Familial Nasopharyngeal Carcinoma 6

Pathology of Nasopharyngeal Carcinoma 79of clinical symptoms and a mass. It is prudent not tomake a firm diagnosis of carcinoma in such cases.Depending on the morphological features, immunohistochemicalstaining for cytokeratin may or maynot be helpful. A crushed crypt with irregular bordersand cytokeratin positivity may mimic carcinoma.A repeat biopsy is a better alternative over afalse-positive diagnosis.Reactive germinal centers: Nasopharyngeal mucosais rich in lymphoid tissue and may contain severalreactive lymphoid follicles. Germinal center cells caneasily mimic malignant cells, as they contain large cellswith vesicular nuclei and prominent nucleoli. This is aproblem when the mantle zone is indistinct and thebiopsy sample is small, compounded by crush artifacts.A useful clue is identification of tingible bodymacrophages. Immunohistochemistry for LCA (positive)and cytokeratins (negative) can be used for confirmationof follicular center cells in difficult cases.Lymphoma: Occasionally, a large cell lymphomaof nasopharyngeal tissue can be difficult to differentiatefrom carcinoma on morphological featuresalone. Generally, carcinomatous cells form cohesivegroups and have ill-defined cell borders. Again, animmunohistochemistry panel (LCA and cytokeratin)would be of great value.Sinonasal carcinoma: Sinonasal undifferentiatedcarcinoma is a rare aggressive neoplasm arising in thenasal cavity and rarely nasopharyngeal region. Thesetumors may resemble undifferentiated NPC but areconsistently negative for EBER-ISH (Jeng et al. 2002).Rhabdomyosarcoma: These tumors can resembleundifferentiated NPC but are most commonly seenin younger individuals while NPC occurs mostly inadults and the elderly population. They present withaural symptoms, nasal obstruction, and pain.Immunohistochemical stains are strongly positivefor desmin and myoglobin. Embryonal and spindlecell variants are the common subtypes (Nascimentoet al. 2005).Melanoma: Melanoma can uncommonly beencountered in the nasopharyngeal location. Thepresence of melanin pigment, multinucleate tumorgiant cells, or positivity for S-100, HMB-45, and melan-A excludes NPC. Histologically, these tumors can beepithelioid, spindled, or undifferentiated (Thompsonet al. 2003).Olfactory neuroblastoma: Olfactory neuroblastoma(Esthesioneuroblastoma) is a malignant neuroendocrinetumor originating in the olfactorymucosa. It is a small blue cell neoplasm with a characteristiclobular architecture, neuroendocrine immunophenotype,and a sustentacular S-100-positivestaining pattern (Ingeholm et al. 2002).7.5Pathological Aspectsof Post-treatment ChangesPostradiation changes – Radiation therapy is themainstay treatment modality for nonmetastatic NPC.Generally, a reasonable tumor response occurs in10–12 weeks following radiation therapy. Residualtumor cells may display vacuolated cytoplasm andbizarre nuclei. Normal epithelium, either surface orcryptal, may sometimes show changes resemblingcarcinoma. A negative EBER-ISH would in most casesrule out malignancy. The stromal cells also exhibitatypical changes in the form of enlarged abnormalnuclei with prominent nucleoli, but these are negativefor cytokeratin.Secondary malignancies – Second malignanciesafter definitive treatment of NPC is a rare but devastatingcomplication. The two most commonly diagnosedmalignancies following treatment for NPCinclude SCC and sarcomas of varying types includingosteosarcoma, malignant fibrous histiocytoma,malignant schwannoma, extraskeletal chondrosarcoma,and angiosarcoma. Of about 3,000 patientstreated with radiotherapy for NPC over a 10-yearperiod in Singapore, only one patient developedpostradiation sarcoma of the sphenoid bone (Teoet al. 2006). The latency period can be anytime from2 to 40 years.7.6SummaryNasopharyngeal carcinoma (NPC) has important andunique clinicopathological features in the field of headand neck pathology. NPC is histopathologically classifiedas nonkeratinizing or keratinizing. The former isfurther subdivided into undifferentiated carcinomaand differentiated carcinoma subgroups and is thepredominant form of NPC encountered worldwide,particularly in NPC-endemic regions. Microscopically,nonkeratinizing NPC is characterized by tumor cellsgrowing in either a cohesive or reticulated patternwith a typical admixture of lymphocytes, while keratinizingNPC shows the features of a well-differentiatedSCC. While light microscopy of H and E-stained