As defined by the World Health Organization classification system, nasopharyngeal carcinoma (NPC) histopathologically can be classified into undifferentiated carcinoma (UC), differentiated nonkeratinizing carcinoma (NKC) and SCC . In the case of our patient, examination of tissues obtained from of the nasopharynx was enough to establish the diagnosis of SCC. Histologically, the tumor shows prominent features of keratinization, including the presence of squamous pearl formation and evident intercellular bridges. Negative serum antibody to EBV and negative EBER-ISH, which is almost invariably positive in UC and NKC and less often positive in SCC, also support the diagnosis [6–8]. However, identification of metastatic or primary nature of nasopharyngeal SCC is difficult and is imperative in making the appropriate prognostic evaluation and choosing the best treatment option. In our patient, a documented previous history of advanced lung SCC associated with recurrence was highly suggestive of the metastatic nature of the lesion in the nasopharynx. However, tumors seldom metastasize to the nasopharynx. In contrast, the incidence of primary lung cancer associated with second primary tumors in the head and neck area is 1% to 2% [9, 10]. Because of the very low prevalence of nasopharyngeal metastasis and relatively more common secondary primary tumors, it could be argued that a history of malignancy does not necessarily imply that a nasopharyngeal lesion is metastatic in nature. It is indeed well-known among pathologists that there are currently no immunohistochemical markers for the determination of the likely site of origin of SCC, even though this is possible for adenocarcinomas in most cases . Some relevant and heuristic studies have been carried out in recent years. Kanthan et al. adopted cytokeratin CK5, p63 and p16 as immunohistochemical markers to confirm the diagnosis of SCC of the cervix metastatic to the duodenum . Huang et al. performed immunohistochemical staining to compare the expression pattern of the epithelial–mesenchymal transition markers between primary SCC of the hypopharynx and a metastatic lesion of the duodenum . Zhang et al. identified the SPLUNC1 and LPLUNC1 genes by suppression subtractive hybridization and cDNA microarray. These genes are specifically expressed in normal adult nasopharyngeal epithelial tissue and trachea and downexpressed in NPC . Gevaert et al. studied the expression profiles of a series of human epithelial cancers and their metastases by microarray technology. Strikingly, they concluded that SCCs do not reflect their primary tissue expression profile because of the absence of a molecular signature in these tumors that reflects their tissue of origin . Therefore, the differentiation between primary and metastasis of nasopharyngeal SCC currently depends mainly on clinical and histological signs. In our region, malignancies in the nasopharynx are largely confined to the pharyngeal recess . Some have argued that the roof of the nasopharyngeal cavity may be the area most likely to develop the original carcinomatous microfocus, followed in frequency by the posterior wall . Early cancers localized to the torus tubarius are rarely reported. Histologically, undifferentiated or NKC is the main subtype, which is associated with the EBV genome within the tumor and intratumoral lymphoid infiltrate. Keratinizing SCC is uncommon and accounts for only about 5% of cases . The clinical clues highly reminiscent of metastasis to the nasopharynx in this case include a documented previous history of advanced lung SCC associated with recurrence, the uncommon location of the lesion, the cauliflower-like tumor growth without paranasopharyngeal space involvement, the absence of enlarged cervical lymph nodes, negative serum antibody to EBV and multiple bronchoscopy intervention therapies. Histological signs suggestive of metastasis include the unusual histological subtype, negative EBER-ISH, lack of local inflammatory response and absence of squamous metaplasia in the mucosa adjacent to the tumor.
The exact mechanism of lung cancer metastatic to the nasopharynx in our patient remains unclear. Significantly, during his treatment, the patient underwent two-course bronchoscopy intervention therapies for obstruction of the airway through his right nostril. Portsite metastasis secondary to instrumentation in laparoscopic surgery has been well-documented. Numerous mechanisms have been proposed, including implantation, leakage of insufflation gas through the ports (the “chimney effect”) and the effect of pneumoperitoneum on local immune reactions . More than 30 cases of metastatic spread to a percutaneous endoscopic gastrostomy site in patients with head and neck cancer have been reported , and direct implantation of cells is considered more likely than hematogenous spread . More rarely, cases of nasal tip metastasis from various malignancies have been reported as well . It can be postulated that the metastatic mechanism is similar with the use of such instrumentation. Implantation is the most likely cause. It has been shown that instruments harbor tumor cells and that tissue trauma, tumor manipulation and spillage increase the chances of tumor seeding . Hematogenous and lymphatic spread must also be considered. It is well-known that metastases often favor sites of trauma. It is possible, therefore, that the nasopharyngeal mucosa traumatized by the bronchoscopy in our patient may have attracted blood-borne metastases. This hypothesis is in agreement with our patient’s advanced cancer stage, which implies that tumor cells were circulating in the lymphatic channels and bloodstream.
Because of the extreme rarity of nasopharyngeal metastasis, there is no consensus regarding the best treatment. Wong et al. reported the case of a patient with adenocarcinoma of the lung with solitary nasopharyngeal metastasis. Their patient received palliation radiotherapy and remained disease-free for 10 years from the date of diagnosis of nasopharyngeal metastasis, and they postulated that solitary nasopharyngeal metastasis from lung primary tumor might be a separate entity that responds well to radiotherapy . Saab et al. reported the case of a patient with breast carcinoma metastatic to the nasopharynx with a dismal result due to delay of treatment . In our present case, we adopted palliative bronchoscopy intervention therapy but not radiotherapy to the nasopharyngeal lesion because of the metastatic nature with implantation as the probable cause, the absence of an enlarged cervical lymph node or paranasopharyngeal space involvement and the advanced primary lung cancer. The long-term result of treatment awaits further evaluation.