Familial Nasopharyngeal Carcinoma 6

78 T. C. Putti and K-B. TanCytological smears are prepared and conventionallystained with Papanicolaou (alcohol-fixed) andGiemsa (air-dried). The former helps highlightnuclear features of the cells, while the latter betterdelineates the cytoplasmic detail; hence the two arecomplementary. Nonkeratinizing NPC features cohesivegroups of tumor cells, although some dispersedsingle tumor cells are often present as well. The almostobligatory presence of associated lymphocytes is alsonoted. The hyperchromatic nuclei of NPC tumor cellsare elongated-to-oval in configuration, are frequentlyoverlapping, and often bear prominent nucleoli(Fig. 7.10). The cytoplasm is scanty in amount. Thekeratinizing SCC subtype of NPC discloses tumorcells with keratinized (dense) cytoplasm with hyperchromaticnuclei; nucleoli are usually not prominent.In assessing a suspected case of nonkeratinizingNPC, the cytological features may occasionally bevery challenging and may mimic those seen in othertumors, notably small cell neuroendocrine carcinomaand large cell lymphoma. In such instances, a cellblock prepared at the time of FNAC can be very usefulas it provides a source of cellular material onwhich ancillary studies can be performed. NPC tumorcells are positive for cytokeratin immunhistochemistryas well as EBER-ISH (vide supra). Large cell lymphomais negative for cytokeratins and positive forleukocyte common antigen (LCA), while small cellcarcinoma is negative for EBER-ISH and positive forneuroendocrine markers such as Synaptophysin andCD56.7.3.4Diagnosis of MetastasesThe cervical lymph nodes are generally the first siteof tumor metastases. Extranodal distant metastasescan occur in bone, lung, and liver. For confirmationof metastases in the cervical lymph nodes, FNAC ispreferred (vide supra). In those cases with inadequatematerial, an open biopsy can be performed. Thetumor cells generally form cohesive islands intermixedwith variable number of lymphocytes, plasmacells, and eosinophils. In a small percentage of metastatictumors, epithelioid granulomas can be noted,some even with caseous necrosis. A diligent search toexclude the possibility of mycobacterial infection isimperative, especially following radiation therapy(Chan et al. 2004).7.4Pathological Differential DiagnosisCrush artifacts: Sometimes, severe crush artifacts ofsmall nasopharyngeal biopsies may give rise to amistaken diagnosis of NPC, especially in the presenceFig. 7.10. Cytologicalsmear showing cohesivespindle-shaped undifferentiatedcarcinoma cells(papanicolaou, originalmagnification ×600)