Nasopharyngeal nonkeratinising carcinoma. Cytokeratin-positivity would indicate an epithelial cell proliferation.

Cells have large nuclei and prominent eosinophilic nucleoli. Often metastasize early because of the rich lymphatic network in this region primarily draining into the superior deep jugular and submandibular lymph nodes. Tumours tend to be less differentiated and more biologically aggressive than their counterparts in the anterior oral cavity. NPC is notorious for its highly malignant behaviour, with extensive loco-regional infiltration, early lymphatic spread, and disproportionately high incidence of haematogenous dissemination. With the rich lymphatic plexus in the nasopharynx, lymphatic spread occurs early in the course of disease. The jugulo-digastric node is by far the most common palpable node at presentation, and involvement of the posterior cervical chain is more frequent than with other head and neck cancers.

Although the exact origin of this amyloid is not known, it is believed to be derived from filamentous degradation of keratin filaments secreted by tumor epithelial cells.

Basaloid SCC. Solid pattern of growth and central comedo-type necrosis. Hematoxylin and eosin staining (original magnification x100). (confirm via p16 immunostaining). Basaloid squamous cell carcinoma is a high-grade variant of SCC composed of both basaloid and squamous components (Barnes et al., 2005). It is an aggressive, rapidly growing tumor characterized by an advanced stage at the time of diagnosis (cervical lymph node metastases) and a poor prognosis. The basaloid component is comprised of small packed cells displaying hyperchromatic nuclei without nucleoli, and scant cytoplasm. The tumor grows in a solid pattern with a lobular configuration, and sometimes a prominent peripheral palisading. Comedo-type necrosis is frequently seen (Fig. 8). Small cystic spaces containing PAS- and Alcian Blue-positive material and stromal hyalinization may be noticed. BSCC is always associated with a SCC component, usually located superficially. The SCC component may also present as focal squamous differentiation within the basaloid lobules. The junction between the two components may be abrupt. The differential diagnosis includes neuroendocrine

carcinoma, adenoid cystic carcinoma, and adenosquamous carcinoma. BSCC requires aggressive multimodality treatment, including radical surgery (including neck dissection), radiotherapy, and chemotherapy (especially for metastatic disease). Survival rate is only 40%.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0083135#abstract0 TNM Primary tumour (T) TX Primary tumour cannot be assessed. Regional lymph nodes (N) The distribution and the prognostic effect of regional lymph node spread from nasopharynx cancer, especially of the undifferentiated type, is different from that of other head and neck mucosal cancers and justifies use of a different N classification scheme. NX N0 N1 Regional lymph nodes cannot be assessed No regional lymph node metastasis Unilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa Bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa Metastasis in a lymph node(s) greater than 6 cm in dimension extension to the supraclavicular fossa

N2

N3 N3a N3b

Distant metastasis (M) MX Distant metastasis cannot be assessed http://www.sciencedirect.com/science/article/pii/S0140673605666986?_rdoc=1&_fmt=high&_origi n=ihub&_docanchor=&md5=9ffa87934275edd7180b52f5e973f002

Diagnostic methods Diagnostic methods include: 1. Clinical evaluation of the size and location of cervical lymph nodes. 2. Indirect nasopharyngoscopy to assess the primary tumour. 3. Neurological examination of cranial nerves. 4. Computed tomography (CT)/magnetic resonance imaging (MRI) scan of the head and neck to below clavicles to assess base of skull erosion. 5. Chest radiotherapy (anteroposterior and lateral) to see if NPC has spread to the lungs. 6. Bone scintigraphy by Tc 99 diphosphonate to show whether cancer has spread to the bones. 7. Full blood count. 8. Urea, electrolyte, creatinine, liver function, Ca, PO4, alkaline phosphate. 9. EBV viral capsid antigen and EBV DNA. 10. Biopsy of either the lymph nodes or primary tumour for histological examination. TX N1 MX

http://www.biomedcentral.com/content/pdf/1750-1172-1-23.pdf The diagnostic evaluation of patients with CUP consists of laboratory or clinical investigations including mainly pathology, imaging and endoscopy studies. Serum tumour markers can contribute, but only in certain cases. Clinicians should follow certain algorithms in searching for the primary tumour, taking into consideration the cost, in terms of time and money, as well as the final benefit in the outcome of these patients.

The role of the pathologist An adequate sample of tumour tissue is of paramount importance in order to perform light microscopy, immunohistochemistry, other markers or receptor studies, as well as more specific investigations such as electron microscopy or genetic analysis. Light microscopic examination is rarely successful in identifying the site of origin in a patient with CUP. Light microscopy can basically characterise cell morphology and tumour differentiation. Apart from the routine staining with haematoxylin and eosin, additional stains can be employed including mucicarmine, Alcian Blue and periodic acid-Schiff to detect mucin and mucopolysaccharides or trichrome and methyl-green pyronine stains to help rule out sarcomas and lymphomas in poorly differentiated and undifferentiated neoplasms. However, the development of immunohistochemical techniques of greater sensitivity and specificity has limited the value of these histochemical procedures. Immunohistochemical studies on metastatic carcinomas of an unknown primary site sometimes results in the identification of the tumour origin, especially if the metastases are poorly differentiated by light microscopy. The ability of immunoperoxidase staining to be performed on formalin-fixed paraffinised tissue facilitates its diagnostic application in the detection of the primary. Several cell components can be identified by a series of monoclonal or polyclonal immunoperoxidase antibodies. http://www.sciencedirect.com/science/article/pii/S0959804903005471