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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 4  |  Page : 750-756
Sarcomatoid carcinoma of the upper aerodigestive tract: An immunohistochemical analysis demonstrating latent Epstein-Barr virus in a subset of eight cases


1 Department of Pathology, Tepecik Research and Training Hospital, Izmir;Department of Pathology, Ataturk Research and Training Hospital, Izmir, Turkey
2 Department of Pathology, Tepecik Research and Training Hospital, Izmir, Turkey

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Date of Web Publication27-Oct-2010
 

   Abstract 

Background: Sarcomatoid or spindle cell carcinomas are rare malignancies which are considered as a poorly differentiated variant of squamous cell carcinoma. Epstein-Barr virus (EBV) is associated with a wide variety of malignancies. Materials and Methods: We examined the expression of EBV latent membrane protein-1 (LMP-1) and EBV EBNA-2 as well as the immunohistochemical profile of AE-1/AE-3, vimentin, desmin, CK 5-6, smooth muscle actin (SMA), p63, S-100, p53 and CD-117 with the clinicopathological correlation of eight patients of sarcomatoid carcinoma (SC) in the upper aerodigestive tract. Results: Four cases showed EBV LMP-1 positivity (50%) and there was no EBV EBNA-2 positivity. However, the EBV LMP-1 results of our series could be considered only as a coincidental finding in the SCs of the upper aerodigestive tract. Conclusions: This finding supports the idea that further studies based on larger series might be helpful enlighting the role played by EBV in carcinogenesis of SC.

Keywords: Aerodigestive tract, Epstein-Barr virus, immunohistochemistry, sarcomatoid carcinoma, squamous cell

How to cite this article:
Etit D, Altinel D, Bayol U, Tan A, Cumurcu S. Sarcomatoid carcinoma of the upper aerodigestive tract: An immunohistochemical analysis demonstrating latent Epstein-Barr virus in a subset of eight cases. Indian J Pathol Microbiol 2010;53:750-6

How to cite this URL:
Etit D, Altinel D, Bayol U, Tan A, Cumurcu S. Sarcomatoid carcinoma of the upper aerodigestive tract: An immunohistochemical analysis demonstrating latent Epstein-Barr virus in a subset of eight cases. Indian J Pathol Microbiol [serial online] 2010 [cited 2019 Aug 25];53:750-6. Available from: http://www.ijpmonline.org/text.asp?2010/53/4/750/70969



   Introduction Top


Sarcomatoid or spindle cell carcinomas are rare malignancies which are considered as a poorly differentiated variant of squamous cell carcinoma composed of neoplastic cells that have a mesenchymal or sarcomatoid phenotype. [1],[2] These tumors are not uncommonly challenging in classification, diagnosis, and treatment. [3],[4],[5],[6],[7],[8] According to the World Health Organization's working group definition, sarcomatoid carcinoma (SC) is a biphasic tumor composed of a SCC, either in the form of in situ or invasive carcinoma, and a malignant spindle component with a mesenchymal appearance but of epithelial origin. [9] While some cases may have obvious epithelial areas, the sarcomatoid component is almost indistinguishable from a true sarcoma. [10] When the malignant surface epithelium is histologically obvious, the diagnosis of a SC is made confidently. However, when the surface epithelium is ulcerated, the diagnosis becomes more difficult. The "epithelial" differentiation of the spindle cell component has only been proposed in mainly single case reports. [3],[7],[10],[11],[12],[13],[14]

Epstein-Barr virus (EBV) causes infectious mononucleosis and is also associated with a wide variety of malignancies, affecting up to 1% of humans worldwide, and warrants increased focus on laboratory assays to detect and characterize the infection. Within a given neoplasm, consistent presence of EBV implies that the virus might contribute to pathogenesis or maintenance of the clonal process. [15] While EBV latent membrane protein-1 (LMP-1) has an oncogenic potential, upregulating the expression of Bcl-2, [16] the EBV EBNA-2 protein is a transcription factor that coordinates latent viral gene expression and induces several cellular genes that are important for proliferation. [17]

As it is well known, some neoplasms such as nasopharyngeal carcinoma and Burkitt's lymphoma are associated with EBV, while some neoplasms such as sinonasal undifferentiated carcinoma are typically non-associated with EBV. [18],[19],[20]

In order to study the role of EBV in the SCs of the upper aerodigestive tract, we examined the expression of EBV LMP-1 and EBV EBNA-2 as well as the immunohistochemical profile of AE-1/AE-3, vimentin, desmin, CK 5-6, smooth muscle actin (SMA), p63, S-100, p53 and CD-117 with the clinicopathological correlation of eight patients.


   Materials and Methods Top


Cases

From the authors' institutional and consultation files, the pathologic material, including the reports and routine formalin-fixed, paraffin-embedded, hematoxylin and eosin (H and E) stained sections of eight cases were reviewed. All cases for which the available tissues for immunohistochemical staining could be retrieved were histologically characterized as SC .

Patients' age, gender, tumor size and the macroscopic findings of the tumors were taken from the reports. Clinical findings of the cases and follow-up data were obtained through contact with the primary physicians or reviews of patients' medical records [Table 1].
Table 1 :Clinicopathological features of the sarcomatoid carcinomas of the upper aerodigestive tract


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Immunohistochemical Stains

Immunohistochemical stainings for EBV LMP-1, EBV EBNA-2, AE-1/AE-3, vimentin, desmin, CK 5-6, SMA, p63, S-100, p53 and CD-117 were performed on the 5-mm, formalin-fixed, paraffin-embedded sections and processed using automated immunostaining (Ventana Benchmark XT, code:E750-BMKXT-FS) [Table 2].
Table 2 :Monoclonal antibodies and their source used in this study


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   Results Top


Clinical Findings

The patients consisted of seven men and one woman. Mean patient age was 63 years (range 42-75 years). Hoarseness was the most common complaint. The patients were neither immunocompromised nor HIV related.

While larynx was the most frequent site of involvement (7/8), in one case tumor was located at the base of the tongue.

Treatment in this group included total laryngectomy (1), partial laryngectomy (3) including cordectomy (1). Those four patients had neck dissection as a part of laryngectomy treatment and the lymph nodes were without metastases. In four patients, tumoral exicision either as an initial surgery or for a recurrent tumor was performed.

In the median follow-up for 15 months (range 2 months-2 years) of four available patients, there was no evidence of disease.

Pathologic Findings

All the tumors (8/8) exhibited a polypoid or exophytic growth pattern. The recorded tumor size in eight patients ranged from 0.3 to 15 cm (mean 3 cm). Seven were located in the larynx. Extensive surface ulceration was a typical feature. A diligent search was necessary to find a residual squamous epithelium. In all cases, squamous epithelial changes from hyperplasia to invasive conventional carcinoma were observed [Figure 1] and [Figure 2]. The spindle cell component was either resembling a pleomorphic sarcoma or showing relatively bland, fibrosarcoma-like appearence [Figure 3] and [Figure 4]. In two cases, focal necrosis was observed. In pleomorphic sarcoma-like cases, cells with spindle, polygonal cytoplasms and eosinophilic macronucleoli with hyperchromatic nuclei were noted, while fibrosarcoma-like cases had relatively bland cellular features. The mean number of mitosis was 11 in 10 HPF (range 2-37). In four cases, atypical mitoses were identified [Table 1].
Figure 1 :In situ squamous cell carcinoma with extensive surface ulceration above neoplastic spindle cell proliferation (H and E, ×40)

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Figure 2 :Sarcomatoid carcinoma underlying hyperplastic squamous epithelium with mild-moderate squamous dysplasia (H and E, ×200)

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Figure 3 :Pleomorphic sarcoma-like spindle cell component with tumor giant cells and atypical mitotic figures (H and E, ×400)

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Figure 4 :Fibrosarcoma-like appearing spindle cell component and focal necrosis in the same lesion (inset upper left) (H and E, ×400)

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The results of immunostaining are shown in [Table 3]. Overall, the spindle cell component showed positivity for at least one keratin marker in seven tumors (87%). While case 6 only showed CK5-6 positivity in the spindle component, case 7 demonstrated only p63 positivity as an epithelial marker. Staining for keratins often was focal. All the cases were stained with vimentin. SMA in two cases, desmin in one, S-100 in one and focal CD-117 positivity in three cases were noted. P53 positivity was variable from 1-5% to 80-90% [Figure 5], [Figure 6], [Figure 7].
Table 3 :Immunohistochemistry results of the sarcomatoid carcinomas of the upper aerodigestive tract (8 cases)

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Figure 5 :Diffuse vimentin positivity (IHC, ×400)

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Figure 6 :P63 positivity both in the squamous epithelial layer and in the spindle cell tumor (IHC, ×100)

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Figure 7 :Diffuse positive reaction in the SC with p53 (IHC, ×400)

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Out of eight cases, four (50%) showed diffuse and strong nuclear positivity for EBV LMP-1, while there was no EBV EBNA-2 positivity in the series. The staining was also seen in in situ carcinoma. There was no staining in inflamatory cells either within tumor or in the areas adjacent to the tumor. In the 10 control cases of conventional SCC of the larynx, EBV LMP-1 and EBV EBNA-2 were performed. None of them showed positivity either within the invasive or in the in situ carcinomas for those two markers. Interestingly, while there was no immunostaining with EBV LMP-1 in the initial specimen in case 1, the recurrent tumor which had more conventional squamous cell carcinoma areas showed diffuse and strong EBV LMP-1 positivity. This patient or any other patients of the series had no radiotherapy or any other immune deficiency history [Figure 8], [Figure 9],[Figure 10], [Figure 11].
Figure 8 :Case 1: Positive immunoreaction with EBV LMP-1; this case was negative in the initial specimen (inset upper left) (IHC, ×200)

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Figure 9 :Case 2: Nuclear positivity by EBV LMP-1 in the tumor (IHC, ×200). The positive cells are also seen in the squamous mucosa (inset upper left)

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Figure 10 :Case 4: Strong and diffuse positive response by EBV LMP-1 (IHC, ×200)

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Figure 11 :Case 7: EBV LMP-1 positive spindle cells (IHC, ×200)

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   Discussion Top


SC of the upper aerodigestive tract is one of the difficult diagnostic challenges for surgical pathologists. Histogenesis has been settled in favor of a divergent (mesenchymal) differentiation of a carcinoma, most often a squamous cell carcinoma. Finding the carcinoma and/or its immunohistochemical marker in the metaplastic cells supports the correct diagnosis. Based on a review of all of the consultation cases of the Armed Forces Institute of Pathology of benign or malignant primary laryngeal neoplasms, laryngeal SC accounted for approximately 2.7%, a finding that shows slightly higher value than the results reported in the literature. Eight primary SCs were identified in our files in a total of 36,237 surgical pathology cases in a 4-year period.

There was a major predominancy of male-to-female ratio in the present study of 7:1, similar to that in the earlier reports. [12],[13],[21],[22],[23],[24],[25] SC usually develops in the seventh decade of life, with the mean age in this clinical series being 65.6 years. [10],[12],[13],[21],[22],[23],[24],[25],[26],[27]

Larynx is among the most common sites in the head and neck. Less frequently, it arises in the hypopharynx. [28],[29] In our study, the larynx was found to be the most common site.

Patients usually present with hoarseness, dysphagia and airway obstruction. [3],[10],[21],[22],[25],[30] In all the cases in the present study, the main complaint was hoarseness.

Most of the tumors recorded in the literature are polypoid, pedunculated, or exophytic in appearance. [2],[10],[12],[13],[21],[22],[23],[25],[26],[31],[32],[33] All the tumors in our series macroscopically showed polypoid or exophitic growth pattern with superficial epithelial ulceration.

The spindle cell component usually forms the bulk of the tumor, which can resemble a fibrosarcoma or malignant fibrous histiocytoma. Some cases can mimic a less malignant neoplasm or a reactive fibroblastic proliferation with or without stromal atypia. [3],[10],[29] Rhabdosarcomatous or osteosarcomatous differentiation may occur particularly in cases with previous radiotherapy history. In the current study, out of eight cases, while five resembled fibrosarcoma, three cases had a more pleomorphic malignant fibrous histiocytoma-like appearance. None of the patients had radiotherapy history. Evidence for squamous epithelial origin can be seen as either in situ carcinoma or as invasive SCC. Sometimes, SCC cannot be seen due to extensive ulceration. Occasionally, only spindle cells are seen. In our series, all the cases showed surface ulceration and all had squamous epithelial changes ranging from squamous dysplasia to invasive SCC.

The results of a variety of immunohistochemical studies have been reported. [4],[10],[14],[22],[31],[34] Among the epithelial markers, the most sensitive and reliable markers in S Cs appear to be keratin (AE1/AE3). Keratin positivity can be seen in spindle cells in 40-85%. [9] In all cases of the present study, while at least one epithelial antibody was positive in each tumor tested, six lesions showed both AE1/AE3 and p63 positivity.

A divergent mesenchymal differentiation of the tumor cells seems to be supported by the carcinoma cells acquiring the potential to express a mesenchymal phenotype at the light microscopic, immunohistochemical, and ultrastructural levels. [3],[4],[8],[10],[13],[14],[22],[26],[27],[31],[32],[35],[36],[37],[38],[39],[40] Spindle cells express vimentin and other mesenchymal filaments such as SMA, S-100 and desmin. [9] As would be expected, the intermediate filament vimentin showed strong immunoreaction in the sarcomatoid component in all patients in the series (100%), with 38% demonstrating reactivity with SMA, 12% with S-100 protein, and 10% each with desmin. In one study, c-kit (CD117) and other kinases in SCCs have shown significantly higher positivity than in benign samples. [41] In our study, CD117 was focally positive in three cases out of eight (38%). Immunostaining of p53 might serve as a potential adjunct in pathologic evaluation of head and neck tumors to predict the risk. [42] In our series, all cases (100%) had P53 immunoreactivity ranging from 5-10% to 80-90%.

Based upon serologic surveys, it can be said that more than 90% of adults worldwide have been infected by the EBV. [43] Nearly all the infections are acquired by oral contact with a person carrying EBV in saliva. [44] While EBV has been linked to various carcinomas such as gastric carcinoma; in the head and neck region, the best known example of this association is nasopharyngeal carcinoma. Recently, the studies on some other carcinomas related with EBV have been reported, such as in oral carcinogenesis and basaloid-squamous carcinoma of the nasopharynx. [45],[46] Some reports have pointed to EBV positivity of the patients such as an undifferentiated carcinoma of the tongue base, [47] a pleomorphic adenoma of the nasal septum. [48] It is well known that some inflamatory, lymphoid disorders and lymphomas, such as Burkitt's lymphoma, are related to EBV. [18],[19],[49],[50],[51],[52] Recently, occasional types of salivary gland carcinomas have also been reported with EBV positivities. [53],[54]

However, some authors claim that EBV might have a role in the pathogenesis in laryngeal supporting a definitive association (SCC). However, there are no studies supporting an association with EBV. [55],[56],[57],[58],[59],[60],[61] In our study, seven control cases of laryngeal conventional SCC were immunohistochemically negative for EBV LMP-1 and EBV EBNA-2.

Till date, there has been no study focusing on the SC of the upper aerodigestive tract with EBV association by IHC . In the current study, while four cases showed EBV LMP-1 positivity (50%), there was no EBV EBNA-2 positivity seen. However, the EBV LMP-1 results of our series could be considered only as a coincidental finding in the SCs of the upper aerodigestive tract. This finding supports the idea that further studies based on larger series might be helpful to enlighten the role played by EBV in carcinogenesis of SC.

 
   References Top

1.Bonnin P, Chapuis H, Lallemant JG. Hypopharyngeal sarcomatoid carcinoma with one time sarcomatous recurrence. A case report. Ann Otolaryngol Chir Cervicofac 1999;116:98-103.  Back to cited text no. 1
[PUBMED]    
2.Leventon GS, Evans HL. Sarcomatoid squamous cell carcinoma of the mucous membranes of the head and neck: A clinicopathologic study of 20 cases. Cancer 1981;48:994-1003.  Back to cited text no. 2
[PUBMED]    
3.Thompson LD, Wieneke JA, Miettinen M, Heffner DK. Spindle cell (sarcomatoid) carcinomas of the larynx: A clinicopathologic study of 187 cases. Am J Surg Pathol 2002;26:153-70.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Takata T, Ito H, Ogawa I, Miyauchi M, Ijuhin N, Nikai H. Spindle cell squamous carcinoma of the oral region. An immunohistochemical and ultrastructural study on the histogenesis and differential diagnosis with a clinicopathological analysis of six cases. Virchows Arch A Pathol Anat Histopathol 1991;419:177-82.  Back to cited text no. 4
[PUBMED]    
5.Mathieu MC, Micheau C, Caillaud JM, Bosq J, Carlu C. Immunohistologic marking of epithelial antigens in sarcomatoid carcinomas of the upper aerodigestive tracts. Ann Pathol 1986;6:313-22.  Back to cited text no. 5
[PUBMED]    
6.Klijanienko J, Vielh P, Duvillard P, Luboinski B. True carcinosarcoma of the larynx. J Laryngol Otol 1992;106:58-60.  Back to cited text no. 6
[PUBMED]    
7.Ellis GL, Langloss JM, Heffner DK, Hyams VJ. Spindle-cell carcinoma of the aerodigestive tract. An immunohistochemical analysis of 21 cases. Am J Surg Pathol 1987;11:335-42.  Back to cited text no. 7
[PUBMED]    
8.Choi HR, Sturgis EM, Rosenthal DI, Luna MA, Batsakis JG, El-Naggar AK. Sarcomatoid carcinoma of the head and neck: Molecular evidence for evolution and progression from conventional squamous cell carcinomas. Am J Surg Pathol 2003;27:1216-20.  Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Cardesa A, Zidar N. Spindle cell carcinoma. In: Barnes L, Eveson J, Reichart P, Sidransky D, editors. PathologyandGenetics, Head and Neck Tumours. Lyon: IARC; 2005. p. 127-8.  Back to cited text no. 9
    
10.Lewis JE, Olsen KD, Sebo TJ. Spindle cell carcinoma of the larynx: Review of 26 cases including DNA content and immunohistochemistry. Hum Pathol 1997;28:664-73.  Back to cited text no. 10
[PUBMED]    
11.Ballo MT, Garden AS, El-Naggar AK, Gillenwater AM, Morrison WH, Goepfert H, et al. Radiation therapy for early stage (T1-T2) sarcomatoid carcinoma of true vocal cords: Outcomes and patterns of failure. Laryngoscope 1998;108:760-3.  Back to cited text no. 11
[PUBMED]  [FULLTEXT]  
12.Hyams VJ. Spindle cell carcinoma of the larynx. Can J Otolaryngol 1975;4:307-13.  Back to cited text no. 12
[PUBMED]    
13.Olsen KD, Lewis JE, Suman VJ. Spindle cell carcinoma of the larynx and hypopharynx. Otolaryngol Head Neck Surg 1997;116:47-52.  Back to cited text no. 13
[PUBMED]  [FULLTEXT]  
14.Zarbo RJ, Crissman JD, Venkat H, Weiss MA. Spindle-cell carcinoma of the upper aerodigestive tract mucosa. An immunohistologic and ultrastructural study of 18 biphasic tumors and comparison with seven monophasic spindle-cell tumors. Am J Surg Pathol 1986;10:741-53.  Back to cited text no. 14
[PUBMED]    
15.Gulley ML, Tang W. Laboratory assays for Epstein-Barr virus-related disease. J Mol Diagn 2008;10:279-92.  Back to cited text no. 15
[PUBMED]  [FULLTEXT]  
16.Murray PG, Swinnen LJ, Constandinou CM, Pyle JM, Carr TJ, Hardwick JM, et al. BCL-2 but not its Epstein-Barr virus-encoded homologue, BHRF1, is commonly expressed in posttransplantation lymphoproliferative disorders. Blood 1996;87:706-11.  Back to cited text no. 16
[PUBMED]  [FULLTEXT]  
17.Spender LC, Cornish GH, Sullivan A, Farrell PJ. Expression of transcription factor AML- 2 (RUNX3, CBF(alpha)-3) is induced by Epstein-Barr virus EBNA-2 and correlates with the B-cell activation phenotype. J Virol 2002;76:4919-27.  Back to cited text no. 17
[PUBMED]  [FULLTEXT]  
18.Chan J, Bray F, McCarron P, Foo W, Lee AW, Yip T, et al. Nasopharyngeal carcinoma. In: Barnes L, Eveson J, Reichart P, Sidransky D, editors. Pathology and Genetics, Head and Neck Pathology. Lyon: IARC Press; 2005. p. 85.  Back to cited text no. 18
    
19.Chan A, Chan J. Haematolymphoid tumours. In: Barnes L, Eveson J, Reichart P, Sidransky D, editors. Pathology and Genetics, Head and Neck Pathology. Lyon: IARC Press; 2005. p. 199-205.  Back to cited text no. 19
    
20.Frierson H. Sinonasal undifferentiated carcinoma. In: Barnes L, Eveson J, Reichart P, Sidransky D, editors. Pathology and Genetics, Head and Neck Tumors. Lyon: IARC; 2005. p. 19.  Back to cited text no. 20
    
21.Brodsky G. Carcino(pseudo)sarcoma of the larynx: The controversy continues. Otolaryngol Clin North Am 1984;17:185-97.  Back to cited text no. 21
[PUBMED]    
22.Hellquist H, Olofsson J. Spindle cell carcinoma of the larynx. APMIS 1989;97:1103-13.  Back to cited text no. 22
[PUBMED]    
23.Lambert PR, Ward PH, Berci G. Pseudosarcoma of the larynx: A comprehensive analysis. Arch Otolaryngol 1980;106:700-8.  Back to cited text no. 23
[PUBMED]    
24.Meijer JW, Ramaekers FC, Manni JJ, Slooff JJ, Aldeweireldt J, Vooys GP. Intermediate filament proteins in spindle cell carcinoma of the larynx and tongue. Acta Otolaryngol 1988;106:306-13.  Back to cited text no. 24
[PUBMED]    
25.Recher G. Spindle cell squamous carcinoma of the larynx. Clinico-pathological study of seven cases. J Laryngol Otol 1985;99:871-9.  Back to cited text no. 25
[PUBMED]    
26.Goellner JR, Devine KD, Weiland LH. Pseudosarcoma of the larynx. Am J Clin Pathol 1973;59:312-26.  Back to cited text no. 26
[PUBMED]    
27.Lane N. Pseudosarcoma (polypoid sarcoma-like masses) associated with squamous-cell carcinoma of the mouth, fauces, and larynx; report of ten cases. Cancer 1957;10:19-41.  Back to cited text no. 27
[PUBMED]    
28.Berthelet E, Shenouda G, Black MJ, Picariello M, Rochon L. Sarcomatoid carcinoma of the head and neck. Am J Surg 1994;168:455-8.  Back to cited text no. 28
[PUBMED]  [FULLTEXT]  
29.Ansari-Lari MA, Hoque MO, Califano J, WestraWH. Immunohistochemical p53 expression patterns in sarcomatoid carcinomas of the upper respiratory tract. Am J Surg Pathol 2002; 26:1024-31.  Back to cited text no. 29
    
30.Ferlito A. Histological classification of larynx and hypopharynx cancers and their clinical implications. Pathologic aspects of 2052 malignant neoplasms diagnosed at the ORL Department of Padua University from 1966 to 1976. Acta Otolaryngol Suppl 1976;342:1-88.  Back to cited text no. 30
[PUBMED]    
31.Nappi O, Wick MR. Sarcomatoid neoplasms of the respiratory tract. Semin Diagn Pathol 1993;10:137-47.  Back to cited text no. 31
[PUBMED]    
32.Sherwin RP, Strong MS, Vaughn CW Jr. Polypoid and junctional squamous cell carcinoma of the tongue and larynx with spindle cell carcinoma ("pseudosarcoma"). Cancer 1963;16:51-60.  Back to cited text no. 32
[PUBMED]    
33.Weidner N. Sarcomatoid carcinoma of the upper aerodigestive tract. Semin Diagn Pathol 1987;4:157-68.  Back to cited text no. 33
[PUBMED]    
34.Toda S, Yonemitsu N, Miyabara S, Sugihara H, Maehara N. Polypoid squamous cell carcinoma of the larynx. An immunohistochemical study for ras p21 and cytokeratin. Pathol Res Pract 1989;185:860-6.  Back to cited text no. 34
[PUBMED]    
35.Batsakis JG, Suarez P. Sarcomatoid carcinomas of the upper aerodigestive tracts. Adv Anat Pathol 2000;7:282-93.  Back to cited text no. 35
[PUBMED]    
36.Battifora H. Spindle cell carcinoma: Ultrastructural evidence of squamous origin and collagen production by the tumor cells. Cancer 1976;37:2275-82.  Back to cited text no. 36
[PUBMED]    
37.Franke WW, Grund C, Jackson BW, Illmensee K. Formation of cytoskeletal elements during mouse embryogenesis. IV. Ultrastructure of primary mesenchymal cells and their cell-cell interactions. Differentiation 1983;25:121-41.  Back to cited text no. 37
    
38.Katholm M, Krogdahl A, Hainau B, Bretlau P. Spindle cell carcinoma of the larynx. Acta Otolaryngol 1984;98:163-6.  Back to cited text no. 38
[PUBMED]    
39.Knapp AC, Franke WW. Spontaneous losses of control of cytokeratin gene expression in transformed, non-epithelial human cells occurring at different levels of regulation. Cell 1989;59:67-79.  Back to cited text no. 39
[PUBMED]  [FULLTEXT]  
40.Van Muijen GN, Ruiter DJ, Franke WW, Achtstatter T, Haasnoot WH, Ponec M, et al. Cell type heterogeneity of cytokeratin expression in complex epithelia and carcinomas as demonstrated by monoclonal antibodies specific for cytokeratins nos. 4 and 13. Exp Cell Res 1986;162:97-113.  Back to cited text no. 40
    
41.Ongkeko WM, Altuna X, Weisman RA, Wang-Rodriguez J. Expression of protein tyrosine kinases in head and neck squamous cell carcinomas. Am J Clin Pathol 2005;124:71-6.  Back to cited text no. 41
[PUBMED]  [FULLTEXT]  
42.Shah NG, Trivedi TI, Tankshali RA, Goswami JV, Jetly DH, Shukla SN, et al. Prognostic significance of molecular markers in oral squamous cell carcinoma: A multivariate analysis. Head Neck 2009;31:1544-56.  Back to cited text no. 42
[PUBMED]  [FULLTEXT]  
43.Henle G, Henle W, Clifford P, Diehl V, Kafuko GW, Kirya BG, et al. Antibodies to Epstein-Barr virus in Burkitt's lymphoma and control groups. J Natl Cancer Inst 1969;43:1147-57.  Back to cited text no. 43
[PUBMED]    
44.Niederman JC, Miller G, Pearson HA, Pagano JS, Dowaliby JM. Infectious mononucleosis. Epstein-Barr-virus shedding in saliva and the oropharynx. N Engl J Med 1976;294:1355-9.  Back to cited text no. 44
[PUBMED]  [FULLTEXT]  
45.Shamaa AA, Zyada MM, Wagner M, Awad SS, Osman MM, Azeem AA. The significance of Epstein Barr Virus (EBV) and DNA Topoisomerase II alpha (DNA-Topo II alpha) immunoreactivity in normal oral mucosa, Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC). Diagn Pathol 2008;3:45.  Back to cited text no. 45
[PUBMED]  [FULLTEXT]  
46.Wan SK, Chan JK, Lau WH, Yip TT. Basaloid-squamous carcinoma of the nasopharynx. An Epstein-Barr virus-associated neoplasm compared with morphologically identical tumors occurring in other sites. Cancer 1995;76:1689-93.  Back to cited text no. 46
[PUBMED]    
47.Wakisaka N, Murono S, Minato H, Furukawa M, Yoshizaki T. A case report: Epstein-Barr virus-associated undifferentiated carcinoma of the tongue base. Auris Nasus Larynx 2006;33:487-91.  Back to cited text no. 47
[PUBMED]  [FULLTEXT]  
48.Malinvaud D, Couloigner V, Badoual C, Halimi P, Bonfils P. Pleomorphic adenoma of the nasal septum and its relationship with Epstein-Barr virus. Auris Nasus Larynx 2006;33:417-21.  Back to cited text no. 48
[PUBMED]  [FULLTEXT]  
49.Volker HU, Scheich M, Holler S, Strobel P, Hagen R, Muller-Hermelink HK, et al. Differential diagnosis of laryngeal spindle cell carcinoma and inflammatory myofibroblastic tumor-report of two cases with similar morphology. Diagn Pathol 2007;2:1.  Back to cited text no. 49
    
50.Costes V. Lymphoid lesions of the head and neck. Ann Pathol 2009;29:323-34.  Back to cited text no. 50
[PUBMED]  [FULLTEXT]  
51.Ng MH, Chan KH, Ng SP, Zong YS. Epstein-Barr virus serology in early detection and screening of nasopharyngeal carcinoma. Ai Zheng 2006;25:250-6.  Back to cited text no. 51
[PUBMED]  [FULLTEXT]  
52.Chan KC, Lo YM. Circulating EBV DNA as a tumor marker for nasopharyngeal carcinoma. Semin Cancer Biol 2002;12:489-96.  Back to cited text no. 52
[PUBMED]  [FULLTEXT]  
53.Saqui-Salces M, Martinez-Benitez B, Gamboa-Dominguez A. EBV+ lymphoepithelial carcinoma of the parotid gland in Mexican Mestizo patients with chronic autoimmune diseases. Pathol Oncol Res 2006;12:41-5.  Back to cited text no. 53
[PUBMED]  [FULLTEXT]  
54.Herbst H, Niedobitek G. Sporadic EBV-associated lymphoepithelial salivary gland carcinoma with EBV-positive low-grade myoepithelial component. Virchows Arch 2006;448:648-54.  Back to cited text no. 54
[PUBMED]  [FULLTEXT]  
55.Tyan YS, Liu ST, Ong WR, Chen ML, Shu CH, Chang YS. Detection of Epstein-Barr virus and human papillomavirus in head and neck tumors. J Clin Microbiol 1993;31:53-6.  Back to cited text no. 55
[PUBMED]  [FULLTEXT]  
56.Ferlito A, Weiss LM, Rinaldo A, Carbone A, Devaney KO, MacMillan C, et al. Clinicopathological consultation. Lymphoepithelial carcinoma of the larynx hypopharynx, and trachea. Ann Otol Rhinol Laryngol 1997;106:437-44.  Back to cited text no. 56
[PUBMED]    
57.Tardio JC, Cristobal E, Burgos F, Menarguez J. Absence of EBV genome in lymphoepithelioma-like carcinomas of the larynx. Histopathology 1997;30:126-8.  Back to cited text no. 57
    
58.Gok U, Ozdarendeli A, Keles E, Bulut Y, Cobanoglu B. Detection of Epstein-Barr virus DNA by polymerase chain reaction in surgical specimens of patients with squamous cell carcinoma of the larynx and vocal cord nodules. Kulak Burun Bogaz Ihtis Derg 2003;11:134-8.  Back to cited text no. 58
    
59.Goldenberg D, Benoit NE, Begum S, Westra WH, Cohen Y, Koch WM. Epstein-Barr virus in head and neck cancer assessed by quantitative polymerase chain reaction. Laryngoscope 2004;114:1027-31.  Back to cited text no. 59
    
60.Coskun BU, Cinar U, Sener BM, Dadas B. Lymphoepithelial carcinoma of the larynx. Auris Nasus Larynx 2005;32:189-93.  Back to cited text no. 60
[PUBMED]  [FULLTEXT]  
61.De Oliveira DE, Bacchi MM, Macarenco RS, Tagliarini JV, Cordeiro RC, Bacchi CE. Human papillomavirus and Epstein-Barr virus infection, p53 expression, and cellular proliferation in laryngeal carcinoma. Am J Clin Pathol 2006;126:284-93.  Back to cited text no. 61
[PUBMED]  [FULLTEXT]  

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Correspondence Address:
Demet Etit
Department of Pathology, Tepecik Research and Training Hospital, Izmir
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.70969

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    Figures

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    Tables

  [Table 1], [Table 2]



 

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