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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 150-152

Squamous Cell Carcinoma of the Tongue Remaining Indolent for 8-Years


Department of Surgical Services, Division of Head and Neck Surgery, Regional Cancer Centre, Thiruvananthapuram, Kerala, India

Date of Submission09-May-2020
Date of Decision23-May-2020
Date of Acceptance01-Jul-2020
Date of Web Publication8-Dec-2020

Correspondence Address:
Bipin Thomas Varghese
Division of Head and Neck Surgery, Department of Surgical Services, Regional Cancer Centre, Thiruvananthapuram, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jhnps.jhnps_20_20

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  Abstract 


Squamous Cell Cancer (SCC) of the tongue is generally known for its overall aggressive behavior. However, there are subsets within this group of cancers that behave differently in its clinical presentation, course, and outcome, and the insights into this are being elucidated with more and more accuracy. It is intriguing to note that some of these cancers present with aggressive primary with the late appearance of lymph nodes, whereas others in the opposite end of the spectrum would show up with very small primary and massive nodes. Knowledge of these variations in presentation and its clinicopathological correlation is essential to plan treatment strategies. Presented here is a case of a 49 year male with no habits, who had a diagnosis of tongue cancer but defaulted treatment and reported after eight years. Surprisingly he had no significant progression of lesion giving room for curative treatment. Besides giving an insight into the unique tumor biology, a possible link to health planning, and economics from a public health perspective is discussed.

Keywords: Medical economics, tongue neoplasms, squamous cell carcinoma, tumorigenesis


How to cite this article:
Varghese BT, Rajan K. Squamous Cell Carcinoma of the Tongue Remaining Indolent for 8-Years. J Head Neck Physicians Surg 2020;8:150-2

How to cite this URL:
Varghese BT, Rajan K. Squamous Cell Carcinoma of the Tongue Remaining Indolent for 8-Years. J Head Neck Physicians Surg [serial online] 2020 [cited 2021 Apr 18];8:150-2. Available from: https://www.jhnps.org/text.asp?2020/8/2/150/302621



A 49-year-old nonsmoker and nonalcoholic male, a manual laborer by profession presented to us with a nonhealing ulcer in the left lateral border of anterior tongue in 2010. Biopsy revealed squamous cell carcinoma. He had a 2.5 cm × 2 cm left lateral tongue lesion without any significant neck node enlargement (c T2N0M0). Although he was offered the surgery as a curative option, he defaulted his appointment and reported after 8 years.

In the second presentation, his performance status was good. There was an ulceroproliferative growth of size 3 cm × 2 cm in the left lateral border of the tongue, abutting the adjacent mandible corresponding to the first premolar to second molar (cT2N0M0). The base of the tongue was free. Biopsy from the lesion re-confirmed squamous cell carcinoma. He did not have any comorbid illness, and his cancer was amenable for resection, and therefore he was counseled for radical surgery.

Under general anesthesia, wide excision [Figure 1] and [Figure 2] of the lesion was done with frozen section control. The tongue defect was closed primarily and an ipsilateral extended supraomohyoid neck dissection was performed. Histopathological report was well-differentiated squamous cell carcinoma, with noncohesive invasive tumor front. The tumor measured 2.8 cm × 2 cm with a depth of invasion of 0.5 cm (p T2N0M0). There was no lymphovascular emboli or perineural invasion. Twenty-one nodes microscopically examined in the neck dissection specimen showed reactive changes only. The patient has now completed 1 year of follow-up and is disease-free.
Figure 1: Per operative view of the lesion

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Figure 2: Wide excision of the lesion

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  Discussion Top


The tongue is the most common subsite of oral cancer reported worldwide. However, its lateral border accounts for 85% of all the cases. In our institute (The Regional Cancer Centre [RCC], Trivandrum, India), tongue cancer represents a majority of all male and female cancers. As per our hospital-based cancer registry of the year 2010, 286 of 428 patients registered with cancer of the mobile tongue were men, and a bare 8.1% of these patients presented in Stage I. Nearly 35 of 286 men had no treatment. Most of these patients were lost to follow-up.[1] However, this patient reported to us after 8 years without any treatment and to our surprise, without any significant progress of the disease, thereby providing us an opportunity to document Marking for a rare and bizarre natural course of a well-differentiated tongue cancer. It is generally perceived that causes for treatment denial are low socioeconomic status, lack of insurance, and poor awareness of the nature of the disease.[2] It was worth noting that the present surgery was done with funding from the recently introduced state government’s health insurance scheme (Karunya Scheme), which was not available in 2010.

In spite of its relatively low income, the state of Kerala in India has a high literacy level and social equality compared to the rest of the states of India. The present report depicts the existing paradox and supports the universal inverse care law, which states that care of a patient is inversely proportional to the resource of the set up because more resources get utilized for the affluent group with less catastrophic illness.[3] With the growing years, this predicament has been sorted out with the help of the initiatives of the state government and the healthy participation of the people. Other issues like fear and isolation and lack of family support have now taken the toll instead of actual financial constrain.[4]

With the growing campaign against smoking, over the past decade, there has been a steady reduction in the incidence of oral cancers, which is perhaps most evident in Kerala. This has led to the increased incidence of detection of nontobacco-related cancers and the human papillomavirus virus-related cancers.[4] At the RCC Trivandrum, we have pioneered epidemiological and molecular research related to this menace and have contributed to the Indian cancer guidelines on tongue.[5] With good research support, we have also been successful in performing clinic to laboratory researches based on the distinct tumor behaviors observed by the clinician and the present case is an example awaiting such studies. We are looking into some of the factors such as the absence of lymph node metastasis despite local tumor progression and aggressive lymph nodes in early lesions at a molecular level with minimal breakthrough which concurs with observations world-wide.[6],[7],[8],[9],[10]

A careful focus on the plausible a priori explanations at the molecular level for this unique indolent course of the disease such as immunology, genomics, or other tangible scientific issues such as tumor microenvironment or Biomics based on our institutional experience and review of the English literature has helped us to compile the following. Inactivation of the p53 tumor suppressor gene as a frequent and early event in the pathogenesis of head-and-neck tumors. Expansion of multiple clones of mutant p53-containing cells, which serves as an important biological step in field cancerization of the aerodigestive tract, which is mirrored by the evolution from normal epithelium to abnormal epithelium phenotypically. Genomic aberrations noted include loss of heterozygosity (LOH), microsatellite alterations, chromosomal instability, mutations in the TP53 gene, X-chromosome inactivation, mitochondrial DNA mutation detected by DNA amplification techniques (polymerase chain reaction), immunohistochemistry and in situ hybridization. Microsatellite alterations gain significance as an overall effective method to demonstrate clonality, LOH at loci on chromosome arms 3p, 9p, and 17p occur early in carcinogenesis and mitochondrial (mt) DNA serves as a reliable marker for clonality assays from microdissected paraffin-embedded tissue samples. Furthermore, the stroma in field cancerized areas can expand at the expense of the normal component and constitute an area of the altered microenvironment. Our own complementary evaluation studies of tongue biopsies have found nuclear and cytoplasmic expression of NF-kappa B and COX-2 at the surgically negative margins.[9]

Some of our relevant works on oral tumorigenesis include single-nucleotide polymorphism, Cyclin D1 Gene, Rb (Retinoblastoma) Pathway (Genomic Study), cyclin-dependent kinase6, p21, P27, tumor growth factor b protein, LOH, DGS162, Micro alterations in qp21 GX2, and loss of CDKN2A and CDKN2B expression.[6],[7],[8],[9] Correlations of invasion to the presence of CD4, CD8, and FoxP3 positive T-cells[11] and, the disruption of E-cadherin function and increased expression of vimentin and the transcriptional oncogene, SOX2 to epithelial-mesenchymal transformation, tumor progression and metastasis are also noteworthy.[12]

Identification and characterization of the rarest form of indolent behavior are of utmost importance in formulating alternative strategies whenever the public health resource[13] is overburdened due to financial and other reasons such as national emergencies as in case of the recent lockdown due to COVID 19 pandemic.[4],[12],[14],[15] Buying time with the help of chemotherapeutic or biological agents or using metronomic chemotherapy as an alternative strategy when surgery or radiotherapy may not be feasible is followed at our center on a case to case basis after multidisciplinary tumor board discussions.[5]


  Conclusions Top


The natural course of early well-differentiated tongue is rarely prolonged, more so in a subset who have nontobacco-related tumors. Not resorting to treatment is a health issue in a low economic society with poor health insurance coverage, which is a plausible explanation for these bizarre presentations, besides the molecular hypothesis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Disclosure

This material has never been published and is not currently under evaluation in any other peer reviewed publication.



 
  References Top

1.
Hospital Based Cancer Registry Regional Cancer Centre, Thiruvananthapuram; 2010.  Back to cited text no. 1
    
2.
Cheraghlou S, Kuo P, Mehra S, Yarbrough WG, Judson BL. Untreated oral cavity cancer: Long-term survival and factors associated with treatment refusal. Laryngoscope 2018;128:664-9.  Back to cited text no. 2
    
3.
Hart JT. The inverse care law. Lancet 1971;1:405-12.  Back to cited text no. 3
    
4.
Varghese BT. The Kerala model of health care delivery and its impact on oral cancer care during the COVID 19 pandemic. Oral Oncol 2020. pii: 104769.  Back to cited text no. 4
    
5.
D’Cruz AK, Sharma S, Agarwal JP Thakar A, Teli A, Arya S, et al. Indian council of medical research consensus document for the management of tongue cancer. ICMR 2014;16-8.  Back to cited text no. 5
    
6.
Epidemiology of Head and Neck Cancers: In: Staffieri A, Sebastian P, Kapre M, Varghese BT, Kazi R, editors. Essentials of Head and Neck Cancer. Ch. No 1. New Delhi: Byword Books;2012. pp. 1-15.  Back to cited text no. 6
    
7.
Sivadas VP, Gulati S, Varghese BT, Balan A, Kannan S. The early manifestation, tumor-specific occurrence and prognostic significance of TGFBR2 aberrant splicing in oral carcinoma. Exp Cell Res 2014;327:156-62.  Back to cited text no. 7
    
8.
Murali A, Sailasree R, Sebastian P, Rejnish Kumar R, Varghese BT, Kannan S. Loss of heterozygosity of D9S162: Molecular predictor for treatment response in oral carcinoma. Oral Oncol 2011;47:571-6.  Back to cited text no. 8
    
9.
Santhi WS, Sebastian P, Varghese BT, Prakash O, Pillai MR. NF-kappaB and COX-2 during oral tumorigenesis and in assessment of minimal residual disease in surgical margins. Exp Mol Pathol 2006;81:123-30.  Back to cited text no. 9
    
10.
Murali A, Varghese BT, Kumar RR, Kannan S. Combination of genetic variants in cyclin D1 and retinoblastoma genes predict clinical outcome in oral cancer patients. Tumour Biol 2016;37:3609-17.  Back to cited text no. 10
    
11.
Wolf GT, Chepeha DB, Bellile E, Nguyen A, Thomas D, McHugh J. University of Michigan Head and Neck SPORE Program. Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study. Oral Oncol.2015;51:90-5.  Back to cited text no. 11
    
12.
Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15:178-96.  Back to cited text no. 12
    
13.
Mallath MK, Taylor DG, Badwe RA, Rath GK, Shanta V, Pramesh CS, et al. The growing burden of cancer in India: Epidemiology and social context. Lancet Oncol 2014;15:e205-12.  Back to cited text no. 13
    
14.
Wang H, ZhangL. Risk of COVID-19 for patients with cancer. Lancet Oncol 2020;21:335-7.  Back to cited text no. 14
    
15.
Varghese BT. Covid19 pandemic: A practicing head and neck surgeon’s perspective of an institutional model. Oral Oncol 2020;106:104765.  Back to cited text no. 15
    


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