Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contact Us Login 
An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists


 
  Table of Contents    
KNOW YOUR FIELD  
Year : 2016  |  Volume : 20  |  Issue : 2  |  Page : 316-319
 

Uncommon features in conventional oral squamous cell carcinoma


Department of Oral and Maxillofacial Pathology, Krishnadevaraya College of Dental Sciences, Bengaluru, Karnataka, India

Date of Submission17-Feb-2016
Date of Acceptance27-Jun-2016
Date of Web Publication11-Jul-2016

Correspondence Address:
M Sudhakara
Department of Oral and Maxillofacial Pathology, Krishnadevaraya College of Dental Sciences, Bengaluru, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-029X.185905

Rights and Permissions

 



How to cite this article:
Sudhakara M, Reshma V, Khan N, Amulya S R. Uncommon features in conventional oral squamous cell carcinoma. J Oral Maxillofac Pathol 2016;20:316-9

How to cite this URL:
Sudhakara M, Reshma V, Khan N, Amulya S R. Uncommon features in conventional oral squamous cell carcinoma. J Oral Maxillofac Pathol [serial online] 2016 [cited 2021 Dec 2];20:316-9. Available from: https://www.jomfp.in/text.asp?2016/20/2/316/185905





   Introduction Top


Oral cancer constitutes about 20 persons per 1 lakh population in India which accounts for about 30% of all types of cancers. Over five people die every hour every day due to oral cancer. International Agency for Research on Cancer has predicted that the Indian incidence of oral cancer will be 1.7 billion by 2035. Around 90-95% of oral cancers in India are squamous cell carcinomas (SCCs).[1]

Conventional SCC is relatively easy to diagnose on histopathology. Oral squamous cell carcinoma (OSCC) can be keratinizing or non-keratinizing. Non-keratinizing SCC shows absence of keratinisation and keratin pearl formation whereas this is the most common feature of keratinizing SCC.[2]

OSCC histologically is composed of dysplastic epithelial cells showing variable degrees of squamous differentiation. Well-differentiated cells almost perfectly recapitulate normal squamous cells. These dysplastic cells demonstrate basement membrane violation and invade the underlying connective tissue in the form of nests, islands, sheets etc. The tumour cells show disorganized growth, loss of polarity, dyskeratosis, keratin pearls, intercellular bridges, an increase in nuclear cytoplasmic ratio, nuclear chromatin irregularities and increased mitotic figures as the most common findings.[3],[4]

The pattern of invasion at the advancing front of the tumour is significant and is an independent predictor of both local recurrence and overall survival. The most unfavourable pattern is described as diffuse infiltration with cellular dissociation, while the most favourable pattern is well defined with ''pushing'' border.[2]

An inflammatory infiltrate consisting predominantly of lymphocytes, plasma cells and macrophages is seen at the tumour-stroma interface. Variable desmoplastic fibrous stroma, tumour associated fibroblasts and endothelial cells can also be seen.[4],[5]

Although OSCC is the most common malignancy of oral cavity which can be diagnosed effortlessly based on the above described features, some cases show rare histopathological deviations which are not commonly found in conventional OSCC. These include clear cell change, epithelial mesenchymal transition (EMT), stromal desmoplasia, hyalinization, neural invasion, vascular invasion, tissue eosinophilia, giant cell and tertiary lymphoid follicle formation.


   Clear Cell Change Top


Clear squamous cells are characterized by empty appearing or “bubbled” cytoplasm. Clear cells in OSCC were first described by Kuo in 1980. He described it to be a degenerative phenomenon, whereas some of the recent studies have demonstrated glycogen accumulations in the cytoplasm of clear cells. The content of the clear cells has to be confirmed using special stains. The presence of glycogen in the cells predicts unfavourable prognosis as it suggests aggressiveness in the tumour cells whereas degenerative phenomenon predicts better prognosis as the cells are about to degenerate [6],[7] [Figure 1].
Figure 1: Photomicrograph showing clear cell change in oral squamous cell carcinoma tumour islands (H&E stain, ×40)

Click here to view



   Epithelial-Mesenchymal Transition Top


EMT is the process by which epithelial cells acquire a mesenchymal phenotype or fibroblast-like property involving reorganization of their cytoskeleton followed by breaking out connections with the adjacent cells. Once the transition process is complete, the cells dissolve the extracellular matrix and spread to the surrounding tissues. The process of EMT is linked with cancer cell metastasis and invasion, which directly correlates with poor prognosis [8] [Figure 2].
Figure 2: Photomicrograph showing epithelial-mesenchymal transition of the tumour cells (H&E stain, ×200)

Click here to view



   Stromal Desmoplasia Top


Stromal desmoplasia is defined as the response of host cells to inductive stimuli exerted by tumour cells. In response to this the host stromal cells produce collagen and extracellular proteins regarded as stromal desmoplasia. The biological relevance of the desmoplastic host reaction is not fully understood. Previously, it was recommended that desmoplasia plays a protective role and borders the process of tumour invasion. Recently, evidences suggest that molecular crosstalk between neoplastic cells and stromal cells, and cancer induced changes in the stroma, modify the differentiation, proliferative capacity and invasive capacity of tumour cells.[9] Tumour desmoplasia occurs in highly developed invasive tumours of OSCC [10] [Figure 3]. The collagen and extracellular matrix proteins secreted by stromal cells initiates the desmoplastic retort to arbitrate the invasion process.[10]
Figure 3: Photomicrograph of oral squamous cell carcinoma showing desmoplasia in the tumour stroma (H&E stain, ×40)

Click here to view



   Stromal Hyalinization Top


Homogenous eosinophilic condensation of collagen with less number of cells characterizes stromal hyalinization. It is an attempt by the host cells to wall-off the invasive tumour cells [Figure 4].
Figure 4: Photomicrograph of oral squamous cell carcinoma showing stromal hyalinization (H&E stain, ×40)

Click here to view



   Neural Invasion Top


The incidence of perineural invasion (PNI) in head and neck cancers is as high as 80% and about 31% of OSCC cases show perineural invasion which is characterized by presence of tumour cells in the perineural space [Figure 5]. The various patterns of PNI include complete encirclement, incomplete “crescent-like” encirclement, sandwiching “onion skin,” partial invasion and neural permeation. It is a form of tumour spread exhibited by neurotropic malignancies that correlate with aggressive behaviour, disease recurrence and increased morbidity and mortality. PNI is due to tropism of tumour cells for nerve bundles in the surrounding stroma, a feature seen either in intra/extra tumoral areas.[11],[12]
Figure 5: Photomicrograph showing perineural invasion by tumour cells of oral squamous cell carcinoma (H&E stain, ×200)

Click here to view



   Vascular Invasion Top


It is defined by the presence of tumour cells in the vascular spaces [Figure 6] and about 17.2% of OSCC cases show vascular invasion. Studies have shown that vascular invasion is significantly associated with increased death rates at 5-year follow up.[11],[13]
Figure 6: Photomicrograph showing vascular invasion by tumour cells (H&E stain, ×100)

Click here to view



   Tissue Eosinophilia Top


Tumour associated tissue eosinophila is intense and seems to reflect the stromal invasion of OSCCs that occur in advanced clinical stage. However, various studies suggest that tumour eosinophila showed no prognostic value in relation to 5-year or 10-year survival rate of OSCC [14] [Figure 7].
Figure 7: Photomicrograph showing tissue eosinophilia (H&E stain, ×400)

Click here to view



   Giant Cells Top


Giant cells in OSCC can be detected as a result of foreign body reaction to keratin or due to the formation of malignant tumour giant cells in poorly differentiated carcinomas. The foreign body giant cells [Figure 8] tend to locate in the vicinity of devitalized and keratinized tumour tissue and are believed to serve a resorptive function. Moreover, areas of extensive keratinization demonstrate large keratin granulomas. These foreign body giant cells are thought to originate from monocyte-macrophage system and are CD68 positive.
Figure 8: Photomicrograph showing (a) Foreign body giant cells (H&E stain, x100) and (b) Tumour giant cells (H&E stain, ×400)

Click here to view


Malignant tumour giant cells are formed by fusion of small tumour cells or arrest in G1 phase of cell division of the tumour cells leading to incomplete DNA synthesis and accumulation of energy substrates. This results in enlargement of cells. Such giant cells can re-enter cell cycle with incomplete division causing multinucleation and polyploidization. The giant cells exhibiting pleomorphism of the nuclei predicts bad prognosis of the tumour.[15],[16],[17]


   Tertiary Lymphoid Follicles Top


The immune cells infiltrating into the sites of chronic inflammation organize themselves both anatomically and functionally similar to secondary lymphoid organs. It consists of B-cells, follicular dendritic cells and T-cells, and is termed as tertiary lymphoid structures. These have been detected in about 21% of oral cancers and have been found to be positive prognostic predictors for a patient with OSCC [Figure 9]. The tertiary lymphoid strucutres (TLSs) are chiefly found in the peri-tumoural stroma within 0.5 mm distance from the tumour front, in lymphocyte rich areas.[18]
Figure 9: Photomicrograph showing tertiary lymphoid follicles among inflammatory cells and tumor cells (H&E stain, ×40)

Click here to view



   Conclusion Top


Although easily diagnosed, certain histopathological features in conventional OSCC gives us a clue to assess the severity of the case even after it has been diagnosed as well differentiated OSCC. Thus tumours of the same clinical stage may respond differently to the same treatment and may also have distinct clinical tertiary outcomes. Features such as lymphoid follicle formation predicts better prognosis for the patient, whereas features such as EMT, neural invasion, vascular invasion and desmoplasia predicts poor prognosis. This article attempts to present some of the infrequent histopathological features that are uncommon in conventional OSCC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Varshitha A. Prevalence of Oral Cancer in India. J Pharm Sci and Res 2015;7(10):845-48.  Back to cited text no. 1
    
2.
Barnes L. Surgical Pathology of the Head and Neck. Vol 1, 3rd ed. New York: Informa Healthcare;2009.  Back to cited text no. 2
    
3.
Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 3rd ed. Missouri: Saunders, Elsevier;2009.  Back to cited text no. 3
    
4.
L.D.R. Thompson. Mini-Symposium: Head and neck Pathology: Squamous cell carcinoma variants of the head and neck. Curr Diagn Pathol 2003;9:384-96.  Back to cited text no. 4
    
5.
Markwell SM and Weed SA. Tumour and Stromal-Based Contributions to Head and Neck Squamous Cell Carcinoma Invasion. Cancer 2015; 7:382-406.  Back to cited text no. 5
    
6.
Nazir H, Salroo IN, Mahadesh J, Laxmidevi BL, Shafi M, Pillai A, et al. Clear Cell Entities of the Head and Neck: A Histopathological Review. IOSR Journal of Dental and Medical Sciences 2015;14(6):125-35.  Back to cited text no. 6
    
7.
Margaritescu I and Chirita AD. Clear Cell and Signet-Ring Cell Squamous Cell Carcinoma. In: Rongioletti F, Magaristescu I, Smoller BR editors. Rare Malignant Skin Tumours. 1st ed. New York: Springer Science+Business Media; 2015.  Back to cited text no. 7
    
8.
Krisanaprakornkit S and Iamaroon A. Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma. ISRN Oncol 2012;2012: 681469.  Back to cited text no. 8
    
9.
B Sis, S Sarioglu, S Sokmen, M Sakar, AKupelioglu, M Fuzun. Desmoplasia measured by computer assisted image analysis: An independent prognostic marker in colorectal carcinoma. J Clin Pathol 2005;58:32–38.  Back to cited text no. 9
    
10.
Kawashiri S, Tanaka A, Noguchi N, Hase T, Nakaya H, Ohara T, et al. Significance of stromal desmoplasia and myofibroblast appearance at the invasive front in squamous cell carcinoma of the oral cavity. Head and Neck 2009;31:1346-53.  Back to cited text no. 10
    
11.
Cavalcante WS, Hsieh R, Lourenço SV, Godoy LM, De Souza LNG, Almeida-Coburn KL, et al. Neural and Vascular Invasions of Oral Squamous Cell Carcinomas. J Oral Hyg Health 2015;3:187-94.  Back to cited text no. 11
    
12.
Varsha BK, Radhika MB, Makarla S, Kuriakose MA, Satya Kiran GVV, Padmalatha GV. Perineural invasion in oral squamous cell carcinoma: Case series and review of literature. J Oral MaxillofacPathol 2015;19:335-14.  Back to cited text no. 12
    
13.
Kurtz KA, Hoffman HT, Zimmerman MB, Robinson RA. Perineural and Vascular Invasion in Oral Cavity Squamous Carcinoma. Arch Pathol Lab Med 2005;129:354–59.  Back to cited text no. 13
    
14.
Oliveira DT, Tjioe KC, Assao A, Sita Faustino SE, Lopes Carvalho LA, et al. Tissue eosinophilia and its association with tumoural invasion of oral cancer. Int J Surg Pathol. 2009;17(3):244-9.  Back to cited text no. 14
    
15.
Patil S, Rao RS, Ganavi BS. A Foreigner in Squamous Cell Carcinoma! J Int Oral Health 2013;5(5):147-50.  Back to cited text no. 15
    
16.
Burkhardt A and Gebbers JO. Giant cell stromal reaction in squamous cell carcinoma. Virchow Arch A Path Anat and Histol 1997;375:263-80.  Back to cited text no. 16
    
17.
Horbay R, Stoika R. Giant cell formation: The way to cell death or cell survival? Cent Eur J Biol 2011;6(5):675-84.  Back to cited text no. 17
    
18.
Wirsing AM, Rikardsen OG, Steigen SE, Hansen LU, Olsen EH. Characterisation and prognostic value of tertiary lymphoid structures in oral squamous cell carcinoma. BMC Clinical Pathology 2014;14-38.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]


This article has been cited by
1 Multiple adenomatoid odontogenic tumours associated with eight impacted teeth
Chané Nel, André Uys, Liam Robinson, Willie F. P. van Heerden
Oral Radiology. 2021; 37(2): 321
[Pubmed] | [DOI]
2 Hyalinization as a histomorphological risk predictor in oral pathological lesions
Dominic Augustine, Roopa S. Rao, Shankargouda Patil
Journal of Oral Biology and Craniofacial Research. 2021; 11(3): 415
[Pubmed] | [DOI]
3 Multifaceted multinucleated giant cells in oral squamous cell carcinoma
Deepak Pandiar, Pratibha Ramani, Reshma Poothakulath Krishnan, K. Monica
Oral Oncology. 2021; 121: 105400
[Pubmed] | [DOI]
4 Fanconi anemia and hematopoietic stem cell transplant as risk factors for oral squamous cell carcinoma: A case report with a 12-year follow-up
Larissa Fernanda dos Santos Lima Macedo, Carina Domaneschi, Lucyene Miguita Luiz, Maria Paula Siqueira de Melo Peres, Juliana Bertoldi Franco
Special Care in Dentistry. 2021;
[Pubmed] | [DOI]
5 Knowing the unknown in oral squamous cell carcinoma: An observational study
Shruti Gupta, Mala Kamboj, Anjali Narwal
Journal of Cancer Research and Therapeutics. 2020; 16(3): 494
[Pubmed] | [DOI]



 

Top
Print this article  Email this article
            

    

 
   Search
 
  
    Similar in PUBMED
    Article in PDF (4,178 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


   Introduction
   Clear Cell Change
    Epithelial-Mesen...
   Stromal Desmoplasia
    Stromal Hyaliniz...
   Neural Invasion
   Vascular Invasion
   Tissue Eosinophilia
   Giant Cells
    Tertiary Lymphoi...
   Conclusion
    References
    Article Figures

 Article Access Statistics
    Viewed2295    
    Printed16    
    Emailed0    
    PDF Downloaded398    
    Comments [Add]    
    Cited by others 5    

Recommend this journal

© Journal of Oral and Maxillofacial Pathology | Published by Wolters Kluwer - Medknow
Online since 15th Aug, 2007