Nasal cavity, paranasal sinuses, nasopharynx
Sinonasal carcinoma
Sinonasal lymphoepithelial carcinoma
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PubMed Search: Sinonasal lymphoepithelial carcinoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: Wei LTE, Bundele MM. Sinonasal lymphoepithelial carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/nasalsinolymphoepicarc.html. Accessed July 15th, 2024.
Definition / general
- Lymphoepithelial carcinoma is an undifferentiated appearing carcinoma that arises within the sinonasal tract
- Shows an associated prominent, nonneoplastic lymphoplasmacytic cell infiltrate
- Strongly associated with Epstein-Barr virus (EBV)
- Exclusion of nasopharyngeal or oropharyngeal primary
Essential features
- Morphologically similar to nasopharyngeal carcinoma, nonkeratinizing, undifferentiated subtype
- Syncytial sheets and diffusely infiltrating undifferentiated cells with vesicular nuclei, prominent nucleoli, ill defined cell borders and pale eosinophilic cytoplasm
- Accompanied by a variably dense lymphoplasmacytic inflammatory infiltrate
- More common in Asian people
- Nearly all cases are positive for EBV
Terminology
- Lymphoepithelioma-like carcinoma
- Primary sinonasal nasopharyngeal type undifferentiated carcinoma
ICD coding
- ICD-O: 8082/3 - lymphoepithelial carcinoma
- ICD-11
- 2C20.4 & XH1E40 - squamous cell carcinoma of nasal cavity & lymphoepithelial carcinoma
- 2C22.1 & XH1E40 - squamous cell carcinoma of accessory sinuses & lymphoepithelial carcinoma
Epidemiology
- Patients are usually in their fifth to seventh decade of life (Semin Diagn Pathol 2015;32:74)
- Median age: 58 years (Am J Surg Pathol 2002;26:371)
- M:F = 2 - 3:1 (Am J Surg Pathol 2002;26:371)
- Increased incidence in ethnic patients from regions where nasopharyngeal carcinoma has a high prevalence (i.e., East and Southeast Asia) (Cancer Med 2023;12:7105)
- Nasal cavity and paranasal sinuses comprised 2.3% of nonnasopharyngeal lymphoepithelial carcinoma of all body sites in Chinese patients (Cancer Med 2023;12:7105)
- Nasal cavity and paranasal sinuses comprised 9.25% of all nonnasopharyngeal head and neck lymphoepithelioma-like carcinoma in predominantly White men in the United States (Head Neck 2016;38:E1294)
Sites
- Affects the nasal cavity and less commonly the paranasal sinuses (Semin Diagn Pathol 2015;32:74)
- Sinonasal tract location defines sinonasal lymphoepithelial carcinoma as a distinct entity from nasopharyngeal carcinoma (Am J Surg Pathol 2002;26:371)
Pathophysiology
- Unknown
Etiology
- Similar to its nasopharyngeal counterpart, strongly associated with EBV infection, especially in endemic areas; however, not all cases are EBV positive (Semin Diagn Pathol 2015;32:74)
Clinical features
- Nasal obstruction, epistaxis, facial swelling or pain (Semin Diagn Pathol 2015;32:74)
- Advanced tumors with skull base invasion may cause proptosis and cranial nerve palsies (Semin Diagn Pathol 2015;32:74)
Diagnosis
- Exclusion of nasopharyngeal / oropharyngeal primary (Arch Pathol Lab Med 2019;143:1416)
- EBV encoded small RNA (EBER) in situ hybridization (especially in endemic cases) (Semin Diagn Pathol 2015;32:74)
- Staging is according to the Union for International Cancer Control (UICC) TNM classification
Laboratory
- Positive EBV serology
- Elevated circulating EBV DNA or RNA; e.g., plasma or serum EBV encoded small RNA (EBERs)
- Increased plasma EBV DNA load of > 513.5 copies/mL is strongly predictive of disease progression (Cancer Med 2023;12:7105)
Radiology description
- CT / MRI to assess extent of disease and presence of skull base invasion (Cureus 2022;14:e31103)
- Irregular soft tissue density with bony destruction / bony sclerosis (Cureus 2022;14:e31103)
- Homogeneous density or signal and obvious enhancement in solid portion accompanied with varying degrees of local invasion (Cureus 2022;14:e31103)
- Localized soft tissue mass or diffuse infiltration along mucosa
- Polypoid strips, spherical masses or diffuse thickening of nasal cavity and turbinate mucosa
Radiology images
Images hosted on other servers:
CT of sphenoid sinus mass
MRI of right sinonasal mass
CT of ethmoid sinus mass
CT of maxillary sinus mass
CT / MRI of maxillary sinus mass
Prognostic factors
- Regional cervical lymph node metastases may be seen at presentation (Semin Diagn Pathol 2015;32:74)
- Appears to metastasize to cervical lymph nodes (15 - 25%) less frequently than nasopharyngeal carcinoma (Auris Nasus Larynx 2009;36:487)
- Distant metastases are exceptional (Am J Surg Pathol 2002;26:371)
- Prognosis is favorable even with cervical lymph node metastases owing to good response to local radiotherapy but survival data is limited by disease rarity (Semin Diagn Pathol 2015;32:74)
- Mortality rate with adequate treatment is low (Semin Diagn Pathol 2015;32:74)
Case reports
- 38 year old man with nasal obstruction, right facial numbness, right sided headache, orbital pain and epistaxis (Case Rep Otolaryngol 2023;2023:4217102)
- 39 year old man with blurring of vision, proptosis and anosmia (Cureus 2022;14:e31103)
- 77 year old man with nasal congestion and persistent sinusitis (Ear Nose Throat J 2022;101:386)
Treatment
- Treatment includes surgery combined with radiotherapy or chemoradiation (Semin Diagn Pathol 2015;32:74)
Clinical images
Images hosted on other servers:
Nasoendoscopy of sphenoid sinus mass
Nasoendoscopy of maxillary sinus mass
Gross description
- Presents with an irregular or polypoid mass that may have erosion and hemorrhagic surfaces (Head Neck Pathol 2011;5:327)
Gross images
Images hosted on other servers:
Tumor with hemorrhagic surface
Frozen section description
- Undifferentiated appearing malignant tumor; differential usually includes but not limited to an undifferentiated carcinoma, hematolymphoid neoplasm, etc.
Microscopic (histologic) description
- Subepithelial infiltrative neoplastic proliferation composed of syncytium of large cells (Regaud pattern) arranged in lobules, nests, trabeculae or cords (Semin Diagn Pathol 2015;32:74)
- Neoplastic cells may diffusely infiltrate the subepithelial tissue (Schmincke pattern) without a desmoplastic stromal reaction and may also be identified in the epithelium (Semin Diagn Pathol 2015;32:74)
- Associated with a dense nonneoplastic lymphoplasmacytic infiltrate, which can be florid (obscuring the tumor cells) but is typically less prominent as compared to nasopharyngeal carcinoma (Semin Diagn Pathol 2015;32:74)
- Malignant cells typically have large round to oval nuclei, vesicular chromatin, one or more prominent nucleoli, abundant amphophilic to pale eosinophilic cytoplasm and poorly defined cell borders (syncytial pattern) (Semin Diagn Pathol 2015;32:74)
- Occasional tumor cell spindling
- Necrosis is rare but may be present, including central comedo type (Semin Diagn Pathol 2015;32:74)
- Keratinization is typically absent
- Thick fibrous septa separating tumor islands may be observed
- Extracellular amyloid deposits may be present
Microscopic (histologic) images
Contributed by Manish Mahadeorao Bundele, M.B.B.S., M.D.
Syncytial nests (Regaud pattern)
Diffusely infiltrating dyscohesive pattern
Stromal hyalinization
Pancytokeratin
EBER ISH
Cytology description
- Smears show irregular tissue fragments of epithelial cells with large, highly pleomorphic nuclei and spindled or epidermoid cytoplasm that may be poorly defined (Semin Diagn Pathol 2015;32:74)
- Often prominent and obscuring lymphoplasmacytic background (Semin Diagn Pathol 2015;32:74)
- Lymphocytes can infiltrate the epithelium
- Epithelial component resembles nonkeratinizing nasopharyngeal carcinoma (Semin Diagn Pathol 2015;32:74)
Positive stains
- Positive for pancytokeratin AE1 / AE3
- Usually positive for squamous markers such as p40, p63 and CK5/6 (Semin Diagn Pathol 2015;32:74)
Negative stains
- p16 is usually negative or patchy and weak (Semin Diagn Pathol 2015;32:74)
- Negative for neuroendocrine, lymphoid and melanocytic markers (Semin Diagn Pathol 2015;32:74)
Molecular / cytogenetics description
- Typically strongly reactive for EBV encoded small RNA (EBER) by in situ hybridization (Semin Diagn Pathol 2015;32:74)
- Rare cases may be EBER negative (Head Neck Pathol 2011;5:327)
Sample pathology report
- Nose, nasal biopsy:
- Lymphoepithelial carcinoma (see comment)
- Sections show pieces of fibrous tissue with a tumor composed of islands and nests of large cells with prominent nucleoli, vesicular nuclei and scant to moderate cytoplasm. The cytoplasmic borders appear indistinct. There is no overt glandular or squamous differentiation seen. Mitotic activity and necrosis are noted. An intimate infiltrate of lymphocytes and plasma cells is noted.
- On immunohistochemistry, the tumor stains for AE1 / AE3 and p40. The stains for synaptophysin, chromogranin, S100 protein, HMB45 and p16 are negative.
- In situ hybridization for Epstein-Barr encoded RNA reveals diffuse positive signals in the tumor cells.
- Comment: A nasopharyngeal primary should be excluded.
Differential diagnosis
- Nonkeratinizing nasopharyngeal carcinoma:
- May be present in the nasal cavity by extension from the nasopharynx
- Radiologic correlation is needed to determine the location of the primary tumor
- Lymphoplasmacytic infiltrate may be dense, expanding the tumor cell islands but it may also be sparse and only represented by native lymphoid tissue
- HPV associated oropharyngeal squamous cell carcinoma:
- Squamous cell carcinoma, usually nonkeratinizing, oropharyngeal origin
- Subtypes with basaloid, papillary, adenosquamous, ciliated adenosquamous, lymphoepithelial (undifferentiated) and sarcomatoid features
- Positivity for high risk HPV as determined by surrogate marker p16 immunohistochemistry alone (70% nuclear and cytoplasmic cut off point) or by p16 immunohistochemistry plus HPV specific testing
- Negative for EBV encoded small RNA (EBER) by in situ hybridization
- SWI / SNF complex deficient sinonasal carcinomas:
- Poorly differentiated to undifferentiated carcinoma defined by the loss of one SWI / SNF complex subunit (either SMARCB1 or SMARCA4) without histological features allowing classification into another specific entity
- SMARCB1 deficient carcinomas display a monomorphic, predominantly basaloid or plasmacytoid / rhabdoid cell morphology; diffuse loss of INI1 staining by IHC is definitional
- SMARCA4 deficient carcinomas are histologically undifferentiated, composed of large epithelioid anaplastic cells in nests and trabeculae; diffuse loss of BRG1 staining by IHC is definitional
- NUT carcinoma:
- Sheets and nests of small to intermediate sized undifferentiated cells with a monomorphic appearance
- Demonstration of NUT gene rearrangement (immunohistochemistry or a molecular technique)
- High grade neuroendocrine carcinoma:
- Small cell neuroendocrine carcinoma: carcinoma cells with scant cytoplasm, hyperchromatic molded nuclei, finely granular chromatin and inconspicuous nucleoli
- Large cell neuroendocrine carcinoma: carcinoma cells with abundant eosinophilic cytoplasm, vesicular chromatin and prominent nucleoli
- Often perinuclear dot-like cytokeratin expression
- Immunoreactive for neuroendocrine markers (e.g., synaptophysin, chromogranin or INSM1)
- Sinonasal undifferentiated carcinoma (SNUC):
- Carcinoma without any identifiable line of differentiation (including squamous, glandular and neuroendocrine) and is a diagnosis of exclusion of other specific entities
- Negative for EBV encoded small RNA (EBER) by in situ hybridization
- Subset may show IDH1 / IDH2 mutations
- Mucosal melanoma:
- Cells may show undifferentiated morphology or varied cytomorphology with plasmacytoid, epithelioid, spindled, rhabdoid, round or clear appearances
- Melanin pigment in tumor cells
- Involving epithelium or submucosa in the absence of any evidence of metastasis from a cutaneous primary
- Positive for melanocytic markers including S100, SOX10, HMB45, MelanA; negative for cytokeratin and EBV
- Extranodal NK / T cell lymphoma, nasal type:
- May be histologically undifferentiated and associated with EBV
- Immunoreactive for hematolymphoid markers including CD3 (cytoplasmic), CD56, cytotoxic granules markers (e.g., granzyme B, cytotoxic granule associated TIA1 and perforin) and negative for cytokeratin
- Rhabdomyosarcoma:
- Several subtypes of rhabdomyosarcoma have been reported in the sinonasal tract (e.g., embryonal rhabdomyosarcoma, including the botryoid variant), alveolar rhabdomyosarcoma, spindle cell / sclerosing rhabdomyosarcoma and pleomorphic rhabdomyosarcoma
- Embryonal rhabdomyosarcoma and alveolar rhabdomyosarcoma can demonstrate a primitive small blue round cell morphology
- Positive for myogenic markers (desmin, myoD1 and myogenin); negative for cytokeratin and EBV
- Undifferentiated sarcoma:
- Sarcoma with no identifiable line of differentiation
- Diagnosis of exclusion
- Pleomorphic high grade morphology
- Complex karyotypes; an absence of distinctive molecular aberrations
Board review style question #1
The image above is of a biopsy from a sinonasal tract mass in a 50 year old Chinese man. Epstein-Barr virus (EBV) encoded small RNA (EBER) by in situ hybridization is positive in the tumor cells. Which of the following statements is true?
- Nasopharyngeal primary must be excluded before diagnosing this as a sinonasal lymphoepithelial carcinoma
- This tumor is generally associated with high risk human papillomavirus (HPV)
- This tumor is more commonly seen in Western populations
- This tumor shows IDH1 / IDH2 mutations
Board review style answer #1
A. Nasopharyngeal primary must be excluded before diagnosing this as a sinonasal lymphoepithelial carcinoma. Nasopharyngeal carcinoma is more common and it can extend into the sinonasal tract from the nasopharynx. Once nasopharyngeal carcinoma is excluded, this is compatible with sinonasal lymphoepithelial carcinoma. Answer B is incorrect because sinonasal lymphoepithelial carcinoma is associated with EBV and not high risk HPV. Answer C is incorrect because sinonasal lymphoepithelial carcinoma is more common in East and Southeast Asia, where nasopharyngeal carcinoma has a high prevalence. Answer D is incorrect because sinonasal lymphoepithelial carcinoma is not associated with IDH1 / IDH2 mutations, which are seen in a subset of sinonasal undifferentiated carcinomas and large cell neuroendocrine carcinomas.
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Reference: Sinonasal lymphoepithelial carcinoma
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Reference: Sinonasal lymphoepithelial carcinoma
