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| RESIDENTS CORNER |
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| Year : 2022 | Volume
: 5
| Issue : 1 | Page : 63-66 |
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The eyes only see what the mind is prepared to comprehend: A rare case
Himanshi Diwan1, Sunil Pasricha1, Anila Sharma1, Anurag Mehta2
1 Department of Pathology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
2 Transfusion and Molecular Services, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
| Date of Submission | 28-May-2022 |
| Date of Decision | 08-Jun-2022 |
| Date of Acceptance | 14-Jun-2022 |
| Date of Web Publication | 02-Sep-2022 |
Correspondence Address:
Dr. Himanshi Diwan
Department of Pathology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jco.jco_7_22
How to cite this article:
Diwan H, Pasricha S, Sharma A, Mehta A. The eyes only see what the mind is prepared to comprehend: A rare case. J Curr Oncol 2022;5:63-6 |
| Case Presentation | |  |
A 38-year-old man, with no significant past/family/personal history, presented with dry cough for 10 days, odynophagia, and difficulty breathing in a supine position for 2 months. The routine laboratory investigations were unremarkable. The COVID test performed was negative. A chest x-ray revealed the prominence of bilateral bronchovascular markings and the widening of the superior mediastinum. Subsequently, contrast-enhanced computed tomography chest revealed a large lobulated moderately enhancing mass lesion (12 × 9 cm) in the prevascular region, extending into the mediastinum encasing superior vena cava, aorta, and main pulmonary artery. A working clinicoradiological diagnosis of lymphoma was suggested. The computed tomography-guided biopsy was performed, and hematoxylin and eosin (H&E)–stained slides revealed undifferentiated malignancy favoring a poorly differentiated carcinoma with tumor cells imparting syncytial appearance having a vesicular nucleus and prominent nucleoli admixed with lymphoplasmacytic cells Figure 1]. | Figure 1: (A) Scanner view revealing the tumor cells arranged in nests admixed with lymphoplasmacytic infiltrate. (B) The low-power view shows the monomorphic tumor cells in the syncytium surrounded by lymphocytes and plasma cells. The tumor cells are large with vesicular nuclei and conspicuous nucleoli. (C) The intermediate-power view shows the tumor cells with vesicular nucleus and prominent nucleoli. (D) The high-power view shows the tumor cells admixed with inflammatory infiltrate. The tumor cells are large round to ovoid and have vesicular nuclei and prominent nucleoli
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On immunohistochemistry, the tumor cells were positive for cytokeratin (CK), P40, cluster of differentiation (CD) 117 [Figure 2], whereas negative for leukocyte common antigen (LCA), nuclear protein in testes (NUT), terminal deoxynucleotidyl transferase (Tdt), Sal-like protein 4 (SALL4), CD5, paired-box gene 8 (PAX-8), and Epstein-Barr virus-encoded RNA. In situ hybridization (EBER-ISH) was found to be strong and diffuse positive [Figure 2]. | Figure 2: (A) The tumor cells are immunopositive for CK. (B) The tumor cells show nuclear staining for p40. (C) The tumor cells display CD117 positivity. (D) The tumor cells are EBER-ISH positive
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Q1: What is your diagnosis based on histopathological examination?
Answer: Thymic lymphoepithelial carcinoma (TLEC).
TLEC is a very rare aggressive tumor accounting for 1.3%–6% of all thymic carcinoma.[1] The rarity of the entity can be reinforced by the fact that mere 58 cases have been reported in the literature to date.[2] The median age of patients with TLEC reported in the literature is 41 years.[1] The patients often present with symptoms associated with the compression effect due to mediastinal mass with lung, liver, bone, and lymph nodes being the most frequent distant sites of metastasis.[1],[3] Rarely the disease is detected as an incidental finding in routine imaging studies. Rarely the disease may be complicated by polymyositis, nephrotic syndrome, and hypertrophic osteoarthropathy.[1],[4],[5],[6],[7],[8]
Histopathological examination supported by immunohistochemistry remains the gold standard for the diagnosis of this rare tumor. The tumor cells are often undifferentiated and arranged in sheets, nests, and cords with syncytial appearance, vesicular chromatin, and prominent nucleoli with admixed dense lymphoplasmacytic infiltration. The tumor cells are immunopositive for p63 and pan-CK.
This tumor has a peculiar immunoprofile with CD117 immunopositivity, whereas CD5 positivity is variable. Almost half of all cases show EBV association.
Q2: What are the differentials in the histopathological examination?
Answer: Differential diagnosis:
- ♦ Thymic undifferentiated carcinoma
- ♦ Malignant germ cell tumor
- ♦ Poorly differentiated squamous cell carcinoma
- ♦ NUT carcinoma
- ♦ Non-Hodgkin lymphoma (NHL)
- ♦ Brahma related gene 1 (BRG1) deficient undifferentiated thoracic tumor.
The diffuse arrangement of undifferentiated tumor cells with lymphoplasmacytic infiltrate along with CD117 immunopositivity in a mediastinal location in this age group can lead to an erroneous diagnosis of germ cell tumor (seminoma). CK, P40, and EBER-ISH positivity and a lack of LCA, SALL4, and NUT ruled out the other differentials and provided the tangible evidence for the final diagnosis of TLEC in this case. The diagnosis is often challenging as squamous cell carcinoma with lymphoplasmacytic infiltrate can mimic TLEC, especially in the setting of EBV-negative TLEC; however, the lack of squamous cell differentiation and syncytium supports the diagnosis of TLEC. The absence of LCA and NUT staining by tumor cells knocked out the possibility of NHL and NUT carcinoma, respectively. The lack of the expression of PAX-8 and the expression of p40/p63 distinguishes it from thymic undifferentiated carcinoma. Intact BRG1 staining ruled out the BRG1 deficient undifferentiated carcinoma.
Q3: How do you stage TLEC?
Answer: TNM staging, or Masaoka-Koga system, is elaborated in [Table 1] and [Table 2].
Q4: Does EBV status affect the prognosis of TLEC? How do you determine the EBV status on biopsy?
Answer: EBV is positive in half of all the affected cases. There is no prognostic difference between EBV-positive and EBV-negative TLEC.
EBV status can be determined by EBER-ISH on biopsy. Infected cells harboring the EBV genome but not producing viral particles (latent) synthesize noncoding RNA (EBER-1 and EBER-2), which is mainly localized to the nucleus. The nuclei of tumor cells thus should be assessed for staining by EBER-ISH.
Q5: Can molecular-based immunohistochemistry aid in the diagnosis?
Answer: Yes, the use of molecular markers such as NUT, BRG1, INI1, and p16 may help in ruling out other undifferentiated tumors such as NUT carcinoma and SMARCA4, SMARCB1-deficient tumors. These can be confirmed subsequently on a molecular platform such as fluorescence in situ hybridization and next-generation sequencing.
However, the molecular signature has not been defined in TLEC till date.
The surgical resection is the standard treatment in the early stages, whereas the multimodal chemotherapy remains the mode of treatment in nonresectable tumors. However, even when diagnosed early, the tumor tends to recur early, thus explaining the grim prognosis and the need for regular and close follow-up. The median survival time is reported to be 36 months.[9]
| Conclusion | | |
The TLEC is a rare but aggressive tumor morphologically equivalent to nasopharyngeal lymphoepithelial carcinoma. The unusual CD117 immunopositivity in a mediastinal tumor may result in a fallacious diagnosis of mediastinal germ cell tumor and hence a judicious use of immunohistochemistry. The panel covering the pertinent differentials will aid in the correct diagnosis. Owing to its adverse prognosis, an accurate and early diagnosis is essential for timely therapeutic intervention.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Authors’ contributions
Concept and design of the study: SP, AS, and AM; drafting the article: HD; revising it critically for important intellectual content: SP; and final approval of the version to be published: SP, AS, and AM.
| References | | |
| 1. | WHO Classification of Tumours Editorial Board. Thoracic tumours. 5th ed. Vol. 5. Lyon, France: International Agency for Research on Cancer; 2021.  |
| 2. | Ose N, Kawagishi S, Funaki S, Kanou T, Fukui E, Kimura K, et al. Thymic lymphoepithelial carcinoma associated with Epstein-Barr virus: Experiences and literature review. Cancers 2021;13:4794. |
| 3. | Pomplun S, Wotherspoon AC, Shah G, Goldstraw P, Ladas G, Nicholson AG Immunohistochemical markers in the differentiation of thymic and pulmonary neoplasms. Histopathology 2002;40:152-8. |
| 4. | Hsueh C, Kuo TT, Tsang NM, Wu YC, Yang CP, Hung IJ Thymic lymphoepithelioma like carcinoma in children: Clinicopathologic features and molecular analysis. J Pediatr Hematol Oncol 2006;28:785-90. |
| 5. | Ilhan I, Kutluk T, Göğüş S, Besim A, Büyükpamukçu M Hypertrophic pulmonary osteoarthropathy in a child with thymic carcinoma: An unusual presentation in childhood. Med Pediatr Oncol 1994;23:140-3. |
| 6. | Di Cataldo A, Villari L, Milone P, Miano AE, Sambataro MP, Florio G, et al. Thymic carcinoma, systemic lupus erythematosus, and hypertrophic pulmonary osteoarthropathy in an 11-year-old boy: A novel association. Pediatr Hematol Oncol 2000;17:701-6. |
| 7. | Niehues T, Harms D, Jürgens H, Göbel U Treatment of pediatric malignant thymoma: Long-term remission in a 14-year-old boy with EBV-associated thymic carcinoma by aggressive, combined modality treatment. Med Pediatr Oncol 1996;26:419-24. |
| 8. | Kiliś-Pstrusińska K, Medyńska A, Zwolińska D, Dobaczewski G Lymphoepithelioma-like thymic carcinoma in a 16-year-old boy with nephrotic syndrome—A case report. Pediatr Nephrol 2008;23:1001-3. |
| 9. | Kawagishi S, Ose N, Minami M, Funaki S, Kanou T, Kimura K, et al. Total thymectomy for thymic lymphoepithelioma-like carcinoma—Report of two cases. Surg Case Rep 2019;5:158. |
[Figure 1], [Figure 2]
[Table 1], [Table 2]
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