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Year : 2017  |  Volume : 60  |  Issue : 2  |  Page : 294-296
Pediatric nasopharyngeal carcinoma with a spectrum of precursor lesions: Cervical lymph node metastasis initially diagnosed by fine needle aspiration cytology

1 Department of Pathology, Faculty of Medicine, Kuwait University; Cytology Unit, Mubarak Al-Kabeer Hospital, Al-Jabriya, Kuwait
2 Cytology Unit, Mubarak Al-Kabeer Hospital, Al-Jabriya, Kuwait
3 Cytology Laboratory, Hussain Maki Al Juma Center for Specialized Surgery, Shuwaikh, Kuwait
4 Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait
5 Department of Histopathology, Al-Sabah Hospital, Shuwaikh, Kuwait

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Date of Web Publication19-Jun-2017

How to cite this article:
Das DK, Haji BI, Jaragh M, John B, Katchy KC. Pediatric nasopharyngeal carcinoma with a spectrum of precursor lesions: Cervical lymph node metastasis initially diagnosed by fine needle aspiration cytology. Indian J Pathol Microbiol 2017;60:294-6

How to cite this URL:
Das DK, Haji BI, Jaragh M, John B, Katchy KC. Pediatric nasopharyngeal carcinoma with a spectrum of precursor lesions: Cervical lymph node metastasis initially diagnosed by fine needle aspiration cytology. Indian J Pathol Microbiol [serial online] 2017 [cited 2022 Jan 20];60:294-6. Available from: https://www.ijpmonline.org/text.asp?2017/60/2/294/208403


Pediatric nasopharyngeal carcinoma (NPC) represents a locally advanced undifferentiated tumor with a great propensity to metastasize to the regional lymph nodes.[1] Concurrent precursor lesion designated nasopharyngeal intraepithelial neoplasia (NPIN) has rarely been demonstrated in the biopsy specimen.[2] As per a few reports, fine-needle aspiration (FNA) cytology has been utilized as a diagnostic tool in metastatic NPC.[3],[4] We present the FNA cytologic features of cervical lymph node metastasis in a pediatric patient with NPC which pointed toward a primary lesion in the nasopharynx. The histopathological findings of the primary nasopharyngeal lesion included a spectrum of progressive precancerous changes leading to invasive carcinoma.

FNA was performed on a 3 cm × 2 cm left cervical lymph node in an 11-year-old girl on September 1, 2004. FNA smears were cellular and showed groups undifferentiated malignant cells in loose cohesive clusters with a sprinkling of lymphocytes throughout and microacinar formation at places [Figure 1]a. The tumor cells had round to oval nuclei with finely dispersed chromatin and prominent nucleoli [Figure 1]b. The FNA cytodiagnosis was an undifferentiated malignant tumor. During discussion with the clinician, a thorough nasopharyngeal examination was advised to rule out a primary lesion. Nasopharyngeal examination by pan-endoscopy revealed a mass lesion, which was subjected to biopsy. Histopathological examination showed sheets of undifferentiated tumor cells and dense lymphocytic infiltration around them [Figure 1]c; the tumor cells had vesicular nuclei and prominent nucleoli [Figure 1]d. The histopathological diagnosis was undifferentiated carcinoma (nasopharynx). The tumor cells were positive for pan-cytokeratin (pan-CK) [Figure 1]e and epithelial membrane antigen (EMA). The Ki-67 index was high, staining above 75% of tumor cells. Staining for p53 revealed positive reaction in a proportion of these cells [Figure 1]f but most cells were positively stained for p63 [Figure 1]g. The tumor cells were negative for Epstein-Barr virus nuclear antigen (EBNA), vimentin, and leukocyte common antigen. The staining for Epstein-Barr virus latent membrane protein (EBV-LMP) on archival paraffin section yielded a negative result. During the review, it was also noticed that the pseudostratified ciliated epithelium had a spectrum of epithelial abnormalities that included reserve cell hyperplasia [Figure 2]a, and NPIN in the form of dysplasia [Figure 2]b, and carcinoma in situ(CIS) [Figure 2]c. A focus of invasive carcinoma was found to be arising from CIS [Figure 2]d and [Figure 2]e; the invasion from NPIN was also highlighted in the section stained for EMA [Figure 2]f.
Figure 1: Fine-needle aspiration smear from 3 cm × 2 cm leticervical lymph node in an 11-year-old girl. Fine-needle aspiration cytodiagnosis was metastatic undiff erentiated malignancy. A thorough nasopharyngeal examination was advised to rule out a primary lesion. Biopsy from the nasopharyngeal growth was diagnosed as nasopharyngeal carcinoma. (a) Undiff erentiated tumor cells in a loose cohesive cluster with sprinkling of lymphocytes showing microacinar formation (MGG, ×400). (b) The tumor cells have round to oval nuclei, fi nely dispersed chromatin, and prominent nucleoli (Pap, ×1000). (c) Biopsy from nasopharyngeal growth shows sheets invasive of undiff erentiated tumor cells surrounded by dense lymphocytic infi ltration (H and E, ×200). (d) The tumor cells had vesicular nuclei and prominent nucleoli (H and E, ×400). (e) The tumor cells were positive for pan-cytokeratin (×400). (f) p53 staining (nuclear) was positive reaction in a few tumor cells (×400). (g) p63 staining (nuclear) was positive in most of the cells (×400)

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Figure 2: Spectrum of histopathological changes in biopsy of nasopharyngeal growth. (a) The pseudostratified ciliated epithelium shows reserve cell hyperplasia (H and E, ×400). (b) Dysplastic changes in the epithelial lining and invasive carcinoma underneath (H and E, ×400). (c) Carcinoma in situ changes in the epithelial lining and an island of invasive carcinoma cells beneath are morphologically similar (H and E, ×400). (d) A focus of invasive carcinoma arising from carcinoma in situ and in contiguous with invasive carcinoma underneath (H and E, ×100). (e) Higher magnification of the focus of invasion from carcinoma in situ (H and E, ×200). (f) The invasive carcinoma arising from superfi cial epithelium is highlighted by EMA staining (×100)

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The patient received external beam radiation therapy and chemotherapy. She had a good clinical response, and there was no residual cervical lymphadenopathy or no nasopharyngeal mass, as evident from clinical examination, endoscopic examination, and computed tomography scan of head and neck region after 1 year. Last seen on February 24, 2015, she had no local recurrence, but tiny subpleural nodules were seen on positron emission tomography scan.

Children with NPC almost always have the undifferentiated variant of disease, which is associated with advanced locoregional spread and distant metastasis.[5] In the nasopharyngeal mucosal brushing from the primary lesion, the cytologic pickup has been substantially lower (specificity 100% and sensitivity 69.1%) than that obtained by biopsy.[2] In the report by Chan et al.,[3] FNA smears of all forty cases metastatic NPC in cervical lymph node showed clusters of cohesive tumor cells intermingled with mature lymphocytes; in most cases, the tumor cells were undifferentiated type with pale cytoplasm having ill-defined boundaries and medium-sized oval vesicular nuclei with mitotic activity but all cases had prominent nucleoli. FNA smears in our case satisfied almost all the features of an undifferentiated type of NPC.

Varying morphologic features such as carcinoma-like morphology, lymphoma-like morphology, or a mixed pattern may lead to diagnostic difficulty in NPC.[4] Original cytodiagnosis in 32 patients with FNA in the study by Viguer et al.[4] included metastatic NPC in 23 cases, metastatic carcinoma not otherwise specified in 3, malignant undifferentiated tumor in 3, metastatic epidermoid carcinoma in 2, and suspicious of Hodgkin lymphoma in one. In cases with diagnostic difficulties, ancillary studies may contribute to the diagnostic process. Archival paraffin sections of primary tumor in our case showed positive reaction for CK as has been observed by Jayaram et al.[1] and EMA. Zhong et al.[6] demonstrated EBV-encoded RNA in 15 cases of early-stage NPC biopsy tissue by nucleic acid in situ hybridization. Our case was negative for EBNA and EBV-LMP. In pediatric NPC with negative EBV status, NUT midline carcinoma (NMC) may be considered as an important candidate for differential diagnosis; however, NMC demonstrates NUT translocation, and with few exceptions, is positive for cytokeratin, and usually diffusely positive for p63 (unlike sinonasal undifferentiated carcinoma).[7] NMC also represents a very aggressive malignancy with poor prognosis; the median overall survival of NMC in a study by Chau et al.[8] was 9.7 months (range, 6.6–15.6 months). In our case, most of the cells were p63+, but we did not have NUT antibody in our laboratory. Despite this limitation, the excellent prognostic outcome in our case almost excludes NMC.

Current findings on NPC have also revealed the involvement of multiple genetic changes such as RB, p53, and RAS mutations in tumorigenesis process that leads to high-grade lesions, carcinoma in situ, and ultimately invasive carcinoma with metastasis.[9] We observed a spectrum of changes including reserve cell hyperplasia, dysplasia, CIS, and origin of the invasive tongue of carcinoma from CIS. This is a very uncommon finding since concurrent NPIN and NPC were detected by Chang et al.[2] in one among 149 cases with positive histology. The tumor cells in our case had high proliferative index and expression of p53 and p63. Zhang et al.[10] found that p53 (P = 0.019) and epidermal growth factor receptor (P = 0.001) were independent prognostic factors, with lower 3-year survival rates. In NPC, the outcome is better in children and adolescents than in adults (P < 0.0011).[11] Our patient had p53 mutation which is a poor prognostic indicator as per some studies; however, younger age at diagnosis and good locoregional disease control (absence residual cervical lymphadenopathy and no nasopharyngeal mass after 1 year) might have contributed to her survival even after 11 years.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Jayaram G, Swain M, Khanijow V, Jalaludin MA. Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma. Diagn Cytopathol 1998;19:168-72.  Back to cited text no. 1
Chang AR, Liang XM, Chan AT, Chan MK, Teo PM, Johnson PJ. The use of brush cytology and directed biopsies for the detection of nasopharyngeal carcinoma and precursor lesions. Head Neck 2001;23:637-45.  Back to cited text no. 2
Chan MK, McGuire LJ, Lee JC. Fine needle aspiration cytodiagnosis of nasopharyngeal carcinoma in cervical lymph nodes. A study of 40 cases. Acta Cytol 1989;33:344-50.  Back to cited text no. 3
Viguer JM, Jiménez-Heffernan JA, López-Ferrer P, Banaclocha M, Vicandi B. Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma. Diagn Cytopathol 2005;32:233-7.  Back to cited text no. 4
Ayan I, Kaytan E, Ayan N. Childhood nasopharyngeal carcinoma: From biology to treatment. Lancet Oncol 2003;4:13-21.  Back to cited text no. 5
Zhong BL, Zong YS, Lin SX, Zhang M, Liang YJ. Epstein-Barr virus infection in precursor lesions of nasopharyngeal carcinoma. Ai Zheng 2006;25:136-42.  Back to cited text no. 6
Bishop JA, French CA, Ali SZ. Cytopathologic features of NUT midline carcinoma: A series of 26 specimens from 13 patients. Cancer 2016;124:901-8.  Back to cited text no. 7
Chau NG, Hurwitz S, Mitchell CM, Aserlind A, Grunfeld N, Kaplan L, et al. Intensive treatment and survival outcomes in NUT midline carcinoma of the head and neck. Cancer 2016;122:3632-40.  Back to cited text no. 8
Lo KW, Huang DP. Genetic and epigenetic changes in nasopharyngeal carcinoma. Semin Cancer Biol 2002;12:451-62.  Back to cited text no. 9
Zhang P, Wu SK, Wang Y, Fan ZX, Li CR, Feng M, et al. p53, MDM2, eIF4E and EGFR expression in nasopharyngeal carcinoma and their correlation with clinicopathological characteristics and prognosis: A retrospective study. Oncol Lett 2015;9:113-8.  Back to cited text no. 10
Sultan I, Casanova M, Ferrari A, Rihani R, Rodriguez-Galindo C. Differential features of nasopharyngeal carcinoma in children and adults: A SEER study. Pediatr Blood Cancer 2010;55:279-84.  Back to cited text no. 11

Correspondence Address:
Dilip Kumar Das
Department of Pathology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_638_16

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