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Table of Contents
ORIGINAL ARTICLE
Year : 2010  |  Volume : 12  |  Issue : 2  |  Page : 68-72

Diagnostic significance of immunohistochemistry in cases of undifferentiated nasopharyngeal carcinoma


1 ENT Department, Zagazig University, Egypt
2 Pathology Department, Zagazig University, Egypt

Date of Web Publication2-Jan-2020

Correspondence Address:
Magdy I Gouda
43 al-Galaa street, Zagazig
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-8491.274635

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  Abstract 


Background: Undifferentiated nasopharyngeal tumors represent a great diagnostic difficulty in pathology laboratories specially in small crushed pathology specimens. Many of such tumors are anaplastic and difficult to distinguish from other neoplasms such as malignant lymphoma or soft tissue sarcoma. Antibodies to cytokeratin (CK) have been shown to be of diagnostic value in assessment of epithelial nature in both primary and metastatic poorly differentiated neoplasms. also common leukocytic antigen (CLA) and desmin help in exclusion of non-hodgkin’s lymphoma and soft tissue sarcoma.
Material and Methods: Twenty eight nasopharyngeal tumors were collected from surgical specimens received at Pathology Department - Zagazig University, Egypt, during the period from may 2005 to december 2008.
All biopsy specimens were subjected to routine histopathological diagnosis and immunohistochemical staining by broad spectum cytokeratin (CK), (CLA), and desmin.
Results: All cases of undifferentiated nasopharyngeal carcinoma revealed variable degree of positive immunoreactivity for cytokeratin, regardless of their degree of differentiation with negative staining reaction for desmin and CLA. The three cases of non-hodgkin’s lymphoma were positive for CLA and negative for desmin and cytokeratin which stained only dendritic cells. The case of rhabdomyosarcoma revealed strong positive staining for desmin with negative reaction for cytokeratin and CLA.
Conclusion: Immunostaining for broad-spectrum cytokeratin, CLA and desmin monoclonal antibodies have a great diagnostic aid in diagnosis of undifferentiated nasopharyngeal tumors with consequent effect on treatment and prognosis. Also the regular positive cytokeratin immunoreactivity in undifferentiated nasopharyngeal carcinomas supports the view that these tumors are homogenous group exhibiting variable degrees of squamous differentiation.

Keywords: undifferentiated nasopharyngeal carcinoma, Squamous cell carcinoma, immunohistochemistery, CLA,Desmin.


How to cite this article:
Gouda MI, Askar SM, Omar MM, Hegazy R. Diagnostic significance of immunohistochemistry in cases of undifferentiated nasopharyngeal carcinoma. Saudi J Otorhinolaryngol Head Neck Surg 2010;12:68-72

How to cite this URL:
Gouda MI, Askar SM, Omar MM, Hegazy R. Diagnostic significance of immunohistochemistry in cases of undifferentiated nasopharyngeal carcinoma. Saudi J Otorhinolaryngol Head Neck Surg [serial online] 2010 [cited 2022 Nov 30];12:68-72. Available from: https://www.sjohns.org/text.asp?2010/12/2/68/274635




  Introduction Top


Nasopharyngeal carcinoma (NPC) was first described as a separate entity by Regaud and Schmincke in 1921 [1]. Nasopharyngeal carcinoma is a neoplasm of the head and neck that is rarely seen in the United States and Western Europe. It is more common however, among southwest asian, north african, and eskimo populations. NPC differs from other squamous cell carcinomas of the head and neck with regard to epidemiology, histologic features, treatment strategies and response to therapy [2]. The most common presenting symptoms of NPC are cervical lymphadenopathy, followed by nasal, aural and neurological symptoms. Only 5% of patients present with distant metastases in series from southern china. once the diagnosis is suspected on clinical grounds histological confirmation of the diagnosis is mandatory [3],[4].

In nasopharyngeal malignancy, many of tumors are undifferentiated carcinoma that can be difficult to distin- guish from other neoplasms such as malignant lymphoma or soft tissue sarcoma [5]. NPC are epithelial neoplasms. Three histopathological types are recognized in the world health organization (WHO) classifications [6]. Type 1 is squamous cell carcinoma (SCC) with varying degrees of differentiation, type 11 is non-keratinizing carcinoma and type III is undifferentiated carcinoma. WHO types II and III can be considered together as undifferentiated carcinoma of the nasopharyngeal type (UCNT). The histological types may be of prognostic significance with UCNT having a higher local control rate after treatment with radiotherapy than keratinizing SCC, and UCNT has also been shown to fail more distantly than locally [7],[8]. Tumor volumes in patients with NPC are heterogeneous in the concurrent T classification and disease stage. those patients with large primary tumor volume have poor survival rate and require more aggressive treatment. Incorporation of primary tumor volume may be further considered to improve the current staging system [9]. Most cases in childhood and adolescence belong to type 3, and to little extent to type 2 cases [10]. Type II and III are associated with elevated epstein-barr virus titers, but type I is not [11]. Types II and III may be accompanied by an inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils, which are abundant, giving rise to the term lympho-epithelioma.

Two histological patterns may occur: regaud type, with a well-defined collection of epithelial cells surrounded by lymphocytes and connective tissue, and schmincke type, in which the tumor cells are distributed diffusely and intermingle with the inflammatory cells. Both patterns may be present in the same tumor [1]. Antibodies to cytokeratin have been shown to be of diagnostic value in assessment of epithelial nature in both primary and metastatic poorly differentiated neoplasms [12]. In a study included 14 paraffin - embedded tissue of nasopharyngeal carcinoma Gusterson et al.[13], reported positive staining reaction for cytokeratin in all cases and negative reactivity in all cases of lymphomas. Immunohistochemical analysis was carried out to examine the characteristics of nasopharyngeal carcinoma (NPC) using 38 biopsy cases obtained from southern china. 6 cases of squamous cell carcinoma, 25 cases of differentiated non-keratinizing carcinoma, 7 cases of undifferentiated carcinoma. all tumor tissues did not react with L26 (CD20), and leukocyte common antigen (CLA). keratin and epithelial membrane antigen (EMA) as epithelial markers focally stained NPC tissues in all cases. On the other hand, squamous cell carcinoma cases did not react with vimentin, and desmin [14].

In this study, diagnosis of 28 cases of nasopharyngeal tumors were evaluated as regarding their histologic type by Hx&E sections and their epithelial nature were verified by immuno-histopathological staining for cytokeratin, demin and LCA (CD45) to rule out the possibility of undifferentiated lymphoid tumors or soft tissue sarcoma. The aim of this study was to evaluate the role of monoclonal antibodies in diagnosis of undifferentiated carcinoma of nasopharyngeal type and to set a simplified immunohistochemical profile that can be easily applied in routine pathology laboratories and assist in solving diagnostic problems in cases of undifferentiated nasopharyngeal tumors, especially in small crushed biopsy specimens.


  Material and Methods Top


Patients with suspected nasopharyngeal tumours were selected from the outpatient clinic of ENT, Zagazig University Hospitals during the period from may 2005 to December 2008. All patients were subjected to thorough ENT examination, fiberoptic nasopharyn-goscopy, CT of the nasopharynx, routine pre-operative laboratory investigations & audiological assessment. All patients underwent nasopharyngoscopy & biopsy under general anesthesia, also panendoscopy of the upper aerodigestive tract is done to exclude the presence of second primary tumours. Twenty eight confirmed cases of nasopharyngeal tumors were received at pathology department - Zagazig University. All biopsy specimens were evaluated for their routine histopathological diagnosis. Unstained tissue sections 4u-thick were cut and blotted on positive charged slides and subjected to immunohistochemical staining by broad spectum cytokeratin (CK), common leukocytic antigen (CLA), and desmin. Antigen retrieval was submitted by heating for 10 minutes in 0.01 mol/litre citric acid at pH 6.0, then incubated with 1% hydrogen peroxide for 15 minutes, to block endogenous peroxidase activity, and subsequently with 1% bovine serum albumin diluted in tris buffered saline (TBS) at pH 7.6 for 20 minutes, to block non-specific binding. The slides were incubated overnight at 40°C in a humid chamber with appropriately diluted primary antibodies to broad spectum cytoker- atin (CK), common leukocytic antige (CLA), and desmin (novocastra laboratories ltd, newcastle, 1/50 dilution) after washing in TBS, the peroxidase reaction was developed in freshly prepared 0.025% diaminoben-zidine 0.1% hydrogen peroxide in TBS. finally, sections were counterstained with haematoxylin.


  Results Top


All cases of primary and metastatic squamous cell carcinoma showed strong positive immunoreactivity for cytokeratin and negative reactivity to desmin and CLA. All cases of undifferentiated nasopharyngeal carcinoma revealed variable degree of positive immunoreactivity for cytokeratin, regardless of their degree of differentiation with negative staining reaction for desmin and CLA. The three cases of non-hodgkin’s lymphoma were positive CLA and negative for desmin and cytokeratin which stained only dendritic cells. The case of rhabdomyosarcoma revealed strong positive membranous and cytoplasmic staining for desmin and negative reaction for cytokeratin and CLA. [Table 1] and [Table 2] [Figure 1], [Figure 2], [Figure 3].
Figure 1: undifferentiated nasopharyngeal carcinoma, strong positive membranous and cytoplasmic immunostaning for broad-spectrum cytokeratin (x400).

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Figure 2: non-hodgkin's lymphoma, negative staining of neoplastic cells and weak positive staning of dendrtic cells for cytokeratin (x 400).

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Figure 3: non-hodgkin's lymphoma, positive membranous staining of neoplastic cells for leukocytic common antigen (x 400).

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Table 1: clinicopathological data of the examined 28 cases of nasopharyngeal carcinoma

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Table 2: immunohistochemical data of the examined 28 cases of nasopharyngeal carcinoma

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  Discussion Top


Undifferentiated carcinoma of nasopharyngeal type represents a single tumor type of epithelial origin. Morphological recognition of such undifferentiated neoplasms requires considerable experience in these tumors and their differentiation from lymphoma and sarcoma which sometimes represents a great diagnostic difficulty [15]. Studies have demonstrated that immuno-histochemical examination is valuable in solving these diagnostic problems [16]. Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) were separately found associated with prognosis in adult patients with nasopharyngeal carcinoma (NPC) [17]. Charles et al, (2007) [18] in his retrospective cohort of patients with locoregionally advanced NPC, COX-2 expression could be detected in 85% of pre-treatment tumor biopsies and was significantly associated with nodal stage. No association was identified between COX-2 expression, clinical prognostic factors (i.e.T-stage, age, sex) and treatment outcome parameters (i.e. progression-free survival, overall survival, time to local and regional failure[18].

In a study included 14 paraffin - embedded tissue of nasopharyngeal carcinoma Gusterson et al. [13] reported positive staining reaction for cytokeratin in all cases and negative reactivity in all cases of lymphomas and concluded that cytokeratin is the most reliable epithelial marker for identifying nasopharyngeal carcinoma and excluding non-hodgkin’s lymphoma. also in another study included 40 nasopharyngeal carcinoma, Kamino et al [19] reported that the antibody to broad spectrum keratin had an overall sensitivity of 87.5% and was positive in all eight keratinizing squamous cell carcinomas, seven nonkeratinizing carcinomas (87.5%), 18 undifferentiated carcinomas (90%), and two adenocarci- nomas (50%).

In this study a panel of routinely used markers (broad spectrum cytokeratin, CLA and desmin) were used to solve diagnostic problems in undifferentiated tumors. Such diagnostic procedures can be done in ordinary laboratories and also can be used in reevaluation of diagnosis of archival paraffin-embedded materials. It was therefore suggested that such panel of monoclonal antibodies should be used as diagnostic aid in all routinely processed cases of undifferentiated nasopha- ryngeal tumors. By the use of such panel of antibodies undifferentiated nasopharyngeal carcinoma can be distinguished from non-epithelial tumors including non- hodgkin’s lymphoma and soft tissue sarcoma.this histopathological distinction is valuable as it affects manegment of the patients, treatment modality and the overall life expectancy of an individual patient. In this panel , both negative and positive immunoreavtivity were informative and carry a diagnostic value. these findings have a great clinical significance as nasopha-ryngeal biopsies are often small, crushed and distorted.


  Conclusion Top


Application of this panel of monoclonal antibodies in cases of undifferentiated nasopharyngeal tumors will solve the dilemma as to whether a nasopharyngeal tumor is carcinoma, sarcoma or lymphoma with its consequent effect on treatment and prognosis. Also the regular positive cytokeratin immunoreactivity in undifferentiated nasopharyngeal carcinomas supports the view that these tumors are homogenous group exhibiting variable degrees of squamous differentiation.

Acknowledgement:

The authers would like to thank Professor Dr. Khaled Lakouz professor of radiology for his contribution in the radiology assessment.



 
  References Top

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Fu-Min Fang, Chien-Feng Li, Chih-Yen Chien, Kwen-Ming Rau, Hsuan-Ying Huang, Immunohistochemical expression of epidermal growth factor receptor and cyclooxygenase-2 in pediatric nasopharyngeal carcinomas: No significant correlations with clinicopath-ological variables and treatment outcomes. Intern J Pediat Otorhinolaryngol. 2007;71:447-455.  Back to cited text no. 17
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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