Mediastinum
Thymic carcinoma
Lymphoepithelioma-like
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 7 May 2019
Minor changes: 10 June 2020
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PubMed Search: Lymphoepithelioma-like thymic carcinoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Etiology | Clinical features | Radiology description | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Suster D, Mackinnon AC. Lymphoepithelioma-like. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/mediastinumLEL.html. Accessed January 24th, 2021.
Definition / general
- Also known as poorly differentiated, nonkeratinizing, squamous cell thymic carcinoma
- Originates from thymic epithelial cells and shows histologic and immunophenotypic evidence of squamous differentiation
- WHO classification: lymphoepithelioma-like carcinoma
Essential features
- Defined as a primary thymic epithelial neoplasm displaying overt cytologic evidence of malignancy with loss of organotypical features of thymic differentiation
- Diagnosis of exclusion
- Invasive growth pattern of nests and cords of tumor cells which grow in a syncytial growth pattern and have vesicular nuclei with prominent nucleoli
- Often have prominent associated lymphoid infiltrate within fibrous stroma
- Rare cases associated with Epstein-Barr virus (EBV)
Terminology
- Thymic carcinoma
- Poorly differentiated, nonkeratinizing, squamous cell thymic carcinoma
- Lymphoepithelioma-like carcinoma
ICD coding
- ICD-10: C37 - thymic carcinoma (malignant)
Epidemiology
- M > F (~3:1)
- Average age of 60 years (range: 20 - 85 years)
Sites
- Predominantly located in the anterior mediastinum (Am J Surg Pathol 2018;42:1224)
Etiology
- Remains unknown
- Epstein-Barr virus has been reported in rare case reports, predominantly in younger patients; however, in the largest study, only 4% of cases were positive for EBER by in situ hybridization (Am J Surg Pathol 2018;42:1224)
- No pathognomonic molecular alterations have been identified
Clinical features
- Present with anterior mediastinal masses, often found incidentally
- When symptomatic, clinical symptoms include chest pain, shortness of breath and weight loss (Am J Surg Pathol 2018;42:1224)
Radiology description
- Typically appear as well demarcated anterior mediastinal masses
- Positron emission tomography (PET) usually shows mild to moderate PET avidity
Prognostic factors
- Staging at time of diagnosis is the most important prognostic factor
- Currently performed using the modified Masaoka staging system (Thorac Cardiovasc Surg 2014;62:153)
- New staging guidelines may replace this system soon (Radiographics 2017;37:758)
- Completeness of resection is an important prognostic factor as well
Case reports
- 14 year old boy with metastatic carcinoma (Oncol Lett 2014;8:2183)
- 42 year old man with multiple lung, bone and brain metastases (Acta Neurol Taiwan 2010;19:41)
- 52 year old man with complaints of left anterior chest pain (Kyobu Geka 2003;56:509)
- 60 year old man with right sided neck mass found to be an intrathyroidal lymphoepithelioma-like thymic carcinoma (APMIS 1996;104:419)
- Young man who presented initially with back pain (BMJ Case Rep 2017 Sep 23;2017)
Treatment
- Surgical resection is still the predominant treatment
- Radiotherapy may increase local regional relapse free survival with mild toxicities in advanced stage patients (Ann Thorac Surg 2017;104:1718)
- In the largest study, 14 of 20 patients had no evidence of disease between 1.5 and 16 years after diagnosis (median survival: 4 years; mean survival: 5.5 years) (Oncol Lett 2014;8:2183)
Microscopic (histologic) description
- Invasive growth pattern of cords, nests and trabeculae separated by fibrous stroma with variable prominent mature lymphoid infiltrates
- 2 patterns of growth described (Am J Surg Pathol 2018;42:1224):
- Lymphoepithelioma-like pattern: irregular cords and islands of tumor cells separated by connective tissue stroma containing dense lymphoplasmacytic infiltrates
- Desmoplastic pattern: irregular cords and nests of tumor cells separated by fibrous stroma with minimal inflammatory infiltrates
- Can have both patterns
- Can show focal areas of abrupt keratinization
- Prominent areas of comedonecrosis
- Uniform, poorly differentiated tumor cell population with round to oval nuclei, vesicular chromatin, prominent round eosinophilic nucleoli and an indistinct rim of eosinophilic cytoplasm
- Syncytial growth pattern of tumor cells with rare pleomorphic and multinucleated cells
Microscopic (histologic) images
Contributed by David Suster, M.D.
Sheets of large round to oval tumor cells
Anastomosing cords, islands, comedonecrosis
Comedonecrosis
Lymphoepithelioma-like pattern
Desmoplastic pattern
Focal abrupt keratinization
p63
Positive stains
- 100%: keratin AE1 / AE3, CK5 / 6, CK18, MOC31, p40, p63 and p16 (Am J Surg Pathol 2018;42:1224)
- CD5 (80%) (Appl Immunohistochem Mol Morphol 2014;22:372)
- CD117 (84%) (Appl Immunohistochem Mol Morphol 2014;22:372)
- Ki67 proliferation index of 35% on average (Am J Surg Pathol 2018;42:1224)
- Variable positivity for p53, CK7, CK19 and synaptophysin (Am J Surg Pathol 2018;42:1224)
- Lymphoid cells: mixture CD3 and CD20 (Am J Surg Pathol 2018;42:1224)
Negative stains
- NUTM1, calcitonin, calretinin and TTF1 (Am J Surg Pathol 2018;42:1224)
- Lymphoid cells: TdT (Am J Surg Pathol 2018;42:1224)
Electron microscopy description
- Cohesive population of large cells with round to oval nuclei containing a single nucleolus and scattered heterochromatin (Am J Surg Pathol 2018;42:1224)
- Abundant junctional complexes, with dense plaques and well formed desmosomes containing attached short tonofilaments (Am J Surg Pathol 2018;42:1224)
Electron microscopy images
Contributed by David Suster, M.D.
Large, round tumor cell
2 desmosomal attachments
Molecular / cytogenetics description
- EBER rarely identified (Am J Surg Pathol 2018;42:1224)
- Molecular studies reveal a heterogeneous group of variants with low numbers of mutations, similar to other molecular studies done on thymic carcinoma
- 5 patients had somatic variants in 6 genes known to play a significant role in tumor development and growth, including IDH1, CDKN2A, FGFR3 and others (Am J Surg Pathol 2018;42:1224)
Sample pathology report
- Thymus, resection:
- Poorly differentiated thymic squamous cell carcinoma, predominantly nonkeratinizing (lymphoepithelioma-like) (see synoptic report and comment)
- Comment: The tumor cells are positive for p40, CD117, CD5 and PDL1.
Differential diagnosis
- Metastatic poorly differentiated lung carcinoma:
- Atypical thymoma:
- Basaloid thymic carcinoma:
- Less comedonecrosis and basal palisading of the nuclei
- Lack distinct nucleoli and cleared out vesicular cytoplasm
- NUT midline carcinoma:
- NUT1+
- NUT-BRD translocations can be identified by FISH
Board review style question #1
A 62 year old patient presents with a 9 cm anterior mediastinal mass (see image below). What specific test would help differentiate this lesion from a metastasis from a head and neck lymphoepithelioma-like thymic carcinoma?
- Immunohistochemistry for p63 and cytokeratins
- In situ hybridization for EBER
- In situ hybridization for HPV
- Next generation sequencing
Board review style answer #1
B. In an older patient, in situ hybridization for EBER would be the most helpful test as nearly 100% of head and neck lymphoepithelial carcinomas are EBER+ while thymic lymphoepithelial carcinomas tend to be EBER-, especially in adults.
Reference: Lymphoepithelioma-like thymic carcinoma
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Reference: Lymphoepithelioma-like thymic carcinoma
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Board review style question #2
Which immunohistochemical stains would be most helpful in distinguishing a primary squamous cell thymic carcinoma from metastatic lesions from other primary sites?
- CD5 and CD117
- Cytokeratins
- p16
- p63
Board review style answer #2
A. CD5 and CD117 would be the most helpful in establishing thymic origin in this scenario. While primary lymphoepithelioma-like thymic carcinoma will express keratins, p16 and p63, so would poorly differentiated squamous cell carcinomas elsewhere in the body. However, few lesions outside the body would have CD5 and CD117 positivity.
Reference: Lymphoepithelioma-like thymic carcinoma
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Reference: Lymphoepithelioma-like thymic carcinoma
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