BY350 2013-14 Semester 2 Case Study 2 (750 words).

The case study consists of an electronic online image of a histological slide. The slide consisted of a haematoxylin and eosin stained section ta en from a clinical case descri!ed as "firm nodule u##er left nec $ metastatic tumour% &rom the image #ro'ided( )dentify and descri!e the normal tissues #resent. *escri!e the malignant tissue mor#hology suggesting cell+tissue origins and #ro#ose a limited anti!ody staining #anel ,hich ,ould ad'ance your diagnostic certainty. -omment on the aggressi'eness of this tumour and$ assuming this ,as the first malignant diagnosis for the #atient$ suggest further in'estigations in order to grade$ stage and treat this #atient%s disease.

.atient #resented ,ith nodal metastasis of the nec from occult #rimary/ metastases in the u##er and middle nec 0le'els )-))-)))-)1-12 are generally attri!uted to head and nec cancers. *iagnostic #rocedures include a careful clinical e'aluation and a fi!ero#tic endosco#ic examination of the head and nec mucosa$ !io#sies from all sus#icious sites or !lindly from the sites of #ossi!le origin of the #rimary$ com#uteri3ed tomogra#hy 0-T2 scan$ and magnetic resonance radiology 045)2. The most fre6uent histological finding is s6uamous cell carcinoma$ #articularly ,hen the u##er nec is in'ol'ed. htt#(++,,,.nc!i.nlm.nih.go'+#mc+articles+.4-273894:+ 5outine ,or -u# includes #hysical examination$ !io#sy or excision of the enlarged lym#h node0s2$ -T and+or 45)$ and #anendosco#y ,ith or ,ithout random or directed !io#sies. -ommonly$ treatment consists of lym#h node dissection and electi'e irradiation of the #utati'e mucosal sites and !ilateral nec $ #lus su#racla'icular$ nodes. ;o,e'er$ unilateral radiothera#y 05T2 to the in'ol'ed side$ as ,ell as com!ination of chemothera#y #lus com#rehensi'e irradiation$ ha'e also !een #ro#osed. )t has !een suggested that 19&-fluorodeoxyglucose #ositron emission tomogra#hy 0&*<-.=T2 is more accurate than -T or 45) for staging of !oth head-and-nec #rimary tumours and lym#h node metastases htt#(++,,,.sciencedirect.com+science+article+#ii+S0370301701014727 *etermining the site of #rimary tumours using an immunohistochemical diagnostic #anel in metastatic cer'ical lym#h nodes( ex#ression #rofiles of cyto eratins$ 5+7/ 9+19/ 10/ 13/ 14/ and 18$ #17$ and #5!. )n contrast to adenocarcinomas$ ,hich ha'e relati'ely s#ecific tumour mar ers$ there are currently no useful immunohistochemical mar ers that can identify the original site of s6uamous cell carcinoma. >hen S-- is identified in a cer'ical lym#h node and no #rimary site is identified$ radical nec dissection and radiothera#y$ or concurrent chemo-radiothera#y are usually a##lied$ ,hich results in increased mor!idity. Therefore$ it is im#ortant to identify the #rimary tumour to #ro'ide targeted thera#y. .re'ious studies ha'e sho,n that molecular methods such as microsatellite analysis or human #a#illoma'irus 0;.12 *?@ detection ,ere clinically useful tools for guiding the search for the sites of origin of these tumours. ;o,e'er$ these methods are often not a'aila!le in daily diagnostic #ractice. The cyto eratin 0-A2 is an intermediate filament #rotein found in the intracyto#lasmic cytos eleton of e#ithelia and their neo#lasms. @t least 20 different -As ha'e !een descri!ed$ and ex#ression of these -As is fre6uently tissues#ecific and differentiation-s#ecific. )n addition to !eing mar ers of normal e#ithelial differentiation$ -A #rofiles ha'e !een used as a diagnostic tool to identify and classify different ty#es of carcinomas/ -A10 may !e used as a mar er for ,ell differentiated eratini3ing S--s$ ,hereas -A18 can !e used as a mar er for non eratini3ing S--.

-lassification tree #ro'ided !y -lassification and 5egression Tree analysis. The #redominant #rimary site is sho,n in !old and the a!solute num!er of cases is sho,n in #arentheses. @!!re'iations( B-$ oral ca'ity #rimary/ B.$ oro#harynx #rimary/ ;.$ hy#o#harynx #rimary/ C@$ larynx #rimary. Dse of this com!ination ,as most hel#ful in identifying oro#haryngeal #rimary tumour. @s occult #rimary ;?S--s are most often found hidden ,ithin >aldeyerEs ring 0lym#hoid tissue of the naso#harynx$ tonsil$ and !ase of tongue2 and early carcinoma arising in the !ase of tongue or the tonsillar area are difficult to detect and e'aluate clinically$ the #rediction of oro#harynx as #rimary tumour site is clinically im#ortant in diagnosing the metastatic ;?S--s. )n a #re'ious study$ ;.1 *?@ ,as detected !y #olymerase chain reaction in 34.5F of cases of ;?S--$ regardless of the site of origin and #atient age grou#. @mong the ;?S--s$ ;.1$ es#ecially ty#e 17$ has most fre6uently !een detected in oro#haryngeal S--s. ;.1-related tumours are characteri3ed !y a non- eratini3ing$ !asaloid cell mor#hology. Because of the high #re'alence of ;.1 *?@ in tonsillar tumours and its characteristic histology$ detection of ;.1-related S-- may !e used as a mar er for determining the site of the #rimary tumours in the metastatic cer'ical lym#h nodes. )n high-ris $ ;.1-infected cells$ ;.1-related =7 and =: onco#roteins can a!rogate the negati'e gro,th regulatory signalling #ath,ays of the host cell through interaction ,ith #53 and #5! tumour su##ressor #roteins$ res#ecti'ely. )n ;.1-#ositi'e ;?S--$ ex#ression of ;.1 =7 and =: is correlated ,ith a #aucity of mutations in #53$ decreased le'els of #5!$ and increased le'els of #17. The functional inacti'ation of #5! !y ;.1 =: results in the reci#rocal o'erex#ression of #17$ ,hich occurs due to a #ositi'e feed!ac loo# !et,een #5! and #17. Therefore$ #17 is considered to !e a com#limentary surrogate !iomar er for ;.1 related cer'ical and 'ul'ar neo#lasia. htt#(++,,,.sciencedirect.com+science+article+#ii+S004791::08003283

;G= stain sho,ing mature smooth muscle cells and adi#ose tissue regularly distri!uted

.hotomicrogra#h Sho,ing a *ilated @fferent Cym#hatic 1essel -onnecting ,ith a *raining Cym#h ?ode that is .artially 5e#laced !y 4etastatic Tumour @ reacti'e lym#h node ,ith follicular hy#er#lasia. &ollicular lym#homa extending into the extraca#sular adi#ose tissue. the lym#h node is re#laced !y nodular lym#homa cells. *iffuse$ large B-cell lym#homa. the lym#h node loses normal architecture and is re#laced !y dense monotonous lym#homa cells 0;G= stain2. The lym#homa #enetrates through the fi!rous ca#sule 0arro,2 into the adHacent connecti'e tissue. =xtraca#sular in'asi'e areas ,ith desmo#lastic reaction 0arro,heads2 connect each other to form a fi!rous mesh,or in the adi#ose tissue. .a#illary thyroid carcinoma metastatic to the cer'ical lym#h node. The metastatic #a#illary carcinoma from the thyroid forms #a#illary or follicular structures$ focally containing thyroglo!ulin colloids. htt#(++,,,.nature.com+sre#+2013+130213+sre#01255+full+sre#01255.html