Liver Metastasis from Nasopharyngeal Carcinoma Diagnosed on Fine Needle Aspiration Cytology

Abstract

A 12-year-old boy presented with abdominal distention for 1 year. On examination, he had massive hepatomegaly. Facial swelling in the maxillary region, palpable left cervical lymph nodes, and a nasal twang to his voice were detected. Imaging showed multiple hypodense liver lesions, necrotic mediastinal and hilar lymph nodes, multiple lytic–sclerotic skeletal lesions, and lesions in the nasopharynx and maxilla. Fine needle aspirate (FNA) from the cervical lymph node yielded blood. FNA from the liver showed singly dispersed and cohesive clusters of tumor cells, with interspersed neutrophils and tingible body macrophages. Cells had scant to moderate fragile cytoplasm, enlarged vesicular nuclei, and prominent nucleoli. Immunohistochemistry on cell block revealed positivity for cytokeratin and Epstein–Barr virus (EBV)-Latent Membrane Protein-1 (LMP1). A diagnosis of metastatic nasopharyngeal carcinoma was made, and was confirmed on a subsequent biopsy from the femur.

INTRODUCTION

Nasopharyngeal carcinoma (NPC) is categorized as keratinizing, non-keratinizing, and basaloid squamous cell carcinoma; non-keratinizing NPC is subdivided into differentiated and undifferentiated subtypes. Non-keratinizing undifferentiated (NKU) NPC is the commonest histological type, accounting for 60%–80% of cases, with a strong association with Epstein–Barr virus (EBV). NPC is most common in the fourth to sixth decades, with 1%–20% of cases reported in children.[1]

Clinical presentation is nonspecific, often causing delayed diagnosis. Pediatric patients present with locoregionally advanced disease, with lymph node metastases found in 70%–90% of cases.[1] Distant metastases from NPC to bone, lung, liver, and distant lymph nodes occur in 17%–54% of patients.[2] Liver metastases are seen in 29%–38%, indicating that aspirates of liver metastases from NPC may frequently be encountered by cytopathologists.[2]

Due to the inaccessible primary location, fine needle aspiration cytology (FNAC) is not usually performed for diagnosis of NPC. Hence, its cytological features are not well documented, being restricted to a few series on metastases in cervical nodes.[3-6] There is a single report of FNAC from NPC metastatic to the liver.[3]

CASE HISTORY

A 12-year-old boy presented with complaints of a nasal twang, facial swelling, proptosis, and abdominal distention for 1 year. Examination revealed a swelling in the maxillary region, along with palpable left cervical lymph nodes and massive hepatomegaly. Imaging [Figure 1a] revealed a nasopharyngeal mass, with bony metastasis in the left maxilla and necrotic cervical lymph nodes. Necrotic mediastinal and right hilar adenopathy [Figure 1b], multiple hypodense liver lesions [Figure 1c], and right external iliac lymphadenopathy were seen on contrast-enhanced computed tomography (CECT). Bone window revealed multiple lytic sclerotic skeletal lesions in the right acetabulum, femur, and vertebrae [Figure 1d]. A clinico-radiological diagnosis of lymphoma was considered, and FNAC from the cervical lymph node and liver lesion was requisitioned. Cervical lymph node FNAC and cell block yielded only blood. Ultrasound-guided FNAC was performed from the liver lesion in the same sitting. Smears [Figure 2a-f] showed tumor cells arranged in loosely cohesive clusters as well as dispersed singly. Tumor cells had scant to moderate amount of fragile cytoplasm with ill-defined outlines. Nuclei were large, round to oval, with vesicular chromatin and prominent eosinophilic nucleoli. There was considerable nuclear pleomorphism, with some cells having multilobate nuclei. On May-Grünwald-Giemsa (MGG), many of the singly dispersed tumor cells appeared to be naked nuclei with macronucleoli and no discernible cytoplasm. There were a few interspersed neutrophils and tingible body macrophages, along with apoptotic debris. Lymphocytes, plasma cells, eosinophils, and granulomas were absent. Possibilities of metastatic germ cell tumor (GCT), lymphoma, and metastatic NPC were considered. However, tigroid background, lymphoglandular bodies, and evidence of squamous differentiation were absent. Immunohistochemistry on the cell block [Figure 2g-i] revealed positivity for cytokeratin and EBV-LMP1 and negativity for Sal-like protein 4 (SALL4) and leukocyte common antigen (LCA), indicating a diagnosis of metastatic NKU-NPC, while excluding GCT and lymphoma, respectively. Subsequent biopsy from the femur lesion showed similar features [Figure 2j-l].

Figure 1.

Axial CECT neck (a) shows a mass in the left fossa of Rosenmuller (arrow), with bony metastasis in the left maxilla (notched arrow). CECT chest (b) shows necrotic mediastinal and right hilar adenopathy (arrow). CECT abdomen (c) shows multiple hypodense liver lesions (arrows); bone window image (d) reveals lytic sclerotic skeletal metastasis in the femur (arrow). CECT = contrast-enhanced computed tomography

Figure 2.

FNAC from the liver shows tumor cells arranged in loosely cohesive clusters as well as dispersed singly (a, Papanicolaou stain (PAP), ×100; b, MGG, ×100). Tumor cells have scant to moderate cytoplasm and large, round to oval nuclei (c, PAP, ×200;); naked nuclei, tingible body macrophages, and apoptotic debris are seen (d, MGG, ×200). Nuclei are vesicular with prominent nucleoli (e, PAP, ×400; f, MGG, ×400). Cell block shows similar tumor cells (g, HE, ×200) positive for cytokeratin (h, IHC, ×200) and EBV-LMP1 (i, IHC, ×200). Biopsy from femur shows similar tumor (j, HE, ×400) positive for cytokeratin (k, IHC, ×200) and EBV-LMP1 (l, IHC, ×200) EBV = Epstein–Barr virus, FNAC = fine needle aspiration cytology, HE = hematoxylin–eosin, IHC = immunohistochemistry

DISCUSSION

NPC is well recognized for its proclivity for metastases.[1,2] Multiorgan involvement is frequent, often metastasizing to lungs, liver, bone, and lymph nodes.[2,3] FNA has proven utility in diagnosing metastatic carcinomas; in the head and neck, results of aspiration cytology of a neck mass may be the sole indication for investigating the nasopharynx for an occult primary.

Diagnosis of NKU-NPC, the commonest subtype in children, on cytology is onerous as its cytomorphological features closely resemble those of lymphomas, GCT, and melanoma.[1] A “mixed pattern” with discohesive tumor cells in a polymorphous lymphoid background is most frequent (46%), followed by “lymphoma-like pattern” with numerous lymphocytes; carcinoma-like morphology is rarest, seen in 20%.[3] Mixed and lymphoma-like patterns exhibit numerous lymphoglandular bodies and lymphoid cells. Differential diagnosis includes lymphoma and GCT. NKU-NPC and Hodgkin lymphoma have similar background of reactive lymphoid tissue with lymphocytes, plasma cells, eosinophils, and, occasionally, granulomas.[6] Jayaram et al.[4] suggested that lymphoepithelial clusters, with lymphoid cells outnumbering malignant cells, are characteristic. Kollur and El Hag[6] reported that intermingled plasma cells in nodal metastasis are a good indicator for a nasopharyngeal primary. However, Grenko and Shabb[5] found that metastases to extranodal sites were almost devoid of lymphocytes. Viguer et al.[3] described hepatic and lung metastasis from NPC; the lung aspirate showed moderate number of lymphocytes admixed with tumor cells, whereas the liver aspirate had sparse lymphocytes. Thus, it appears that the site of metastasis impacts the cytomorphology of metastatic NPC.

Ancillary testing on cell blocks can aid in arriving at the correct diagnosis. In the present case, cytokeratin proved the epithelial origin of the tumor, immunonegativity for LCA ruled out lymphoma, and negative SALL4 excluded GCT. A study has shown that EBV Epstein-Barr encoding region (EBER) in-situ hybridization (ISH) or LMP1 immunohistochemistry on cell blocks can increase the diagnostic accuracy of identifying metastatic NPC.

This case highlights that lymphoid cells intermixed with tumor cells may not always be evident in aspirates from NPC. Cytologists should be aware of the spectrum of morphological features of NPC to suspect the diagnosis at metastatic sites. FNAC with ancillary techniques on cell block is valuable in localizing an unknown primary to the nasopharynx.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.