OBAFEMI AWOLOWO UNIVERSITY ILE-IFE, NIGERIA

DEPARTMENT OF MORBID ANATOMY

& FORENSIC MEDICINE 7TH FEBRUARY,

LECTURE NOTES ON BREAST PATHOLOGY,

2011. BY DR A.E OMONISI

Ou !"#$ 1) The Normal Breast i) Normal Anatomic Position and Relations ii) Microanatomy iii)Physiology of the Breasts 2).Develo mental and Physiologic A!normalities of the Breast. "). #linical Manifestations of Breast Disease $).%nflammatory Disorders i).Ac&te Mastitis and Breast A!scess ii).#hronic Mastitis iii).Perid&ctal Mastitis iv).Mammary D&ct 'ctasia

().)ym hocytic Masto athy vi).*at Necrosis +) A!normalities of the Breast d&e to Ne&ro,endocrine disorders. -T&mo&rs of the Breasts i).Benign Breast Diseases ii).#arcinoma of the Breast

B%&'()*u#+. .ne of the ma/or disting&ishing feat&res of h&mans from other animals is the level of develo ment of the !reasts0 1hich serve as a so&rce of !reast mil2 rod&ction0 transfer of imm&noglo!&lin to the offs ring and also serve as one of the second se3&al characteristics. The disorders of the !reast are !est &nderstood in the conte3t of its normal anatomy. N*),%! A#% *,- *. /$ B)$%0 . The !reast is a modified s1eat gland covered !y a s2in and s&!c&taneo&s tiss&e. %t rests on the ectoralis m&scle0 from 1hich it is se arated !y a fascia. %ts manifests in h&man as a aired str&ct&re on the chest 1all. L*&% "*# 1 A#% *,"& B*u#+%)"$0. The ad&lt !reast lies !et1een the second and the si3th ri!s in the vertical lane and !et1een the sternal edge medially and mida3illary line laterally. The average !reast meas&res 14,12cm in diameter0 and thic2ness centrally is 5,-cm.%t is concentric 1ith a lateral ro/ection into the a3illa0 referred to as the a3illary tail of 6 ence.

A thin layer of mammary tiss&e e3tends from the clavicle a!ove to the seventh or eighth ri!s !elo1 and from the midline to the edge of the latissim&s dorsi osteriorly. M"&)*%#% *,The ad&lt !reast consists of three ma/or str&ct&res7 s2in0 s&!c&taneo&s fatty tiss&e and !reast tiss&e 8 arenchyma and stroma).The s2in contains of hair follicles0 se!aceo&s glands and eccrine s1eat glands. The gland&lar !reast is divided into 15,24 segments 8lo!es) that converge at the ni le in a radial arrangement. These lo!es are made & of 24,$4 lo!&les. 'ach lo!&le in t&rn consists of 14,144 alveoli 8t&!&losacc&lar secretory &nits).#ollecting mil2 d&cts0 meas&ring a ro3imately 2mm in diameter0 drain each segment. Bet1een five to ten ma/or collecting mil2 o en at the ni le into s&!areolar lactifero&s sin&ses0 1hich are a!o&t +,9mm in diameter. The mor hof&ctional &nit of the organ is the single gland0 a com le3 !ranching str&ct&re that is com osed of t1o ma/or arts in the terminal d&ct lo!&lar &nit 8TD):) and the large d&ct system.

The s& erficial ectoral fascia envelo s the !reast and is contin&o&s 1ith the s& erficial a!dominal fascia of #am er. The &nders&rface of the !reast lies on the dee ectoral fascia. #oo er s&s ensory ligaments rovide s& orts for the !reast and are fi!ro&s !ands connecting the t1o fascial layers. N"22!$1A)$*!% The e idermis of the ni le 8mammary a illa) and areola is igmented and 1rin2ed and consists of 2eratini;ing0 stratified s<&amo&s e itheli&m. %t is 15,+4mm in diameter. These are !&ndles of smooth m&scle fi!res that are circ&mferentially arranged in dense connective tiss&e and are res onsi!le for the contractile f&nction and erection of the ni le. T1o rece tor,ty e nerve endings 8R&ffini,li2e !odies and end !&l! of =ra&se) are resent on the ni le and are associated 1ith the tactile rece tor of stretch and ress&re.

The Areola has no hair follicles. %t has se!aceo&s glands0 a ocrine s1eat glands and accessory areolar glands 8Montgomery glands).Montgomery glands are intermediate !et1een tr&e mammary glands and s1eat glands and o en on the s&rface of the areola as small elevations called Morgagni t&!ercles. T/$ 3%0&u!%) 0u22!- %#+ 3$#*u0 +)%"#%($. The arterial !lood s& ly to the !reasts is derived from the 1.%nternal thoracic artery 2. )ateral thoracic artery ".Thoracoacromial artery $. Posterior intercostal arteries Both se3es have a large concentration of !lood vessels and nerves in their ni les. The ni les of !oth 1omen and men can !ecome erect in res onse to se3&al stim&li to to&ch and to cold

(eno&s drainage The veno&s drainage of the !reast is mainly to the a3illary vein !&t there is some drainage to the internal thoracic vein and the intercostal veins. I##$)3% "*#0 *. /$ 4)$%0 The !reast is innervated !y the anterior and lateral c&taneo&s !ranches of the fo&rth thro&gh si3th intercostal nerves. The ni le is s& lied !y the T$ dermatome. L-,2/% "& +)%"#%($ )ym hatic drainage A!o&t -5 ercent of lym h from the !reast travels to the i silateral a3illary lym h nodes The rest travels to arasternal nodes to the other !reast or a!dominal lym h nodes The a3illary nodes incl&de the ectoral s&!sca &lar and h&meral gro& s of lym h nodes These drain to the central a3illary lym h nodes then to the a ical a3illary lym h nodes The lym hatic drainage of the !reasts is artic&larly relevant to oncology since !reast cancer is a common cancer and cancer cells can !rea2 a1ay from a t&mo&r and s read to other arts of the !ody thro&gh the lym h system !y metastasis

BREAST PHYSIOLOGY 1. Menstr&al #ycle> The mammary arenchyma &ndergoes changes d&ring the menstr&al cycle arallel to0 al!eit less rono&nced than com ara!le changes in the 'ndometri&m. These changes are reflected redominantly in lo!&lar d&cts and in the intralo!&lar stroma. )o!&lar d&cts !ecome increasingly n&mero&s d&ring the oestrogenic hase of the cycle0 res&lting in an increase in lo!&lar si;e. (ac&olation of myoe itheli&m !ecomes more cons ic&o&s d&ring the menstr&al hase of the cycle. 2. Pregnancy> Mammary enlargement 1ith increased firmness is one of the earliest signs of regnancy. This is attri!&ta!le to roliferation of terminal lo!&lar d&cts0 res&lting in lo!&lar enlargement0 rogressive effacement of interlo!&lar stroma0 and com romise of interlo!&lar stroma. Pregnancy ?li2e hy er lasia or so,called se&dolactational changes have !een associated 1ith hy er rolactinaemia as 1ell as henothia;ines0 hormonal and anti,hy ertensive agents.

D$3$!*2,$# %! %#+ P/-0"*!*("& A4#*),%!" "$0 *. /$ B)$%0 Tr&e develo mental a!normalities of the !reast are &ncommon. Accessory ni les are more common than a!sent !reast and mal ositions. Develo mental defects of the !reasts incl&de> a).Amastia> This is a congenital a!normality consisting of a!sence of a ni le0 !reast d&cts0 and occasionally the ectoralis ma/or m&scle. Amastia is ro!a!ly a manifestation of congenital ectodermal dys lasia0 !ased & on se3,lin2ed recessive inheritance0 1hereas isolated !ilateral a!sence of the !reasts re resents a&tosomal recessive transmission. %ts may occ&r 1ith T&rner@s syndrome0 ovarian agenesis0 congenital adrenal hy er lasia or delayed menarche.

!).Ay o lasia> This may !e defined as lac2 of mat&ration of the !reast .Bhile a modest degree of asymmetry of the !reasts sho&ld !e considered normal0 &nilateral hy o lasia is an &ncommon develo mental occ&rrence0 often associated 1ith overdevelo ment of the contralateral !reast. Ay o lasia may also !e ac<&ired a!normalities0 often attri!&ta!le to irradiation of intrathoracic or chest 1all t&mo&rs in the re &!ertal atients. This condition may occ&r in association 1ith an &nderdevelo ed ectoralis m&scle. Ay o lasia of the !reast may !e associated 1ith other congenital a!normalities0 es ecially renal a!normalities. Breast asymmetry may necessitate corrective s&rgery.

c).Macromastia7 the si;e of the !reast is largely determined !y !ody ha!it&s and age0 its stores fat. Massive !reast enlargement 8macromastia) may !e res&lt from intrinsic lesion0 s&ch as a neglected or ra idly gro1ing malignant neo lasm or0 es ecially in adolescents0 from a so,called /&venile fi!roadenoma or m&lti le fi!roadenomas. %n s&ch instances only one of the !reasts is &s&ally involved. %n contrast 0diff&se enlargement of !oth !reasts0 &nassociated 1ith any discerna!le mass0 resents most often in adolescence or regnancy. The aetiology is &n2no1n. %t is conceiva!le that the !reast might !e the seat of a!normal Ctarget res onse Cto normal hormonal stim&lation. #ases have !een descri!ed from =enya0 6&dan and Nigeria. d).6& ern&merary Breast 8Mil2line Remnants)> 6& ern&merary !reast arise from ecto ic !reast tiss&e along the mil2 lines 1hich e3tend !ilaterally from mida3illae thro&gh the normal !reasts inferiorly to the medial groin and v&lva. 6& ern&merary !reasts develo from ortions of the mil2 ridges that fail to atro hy.

6& ern&merary !reast tiss&e is s&!/ect to changes that occ&r in the !reast 1ith hormonal stim&lation0 as in regnancy and lactation. e).Accessory A3illary Breast Tiss&e> This is not &ncommon in Nigeria. The normal d&ctal system e3tends into the a3illary tail of 6 ence or the s&!c&taneo&s tiss&e of the chest 1all. :s&ally0 no ni les are seen. The &s&al cyclical changes occ&r0 a al a!le mass may !e al ated or its may give rise to carcinomas o&tside the !reast ro er. f).%nfantile Breast and P&!erty> At !irth male and female !reasts may have active secretion ca&sed !y the trans lacental assage of maternal hormones. %n some infants0 this res&lts in !ilateral !reast enlargement 1ith ela!oration of a colostr&ms li2e secretion termed D1itch@s mil2E. Microsco ically0 this is associated 1ith d&ct dilatation 1itho&t acin&s formation. g).#ongenital Ni le %nversion> may !e d&e to the fail&re of the ni le to evert d&ring develo ment and is &nilateral. Ni le inversion may !e a sign of malignancy or an inflammatory disorder in an ac<&ired setting. #ongenital inverted ni les &s&ally correct d&ring regnancy0 or can sometimes !e everted !y sim le traction.

h).A!errant Breast> is defined as mammary gland&lar arenchyma fo&nd !eyond the &s&al anatomic e3tent of the !reast or mil2 line. A!errant tiss&e does not form a ni le or areola0 and is rarely clinically a arent &nless it !ecomes the sites of a athologic rocess #linical Manifestations of Breast Disease. The manner of clinical manifestation of !reast disease may rovide &sef&l cl&es that are ertinent to the s ecific diagnosis. Breast disease may resent 1ith one of the follo1ings> 1. Breast Pain> also 2no1n as mastalgia or mastodynia is a very common 1ay of manifestation of !reast disease in o&r setting. The ain may !e associated 1ith menstr&al cycle !&t sometimes they are not. As a r&le of the th&m!0 ma/ority of ainf&l masses are !enign.

2. Ni le Discharge7 de ending on the colo&r and the <&antity of the discharge0 its may !e a ointer to an &nderlying malignancy. Mil2y discharges seen in galatorrhea are &s&ally associated 1ith elevated rolactin levels associated 1ith conditions li2e hy othyroidism0 endocrine anov&latory syndromes0 it&itary adenoma and in atients on dr&gs for e3am les oral contrace tives0 tricyclic antide ressants and methyldo a. Bloody or sero&s discharges altho&gh are often associated 1ith !enign conditions0 they sometimes may !e associated 1ith malignancies. =indly note that the ris2 of malignancy 1ith discharge increases 1ith age.

". Pal a!le mass> is most common mode of manifestation of !reast disease in o&r setting. Most al a!le masses in the yo&ng are most li2ely to !e fi!roadenoma and in most cases are &nilateral. 6ometimes these masses are ointers to &nderlying invasive carcinomas or cystic diseases. These masses m&st ho1ever !e differentiated from the normal l&m iness of the !reast. The ro!a!ility of a mass !eing malignant increases 1ith age. I#.!%,,% *)- %#+ R$%& "3$ C*#+" "*#0 *. /$ B)$%0 %nflammation of the !reast is called mastitis. The im ortant ty es of mastitis seen in o&r environment are> ac&te mastitis and !reast a!scess0 chronic mastitis0 mammary d&ct 'ctasia also 2no1n as lasma cell mastitis0 tra&matic fat necrosis and galactocele.

1. Ac&te Mastitis and Breast A!scess> ac&te yogenic infection of the !reast occ&rs mainly d&ring the early hase of lactation. A !acteria gains entry into the !reast !y develo ment of crac2s and fiss&res in the ni le. #ommon !acterial agents res onsi!le for the infection are sta hylococc&s a&re&s and stre tococc&s yogenic. The end res&lt of the esta!lished infection is the formation of a locali;ed area of ac&te inflammation 1hich if not treated0 may ca&se single or m&lti le !reast a!scesses. 2. #hronic mastitis> chronic inflammation affecting the !reast is called chronic mastitis. %t co&ld !e f&rther divided into chronic non,s ecific mastitis 1hich is relatively &ncommon and chronic gran&lomato&s inflammation. #hronic gran&lomato&s disease in the !reast may occ&r as a res&lt of the follo1ing> i). 6ystemic gran&lomato&s disease e.g. as sarcoidosis. art of systemic

ii).%nfections> this is artic&larly im ortant in the tro ics. %nfections s&ch as t&!erc&losis and f&ngal infection of the !reast may occ&r in imm&nocom romised atients.

These conditions may !e misdiagnosed as !reast cancer es ecially t&!erc&losis of the !reast o1ing to a3illary nodal involvement. T&!ercle !acilli reach the !reast via the hematogeno&s0 lym hatic or direct s read. Pathologically0 ty ical caseating t&!ercles 1ith discharging sin&ses thro&gh the s&rface of the !reast are fo&nd. iii).6ilicone !reast im lants> im lant on either !reast after mastectomy or as !reast a&gmentation cosmetic s&rgery may r& t&re or silicone may slo1ly lea2 into the s&rro&nding !reast tiss&e. This incites chronic inflammatory reaction. iv).%dio athic gran&lomato&s mastitis> the aetiology is &n2no1n. This is an &ncommon form of reaction aro&nd lo!&les and d&cts. The e3act athogenesis is &n2no1n !&t it have !een s&ggested that l&minal secretion of the !reast e itheli&m d&ring lactation may !e the trigger factor. ". Perid&ctal Mastitis> also 2no1n as F&s2a disease or rec&rrent s&!areolar a!scess or s<&amo&s meta lasia of lactifero&s d&cts. This condition has a strong association 1ith cigarette smo2ing. Patients 1ith this lesion may resent 1ith a ainf&l erythemato&s s&!areolar mass or have an inverted ni le and in rec&rrent cases a fist&la tract may !e seen.

The hallmar2 of diagnosis is 2eratini;ing s<&amo&s meta lasia of the ni le d&cts 1ith ca&sing dilation of the d&ctal system d&e to acc&m&lation of 2eratin l&gs. 6 illage of these 2eratins into the erid&ctal tiss&e may res&lt in an intense chronic and gran&lomato&s inflammation res onse aro&nd the erid&ctal tiss&e leading to erid&ctal mastitis. $. Mammary D&ct 'ctasia> this is also 2no1n as lasma cell mastitis. This is a condition in 1hich one or more of the larger d&cts of the !reast are dilated and filled 1ith ins issated secretions. D&ct 'ctasia affects 1omen in their $ th to -th decades of life. The aetiolgy is &n2no1n !&t its a ears to !egin 1ith erid&ctal inflammation follo1ed !y destr&ction of the elastic tiss&e to ca&se ectasia and erid&ctal fi!rosis. Grossly0 the condition a ears as a single0 oorly,defined ind&rated area in the !reast 1ith ro iness of the s&rface. #&t section sho1s dilated d&cts containing cheesy ins issated secretions.

Aistologically0 the feat&res are> i). Dilated d&cts 1ith either necrotic or atro hic lining !y flattening e itheli&m and l&men containing gran&lar0 amor ho&s0 in2 de!ris and foam cells. ii).Mar2ed erid&ctal and interstitial chronic gran&lomato&s inflammatory res onse0 chiefly lym hocytes0 histiocytes 1ith m&ltin&cleated giant cells. 6ometimes0 lasma cells are resent in im ressive n&m!ers and the condition is then termed lasma cell mastitis. iii)..ccasionally0 there may !e o!literation of the d&cts !y fi!ro&s tiss&e and varying amo&nt of inflammation0 this is referred to o!literative mastitis. Please note that the ma/or disting&ishing feat&re !et1een &re erid&ctal mastitis and mammary ectasia is that s<&amo&s meta lasia of the ni le d&cts is a!sent. 5. )ym hocytic Masto athy> this is also 2no1n as scleosing lym hocytic lo!&litis. The masses are &s&ally hard and may !e solitary or m&lti le at resentation. The e3act aetiology is &n2no1n !&t there are e3 lanations of ossi!le a&toimm&ne

aetiology as the lesion is mostly seen in 1omen 1ith ty e 1 8ins&lin ?de endent).

+. *at Necrosis> *at necrosis of the !reast ass&mes im ortance !eca&se it can sim&late carcinoma !oth clinically and mammagra hically. Bhile a history of antecedent tra&ma may !e o!tained0 may also res&lts from rior s&rgical intervention or radiation thera y follo1ing !reast conserving treatment of a carcinoma. Grossly0 the e3cised l&m has central ale cystic area of necrosis. Aistologically0 there is disr& tion of the reg&lar attern of li ocytes 1ith formation of li id,filled s aces s&rro&nded !y ne&tro hils0 lym hocytes0 lasma cells and histiocytes having foamy cyto lasm and fre<&ent foreign !ody cell formation. %n late stage0 there is re lacement fi!rosis and even calcification. Ne&roendocrine Disorders Ne&roendocrine disorders s&ch as may occ&r in =linefelter@s syndrome 8HHY disease)0 adrenal hy er lasia and the vario&s degrees of hy ogonadism may ca&se an a arently normal !reast to develo a!normally. .ther rare ca&ses are adrenal t&mo&rs0 gran&losa cell t&mo&rs and !rain t&mo&rs in the hy othalam&s.

. *i!rocystic #hange %t 1as revio&sly termed fi!rocystic disease !&t is c&rrently considered as an e3aggerated hysiological henomena and not a disease. Many other names have !een ro osed over the years for this disorder> cystic disease0 cystic masto athy0 cystic hy er lasia0 mammary dys lasia0 Recl&s disease0 !enign !reast disease0 and others. *i!rocystic change is an e3tremely im ortant lesion !eca&se of its high fre<&ency and the a!ility of some of its s&!ty es to sim&late the clinical0 radiogra hic0 gross0 and microsco ic a earance of carcinoma7 and the ossi!le relationshi of some of its forms to carcinoma. %t is the most common !enign !reast condition rod&cing vag&e Cl&m y@ !reast rather than al a!le l&m in the !reast of ad&lt 1omen. %ts incidence has !een re orted to range from 14,24I in ad&lt 1omen. Most of the atients 1ith fi!rocystic change are !et1een "rd and 5th decades of life0 1ith dramatic decline in its incidence after meno a&se &nless atient is on hormone re lacement thera y s&ggesting the role of oestrogen in the athogenesis.

This disorder affects rimarily the Terminal D&ct )o!&lar :nit 8TD):). The mor hological changes seen in !reasts 1ith fi!rocystic change incl&de the follo1ings> 1. *ormation of cysts 2. A ocrine meta lasia ". *i!rosis of the stroma $. #alcification 5. #hronic inflammation +. ' ithelial hy er lasia -. *i!roadenomatoid change %n recent times0 the s ectr&ms of microsco ic changes seen in fi!rocystic change are divided into t1o #linico athological gro& s> A.Proliferative changes7 feat&ring e ithelial hy er lasia and sclerosing adenosis. B.Non, roliferative changes7 feat&ring cyst formation and fi!rosis. The roliferative changes 1ith or 1itho&t cell&lar aty ia are associated 1ith increase in the ris2 of !reast cancer.

F"4)*$2" /$!"%! N$*2!%0, These are clinically and athologically discrete t&mo&rs that manifest roliferation of e ithelial and stromal elements. .f im ortant to &s in this lect&re is fi!roadenoma. F"4)*%+$#*,% *i!roadenomas are the most common !reast t&mo&r in adolescent and yo&ng ad&lt 1omen0 1ith a ea2 age incidence in the third decade. They acco&nt for the ma/ority of all lesions 1hich occasion !reast !io sy in this age gro& 0 resenting as 1ell,circ&mscri!ed0 freely mova!le0 non ainf&l masses. The t&mo&r are often solitary7 ho1ever0 as many as 25 ercent of atients have m&lti le in one or !oth !reasts and they develo s&!se<&ent t&mo&rs. There is a higher incidence in !lac2 atients. The aetiology is &n2no1n !&t several genetic factors incl&ding BR#A 1 and BR#A 2 increase the ris2. Pathologic changes> Grossly0 ty ical fi!roadenoma is a small 82,$cm diameter)0 solitary ro&nd to oval0 r&!!ery0 firm masses and 1ell enca s&lation. The circ&mscri tion allo1s them to !e Cshelled o&t@ !y the s&rgeon.

The c&t s&rface is firm0 greyish,1hite0 slightly my3oid and may sho1 slit,li2e s aces formed !y com ressed d&cts. .ccasionally0 m&lti le fi!roadenoma may form art of fi!rocystic disease and is termed fi!roadenomatosis. )ess commonly0 a fi!roadenoma may !e fairly large in si;e0 & to 15cm in diameter0 and is called giant fi!roadenoma. Microsco ically0 there is !enign roliferation of !oth d&cts and fi!rocollageno&s stroma. The fi!ro&s tiss&e com rises most of fi!roadenoma.The arrangements !et1een fi!ro&s overgro1th and d&cts may rod&ce t1o ty es of atterns 1hich may coe3ist in the same t&mo&r. These are intracanalic&lar and ericanalic&lar atterns. The intracanalic&lar attern is the one in 1hich the stroma com resses the d&cts into a slit,li2e s aces 1hile the ericanalic&lar attern is characteri;ed !y encircling masses of fi!ro&s stroma aro&nd the atent or dilated d&cts. .vertime the lesion may &ndergo fi!rosis and calcification. A /&venile variant may !e larger and more cell&lar. D&ring regnancy they may &ndergo ra id gro1th. The s&!/ect of ossi!le increased ris2 of !reast cancer in 1omen 1ith a history of fi!roadenoma is controversial. Altho&gh most0 !&t not all a&thorities !elieve that 1omen 1ith a history of fi!roadenoma are at a slightly increased ris2 of the develo ment of !reast cancer.

Gynaecomastia 8Ay ertro hy of male !reast) :nilateral or !ilateral enlargement of the male !reast is 2no1n as gynaecomastia. 6ince the male !reast does not contain secretory lo!&les0 the enlargement is mainly d&e to roliferation of d&cts and increased erid&ctal stroma. Gynaecomastia occ&rs in res ond to hormonal stim&lation artic&larly oestrogen. 6&ch e3cessive oestrogen activity in males is seen in yo&ng !oys !et1een 1" and 1- years of age 8 &!ertal gynaecomastia). #a&ses> 1. 'ndocrine diseases associated 1ith increase oestrogen secretion or red&ction in androgenic activity e.g. in liver cirrhosis0 testic&lar t&mo&rs0 it&itary t&mo&rs0 carcinoma of the l&ngs. 2. '3ogeno&s oestrogen administration> As a form of thera y in atients 1ith rostatic carcinoma. ". %dio athic> 'nlargement 1itho&t any o!vio&s ca&se termed idio athic gynaecomastia.

#arcinoma of the Breast Breast carcinoma is the most common malignant t&mo&r and the leading ca&se of carcinoma death in 1omen in !oth the ind&striali;ed and the develo ing co&ntries. The earliest recorded history of !reast t&mo&r came from ancient 'gy t in 1+44 B# in a Pa r&s o!tained !y 'd1in 6mith 81922,1J4+).6ince then0 thro&gh the classical Gree2 eriod0 the Medieval and Renaissance eriod different efforts 1ere made to manage the entity no1 called !reast cancer %t is also the commonest malignancy in Nigeria. %t is estimated that a ro3imately one in 12 1omen 1ill develo !reast cancer in their lifetime. The ma/ority of !reast cancers 8J5I) are s oradic7 only a small ro ortion0 artic&larly those diagnosed in yo&ng 1omen are d&e to a highly enetrant a&tosomal ?dominant trait. ' idemiology )iterat&re is re lete 1ith claims a!o&t differences in e idemiology0 !iology and o&tcome of treatment in !reast cancer com aring Non,Ais anic 1hite and African Americans on the one hand0 and 1ith Africans on the other

 These differences incl&de ? ra idly increasing incidence0 earlier age of onset0 more advanced disease at diagnosis0 higher revalence of oor redictive and rognostic mar2ers0 and oorer o&tcome of treatment There are vario&s st&dies in Nigeria that doc&mented the e idemiological and the histo athological atterns of !reast cancer in Nigeria. Ma/ority of !reast cancer cases in Nigeria 1ere of high grade and carried a very oor rognosis .Most of atients resent 1ith the advanced stage of the disease. The %le,%fe '3 erience .ne of the earliest st&dies on !reast diseases in %le,%fe 1as !y .l&1ole et al. They revie1ed cases of !reast diseases seen in %le,%fe !et1een 1J-- and 1J9+.The findings sho1ed 21 I of all the atients 1ith !reast disease had !reast cancer. Adel&sola et al in the year 1JJ+ st&died 2"+ cases of histologically diagnosed !reast cancers in %le,%fe. They recorded t1o ea2 age incidences 1hich 1ere $4,$J years and +4,+J years.1J$ cases 892.2I) had the diagnosis of infiltrating d&ctal carcinoma 8N.6). %n 1JJ- Adeni/i et al analy;ed cases of !reast cancer in %le,%fe over a eriod of nineteen years and only fo&nd ten cases occ&rring in men giving an incidence rate of 1.JI.

This agreed 1ith the general glo!al 2no1ledge that !reast cancer is rare in men. Ades&n2anmi et al in same %le,%fe0 sho1ed in their series that the atterns of !reast cancer had not changed m&ch over the year. Titiloye et al in a st&dy s& ervised !y .moniyi,'san and Adel&sola in 2449 analysed "4$ cases 1ith age range of 24,9J years. They fo&nd o&t that the male> female 1as 1>"-0 ositivity for oestrogen and rogesterone rece tors 1ere lo1 and 1as seen in "9.$5I and 2".JI res ectively.Aer2Kne& ositivity 1as seen in only 9.2I.Ma/ority of their cases 1ere tri le negative. Aetiology Des ite the vario&s research and st&dies carried o&t in the field of !reast cancer0 its e3act aetiology of !reast cancer remains el&sive. Ao1ever0 some redis osing factors or ris2ed factors are considered significant in its aetiology>

1. Genetic factors. 6ome &!lished 1or2s have sho1n the infl&ence of family history and inherited m&tations in !reast cancer> i. *amily history> *irst degree relatives 8mother0 sister0 and da&ghter) of 1omen 1ith !reast cancer have 2 to +,fold higher ris2 of develo ment of !reast cancer.

The ris2 is ro ortionate to any of these factors> a).N&m!er of !lood relatives 1ith !reast cancer !).Yo&nger age at the time of develo ment of !reast cancer c).Bilateral cancers d).Aigh ris2 cancer families having !reast and ovarian carcinomas. ii. Genetic m&tation> A!o&t 14I !reast cancers have !een fo&nd to have inherited m&tations. These m&tations incl&de the follo1ings> a).BR#A genes> These are the most im ortant s&sce ti!ility genes in inherited !reast cancer. There are BR#A 1 and BR#A 2 genes. BR#A 1 gene is located on chromosome 1-0a DNA re air gene0 is res onsi!le for !oth !reast and ovarian cancer in inherited cases. The deletion of this gene is seen in a!o&t t1o,third of 1omen 1ith inherited !reast cancer having family history !&t BR#A 1 m&tation is &ncommon in s oradic cases. Men 1ho have m&tated BR#A 1 have increased ris2 of develo ing rostate cancer !&t not of male !reast. BR#A 2 gene is ho1ever located on chromosome 1"0 also a DNA re air gene0 in its m&tated form0 has a similarly higher incidence of inherited cancer of the !reast 8one,third cases) and its confers a smaller ris2 for ovarian carcinoma in females.

B#A1 and BR#A 2 carriers are also at higher ris2 of develo ment of other e ithelial cancers0 s&ch as rostatic and ancreatic carcinomas. !).M&tation in P5" t&mo&r s& ressor gene on chromosome 1as an ac<&ired defect acco&nts for $4I cases of s oradic !reast cancer in 1omen !&t rarely in 1omen 1ith family history of !reast cancer.P5" m&tation is also seen in )i,*ra&meni syndrome having m&lti le cancers incl&ding !reast cancer in yo&ng 1omen7 others are t&mo&rs of the !rain0 sarcomas0 and adrenal cortical t&mo&rs.

c)..ther m&tations seen less commonly in !reast cancer> i.Ata3ia telangiectasia gene ii. PT'N 8Phos hate and tensin) t&mo&r s& ressor gene.

2. Geogra hy. Breast cancer incidence rates in the develo ed 1orld are a!o&t si3 times higher than the develo ing co&ntries0 1ith a nota!le e3ce tion in La an. These geogra hic differences are considered to !e d&e to 1estern life style 1hich is characteri;ed !y a highly caloric diet0 rich in fats0 refined car!ohydrates and animal roteins 1ith lo1 hysical activity. " Aigh state of .estrogen. There is s&fficient evidence to s&ggest that e3cess endogeno&s oestrogen or e3ogeno&sly

administered oestrogen or e3ogeno&sly administered oestrogen for rolonged d&ration is an im ortant factor in the develo ment of !reast cancer. These evidences incl&de some of the follo1ings> i.Bomen 1ith rolonged re rod&ctive life0 1ith menarche setting in at an early age and meno a&se relatively late have greater ris2. ii. Aigher ris2 in &nmarried and n&lli aro&s 1omen than in married and m&lti aro&s 1omen. iii. Bomen 1ith first child!irth at a late age 8over "4 years) are at greater ris2.

iv. )actation is said to red&ce the ris2 of !reast cancer on the long r&n. v. .estrogen re lacement thera y administered to ostmeno a&sal 1omen may res&lt in increased ris2 of !reast cancer. vi. Men 1ho have !een treated 1ith oestrogen for rostatic cancer have increased ris2 of develo ing cancer of the male !reast. The mechanism of oestrogen e3cess> Normal !reast e itheli&m ossesses oestrogen and rogesterone rece tors. The !reast cancer cells secrete many gro1th factors

1hich are oestrogen,de endent. %n this 1ay0 the ma/ority of high circ&lating levels of oestrogen0 oestrogen rece tors and gro1th factors !ring rogression of !reast cancer. $. 'nvironmental and dietary factors. These incl&de large cons&m tion of animal fats0 high calorie foods0 cigarette smo2ing0 radiation e3 os&re to the chest and alcohol. 5. Aty ical d&ctal hy er lasia. A history of rior !reast !io sies0 es ecially if revealed aty ical hy er lasia0 increases the ris2 of invasive carcinoma. #lassification of Breast #arcinoma Ma/ority of the carcinoma of the !reast are adenocarcinomas0 1hich com osed of> i.#arcinoma,in,sit& ii. %nvasive carcinoma. i.#arcinoma,in,sit&> The neo lastic roliferation is confined 1ithin the d&ct or lo!&le. The malignant cells do not e3ceed the !asement mem!rane. The t&mo&r initially !egins 1ith aty ical hy er lasia of d&ctal e itheli&m follo1ed !y filling of the d&ct 1ith t&mo&r cells.#linically0 it rod&ces a al a!le mass in "4,-5I of cases and resence of ni le discharge in a!o&t "4I atients.

Pathology changes. Macrosco ically0 the t&mo&r may vary from a small oorly, defined foc&s to ",5cm diameter mass. .n c&t section0 the involved area sho1s #ystically dilated d&cts containing cheesy necrotic material 8comedo attern)0or the intrad&ctal t&mo&r may !e oly oid and fria!le resem!ling intrad&ctal a illoma 8 a illary attern). Aistologically0 the roliferating t&mo&r cells 1ithin the d&ctal l&mina may have $ ty es of atterns in different com!inations> comedo0 solid0 a illary and cri!riform. ii. %nvasive 8%nfiltrating) #arcinoma. %n the develo ing co&ntries li2e o&rs0 atients 1ith invasive carcinoma of the !reasts almost al1ays resent 1ith al a!le mass. Any of the follo1ings may also !e seen> a3illary lym h nodes involvement0 dim ling of the s2in d&e to fi3ing of larger t&mo&r to the chest 1all0 retraction of the ni les 1hen the central ortion of the !reast is involved and lym oedema 1hen the lym hatics are !loc2ed. The invasive !reast cancer has vario&s mor hologic ty es 1hich have clinical and rognostic correlates. a).%nvasive D&ctal #arcinoma,N.6

%nvasive D&ctal #arcinoma,N.6 8Not .ther1ise 6 ecified) is the classic !reast cancer and is the most common Aistologic attern acco&nting for -4I to 94I cases of !reast cancer. %n fact0 this is the attern of cancer for 1hich the terms Ccancer@ and Ccarcinoma@ 1ere first coined !y Ai ocrates. #linically0 ma/ority of infiltrating d&cts carcinomas have a hard consistency d&e to dense collageno&s stroma 8scirrho&s carcinoma).They are fo&nd more fre<&ently in the left !reast0 often in the & er o&ter <&adrant.

Pathologic changes. Macrosco ically0 the t&mo&r is irreg&lar0 1,5cm in diameter0 hard cartilage ?li2e mass that c&ts 1ith a grating so&nd. The sectioned s&rface of the t&mo&r is grey,1hite to yello1ish 1ith chal2y strea2s. Aistologically0 as the N.6 s&ggests0 the t&mo&r is different from other s ecial ty es in lac2ing a reg&lar and &niform attern thro&gho&t the t&mo&r. !).%nvasive )o!&lar #arcinoma #om rises of a!o&t 5I of all !reast cancers. This mor hologic form differs from other invasive cancers in !eing more fre<&ently !ilateral7 and 1ithin the same !reast0 it may have m&lticentric origin.

Aistologically0 a characteristic single file 8%ndian file) linear arrangement of stromal infiltration !y the t&mo&r cells 1ith very little tendency to gland formation is seen. c).Med&llary carcinoma %s a variant of d&ctal carcinoma and com rises a!o&t 1I of all !reast cancers. The t&mo&r has a significant !etter rognosis than the &s&al infiltrating d&ctal carcinoma. This is d&e to the good host imm&ne res onse in the form of lym hoid infiltrate in the t&mo&r stroma.

d).#olloid 8M&cino&s)#arcinoma This slo1,gro1ing attern is commonly seen in the older atients and is relatively &ncommon. #olloid carcinoma has !etter rognosis than the &s&al infiltrating d&ct carcinoma. Aistologically0 colloid carcinoma contains large amo&nt of e3tracell&lar e ithelial m&cin and acini filled 1ith m&cin. #&!oidal to tall col&mnar t&mo&r cells0 some sho1ing m&c&s vac&olation0 are seen floating in large la2es of m&cin. e).Pa illary #arcinoma This is a very rare variety of infiltrating d&ct carcinoma in 1hich the stromal invasion is in form of a illary str&ct&res. %nvasive a illary carcinomas are &s&ally 'R ositive and have a favo&ra!le rognosis.

f).T&!&lar #arcinoma This is another rare variant of invasive d&ctal carcinoma 1hich has more favora!le rognosis. Aistologically0 the t&mo&r is highly 1ell differentiated and has an orderly attern. The t&mo&r cells are reg&lar and form a single layer in 1ell ?defined t&!&les. The t&!&les are <&ite 1ell even and distri!&ted in dense fi!ro&s stroma. g) Meta lastic #arcinoma Rarely0 infiltrating d&ctal carcinomas may have vario&s ty es of Meta lastic alterations s&ch as s<&amo&s meta lasia0 cartilagino&s and osseo&s meta lasia0 or their com!ination. They are 'R,PR,A'R2Kne& Dtri le negativeE often e3 ress myoe ithelial roteins and a ear to !e related to the !asal,li2e carcinomas. i) .thers incl&de7 Adenoid cystic 8%nvasive #ri!riform) #arcinoma0 6ecretory 8L&venile)#arcinoma and %nflammatory #arcinoma.

Grading0 6taging and Prognosis. Aistologic grading and #linical staging of !reast cancer determine the o&tcomes of atients 1ith !reast cancers. A. Aistologic Grading> Breast cancers are s&!divided into vario&s Aistologic grades de ending & on the follo1ing arameters> 1. Aistologic ty e of the t&mo&r7 i. Non,metastasi;ing, %ntrad&ctal and lo!&lar carcinoma in sit& ii. )ess commonly metastasi;ing,Med&llary0 colloid0 a illary0 t&!&lar0 adenoid cystic and secretary 8/&venile) carcinomas. iii. #ommonly metastasi;ing,%nfiltrating d&ct0 invasive lo!&lar and inflammatory carcinomas. 2.Microsco ic grade> #&rrently0 the most 1idely &sed system for microsco ic grading system is the Nottingham Aistological Grading 6ystem81hich is the modification of the Bloom,Richardson 6ystem). %t is !ased on " feat&res> i.T&!&le formation ii.N&clear formation

iii.Mitotic co&nt ". T&mo&r si;e There is generally an inverse relationshi !et1een diameter of rimary !reast cancer at the time of mastectomy and long,term s&rvival. $. A3illary lym h node metastasis The s&rvival rate of the atient is sometimes !ased on the n&m!er and level of lym h nodes involved !y metastasis .The more the n&m!er of loco,regional lym h nodes involved0 the 1orse 1ill !e the s&rvival rate of the atient.

The identification and dissection of sentinel lym h node follo1ed !y histo athologic e3amination has attained immense rognostic val&e. 86entinel lym h node is the first node in the vicinity to receive drainage from rimary cancer i.e. Csentinel@ over the t&mo&r). 5. .estrogen and Progesterone Rece tors. .estrogen is 2no1n to romote the !reast cancer. Presence or a!sence of oestrogen rece tors on the t&mo&r cells can hel in redicting the res onse of !reast cancer to endocrine thera y. Accordingly0 atients 1ith high levels of oestrogen rece tors on !reast t&mo&r cells have a !etter rognosis. A rec&rrent t&mo&r

that is rece tor ositive is more li2ely to res ond to anti, oestrogen thera y than one that is rece tor, negative. +. DNA #ontent T&mo&r cell s&! o &lations 1ith ane& loid DNA content as eval&ated !y flo1 have a 1orse rognosis than &rely di loid t&mo&rs. B. #linical 6taging. The American Loint #ommittee 8AL#) on cancer staging has modified the TNM 8 rimary T&mo&r0 Nodal0 and distant Metastasis) staging ro osed !y :%##8:nion %nternational for #ontrol of #ancer).

AL# #linical 6taging of Breast #ancer 6tage T%6> %n sit& carcinoma 6tage % > T&mo&r 2cm or less in diameter No nodal s read 6tage %% > T&mo&r M 2cm in diameter Regional lym h nodes involved 6tage %%% A> T&mo&r M or N 5cm in diameter Regional lym h node involved on same side 6tage %%% B> T&mo&r M or N 5cm in diameter

6& raclavic&lar and infraclavic&lar lym h nodes involved. 6tage %( > T&mo&r of any si;e Bith or 1itho&t regional s read !&t 1ith distant metastasis.

Prognostic and Predictive *actors Prognostic information is cr&cial in co&nseling atients of their chances of s&rvival. The ma/or determinants of rognosis in any atient 1ith !reast cancers are the histo athological characteristics of the rimary t&mo&r and the a3illary lym h nodes. The ma/or rognostic factors are> 1. %nvasive carcinoma vers&s in sit& disease> Prognosis is !etter in carcinoma in sit&. 2. Distant metastasis> #&re is &nli2ely in the setting 1ith evidence of metastasis. ". T&mo&r si;e> The larger the si;e of the t&mo&r the higher the chances of metastasis. )arger t&mo&rs are &s&ally associated 1ith oorer rognosis.

$. )ocally advanced t&mo&r> )ocally invasive cancers e3tending into the s&rro&nding str&ct&res are &s&ally larger and may !e diffic&lt to !e resected com letely. 5. )ym h node stat&s> A3illary lym h node stat&s is the gold standard for invasive carcinoma in the a!sent of any clear evidence of metastasis. Minor rognostic factors> 1. Proliferative inde3> Proliferation is conventionally meas&red &sing the mitotic co&nts as art of the microsco ic grading .B&t 1ith the introd&ction of imm&nohistochemistry cell&lar roteins s&ch cyclins0 =i+- have !een &sef&l in assessing the inde3. A high roliferative inde3 1ill confer a oor rognosis and the reverse. 2. Aer2Kne&> Aer2Kne& over e3 ression is redictive of a oorer o&tcome. ". )ym hovasc&lar invasion> %nvasion of lym hovasc&lar s aces !y t&mo&r cells is strongly associated 1ith oorer rognosis. $. .estrogen and rogesterone rece tors> 'R and PR ositive t&mo&rs res ond to hormonal treatment and hence confer !etter rognosis.

5. Positive res onse to neoad/&vant thera y> The e3tent to 1hich t&mo&rs res ond to cytoto3ic dr&gs and other medications !efore s&rgery is a rognostic signal in some t&mo&rs. +. DNA content> Ane& loid t&mo&rs are associated 1ith 1orst rognosis. -. Aistologic variant> T&!&lar0 m&cino&s0 a illary0 med&llary and lo!&lar carcinomas are associated 1ith favo&ra!le rognosis 1hen com ared 1ith the other variants of invasive carcinoma. 9. Aistologic grade> Nottingham Aistologic grade % and %% are associated 1ith slightly good rognosis 1hen com ared 1ith grade %%% t&mo&rs. J. Molec&lar rofiling of t&mo&rs> Molec&lar rofiling of t&mo&rs rovide a vast amo&nt of information a!o&t carcinomas .The genes e3 ressed !y these carcinomas may correlate 1ell in some cases 1ith the rognosis.

Male Breast #arcinoma The occ&rrence of this condition in the males is said to !e very rare. The redis osing factors are !asically same 1ith that o!taina!le in the females. The males !reast are smaller 1hen com ared 1ith the females0 this ma2es most male atients 1ith !reast cancer to resent 1ith al a!le s&!areolar mass. Bloody ni le discharge is a common sym tom in them. The same histologic variants of invasive cancer are resent0 !&t the a illary s&!ty e is commonly seen in the males. The modalities of treatment are essentially same for !oth men and 1omen 1ith !reast carcinoma. 'ND