o� OM� �ut it i� well e�ta�li��ed t�at treatment i� �ur�ical wit� a �ery �oor �ro�no�i�� wit� 1 and 5 year� �ur�i�al o� 75% and 15% re��ecti�ely (4).�n �ummary� �rimary OM i� rare� occur� in adult and elderly �atient� and u�ually are dia�no�ed at ad�anced �ta�e�� wit� �ery �oor �ro�no�i�. �t i� �ormed �y e�i-t�elioid� ��indle� �la�macytoid or a mixture o� t�e�e cell� arran�ed in �olid� al�eolar and �a�etoid �attern. �-100 and HMB-45 are more �requently ex�re��ed t�an Melan-A and these markers are helpful to confirm the dia�no�i�.

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